WorldWideScience

Sample records for drug safety oversight

  1. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, Kevin C., E-mail: ke@sc.edu [University of South Carolina, Department of Philosophy, USC NanoCenter (United States); Volz, David C. [University of South Carolina, Department of Environmental Health Sciences, Arnold School of Public Health (United States)

    2012-01-15

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  2. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    International Nuclear Information System (INIS)

    Elliott, Kevin C.; Volz, David C.

    2012-01-01

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345–1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  3. Addressing conflicts of interest in nanotechnology oversight: lessons learned from drug and pesticide safety testing

    Science.gov (United States)

    Elliott, Kevin C.; Volz, David C.

    2012-01-01

    Financial conflicts of interest raise significant challenges for those working to develop an effective, transparent, and trustworthy oversight system for assessing and managing the potential human health and ecological hazards of nanotechnology. A recent paper in this journal by Ramachandran et al., J Nanopart Res, 13:1345-1371 (2011) proposed a two-pronged approach for addressing conflicts of interest: (1) developing standardized protocols and procedures to guide safety testing; and (2) vetting safety data under a coordinating agency. Based on past experiences with standardized test guidelines developed by the international Organization for Economic Cooperation and Development (OECD) and implemented by national regulatory agencies such as the U.S. Environmental Protection Agency (EPA) and Food and Drug Administration (FDA), we argue that this approach still runs the risk of allowing conflicts of interest to influence toxicity tests, and it has the potential to commit regulatory agencies to outdated procedures. We suggest an alternative approach that further distances the design and interpretation of safety studies from those funding the research. In case the two-pronged approach is regarded as a more politically feasible solution, we also suggest three lessons for implementing this strategy in a more dynamic and effective manner.

  4. 76 FR 71081 - Public Aircraft Oversight Safety Forum

    Science.gov (United States)

    2011-11-16

    ... NATIONAL TRANSPORTATION SAFETY BOARD Public Aircraft Oversight Safety Forum The National Transportation Safety Board (NTSB) will convene a Public Aircraft Oversight Safety Forum which will begin at 9 a... ``Public Aircraft Oversight Forum: Ensuring Safety for Critical Missions'', are to (1) raise awareness of...

  5. ENSI Approach to Oversight of Safety Culture

    International Nuclear Information System (INIS)

    Humbel Haag, Claudia

    2012-01-01

    Claudia Humbel Haag presented developments in ENSI approach to safety culture oversight. ENSI has developed a definition/understanding of Safety Culture and a concept of how to perform oversight of Safety Culture. ENSI defines safety culture in the following way: Safety Culture comprises the behaviour, world views (in the sense of conceptualisations of reality and explanation models), values (in the sense of aims and evaluation scales), and features of the physical environment (specifically, the nuclear power plant and the documents used) which are shared by many members of an organization, in as much as these are of significance to nuclear safety. A model of the accessibility of safety culture was presented ranging from the observable (external aspects of safety culture), to aspects that are accessible by asking questions, through to aspects that are not accessible (internal part of safety culture). ENSI considers observable aspects through the existing systematic safety assessment compliance program. Aspects that are observable by asking questions will be addressed by additional oversight activities outside the systematic assessment program. Aspects that are not accessible are addressed by helping the licensee to re-think its safety culture through proactive discussions on safety culture. Reports are issued to the licensee on assumptions and observations identified through the discussions. The conclusions of the presentation emphasised the importance of basing any interventions in this area on a solid understanding of the concept of safety culture. ENSI safety culture oversight principles were also described. These include licensee responsibility for safety, and the need for the regulator to critically review their own activities to ensure a positive influence on the licensee

  6. Regulatory Oversight of Safety Culture — Korea’s Experience

    International Nuclear Information System (INIS)

    Jung, S.J.; Choi, Y.S.; Kim, J.T.

    2016-01-01

    In Korea, a regulatory oversight program of safety culture was launched in 2012 to establish regulatory measures against several events caused by weak safety culture in the nuclear industry. This paper is intended to introduce the preliminary regulatory oversight framework, development and validation of safety culture components, pilot safety culture inspection results and lessons learned. The safety culture model should be based on a sound understanding of the national culture and industry characteristics where the model will be applied. The nuclear safety culture oversight model is being developed and built on the Korean regulatory system to independently assess the nuclear power operating organizations’ safety culture.

  7. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  8. Human factors in nuclear safety oversight

    International Nuclear Information System (INIS)

    Taylor, K.

    1989-01-01

    The mission of the nuclear safety oversight function at the Savannah River Plant is to enhance the process and nuclear safety of site facilities. One of the major goals surrounding this mission is the reduction of human error. It is for this reason that several human factors engineers are assigned to the Operations assessment Group of the Facility Safety Evaluation Section (FSES). The initial task of the human factors contingent was the design and implementation of a site wide root cause analysis program. The intent of this system is to determine the most prevalent sources of human error in facility operations and to assist in determining where the limited human factors resources should be focused. In this paper the strategy used to educate the organization about the field of human factors is described. Creating an awareness of the importance of human factors engineering in all facets of design, operation, and maintenance is considered to be an important step in reducing the rate of human error

  9. 49 CFR 659.29 - Oversight agency safety and security reviews.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Oversight agency safety and security reviews. 659... Role of the State Oversight Agency § 659.29 Oversight agency safety and security reviews. At least... safety program plan and system security plan. Alternatively, the on-site review may be conducted in an on...

  10. U.S. Nuclear Regulatory Commission Safety Culture Oversight

    International Nuclear Information System (INIS)

    Sieracki, D. J.

    2016-01-01

    The NRC recognises that it is important for all organizations performing or overseeing regulated activities to establish and maintain a positive safety culture commensurate with the safety and security significance of their activities and the nature and complexity of their organizations and functions. The NRC’s approach to safety culture is based on the premise that licencees bear the primary responsibility for safety. The NRC provides oversight of safety culture through expectations detailed in policy statements, safety culture assessor training for NRC inspectors, the oversight process, and the Allegations and Enforcement Programs. The NRC’s Safety Culture Policy Statement (SCPS) sets forth the Commission’s expectation that individuals and organizations establish and maintain a positive safety culture commensurate with the safety and security significance of their activities and the nature and complexity of their organizations and functions. The SCPS is not a regulation. It applies to all licencees, certificate holders, permit holders, authorisation holders, holders of quality assurance program approvals, vendors and suppliers of safety-related components, and applicants for a licence, certificate, permit, authorisation, or quality assurance program approval, subject to NRC authority.

  11. Safety Oversight of Decommissioning Activities at DOE Nuclear Sites

    International Nuclear Information System (INIS)

    Zull, Lawrence M.; Yeniscavich, William

    2008-01-01

    The Defense Nuclear Facilities Safety Board (Board) is an independent federal agency established by Congress in 1988 to provide nuclear safety oversight of activities at U.S. Department of Energy (DOE) defense nuclear facilities. The activities under the Board's jurisdiction include the design, construction, startup, operation, and decommissioning of defense nuclear facilities at DOE sites. This paper reviews the Board's safety oversight of decommissioning activities at DOE sites, identifies the safety problems observed, and discusses Board initiatives to improve the safety of decommissioning activities at DOE sites. The decommissioning of former defense nuclear facilities has reduced the risk of radioactive material contamination and exposure to the public and site workers. In general, efforts to perform decommissioning work at DOE defense nuclear sites have been successful, and contractors performing decommissioning work have a good safety record. Decommissioning activities have recently been completed at sites identified for closure, including the Rocky Flats Environmental Technology Site, the Fernald Closure Project, and the Miamisburg Closure Project (the Mound site). The Rocky Flats and Fernald sites, which produced plutonium parts and uranium materials for defense needs (respectively), have been turned into wildlife refuges. The Mound site, which performed R and D activities on nuclear materials, has been converted into an industrial and technology park called the Mound Advanced Technology Center. The DOE Office of Legacy Management is responsible for the long term stewardship of these former EM sites. The Board has reviewed many decommissioning activities, and noted that there are valuable lessons learned that can benefit both DOE and the contractor. As part of its ongoing safety oversight responsibilities, the Board and its staff will continue to review the safety of DOE and contractor decommissioning activities at DOE defense nuclear sites

  12. Regulatory Oversight of Safety Culture in Finland: A Systemic Approach to Safety

    International Nuclear Information System (INIS)

    Oedewald, P.; Väisäsvaara, J.

    2016-01-01

    In Finland the Radiation and Nuclear Safety Authority STUK specifies detailed regulatory requirements for good safety culture. Both the requirements and the practical safety culture oversight activities reflect a systemic approach to safety: the interconnections between the technical, human and organizational factors receive special attention. The conference paper aims to show how the oversight of safety culture can be integrated into everyday oversight activities. The paper also emphasises that the scope of the safety culture oversight is not specific safety culture activities of the licencees, but rather the overall functioning of the licence holder or the new build project organization from safety point of view. The regulatory approach towards human and organizational factors and safety culture has evolved throughout the years of nuclear energy production in Finland. Especially the recent new build projects have highlighted the need to systematically pay attention to the non-technical aspects of safety as it has become obvious how the HOF issues can affect the design processes and quality of construction work. Current regulatory guides include a set of safety culture related requirements. The requirements are binding to the licence holders and they set both generic and specific demands on the licencee to understand, monitor and to develop safety culture of their own organization but also that of their supplier network. The requirements set for the licence holders has facilitated the need to develop the regulator’s safety culture oversight practices towards a proactive and systemic approach.

  13. Regulatory oversight on nuclear safety in Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Huang, T-T. [Atomic Energy Council, New Taipei City, Taiwan (China)

    2014-07-01

    Taiwan is a densely populated island and over 98% of its energy is imported, 16.5% of which is nuclear, in the form of materials and services. Ensuring that the most stringent nuclear safety standards are met therefore remains a priority for the government and the operator, Taiwan power Company (Taipower). There are eight nuclear power reactors in Taiwan, six of which are in operation and two are under construction. The first began operating nearly 40 years ago. For the time being the issue of whether to decommission or extend life of the operating units is also being discussed and has no conclusion yet. Nuclear energy has been a hot issue in debate over the past decades in Taiwan. Construction of Lungmen nuclear power plant, site selection of a final low-level waste disposal facility, installation of spent fuel dry storage facilities and safety of the currently operating nuclear power reactors are the issues that all Taiwanese are concerned most. In order to ensure the safety of nuclear power plant, the Atomic Energy Council (AEC) has implemented rigorous regulatory work over the past decades. After the Fukushima accident, AEC has conducted a reassessment program to re-evaluate all nuclear power plants in Taiwan, and asked Taipower to follow the technical guidelines, which ENSREG has utilized to implement stress test over nuclear power plants in Europe. In addition, AEC has invited two expert teams from OECD/NEA and ENSREG to conduct peer reviews of Taiwan's stress test national report in 2013. My presentation will focus on activities regulating safety of nuclear power programs. These will cover (A) policy of nuclear power regulation in Taiwan, (B)challenges of the Lungmen Plant, (C) post-Fukushima safety re-assessment, and (D)radioactive waste management. (author)

  14. The impact of masculinity on safety oversights, safety priority and safety violations in two male-dominated occupations

    DEFF Research Database (Denmark)

    Nielsen, Kent; Hansen, Claus D.; Bloksgaard, Lotte

    2015-01-01

    Background Although men have a higher risk of occupational injuries than women the role of masculinity for organizational safety outcomes has only rarely been the object of research. Aim The current study investigated the association between masculinity and safety oversights, safety priority......-related context factors (safety leadership, commitment of the safety representative, and safety involvement) and three safety-related outcome factors (safety violations, safety oversights and safety priority) were administered twice 12 months apart to Danish ambulance workers (n = 1157) and slaughterhouse workers...

  15. Regulatory Oversight of Safety Culture in Nuclear Installations

    International Nuclear Information System (INIS)

    2013-03-01

    Experience across the international nuclear industry and in other technical fields over the past few decades has demonstrated the importance of a healthy safety culture in maintaining the safety of workers, the public and the environment. Both regulators and the nuclear industry recognize the need for licensees to develop a strong safety culture in order to support successful and sustainable nuclear safety performance. Progress over recent years can be observed in the rapid development of approaches to overseeing licensees' safety culture. This publication follows on and complements earlier publications on safety culture, from the publication Safety Culture (Safety Series No. 75-INSAG-4 (1991)), published after the Chernobyl accident, to the more recently published Safety Requirements on The Management System for Facilities and Activities (IAEA Safety Standards Series No. GS-R-3 (2006)), which states that the management system is to be used to promote and support a strong safety culture. A number of attempts have been made at both the international and national levels to establish practical approaches to regulatory oversight of safety culture. During 2010 and 2011, two projects were conducted by the IAEA under the scope of the Safe Nuclear Energy - Regional Excellence Programme within the Norwegian Cooperation Programme with Bulgaria and Romania. These projects were implemented at the Bulgarian and Romanian regulatory bodies. They encompassed the development of a specific process to oversee licensees' safety culture, and involved 30 experts from 17 countries and 22 organizations. The IAEA continues to support Member States in the area of safety culture through its projects on safety management and capacity building. This publication addresses the basics of regulatory oversight of safety culture, describes the approaches currently implemented at several regulatory bodies around the world and, based on these examples, proposes a path to developing such a process

  16. Regulatory oversight of nuclear safety in Finland. Annual report 2011

    Energy Technology Data Exchange (ETDEWEB)

    Kainulainen, E. (ed.)

    2012-07-01

    The report constitutes the report on regulatory control in the field of nuclear energy which the Radiation and Nuclear Safety Authority (STUK) is required to submit once a year to the Ministry of Employment and the Economy pursuant to Section 121 of the Nuclear Energy Decree. The report is also delivered to the Ministry of Environment, the Finnish Environment Institute, and the regional environmental authorities of the localities in which a nuclear facility is located. The regulatory control of nuclear safety in 2011 included the design, construction and operation of nuclear facilities, as well as nuclear waste management and nuclear materials. The first parts of the report explain the basics of nuclear safety regulation included as part of STUK's responsibilities, as well as the objectives of the operations, and briefly introduce the objects of regulation. The chapter concerning the development and implementation of legislation and regulations describes changes in nuclear legislation, as well as the progress of STUK's YVL Guide revision work. The section concerning the regulation of nuclear facilities contains an overall safety assessment of the nuclear facilities currently in operation or under construction. The chapter concerning the regulation of the final disposal project for spent nuclear fuel de-scribes the preparations for the final disposal project and the related regulatory activities. The section concerning nuclear non-proliferation describes the nuclear non-proliferation control for Finnish nuclear facilities and final disposal of spent nuclear fuel, as well as measures required by the Additional Protocol of the Safeguards Agreement. The chapter describing the oversight of security arrangements in the use of nuclear energy discusses oversight of the security arrangements in nuclear power plants and other plants, institutions and functions included within the scope of STUK's regulatory oversight. The chapter also discusses the national and

  17. 77 FR 11553 - Draft Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug...

    Science.gov (United States)

    2012-02-27

    ... Oversight of PET Drug Products--Questions and Answers.'' The draft guidance provides questions and answers... assist that office in processing your requests. See the SUPPLEMENTARY INFORMATION section for electronic... PET Drug Products--Questions and Answers.'' In 1997, Congress passed the Food and Drug Administration...

  18. 77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

    Science.gov (United States)

    2012-12-04

    ... PET Drug Products--Questions and Answers.'' This guidance provides questions and answers that address.... 2201, Silver Spring, MD 20993-0002. Send one self-addressed adhesive label to assist that office in... availability of a guidance entitled ``FDA Oversight of PET Drug Products--Questions and Answers.'' In 1997...

  19. Governmental oversight of prescribing medications: history of the US Food and Drug Administration and prescriptive authority.

    Science.gov (United States)

    Plank, Linda S

    2011-01-01

    The evolution of drug regulation and awarding of prescriptive authority is a complex and sometimes convoluted process that can be confusing for health care providers. A review of the history of how drugs have been manufactured and dispensed helps explain why this process has been so laborious and complicated. Because the federal and state governments have the responsibility for protecting the public, most regulations have been passed with the intentions of ensuring consumer safety. The current system of laws and regulations is the result of many years of using the legal system to correct drug marketing that had adverse health consequences. Government oversight will continue as prescribing medications transitions to an electronic form and as health care professionals in addition to physicians seek to gain prescriptive authority. © 2011 by the American College of Nurse-Midwives.

  20. Aviation Safety: FAA Oversight of Repair Stations Needs Improvement

    Science.gov (United States)

    1997-10-24

    This report by the General Accounting Office examines the Federal Aviation : Administration's (FAA) oversight of the aviation repair station industry. : Specifically, this report addresses the following questions: (1) What is the : nature and scope o...

  1. A Study on the Construct Validity of Safety Culture Oversight Model for Nuclear Power Operating Organization

    International Nuclear Information System (INIS)

    Jung, Su Jin; Choi, Young Sung; Oh, Jang Jin

    2015-01-01

    In Korea, the safety policy statement declared in 1994 by government stressed the importance of safety culture and licensees were encouraged to manage and conduct their self-assessments. A change in regulatory position about safety culture oversight was made after the event of SBO cover-up in Kori unit 1 and several subsequent falsification events. Since then KINS has been developing licensee's safety culture oversight system including conceptual framework of oversight, prime focus area for oversight, and specific details on regulatory expectations, all of which are based on defence-in-depth (DiD) safety enhancement approach. Development and gathering of performance data which is related to actual 'safety' of nuclear power plant are needed to identify the relationship between safety culture and safety performance. Authors consider this study as pilot which has a contribution on verifying the construct validity of the model and the effectiveness of survey based research. This is the first attempt that the validity of safety culture oversight model has been investigated with empirical data obtained from Korean nuclear power operating organization

  2. A Study on the Construct Validity of Safety Culture Oversight Model for Nuclear Power Operating Organization

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Su Jin; Choi, Young Sung; Oh, Jang Jin [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2015-05-15

    In Korea, the safety policy statement declared in 1994 by government stressed the importance of safety culture and licensees were encouraged to manage and conduct their self-assessments. A change in regulatory position about safety culture oversight was made after the event of SBO cover-up in Kori unit 1 and several subsequent falsification events. Since then KINS has been developing licensee's safety culture oversight system including conceptual framework of oversight, prime focus area for oversight, and specific details on regulatory expectations, all of which are based on defence-in-depth (DiD) safety enhancement approach. Development and gathering of performance data which is related to actual 'safety' of nuclear power plant are needed to identify the relationship between safety culture and safety performance. Authors consider this study as pilot which has a contribution on verifying the construct validity of the model and the effectiveness of survey based research. This is the first attempt that the validity of safety culture oversight model has been investigated with empirical data obtained from Korean nuclear power operating organization.

  3. State safety oversight program : audit of the tri-state oversight committee and the Washington metropolitan area transit authority, final audit report, March 4, 2010.

    Science.gov (United States)

    2010-03-04

    The Federal Transit Administration (FTA) conducted an on-site audit of the safety program implemented by the Washington Metropolitan Area Transit Authority (WMATA) and overseen by the Tri-State Oversight Committee (TOC) between December 14 and 17, 20...

  4. 77 FR 6411 - Training, Qualification, and Oversight for Safety-Related Railroad Employees

    Science.gov (United States)

    2012-02-07

    ... Oversight for Safety-Related Railroad Employees AGENCY: Federal Railroad Administration (FRA), Department of... establishing minimum training standards for each category and subcategory of safety-related railroad employee... or contractor that employs one or more safety-related railroad employee to develop and submit a...

  5. Approaches to the mathematical description of NPP operational safety management and oversight

    International Nuclear Information System (INIS)

    Bilej, D.V.; Berzhanskij, S.V.

    2014-01-01

    The paper presents analysis of features related to NPP operational safety management and oversight. According to analysis results, approaches are proposed to perform mathematical description of specific processes and to develop a scale for management to the current safety level as regards NPP power generation. Proposed approaches are making experimental equations and process approach of ISO-9001 quality system

  6. Regulatory oversight of safety culture in nuclear installations - New IAEA developments

    International Nuclear Information System (INIS)

    Kerhoas, Anne; )

    2012-01-01

    Ms. Anne Kerhoas described the IAEA work on guidance for regulatory oversight of safety culture. She summarised the various IAEA, OECD/NEA and ANS meetings that have been held on the topic between 1995 and 2011. The IAEA has carried out two recent projects with the Bulgarian and Romanian regulatory bodies to develop a safety culture oversight program. The work was funded by the Norwegian government and has involved 30 experts from 17 different countries. Draft guidance for regulators on how to monitor licensee safety culture has also been produced (IAEA-TECDOC-DD1070). The document is intended to provide practical guidance on oversight strategies and is applicable to a wide range of nuclear installations, including nuclear power plants, fuel cycle facilities, research reactors and waste management facilities. A number of principles for regulatory oversight of safety culture were summarised. For example, the primary responsibility for safety remains with the licensee, safety culture oversight should be performed at all stages of the life cycle of the nuclear installation, and multiple data collection methods should be used. The overall approach to safety culture described in the draft IAEA Tech doc includes a range of approaches to build up a meaningful picture of the licensee's safety culture. These include interviews, observations, review of documents, review of events, discussions and surveys. The importance of ongoing discussion with the licensee throughout the process to develop a deeper shared understanding of issues was emphasised. The results of the Chester 2 workshop will be used as an input to finalization of the draft Tech Doc

  7. Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards.

    Science.gov (United States)

    Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

    2017-06-01

    Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take appropriate steps to mitigate the risks of working with these biologic hazards. This article will review responsibilities for institutional oversight of occupational health and safety for research involving biologic hazards.

  8. Nuclear safety and security culture - an integrated approach to regulatory oversight

    International Nuclear Information System (INIS)

    Tronea, M.; Ciurea Ercau, C.

    2013-01-01

    The paper presents the development and implementation of regulatory guidelines for the oversight of safety and security culture within licensees organizations. CNCAN (the National Commission for Nuclear Activities of Romania) has used the International Atomic Energy Agency (IAEA) attributes for a strong safety culture as the basis for its regulatory guidelines providing support to the reviewers and inspectors for recognizing and gathering information relevant to safety culture. These guidelines are in process of being extended to address also security culture, based on the IAEA Nuclear Security Series No. 7 document Nuclear Security Culture: Implementing Guide. Recognizing that safety and security cultures coexist and need to reinforce each other because they share the common objective of limiting risk and that similar regulatory review and inspection processes are in place for nuclear security oversight, an integrated approach is considered justified, moreover since the common elements of these cultures outweigh the differences. (authors)

  9. Lessons Learned from a Five-year Evaluation of the Belgian Safety Culture Oversight Process

    International Nuclear Information System (INIS)

    Bernard, B.

    2016-01-01

    The Belgian Regulatory Body has implemented a Safety Culture oversight process since 2010. In a nutshell, this process is based on field observations provided by inspectors or safety analysts during any contact with a licencee (inspections, meetings, phone calls, etc). These observations are recorded within an observation (excel) sheet—aiming at describing factual and contextual issues — and are linked to IAEA Safety Culture attributes. It should be stressed that the purpose of the process is not to give a comprehensive view of a licencee safety culture but to address findings that require attention or action on the part of a licencee. In other words, gathering safety culture observations aims at identifying cultural, organizational or behavioural issues in order to feed a regulatory response to potential problems. Safety Culture Observations (SCO) are then fully integrated in routine inspection activities and must be seen as an input of the overall oversight process. As a result, the assessment of the SCO is inserted within the yearly safety evaluation report performed by Bel V and transmitted to the licencee. However, observing safety culture is not a natural approach for engineers. Guidance, training and coaching must be provided in order to open up safety dimensions to be captured. In other words, a SCO process requires a continuous support in order to promote a holistic and systemic view of safety.

  10. Maintaining Oversight of Licensee Safety Culture. CSNI/WGHOF Survey Results

    International Nuclear Information System (INIS)

    2008-01-01

    In preparation for this workshop, a survey was sent to members of the WGHOF in Autumn 2006. Purpose of the Survey was to explore and share the methods and approaches used to maintain oversight of licensee safety culture. 13 countries responded to the survey. The responses were used in the development of discussion topics and themes for this workshop. This presentation (slides) summarizes the results of the survey

  11. Adverse weather impact on aviation safety, investigation and oversight

    Science.gov (United States)

    Smith, M. J.

    1985-01-01

    A brief review of the weather factors that effect aviation safety with respect to U.S. Coast Guard operations is presented. Precise meteorological information is an absolute necessity to the Coast Guard which must conduct life saving and rescue operations under the worst of weather conditions. Many times the weather conditions in which they operate are the cause of or a contributing factor to the predicament from which they must execute a rescue operation.

  12. Hospital board oversight of quality and safety: a stakeholder analysis exploring the role of trust and intelligence.

    Science.gov (United States)

    Millar, Ross; Freeman, Tim; Mannion, Russell

    2015-06-16

    Hospital boards, those executive members charged with developing appropriate organisational strategies and cultures, have an important role to play in safeguarding the care provided by their organisation. However, recent concerns have been raised over boards' ability to enact their duty to ensure the quality and safety of care. This paper offers critical reflection on the relationship between hospital board oversight and patient safety. In doing so it highlights new perspectives and suggestions for developing this area of study. The article draws on 10 interviews with key informants and policy actors who form part of the 'issue network' interested in the promotion of patient safety in the English National Health Service. The interviews surfaced a series of narratives regarding hospital board oversight of patient safety. These elaborated on the role of trust and intelligence in highlighting the potential dangers and limitations of approaches to hospital board oversight which have been narrowly focused on a risk-based view of organisational performance. In response, a need to engage with the development of trust based organisational relationships is identified, in which effective board oversight is built on 'trust' characterised by styles of leadership and behaviours that are attentive to the needs and concerns of both staff and patients. Effective board oversight also requires the gathering and triangulating of 'intelligence' generated from both national and local information sources. We call for a re-imagination of hospital board oversight in the light of these different perspectives and articulate an emerging research agenda in this area.

  13. Regulatory Oversight of Radioactive Sources through the Integrated Management of Safety and Security

    International Nuclear Information System (INIS)

    Horvath, K.

    2016-01-01

    The Hungarian Atomic Energy Authority (HAEA) has full regulatory competence; its mission is to oversee the safety and security of all the peaceful applications of atomic energy. All the radioactive sources having activity above the exemption level is registered and licensed both from safety and security points of view. The Hungarian central register of radioactive sources contains about 7,000 radioactive sources and 450 license holders. In order to use its limited resources the HAEA has decided to introduce an integrated regulatory oversight programme. Accordingly, during the licensing process and inspection activities the HAEA intends to assess both safety and security aspects at the same time. The article describes the Hungarian the various applications of radioactive materials, and summarizes the preparation activities of the HAEA. (author)

  14. Environment, safety, and health. Status of DOE's reorganization of its safety oversight function

    International Nuclear Information System (INIS)

    Bannerman, Carl J.; Cannon, Doris E.; Jones, Gary L.; Ulrich, Timothy W.

    1990-01-01

    Several major events that preceded the Secretary's decision to restructure DOE's management of its nuclear facilities were identified. The proposed restructuring plan, in concept, is designed to set in place an oversight framework, which will provide confidence in DOE's ability to operate its nuclear facilities in a safe manner. Further, on the basis of the previous work in this area as well as other independent studies, several issues were identified that may affect the success of the proposed restructuring plan

  15. Contemporary Approaches to Safety Culture: Lessons from Developing a Regulatory Oversight Approach

    International Nuclear Information System (INIS)

    Goebel, V.; Heppell-Masys, K.

    2016-01-01

    The Canadian Nuclear Safety Commission (CNSC) regulates the use of nuclear energy and materials to protect health, safety, security and the environment, and to implement Canada’s international commitments on the peaceful use of nuclear energy; and to disseminate objective scientific, technical and regulatory information to the public. In the late 1990s, the CNSC conducted research into an Organization and Management (O&M) assessment method. Based on this research the CNSC conducted O&M assessments at all Canadian nuclear power plants and conducted additional assessments of nuclear research and uranium mine and mill operations. The results of these assessments were presented to licencees and used to inform their ongoing actions related to safety culture. Additional safety culture outreach and oversight activities provided licencees with opportunities to develop effective safety culture assessment methods, to share best practices across industry, and to strive for continual improvement of their organizations. Recent changes to the Canadian Standards Association (CSA) management system standard have resulted in the inclusion of requirements associated to safety culture and human performance. Representatives from several sectors of Canada’s nuclear industry, as well as participation from regulators such as the CNSC took part to the development of this consensus standard. Specifically, these requirements focus on monitoring and understanding safety culture, integrating safety into all of the requirements of the management system, committing workers to adhere to the management system and supporting excellence in workers’ performance. The CNSC is currently developing a regulatory document on safety culture which includes key concepts applicable to all licencees and specific requirements related to self-assessment, and additional guidance for nuclear power plants. Developing a regulatory document on safety culture requires consultation and fact finding initiatives at

  16. 42 CFR 137.368 - Is the Secretary responsible for oversight and compliance of health and safety codes during...

    Science.gov (United States)

    2010-10-01

    ... compliance of health and safety codes during construction projects being performed by a Self-Governance Tribe... SERVICES TRIBAL SELF-GOVERNANCE Construction Roles of the Secretary in Establishing and Implementing Construction Project Agreements § 137.368 Is the Secretary responsible for oversight and compliance of health...

  17. Drug Safety: Managing Multiple Drugs

    Science.gov (United States)

    ... This series is produced by Consumers Union and Consumer Reports Best Buy Drugs , a public information project sup- ported by grants from the Engelberg Foundation and the National Library of Medicine of ... Consumer and Prescriber Education Grant Program which is funded ...

  18. Oversight and enforcement at DOE

    International Nuclear Information System (INIS)

    Fergus, I.E., Christopher, R.K.

    1996-01-01

    This paper addresses recent changes to the independent oversight and enforcement programs within the U.S. Department of Energy (DOE) and applications to criticality safety. DOE's Office of Oversight (Oversight hereafter), in the Office of Environment, Safety, and Health (EH), independently evaluates whether management systems ensure adequate protection of the worker, public, and environment. Oversight has adopted a new approach to performing evaluations based on the guiding principles for safety management identified by the Secretary of Energy. The principles Oversight evaluates are line management responsibility for safety and health, comprehensive requirements, and competence commensurate with responsibilities. Recently, the DOE codified the implementation of integrated safety management, further expounding on these basic guiding principles and Oversight's role. The Office of Enforcement and Investigations in EH (Enforcement hereafter) is responsible for enforcement, and relevant documents describe its role. This paper briefly discusses criticality safety aspects of the twin initiatives of Oversight and Enforcement

  19. Overseeing oversight: governance of quality and safety by hospital boards in the English NHS.

    Science.gov (United States)

    Mannion, Russell; Davies, Huw; Freeman, Tim; Millar, Ross; Jacobs, Rowena; Kasteridis, Panos

    2015-01-01

    To contribute towards an understanding of hospital board composition and to explore board oversight of patient safety and health care quality in the English NHS. We reviewed the theory related to hospital board governance and undertook two national surveys about board management in NHS acute and specialist hospital trusts in England. The first survey was issued to 150 trusts in 2011/2012 and was completed online via a dedicated web tool. A total 145 replies were received (97% response rate). The second online survey was undertaken in 2012/2013 and targeted individual board members, using a previously validated standard instrument on board members' attitudes and competencies (the Board Self-Assessment Questionnaire). A total of 334 responses were received from 165 executive and 169 non-executive board members, providing at least one response from 95 of the 144 NHS trusts then in existence (66% response rate). Over 90% of the English NHS trust boards had 10-15 members. We found no significant difference in board size between trusts of different types (e.g. Foundation Trusts versus non-Foundation Trusts and Teaching Hospital Trusts versus non-Teaching Hospital Trusts). Clinical representation on boards was limited: around 62% had three or fewer members with clinical backgrounds. For about two-thirds of the trusts (63%), board members with a clinical background comprised less than 30% of the members. Boards were using a wide range and mix of quantitative performance metrics and soft intelligence (e.g. walk-arounds, patient stories) to monitor their organisations with regard to patient safety. The Board Self-Assessment Questionnaire data showed generally high or very high levels of agreement with desirable statements of practice in each of its six dimensions. Aggregate levels of agreement within each dimension ranged from 73% (for the dimension addressing interpersonal issues) to 85% (on the political). English NHS boards largely hold a wide range of attitudes and

  20. Safety-Related Contractor Activities at Nuclear Power Plants. New Challenges for Regulatory Oversight

    Energy Technology Data Exchange (ETDEWEB)

    Chockie, Alan [Chockie Group International, Inc., Seattle, WA (United States)

    2005-09-15

    The use of contractors has been an integral and important part of the design, construction, operation, and maintenance of nuclear power plants. To ensure the safe and efficient completion of contracted tasks, each nuclear plant licensee has developed and refined formal contract management processes to meet their specific needs and plant requirements. Although these contract management processes have proven to be effective tools for the procurement of support and components tailored to the needs of nuclear power plants, contractor-related incidents and accidents have revealed some serious weaknesses with the implementation of these processes. Identifying and addressing implementation problems are becoming more complicated due to organizational and personnel changes affecting the nuclear power industry. The ability of regulators and licensees to effectively monitor and manage the safety-related performance of contractors will likely be affected by forthcoming organization and personnel changes due to: the aging of the workforce; the decline of the nuclear industry; and the deregulation of nuclear power. The objective of this report is to provide a review of current and potential future challenges facing safety-related contractor activities at nuclear power plants. The purpose is to assist SKI in establishing a strategy for the proactive oversight of contractor safety-related activities at Swedish nuclear power plants and facilities. The nature and role of contractors at nuclear plants is briefly reviewed in the first section of the report. The second section describes the essential elements of the contract management process. Although organizations have had decades of experience with the a contract management process, there remain a number of common implantation weaknesses that have lead to serious contractor-related incidents and accidents. These implementation weaknesses are summarized in the third section. The fourth section of the report highlights the

  1. Safety-Related Contractor Activities at Nuclear Power Plants. New Challenges for Regulatory Oversight

    International Nuclear Information System (INIS)

    Chockie, Alan

    2005-09-01

    The use of contractors has been an integral and important part of the design, construction, operation, and maintenance of nuclear power plants. To ensure the safe and efficient completion of contracted tasks, each nuclear plant licensee has developed and refined formal contract management processes to meet their specific needs and plant requirements. Although these contract management processes have proven to be effective tools for the procurement of support and components tailored to the needs of nuclear power plants, contractor-related incidents and accidents have revealed some serious weaknesses with the implementation of these processes. Identifying and addressing implementation problems are becoming more complicated due to organizational and personnel changes affecting the nuclear power industry. The ability of regulators and licensees to effectively monitor and manage the safety-related performance of contractors will likely be affected by forthcoming organization and personnel changes due to: the aging of the workforce; the decline of the nuclear industry; and the deregulation of nuclear power. The objective of this report is to provide a review of current and potential future challenges facing safety-related contractor activities at nuclear power plants. The purpose is to assist SKI in establishing a strategy for the proactive oversight of contractor safety-related activities at Swedish nuclear power plants and facilities. The nature and role of contractors at nuclear plants is briefly reviewed in the first section of the report. The second section describes the essential elements of the contract management process. Although organizations have had decades of experience with the a contract management process, there remain a number of common implantation weaknesses that have lead to serious contractor-related incidents and accidents. These implementation weaknesses are summarized in the third section. The fourth section of the report highlights the

  2. Diabetes Drugs and Cardiovascular Safety

    Directory of Open Access Journals (Sweden)

    Ji Cheol Bae

    2016-06-01

    Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

  3. Institutional Oversight of Occupational Health and Safety for Research Programs Involving Biohazards

    OpenAIRE

    Dyson, Melissa C; Carpenter, Calvin B; Colby, Lesley A

    2017-01-01

    Research with hazardous biologic materials (biohazards) is essential to the progress of medicine and science. The field of microbiology has rapidly advanced over the years, partially due to the development of new scientific methods such as recombinant DNA technology, synthetic biology, viral vectors, and the use of genetically modified animals. This research poses a potential risk to personnel as well as the public and the environment. Institutions must have appropriate oversight and take app...

  4. ISSUES OF FETUS DRUG SAFETY

    Directory of Open Access Journals (Sweden)

    A.V. Ostrovskaya

    2010-01-01

    Full Text Available The article is focused on the issue of fetus drug safety. Development of a child’s health depends both on hereditary information and environment factors. The reason for deviation from the process of normal prenatal development could be any xenobiotics, physical factors and some medications having a pathogenic effect during pregnancy on the embryo and fetus. Due to that, the physician’s preventive work based on the knowledge of embryogenesis processes and critical development periods. Key words: teratogenic action, medications, prenatal development, congenital malformation, newborns, children.(Pediatric Pharmacology. – 2010; 7(1:25-28

  5. How can nanobiotechnology oversight advance science and industry: examples from environmental, health, and safety studies of nanoparticles (nano-EHS)

    International Nuclear Information System (INIS)

    Wang Jing; Asbach, Christof; Fissan, Heinz; Hülser, Tim; Kuhlbusch, Thomas A. J.; Thompson, Drew; Pui, David Y. H.

    2011-01-01

    Nanotechnology has great potential to transform science and industry in the fields of energy, material, environment, and medicine. At the same time, more concerns are being raised about the occupational health and safety of nanomaterials in the workplace and the implications of nanotechnology on the environment and living systems. Studies on environmental, health, and safety (EHS) issues of nanomaterials have a strong influence on public acceptance of nanotechnology and, eventually, affect its sustainability. Oversight and regulation by government agencies and non-governmental organizations (NGOs) play significant roles in ensuring responsible and environmentally friendly development of nanotechnology. The EHS studies of nanomaterials can provide data and information to help the development of regulations and guidelines. We present research results on three aspects of EHS studies: physico-chemical characterization and measurement of nanomaterials; emission, exposure, and toxicity of nanomaterials; and control and abatement of nanomaterial releases using filtration technology. Measurement of nanoparticle agglomerates using a newly developed instrument, the Universal NanoParticle Analyzer (UNPA), is discussed. Exposure measurement results for silicon nanoparticles in a pilot scale production plant are presented, as well as exposure measurement and toxicity study of carbon nanotubes (CNTs). Filtration studies of nanoparticle agglomerates are also presented as an example of emission control methods.

  6. Management Oversight and Risk Tree (MORT): a new system safety program

    International Nuclear Information System (INIS)

    Clark, J.L.

    Experiences of Aerojet Nuclear Company (ANC), in the development and implementation of a system safety program for ANC and for the Energy Research and Development Administration (ERDA) are discussed. Aerojet Nuclear is the prime operating contractor for ERDA, formerly AEC, at the Idaho National Engineering Laboratory. The ERDA sponsored ''MORT'' system safety program is described along with the process whereby formal system safety methods are incorporated into a stable organization. Specifically, a discussion is given of initial development of MORT; pilot program trials conducted at ANC; implementation methodology; and reaction of the ANC organization. (auth)

  7. DEPARTMENT OF ENERGY: Views on Proposed Civil Penalties, Security Oversight, and External Safety Regulation Legislation

    National Research Council Canada - National Science Library

    Jones, Gary

    2000-01-01

    This report provides the General Accounting Office's views on three bills designed to improve worker and nuclear facility safety and health as well as to enhance security for the Department of Energy (DOE...

  8. DEPARTMENT OF ENERGY: Views on Proposed Civil Penalties, Security Oversight, and External Safety Regulation Legislation

    National Research Council Canada - National Science Library

    Jones, Gary

    2000-01-01

    .... 3383 would amend the Atomic Energy Act by eliminating the exemption that currently allows certain nonprofit contractors to avoid paying civil penalties if they violate DOE's nuclear safety rules...

  9. Romania - NPP PLiM Between Regulatory Requirement / Oversight and Operator Safety / Financial Interest

    International Nuclear Information System (INIS)

    Goicea, Lucian

    2012-01-01

    Cernavoda Unit 1 PLiM started in the first third of its design life, to develop as regulatory requirements of the components of standards and programmes and to benefit by earlier implementation of the measures for achieving maximum operating life. CNCAN regulatory present approach on the utility PLiM combines the regulatory requirements on management system, ageing management provisions of periodic safety review, detailed technical requirements of ageing programmes and different techniques focusing only on safety issues. (author)

  10. Regulatory oversight report 2008 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2009-04-01

    This annual report issued by the Swiss Federal Nuclear Inspectorate (ENSI) reports on the work carried out by the Inspectorate in 2008. This report reviews the regulatory activities in the four Swiss nuclear power stations and in four further nuclear installations in various Swiss research facilities. It deals with topics such as operational details, technologies in use, radiation protection, radioactive wastes, emergency dispositions, personnel and provides an assessment of operations from the safety point of view. Also, the transportation of nuclear materials - both nuclear fuels and nuclear wastes - is reported on. General topics discussed include probabilistic safety analyses and accident management, earthquake damage analysis and agreements on nuclear safety. The underground disposal of highly-radioactive nuclear wastes and work done in the rock laboratories are discussed, as are proposals for additional nuclear power stations

  11. The oversight of nuclear safety - a mission in the service of the public

    International Nuclear Information System (INIS)

    Melin, J.

    2001-01-01

    A country introducing nuclear power in their energy strategy has a life long obligation to the public. The obligation is not a question of energy production. It is an obligation to maintain safety during the phase of construction, energy production as well as for the disposal of waste and spent fuel. One part of this obligation and responsibility to the public is a matter of trust. A responsible government should never accept that fear related to Nuclear Power is a lack in trust. Trust can never be regulated or forced upon the public. Trust is something you have to earn. We must remember that we as Nuclear Safety Regulators have a mission in the service of the public. We are by the public seen as guarantor for the safety of Nuclear Installations in our countries. Our aim must be that the public is trusting that our work will lead to a safe operation of Nuclear Installations. (author)

  12. Regulatory oversight report 2007 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2008-04-01

    This annual report issued by the Swiss Federal Nuclear Inspectorate (HSK) reports on the work carried out by the Inspectorate in 2007. This report reviews the regulatory activities in the four Swiss nuclear power stations and in four further nuclear installations in various Swiss research facilities. It deals with topics such as operational details, technologies in use, radiation protection, radioactive wastes, emergency dispositions and personnel and provides an assessment of operations from the point of view of safety. Also, the transportation of nuclear materials - both nuclear fuels and nuclear wastes - is reported on. General topics discussed include probabilistic safety analyses and accident management. Finally, the disposal of nuclear wastes and work done in the rock laboratories in Switzerland is commented on

  13. Drug safety and the impact of drug warnings

    DEFF Research Database (Denmark)

    Hostenkamp, G.; Fischer, K. E.; Borch-Johnsen, K.

    2016-01-01

    Objective To analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies. Methods Insurance claims data on anti-diabetic drug prescriptions in primary care in Germany...

  14. Regulatory oversight report 2012 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2013-04-01

    The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants, the interim storage facilities based at each plant, the Central Interim Storage Facility (ZWILAG) and the nuclear facilities at the Paul Scherrer Institute (PSI), at the Federal Institute of Technology in Lausanne (EPFL) and at the University of Basel. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in the relevant facilities. It ensures that the facilities comply with the regulations and operate as required by law. Its regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and the preparations for a deep geological repository for nuclear waste. ENSI maintains its own emergency organisation. It formulates and updates its own guidelines which stipulate the criteria for evaluating the current activities and future plans of the operators of nuclear facilities. ENSI produces regular reports on its regulatory activities and nuclear safety in Swiss nuclear facilities. It fulfils its statutory obligation to provide the public with information on particular events and findings in nuclear facilities. In 2012, the five nuclear power plants in Switzerland were all operated safely. 34 events were reported; on the international INES scale of 0 to 7, ENSI rated 33 events as Level 0 and 1 as Level 1. ENSI evaluates the safety of each nuclear power plant as part of a systematic safety evaluation taking account of both reportable events and other findings, in particular the results of more than 400 inspections conducted by ENSI during 2012. ZWILAG consists of several interim storage halls, a conditioning plant and an incineration/melting plant. At the end of 2012, the cask storage hall contained 40 transport/storage casks

  15. Regulatory oversight report 2016 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2017-06-01

    ENSI, the Swiss Federal Nuclear Safety Inspectorate, assesses and monitors safety in the Swiss nuclear facilities. These include the five nuclear power plants: Beznau Units 1 and 2 (KKB1 and KKB2), Muehleberg (KKM), Goesgen (KKG) and Leibstadt (KKL), the interim storage facilities based at each plant, the Central Interim Storage Facility (Zwilag) in Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI), the University of Basel (UniB) and the Federal Institute of Technology in Lausanne (EPFL). Using a combination of inspections, regulatory meetings, checks, analyses and the reporting of the operators of individual facilities, ENSI obtains the required overview of nuclear safety in these facilities. It ensures that they operate as required by law. ENSI's regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and preparations for a deep geological repository for radioactive waste. ENSI maintains its own emergency organisation, which is an integral part of the national emergency structure that would be activated in the event of a serious incident at a nuclear facility in Switzerland. ENSI reports periodically on its supervisory activities. It informs the public about special events and findings in the nuclear installations. All five nuclear power plants in Switzerland operated safely during the past year. Nuclear safety at all plants in operation was rated as good or satisfactory. In 2016, there were 31 reportable events at the nuclear power plants. 30 events were rated Level 0 (event of no or low safety significance) on the International Nuclear and Radiological Event Scale (INES) and one was rated Level 1 (anomaly) at KKL. Zwilag consists of several interim storage buildings, a conditioning plant and a plasma plant (incineration/melting plant). At the end of 2016, the cask storage hall contained 56 transport/storage casks with spent fuel assemblies and vitrified residue

  16. Predictive toxicology in drug safety

    National Research Council Canada - National Science Library

    Xu, Jinghai J; Urban, Laszlo

    2011-01-01

    .... It provides information on the present knowledge of drug side effects and their mitigation strategy during drug discovery, gives guidance for risk assessment, and promotes evidence-based toxicology...

  17. Regulatory oversight report 2015 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2016-06-01

    The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants (Beznau Units 1 and 2, Muehleberg, Goesgen and Leibstadt), the interim storage facilities based at each plant, the Central Interim Storage Facility (Zwilag) at Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI), the University of Basel and the Federal Institute of Technology in Lausanne (EPFL), as well as the transport of radioactive materials and the preparatory work for a deep geological repository for nuclear waste. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in these facilities. ENSI maintains its own emergency organization. It provides the public with information on particular events and findings in nuclear facilities. ENSI publishes an annual Radiological Protection Report and a Research and Experience Report. Chapters 1 to 4 of this Surveillance Report deal with operational experience, systems technology, radiological protection and management of the 5 Swiss nuclear power plants. Chapter 5 deals with Zwilag. Chapters 6 and 7 are devoted to the nuclear facilities at PSI and the research reactor at EPFL as well as the decommissioned University of Basel’s research reactor. Chapter 8 covers the transport of radioactive materials. The subject of Chapter 9 is the deep geological storage of radioactive waste including work within the framework of the Sectoral Plan. Finally, Chapter 10 deals with generic issues relevant to all facilities such as probabilistic safety analyses. In 2015, all five nuclear power plants in Switzerland were safely operated and ENSI concluded that each had adhered to its approved operating conditions. There were 34 reportable events at the nuclear power plants; 32 events were rated at Level 0 on

  18. Regulatory oversight report 2010 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2011-06-01

    Acting as the regulatory body of the Swiss Confederation, the Swiss Federal Nuclear Safety Inspectorate, ENSI, assesses and monitors nuclear facilities in Switzerland. This includes the five nuclear power plants (NPPs), the plant-based interim storage facilities, the Central Interim Storage Facility (ZWILAG) at Wuerenlingen, the nuclear facilities at the Paul Scherrer Institute (PSI), the two universities of Basel and Lausanne, the transport of radioactive materials from and to nuclear facilities and the preparation for a deep geologic repository for radioactive waste. Using inspections, surveillance meetings, reviews and analyses as well as reports from plant licensees, ENSI obtains the required overview of the safety of the nuclear facilities. It maintains its own emergency organisation, which is an integral part of the national emergency structure. The legislative framework at the basis of the activity of ENSI specifies the criteria by which it evaluates the activities and plans of the operators of nuclear facilities. ENSI provides the public with information on particular events and observations relating to nuclear facilities. The five nuclear power plants in Switzerland (Beznau Units 1 und 2, Muehleberg, Goesgen and Leibstadt) were all operated safely in 2010. Last year, there were 39 notifiable events in Switzerland: 4 events affected both Beznau Units, 10 events the Goesgen NPP, 6 the Leibstadt NPP and 13 the Muehleberg NPP and 6 in other facilities. Based on the International Nuclear Event Scale (INES) of 0-7, ENSI rated 38 events as Level 0, and as INES Level 2 the event on 31 August 2010 during maintenance work at the Leibstadt NPP, where a diver was exposed to radiation in excess of the maximum annual exposure rate of 20 mSv. The ZWILAG at Wuerenlingen consists of several interim storage halls, a conditioning plant and the plasma plant (incineration/melting plant). At the end of 2010, the cask storage hall contained 34 transport/storage casks with spent

  19. Regulatory oversight report 2011 concerning nuclear safety in Swiss nuclear installations

    International Nuclear Information System (INIS)

    2012-06-01

    The Swiss Federal Nuclear Safety Inspectorate ENSI, acting as the regulatory body of the Swiss Confederation, assesses and monitors nuclear facilities in Switzerland. These include five nuclear power plants, the interim storage facilities based at each plant, the Central Interim Storage Facility (ZWILAG) at Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI) and the two universities of Basel and Lausanne. ENSI ensures that the facilities comply with regulations and operate according to the law. Its regulatory responsibilities also include the transport of radioactive materials to and from nuclear facilities and the preparations for a deep geologic repository for nuclear waste. It maintains its own emergency organisation, which is an integral part of a national emergency structure. Building on the legislative framework, ENSI also formulates and updates its own guidelines. It provides the public with information on particular events and findings in nuclear facilities. In 2011, all five nuclear power reactors in Switzerland (Beznau Units 1 and 2, Muehleberg, Goesgen and Leibstadt) were operated safely and ENSI concluded that they had complied with their approved operating conditions. There were 27 reportable events in the nuclear power plants in Switzerland: 7 at Beznau, 5 at Goesgen, 11 at Leibstadt und 4 at Muehleberg. On the international INES scale of 0 to 7, ENSI rated 26 events as Level 0. One event, at the Muehleberg nuclear power plant, was rated as INES Level 1. This related to a potential blockage of the emergency water intake system in the event of extreme flooding. The operator BKW shut down the Muehleberg plant ahead of the scheduled maintenance date and upgraded the system. ZWILAG consists of several interim storage halls, a conditioning plant and a plasma plant (incineration/melting plant). At the end of 2011, the cask storage hall contained 34 transport/storage casks with fuel assemblies and vitrified residue packages

  20. Drug Safety Crises Management in Pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Gloria Shalviri

    2018-05-01

    Full Text Available Background: Adverse drug events can cause serious consequences including death. A published report by Lazarou et al in 1998 showed that adverse drug events were the 4th to 6th leading cause of death in the United States. These events may lead to drug safety crises in some issues, which need to take crises management process for solving the problem and/or preventing similar events.Objectives: To evaluate nature of drug safety crises based on adverse events reported to Iranian Pharmacovigilance Center from 1999 through 2012. To mention success and failure outcomes of crises management process taken against detected crises.Methods: All adverse drug events received by Iranian Pharmacovigilance Center from 1999 through 2012 were evaluated for reports with fatal outcome. All alerting letters and manuscripts published by the Center during the same period were reviewed for detailed information on detected crises. World Health Organization definition was used for detecting drug safety crises.Results: Among 42036 registered cases in our database, 463 deaths were recorded. The most frequent suspected drug for adverse events with fatal outcome was ceftriaxone (100 cases. Ten different drug safety crises issues were detected during the study period and their successful or failure outcomes were evaluated. There were 112 issued alerting letters and 17 published manuscript during the same period which was monitored for detailed information.  Conclusion: It is necessary for national pharmacovigilance centers to have prepared programs for crises management. This could be useful for reducing drug related mortality.

  1. Drug safety evaluation of defibrotide.

    Science.gov (United States)

    Richardson, Paul G; Corbacioglu, Selim; Ho, Vincent Trien-Vinh; Kernan, Nancy A; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Hoyle, Margaret; Sardella, Marco; Giralt, Sergio; Holler, Ernst; Carreras, Enric; Niederwieser, Dietger; Soiffer, Robert

    2013-01-01

    Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

  2. Proceedings of the CSNI/IAEA workshop on maintaining oversight of licensee safety culture - methods and approaches. Held from 21 to 23 May 2007 in Chester, UK

    International Nuclear Information System (INIS)

    2008-01-01

    Weaknesses in safety culture have contributed to a number of high profile events in the nuclear and other high hazard sectors. The nuclear industry also faces challenges such as deregulation, out-sourcing, phase-out, upgrading and new builds which, if not properly planned and implemented, have the potential to make a negative impact on safety culture. These factors have fostered an increasing awareness of the need for licensees to develop a strong safety culture to support successful and sustainable nuclear safety performance. Regulatory bodies are taking a growing interest in this issue, and several are actively working to develop and implement approaches to maintaining oversight of licensee safety culture. However, these approaches are not yet well-established, and it was considered prudent to share experiences and developing methodologies in order to disseminate good practices and avoid potential pitfalls. An NEA/CSNI/IAEA workshop was therefore held in Chester, UK, in May 2007 in order to explore and discuss the approaches that different regulatory bodies are taking to maintain oversight of licensee safety culture. It was organised by the UK Nuclear Installations Inspectorate on behalf of the CSNI's Working Group on Human and Organisational Factors. This report sets out the findings of the Chester workshop. The workshop was attended by 50 representatives of nuclear regulatory bodies in 20 countries plus IAEA, WANO, EU and NEA. It included both specialists in safety culture and site/resident inspectors, whose attendance was facilitated by the CNRA's Working Group on Inspection Practices. The workshop comprised structured discussion sessions, in which a set of issues were explored by small discussion groups and then discussed in plenary, complemented by short presentations on national regulatory positions. The workshop revealed a broad consensus that nuclear regulators should have processes in place to maintain oversight of licensee safety culture. The approaches

  3. Safety and efficacy of drugs in pregnancy.

    Science.gov (United States)

    Knoppert, David

    2011-01-01

    Although most drugs are used to treat chronic or pregnancy-induced conditions during pregnancy and lactation, very few are studied in pregnant or breastfeeding women. The information we have on drugs taken during pregnancy and lactation is usually obtained after market approval through published case reports or case series and from pregnancy exposure or retrospective birth defect registries. Furthermore, generic drugs approved for use in this vulnerable population may be approved based on results from a male trial population. This disregards the changes that can occur during pregnancy which can affect the pharmacokinetics of drugs. In an effort to improve the information provided to prescribers, in 2008 the United States Food and Drug Administration proposed a change in product labelling where information from pregnancy exposure registries would be required. As of 2009, European Medicines Agency requires additional statements on use during pregnancy within drug labelling information. In Canada, it is anticipated that the efficacy and safety of drugs in pregnancy will be included under the Drug Safety and Effectiveness Network initiative, and that this will offer a unified approach for such assessments. Pregmedic, a non-profit organization for the advancement of safe and effective use of drugs in pregnancy, has presented a number of proposals and draft guidelines to Health Canada on the inclusion of pregnant women in pharmacokinetic studies and the establishment of registries for women who take drugs during pregnancy. Pregmedic advocates for ensuring that drugs indicated for women are studied in women.

  4. Information exchange - DOE oversight programs

    International Nuclear Information System (INIS)

    Tubbs, D.C.; Field, H.C.

    1988-01-01

    Oversight programs are conducted by the U.S. Department of Energy to review activities carried out by field and contractor organizations. Two of these oversight programs focus on safeguards and security and on safety and health activities. These two programs are independent, but share many common objectives and review techniques. The mutual potential benefit was recognized from an exchange of information on review techniques. The first step in this exchange was the participation by an Office of Security Evaluations (OSE) staff member with the Office of Nuclear Safety (ONS) during their planning, conduct and reporting of a Technical Safety Appraisal (TSA). This paper briefly describes the OSE and ONS programs. It also identifies and analyzes the similarities and differences of the two programs. The purpose of this paper is to provide perspectives on the approach taken, the techniques used and the differences between two oversight programs conducted by the Department of Energy

  5. Toxicophores: Investigations in drug safety

    International Nuclear Information System (INIS)

    Williams, Dominic P.

    2006-01-01

    Adverse drug reactions, such as hepatotoxicity, blood dyscrasias and hypersensitivity are a major obstacle for the use and the development of new medicines. Many forms of organ-directed toxicity can arise from the bioactivation of drugs to the so-called chemically reactive metabolites, which can modify tissue macromolecules. It is well established that the toxicities of model hepatotoxins, such as acetaminophen, furosemide, bromobenzene and methapyrilene can be correlated with the generation of chemically reactive metabolites, which can be detected by measurement of the irreversible binding of radiolabelled material to hepatic protein and/or the detection of stable phase II metabolites such as glutathione conjugates. The basic chemistry of the reaction of such metabolites with model nucleophiles is relatively well understood. A major challenge is to define how certain reactive intermediates may chemically modify critical proteins and how modification of specific amino acids may alter protein function which in turn may affect cell signalling, regulation, defence, function and viability. This in turn will determine whether or not bioactivation will result in a particular form of drug-induced injury. It is now clear that even relatively simple reactive intermediates can react in a discriminative manner with particular cellular proteins and even with specific amino acids within those proteins. Therefore, both non-covalent, as well as covalent bonds will be important determinants of the target protein for a particular reactive metabolite. Mammalian cells have evolved numerous defence systems against reactive intermediates. Sensitive redox proteins such as Nrf-2 recognise oxidative stress and electrophilic agents, through oxidation or covalent modification of thiol groups. Defence genes, such as epoxide hydrolase and glutamate cysteine ligase then become up-regulated in an attempt to reduce the oxidising environment. However, whether the liver receives mild or severe

  6. Investigation and consideration on the framework of oversight-based safety regulation. U.S. NRC 'Risk-Informed, Performance-Based' Regulation

    International Nuclear Information System (INIS)

    Saji, Gen

    2001-01-01

    Regulation on safety, environment and health in Japan has before today been intended to correspond with an accident at forms of reinforcement of national standards and monitoring, if any. However, as it was thought that such regulation reinforcement was afraid to bring some social rigidity, and to weaken independent responsibility, as a result, because of anxiety of losing peoples' merits inversely, some fundamental directivity such as respect of self-responsibility principle' and 'necessary and least limit of regulation' were selected as a part of political innovation. On the other hand, at a background of wide improvements on various indexing values showing operation results of nuclear power stations in U.S.A., private independent effort on upgrading of safety is told to largely affect at beginning of INPO (Institute of Nuclear Power Operations), without regulation reinforcement of NRC side. This is a proof of concrete effect of transfer to oversight-based safety regulation. Here were introduced on nuclear safety in U.S.A. at a base of some references obtained on entering the 'MIT summer specialist program. Nuclear system safety', on focussing at new safety regulation of NRC and its effect and so on, and adding some considerations based on some knowledge thereafter. (G.K.)

  7. MORT User's Manual for use with the Management Oversight and Risk Tree analytical logic diagram. [Contains a list of System Safety Development Center publications

    Energy Technology Data Exchange (ETDEWEB)

    Knox, N.W.; Eicher, R.W.

    1992-02-01

    This report contains the User's Manual for MORT (Management Oversight and Risk Tree), a logic diagram in the form of a work sheet'' that illustrates a long series of interrelated questions. MORT is a comprehensive analytical procedure that provides a disciplined method for determining the causes and contributing factors of major accidents. Alternatively, it serves as a tool to evaluate the quality of an existing system. While similar in many respects to fault tree analysis, MORT is more generalized and presents over 1,500 specific elements of an ideal universal'' management program for optimizing environment, safety and health, and other programs. This User's Manual is intended to be used with the MORT diagram dated February 1992.

  8. Oversight Hearing on Drug Abuse Education Programs. Hearing before the Subcommittee on Elementary, Secondary, and Vocational Education of the Committee on Education and Labor. House of Representatives, 101st Congress, 2nd Session (Vancouver, Washington, September 6, 1990).

    Science.gov (United States)

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    The text of an oversight hearing on Drug Abuse Resistance Education (DARE) programs is presented in this document. Introductory statements by Representatives Jolene Unsoeld and Dale E. Kildee are presented. Testimony by these witnesses is included: (1) Roy Bondurant, student, and Roy "Skip" Bondurant, parent, Tenino, Washington; (2) Paul…

  9. Drug safety: Pregnancy rating classifications and controversies.

    Science.gov (United States)

    Wilmer, Erin; Chai, Sandy; Kroumpouzos, George

    2016-01-01

    This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Tolerability and safety of antifungal drugs

    Directory of Open Access Journals (Sweden)

    Francesco Scaglione

    2013-08-01

    Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

  11. Oversight and Influencing of Licensee Leadership and Management for Safety, Including Safety Culture - Regulatory Approaches and Methods. Proceedings of an NEA/IAEA Workshop, Chester, United Kingdom, 26-28 September 2011

    International Nuclear Information System (INIS)

    2012-01-01

    Both regulators and the nuclear industry recognise the need for licensees to develop a strong, positive safety culture to support successful and sustainable nuclear safety performance. A number of reports have been issued by the IAEA and the NEA on the role of the regulator in relation to oversight of safety culture (References 1 to 5). There has been less clarity on how this should be achieved - in particular, with regard to strategies and practical approaches for maintaining oversight of, and influencing, those facets of licensee leadership and management which have a profound influence on safety culture. In recognition of this, the CSNI Working Group on Human and Organisational Factors (WGHOF), together with the CNRA Working Group on Inspection Practices (WGIP) and the IAEA, organised a workshop in Chester, United Kingdom, in May 2007 to provide a forum for gathering and sharing international experience, including good practices and learning points. The results of the workshop are reported in Reference 6. Workshop participants agreed that, in view of the rapidly developing approaches in this area, it would be sensible to hold a further workshop ('Chester 2') in 3-5 years in order to discuss how regulatory approaches have moved on and to share lessons learned from their application. In 2010, the WGIP hosted a workshop which included regulatory approaches for the assessment of licensee safety culture as a discussion topic. The outputs of the workshop included a list of commendable practices for monitoring and evaluating licensee safety culture (Reference 7). The 'Chester 2' workshop took place in September 2011. This report sets out the findings of the workshop, organised by the UK Office for Nuclear Regulation (ONR) on behalf of the CSNI/WGHOF and the IAEA. The workshop was attended by over 40 representatives of nuclear regulatory bodies and licensees from 15 countries plus IAEA and NEA. The workshop featured keynote papers on learning from major events, and from

  12. Regulatory oversight report 2012 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2012 zur nuklearen Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-04-15

    The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants, the interim storage facilities based at each plant, the Central Interim Storage Facility (ZWILAG) and the nuclear facilities at the Paul Scherrer Institute (PSI), at the Federal Institute of Technology in Lausanne (EPFL) and at the University of Basel. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in the relevant facilities. It ensures that the facilities comply with the regulations and operate as required by law. Its regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and the preparations for a deep geological repository for nuclear waste. ENSI maintains its own emergency organisation. It formulates and updates its own guidelines which stipulate the criteria for evaluating the current activities and future plans of the operators of nuclear facilities. ENSI produces regular reports on its regulatory activities and nuclear safety in Swiss nuclear facilities. It fulfils its statutory obligation to provide the public with information on particular events and findings in nuclear facilities. In 2012, the five nuclear power plants in Switzerland were all operated safely. 34 events were reported; on the international INES scale of 0 to 7, ENSI rated 33 events as Level 0 and 1 as Level 1. ENSI evaluates the safety of each nuclear power plant as part of a systematic safety evaluation taking account of both reportable events and other findings, in particular the results of more than 400 inspections conducted by ENSI during 2012. ZWILAG consists of several interim storage halls, a conditioning plant and an incineration/melting plant. At the end of 2012, the cask storage hall contained 40 transport/storage casks

  13. 76 FR 59142 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-09-23

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the...., [[Page 59143

  14. Regulatory oversight report 2016 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2016 zur nuklearen Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2017-06-15

    ENSI, the Swiss Federal Nuclear Safety Inspectorate, assesses and monitors safety in the Swiss nuclear facilities. These include the five nuclear power plants: Beznau Units 1 and 2 (KKB1 and KKB2), Muehleberg (KKM), Goesgen (KKG) and Leibstadt (KKL), the interim storage facilities based at each plant, the Central Interim Storage Facility (Zwilag) in Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI), the University of Basel (UniB) and the Federal Institute of Technology in Lausanne (EPFL). Using a combination of inspections, regulatory meetings, checks, analyses and the reporting of the operators of individual facilities, ENSI obtains the required overview of nuclear safety in these facilities. It ensures that they operate as required by law. ENSI's regulatory responsibilities also include the transport of radioactive materials from and to nuclear facilities and preparations for a deep geological repository for radioactive waste. ENSI maintains its own emergency organisation, which is an integral part of the national emergency structure that would be activated in the event of a serious incident at a nuclear facility in Switzerland. ENSI reports periodically on its supervisory activities. It informs the public about special events and findings in the nuclear installations. All five nuclear power plants in Switzerland operated safely during the past year. Nuclear safety at all plants in operation was rated as good or satisfactory. In 2016, there were 31 reportable events at the nuclear power plants. 30 events were rated Level 0 (event of no or low safety significance) on the International Nuclear and Radiological Event Scale (INES) and one was rated Level 1 (anomaly) at KKL. Zwilag consists of several interim storage buildings, a conditioning plant and a plasma plant (incineration/melting plant). At the end of 2016, the cask storage hall contained 56 transport/storage casks with spent fuel assemblies and vitrified residue

  15. A Study on Drug Safety Monitoring Program in India

    Science.gov (United States)

    Ahmad, A.; Patel, Isha; Sanyal, Sudeepa; Balkrishnan, R.; Mohanta, G. P.

    2014-01-01

    Pharmacovigilance is useful in assuring the safety of medicines and protecting the consumers from their harmful effects. A number of single drugs as well as fixed dose combinations have been banned from manufacturing, marketing and distribution in India. An important issue about the availability of banned drugs over the counter in India is that sufficient adverse drug reactions data about these drugs have not been reported. The most common categories of drugs withdrawn in the last decade were nonsteroidal antiinflammatory drugs (28%), antidiabetics (14.28%), antiobesity (14.28%), antihistamines (14.28%), gastroprokinetic drugs (7.14%), breast cancer and infertility drugs (7.14%), irritable bowel syndrome and constipation drugs (7.14%) and antibiotics (7.14%). Drug withdrawals from market were made mainly due to safety issues involving cardiovascular events (57.14%) and liver damage (14.28%). Majority of drugs have been banned since 3-5 years in other countries but are still available for sale in India. The present study compares the drug safety monitoring systems in the developed countries such as the USA and UK and provides implications for developing a system that can ensure the safety and efficacy of drugs in India. Absence of a gold standard for a drug safety surveillance system, variations in culture and clinical practice across countries makes it difficult for India to completely adopt another country's practices. There should be a multidisciplinary approach towards drug safety that should be implemented throughout the entire duration spanning from drug discovery to usage by consumers. PMID:25425751

  16. Regulatory oversight report 2015 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2015 zur nuklearen Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    The Swiss Federal Nuclear Safety Inspectorate (ENSI) assesses and monitors nuclear facilities in Switzerland. These include the five nuclear power plants (Beznau Units 1 and 2, Muehleberg, Goesgen and Leibstadt), the interim storage facilities based at each plant, the Central Interim Storage Facility (Zwilag) at Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI), the University of Basel and the Federal Institute of Technology in Lausanne (EPFL), as well as the transport of radioactive materials and the preparatory work for a deep geological repository for nuclear waste. Using a combination of inspections, regulatory meetings, examinations and analyses together with reports from the licensees of individual facilities, ENSI obtains the required overview of nuclear safety in these facilities. ENSI maintains its own emergency organization. It provides the public with information on particular events and findings in nuclear facilities. ENSI publishes an annual Radiological Protection Report and a Research and Experience Report. Chapters 1 to 4 of this Surveillance Report deal with operational experience, systems technology, radiological protection and management of the 5 Swiss nuclear power plants. Chapter 5 deals with Zwilag. Chapters 6 and 7 are devoted to the nuclear facilities at PSI and the research reactor at EPFL as well as the decommissioned University of Basel’s research reactor. Chapter 8 covers the transport of radioactive materials. The subject of Chapter 9 is the deep geological storage of radioactive waste including work within the framework of the Sectoral Plan. Finally, Chapter 10 deals with generic issues relevant to all facilities such as probabilistic safety analyses. In 2015, all five nuclear power plants in Switzerland were safely operated and ENSI concluded that each had adhered to its approved operating conditions. There were 34 reportable events at the nuclear power plants; 32 events were rated at Level 0 on

  17. Regulatory oversight report 2010 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2010 zur nuklearen Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2011-06-15

    Acting as the regulatory body of the Swiss Confederation, the Swiss Federal Nuclear Safety Inspectorate, ENSI, assesses and monitors nuclear facilities in Switzerland. This includes the five nuclear power plants (NPPs), the plant-based interim storage facilities, the Central Interim Storage Facility (ZWILAG) at Wuerenlingen, the nuclear facilities at the Paul Scherrer Institute (PSI), the two universities of Basel and Lausanne, the transport of radioactive materials from and to nuclear facilities and the preparation for a deep geologic repository for radioactive waste. Using inspections, surveillance meetings, reviews and analyses as well as reports from plant licensees, ENSI obtains the required overview of the safety of the nuclear facilities. It maintains its own emergency organisation, which is an integral part of the national emergency structure. The legislative framework at the basis of the activity of ENSI specifies the criteria by which it evaluates the activities and plans of the operators of nuclear facilities. ENSI provides the public with information on particular events and observations relating to nuclear facilities. The five nuclear power plants in Switzerland (Beznau Units 1 und 2, Muehleberg, Goesgen and Leibstadt) were all operated safely in 2010. Last year, there were 39 notifiable events in Switzerland: 4 events affected both Beznau Units, 10 events the Goesgen NPP, 6 the Leibstadt NPP and 13 the Muehleberg NPP and 6 in other facilities. Based on the International Nuclear Event Scale (INES) of 0-7, ENSI rated 38 events as Level 0, and as INES Level 2 the event on 31 August 2010 during maintenance work at the Leibstadt NPP, where a diver was exposed to radiation in excess of the maximum annual exposure rate of 20 mSv. The ZWILAG at Wuerenlingen consists of several interim storage halls, a conditioning plant and the plasma plant (incineration/melting plant). At the end of 2010, the cask storage hall contained 34 transport/storage casks with spent

  18. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

    Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

  19. Regulatory oversight report 2011 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2011 zur nuklearen Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-06-15

    The Swiss Federal Nuclear Safety Inspectorate ENSI, acting as the regulatory body of the Swiss Confederation, assesses and monitors nuclear facilities in Switzerland. These include five nuclear power plants, the interim storage facilities based at each plant, the Central Interim Storage Facility (ZWILAG) at Wuerenlingen together with the nuclear facilities at the Paul Scherrer Institute (PSI) and the two universities of Basel and Lausanne. ENSI ensures that the facilities comply with regulations and operate according to the law. Its regulatory responsibilities also include the transport of radioactive materials to and from nuclear facilities and the preparations for a deep geologic repository for nuclear waste. It maintains its own emergency organisation, which is an integral part of a national emergency structure. Building on the legislative framework, ENSI also formulates and updates its own guidelines. It provides the public with information on particular events and findings in nuclear facilities. In 2011, all five nuclear power reactors in Switzerland (Beznau Units 1 and 2, Muehleberg, Goesgen and Leibstadt) were operated safely and ENSI concluded that they had complied with their approved operating conditions. There were 27 reportable events in the nuclear power plants in Switzerland: 7 at Beznau, 5 at Goesgen, 11 at Leibstadt und 4 at Muehleberg. On the international INES scale of 0 to 7, ENSI rated 26 events as Level 0. One event, at the Muehleberg nuclear power plant, was rated as INES Level 1. This related to a potential blockage of the emergency water intake system in the event of extreme flooding. The operator BKW shut down the Muehleberg plant ahead of the scheduled maintenance date and upgraded the system. ZWILAG consists of several interim storage halls, a conditioning plant and a plasma plant (incineration/melting plant). At the end of 2011, the cask storage hall contained 34 transport/storage casks with fuel assemblies and vitrified residue packages

  20. Designing oversight for nanomedicine research in human subjects: systematic analysis of exceptional oversight for emerging technologies

    International Nuclear Information System (INIS)

    Wolf, Susan M.; Jones, Cortney M.

    2011-01-01

    The basic procedures and rules for oversight of U.S. human subjects research have been in place since 1981. Certain types of human subjects research, however, have provoked creation of additional mechanisms and rules beyond the Department of Health and Human Services (DHHS) Common Rule and Food and Drug Administration (FDA) equivalent. Now another emerging domain of human subjects research—nanomedicine—is prompting calls for extra oversight. However, in 30 years of overseeing research on human beings, we have yet to specify what makes a domain of scientific research warrant extra oversight. This failure to systematically evaluate the need for extra measures, the type of extra measures appropriate for different challenges, and the usefulness of those measures hampers efforts to respond appropriately to emerging science such as nanomedicine. This article evaluates the history of extra oversight, extracting lessons for oversight of nanomedicine research in human beings. We argue that a confluence of factors supports the need for extra oversight, including heightened uncertainty regarding risks, fast-evolving science yielding complex and increasingly active materials, likelihood of research on vulnerable participants including cancer patients, and potential risks to others beyond the research participant. We suggest the essential elements of the extra oversight needed.

  1. Designing oversight for nanomedicine research in human subjects: systematic analysis of exceptional oversight for emerging technologies

    Science.gov (United States)

    Wolf, Susan M.; Jones, Cortney M.

    2011-04-01

    The basic procedures and rules for oversight of U.S. human subjects research have been in place since 1981. Certain types of human subjects research, however, have provoked creation of additional mechanisms and rules beyond the Department of Health & Human Services (DHHS) Common Rule and Food and Drug Administration (FDA) equivalent. Now another emerging domain of human subjects research—nanomedicine—is prompting calls for extra oversight. However, in 30 years of overseeing research on human beings, we have yet to specify what makes a domain of scientific research warrant extra oversight. This failure to systematically evaluate the need for extra measures, the type of extra measures appropriate for different challenges, and the usefulness of those measures hampers efforts to respond appropriately to emerging science such as nanomedicine. This article evaluates the history of extra oversight, extracting lessons for oversight of nanomedicine research in human beings. We argue that a confluence of factors supports the need for extra oversight, including heightened uncertainty regarding risks, fast-evolving science yielding complex and increasingly active materials, likelihood of research on vulnerable participants including cancer patients, and potential risks to others beyond the research participant. We suggest the essential elements of the extra oversight needed.

  2. Advancing Drug Safety Through Prospective Pharmacovigilance.

    Science.gov (United States)

    Pitts, Peter J; Le Louet, Hervé

    2018-01-01

    Much has changed in a relatively short period of time. There is a raging debate over the level of evidence expected to first introduce a treatment to patients based on smaller, more adaptive data sets. Some argue for less data followed by postapproval follow-up, others for more adaptive clinical trial designs and end-point modification driven by patient-focused drug development and use of real-world evidence. The transition in both the review and postmarketing regulatory framework is happening in front of our eyes in real time. To improve the ability of patients to receive high-quality, safe, effective, and timely care, better information via pharmacovigilance must be a priority as the world's many regulatory systems build the capacity to harness electronic health information to improve health, care quality, and safety. Globally, the widely variable ability of nations to build reliable regulatory systems (from precise review to robust pharmacovigilance) is a dangerous source of health care inequality. Developing validated tools and techniques for "predictive pharmacovigilance" will assist all health systems in better understanding the risks and benefits of the medicines they regulate by understanding what should be happening once a new medicine moves from risk-benefit regulatory efficacy to real-world risk-effectiveness. This will be of particular utility for smaller regulatory agencies with fewer resources. By comparing preapproval predictive pharmacovigilance data, developing regulatory authorities will be able to better understand the potential gap between what was predicted and what was actually measured (via more traditional pharmacovigilance methodologies). Predictive pharmacovigilance recognizes the value of understanding the imperfect reporting of real-world clinical use and that the absence of reporting is, in itself, an important postmarketing signal.

  3. Drug safety: withdrawn medications are only part of the picture.

    Science.gov (United States)

    Rawson, Nigel S B

    2016-02-13

    In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different. To more fully understand drug safety management and regulatory agency actions, withdrawals should be evaluated within the setting and timeframe in which the medications are approved, which requires information about approvals and safety warnings. Studies are needed that provide a more comprehensive current picture of the identification and evaluation of drug safety risks as well as how regulatory agencies deal with them. Please see related research article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0553-2.

  4. Alcohol and prescription drug safety in older adults

    Directory of Open Access Journals (Sweden)

    Zanjani F

    2013-02-01

    Full Text Available Faika Zanjani,1,2 Aasha I Hoogland,1 Brian G Downer11Department of Gerontology, 2Building Interdisciplinary Research Careers in Women's Health University of Kentucky, Lexington, KY, USABackground: The objectives of this study were to investigate older adults' knowledge of prescription drug safety and interactions with alcohol, and to identify pharmacists' willingness to disseminate prescription drug safety information to older adults.Methods: The convenience sample consisted of 48 older adults aged 54–89 years who were recruited from a local pharmacy and who completed surveys addressing their alcohol consumption, understanding of alcohol and prescription drug interactions, and willingness to change habits regarding alcohol consumption and prescription drugs. To address pharmacist willingness, 90 pharmacists from local pharmacies volunteered and answered questions regarding their willingness to convey prescription drug safety information to older adults.Results: Older adults reported low knowledge of alcohol and prescription drug safety, with women tending to be slightly more knowledgeable. More importantly, those who drank in the previous few months were less willing to talk to family and friends about how alcohol can have harmful interactions with prescription drugs, or to be an advocate for safe alcohol and prescription drug use than those who had not had a drink recently. Pharmacists reported that they were willing to convey prescription drug safety information to older adults via a variety of formats, including displaying or distributing a flyer, and directly administering a brief intervention.Conclusion: In this study, older adults were found to have inadequate knowledge of prescription drug safety and interactions with alcohol, but pharmacists who regularly come in contact with older adults indicated that they were ready and willing to talk to older adults about prescription drug safety. Future research should focus on interventions

  5. Nuclear Oversight Function at Krsko NPP

    International Nuclear Information System (INIS)

    Bozin, B.; Kavsek, D.

    2010-01-01

    The nuclear oversight function is used at the Krsko NPP constructively to strengthen safety and improve performance. Nuclear safety is kept under constant examination through a variety of monitoring techniques and activities, some of which provide an independent review. The nuclear oversight function at the Krsko NPP is accomplished by Quality and Nuclear Oversight Division (SKV). SKV has completed its mission through a combination of compliance, performance and effectiveness-based assessments. The performance-based assessment is an assessment using various techniques (observations, interviews, walk-downs, document reviews) to assure compliance with standards and regulations, obtain insight into performance, performance trends and also to identify opportunities to improve effectiveness of implementation. Generally, the performance-based approach to oversight function is based on some essential elements. The most important one which is developed and implemented is an oversight program (procedure). The program focuses on techniques, activities and objectives commensurate with their significance to plant operational safety. These techniques and activities are: self-assessments, assessments, audits, performance indicators, monitoring of corrective action program (CAP), industry independent reviews (such as IAEA's OSART and WANO Peer Review), industry benchmarking etc. Graded approach is an inherent product of a performance based program and ranking process. It is important not only to focus on the highest ranked performance based attributes but to lead to effective utilization of an oversight program. The attributes selected for oversight need to be based on plant specific experience, current industry operating experience, supplier's performance and quality issues. Collaboration within the industry and effective utility oversight of processes and design activities are essential for achieving good plant performance. So the oversight program must integrate relevant

  6. Dynamic oversight: implementation gaps and challenges

    Science.gov (United States)

    Howard, John

    2011-04-01

    Nanotechnology is touted as a transformative technology in that it is predicted to improve many aspects of human life. There are hundreds of products in the market that utilize nanostructures in their design, such as composite materials made out of carbon or metal oxides. Potential risks to consumers, to the environment, and to workers from the most common passive nanomaterial—carbon nanotubes—are emerging through scientific research. Newer more active nanostructures—such as cancer therapies and targeted drug systems—are also increasing in use and are raising similar risk concerns. Governing the risks to workers is the subject of this commentary. The Occupational Safety and Health Act of 1970 grants the Occupational Safety and Health Administration the legal authority to set occupational health standards to insure that no worker suffers material impairment of health from work. However, setting a standard to protect workers from nanotechnology risks may occur some time in the future because the risks to workers have not been well characterized scientifically. Alternative risk governances—such as dynamic oversight through stakeholder partnerships, "soft law" approaches, and national adoption of international consensus standards—are evaluated in this article.

  7. Dynamic oversight: implementation gaps and challenges

    International Nuclear Information System (INIS)

    Howard, John

    2011-01-01

    Nanotechnology is touted as a transformative technology in that it is predicted to improve many aspects of human life. There are hundreds of products in the market that utilize nanostructures in their design, such as composite materials made out of carbon or metal oxides. Potential risks to consumers, to the environment, and to workers from the most common passive nanomaterial—carbon nanotubes—are emerging through scientific research. Newer more active nanostructures—such as cancer therapies and targeted drug systems—are also increasing in use and are raising similar risk concerns. Governing the risks to workers is the subject of this commentary. The Occupational Safety and Health Act of 1970 grants the Occupational Safety and Health Administration the legal authority to set occupational health standards to insure that no worker suffers material impairment of health from work. However, setting a standard to protect workers from nanotechnology risks may occur some time in the future because the risks to workers have not been well characterized scientifically. Alternative risk governances—such as dynamic oversight through stakeholder partnerships, “soft law” approaches, and national adoption of international consensus standards—are evaluated in this article.

  8. 77 FR 2606 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2012-01-18

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2012-0004] Pipeline Safety: Random Drug Testing Rate AGENCY: Pipeline and Hazardous Materials... pipelines and operators of liquefied natural gas facilities must select and test a percentage of covered...

  9. 75 FR 9018 - Pipeline Safety: Random Drug Testing Rate

    Science.gov (United States)

    2010-02-26

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID PHMSA-2010-0034] Pipeline Safety: Random Drug Testing Rate AGENCY: Pipeline and Hazardous Materials... pipelines and operators of liquefied natural gas facilities must select and test a percentage of covered...

  10. Determining animal drug combinations based on efficacy and safety.

    Science.gov (United States)

    Kratzer, D D; Geng, S

    1986-08-01

    A procedure for deriving drug combinations for animal health is used to derive an optimal combination of 200 mg of novobiocin and 650,000 IU of penicillin for nonlactating cow mastitis treatment. The procedure starts with an estimated second order polynomial response surface equation. That surface is translated into a probability surface with contours called isoprobs. The isoprobs show drug amounts that have equal probability to produce maximal efficacy. Safety factors are incorporated into the probability surface via a noncentrality parameter that causes the isoprobs to expand as safety decreases, resulting in lower amounts of drug being used.

  11. Adverse drug reaction and concepts of drug safety in Ayurveda: An overview

    Science.gov (United States)

    Ajanal, Manjunath; Nayak, Shradda; Prasad, Buduru Sreenivasa; Kadam, Avinash

    2013-01-01

    Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb–herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analysed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance. PMID:24563588

  12. Drug safety in pregnancy - monitoring congenital anomalies

    NARCIS (Netherlands)

    Morgan, Margery; De Jong-Van Den Berg, Lolkje T. W.; Jordan, Sue

    Aim This paper outlines research into the causes of congenital anomalies, and introduces a pan-European study. The potential roles of nurses and midwives in this area are illustrated by a case report. Background Since the thalidomide disaster, use of drugs in pregnancy has been carefully monitored

  13. 78 FR 20327 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-04-04

    ... Management Advisory Committee; Amendment of Notice AGENCY: Food and Drug Administration, HHS. ACTION: Notice... of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management... Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee...

  14. Safety learning from drugs of the same class

    DEFF Research Database (Denmark)

    Stefansdottir, G; Knol, M J; Arnardottir, A H

    2012-01-01

    This study was aimed at assessing the extent of safety learning from data pertaining to other drugs of the same class. We studied drug classes for which the first and second drugs were centrally registered in the European Union from 1995 to 2008. We assessed whether adverse drug reactions (ADRs......) associated with one of the drugs also appeared in the Summary of Product Characteristics (SPC) of the other drug, either initially or during the postmarketing phase. We identified 977 ADRs from 19 drug pairs, of which 393 ADRs (40.2%) were listed in the SPCs of both drugs of a pair. Of these 393 that were...... present in both SPCs of a drug pair, 241 (61.3%) were present when the drug entered the market and 152 (30.7%) appeared in the postmarketing phase. The mention of ADRs in the SPCs of both same-class drugs in the postmarketing phase was associated with type A ADRs, marketing in the same regulator country...

  15. Oversight and management of a cell therapy clinical trial network: experience and lessons learned.

    Science.gov (United States)

    Moyé, Lemuel A; Sayre, Shelly L; Westbrook, Lynette; Jorgenson, Beth C; Handberg, Eileen; Anwaruddin, Saif; Wagner, Kristi A; Skarlatos, Sonia I

    2011-09-01

    The Cardiovascular Cell Therapy Research Network (CCTRN), sponsored by the National Heart, Lung, and Blood Institute (NHLBI), was established to develop, coordinate, and conduct multiple collaborative protocols testing the effects of cell therapy on cardiovascular diseases. The Network was born into a difficult political and ethical climate created by the recent removal of a dozen drugs from the US formulary and the temporary halting of 27 gene therapy trials due to safety concerns. This article describes the Network's challenges as it initiated three protocols in a polarized cultural atmosphere at a time when oversight bodies were positioning themselves for the tightest vigilance of promising new therapies. Effective strategies involving ongoing education, open communication, and relationship building with the oversight community are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Trust in the pharmaceutical sector : Analysis of drug safety controversies by means of drug life cycles

    NARCIS (Netherlands)

    Hernández, J.F.

    2015-01-01

    Before obtaining a marketing approval, the efficacy and safety profile of drugs is studied in specific populations and under well-controlled circumstances. After marketing approval, the drug is made available and used in ‘real world conditions’, which are known to deviate from the trial setting.

  17. Drug research methodology. Volume 2, The identification of drugs of interest in highway safety

    Science.gov (United States)

    1980-03-01

    This report presents findings of a workshop on the identification of drugs that should be the focus of near-term highway safety research. Drugs of interest are those that have a potential to increase the likelihood of traffic crashes and their attend...

  18. Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse.

    Science.gov (United States)

    Swedberg, Michael D B

    2016-01-01

    Drug discrimination studies for assessment of psychoactive properties of drugs in safety pharmacology and drug abuse and drug dependence potential evaluation have traditionally been focused on testing novel compounds against standard drugs for which drug abuse has been documented, e.g. opioids, CNS stimulants, cannabinoids etc. (e.g. Swedberg & Giarola, 2015), and results are interpreted such that the extent to which the test drug causes discriminative effects similar to those of the standard training drug, the test drug would be further characterized as a potential drug of abuse. Regulatory guidance for preclinical assessment of abuse liability by the European Medicines Agency (EMA, 2006), the U.S. Food and Drug Administration (FDA, 2010), the International Conference of Harmonization (ICH, 2009), and the Japanese Ministry of Health Education and Welfare (MHLW, 1994) detail that compounds with central nervous system (CNS) activity, whether by design or not, need abuse and dependence liability assessment. Therefore, drugs with peripheral targets and a potential to enter the CNS, as parent or metabolite, are also within scope (see Swedberg, 2013, for a recent review and strategy). Compounds with novel mechanisms of action present a special challenge due to unknown abuse potential, and should be carefully assessed against defined risk criteria. Apart from compounds sharing mechanisms of action with known drugs of abuse, compounds intended for indications currently treated with drugs with potential for abuse and or dependence are also within scope, regardless of mechanism of action. Examples of such compounds are analgesics, anxiolytics, cognition enhancers, appetite control drugs, sleep control drugs and drugs for psychiatric indications. Recent results (Swedberg et al., 2014; Swedberg & Raboisson, 2014; Swedberg, 2015) on the metabotropic glutamate receptor type 5 (mGluR5) antagonists demonstrate that compounds causing hallucinatory effects in humans did not exhibit

  19. 78 FR 16271 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-03-14

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably...

  20. 76 FR 40735 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-07-11

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... East, Adelphi, MD. The conference center telephone number is: 301 985-7300. Contact Person: Kalyani...

  1. 78 FR 2677 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-01-14

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the... before February 7, 2013. Time allotted for each presentation may be limited. If the number of registrants...

  2. 76 FR 59143 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2011-09-23

    ...] Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk... Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee. General Function of the..., Adelphi, MD. The conference center telephone number is 301-985-7300. Contact Person: Kalyani Bhatt, Center...

  3. 75 FR 10490 - Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-03-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Drugs Advisory Committee and the Drug Safety and Risk Management Advisory... Drug Safety and Risk Management Advisory Committee. General Function of the Committees: To provide...

  4. Exploring Machine Learning Techniques Using Patient Interactions in Online Health Forums to Classify Drug Safety

    Science.gov (United States)

    Chee, Brant Wah Kwong

    2011-01-01

    This dissertation explores the use of personal health messages collected from online message forums to predict drug safety using natural language processing and machine learning techniques. Drug safety is defined as any drug with an active safety alert from the US Food and Drug Administration (FDA). It is believed that this is the first…

  5. 77 FR 65000 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-24

    ...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... Use (ETASU) before CDER's Drug Safety and Risk Management Advisory Committee (DSaRM). The Agency plans...

  6. 78 FR 30929 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-05-23

    ...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide... (REMS) with elements to assure safe use (ETASU) before its Drug Safety and Risk Management Advisory...

  7. 77 FR 75176 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-12-19

    ...] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug... being rescheduled due to the postponement of the October 29-30, 2012, Drug Safety and Risk Management... Committee: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

  8. Effects of Prescription Drugs During Pregnancy. Hearing Before the Subcommittee on Investigations and Oversight of the Committee on Science and Technology, U.S. House of Representatives, Ninety-Seventh Congress, First Session (July, 30, 1981).

    Science.gov (United States)

    Congress of the U.S., Washington, DC. House Committee on Science and Technology.

    This hearing focuses on scientific and policy deficiencies in the area of drug-induced birth defects. Witnesses charge that (1) the Food and Drug Administration (FDA) does not require the kinds of clinical studies that are necessary to actually determine the safety of drugs used in pregnancy, (2) the FDA does nothing to enable women to find out…

  9. Pooling, meta-analysis, and the evaluation of drug safety

    Directory of Open Access Journals (Sweden)

    Leizorovicz Alain

    2002-03-01

    Full Text Available Abstract Background The "integrated safety report" of the drug registration files submitted to health authorities usually summarizes the rates of adverse events observed for a new drug, placebo or active control drugs by pooling the safety data across the trials. Pooling consists of adding the numbers of events observed in a given treatment group across the trials and dividing the results by the total number of patients included in this group. Because it considers treatment groups rather than studies, pooling ignores validity of the comparisons and is subject to a particular kind of bias, termed "Simpson's paradox." In contrast, meta-analysis and other stratified analyses are less susceptible to bias. Methods We use a hypothetical, but not atypical, application to demonstrate that the results of a meta-analysis can differ greatly from those obtained by pooling the same data. In our hypothetical model, a new drug is compared to 1 a placebo in 4 relatively small trials in patients at high risk for a certain adverse event and 2 an active reference drug in 2 larger trials of patients at low risk for this event. Results Using meta-analysis, the relative risk of experiencing the adverse event with the new drug was 1.78 (95% confidence interval [1.02; 3.12] compared to placebo and 2.20 [0.76; 6.32] compared to active control. By pooling the data, the results were, respectively, 1.00 [0.59; 1.70] and 5.20 [2.07; 13.08]. Conclusions Because these findings could mislead health authorities and doctors, regulatory agencies should require meta-analyses or stratified analyses of safety data in drug registration files.

  10. Review of the OSHA framework for oversight of occupational environments.

    Science.gov (United States)

    Choi, Jae-Young; Ramachandran, Gurumurthy

    2009-01-01

    The OSHA system for oversight of chemicals in the workplace was evaluated to derive lessons for oversight of nanotechnology. Criteria relating to the development, attributes, evolution, and outcomes of the system were used for evaluation that was based upon quantitative expert elicitation and historical literature analysis. The oversight system had inadequate resources in terms of finances, expertise, and personnel, and insufficient incentive for compliance. The system showed a lack of flexibility in novel situations. There were minimal requirements on companies for data on health and safety of their products. These factors have a strong influence on public confidence and health and safety. The oversight system also scored low on attributes such as public input, transparency, empirical basis, conflict of interest, and informed consent. The experts in our sample tend to believe that the current oversight system for chemicals in the workplace is neither adequate nor effective. It is very likely that the performance of the OSHA oversight system for nanomaterials will be equally inadequate.

  11. 78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

    Science.gov (United States)

    2013-06-19

    ... inspections, and drive safety and quality throughout the supply chain. Implementation of these authorities... authorities granted to FDA under Title VII and their importance in ensuring drug safety, effectiveness, and.... FDA-2013-N-0683, FDA-2013-N-0684, and FDA-2013-N-0685] Food and Drug Administration Safety and...

  12. Global patient safety and antiretroviral drug-drug interactions in the resource-limited setting.

    Science.gov (United States)

    Seden, Kay; Khoo, Saye H; Back, David; Byakika-Kibwika, Pauline; Lamorde, Mohammed; Ryan, Mairin; Merry, Concepta

    2013-01-01

    Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource-limited settings suggest that medication error and antiretroviral drug-drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug-drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug-drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies.

  13. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Jinsoo Lee

    2016-01-01

    Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

  14. Evaluating oversight systems for emerging technologies: a case study of genetically engineered organisms.

    Science.gov (United States)

    Kuzma, Jennifer; Najmaie, Pouya; Larson, Joel

    2009-01-01

    The U.S. oversight system for genetically engineered organisms (GEOs) was evaluated to develop hypotheses and derive lessons for oversight of other emerging technologies, such as nanotechnology. Evaluation was based upon quantitative expert elicitation, semi-standardized interviews, and historical literature analysis. Through an interdisciplinary policy analysis approach, blending legal, ethical, risk analysis, and policy sciences viewpoints, criteria were used to identify strengths and weaknesses of GEOs oversight and explore correlations among its attributes and outcomes. From the three sources of data, hypotheses and broader conclusions for oversight were developed. Our analysis suggests several lessons for oversight of emerging technologies: the importance of reducing complexity and uncertainty in oversight for minimizing financial burdens on small product developers; consolidating multi-agency jurisdictions to avoid gaps and redundancies in safety reviews; consumer benefits for advancing acceptance of GEO products; rigorous and independent pre- and post-market assessment for environmental safety; early public input and transparency for ensuring public confidence; and the positive role of public input in system development, informed consent, capacity, compliance, incentives, and data requirements and stringency in promoting health and environmental safety outcomes, as well as the equitable distribution of health impacts. Our integrated approach is instructive for more comprehensive analyses of oversight systems, developing hypotheses for how features of oversight systems affect outcomes, and formulating policy options for oversight of future technological products, especially nanotechnology products.

  15. Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

    Directory of Open Access Journals (Sweden)

    José Cabrita

    2017-04-01

    Full Text Available Observational epidemiological studies have been used in the medicines context for more than 40 years, contributing to characterize drug use patterns and safety, efficacy and effectiveness profiles. Its use has been increased in recognition of the clinical trials limitations to assess the therapeutic and iatrogenic potential of the medicines after its commercialization. The evolution of the regulatory framework for pharmacovigilance, requiring post-marketing studies, post-authorization safety studies (PASS and the post-authorization efficacy studies (PAES to approve certain drugs, reinforced the importance of observational pharmacoepidemiology for the characterization of the medicines safety and effectiveness profiles. Pharmacoepidemiological research can be carried out from field studies designed to obtain the necessary information or in databases with health records of population samples that already contain the information. This 2nd option is more efficient and more and more frequent. Although, observational research from field studies continues to have its space, the increasing availability of databases allowed a new development to observational pharmacoepidemiology. Indeed, access to automated records databases with up-to-date information on medical prescriptions and global health care to representative population samples with long follow-up periods is a valuable tool for the study of drug use patterns and therapeutic and iatrogenic potential in routine clinical practice. In this context, observational pharmacoepidemiology reinforces its role as a scientific area particularly suitable for evaluating the safety and the effectiveness of the medicines in the “real world”, making a relevant contribution to overcome the gap in translating the evidence from the clinical trials for clinical practice.

  16. 75 FR 23782 - Drug Safety and Risk Management Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-05-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug...: Drug Safety and Risk Management Advisory Committee. General Function of the Committee: To provide...

  17. Regulatory Oversight Program, July 1, 1993 - March 3, 1997. Volume 2: Appendices

    International Nuclear Information System (INIS)

    1997-01-01

    On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition

  18. Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 2: Appendices

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition.

  19. Analyzing research trends on drug safety using topic modeling.

    Science.gov (United States)

    Zou, Chen

    2018-04-06

    Published drug safety data has evolved in the past decade due to scientific and technological advances in the relevant research fields. Considering that a vast amount of scientific literature has been published in this area, it is not easy to identify the key information. Topic modeling has emerged as a powerful tool to extract meaningful information from a large volume of unstructured texts. Areas covered: We analyzed the titles and abstracts of 4347 articles in four journals dedicated to drug safety from 2007 to 2016. We applied Latent Dirichlet allocation (LDA) model to extract 50 main topics, and conducted trend analysis to explore the temporal popularity of these topics over years. Expert Opinion/Commentary: We found that 'benefit-risk assessment and communication', 'diabetes' and 'biologic therapy for autoimmune diseases' are the top 3 most published topics. The topics relevant to the use of electronic health records/observational data for safety surveillance are becoming increasingly popular over time. Meanwhile, there is a slight decrease in research on signal detection based on spontaneous reporting, although spontaneous reporting still plays an important role in benefit-risk assessment. The topics related to medical conditions and treatment showed highly dynamic patterns over time.

  20. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    Science.gov (United States)

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  1. Safety of diabetes drugs in patients with heart failure.

    Science.gov (United States)

    Carrasco-Sánchez, F J; Ostos-Ruiz, A I; Soto-Martín, M

    2018-03-01

    Heart failure (HF) and diabetes mellitus are 2 clinical conditions that often coexist, particularly in patients older than 65 years. Diabetes mellitus promotes the development of HF and confers a poorer prognosis. Hypoglycaemic agents (either by their mechanism of action, hypoglycaemic action or adverse effects) can be potentially dangerous for patients with HF. In this study, we performed a review of the available evidence on the safety of diabetes drugs in HF, focused on the main observational and experimental studies. Recent studies on cardiovascular safety have evaluated, although as a secondary objective, the impact of new hypoglycaemic agents on HF, helping us understand the neutrality, risks and potential benefits of these agents. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  2. 75 FR 39954 - Oversight of Laboratory Developed Tests; Public Meeting; Change of Meeting Location

    Science.gov (United States)

    2010-07-13

    ...] Oversight of Laboratory Developed Tests; Public Meeting; Change of Meeting Location AGENCY: Food and Drug... location for the upcoming public meeting entitled ``Oversight of Laboratory Developed Tests.'' A new... the public meeting, FDA is announcing in this notice a new location for the public meeting. II. New...

  3. Patient Drug Safety Reporting: Diabetes Patients' Perceptions of Drug Safety and How to Improve Reporting of Adverse Events and Product Complaints.

    Science.gov (United States)

    Patel, Puja; Spears, David; Eriksen, Betina Østergaard; Lollike, Karsten; Sacco, Michael

    2018-03-01

    Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices. We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study. Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%). Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

  4. Regulatory oversight report 2008 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2008 ueber die nukleare Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-04-15

    This annual report issued by the Swiss Federal Nuclear Inspectorate (ENSI) reports on the work carried out by the Inspectorate in 2008. This report reviews the regulatory activities in the four Swiss nuclear power stations and in four further nuclear installations in various Swiss research facilities. It deals with topics such as operational details, technologies in use, radiation protection, radioactive wastes, emergency dispositions, personnel and provides an assessment of operations from the safety point of view. Also, the transportation of nuclear materials - both nuclear fuels and nuclear wastes - is reported on. General topics discussed include probabilistic safety analyses and accident management, earthquake damage analysis and agreements on nuclear safety. The underground disposal of highly-radioactive nuclear wastes and work done in the rock laboratories are discussed, as are proposals for additional nuclear power stations.

  5. Drug research methodology. Volume 5, Experimentation in drugs and highway safety : the study of drug effects on skills related to driving

    Science.gov (United States)

    1980-06-01

    This report presents the findings of a workshop on experimental research in the area of drugs and highway safety. Complementing studies of drug use in different driving populations, experimentation here refers to studies performed under controlled co...

  6. Drug research methodology. Volume 4, Epidemiology in drugs and highway safety : the study of drug use among drivers and its role in traffic crashes

    Science.gov (United States)

    1980-06-01

    This report presents the findings of a workshop on epidemiology in drugs and highway safety. A cross-disciplinary panel of experts (1) identified methodological issues and constraints present in research to define the nature and magnitude of the drug...

  7. Improving regulatory oversight of maintenance programs

    International Nuclear Information System (INIS)

    Cook, S.

    2008-01-01

    Safe nuclear power plant operation requires that risks due to failure or unavailability of Structures, Systems and Components (SSCs) be minimized. Implementation of an effective maintenance program is a key means for achieving this goal. In its regulatory framework, the important relationship between maintenance and safety is acknowledged by the CNSC. A high level maintenance program requirement is included in the Class I Facilities Regulations. In addition, the operating licence contains a condition based on the principle that the design function and performance of SSCs needs to remain consistent with the plant's design and analysis documents. Nuclear power plant licensees have the primary responsibility for safe operation of their facilities and consequently for implementation of a successful maintenance program. The oversight role of the Canadian Nuclear Safety Commission (CNSC) is to ensure that the licensee carries out that responsibility. The challenge for the CNSC is how to do this consistently and efficiently. Three opportunities for improvement to regulatory maintenance oversight are being pursued. These are related to the regulatory framework, compliance verification inspection activities and monitoring of self-reporting. The regulatory framework has been improved by clarifying expectations through the issuance of S-210 'Maintenance Programs for Nuclear Power Plants'. Inspection activities have been improved by introducing new maintenance inspections into the baseline program. Monitoring is being improved by making better use of self-reported and industry produced maintenance related performance indicators. As with any type of program change, the challenge is to ensure the consistent and optimal application of regulatory activities and resources. This paper is a summary of the CNSC's approach to improving its maintenance oversight strategy. (author)

  8. Regulatory oversight report 2007 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2007 ueber die nukleare Sicherheit in den schweizerischen Kernanlagen

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-04-15

    This annual report issued by the Swiss Federal Nuclear Inspectorate (HSK) reports on the work carried out by the Inspectorate in 2007. This report reviews the regulatory activities in the four Swiss nuclear power stations and in four further nuclear installations in various Swiss research facilities. It deals with topics such as operational details, technologies in use, radiation protection, radioactive wastes, emergency dispositions and personnel and provides an assessment of operations from the point of view of safety. Also, the transportation of nuclear materials - both nuclear fuels and nuclear wastes - is reported on. General topics discussed include probabilistic safety analyses and accident management. Finally, the disposal of nuclear wastes and work done in the rock laboratories in Switzerland is commented on.

  9. Challenges in ethics, safety, best practices, and oversight regarding HIT vendors, their customers, and patients: a report of an AMIA special task force

    Science.gov (United States)

    Berner, Eta S; Dente, Mark A; Kaplan, Bonnie; Koppel, Ross; Rucker, Donald; Sands, Daniel Z; Winkelstein, Peter

    2010-01-01

    The current commercial health information technology (HIT) arena encompasses a number of competing firms that provide electronic health applications to hospitals, clinical practices, and other healthcare-related entities. Such applications collect, store, and analyze patient information. Some vendors incorporate contract language whereby purchasers of HIT systems, such as hospitals and clinics, must indemnify vendors for malpractice or personal injury claims, even if those events are not caused or fostered by the purchasers. Some vendors require contract clauses that force HIT system purchasers to adopt vendor-defined policies that prevent the disclosure of errors, bugs, design flaws, and other HIT-software-related hazards. To address this issue, the AMIA Board of Directors appointed a Task Force to provide an analysis and insights. Task Force findings and recommendations include: patient safety should trump all other values; corporate concerns about liability and intellectual property ownership may be valid but should not over-ride all other considerations; transparency and a commitment to patient safety should govern vendor contracts; institutions are duty-bound to provide ethics education to purchasers and users, and should commit publicly to standards of corporate conduct; and vendors, system purchasers, and users should encourage and assist in each others' efforts to adopt best practices. Finally, the HIT community should re-examine whether and how regulation of electronic health applications could foster improved care, public health, and patient safety. PMID:21075789

  10. Challenges in ethics, safety, best practices, and oversight regarding HIT vendors, their customers, and patients: a report of an AMIA special task force.

    Science.gov (United States)

    Goodman, Kenneth W; Berner, Eta S; Dente, Mark A; Kaplan, Bonnie; Koppel, Ross; Rucker, Donald; Sands, Daniel Z; Winkelstein, Peter

    2011-01-01

    The current commercial health information technology (HIT) arena encompasses a number of competing firms that provide electronic health applications to hospitals, clinical practices, and other healthcare-related entities. Such applications collect, store, and analyze patient information. Some vendors incorporate contract language whereby purchasers of HIT systems, such as hospitals and clinics, must indemnify vendors for malpractice or personal injury claims, even if those events are not caused or fostered by the purchasers. Some vendors require contract clauses that force HIT system purchasers to adopt vendor-defined policies that prevent the disclosure of errors, bugs, design flaws, and other HIT-software-related hazards. To address this issue, the AMIA Board of Directors appointed a Task Force to provide an analysis and insights. Task Force findings and recommendations include: patient safety should trump all other values; corporate concerns about liability and intellectual property ownership may be valid but should not over-ride all other considerations; transparency and a commitment to patient safety should govern vendor contracts; institutions are duty-bound to provide ethics education to purchasers and users, and should commit publicly to standards of corporate conduct; and vendors, system purchasers, and users should encourage and assist in each others' efforts to adopt best practices. Finally, the HIT community should re-examine whether and how regulation of electronic health applications could foster improved care, public health, and patient safety.

  11. Epigenetics and cancer: implications for drug discovery and safety assessment

    International Nuclear Information System (INIS)

    Moggs, Jonathan G.; Goodman, Jay I.; Trosko, James E.; Roberts, Ruth A.

    2004-01-01

    It is necessary to determine whether chemicals or drugs have the potential to pose a threat to human health. Research conducted over the last two decades has led to the paradigm that chemicals can cause cancer either by damaging DNA or by altering cellular growth, probably via receptor-mediated changes in gene expression. However, recent evidence suggests that gene expression can be altered markedly via several diverse epigenetic mechanisms that can lead to permanent or reversible changes in cellular behavior. Key molecular events underlying these mechanisms include the alteration of DNA methylation and chromatin, and changes in the function of cell surface molecules. Thus, for example, DNA methyltransferase enzymes together with chromatin-associated proteins such as histone modifying enzymes and remodelling factors can modify the genetic code and contribute to the establishment and maintenance of altered epigenetic states. This is relevant to many types of toxicity including but not limited to cancer. In this paper, we describe the potential for interplay between genetic alteration and epigenetic changes in cell growth regulation and discuss the implications for drug discovery and safety assessment

  12. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

    Directory of Open Access Journals (Sweden)

    Roth SH

    2011-05-01

    Full Text Available Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.Keywords: NSAIDs, osteoarthritis, topical administration, synovial fluid, peptic ulcer, Helicobacter pylori

  13. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.

    Science.gov (United States)

    Roth, Sanford H

    2011-01-01

    Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.

  14. A primer of drug safety surveillance: an industry perspective. Part I: Information flow, new drug development, and federal regulations.

    Science.gov (United States)

    Allan, M C

    1992-01-01

    To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part I of this series provides a background for the discussion of drug safety by defining the basic terms and showing the flow of safety information through a pharmaceutical company. The customers for adverse drug event data are identified to provide a basis for providing quality service. The development of a drug product is briefly reviewed to show the evolution of safety data. Drug development and safety are defined by federal regulations. These regulations are developed by the FDA with information from pharmaceutical manufacturers. The intent of the regulations and the accompanying guidelines is described. An illustration from the news media is cited to show an alternative, positive approach to handling an adverse event report. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text and additional readings are presented in an appendix. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction ;of the components

  15. Regulatory aspects of oncology drug safety evaluation: Past practice, current issues, and the challenge of new drugs

    International Nuclear Information System (INIS)

    Rosenfeldt, Hans; Kropp, Timothy; Benson, Kimberly; Ricci, M. Stacey; McGuinn, W. David; Verbois, S. Leigh

    2010-01-01

    The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.

  16. [Post-marketing drug safety-risk management plan(RMP)].

    Science.gov (United States)

    Ezaki, Asami; Hori, Akiko

    2013-03-01

    The Guidance for Risk Management Plan(RMP)was released by the Ministry of Health, Labour and Welfare in April 2012. The RMP consists of safety specifications, pharmacovigilance plans and risk minimization action plans. In this paper, we outline post-marketing drug safety operations in PMDA and the RMP, with examples of some anticancer drugs.

  17. The role of the Australian Adverse Drug Reactions Advisory Committee (ADRAC) in monitoring drug safety

    International Nuclear Information System (INIS)

    Boyd, Ian W.

    2002-01-01

    The Australian adverse drug reaction reporting system is acknowledged as one of the best in the world. Despite its small population of less than 20 million people, Australia's current ADR reporting rate of over 12000 reports per year places it in the top few nations in terms of reports per capita. The ADRAC program has been in operation for over 30 years. Australia was a founding member of the WHO International Drug Monitoring Programme which commenced in 1968 and currently there are about 153000 reports in the ADRAC database. Reports from health professionals have uncovered a number of significant safety problems over the years. Of particular importance are flucloxacillin-induced hepatitis, amoxycillin/clavulanate-induced hepatitis, and the association of cystitis with tiaprofenic acid. The number and quality of the reports has allowed an understanding of the characteristics of the reactions and, using ADRAC reporters as a major source of cases, case-control studies have been completed which have identified risk factors. ADRAC's review of Australian reports has highlighted many important associations that have been disseminated through the Australian Adverse Drug Reactions Bulletin

  18. From Drug Safety to Drug Security: A Contemporary Shift in the Policing of Health.

    Science.gov (United States)

    Hornberger, Julia

    2018-01-29

    The counterfeiting of medication is increasingly seen as a major threat to health, especially in the light of both the everyday reliance on and a broadening of world-wide access to pharmaceuticals. Exaggerated or real, this threat has inaugurated, this article argues, a shift from a drug safety regime to a drug security regime that governs the flow of pharmaceuticals and brings together markets, police, and health actors in new ways. This entails a shift from soft disciplinary means aimed at incremental and continued inclusion of defaulters, to one of drastically sovereign measures of exclusion and banishment aimed at fake goods and the people associated with them, in the name of health. Through a multi-sited ethnographic study, this article shows how such new drug security efforts play themselves out especially in (South) Africa, highlighting a modus operandi of spectacular performativity and of working through suspicion and association rather than factuality, producing value less so for those in need of health than for a petty security industry itself. © 2018 by the American Anthropological Association.

  19. Brief introduction of USA new reactor oversight process and suggestions for our country

    International Nuclear Information System (INIS)

    Hao Xiaofeng; Chen Rui; Zhou Limin; Wang Xiuqing

    2002-01-01

    The NRC New Reactor Oversight Process focuses the nuclear safety supervision on the 3 areas: Reactor Safety, Radiation safety and Plant Security. Within the 3 areas, 7 cornerstones are detailed for the purpose. They are Initiating Events, Mitigating Systems, Barrier Integrity, Emergency Preparedness, Occupational Radiation Protection, Public Radiation Safety and Physical Protection. On cooperating with the inspections, the new process ensures a more effective, objective and timely evaluation of the safety level of the operating nuclear power plants. On considering the practices and the status in China nuclear safety supervision, the authors have to learn something from the NRC New Reactor Oversight Process. The authors must make an optimization on Chinese limited resources and put the emphasis on the issues with high risk in order to prevent the occurrence of the accidents. Properly inducing some ideas and methodology from the NRC New Reactor Oversight Process will benefit the development and perfection of the supervision mode of the NNSA

  20. Prescription for antibiotics at drug shops and strategies to improve quality of care and patient safety

    DEFF Research Database (Denmark)

    Mbonye, Anthony K; Buregyeya, Esther; Rutebemberwa, Elizeus

    2016-01-01

    OBJECTIVES: The main objective of this study was to assess practices of antibiotic prescription at registered drug shops with a focus on upper respiratory tract infections among children in order to provide data for policy discussions aimed at improving quality of care and patient safety......-line drug for treatment of pneumonia in children according to the guidelines. CONCLUSIONS: There is urgent need to regulate drug shop practices of prescribing and selling antibiotics, for the safety of patients seeking care at these outlets....

  1. 77 FR 10666 - Pipeline Safety: Post Accident Drug and Alcohol Testing

    Science.gov (United States)

    2012-02-23

    ... 199 [Docket No. PHMSA-2011-0335] Pipeline Safety: Post Accident Drug and Alcohol Testing AGENCY... operators of Liquefied Natural Gas (LNG) facilities to conduct post- accident drug and alcohol tests of..., operators must drug and alcohol test each covered employee whose performance either contributed to the...

  2. Probing cardiac repolarization reserve in drug safety assessment

    NARCIS (Netherlands)

    Nalos, L.

    2011-01-01

    Excessive prolongation of cardiac repolarization, manifested as QT prolongation on ECG, is common unwanted side effect of many drugs and drug candidates. Prolongation of QT interval may lead to life threatening cardiac arrhythmia – Torsade de Point (TdP). Number of drugs was withdrawn from the

  3. Online availability and safety of drugs in shortage: a descriptive study of internet vendor characteristics.

    Science.gov (United States)

    Liang, Bryan A; Mackey, Tim K

    2012-02-09

    Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. We performed a descriptive study of the prevalence of online marketing for shortage drugs-that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing.

  4. 76 FR 63929 - Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and...

    Science.gov (United States)

    2011-10-14

    ...] Joint Meeting of the Drug Safety and Risk Management Advisory Committee and the Dermatologic and... Administration (FDA). The meeting will be open to the public. Name of Committees: Drug Safety and Risk Management... Safe Use (ETASU) before its Drug Safety and Risk Management Advisory Committee (DSaRM). On December 1...

  5. 75 FR 17417 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-04-06

    ...] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory... Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee. This meeting was... Drug Safety and Risk Management Advisory Committee would be held on May 12, 2010. On page 10490, in the...

  6. Online Availability and Safety of Drugs in Shortage: A Descriptive Study of Internet Vendor Characteristics

    Science.gov (United States)

    Mackey, Tim K

    2012-01-01

    Background Unprecedented drug shortages announced by the US Food and Drug Administration (FDA) have severely affected therapeutic access, patient safety, and public health. With continued shortages, patients may seek drugs online. Objective To assess the prevalence of online marketing for current FDA shortage drugs and potential patient safety risks. Methods We performed a descriptive study of the prevalence of online marketing for shortage drugs—that is, offers for sale of each drug, including characteristics of online drug sellers and intermediary sites marketing these drugs. Results Of the 72 FDA shortage-listed drugs, 68 (94%) were offered for sale online. We found 291 offers for these drugs, the vast majority (n = 207, 71.1%) by online drug sellers selling direct to consumers. Intermediary sites included data aggregators (n = 22, 8%), forum links (n = 23, 8%), and personal page data links (n = 34, 12%), as well as Flickr social media links (n = 5, 2%), all advertising drugs without a prescription. Of the 91 online drug sellers identified, 31 (34%) had more than 1 shortage drug offered for sale, representing most (n = 148, 71%) of all online drug seller sales offers. The majority of these online drug sellers (n = 21, 68%) were on the National Association of Boards of Pharmacy (NABP) Not Recommended Sites list. Finally, for shortage drugs with an online drug seller (n = 58, 85%), 53 (91%) had at least one site on the Not Recommended list and 21 (36%) had only sites on the Not Recommended list. Conclusions FDA shortage drugs are widely marketed over the Internet. Suspect online drug sellers and intermediaries dominate these sales offers. As a critical risk management issue, patients, providers, and policymakers should be extremely cautious in procuring shortage drugs through Internet sourcing. PMID:22321731

  7. Advice on drug safety in pregnancy: are there differences between commonly used sources of information?

    Science.gov (United States)

    Frost Widnes, Sofia K; Schjøtt, Jan

    2008-01-01

    Safety regarding use in pregnancy is not established for many drugs. Inconsistencies between sources providing drug information can give rise to confusion with possible therapeutic consequences. Therefore, it is important to measure clinically important differences between drug information sources. The objective of this study was to compare two easily accessible Norwegian sources providing advice on drug safety in pregnancy - the product monographs in the Felleskatalog (FK), published by the pharmaceutical companies, and the five regional Drug Information Centres (DICs) in Norway - in addition to assessing the frequency of questions regarding drug safety in pregnancy made to the DICs according to the Anatomical Therapeutic Chemical (ATC) classification system. Advice on drug use in pregnancy provided by the DICs in 2003 and 2005 were compared with advice in the product monographs for the respective drugs in the FK. Comparison of advice was based on categorization to one of four categories: can be used, benefit-risk assessment, should not be used, or no available information. A total of 443 drug advice were categorized. Seven out of ten of drugs frequently enquired about, according to the ATC system, were drugs acting on the nervous system (group N). For 208 (47%) of the drugs, advice differed between the DICs and FK. Advice from the FK was significantly (p drugs that were newly introduced and those that had been on the market for a longer time, advice regarding use of drugs in the first trimester and advice regarding use of drugs in the second or third trimester, or between advice provided during 2003 and during 2005. The results of this study show considerable differences between two Norwegian sources providing advice on the use of drugs in pregnancy. Based on the knowledge that healthcare providers choose sources of information in a random manner, our results may be of clinical importance. We believe that the problem with heterogeneous drug information on this

  8. Enhancing food safety: the role of the Food and Drug Administration

    National Research Council Canada - National Science Library

    Wallace, Robert B; Oria, Maria

    2010-01-01

    .... Food and Drug Administration's abilities to discover potential threats to food safety and prevent outbreaks of foodborne illness are hampered by impediments to efficient use of its limited resources...

  9. National Institute for Occupational Safety and Health Oversight: OMB Involvement in VDT Study. Hearing before the Subcommittee on Health and Safety of the Committee on Education and Labor. House of Representatives, Ninety-Ninth Congress, Second Session (June 4, 1986).

    Science.gov (United States)

    Congress of the U.S., Washington, DC. House Committee on Education and Labor.

    This hearing addressed the issue of whether the delays in producing a proposed National Institute for Occupational and Safety Health (NIOSH) study on the possible health hazards associated with video display terminals (VDTs) are due to concerns about scientific methodology or unwarranted interference by the Office of Management and Budget (OMB).…

  10. Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients

    DEFF Research Database (Denmark)

    Kristensen, L E; Jakobsen, A K; Askling, J

    2015-01-01

    OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardio......OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular...

  11. Regulatory oversight report 2009 concerning nuclear safety in Swiss nuclear installations; Aufsichtsbericht 2009 zur nuklearen Sicherheit in den schweizerischen Kernanlagen/Rapport de surveillance 2009 sur la securite nucleaire dans les installations nucleaires en Suisse/Regulatory oversight report 2009 concerning nuclear safety in Swiss nuclear installations

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-04-15

    ENSI, the regulatory body of the Swiss Confederation, assesses and monitors the nuclear safety of nuclear facilities in Switzerland. These include the five nuclear power plants (NPPs), the plant-based interim storage facilities, the Central Interim Storage Facility (ZWILAG) at Wuerenlingen, as well as the nuclear facilities at the Paul Scherrer Institute (PSI) and the two universities of Basel and Lausanne (EPFL). Its regulatory obligations also include the transport of radioactive materials from and to nuclear facilities and the preparation of a deep geological repository for radioactive waste. ENSI maintains its own emergency organisation that would be activated in case of a serious incident at a nuclear facility in Switzerland. The legislative framework for ENSI's regulatory functions are the Nuclear Energy Act (KEG), the Nuclear Energy Ordinance (KEV), the Radiological Protection Act (StSG), the Radiological Protection Ordinance (StSV), as well as other ordinances and regulations related to reactor safety, the training of operating personnel, the organisation of the emergency response to increases in radioactivity, the transport of radioactive materials, and the deep geological repository. ENSI formulates and updates guidelines that stipulate the criteria by which it evaluates the activities and plans put forward by the operators of nuclear facilities. It regularly publishes reports and provides the public with information on events and findings at nuclear facilities. Chapters 1 to 4 of this Surveillance Report are devoted to the five Swiss NPPs. For each plant, the ENSI evaluation concludes with a safety ranking: high, good, satisfactory and unsatisfactory. Chapter 5 deals with ZWILAG for the processing and interim storage of radioactive waste from Swiss nuclear facilities. Chapters 6 and 7 deal with the nuclear facilities at PSI and with the research reactors at Basel and at EPFL. Chapter 8 deals with the transport of radioactive materials from and to

  12. Drug and alcohol crash risk : traffic safety facts : research note.

    Science.gov (United States)

    2015-02-01

    While the extent of use of alcohol by drivers and the risks posed by alcohol use have been well known for many decades, relatively little has been known about the use of other drugs by drivers and the associated risks. However, drug-impaired driving ...

  13. Legacy data sharing to improve drug safety assessment: the eTOX project

    DEFF Research Database (Denmark)

    Sanz, Ferran; Pognan, François; Steger-Hartmann, Thomas

    2017-01-01

    The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through...

  14. Safety, efficacy, and drug survival of biologics and biosimilars for moderate-to-severe plaque psoriasis

    DEFF Research Database (Denmark)

    Egeberg, A; Ottosen, M B; Gniadecki, R

    2018-01-01

    BACKGROUND: Real-life data on newer biologic and biosimilar agents for moderate-to-severe psoriasis are lacking. OBJECTIVES: To examine safety, efficacy, and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab, and ustekinumab) and compare origina...... the long-term safety of novel biologics for psoriasis. This article is protected by copyright. All rights reserved....

  15. The Influence of Safety, Efficacy, and Medical Condition Severity on Natural versus Synthetic Drug Preference.

    Science.gov (United States)

    Meier, Brian P; Lappas, Courtney M

    2016-11-01

    Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as safer than the synthetic drug, and as that difference increased, the odds of choosing the natural over synthetic drug increased. In studies 2 and 3, approximately 20% of participants selected the natural drug even when they were informed that it was less safe (study 2) or less effective (study 3) than the synthetic drug. Finally, in study 4, approximately 65% of participants chose a natural over synthetic drug regardless of the severity of a specific medical condition (mild v. severe hypertension), and this choice was predicted by perceived safety and efficacy differences. Overall, these data indicate that there is a bias for natural over synthetic drugs. This bias could have implications for drug choice and usage. © The Author(s) 2015.

  16. Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 3 contains copies of two reports that document the DOE/ORO regulatory oversight inspection and enforcement history for each gaseous diffusion plant site. Each report provides a formal mechanism by which DOE/ORO could communicate the inspection and enforcement history to NRC. The reports encompass the inspection activities that occurred during July 1, 1993 through March 2, 1997.

  17. Pancreatic Safety of Incretin-Based Drugs - FDA and EMA Assessment

    NARCIS (Netherlands)

    Egan, Amy G.; Blind, Eberhard; Dunder, Kristina; de Graeff, Pieter A.; Hummer, B. Timothy; Bourcier, Todd; Rosebraugh, Curtis

    2014-01-01

    After evaluating a safety signal regarding pancreatitis and pancreatic cancer in patients using incretin-based drugs, the Food and Drug Administration and the European Medicines Agency conclude that assertions of a causal association are inconsistent with the data. With approximately 25.8 million

  18. 78 FR 71036 - Pipeline Safety: Random Drug Testing Rate; Contractor Management Information System Reporting...

    Science.gov (United States)

    2013-11-27

    ... PHMSA-2013-0248] Pipeline Safety: Random Drug Testing Rate; Contractor Management Information System Reporting; and Obtaining Drug and Alcohol Management Information System Sign-In Information AGENCY: Pipeline... Management Information System (MIS) Data; and New Method for Operators to Obtain User Name and Password for...

  19. Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification

    NARCIS (Netherlands)

    O.U. Osokogu (Osemeke); C. Dodd (Caitlin); A.C. Pacurariu (Alexandra C.); F. Kaguelidou (Florentia); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

    2016-01-01

    textabstractIntroduction: Spontaneous reports of suspected adverse drug reactions (ADRs) can be analyzed to yield additional drug safety evidence for the pediatric population. Signal detection algorithms (SDAs) are required for these analyses; however, the performance of SDAs in the pediatric

  20. Assessment of pharmacovigilance approaches for monitoring the safety of antimalarial drugs in pregnancy

    NARCIS (Netherlands)

    Dellicour, S.O.M.C.

    2014-01-01

    Post-marketing surveillance of drugs used in pregnancy is challenging, especially in developing countries where resources for pharmacovigilance are rare. There is a need to establish simple but effective systems to monitor safety of drugs given during pregnancy in resource constrained countries.

  1. Drug safety alerts of pharmacovigilance programme of India: A scope for targeted spontaneous reporting in India

    Directory of Open Access Journals (Sweden)

    Prasad Thota

    2018-01-01

    Conclusion: In India, spontaneous reporting of ADRs existed since 1998 under passive surveillance method, but there is an urgent need to initiate TSR, which is a complementary method to spontaneous reporting on these drug safety alerts for further regulatory action by Central Drugs Standard Control Organization.

  2. Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication

    Directory of Open Access Journals (Sweden)

    Bander Balkhi

    2018-02-01

    Conclusions: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

  3. A primer of drug safety surveillance: an industry perspective. Part II: Product labeling and product knowledge.

    Science.gov (United States)

    Allan, M C

    1992-01-01

    To place the fundamentals of clinical drug safety surveillance in a conceptual framework that will facilitate understanding and application of adverse drug event data to protect the health of the public and support a market for pharmaceutical manufacturers' products. Part II of this series discusses specific issues regarding product labeling, such as developing the labeling, changing the labeling, and the legal as well as commercial ramifications of the contents of the labeling. An adverse event report scenario is further analyzed and suggestions are offered for maintaining the product labeling as an accurate reflection of the drug safety surveillance data. This article also emphasizes the necessity of product knowledge in adverse event database management. Both scientific and proprietary knowledge are required. Acquiring product knowledge is a part of the day-to-day activities of drug safety surveillance. A knowledge of the history of the product may forestall adverse publicity, as shown in the illustration. This review uses primary sources from the federal laws (regulations), commentaries, and summaries. Very complex topics are briefly summarized in the text. Secondary sources, ranging from newspaper articles to judicial summaries, illustrate the interpretation of adverse drug events and opportunities for drug safety surveillance intervention. The reference materials used were articles theoretically or practically applicable in the day-to-day practice of drug safety surveillance. The role of clinical drug safety surveillance in product monitoring and drug development is described. The process of drug safety surveillance is defined by the Food and Drug Administration regulations, product labeling, product knowledge, and database management. Database management is subdivided into the functions of receipt, retention, retrieval, and review of adverse event reports. Emphasis is placed on the dynamic interaction of the components of the process. Suggestions are offered

  4. Application of the Pareto principle to identify and address drug-therapy safety issues.

    Science.gov (United States)

    Müller, Fabian; Dormann, Harald; Pfistermeister, Barbara; Sonst, Anja; Patapovas, Andrius; Vogler, Renate; Hartmann, Nina; Plank-Kiegele, Bettina; Kirchner, Melanie; Bürkle, Thomas; Maas, Renke

    2014-06-01

    Adverse drug events (ADE) and medication errors (ME) are common causes of morbidity in patients presenting at emergency departments (ED). Recognition of ADE as being drug related and prevention of ME are key to enhancing pharmacotherapy safety in ED. We assessed the applicability of the Pareto principle (~80 % of effects result from 20 % of causes) to address locally relevant problems of drug therapy. In 752 cases consecutively admitted to the nontraumatic ED of a major regional hospital, ADE, ME, contributing drugs, preventability, and detection rates of ADE by ED staff were investigated. Symptoms, errors, and drugs were sorted by frequency in order to apply the Pareto principle. In total, 242 ADE were observed, and 148 (61.2 %) were assessed as preventable. ADE contributed to 110 inpatient hospitalizations. The ten most frequent symptoms were causally involved in 88 (80.0 %) inpatient hospitalizations. Only 45 (18.6 %) ADE were recognized as drug-related problems until discharge from the ED. A limited set of 33 drugs accounted for 184 (76.0 %) ADE; ME contributed to 57 ADE. Frequency-based listing of ADE, ME, and drugs involved allowed identification of the most relevant problems and development of easily to implement safety measures, such as wall and pocket charts. The Pareto principle provides a method for identifying the locally most relevant ADE, ME, and involved drugs. This permits subsequent development of interventions to increase patient safety in the ED admission process that best suit local needs.

  5. [Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital].

    Science.gov (United States)

    Bedouch, P; Baudrant, M; Detavernier, M; Rey, C; Brudieu, E; Foroni, L; Allenet, B; Calop, J

    2009-01-01

    Drug supply chain safety has become a priority for public health which implies a collective process. This process associates all health professionals including the pharmacist who plays a major role. The objective of this present paper is to describe the several approaches proven effective in the reduction of drug-related problem in hospital, illustrated by the Grenoble University Hospital experience. The pharmacist gets involved first in the general strategy of hospital drug supply chain, second by his direct implication in clinical activities. The general strategy of drug supply chain combines risk management, coordination of the Pharmacy and Therapeutics Committee, selection and purchase of drugs and organisation of drug supply chain. Computer management of drug supply chain is a major evolution. Nominative drug delivering has to be a prior objective and its implementation modalities have to be defined: centralized or decentralized in wards, manual or automated. Also, new technologies allow the automation of overall drug distribution from central pharmacy and the implementation of automated drug dispensing systems into wards. The development of centralised drug preparation allows a safe compounding of high risk drugs, like cytotoxic drugs. The pharmacist should develop his clinical activities with patients and other health care professionals in order to optimise clinical decisions (medication review, drug order analysis) and patients follow-up (therapeutic monitoring, patient education, discharge consultation).

  6. Oversight Institutions Within the United Nations

    DEFF Research Database (Denmark)

    Pontoppidan, Caroline Aggestam

    2015-01-01

    This article will give a description of the role of internal audit and governance functions within the United Nations system. The United Nations has, during the last 10 years, worked to establish effective oversight services. Oversight, governance and hereunder the internal audit function has been...

  7. 5 CFR 330.611 - Oversight.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Oversight. 330.611 Section 330.611 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS RECRUITMENT, SELECTION, AND... Employees § 330.611 Oversight. OPM provides advice and assistance to agencies in implementing their Career...

  8. 12 CFR 370.10 - Oversight.

    Science.gov (United States)

    2010-01-01

    ... LIQUIDITY GUARANTEE PROGRAM § 370.10 Oversight. (a) Participating entities are subject to the FDIC's oversight regarding compliance with the terms of the temporary liquidity guarantee program. (b) A..., for the duration of the temporary liquidity guarantee program, to be subject to the FDIC's authority...

  9. Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

    Science.gov (United States)

    Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

    2018-01-01

    Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

  10. Exploiting pluripotent stem cell technology for drug discovery, screening, safety, and toxicology assessments.

    Science.gov (United States)

    McGivern, Jered V; Ebert, Allison D

    2014-04-01

    In order for the pharmaceutical industry to maintain a constant flow of novel drugs and therapeutics into the clinic, compounds must be thoroughly validated for safety and efficacy in multiple biological and biochemical systems. Pluripotent stem cells, because of their ability to develop into any cell type in the body and recapitulate human disease, may be an important cellular system to add to the drug development repertoire. This review will discuss some of the benefits of using pluripotent stem cells for drug discovery and safety studies as well as some of the recent applications of stem cells in drug screening studies. We will also address some of the hurdles that need to be overcome in order to make stem cell-based approaches an efficient and effective tool in the quest to produce clinically successful drug compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

    Science.gov (United States)

    Banerjee, Tannista; Nayak, Arnab

    2017-01-01

    This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

  12. Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

    OpenAIRE

    Castleden, C M; Pickles, H

    1988-01-01

    1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age grou...

  13. Drug safety data mining with a tree-based scan statistic.

    Science.gov (United States)

    Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

    2013-05-01

    In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety

    OpenAIRE

    Roth, Sandford

    2011-01-01

    Sanford H RothArizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USAAbstract: Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less...

  15. Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Giovanni Sotgiu

    2015-03-01

    Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

  16. Safety and problems in using radioactive drugs in hospitals

    International Nuclear Information System (INIS)

    Arimizu, Noboru

    1975-01-01

    The safety and the control problem of non-closed RI (radiopharmaceuticals) of which use has rapidly been increased, were studied. At present, the hospitals with an independent clinic for the nuclear medicine are very limited and many doctors, nurses and safety controllers who are working in the clinic belong to other clinics. As for the diagnosis using RI examination, the dangers of the persons who are working with radioimmunoassay, especially using Au-antigen kit were studied. Furthermore, the problems concerning the reduction of exposure dose by the use of a short half-life RI, such as sup(99m)Tc and the dangers of external exposure on the persons who use the isotope were studied. In addition, the control of RI ward for RI therapy was discussed. The author considered the specialization and fixation of doctors, nurses and technicians are becoming of necessity with the advancement of RI therapy. In addition, the necessity of training nurses for the nuclear medicine was insisted on. (Tsukamoto, Y.)

  17. Safety and problems in using radioactive drugs in hospitals

    Energy Technology Data Exchange (ETDEWEB)

    Arimizu, N [National Inst. of Radiological Sciences, Chiba (Japan)

    1975-01-01

    The safety and the control problem of non-closed RI (radiopharmaceuticals) of which use has rapidly been increased, were studied. At present, the hospitals with an independent clinic for the nuclear medicine are very limited and many doctors, nurses and safety controllers who are working in the clinic belong to other clinics. As for the diagnosis using RI examination, the dangers of the persons who are working with radioimmunoassay, especially using Au-antigen kit were studied. Furthermore, the problems concerning the reduction of exposure dose by the use of a short half-life RI, such as sup(99m)Tc and the dangers of external exposure on the persons who use the isotope were studied. In addition, the control of RI ward for RI therapy was discussed. The author considered the specialization and fixation of doctors, nurses and technicians are becoming of necessity with the advancement of RI therapy. In addition, the necessity of training nurses for the nuclear medicine was insisted on.

  18. Safety risks with investigational drugs: Pharmacy practices and perceptions in the veterans affairs health system.

    Science.gov (United States)

    Cruz, Jennifer L; Brown, Jamie N

    2015-06-01

    Rigorous practices for safe dispensing of investigational drugs are not standardized. This investigation sought to identify error-prevention processes utilized in the provision of investigational drug services (IDS) and to characterize pharmacists' perceptions about safety risks posed by investigational drugs. An electronic questionnaire was distributed to an audience of IDS pharmacists within the Veteran Affairs Health System. Multiple facets were examined including demographics, perceptions of medication safety, and standard processes used to support investigational drug protocols. Twenty-one respondents (32.8% response rate) from the Northeast, Midwest, South, West, and Non-contiguous United States participated. The mean number of pharmacist full-time equivalents (FTEs) dedicated to the IDS was 0.77 per site with 0.2 technician FTEs. The mean number of active protocols was 22. Seventeen respondents (81%) indicated some level of concern for safety risks. Concerns related to the packaging of medications were expressed, most notably lack of product differentiation, expiration dating, barcodes, and choice of font size or color. Regarding medication safety practices, the majority of sites had specific procedures in place for storing and securing drug supply, temperature monitoring, and prescription labeling. Repackaging bulk items and proactive error-identification strategies were less common. Sixty-seven percent of respondents reported that an independent double check was not routinely performed. Medication safety concerns exist among pharmacists in an investigational drug service; however, a variety of measures have been employed to improve medication safety practices. Best practices for the safe dispensing of investigational medications should be developed in order to standardize these error-prevention strategies.

  19. Independent oversight review of the Department of Energy Quality Assurance Program for suspect/counterfeit parts. Revision 1

    International Nuclear Information System (INIS)

    1996-05-01

    To address the potential threat that suspect/counterfeit parts could pose to DOE workers and the public, the Office of the Deputy Assistant Secretary for Oversight initiated a number of activities beginning in mid-1995. Oversight placed increased emphasis on the field's quality assurance-suspect/counterfeit parts programs during safety management evaluations, in keeping with the Office of Environment, Safety and Health (EH) oversight responsibilities, which include oversight of the Department's quality assurance (QA) programs. In addition, Oversight reviewed relevant policy documents and occurrence reports to determine the nature and magnitude of the problem within the Department. The results of that review, contained in an Office of Oversight report, Independent Oversight Analysis of Suspect/Counterfeit Parts Within the Department of Energy (November 1995), indicate a lack of consistency and comprehensiveness in the Department's QA-suspect/counterfeit parts program. A detailed analysis of the causes and impacts of the problem was recommended. In response, this review was initiated to determine the effectiveness of the Department's QA program for suspect/counterfeit parts. This study goes beyond merely assessing and reporting the status of the program, however. It is the authors intention to highlight the complex issues associated with suspect/counterfeit parts in the Department today and to present approaches that DOE managers might consider to address these issues

  20. Independent oversight review of the Department of Energy Quality Assurance Program for suspect/counterfeit parts. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-05-01

    To address the potential threat that suspect/counterfeit parts could pose to DOE workers and the public, the Office of the Deputy Assistant Secretary for Oversight initiated a number of activities beginning in mid-1995. Oversight placed increased emphasis on the field`s quality assurance-suspect/counterfeit parts programs during safety management evaluations, in keeping with the Office of Environment, Safety and Health (EH) oversight responsibilities, which include oversight of the Department`s quality assurance (QA) programs. In addition, Oversight reviewed relevant policy documents and occurrence reports to determine the nature and magnitude of the problem within the Department. The results of that review, contained in an Office of Oversight report, Independent Oversight Analysis of Suspect/Counterfeit Parts Within the Department of Energy (November 1995), indicate a lack of consistency and comprehensiveness in the Department`s QA-suspect/counterfeit parts program. A detailed analysis of the causes and impacts of the problem was recommended. In response, this review was initiated to determine the effectiveness of the Department`s QA program for suspect/counterfeit parts. This study goes beyond merely assessing and reporting the status of the program, however. It is the authors intention to highlight the complex issues associated with suspect/counterfeit parts in the Department today and to present approaches that DOE managers might consider to address these issues.

  1. Integrated safety analysis of rolapitant with coadministered drugs from phase II/III trials

    DEFF Research Database (Denmark)

    Barbour, S; Smit, T.; Wang, X

    2017-01-01

    adverse events by use versus non-use of drug substrates of CYP2D6 or BCRP. Patients and methods: Patients were randomized to receive either 180 mg oral rolapitant or placebo approximately 1-2 hours before chemotherapy in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Data...... cytochrome P450 (CYP) 3A4, but it does inhibit CYP2D6 and breast cancer resistance protein (BCRP). To analyze potential drug-drug interactions between rolapitant and concomitant medications, this integrated safety analysis of four double-blind, randomized phase II or III studies of rolapitant examined...... for treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) during cycle 1 were pooled across the four studies and summarized in the overall population and by concomitant use/non-use of CYP2D6 or BCRP substrate drugs. Results: In the integrated safety population, 828...

  2. 13 CFR 120.1005 - Bureau of PCLP Oversight.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Bureau of PCLP Oversight. 120.1005 Section 120.1005 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Supervision § 120.1005 Bureau of PCLP Oversight. SBA's Bureau of PCLP Oversight within...

  3. 12 CFR 985.4 - Finance Board oversight.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Finance Board oversight. 985.4 Section 985.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD OFFICE OF FINANCE THE OFFICE OF FINANCE § 985.4 Finance Board oversight. (a) Oversight and enforcement actions. The Finance Board shall have the same regulatory oversight authority and enforcement powers...

  4. Preventing errors in administration of parenteral drugs: the results of a four-year national patient safety program.

    NARCIS (Netherlands)

    Blok, C. de; Schilp, J.; Wagner, C.

    2013-01-01

    Objectives: To evaluate the implementation of a four-year national patient safety program concerning the parenteral drug administration process in the Netherlands. Methods: Structuring the preparation and administration process of parenteral drugs reduces the number of medication errors. A

  5. 49 CFR 659.27 - Internal safety and security reviews.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Internal safety and security reviews. 659.27... State Oversight Agency § 659.27 Internal safety and security reviews. (a) The oversight agency shall... safety and security reviews in its system safety program plan. (b) The internal safety and security...

  6. The Patient's Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization.

    Science.gov (United States)

    Smith, Meredith Y; Benattia, Isma

    2016-09-01

    Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance systems in place to detect and assess adverse drug reactions (ADRs). At the same time, the practice of pharmacovigilance is being transformed by a host of recent regulatory guidances and related initiatives which emphasize the importance of the patient's perspective in drug safety. Collectively, these initiatives impact the full range of activities that fall within the remit of pharmacovigilance, including ADR reporting, signal detection and evaluation, risk management, medication error assessment, benefit-risk assessment and risk communication. Examples include the fact that manufacturing authorization holders are now expected to monitor all digital sources under their control for potential reports of ADRs, and the emergence of new methods for collecting, analysing and reporting patient-generated ADR reports for signal detection and evaluation purposes. A drug safety department's ability to transition successfully into a more patient-centric organization will depend on three defining attributes: (1) a patient-centered culture; (2) deployment of a framework to guide patient engagement activities; and (3) demonstrated proficiency in patient-centered competencies, including patient engagement, risk communication and patient preference assessment. Whether, and to what extent, drug safety departments embrace the new patient-centric imperative, and the methods and

  7. Safety and efficacy of generic drugs with respect to brand formulation

    OpenAIRE

    Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

    2013-01-01

    Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to gener...

  8. Pharmacovigilance in Crisis: Drug Safety at a Crossroads.

    Science.gov (United States)

    Price, John

    2018-05-01

    Pharmacovigilance (PV) is under unprecedented stress from fundamental changes in a booming pharmaceutical industry, from the challenges of creating and maintaining an increasingly complex PV system in a globally diverse regulatory environment, and from unpredicted consequences of historical PV cost-reduction strategies. At the same time, talent availability lags demand, and many PV professionals may no longer be finding personal fulfillment in their careers. The situation creates risks for companies. Advantages and disadvantages of potential strategies to address this increasing problem at a corporate and industry level and in collaboration with regulatory agencies are discussed, as well as opportunities to adopt new technologies, including artificial intelligence and machine-learning to automate pharmacovigilance operations. These approaches would address burdensome and wasteful effort assuring regulatory compliance and free up resources to support the original mission of PV as an important public health activity and to reinvest in the development of new drugs. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  9. What can nanosafety learn from drug development? The feasibility of “safety by design”

    DEFF Research Database (Denmark)

    Hjorth, Rune; van Hove, Lilian; Wickson, Fern

    2017-01-01

    Safety by design” (SbD) is an intuitively appealing concept that is on the rise within nanotoxicology and nanosafety research, as well as within nanotechnology research policy. It leans on principles established within drug discovery and development (DDD) and seeks to address safety early, as well...... as throughout product development. However, it remains unclear what the concept of SbD exactly entails for engineered nanomaterials (ENMs) or how it is envisioned to be implemented. Here, we review the concept as it is emerging in European research and compare its resemblance with the safety testing...

  10. Drug safety is a barrier to the discovery and development of new androgen receptor antagonists.

    Science.gov (United States)

    Foster, William R; Car, Bruce D; Shi, Hong; Levesque, Paul C; Obermeier, Mary T; Gan, Jinping; Arezzo, Joseph C; Powlin, Stephanie S; Dinchuk, Joseph E; Balog, Aaron; Salvati, Mark E; Attar, Ricardo M; Gottardis, Marco M

    2011-04-01

    Androgen receptor (AR) antagonists are part of the standard of care for prostate cancer. Despite the almost inevitable development of resistance in prostate tumors to AR antagonists, no new AR antagonists have been approved for over a decade. Treatment failure is due in part to mutations that increase activity of AR in response to lower ligand concentrations as well as to mutations that result in AR response to a broader range of ligands. The failure to discover new AR antagonists has occurred in the face of continued research; to enable progress, a clear understanding of the reasons for failure is required. Non-clinical drug safety studies and safety pharmacology assays were performed on previously approved AR antagonists (bicalutamide, flutamide, nilutamide), next generation antagonists in clinical testing (MDV3100, BMS-641988), and a pre-clinical drug candidate (BMS-501949). In addition, non-clinical studies with AR mutant mice, and EEG recordings in rats were performed. Non-clinical findings are compared to disclosures of clinical trial results. As a drug class, AR antagonists cause seizure in animals by an off-target mechanism and are found in vitro to inhibit GABA-A currents. Clinical trials of candidate next generation AR antagonists identify seizure as a clinical safety risk. Non-clinical drug safety profiles of the AR antagonist drug class create a significant barrier to the identification of next generation AR antagonists. GABA-A inhibition is a common off-target activity of approved and next generation AR antagonists potentially explaining some side effects and safety hazards of this class of drugs. Copyright © 2010 Wiley-Liss, Inc.

  11. The Expected Net Present Value of Developing Weight Management Drugs in the Context of Drug Safety Litigation.

    Science.gov (United States)

    Chawla, Anita; Carls, Ginger; Deng, Edmund; Tuttle, Edward

    2015-07-01

    Following withdrawals, failures, and significant litigation settlements, drug product launches in the anti-obesity category slowed despite a large and growing unmet need. Litigation concerns, a more risk-averse regulatory policy, and the difficulty of developing a product with a compelling risk-benefit profile in this category may have limited innovators' expected return on investment and restricted investment in this therapeutic area. The objective of the study was to estimate perceived manufacturer risk associated with product safety litigation and increased development costs vs. revenue expectations on anticipated return on investment and to determine which scenarios might change a manufacturer's investment decision. Expected net present value of a weight-management drug entering pre-clinical trials was calculated for a range of scenarios representing evolving expectations of development costs, revenue, and litigation risk over the past 25 years. These three factors were based on published estimates, historical data, and analogs from other therapeutic areas. The main driver in expected net present value calculations is expected revenue, particularly if one assumes that litigation risk and demand are positively correlated. Changes in development costs associated with increased regulatory concern with potential safety issues for the past 25 years likely did not impact investment decisions. Regulatory policy and litigation risk both played a role in anti-obesity drug development; however, product revenue-reflecting efficacy at acceptable levels of safety-was by far the most important factor. To date, relatively modest sales associated with recent product introductions suggest that developing a product that is sufficiently efficacious with an acceptable level of safety continues to be the primary challenge in this market.

  12. Drug packaging in 2014: authorities should direct more efforts towards medication safety.

    Science.gov (United States)

    2015-05-01

    In 2014, Prescrire examined the packaging quality of about 250 drugs. A few advances stand out, mainly involving recent drugs, but on the whole, the situation is worrisome in terms of medication safety. Although pharmaceutical companies and drug regulatory agencies seem to be taking more account of the risk of accidental poisoning in children, the level of protection remains low overall in the absence of stringent measures on the part of the authorities. New drugs too often have poor-quality or even dangerous packaging at the time of their market introduction. And the packaging quality of older drugs is disturbing. Pharmaceutical companies no longer invest in the packaging of these products, and agencies often fail to take advantage of the opportunities provided by their reassessment to improve the situation. The inappropriate labelling of certain injectable drugs remains a source of medication errors, sometimes resulting in very serious consequences. In 2014, signs of progress in the packaging of several drugs show that its role in medication safety is better appreciated. But the persistence of dangers in the pharmaceuticals market, created by "unfinished", overly complex or poor-quality packaging, raises the question of the responsibility of pharmaceutical companies and agencies for past and present accidents.

  13. FDA drug safety communications: a narrative review and clinical considerations for older adults.

    Science.gov (United States)

    Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A

    2012-08-01

    The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older

  14. Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety

    DEFF Research Database (Denmark)

    Fosbøl, Emil L; Olsen, Anne-Marie Schjerning; Olesen, Jonas Bjerring

    2014-01-01

    BACKGROUND: Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people. AIMS: The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use...... stroke). RESULTS: We selected 1,028,437 healthy individuals (median age 39 years). At least one nonsteroidal anti-inflammatory drug was claimed by 44·7% of the study population, and the drugs were generally used for a short period of time and in low doses. High-dose ibuprofen and diclofenac were......·35-3·42)]. CONCLUSIONS: In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke....

  15. Safety pharmacology of sibutramine mesylate, an anti-obesity drug.

    Science.gov (United States)

    Kim, Eun-Joo; Park, Eun-Kyung; Suh, Kwee-Hyun

    2005-03-01

    Sibutramine mesylate is a new anti-obesity drug. It is a crystalline salt of sibutramine developed to improve the solubility of sibutramine hydrochloride. Methanesulfonic acid was used as a salt-forming acid instead of hydrochloric acid, resulting in a greatly improved solubility of 1000 mg/mL in water. Sibutramine mesylate was administered orally to ICR mice, Sprague-Dawley rats, and beagle dogs at dose levels of 1.15, 3.45, and 11.50 mg/kg to measure its effects on the central nervous system (CNS), general behaviour, cardiovascular-respiratory system and the other organ systems. Following administration of sibutramine mesylate, spontaneous locomotor activity was significantly increased from 120 min to 24 hours at 3.45 mg/kg and from 30 min to 24 hours at 11.50 mg/kg. Furthermore, there were a decrease in hexobarbital-induced sleep time, an increase in respiratory rate at 120 min, increases in intestinal transport capacity and gastric pH at 11.50 mg/kg, and decreases in gastric volume and total acidity at 3.45 and 11.50 mg/kg. However sibutramine mesylate caused no effects on general behaviour, motor coordination, body temperature, analgesia, convulsion, blood pressure, heart rate, electrocardiogram, cardiac functions of the isolated rat heart, isolated smooth muscles and renal function. Based on the above results, it was concluded that sibutramine mesylate caused effects on the spontaneous locomotor activity, hexobarbital-induced sleep time, respiration, gastrointestinal transport, and gastric secretion at a dose level of 3.45 mg/kg or greater but caused no effects on other general pharmacological reactions.

  16. The nuts and bolts of pills and portions: the functions of a drug safety working group.

    Science.gov (United States)

    Nath, Noleen S; Jones, Ellen H; Stride, Peter; Premaratne, Manuja; Thaker, Darshit; Lim, Ivan

    2011-11-01

    Hospitalised patients commonly experience adverse drug events (ADEs) and medication errors. Runciman reported that ADEs in hospitals account for 20% of reported adverse events and contribute to 27% of deaths where death followed an adverse event. Hughes recommends multidisciplinary hospital drug committees to assess performance and raise standards. The new Code of Conduct of the Medical Board of Australia recommends participation in systems for surveillance and monitoring of adverse events, and to improve patient safety. We describe the functions and role of a Drug Safety Working Group (DSWG) in a suburban hospital, which aims to audit and promote a culture of prescribing and medication administration that is prudent and cautious to minimise the risk of harm to patients. We believe that regular prescription monitoring and feedback to Resident Medical Officers (RMOs) improves medication management in our hospital.

  17. Metabolic drug interactions - the impact of prescribed drug regimens on the medication safety.

    NARCIS (Netherlands)

    Fialova, D.; Vrbensky, K.; Topinkova, E.; Vlcek, J.; Soerbye, L.W.; Wagner, C.; Bernabei, R.

    2005-01-01

    Background and objective: Risk/benefit profile of prescribed drug regimens is unkown. Over 60% of commonly used medications interact on metabolic pathways (cytochrom P450 (CYP450), uridyl-glucuronyl tranferasis (UGT I, II) and P-glycoprotein (PGP) transport). Using an up-to-date knowledge on

  18. The practice of pre-marketing safety assessment in drug development.

    Science.gov (United States)

    Chuang-Stein, Christy; Xia, H Amy

    2013-01-01

    The last 15 years have seen a substantial increase in efforts devoted to safety assessment by statisticians in the pharmaceutical industry. While some of these efforts were driven by regulations and public demand for safer products, much of the motivation came from the realization that there is a strong need for a systematic approach to safety planning, evaluation, and reporting at the program level throughout the drug development life cycle. An efficient process can help us identify safety signals early and afford us the opportunity to develop effective risk minimization plan early in the development cycle. This awareness has led many pharmaceutical sponsors to set up internal systems and structures to effectively conduct safety assessment at all levels (patient, study, and program). In addition to process, tools have emerged that are designed to enhance data review and pattern recognition. In this paper, we describe advancements in the practice of safety assessment during the premarketing phase of drug development. In particular, we share examples of safety assessment practice at our respective companies, some of which are based on recommendations from industry-initiated working groups on best practice in recent years.

  19. 76 FR 64354 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

    Science.gov (United States)

    2011-10-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA). In particular...

  20. 76 FR 45818 - Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small...

    Science.gov (United States)

    2011-08-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0529] Burden of Food and Drug Administration Food Safety Modernization Act Fee Amounts on Small Business... burden of fee amounts on small business, as set forth in the FDA Food Safety Modernization Act (FSMA...

  1. Safety and efficacy of generic drugs with respect to brand formulation.

    Science.gov (United States)

    Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

    2013-12-01

    Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.

  2. Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

    Directory of Open Access Journals (Sweden)

    Benjamin Hixon

    2017-02-01

    Full Text Available Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC. The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9% of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%. The three most frequently reported labeling changes were warnings (68.7%, precautions (58.6%, and patient package insert/medication guide (23.2%. Case reports resulted in the greatest number of documented literature types (n = 791, followed by randomized controlled trials (n = 76, and case control/cohort studies (n = 74. Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%, compared to LOE A (17.1%, and LOE C (14.1% (p = 0.007. Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Research

  3. 76 FR 20686 - Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug...

    Science.gov (United States)

    2011-04-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0164] Draft Guidance for Industry on Safety Labeling Changes; Implementation of the Federal Food, Drug, and Cosmetic Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  4. 75 FR 36427 - Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management...

    Science.gov (United States)

    2010-06-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice...

  5. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    Science.gov (United States)

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  6. The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies.

    Science.gov (United States)

    Orriols, Ludivine; Salmi, Louis-Rachid; Philip, Pierre; Moore, Nicholas; Delorme, Bernard; Castot, Anne; Lagarde, Emmanuel

    2009-08-01

    To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area. The bibliographic search was done in Medline electronic database using the keywords: ((accident* or crash*) and traffic and drug*) leading to 1141 references. Additional references were retrieved from the Safetylit website and the reference lists of selected studies. Original articles published in English or French, between 1 April 1979 and 31 July 2008, were considered for inclusion. We excluded descriptive studies, studies limited to alcohol or illicit drug involvement and investigations of injuries other than from traffic crashes. Studies based on laboratory tests, driving simulators or on-the-road driving tests were also excluded. Eligible studies had to evaluate the causal relationship between the use of medicinal drugs and the risk of traffic crashes. Study quality was assessed by two independent experts, according to a grid adapted from the strengthening the reporting of observational studies in epidemiology (STROBE) statement. Twenty two studies of variable methodological quality were included. Definition of drug exposure varied across studies and depended on the data sources. Potential confounding due to the interaction between the effects of the medicinal drug and disease-related symptoms was often not controlled. The risk of motor-vehicle crashes related to benzodiazepines has been amply studied and demonstrated. Results for other medicinal drugs remain controversial. There is a need for large studies, investigating the role of individual substances in the risk of road traffic crashes. Copyright 2009 John Wiley & Sons, Ltd.

  7. Holes in the safety net: a case study of access to prescription drugs and specialty care.

    Science.gov (United States)

    Stanley, Ava; Cantor, Joel C; Guarnaccia, Peter

    2008-07-01

    The health care safety net in the United States is intended to fill gaps in health care services for uninsured and other vulnerable populations. This paper presents a case study of New Brunswick, NJ, a small city rich in safety net resources, to examine the adequacy of the American model of safety net care. We find substantial gaps in access to care despite the presence of a medical school, an abundance of primary care and specialty physicians, two major teaching hospitals, a large federally qualified health center and other safety net resources in this community of about 50,000 residents. Using a blend of random-digit-dial and area probability sampling, a survey of 595 households was conducted in 2001 generating detailed information about the health, access to care, demographic and other characteristics of 1,572 individuals. Confirming the great depth of the New Brunswick health care safety net, the survey showed that more than one quarter of local residents reported a hospital or community clinic as their usual source of care. Still, barriers to prescription drugs were reported for 11.0% of the area population and more than two in five (42.8%) local residents who perceived a need for specialty care reported difficulty getting those services. Bivariate analyses show significantly elevated risk of access problems among Hispanic and black residents, those in poor health, those relying on hospital and community clinics or with no usual source of care, and those living at or below poverty. In multivariate analysis, lack of health insurance was the greatest risk factor associated with both prescription drug and specialty access problems. Few local areas can claim the depth of safety net resources as New Brunswick, NJ, raising serious concerns about the adequacy of the American safety net model, especially for people with complex and chronic health care needs.

  8. Tennessee Oversight Agreement annual report, May 31, 1994--June 30, 1995

    International Nuclear Information System (INIS)

    1995-01-01

    The Tennessee Department of Environment and Conservation's DOE Oversight Division (TDEC/DOE-O) is responsible for assuring the citizens of Tennessee that their health, safety and environment on the Oak Ridge Reservation are protected and that appropriate remedial action is taken to provide this protection. TDEC/DOE-O has five program sections that reflect the organizational structure of the TDEC Bureau of Environment Divisions, as well as DOE's Environmental Safety and Health, Waste Management, and Environmental Restoration Programs

  9. Does the Early Adopter of Drugs Exist? A Population Based Study of General Practitioners’ Prescribing of New Drugs.20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158

    DEFF Research Database (Denmark)

    Dybdahl, Torben; Andersen, Morten; Søndergaard, Jens

    2004-01-01

    20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158......20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:158...

  10. Permitting product liability litigation for FDA-approved drugs and devices promotes patient safety.

    Science.gov (United States)

    Kesselheim, A S

    2010-06-01

    In 2008 and 2009, the Supreme Court reviewed the question of whether patients injured by dangerous prescription drugs or medical devices can bring tort lawsuits against pharmaceutical and device manufacturers. The Court ruled that claims against device manufacturers were preempted while claims against pharmaceutical manufacturers were not. The threat of product liability lawsuits promotes patient safety by encouraging manufacturers to take greater responsibility in providing clear warnings about known adverse effects of their products.

  11. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

    Science.gov (United States)

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Investigation of the cognition and behavior on drug safety in Beijing middle school students].

    Science.gov (United States)

    Cheng, Y C; Pan, Y P; Zhang, Y; Pan, Y T; Ding, C Y; Cao, Y; Zhuo, L; Fang, R F; Gao, A Y; Guo, J; Li, A J; Fu, Q; Ma, J; Zhan, S Y

    2017-12-18

    To understand the cognition and behavior of drug safety in Beijing middle school students and provide advice for relevant education. A cross-sectional survey using paper questionnaires was carried out on the student body of nine Beijing middle schools. Multi-stage proportionate stratified cluster sampling was adopted to enroll participants. In addition to demographic questions, the questionnaire included 17 questions assessing the cognition and behavior of safe drug use, prioritizing questions that aligned with the health education guideline for primary and secondary school students from Chinese Ministry of Education. Descriptive statistical methods were applied using the SAS 9.2 software. Of the 4 220 students investigated, 2 097(49.7%) were males and 2 123(50.3%) were females. The average age was (14.3±1.7) years. 2 030(48.1%) students were from downtown areas, 1 511(35.8%) were from urban-rural linking areas and 679(16.1%) were from rural areas. Half (51.5%) of the respondents were junior high school students, and the others were from senior high schools (34.2%) and vocational high schools (14.3%). Most of the students (89.6%) lived off campus. The awareness rate of drug safety knowledge was 74.4%, the median score of drug safety behavior was 4 points (full score was 5 points) and there was a statistically positive correlation between the two (Spearman's correlation coefficient was 0.156, Pmiddle school students is good, but problems still exist in medication adherence, the management of expired drugs and the antibiotics cognition, which need to be fixed through specific, pointed way of education. And more efforts should be made to improve the cognition in rural regions, vocational high schools and on campus students.

  13. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

    Science.gov (United States)

    Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

    2012-01-01

    Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

  14. [Evaluation of the safety of innovative drugs against viruses and infectious agents].

    Science.gov (United States)

    Kobayashi, Tetsu; Yusa, Keisuke; Kawasaki, Nana

    2013-01-01

    Recently, several novel cellular therapy products and biological drugs are being developed to treat various previously untreatable diseases. One of the most important issues regarding these innovations is how to ensure safety over infectious agents, including viruses and prions, in the earliest treatments with these products. The object of this study is a risk assessment of cases of human infectious with the agents and to present a sample risk management plan based on a collaboration among the National Institute of Health Sciences, universities, marketing authorization holders, and scientific societies. There are three subjects of study: (1) the viral safety of cellular therapy products, (2) the viral safety of biological drugs, and (3) the safety of prions. In this report, we describe the objects of the study, the project members, the study plan outline, and the ongoing plans. The results of the viral risk identification and the risk analysis of cellular therapy products will also be described, based on a review of the literature and case reports obtained during the first year of this project.

  15. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kejian, E-mail: kejian.wang.bio@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)

    2015-02-13

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

  16. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

    International Nuclear Information System (INIS)

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-01-01

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development

  17. Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy

    Directory of Open Access Journals (Sweden)

    Fegert Jörg M

    2009-04-01

    Full Text Available Abstract Most psychotropic drugs used in the treatment of children and adolescents are applied "off label" with a direct risk of under- or overdosing and a delayed risk of long-term side effects. The selection of doses in paediatric psychiatric patients requires a consideration of pharmacokinetic parameters and the development of central nervous system, and warrants specific studies in children and adolescents. Because these are lacking for most of the psychotropic drugs applied in the Child and Adolescent and Psychiatry, therapeutic drug monitoring (TDM is a valid tool to optimise pharmacotherapy and to enable to adjust the dosage of drugs according to the characteristics of the individual patient. Multi-centre TDM studies enable the identification of age- and development-dependent therapeutic ranges of blood concentrations and facilitate a highly qualified standardized documentation in the child and adolescent health care system. In addition, they will provide data for future research on psychopharmacological treatment in children and adolescents, as a baseline for example for clinically relevant interactions with various co-medications. Therefore, a German-Austrian-Swiss "Competence Network on Therapeutic Drug Monitoring in Child and Adolescent Psychiatry" was founded 1 introducing a comprehensive internet data base for the collection of demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents.

  18. Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

    Science.gov (United States)

    Castleden, C M; Pickles, H

    1988-10-01

    1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

  19. Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

    Science.gov (United States)

    Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

    2017-01-01

    Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Ayurpharmacoepidemiology en Route to Safeguarding Safety and Efficacy of Ayurvedic Drugs in Global Outlook

    Science.gov (United States)

    Debnath, Parikshit; Banerjee, Subhadip; Adhikari, Anjan; Debnath, Pratip K.

    2016-01-01

    Ayurpharmacoepidemiology is a new field developed by synergy of the fields of clinical pharmacology, epidemiology, and ayurveda. It will use the effects of ayurvedic medicinal products on large populations to describe and analyze the practices, evaluate the safety and efficacy, and carry out medicoeconomic evaluations. Good pharmacoepidemiology practices in ayurveda is projected to assist with issues of ayurpharmacoepidemiologic research. The embraced good pharmacoepidemiology practices guideline in this viewpoint will be able to provide valuable evidence about the health effects of ayurvedic herbs/drugs and consider different fields like pharmacovigilance, pharmacoeconomics, and drug discovery with ayurvedic reverse pharmacology approach, also pass out significant data for further basic sciences study in ayurveda biology, ayurgenomics, ayurnutrigenomics, and systems biology. Several unanswered questions about ayurvedic drug use and informed interventions or policies that can be addressed by informatics database, which will eventually demonstrate the credibility and rationality of ayurceuticals in the future. PMID:26721554

  1. Anti-Obesity Drugs: A Review about Their Effects and Safety

    Directory of Open Access Journals (Sweden)

    Jun Goo Kang

    2012-02-01

    Full Text Available The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

  2. Enabling social listening for cardiac safety monitoring: Proceedings from a drug information association-cardiac safety research consortium cosponsored think tank.

    Science.gov (United States)

    Seifert, Harry A; Malik, Raleigh E; Bhattacharya, Mondira; Campbell, Kevin R; Okun, Sally; Pierce, Carrie; Terkowitz, Jeffrey; Turner, J Rick; Krucoff, Mitchell W; Powell, Gregory E

    2017-12-01

    This white paper provides a summary of the presentations and discussions from a think tank on "Enabling Social Listening for Cardiac Safety Monitoring" trials that was cosponsored by the Drug Information Association and the Cardiac Safety Research Consortium, and held at the White Oak headquarters of the US Food and Drug Administration on June 3, 2016. The meeting's goals were to explore current methods of collecting and evaluating social listening data and to consider their applicability to cardiac safety surveillance. Social listening is defined as the act of monitoring public postings on the Internet. It has several theoretical advantages for drug and device safety. First, these include the ability to detect adverse events that are "missed" by traditional sources and the ability to detect adverse events sooner than would be allowed by traditional sources, both by affording near-real-time access to data from culturally and geographically diverse sources. Social listening can also potentially introduce a novel patient voice into the conversation about drug safety, which could uniquely augment understanding of real-world medication use obtained from more traditional methodologies. Finally, it can allow for access to information about drug misuse and diversion. To date, the latter 2 of these have been realized. Although regulators from the Food and Drug Administration and the United Kingdom's Medicines and Healthcare Products Regulatory Agency participated in the think tank along with representatives from industry, academia, and patient groups, this article should not be construed to constitute regulatory guidance. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 32 CFR 2103.51 - Information Security Oversight Committee.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Information Security Oversight Committee. 2103... BE DECLASSIFIED Implementation and Review § 2103.51 Information Security Oversight Committee. The NCS Information Security Oversight Committee shall be chaired by the Staff Counsel of the National Security...

  4. 32 CFR 2700.51 - Information Security Oversight Committee.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Information Security Oversight Committee. 2700... MICRONESIAN STATUS NEGOTIATIONS SECURITY INFORMATION REGULATIONS Implementation and Review § 2700.51 Information Security Oversight Committee. The OMSN Information Security Oversight Committee shall be chaired...

  5. 13 CFR 120.1000 - Risk-Based Lender Oversight.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Risk-Based Lender Oversight. 120.1000 Section 120.1000 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Supervision § 120.1000 Risk-Based Lender Oversight. (a) Risk-Based Lender...

  6. Safety studies of homoeopathic drugs in acute, sub-acute and chronic toxicity in rats

    Directory of Open Access Journals (Sweden)

    Surender Singh

    2017-01-01

    Full Text Available Background: Homoeopathic drugs are frequently recommended in day to day life as therapeutic agents by homoeopathic practitioners. However, safety of homoeopathic drugs remains a challenge because of the high variability of chemical components involved. Aim: The objective of the present study was to investigate the acute, subacute, and chronic oral toxicity of different homoeopathic drugs (Ferrum phosphoricum 3X, Ferrum phosphoricum 6X, Calcarea phosphoricum 6X, and Magnesium phosphoricum 6X in experimental models. Materials and Methods: In acute oral toxicity study, homoeopathic drugs were administered orally at 2000mg/kg body weight, and animals were observed for toxic symptoms till 10 days as per the OECD guidelines. For subacute and chronic toxicity study, homoeopathic drugs were administered for 28 and 180 days, respectively, as per the OECD guidelines. At the end of 28 and 180 days, the animals were sacrificed and toxicity parameters were assessed. Histopathological evaluation of different organs was also performed to assess any toxicity. Results: In acute toxicity study, no mortality was found at a dose of 2000 mg/kg which indicates that oral LD50of homoeopathic drugs were more than 2000 mg/kg. The administration of drugs at a dose of 70 mg/kg body weight for 28 and 180 days did not produce any significant change in haematological and biochemical parameters of male and female rats as compared to normal control group. No pathological changes were observed in histology of various organs of treated rats as compared to normal control animals. Conclusion: These homoeopathic drugs are safe & produce no toxicity when administered for longer duration.

  7. Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

    Science.gov (United States)

    Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

    2018-01-05

    The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the

  8. Transparency and Oversight in Local Wellness Policies

    Science.gov (United States)

    Chriqui, Jamie F.; Chaloupka, Frank J.

    2011-01-01

    Background: Advocates have called for increased wellness policy transparency and oversight through the use of health advisory councils. This study examines (1) wellness policy transparency, (2) advisory council requirements, (3) factors associated with each, and (4) whether transparency or advisory council requirements are indicative of a stronger…

  9. The concept of oversight, its connection to memory keeping and its relevance for the medium term: The findings of the RK and M initiative

    International Nuclear Information System (INIS)

    Hotzel, Stephan

    2015-01-01

    The medium term was introduced as the period of indirect oversight after repository closure, with timescales in the order of a few hundred years. While the importance of intrinsic control or 'passive' safety features in the post-closure phase of a geological repository has been recognised and stressed before, the role of oversight, by providing the capability to reduce or avoid some exposures, has come to the fore only recently. Oversight for the time being generally refers to 'watchful care' and society 'keeping an eye' on the technical system and the actual implementation of plans and decisions. In some regulatory frameworks oversight is indirectly required, for instance when mandating the creation of a land exclusion zone. In other frameworks, oversight is directly required, as illustrated, for instance, by the long-term stewardship concept of the US Environmental Protection Agency. Although sheer memory of the presence of the facility cannot be enough to constitute oversight, oversight and RK and M preservation do go hand in hand. For example, monitoring after repository closure fosters RK and M preservation, and vice versa. The presenter focused on terminology, potential oversight measures, and on roles and responsibilities of different stakeholders

  10. The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety.

    Science.gov (United States)

    Heal, D J; Cheetham, S C; Smith, S L

    2009-12-01

    Results from in vivo techniques, especially intracerebral microdialysis in freely-moving rats, have provided insights into potential mechanisms responsible for the efficacy and safety of catecholaminergic drugs for ADHD treatment. The drugs reviewed come from distinct pharmacological classes: psychostimulant releasing agents, eg d-amphetamine; psychostimulant reuptake inhibitors, eg dl-threo-methylphenidate (dl-MPH), and non-stimulant reuptake inhibitors, eg atomoxetine. Psychostimulants, which currently deliver the best efficacy in treating ADHD, exhibit the following characteristics on extraneuronal catecholamine concentrations in rodent brain in vivo: 1) They enhance the efflux and function of both noradrenaline and dopamine in the central nervous system. 2) The increase of dopamine efflux that they produce is not limited to cortical regions. 3) They have a rapid onset of action with no ceiling on drug effect. d-Amphetamine has a mechanism independent of neuronal firing rate, displacing intraneuronal stores of catecholamines, delaying their reuptake and inhibiting catabolism by monoamine oxidase. dl-MPH has an enigmatic, extraneuronal action that is neuronal firing rate-dependent and reuptake transporter-mediated, yet paradoxically, almost as powerful as that of d-amphetamine. In safety terms, these powerful catecholaminergic effects also make the psychostimulants liable for abuse. Since efficacy and safety derive from the same pharmacological mechanisms, it has not yet been possible to separate these two components. However, the development of once-daily psychostimulant formulations and a prodrug, lisdexamfetamine, has improved patient compliance and markedly reduced scope for their diversion/abuse. This review will discuss the in vivo pharmacological profiles of approved catecholaminergic drugs for treatment of ADHD and implications for their clinical efficacy and abuse liability.

  11. Recommendations for oversight of nanobiotechnology: dynamic oversight for complex and convergent technology

    International Nuclear Information System (INIS)

    Ramachandran, Gurumurthy; Wolf, Susan M.; Paradise, Jordan; Kuzma, Jennifer; Hall, Ralph; Kokkoli, Efrosini; Fatehi, Leili

    2011-01-01

    Federal oversight of nanobiotechnology in the U.S. has been fragmented and incremental. The prevailing approach has been to use existing laws and other administrative mechanisms for oversight. However, this “stay-the-course” approach will be inadequate for such a complex and convergent technology and may indeed undermine its promise. The technology demands a new, more dynamic approach to oversight. The authors are proposing a new oversight framework with three essential features: (a) the oversight trajectory needs to be able to move dynamically between “soft” and “hard” approaches as information and nano-products evolve; (b) it needs to integrate inputs from all stakeholders, with strong public engagement in decision-making to assure adequate analysis and transparency; and (c) it should include an overarching coordinating entity to assure strong inter-agency coordination and communication that can meet the challenge posed by the convergent nature of nanobiotechnology. The proposed framework arises from a detailed case analysis of several key oversight regimes relevant to nanobiotechnology and is informed by inputs from experts in academia, industry, NGOs, and government.

  12. A survey of front-line paramedics examining the professional relationship between paramedics and physician medical oversight.

    Science.gov (United States)

    Foerster, Christopher R; Tavares, Walter; Virkkunen, Ilkka; Kämäräinen, Antti

    2018-03-01

    Paramedicine is often dependent on physician medical directors and their associated programs for direction and oversight. A positive relationship between paramedics and their oversight physicians promotes safety and quality care while a strained or ineffective one may threaten these goals. The objective of this study was to explore and understand the professional relationship between paramedics and physician medical oversight as viewed by front-line paramedics. All active front-line paramedics from four municipal paramedic services involving three medical oversight groups in Ontario were invited to complete an online survey. Five hundred and four paramedics were invited to participate in the study, with 242 completing the survey (48% response rate); 66% male, 76% primary care paramedics with an average of 13 (SD=9) years of experience. Paramedics had neutral or positive perceptions regarding their autonomy, opportunities to interact with their medical director, and medical director understanding of the prehospital setting. Paramedics perceived medical directives as rigid and ambiguous. A significant amount of respondents reported a perception of having provided suboptimal patient care due to fear of legal or disciplinary consequences. Issues of a lack of support for critical thinking and a lack of trust between paramedics and medical oversight groups were often raised. Paramedic perceptions of physician medical oversight were mixed. Concerning areas identified were perceptions of ambiguous written directives and concerns related to the level of trust and support for critical thinking. These perceptions may have implications for the system of care and should be explored further.

  13. Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

    Directory of Open Access Journals (Sweden)

    Rosângela Teixeira

    Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

  14. Safety aspects of protease inhibitors for chronic hepatitis C: adverse events and drug-to-drug interactions

    Directory of Open Access Journals (Sweden)

    Rosângela Teixeira

    2013-04-01

    Full Text Available The standard of care therapy of chronic hepatitis C with the combination of pegylated interferon and ribavirin for 24 or 48 weeks was a remarkable accomplishment of the past decade. However, sustained virological responses rates of about 80% (genotypes 2-3 and 50% (geno 3 type 1 were not satisfactory especially for patients infected with genotype 1. Important advances in the biology of HCV have made possible the development of the direct-acting antiviral agents boceprevir and telaprevir with substantial increase in the rates of sustained virological response with shorter duration of therapy for a large number of patients. However, the complexity of triple therapy is higher and several new side effects are expected suggesting greater expertise in the patient management. Anemia and disgeusia are frequent with boceprevir while cutaneous rash, ranging from mild to severe, is expected with telaprevir. Higher risk of drug-drug interactions demand further clinical consideration of the previous well-known adverse events of pegylated interferon and ribavirin. Identification and prompt management of these potential new problems with boceprevir and telaprevir are crucial in clinical practice for optimizing treatment and assuring safety outcomes to HCV-genotype 1 patients.

  15. Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

    International Nuclear Information System (INIS)

    Nabili, Marjan; Geist, Craig; Zderic, Vesna

    2015-01-01

    Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm 2 , and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm 2 (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this

  16. Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

    Energy Technology Data Exchange (ETDEWEB)

    Nabili, Marjan, E-mail: mnabili@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, 800 22nd Street NW, Room 5000, Washington, DC 20052 (United States); Geist, Craig, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Ophthalmology, The George Washington University, 2150 Pennsylvania Avenue NW, Floor 2A, Washington, DC 20037 (United States); Zderic, Vesna, E-mail: cgeist@mfa.gwu.edu, E-mail: zderic@gwu.edu [Department of Biomedical Engineering, The George Washington University, 800 22nd Street NW, Room 6670, Washington, DC 20052 (United States)

    2015-10-15

    Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm{sup 2}, and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm{sup 2} (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety

  17. Best practices: an electronic drug alert program to improve safety in an accountable care environment.

    Science.gov (United States)

    Griesbach, Sara; Lustig, Adam; Malsin, Luanne; Carley, Blake; Westrich, Kimberly D; Dubois, Robert W

    2015-04-01

    The accountable care organization (ACO), one of the most promising and talked about new models of care, focuses on improving communication and care transitions by tying potential shared savings to specific clinical and financial benchmarks. An important factor in meeting these benchmarks is an ACO's ability to manage medications in an environment where medical and pharmacy care has been integrated. The program described in this article highlights the critical components of Marshfield Clinic's Drug Safety Alert Program (DSAP), which focuses on prioritizing and communicating safety issues related to medications with the goal of reducing potential adverse drug events. Once the medication safety concern is identified, it is reviewed to evaluate whether an alert warrants sending prescribers a communication that identifies individual patients or a general communication to all physicians describing the safety concern. Instead of basing its decisions regarding clinician notification about drug alerts on subjective criteria, the Marshfield Clinic's DSAP uses an internally developed scoring system. The scoring system includes criteria developed from previous drug alerts, such as level of evidence, size of population affected, severity of adverse event identified or targeted, litigation risk, available alternatives, and potential for duration of medication use. Each of the 6 criteria is assigned a weight and is scored based upon the content and severity of the alert received.  In its first 12 months, the program targeted 6 medication safety concerns involving the following medications: topiramate, glyburide, simvastatin, citalopram, pioglitazone, and lovastatin. Baseline and follow-up prescribing data were gathered on the targeted medications. Follow-up review of prescribing data demonstrated that the DSAP provided quality up-to-date safety information that led to changes in drug therapy and to decreases in potential adverse drug events. In aggregate, nearly 10,000 total

  18. Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2013-04-01

    Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the second in a 2-part series is to review published data on the efficacy and safety of antipsychotic medications currently available for managing situations of this type. Arrhythmias caused by QT-prolonging drugs occur infrequently, and multiple factors are often involved, including concomitant use of other drugs affecting the same pathway (most antipsychotic drugs prolong the QT interval by blocking potassium IKr current in HERG channels of myocardial cells, electrolyte disorders and, possibly, genetic predisposition. Judicious use of typical antipsychotics (mainly haloperidol and benzodiazepines (mainly lorazepam, given intramuscularly alone or in combination, has proved to be safe and effective for controlling acute motor agitation related to psychiatric illness; cocaine, methamphetamine, and ethanol toxicity; ethanol withdrawal; and other factors. They are still widely used and are particularly useful when limited data are available on the patient’s history of cardiovascular disease, current use of medication, and/or the likelihood of illicit drug or alcohol intoxication; when the diagnosis involves medical comorbidity or intoxication; or when there is no specific treatment (e.g., personality disorders, learning disabilities, mental retardation, organic brain damage. If rapid tranquillization is necessary before a formal diagnosis can be made and there are uncertainties regarding the patient’s medical history, lorazepam is often considered the first-line drug of choice. In

  19. Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

    Science.gov (United States)

    Buckley, Lorrene A; Salunke, Smita; Thompson, Karen; Baer, Gerri; Fegley, Darren; Turner, Mark A

    2018-02-05

    A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward. Leveraging orthogonal sources of data (eg. food industry, agro science), collaborative data sharing, and increased awareness of the existing sources such as the Safety and Toxicity of Excipients for Paediatrics (STEP) database will be important to address the gap in excipients knowledge needed for risk assessment. The importance of defining risk-based approaches to safety assessments for excipients vital to pediatric formulations was emphasized, as was the need for meaningful stakeholder (eg, patient, caregiver) engagement. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Zero-inflated Poisson model based likelihood ratio test for drug safety signal detection.

    Science.gov (United States)

    Huang, Lan; Zheng, Dan; Zalkikar, Jyoti; Tiwari, Ram

    2017-02-01

    In recent decades, numerous methods have been developed for data mining of large drug safety databases, such as Food and Drug Administration's (FDA's) Adverse Event Reporting System, where data matrices are formed by drugs such as columns and adverse events as rows. Often, a large number of cells in these data matrices have zero cell counts and some of them are "true zeros" indicating that the drug-adverse event pairs cannot occur, and these zero counts are distinguished from the other zero counts that are modeled zero counts and simply indicate that the drug-adverse event pairs have not occurred yet or have not been reported yet. In this paper, a zero-inflated Poisson model based likelihood ratio test method is proposed to identify drug-adverse event pairs that have disproportionately high reporting rates, which are also called signals. The maximum likelihood estimates of the model parameters of zero-inflated Poisson model based likelihood ratio test are obtained using the expectation and maximization algorithm. The zero-inflated Poisson model based likelihood ratio test is also modified to handle the stratified analyses for binary and categorical covariates (e.g. gender and age) in the data. The proposed zero-inflated Poisson model based likelihood ratio test method is shown to asymptotically control the type I error and false discovery rate, and its finite sample performance for signal detection is evaluated through a simulation study. The simulation results show that the zero-inflated Poisson model based likelihood ratio test method performs similar to Poisson model based likelihood ratio test method when the estimated percentage of true zeros in the database is small. Both the zero-inflated Poisson model based likelihood ratio test and likelihood ratio test methods are applied to six selected drugs, from the 2006 to 2011 Adverse Event Reporting System database, with varying percentages of observed zero-count cells.

  1. Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

    International Nuclear Information System (INIS)

    Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

    2006-01-01

    This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

  2. Exploiting heterogeneous publicly available data sources for drug safety surveillance: computational framework and case studies.

    Science.gov (United States)

    Koutkias, Vassilis G; Lillo-Le Louët, Agnès; Jaulent, Marie-Christine

    2017-02-01

    Driven by the need of pharmacovigilance centres and companies to routinely collect and review all available data about adverse drug reactions (ADRs) and adverse events of interest, we introduce and validate a computational framework exploiting dominant as well as emerging publicly available data sources for drug safety surveillance. Our approach relies on appropriate query formulation for data acquisition and subsequent filtering, transformation and joint visualization of the obtained data. We acquired data from the FDA Adverse Event Reporting System (FAERS), PubMed and Twitter. In order to assess the validity and the robustness of the approach, we elaborated on two important case studies, namely, clozapine-induced cardiomyopathy/myocarditis versus haloperidol-induced cardiomyopathy/myocarditis, and apixaban-induced cerebral hemorrhage. The analysis of the obtained data provided interesting insights (identification of potential patient and health-care professional experiences regarding ADRs in Twitter, information/arguments against an ADR existence across all sources), while illustrating the benefits (complementing data from multiple sources to strengthen/confirm evidence) and the underlying challenges (selecting search terms, data presentation) of exploiting heterogeneous information sources, thereby advocating the need for the proposed framework. This work contributes in establishing a continuous learning system for drug safety surveillance by exploiting heterogeneous publicly available data sources via appropriate support tools.

  3. Nuclear health and safety

    International Nuclear Information System (INIS)

    1991-04-01

    Numerous environmental, safety, and health problems found at other Department of Energy (DOE) defense nuclear facilities precipitated a review of these conditions at DOE's contractor-operated Pantex Plant, where our nation's nuclear weapons are assembled. This book focuses the review on examining key safety and health problems at Pantex and determining the need for external safety oversight of the plant

  4. Safety at DOE Nuclear Weapons Facilities. Hearings before the Subcommittee on Oversight and Investigations of the Committee on Energy and Commerce, House of Representatives, One Hundredth Congress, October 22, 1987 and May 11, 1988

    International Nuclear Information System (INIS)

    Anon.

    1988-01-01

    The hearings address the adequacy of health and safety programs at the Department of Energy's (DOE) nuclear weapons facilities. All the facilities are owned by the government and operated by contractors. Statements and documents are provided by officials from the DOE and its operating contractors

  5. Flaws found in Los Alamos safety procedures

    Science.gov (United States)

    Gwynne, Peter

    2017-12-01

    A US government panel on nuclear safety has discovered a series of safety issues at the Los Alamos National Laboratory, concluding that government oversight of the lab's emergency preparation has been ineffective.

  6. Human rights vs. Public safety -- When can you test your workers for drugs?

    Energy Technology Data Exchange (ETDEWEB)

    Kossowan, B. L.

    2002-06-01

    Legislative and regulatory aspects of drug testing of employees vs. public safety are discussed. While in Canada federal and provincial laws concerning human rights take precedence over public safety issues, laws and regulations vary from province to province, therefore there is good reason for concern about uncertainty. To compound the uncertainty, certain relevant laws of the United States are different (generally more stringent than corresponding Canadian laws), consequently there is the possibility that certain American companies might feel justified in refusing to do business with Canadian firms that do not follow their rigid standards. The conclusion is that while the situation may be clear enough in a legal situation, it does not always work equally well in practice. Unfortunately, at the present time there is not a whole lot of guidance available for companies to manage the workplace in a practical sense.

  7. Long-Term Safety of Drug-Eluting and Bare-Metal Stents

    DEFF Research Database (Denmark)

    Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

    2015-01-01

    BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

  8. Evaluation of Electronic Healthcare Databases for Post-Marketing Drug Safety Surveillance and Pharmacoepidemiology in China.

    Science.gov (United States)

    Yang, Yu; Zhou, Xiaofeng; Gao, Shuangqing; Lin, Hongbo; Xie, Yanming; Feng, Yuji; Huang, Kui; Zhan, Siyan

    2018-01-01

    Electronic healthcare databases (EHDs) are used increasingly for post-marketing drug safety surveillance and pharmacoepidemiology in Europe and North America. However, few studies have examined the potential of these data sources in China. Three major types of EHDs in China (i.e., a regional community-based database, a national claims database, and an electronic medical records [EMR] database) were selected for evaluation. Forty core variables were derived based on the US Mini-Sentinel (MS) Common Data Model (CDM) as well as the data features in China that would be desirable to support drug safety surveillance. An email survey of these core variables and eight general questions as well as follow-up inquiries on additional variables was conducted. These 40 core variables across the three EHDs and all variables in each EHD along with those in the US MS CDM and Observational Medical Outcomes Partnership (OMOP) CDM were compared for availability and labeled based on specific standards. All of the EHDs' custodians confirmed their willingness to share their databases with academic institutions after appropriate approval was obtained. The regional community-based database contained 1.19 million people in 2015 with 85% of core variables. Resampled annually nationwide, the national claims database included 5.4 million people in 2014 with 55% of core variables, and the EMR database included 3 million inpatients from 60 hospitals in 2015 with 80% of core variables. Compared with MS CDM or OMOP CDM, the proportion of variables across the three EHDs available or able to be transformed/derived from the original sources are 24-83% or 45-73%, respectively. These EHDs provide potential value to post-marketing drug safety surveillance and pharmacoepidemiology in China. Future research is warranted to assess the quality and completeness of these EHDs or additional data sources in China.

  9. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

    Science.gov (United States)

    Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M; Egger, Matthias; Jüni, Peter

    2011-01-11

    To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Network meta-analysis. Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

  10. Regulatory Oversight for New Projects - Challenges and Improvement in Regulation

    International Nuclear Information System (INIS)

    Lall, F.

    2016-01-01

    From inception, there has been rise in number of Nuclear Power Plants (NPP) even though very few accidents / events led to intermittent setbacks. However these accidents / events have posed challenges towards enhancement of safety and scope of regulation in all phases of NPP such as siting, design, construction, commissioning and decommissioning. It is essential to ensure compliance to these enhanced safety requirements during all phases of NPP. New and evolutionary reactors are under threshold for regulatory consideration world over. The variety of technologies and genres by themselves pose challenges to regulatory bodies. These challenges are to be addressed through systematic enhancement of the regulation including updating of regulatory documents. The paper touches upon some key elements to be considered towards such enhancement of regulation during all stages of NPP. These being; ensuring quality assurance, regulatory oversight especially over supply chain and contractors, counterfeit material specifically in case of international dealings, emergency handling in case of multi-unit site, feedback and associated enhancements from international events, construction experience database and feedback for safety enhancement, qualification and acceptance of first of a kind systems, regulatory enforcement specifically in case of imported reactors and maintaining interface between safety and security. Regulation in present context has become dynamic and Regulatory bodies need to continue enhancement of its current regulation taking into account the technological developments, feedback from construction, operation and accidents in the current fleet of plants. The paper touches upon some of these elements and highlights the challenges and improvements in regulation. (author)

  11. Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis.

    Science.gov (United States)

    Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2013-12-01

    Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

  12. Pharmacovigilance and drug safety 2011 in Calabria (Italy: Adverse events analysis

    Directory of Open Access Journals (Sweden)

    Francesca Scicchitano

    2012-01-01

    Full Text Available Background : Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs. The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results : Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100 in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %. Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%. There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it, and there is a strong interest in participating to training courses in the field (95% are interested. Conclusions : Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

  13. Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

    Science.gov (United States)

    Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2012-09-01

    Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

  14. Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

    Science.gov (United States)

    Silva, Ivair R

    2018-01-15

    Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Corporate social responsibility for nanotechnology oversight.

    Science.gov (United States)

    Kuzma, Jennifer; Kuzhabekova, Aliya

    2011-11-01

    Growing public concern and uncertainties surrounding emerging technologies suggest the need for socially-responsible behavior of companies in the development and implementation of oversight systems for them. In this paper, we argue that corporate social responsibility (CSR) is an important aspect of nanotechnology oversight given the role of trust in shaping public attitudes about nanotechnology and the lack of data about the health and environmental risks of nanoproducts. We argue that CSR is strengthened by the adoption of stakeholder-driven models and attention to moral principles in policies and programs. In this context, we examine drivers of CSR, contextual and leadership factors that influence CSR, and strategies for CSR. To illustrate these concepts, we discuss existing cases of CSR-like behavior in nanotechnology companies, and then provide examples of how companies producing nanomedicines can exhibit morally-driven CSR behavior.

  16. Regulatory Oversight Program, July 1, 1993 - March 3, 1997. Volume 1

    International Nuclear Information System (INIS)

    1997-09-01

    On July 1, 1993, a Regulatory Oversight (RO) organization was established within the United States Department of Energy (DOE), Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the RO program was to ensure continued plant safety, safeguards and security while the Paducah and Portsmouth gaseous diffusion plants (GDPs) transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). These activities were performed under the authority of the lease agreement between DOE and USEC until NRC issued a Certificate of Compliance or approved a Compliance Plan pursuant to Section 1701 of the Atomic Energy Act of 1954, as amended, and assumed regulatory responsibility. This report chronicles the formal development, operation and key activities of the RO organization from its beginning in July 1993, until the turnover of the regulatory oversight responsibility to the NRC on March 3, 1997. Through its evolution to closure, the RO program was a formal, proceduralized effort designed to provide consistent regulation and to facilitate transition to NRC. The RO Program was also a first-of-a-kind program for DOE. The process, experience, and lessons learned summarized herein should be useful as a model for transition of other DOE facilities to privatization or external regulation

  17. Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    On July 1, 1993, a Regulatory Oversight (RO) organization was established within the United States Department of Energy (DOE), Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the RO program was to ensure continued plant safety, safeguards and security while the Paducah and Portsmouth gaseous diffusion plants (GDPs) transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). These activities were performed under the authority of the lease agreement between DOE and USEC until NRC issued a Certificate of Compliance or approved a Compliance Plan pursuant to Section 1701 of the Atomic Energy Act of 1954, as amended, and assumed regulatory responsibility. This report chronicles the formal development, operation and key activities of the RO organization from its beginning in July 1993, until the turnover of the regulatory oversight responsibility to the NRC on March 3, 1997. Through its evolution to closure, the RO program was a formal, proceduralized effort designed to provide consistent regulation and to facilitate transition to NRC. The RO Program was also a first-of-a-kind program for DOE. The process, experience, and lessons learned summarized herein should be useful as a model for transition of other DOE facilities to privatization or external regulation.

  18. Pharmacokinetics in Drug Discovery: An Exposure-Centred Approach to Optimising and Predicting Drug Efficacy and Safety.

    Science.gov (United States)

    Reichel, Andreas; Lienau, Philip

    2016-01-01

    The role of pharmacokinetics (PK) in drug discovery is to support the optimisation of the absorption, distribution, metabolism and excretion (ADME) properties of lead compounds with the ultimate goal to attain a clinical candidate which achieves a concentration-time profile in the body that is adequate for the desired efficacy and safety profile. A thorough characterisation of the lead compounds aiming at the identification of the inherent PK liabilities also includes an early generation of PK/PD relationships linking in vitro potency and target exposure/engagement with expression of pharmacological activity (mode-of-action) and efficacy in animal studies. The chapter describes an exposure-centred approach to lead generation, lead optimisation and candidate selection and profiling that focuses on a stepwise generation of an understanding between PK/exposure and PD/efficacy relationships by capturing target exposure or surrogates thereof and cellular mode-of-action readouts in vivo. Once robust PK/PD relationship in animal PD models has been constructed, it is translated to anticipate the pharmacologically active plasma concentrations in patients and the human therapeutic dose and dosing schedule which is also based on the prediction of the PK behaviour in human as described herein. The chapter outlines how the level of confidence in the predictions increases with the level of understanding of both the PK and the PK/PD of the new chemical entities (NCE) in relation to the disease hypothesis and the ability to propose safe and efficacious doses and dosing schedules in responsive patient populations. A sound identification of potential drug metabolism and pharmacokinetics (DMPK)-related development risks allows proposing of an effective de-risking strategy for the progression of the project that is able to reduce uncertainties and to increase the probability of success during preclinical and clinical development.

  19. Nonclinical safety biomarkers of drug-induced vascular injury: current status and blueprint for the future.

    Science.gov (United States)

    Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S

    2014-06-01

    Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).

  20. Impact of regulatory guidances and drug regulation on risk minimization interventions in drug safety: a systematic review.

    Science.gov (United States)

    Nkeng, Lenhangmbong; Cloutier, Anne-Marie; Craig, Camille; Lelorier, Jacques; Moride, Yola

    2012-07-01

    Therapeutic risk management has received growing interest in recent years, particularly since the publication of regulatory guidances in 2005 and 2006, paralleled with a change in drug regulation. The characteristics of risk minimization interventions (RMIs) that have been implemented or approved remain inadequately explored. The aim of this study was to review RMIs published in the literature or posted on regulatory agency websites over the past 10 years, and to assess whether publication of regulatory guidances on risk management is associated with changes in the number and types of interventions. Sources were searched for RMIs published/posted between 1 January 2000 and 31 December 2009. For the literature search, MEDLINE and EMBASE databases were used using key words related to drug safety (i.e. 'drug toxicity') and the individual RMI names. The website review involved searches of major regulatory authority websites such as the European Medicines Agency, US FDA, Health Canada, the UK's Medicines and Healthcare products Regulatory Agency, Japan's Pharmaceutical and Medical Devices Agency and Australia's Therapeutic Goods Administration. The following eligibility criteria were applied for inclusion in the review: published/posted between the years 2000 and 2009, inclusive; involving drug products; use in humans; and involving RMIs, or tools used to increase the reporting of adverse events (AEs). Natural healthcare products, devices, diagnostic chemicals, pregnancy registries without follow-up, medication errors and products not used as therapy for illness were not retained. For each source, the following characteristics were extracted: nature of the intervention, target population, therapeutic area, AE(s) of special interest, country/regulatory agency and year of publication. A total of 119 unique interventions were identified in the literature (54 published in 2000-4 and 65 published in 2005-9). Interventions included educational material (n = 37; 31%), black

  1. Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

    Science.gov (United States)

    Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

    2013-11-01

    Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

  2. Considerations for the nonclinical safety evaluation of antibody drug conjugates for oncology.

    Science.gov (United States)

    Roberts, Stanley A; Andrews, Paul A; Blanset, Diann; Flagella, Kelly M; Gorovits, Boris; Lynch, Carmel M; Martin, Pauline L; Kramer-Stickland, Kimberly; Thibault, Stephane; Warner, Garvin

    2013-12-01

    Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to cytotoxic small molecules. A number of these agents are currently being developed as anti-cancer agents designed to improve the therapeutic index of the cytotoxin (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it to tumor cells. This paper presents primary considerations for the nonclinical safety evaluation of ADCs and includes strategies for the evaluation of the entire ADC or the various individual components (i.e., antibody, linker or the cytotoxin). Considerations are presented on how to design a nonclinical safety assessment program to identify the on- and off-target toxicities to enable first-in-human (FIH) studies. Specific discussions are also included that provide details as to the need and how to conduct the studies for evaluating ADCs in genetic toxicology, tissue cross-reactivity, safety pharmacology, carcinogenicity, developmental and reproductive toxicology, biotransformation, toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test article stability and the selection of the FIH dose. Given the complexity of these molecules and our evolving understanding of their properties, there is no single all-encompassing nonclinical strategy. Instead, each ADC should be evaluated on a case-by-case scientifically-based approach that is consistent with ICH and animal research guidelines. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

    Science.gov (United States)

    Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

    2018-06-01

    Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Safety of Therapeutic Fever Induction in Cancer Patients Using Approved PAMP Drugs

    Directory of Open Access Journals (Sweden)

    Uwe Rudolf Max Reuter

    2018-04-01

    Full Text Available William Coley, between 1895 and 1936, treated hundreds of cancer patients using infusions of fever inducing bacerial extracts. Similar experiments were done by Klyuyeva and co-workers in the 1940ies in Russia using trypanosoma extracts. Many remissions and cures were reported. We have conjectured that pathogen associated molecular pattern substances (PAMP are the molecular explanation for the beneficial treatments in both groups. We could show that a combination of PAMP can eradicate solid tumours in cancer mice if applied several times. Accordingly, we suggested to combine PAMP containing approved drugs to treat cancer patients using a protocol similar to the old fever induction regimen. In this retrospective phase-1 study we report on the fever induction capacity and safety of applications of bacterial extracts, combinations of bacterial extracts with approved drugs, and combinations of approved drugs in 131 mainly cancer patients. Adverse reactions were those which can be expected during a feverish infection and mild. Over 523 fever inductions, no severe adverse reaction was observed.

  5. Safety profile of drugs used in the treatment of osteoporosis: a systematical review of the literature

    Directory of Open Access Journals (Sweden)

    M. Varenna

    2013-10-01

    Full Text Available The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction.

  6. A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

    International Nuclear Information System (INIS)

    Harush-Frenkel, Oshrat; Bivas-Benita, Maytal; Nassar, Taher; Springer, Chaim; Sherman, Yoav; Avital, Avraham; Altschuler, Yoram; Borlak, Jurgen; Benita, Simon

    2010-01-01

    Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

  7. Comparison of the safety information on drug labels in three developed countries: The USA, UK and Canada

    Directory of Open Access Journals (Sweden)

    Thamir M. Alshammari

    2017-12-01

    Full Text Available The safety information on drug labels of a company marketing the same drugs in different countries is sometimes different. The aim of the present study is to understand the differences in the volume and content of safety information on the drug labels from the same manufacturers in three developed countries: the United States of America (USA, the United Kingdom (UK and Canada. This study involved the calculation of the proportion of total safety information (PSI and of contraindications (PCI in comparison to all information on the label and the percentage of boxed warnings (PBW among the 100 labels studied from each country. The PSI on the labels of different countries is different with USA labels bearing lesser value PSI and UK labels bearing higher value PSI. The qualitative information provided on these drug labels from each country in ‘contraindications’ sections, ‘boxed/serious warnings’ and ‘overdosage’ sections presented differences in the information provided on most of the labels. We have found distinct differences between the safety information available on drug labels in terms of volume and content. We conclude that the safety information for the same products should be standardised across all countries.

  8. The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery.

    Science.gov (United States)

    Thomas, Craig E; Will, Yvonne

    2012-02-01

    Attrition in the drug industry due to safety findings remains high and requires a shift in the current safety testing paradigm. Many companies are now positioning safety assessment at each stage of the drug development process, including discovery, where an early perspective on potential safety issues is sought, often at chemical scaffold level, using a variety of emerging technologies. Given the lengthy development time frames of drugs in the pharmaceutical industry, the authors believe that the impact of new technologies on attrition is best measured as a function of the quality and timeliness of candidate compounds entering development. The authors provide an overview of in silico and in vitro models, as well as more complex approaches such as 'omics,' and where they are best positioned within the drug discovery process. It is important to take away that not all technologies should be applied to all projects. Technologies vary widely in their validation state, throughput and cost. A thoughtful combination of validated and emerging technologies is crucial in identifying the most promising candidates to move to proof-of-concept testing in humans. In spite of the challenges inherent in applying new technologies to drug discovery, the successes and recognition that we cannot continue to rely on safety assessment practices used for decades have led to rather dramatic strategy shifts and fostered partnerships across government agencies and industry. We are optimistic that these efforts will ultimately benefit patients by delivering effective and safe medications in a timely fashion.

  9. The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

    Science.gov (United States)

    Horii, Ikuo

    2016-01-01

    Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision

  10. Drug research methodology. Volume 1, The alcohol-highway safety experience and its applicability to other drugs

    Science.gov (United States)

    1980-03-01

    This report presents the findings of a workshop concerning the alcohol and highway safety experience, which includes research efforts to define the drinking-driving problem and societal responses to reduce the increased highway safety risk attributab...

  11. Safety and effectiveness of drug therapy for the acutely agitated patient (Part I

    Directory of Open Access Journals (Sweden)

    Gianluca Airoldi

    2013-04-01

    Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone. Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5 and Fridericia

  12. The Internet and drug safety: what are the implications for pharmacovigilance?

    Science.gov (United States)

    Cobert, B; Silvey, J

    1999-02-01

    Use of the Internet is becoming widespread throughout the world. Its use in the domain of drug safety and pharmacovigilance is spreading rapidly. Governments and industry have taken the lead in developing extensive web sites. The US Food and Drug Administration (FDA), the European Agency for the Evaluation of Medicinal Products (EMEA) and other agencies have developed sites containing enormous amounts of information both on pharmacovigilance in general and on specific drugs in particular. Under the US 'Freedom of Information Act' the FDA has put major parts of its adverse event database on line. Regulatory documents are also available from the FDA site or from hyperlinks described in the site. The US Center for Drug Evaluation and Research updates its site most days and maintains a free automated e-mail announcement service of these updates. Similarly, the EMEA updates its site frequently and publishes extensive material including regulatory documents, guidelines, European Public Assessment Reports on newly approved medications and other useful information. A free update service by e-mail is also available. Although English is the primary language used on the EMEA site, some of the information is available in other languages. Pharmaceutical companies are not using the Internet for pharmacovigilance yet. Rather, the Internet is being used for promotion of their products and for informing consumers on general information on diseases, for financial and investor data and for employment opportunities, etc. Other organisations such as lobbies, consumer groups and medical journals are also beginning to use the Internet. The electronic transmission of safety information, using the standards developed by the International Conference on Harmonization, is currently being tested for the transmission of individual patient adverse event information between companies and governments. In addition, the FDA has begun to accept adverse events from healthcare providers and consumers

  13. Spillover Effects of Drug Safety Warnings on Preventive Health Care Use

    DEFF Research Database (Denmark)

    Daysal, N. Meltem; Orsini, Chiara

    2015-01-01

    We examine how new medical information on drug safety impacts preventive health care use. We exploit the release of the findings of the Women’s Health Initiative Study (WHIS) – the largest randomized controlled trial of women’s health – which demonstrated in 2002 the health risks associated...... with the long-term use of hormone replacement therapy (HRT). We first show that, after the release of the WHIS findings, HRT use dropped sharply among post-menopausal women. We then estimate the spillover effects of the WHIS findings on preventive care by means of a difference-in-differences methodology...... comparing changes in preventive care use among 60 to 69 year-old women (who have high rates of HRT use) with the change among women aged 75 and above (who have much lower rates of HRT use). Using data from the Behavioral Risk Factor Surveillance System for the period 1998–2007, we find that women aged 60...

  14. Open-label extension studies: do they provide meaningful information on the safety of new drugs?

    Science.gov (United States)

    Day, Richard O; Williams, Kenneth M

    2007-01-01

    The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the

  15. Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Kenji Ikemura

    2017-12-01

    Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

  16. Specialty pharmacies and other restricted drug distribution systems: financial and safety considerations for patients and health-system pharmacists.

    Science.gov (United States)

    Kirschenbaum, Bonnie E

    2009-12-15

    To discuss the role of restricted drug distribution systems in the implementation of risk evaluation and mitigation strategies (REMS), health-system pharmacists' concerns associated with the use of specialty pharmacies and other restricted drug distribution systems, reimbursement policies for high-cost specialty drugs, supply chain models for traditional and specialty drugs, and emerging trends in the management of and reimbursement for specialty pharmaceuticals. Restricted drug distribution systems established by pharmaceutical manufacturers, specialty pharmacies, or other specialty suppliers may be a component of REMS, which are required by the Food and Drug Administration for the management of known or potential serious risks from certain drugs. Concerns of health-system pharmacists using specialty suppliers include access to pharmaceuticals, operational challenges, product integrity, financial implications, continuity of care, and patient safety. An ambulatory care patient taking a specialty drug product from home to a hospital outpatient clinic or inpatient setting for administration, a practice known as "brown bagging," raises concerns about product integrity and institutional liability. An institution's finances, tolerance for liability, and ability to skillfully manage the processes involved often determine its choice between an approach that prohibits brown bagging but is costly and one that permits the practice under certain conditions and is less costly. The recent shift from a traditional supply chain model to a specialty pharmacy supply chain model for high-cost pharmaceuticals has the potential to increase pharmaceutical costs for health systems. A dialogue is needed between health-system pharmacists and group purchasing organizations to address the latter's role in mitigating the financial implications of this change and to help clarify the safety issues. Some health plans have shifted part of the cost of expensive drugs to patients by establishing a

  17. Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

    Science.gov (United States)

    Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

    2017-11-01

    Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

  18. Predicting Drug Safety and Communicating Risk: Benefits of a Bayesian Approach.

    Science.gov (United States)

    Lazic, Stanley E; Edmunds, Nicholas; Pollard, Christopher E

    2018-03-01

    Drug toxicity is a major source of attrition in drug discovery and development. Pharmaceutical companies routinely use preclinical data to predict clinical outcomes and continue to invest in new assays to improve predictions. However, there are many open questions about how to make the best use of available data, combine diverse data, quantify risk, and communicate risk and uncertainty to enable good decisions. The costs of suboptimal decisions are clear: resources are wasted and patients may be put at risk. We argue that Bayesian methods provide answers to all of these problems and use hERG-mediated QT prolongation as a case study. Benefits of Bayesian machine learning models include intuitive probabilistic statements of risk that incorporate all sources of uncertainty, the option to include diverse data and external information, and visualizations that have a clear link between the output from a statistical model and what this means for risk. Furthermore, Bayesian methods are easy to use with modern software, making their adoption for safety screening straightforward. We include R and Python code to encourage the adoption of these methods.

  19. Toxicological study on the safety of DTPA as a drug, (1)

    International Nuclear Information System (INIS)

    Fukuda, Satoshi; Iida, Haruzo

    1983-01-01

    In order to clarify the safety of Ca-DTPA and Zn-DTPA recommended to use as drugs in the therapeutic removal of incorporated radionuclides from the human body, the teratological study on these two agents was carried out in rats as one of a series of the toxicological tests. The teratological effects of DTPA were observed because the fetus is highly susceptible to any drug. The pregnant females of Wistar rat were injected subcutaneously daily on days 9-13 of gestation with 1, 6, 12, 24 and 36 H.D. (H.D. = human dose, 1 H.D. = 30μmol/kg body weight) of Ca-DTPA or Zn-DTPA, respectively. In the dams, no toxic effects were observed. In the fetuses, the decrease of the survival rate was observed in only the group injected daily with 36 H.D. of Ca-DTPA. Some cases of gross defects of fetuses: the exencephaly, microphthalmia, anophthalmia and fusion of ribs were observed in the groups injected daily with 12, 24 and 36 H.D. of Ca-DTPA. The results obtained show that Ca-DTPA should not be given to a pregnant woman. However, no toxic effects of either Ca-DTPA or Zn-DTPA observed in the dams ana of Zn-DTPA even in the fetuses indicate that these agents can be used by a radiation worker who usually is an adult man. (author)

  20. Toxicological study on the safety of DTPA as a drug, (1). Teratological study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Satoshi; Iida, Haruzo (National Inst. of Radiological Sciences, Chiba (Japan))

    1983-03-01

    In order to clarify the safety of Ca-DTPA and Zn-DTPA recommended to use as drugs in the therapeutic removal of incorporated radionuclides from the human body, the teratological study on these two agents was carried out in rats as one of a series of the toxicological tests. The teratological effects of DTPA were observed because the fetus is highly susceptible to any drug. The pregnant females of Wistar rat were injected subcutaneously daily on days 9-13 of gestation with 1, 6, 12, 24 and 36 H.D. (H.D. = human dose, 1 H.D. = 30..mu..mol/kg body weight) of Ca-DTPA or Zn-DTPA, respectively. In the dams, no toxic effects were observed. In the fetuses, the decrease of the survival rate was observed in only the group injected daily with 36 H.D. of Ca-DTPA. Some cases of gross defects of fetuses: the exencephaly, microphthalmia, anophthalmia and fusion of ribs were observed in the groups injected daily with 12, 24 and 36 H.D. of Ca-DTPA. The results obtained show that Ca-DTPA should not be given to a pregnant woman. However, no toxic effects of either Ca-DTPA or Zn-DTPA observed in the dams or of Zn-DTPA even in the fetuses indicate that these agents can be used by a radiation worker who usually is an adult man.

  1. Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis

    Science.gov (United States)

    Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; de Morales, José M. García Ruiz; Herreras, Jose M.; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

    2017-01-01

    Abstract Background: To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Methods: Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). Results: We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Conclusions: Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients. PMID:29049193

  2. Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis: A systematic literature review.

    Science.gov (United States)

    Gómez-Gómez, Alejandro; Loza, Estíbaliz; Rosario, Maria Piedad; Espinosa, Gerard; Morales, José M García Ruiz de; Herreras, Jose M; Muñoz-Fernández, Santiago; Cordero-Coma, Miguel

    2017-10-01

    To assess the efficacy and safety of immunomodulatory drugs in patients with noninfectious anterior uveitis (AU). Systematic review of studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March 2016), and Cochrane Library (up to March 2016), and a complementary hand search was also performed. The selection criteria were as follows: (population) noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any dose, regimen, route of administration, duration of treatment); (outcome) control of inflammation, steroid-sparing effect, AU flares, adverse events, and so on; (study design) systematic literature reviews, randomized controlled trials, and observational studies. The study quality was assessed using the Jadad scale and according to The Oxford Centre for Evidence-based Medicine (update 2009). We included 13 studies of moderate-poor quality, with a mean duration from 5 months to 20 years, and number of AU patients ranging from 9 to 274. Patient's demographic and clinical characteristics were very heterogeneous. In most cases, uveitis anatomic classification criteria and outcomes definitions were unclear. Some of the studies only included AU patients with a systemic disease associated, mostly spondyloarthritis, others, mixed populations (idiopathic and systemic disease associated patients), and in some articles this data is not described. We found that methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might prevent AU flares, improve ocular inflammation and visual acuity, and decrease systemic steroids doses. Although there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine, adalimumab, and golimumab might be effective in AU patients.

  3. Pharmaceutical quality of "party pills" raises additional safety concerns in the use of illicit recreational drugs.

    Science.gov (United States)

    Young, Simon A; Thrimawithana, Thilini R; Antia, Ushtana; Fredatovich, John D; Na, Yonky; Neale, Peter T; Roberts, Amy F; Zhou, Huanyi; Russell, Bruce

    2013-06-14

    To determine the content and release kinetics of 1-benzylpiperazine (BZP) and 1-(3-trifluoromethyl-phenyl)piperazine (TFMPP) from "party pill" formulations. From these data, the possible impact of pharmaceutical quality upon the safety of such illicit formulations may be inferred. The amount of BZP and TFMPP in party pill formulations was determined using a validated HPLC method. The in-vitro release kinetics of selected party pill brands were determined using a USP dissolution apparatus (75 rpm, 37.5 degrees Celsius). The release data were then fitted to a first order release model using PLOT software and the time taken to achieve 90% release reported. Many of the tested party pill brands contained amounts of BZP and TFMPP that varied considerably from that stated on the packaging; including considerable TFMPP content in some brands not labelled to contain this drug. Dissolution studies revealed that there was considerable variability in the release kinetics between brands; in one case 90% release required >30 minutes. Lack of quality control in party pill manufacture may have led to the toxic effects reported by users unaware of the true content and release of drug from pills. More stringent regulation in the manufacture and quality control of "new generation party pills" is essential to the harm reduction campaign.

  4. The Nuclear Regulator's Role in Assessing Licensee. Oversight of Vendor and Other Contracted Services

    International Nuclear Information System (INIS)

    2011-01-01

    Contracted services are an integral part of the design, construction and operation of a nuclear facility. Changes in the nuclear industry sector, including varied availability of nuclear expertise, the expansion of the international supply market and the introduction of new technologies, have tended to increase licensees' use of contracted services. These changes have created challenges for licensees and regulators related to the retention of nuclear expertise, the effective management of the interfaces between the licensees and contractors, and the oversight of contractor manufacturing quality in the context of greater multinational diversity. The regulatory body must address these challenges to provide assurance that the licensees maintain their responsibility for the safety of the facilities, regardless of who provides goods and services or where the activities involved in the supply chain take place. This report is intended to assist regulatory bodies in assessing their current practices for the regulatory oversight of licensees' use of contractors, and adapting them where necessary to meet the evolving situation

  5. Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

    Directory of Open Access Journals (Sweden)

    Denilson C. Albuquerque

    2005-08-01

    Full Text Available OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity. During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively. In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001. The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%, vasodilation (11.4% and dyspepsia (6.5%. There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

  6. Restart oversight assessment of Hanford 242-A evaporator: Summary report

    International Nuclear Information System (INIS)

    1994-08-01

    This report summarizes a January 17--28, 1994, oversight assessment of restart activities for the 242-A Evaporator at the US Department of Energy's (DOE's) Hanford Site about 25 miles northeast of Hanford, Washington. The assessment was conducted by qualified staff and consultants from the DOE Office of Environment, Safety and Health (EH). Its focus was the readiness of the facility for the resumption of safe operations, in particular those operations involved in the treatment and disposal of condensate from the evaporation of liquid radioactive waste, a key element of the tank waste remediation project administered by the DOE Richland Operations Office (DOE-RL). Overall, the assessment yielded eight programmatic concerns, supported by 38 individual findings. Of the concerns, four have already been closed, and the other four have been resolved. Results pointed up strengths in management and engineering design, as well as effective support of facility training programs by the management and operating contractor, Westinghouse Hanford Company (WHC). Weaknesses were evident, however, in conduct of operations, maintenance, and radiological practices. Furthermore, problems in the submittal and approval of Compliance Schedule Approvals--that is, WHC documentation of the status of compliance with DOE orders--were indicative of a programmatic breakdown in the DOE Order compliance process. According to the results of this assessment, there are no safety and health issues that would preclude or delay restart of the evaporator

  7. Safety

    International Nuclear Information System (INIS)

    1998-01-01

    A brief account of activities carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. These activities are reported under the headings: (1) Nuclear safety; (2) Industrial and health safety; (3) Radiation safety; and Fire protection

  8. The potential of the European network of congenital anomaly registers (EUROCAT) for drug safety surveillance: a descriptive study.

    Science.gov (United States)

    Meijer, Willemijn M; Cornel, Martina C; Dolk, Helen; de Walle, Hermien E K; Armstrong, Nicola C; de Jong-van den Berg, Lolkje T W

    2006-09-01

    European Surveillance of Congenital Anomalies (EUROCAT) is a network of population-based congenital anomaly registries in Europe surveying more than 1 million births per year, or 25% of the births in the European Union. This paper describes the potential of the EUROCAT collaboration for pharmacoepidemiology and drug safety surveillance. The 34 full members and 6 associate members of the EUROCAT network were sent a questionnaire about their data sources on drug exposure and on drug coding. Available data on drug exposure during the first trimester available in the central EUROCAT database for the years 1996-2000 was summarised for 15 out of 25 responding full members. Of the 40 registries, 29 returned questionnaires (25 full and 4 associate members). Four of these registries do not collect data on maternal drug use. Of the full members, 15 registries use the EUROCAT drug code, 4 use the international ATC drug code, 3 registries use another coding system and 7 use a combination of these coding systems. Obstetric records are the most frequently used sources of drug information for the registries, followed by interviews with the mother. Only one registry uses pharmacy data. Percentages of cases with drug exposure (excluding vitamins/minerals) varied from 4.4% to 26.0% among different registries. The categories of drugs recorded varied widely between registries. Practices vary widely between registries regarding recording drug exposure information. EUROCAT has the potential to be an effective collaborative framework to contribute to post-marketing drug surveillance in relation to teratogenic effects, but work is needed to implement ATC drug coding more widely, and to diversify the sources of information used to determine drug exposure in each registry.

  9. 12 CFR 4.66 - Oversight and monitoring.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Oversight and monitoring. 4.66 Section 4.66 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY ORGANIZATION AND FUNCTIONS...; Contracting for Goods and Services § 4.66 Oversight and monitoring. The Deputy Comptroller for Resource...

  10. 41 CFR 105-53.133 - Information Security Oversight Office.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Information Security... FUNCTIONS Central Offices § 105-53.133 Information Security Oversight Office. (a) Creation and authority. The Information Security Oversight Office (ISOO), headed by the Director of ISOO, who is appointed by...

  11. 10 CFR 440.23 - Oversight, training, and technical assistance.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Oversight, training, and technical assistance. 440.23... PERSONS § 440.23 Oversight, training, and technical assistance. (a) The Secretary and the appropriate..., directly or indirectly, training and technical assistance to any grantee or subgrantee. Such training and...

  12. 10 Standards for Oversight and Transparency of National Intelligence Services

    NARCIS (Netherlands)

    Eskens, S.; van Daalen, O.; van Eijk, N.

    2016-01-01

    This report aims to enhance the policy debate on surveillance by intelligence services by focusing on two key components: oversight and transparency. Both oversight and transparency are essential to devising checks and balances in a way that respects human rights. By offering this concise list of

  13. 27 | Page OVERSIGHT FUNCTIONS OF THE LEGISLATURE: AN ...

    African Journals Online (AJOL)

    Fr. Ikenga

    2004-09-06

    Sep 6, 2004 ... its oversight functions remains weak because legislative role and ... ministers of his government and other officers in the public service of the Federation9, while .... 22 “Parliamentary Oversight of Finance and the Budgetary Process” - The ... Association of First Nations National, Chief Matthew Coon29 ...

  14. Navy Acquisition Executive's Management Oversight and Procurement Authority Category I and II Programs

    National Research Council Canada - National Science Library

    2007-01-01

    .... This report discusses the management oversight and procurement authority within the Navy. Two other reports discussed the management oversight and procurement authority within the Army and Air Force...

  15. A comprehensive review of assay methods to determine drugs in breast milk and the safety of breastfeeding when taking drugs.

    Science.gov (United States)

    Fríguls, Bibiana; Joya, Xavier; García-Algar, Oscar; Pallás, C R; Vall, Oriol; Pichini, Simona

    2010-06-01

    Most of the licit and illicit drugs consumed by the breastfeeding woman pass into the milk and can modify the production, volume and composition of the milk, as well as hypothetically have short- and long-term harmful effects on the infant. There is much confusion in the scientific community regarding this issue: should a woman breastfeed her baby while continuing to use prescription drugs and/or drugs of abuse? There are many case reports of clinically significant toxicity in breast-fed infants from some substances used by mothers (such as irritability, vomiting, sedation, respiratory depression, shock), but there are too few data on studies conducted in breastfeeding women and their infants to make a realistic risk assessment. The objective measurement of a drug and/or metabolites in maternal milk is the first step when investigating the amount of drug excreted in milk and subsequently calculating the daily dose administered to the breast-fed infant. The present review reports the analytical methods developed to detect different drugs in the breast milk, listing the principal characteristics and validation parameters, advantages and disadvantages. Furthermore, the mechanisms of drug transfer into breast milk are discussed, the correlation between the concentration of the drug in breast milk and potential adverse outcomes on the infant are described for each drug, and suggested harm minimization strategies and approved breastfeeding recommendations are indicated.

  16. The algorithmic performance of J-Tpeak for drug safety clinical trial.

    Science.gov (United States)

    Chien, Simon C; Gregg, Richard E

    The interval from J-point to T-wave peak (JTp) in ECG is a new biomarker able to identify drugs that prolong the QT interval but have different ion channel effects. If JTp is not prolonged, the prolonged QT may be associated with multi ion channel block that may have low torsade de pointes risk. From the automatic ECG measurement perspective, accurate and repeatable measurement of JTp involves different challenges than QT. We evaluated algorithm performance and JTp challenges using the Philips DXL diagnostic 12/16/18-lead algorithm. Measurement of JTp represents a different use model. Standard use of corrected QT interval is clinical risk assessment on patients with cardiac disease or suspicion of heart disease. Drug safety trials involve a very different population - young healthy subjects - who commonly have J-waves, notches and slurs. Drug effects include difficult and unusual morphology such as flat T-waves, gentle notches, and multiple T-wave peaks. The JTp initiative study provided ECGs collected from 22 young subjects (11 males and females) in randomized testing of dofetilide, quinidine, ranolazine, verapamil and placebo. We compare the JTp intervals between DXL algorithm and the FDA published measurements. The lead wise, vector-magnitude (VM), root-mean-square (RMS) and principal-component-analysis (PCA) representative beats were used to measure JTp and QT intervals. We also implemented four different methods for T peak detection for comparison. We found that JTp measurements were closer to the reference for combined leads RMS and PCA than individual leads. Differences in J-point location led to part of the JTp measurement difference because of the high prevalence of J-waves, notches and slurs. Larger differences were noted for drug effect causing multiple distinct T-wave peaks (Tp). The automated algorithm chooses the later peak while the reference was the earlier peak. Choosing among different algorithmic strategies in T peak measurement results in the

  17. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Cros, C., E-mail: caroline.cros@hotmail.co.uk [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Skinner, M., E-mail: Matthew.Skinner@astrazeneca.com [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Moors, J. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom); Lainee, P. [Sanofi-Aventis R and D, 371, rue du Pr Joseph Blayac, 34184 Montpellier Cedex 04 (France); Valentin, J.P. [Safety Pharmacology, Global Safety Assessment, Safety Assessment UK, AstraZeneca R and D, Alderley Park, Macclesfield, SK10 4TG (United Kingdom)

    2012-12-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two

  18. Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

    International Nuclear Information System (INIS)

    Cros, C.; Skinner, M.; Moors, J.; Lainee, P.; Valentin, J.P.

    2012-01-01

    Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I Na ) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I Na , this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E max 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three

  19. 77 FR 44256 - Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510...

    Science.gov (United States)

    2012-07-27

    ...] Draft Guidance for Industry and Food and Drug Administration Staff; Safety Considerations for 510(k... serious and sometimes fatal consequences to patients. This guidance provides recommendations to 510(k... unintended connections between enteral and nonenteral devices. This draft guidance is not final nor is it in...

  20. Data-driven drug safety signal detection methods in pharmacovigilance using electronic primary care records: A population based study

    Directory of Open Access Journals (Sweden)

    Shang-Ming Zhou

    2017-04-01

    Data-driven analytic methods are a valuable aid to signal detection of ADEs from large electronic health records for drug safety monitoring. This study finds the methods can detect known ADE and so could potentially be used to detect unknown ADE.

  1. Patient centric drug product design in modern drug delivery as an opportunity to increase safety and effectiveness.

    Science.gov (United States)

    Stegemann, Sven

    2018-06-01

    The advances in drug delivery technologies have enabled pharmaceutical scientists to deliver a drug through various administration routes and optimize the drug release and absorption. The wide range of drug delivery systems and dosage forms represent a toolbox of technology for the development of pharmaceutical drug products but might also be a source of medication errors and nonadherence. Patient centric drug product development is being suggested as an important factor to increase therapeutic outcomes. Areas covered: Patients have impaired health and potentially disabilities and they are not medical or pharmaceutical experts but are requested to manage complex therapeutic regimens. As such the application of technology should also serve to reduce complexity, build on patients' intuition and ease of use. Patients form distinct populations based on the targeted disease, disease cluster or age group with specific characteristics or therapeutic contexts. Expert opinion: Establishing a target product and patient profile is essential to guide drug product design development. Including the targeted patient populations in the process is a prerequisite to achieve patient-centric pharmaceutical drug product design. Addressing the needs early on in the product design process, will create more universal design, avoiding the necessity for multiple product presentations to cover the different patient populations.

  2. How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.

    Science.gov (United States)

    Fleuranceau-Morel, P

    2002-01-01

    It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated

  3. Experience gained in enhancing operational safety at ComEd`s nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Elias, D [Commonwealth Edison Co. (United States)

    1997-09-01

    The following aspects of experience gained in enhancing operational safety at Comed`s nuclear power plants are discussed: nuclear safety policy; centralization/decentralization; typical nuclear operating organization; safety review boards; human performance enhancement; elements of effective nuclear oversight.

  4. Experience gained in enhancing operational safety at ComEd's nuclear power plants

    International Nuclear Information System (INIS)

    Elias, D.

    1997-01-01

    The following aspects of experience gained in enhancing operational safety at Comed's nuclear power plants are discussed: nuclear safety policy; centralization/decentralization; typical nuclear operating organization; safety review boards; human performance enhancement; elements of effective nuclear oversight

  5. Aviation Safety: FAA Oversight of Aviation Repair Stations

    Science.gov (United States)

    1998-05-07

    Testimony of Gerald L. Dillingham, Associate Director, Transportation Issues, : Resources, Community, and Economic Development Division before the Subcommittee : on Aviation, Committee on Commerce, Science, and Transportation, U.S. Senate on : the Fe...

  6. Creating a passion for safety vs. management oversight and inspection

    Science.gov (United States)

    Jim. Saveland

    1995-01-01

    I was disappointed with the OSHA report of the South Canyon Fire. My feelings are not the result of any need to defend my agency (USDA Forest Service). In another time and place, I thought the OSHA report following the death of Bill Martin (a smokejumper who died in a training jump) was right on target. In that instance I was disappointed with my agency's response...

  7. Cardiovascular safety of non-steroidal anti-inflammatory drugs among healthy individuals

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Køber, Lars; Torp-Pedersen, Christian

    2010-01-01

    Studies have raised concern on the cardiovascular safety of NSAIDs. We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.......Studies have raised concern on the cardiovascular safety of NSAIDs. We studied safety of NSAID therapy in a nationwide cohort of healthy individuals....

  8. Sponsors’ and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials

    Science.gov (United States)

    Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

    2017-01-01

    Background/aims: The Food and Drug Administration’s final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. Methods: In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative–nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. Results: The investigative site’s responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors’“filtering” of

  9. Sponsors' and investigative staffs' perceptions of the current investigational new drug safety reporting process in oncology trials.

    Science.gov (United States)

    Perez, Raymond; Archdeacon, Patrick; Roach, Nancy; Goodwin, Robert; Jarow, Jonathan; Stuccio, Nina; Forrest, Annemarie

    2017-06-01

    The Food and Drug Administration's final rule on investigational new drug application safety reporting, effective from 28 March 2011, clarified the reporting requirements for serious and unexpected suspected adverse reactions occurring in clinical trials. The Clinical Trials Transformation Initiative released recommendations in 2013 to assist implementation of the final rule; however, anecdotal reports and data from a Food and Drug Administration audit indicated that a majority of reports being submitted were still uninformative and did not result in actionable changes. Clinical Trials Transformation Initiative investigated remaining barriers and potential solutions to full implementation of the final rule by polling and interviewing investigators, clinical research staff, and sponsors. In an opinion-gathering effort, two discrete online surveys designed to assess challenges and motivations related to management of expedited (7- to 15-day) investigational new drug safety reporting processes in oncology trials were developed and distributed to two populations: investigators/clinical research staff and sponsors. Data were collected for approximately 1 year. Twenty-hour-long interviews were also conducted with Clinical Trials Transformation Initiative-nominated interview participants who were considered as having extensive knowledge of and experience with the topic. Interviewees included 13 principal investigators/study managers/research team members and 7 directors/vice presidents of pharmacovigilance operations from 5 large global pharmaceutical companies. The investigative site's responses indicate that too many individual reports are still being submitted, which are time-consuming to process and provide little value for patient safety assessments or for informing actionable changes. Fewer but higher quality reports would be more useful, and the investigator and staff would benefit from sponsors'"filtering" of reports and increased sponsor communication. Sponsors

  10. Use of toxicogenomics in drug safety evaluation: Current status and an industry perspective.

    Science.gov (United States)

    Vahle, John L; Anderson, Ulf; Blomme, Eric A G; Hoflack, Jean-Christophe; Stiehl, Daniel P

    2018-04-18

    Toxicogenomics held great promise as an approach to enable early detection of toxicities induced by xenobiotics; however, there remain questions regarding the impact of the discipline on pharmaceutical nonclinical safety assessment. To understand the current state of toxicogenomics in the sector, an industry group surveyed companies to determine the frequency of toxicogenomics use in in vivo studies at various stages of drug discovery and development and to assess how toxicogenomics use has evolved over time. Survey data were compiled during 2016 from thirteen pharmaceutical companies. Toxicogenomic analyses were infrequently conducted in the development phase and when performed were done to address specific mechanistic questions. Prior to development, toxicogenomics use was more frequent; however, there were significant differences in approaches among companies. Across all phases, gaining mechanistic insight was the most frequent reason cited for pursing toxicogenomics with few companies using toxicogenomics to predict toxicities. These data were consistent with the commentary submitted in response to survey questions asking companies to describe the evolution of their toxicogenomics strategy. Overall, these survey data indicate that toxicogenomics is not widely used as a predictive tool in the pharmaceutical industry but is used regularly by some companies and serves a broader role in mechanistic investigations and as a complement to other technologies. Copyright © 2018. Published by Elsevier Inc.

  11. Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

    Science.gov (United States)

    Somogyi, A

    1979-01-01

    The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

  12. 78 FR 22270 - Joint Meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety...

    Science.gov (United States)

    2013-04-15

    ..., indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes... Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) trial, for new drug...

  13. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  14. Regulatory oversight strategy for chemistry program at Canadian nuclear power plants

    International Nuclear Information System (INIS)

    Kameswaran; Ram

    2012-09-01

    Chemistry program is one of the essential programs for the safe operation of a nuclear power plant. It helps to ensure the necessary integrity, reliability and availability of plant structures, systems and components important to safety. Additionally, the program plays an important role in asset preservation, limiting radiation exposure and environmental protection. A good chemistry program will minimize corrosion of materials, reduce activation products, minimize of the buildup of radioactive material leading to occupational radiation exposure and it helps limit the release of chemicals and radioactive materials to the environment. The legal basis for the chemistry oversight at Canadian NPPs is established by the Nuclear Safety and Control Act and its associated regulations. It draws on the Canadian Nuclear Safety Commission's regulatory framework and NPP operating license conditions that include applicable standards such as CAN/CSA N286-05 Management System Requirements for Nuclear Power Plants. This paper focuses on the regulatory oversight strategy used in Canada to assess the performance of chemistry program at the nuclear power plants (NPPs) licensed by CNSC. The strategy consists of a combination of inspection and performance monitoring activities. The activities are further supported from information gathered through staff inspections of cross-cutting areas such as maintenance, corrective-action follow-ups, event reviews and safety related performance indicators. (authors)

  15. The safety, efficacy and regulatory triangle in drug development: Impact for animal models and the use of animals.

    Science.gov (United States)

    van Meer, Peter J K; Graham, Melanie L; Schuurman, Henk-Jan

    2015-07-15

    Nonclinical studies in animals are conducted to demonstrate proof-of-concept, mechanism of action and safety of new drugs. For a large part, in particular safety assessment, studies are done in compliance with international regulatory guidance. However, animal models supporting the initiation of clinical trials have their limitations, related to uncertainty regarding the predictive value for a clinical condition. The 3Rs principles (refinement, reduction and replacement) are better applied nowadays, with a more comprehensive application with respect to the original definition. This regards also regulatory guidance, so that opportunities exist to revise or reduce regulatory guidance with the perspective that the optimal balance between scientifically relevant data and animal wellbeing or a reduction in animal use can be achieved. In this manuscript we review the connections in the triangle between nonclinical efficacy/safety studies and regulatory aspects, with focus on in vivo testing of drugs. These connections differ for different drugs (chemistry-based low molecular weight compounds, recombinant proteins, cell therapy or gene therapy products). Regarding animal models and their translational value we focus on regulatory aspects and indications where scientific outcomes warrant changes, reduction or replacement, like for, e.g., biosimilar evaluation and safety testing of monoclonal antibodies. On the other hand, we present applications where translational value has been clearly demonstrated, e.g., immunosuppressives in transplantation. Especially for drugs of more recent date like recombinant proteins, cell therapy products and gene therapy products, a regulatory approach that allows the possibility to conduct combined efficacy/safety testing in validated animal models should strengthen scientific outcomes and improve translational value, while reducing the numbers of animals necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Nuclear health and safety

    International Nuclear Information System (INIS)

    1991-08-01

    This paper is a review of environmental and safety programs at facilities in the Naval Reactors Program which shows no basis for allegations that unsafe conditions exist there or that the environment is being harmed by activities conducted there. The prototype reactor design provides safety measures that are consistent with commercial nuclear power plants. Minor incidents affecting safety and the environment have occurred, however, and dents affecting safety and the environment have occurred, however, and as with other nuclear facilities, past activities have caused environmental problems that require ongoing monitoring and vigilance. While the program has historically been exempt from most oversight, some federal and state environmental oversight agencies have recently been permitted access to Naval Reactors facilities for oversight purposes. The program voluntarily cooperates with the Nuclear Regulatory Commission regarding reactor modifications, safety improvements, and component reliability. In addition, the program and its contractors have established an extensive internal oversight program that is geared toward reporting the slightest deviations from requirements or procedures. Given the program's classification policies and requirements, it does not appear that the program routinely overclassifies information to prevent its release to the public or to avoid embarrassment. However, GAO did not some instances in which documents were improperly classified

  17. 75 FR 2926 - Pipeline Safety: Reporting Drug and Alcohol Test Results for Contractors and Multiple Operator...

    Science.gov (United States)

    2010-01-19

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket No... Operator Identification Numbers AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT... liquid, and carbon dioxide pipelines and liquefied natural gas facilities that the Pipeline and Hazardous...

  18. SAFETY

    CERN Multimedia

    Niels Dupont

    2013-01-01

    CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

  19. Applicability and safety of dual-frequency ultrasonic treatment for the transdermal delivery of drugs

    Science.gov (United States)

    Schoellhammer, Carl M.; Srinivasan, Sharanya; Barman, Ross; Mo, Stacy H.; Polat, Baris E.; Langer, Robert; Blankschtein, Daniel

    2016-01-01

    Low-frequency ultrasound presents an attractive method for transdermal drug delivery. The controlled, yet nonspecific nature of enhancement broadens the range of therapeutics that can be delivered, while minimizing necessary reformulation efforts for differing compounds. Long and inconsistent treatment times, however, have partially limited the attractiveness of this method. Building on recent advances made in this area, the simultaneous use of low- and high-frequency ultrasound is explored in a physiologically relevant experimental setup to enable the translation of this treatment to testing in vivo. Dual-frequency ultrasound, utilizing 20 kHz and 1 MHz wavelengths simultaneously, was found to significantly enhance the size of localized transport regions (LTRs) in both in vitro and in vivo models while decreasing the necessary treatment time compared to 20 kHz alone. Additionally, LTRs generated by treatment with 20 kHz + 1 MHz were found to be more permeable than those generated with 20 kHz alone. This was further corroborated with pore-size estimates utilizing hindered-transport theory, in which the pores in skin treated with 20 kHz + 1 MHz were calculated to be significantly larger than the pores in skin treated with 20 kHz alone. This demonstrates for the first time that LTRs generated with 20 kHz + 1 MHz are also more permeable than those generated with 20 kHz alone, which could broaden the range of therapeutics and doses administered transdermally. With regard to safety, treatment with 20 kHz + 1 MHz both in vitro and in vivo appeared to result in no greater skin disruption than that observed in skin treated with 20 kHz alone, an FDA-approved modality. This study demonstrates that dual-frequency ultrasound is more efficient and effective than single-frequency ultrasound and is well-tolerated in vivo. PMID:25662228

  20. 22 CFR 96.32 - Internal structure and oversight.

    Science.gov (United States)

    2010-04-01

    ... Accreditation and Approval Licensing and Corporate Governance § 96.32 Internal structure and oversight. (a) The... number of such other provider; and (3) The name, address, and phone number of any entity it uses or...

  1. Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

    Science.gov (United States)

    Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

    2016-12-15

    Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

  2. The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

    Science.gov (United States)

    Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

    2016-01-01

    With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Health physics self-assessment and the nuclear regulatory oversight process at a nuclear power plant

    International Nuclear Information System (INIS)

    Schofield, R.S.

    2003-01-01

    The U.S. Nuclear Regulatory Commission has developed improvements in their Nuclear Power Plant inspection, assessment and enforcement practices. The objective of these changes was to link regulatory action with power plant performance through a risk- informed process which is intended to enhance objectivity. One of the Strategic Performance Areas of focus by the U.S. NRC is radiation safety. Two cornerstones, Occupational Radiation Safety and Public Radiation Safety, make up this area. These cornerstones are being evaluated through U.S. NRC Performance Indicators (PI) and baseline site inspections. Key to the U.S. NRC's oversight program is the ability of the licensee to implement a self-assessment program which pro-actively identifies potential problems and develops improvements to enhance management's effectiveness. The Health Physics Self-Assessment Program at San Onofre Nuclear Generating Station (SONGS) identifies radiation protection-related weakness or negative trends. The intended end result is improved performance through rapid problem identification, timely evaluation, corrective action and follow-up effectiveness reviews. A review of the radiation protection oversight process and the SONGS Health Physics Self-Assessment Program will be presented. Lessons learned and management tools, which evaluate workforce and Health Physics (HP) staff performance to improve radiological practices, are discussed. (author)

  4. Efficacy and safety of rabeprazole in non-steroidal anti-inflammatory drug-induced ulcer in Japan.

    Science.gov (United States)

    Mizokami, Yuji

    2009-10-28

    To investigate the efficacy and safety of rabeprazole under continuous non-steroidal anti-inflammatory drug (NSAID) administration for NSAID-induced ulcer in Japan. Subjects comprised patients undergoing NSAID treatment in whom upper gastrointestinal endoscopy revealed an ulcerous lesion (open ulcer) with diameter > or = 3 mm, who required continuous NSAID treatment. Endoscopies were performed at the start of treatment, during the treatment period, and at the conclusion (or discontinuation) of treatment. Findings were evaluated as size (maximum diameter) and stage based on the Sakita-Miwa classification. An ulcer was regarded as cured when the "white coating" was seen to have disappeared under endoscopy. As criteria for evaluating safety, all medically untoward symptoms and signs (adverse events, laboratory abnormalities, accidental symptoms, etc.) occurring after the start of rabeprazole treatment were handled as adverse events. Endoscopic cure rate in 38 patients in the efficacy analysis (endoscopic evaluation) was 71.1% (27/38). Among those 38 patients, 35 had gastric ulcer with a cure rate of 71.4% (25/35), and 3 had duodenal ulcer with a cure rate of 66.7% (2/3). Three adverse drug reactions were reported from 64 patients in the safety analysis (interstitial pneumonia, low white blood cell count and pruritus); thus, the incidence rate for adverse drug reactions was 4.7% (3/64). The treatment efficacy of rabeprazole for NSAID-induced ulcer under continuous NSAID administration was confirmed.

  5. 78 FR 10107 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules To Establish Standards...

    Science.gov (United States)

    2013-02-13

    ... AGENCY: Food and Drug Administration, HHS. ACTION: Notification of public meeting. SUMMARY: The Food and Drug Administration (FDA) is providing public meeting registration information for two FSMA related... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 1, 16, 106, 110...

  6. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    Energy Technology Data Exchange (ETDEWEB)

    Marks, Louise, E-mail: louise.marks@astrazeneca.com [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Kirk, Sarah [Innovative Medicines, Discovery Sciences, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom); Valentin, Jean-Pierre [Safety Assessment UK, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG (United Kingdom)

    2012-09-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt{sub max} and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability.

  7. The role of the anaesthetised guinea-pig in the preclinical cardiac safety evaluation of drug candidate compounds

    International Nuclear Information System (INIS)

    Marks, Louise; Borland, Samantha; Philp, Karen; Ewart, Lorna; Lainée, Pierre; Skinner, Matthew; Kirk, Sarah; Valentin, Jean-Pierre

    2012-01-01

    Despite rigorous preclinical and clinical safety evaluation, adverse cardiac effects remain a leading cause of drug attrition and post-approval drug withdrawal. A number of cardiovascular screens exist within preclinical development. These screens do not, however, provide a thorough cardiac liability profile and, in many cases, are not preventing the progression of high risk compounds. We evaluated the suitability of the anaesthetised guinea-pig for the assessment of drug-induced changes in cardiovascular parameters. Sodium pentobarbitone anaesthetised male guinea-pigs received three 15 minute intravenous infusions of ascending doses of amoxicillin, atenolol, clonidine, dobutamine, dofetilide, flecainide, isoprenaline, levosimendan, milrinone, moxifloxacin, nifedipine, paracetamol, verapamil or vehicle, followed by a 30 minute washout. Dose levels were targeted to cover clinical exposure and above, with plasma samples obtained to evaluate effect/exposure relationships. Arterial blood pressure, heart rate, contractility function (left ventricular dP/dt max and QA interval) and lead II electrocardiogram were recorded throughout. In general, the expected reference compound induced effects on haemodynamic, contractility and electrocardiographic parameters were detected confirming that all three endpoints can be measured accurately and simultaneously in one small animal. Plasma exposures obtained were within, or close to the expected clinical range of therapeutic plasma levels. Concentration–effect curves were produced which allowed a more complete understanding of the margins for effects at different plasma exposures. This single in vivo screen provides a significant amount of information pertaining to the cardiovascular risk of drug candidates, ultimately strengthening strategies addressing cardiovascular-mediated compound attrition and drug withdrawal. -- Highlights: ► Evaluation of the anaesthetised guinea-pig to determine cardiac liability. ► Haemodynamic

  8. Safety

    International Nuclear Information System (INIS)

    2001-01-01

    This annual report of the Senior Inspector for the Nuclear Safety, analyses the nuclear safety at EDF for the year 1999 and proposes twelve subjects of consideration to progress. Five technical documents are also provided and discussed concerning the nuclear power plants maintenance and safety (thermal fatigue, vibration fatigue, assisted control and instrumentation of the N4 bearing, 1300 MW reactors containment and time of life of power plants). (A.L.B.)

  9. Strategies for the early detection of drug-induced hepatic steatosis in preclinical drug safety evaluation studies

    International Nuclear Information System (INIS)

    Amacher, David E.

    2011-01-01

    Hepatic steatosis is characterized by the accumulation of lipid droplets in the liver. Although relatively benign, simple steatosis can eventually lead to the development of steatohepatitis, a more serious condition characterized by fibrosis, cirrhosis, and eventual liver failure if the underlying cause is not eliminated. According to the 'two hit' theory of steatohepatitis, the initial hit involves fat accumulation in the liver, and a second hit leads to inflammation and subsequent tissue injury. Because some xenobiotics target liver fatty acid metabolism, especially mitochondrial β-oxidation, it is important to avoid potential drug candidates that can contribute to either the initiation of liver steatosis or progression to the more injurious steatohepatitis. The gold standard for the detection of these types of hepatic effects is histopathological examination of liver tissue. In animal studies, these examinations are slow, restricted to a single sampling time, and limited tissue sections. Recent literature suggests that rapid in vitro screening methods can be used early in the drug R and D process to identify compounds with steatotic potential. Further, progress in the identification of potential serum or plasma protein biomarkers for these liver changes may provide additional in vivo tools to the preclinical study toxicologist. This review summarizes recent developments for in vitro screening and in vivo biomarker detection for steatotic drug candidates.

  10. Influence of companion diagnostics on efficacy and safety of targeted anti-cancer drugs: systematic review and meta-analyses.

    Science.gov (United States)

    Ocana, Alberto; Ethier, Josee-Lyne; Díez-González, Laura; Corrales-Sánchez, Verónica; Srikanthan, Amirrtha; Gascón-Escribano, María J; Templeton, Arnoud J; Vera-Badillo, Francisco; Seruga, Bostjan; Niraula, Saroj; Pandiella, Atanasio; Amir, Eitan

    2015-11-24

    Companion diagnostics aim to identify patients that will respond to targeted therapies, therefore increasing the clinical efficacy of such drugs. Less is known about their influence on safety and tolerability of targeted anti-cancer agents. Randomized trials evaluating targeted agents for solid tumors approved by the US Food and Drug Administration since year 2000 were assessed. Odds ratios (OR) and and 95% confidence intervals (CI) were computed for treatment-related death, treatment-discontinuation related to toxicity and occurrence of any grade 3/4 adverse events (AEs). The 12 most commonly reported individual AEs were also explored. ORs were pooled in a meta-analysis. Analysis comprised 41 trials evaluating 28 targeted agents. Seventeen trials (41%) utilized companion diagnostics. Compared to control groups, targeted drugs in experimental arms were associated with increased odds of treatment discontinuation, grade 3/4 AEs, and toxic death irrespective of whether they utilized companion diagnostics or not. Compared to drugs without available companion diagnostics, agents with companion diagnostics had a lower magnitude of increased odds of treatment discontinuation (OR = 1.12 vs. 1.65, p diagnostics were greatest for diarrhea (OR = 1.29 vs. 2.43, p diagnostics are associated with improved safety, and tolerability. Differences were most marked for gastrointestinal, cutaneous and neurological toxicity.

  11. Development of novel, 384-well high-throughput assay panels for human drug transporters: drug interaction and safety assessment in support of discovery research.

    Science.gov (United States)

    Tang, Huaping; Shen, Ding Ren; Han, Yong-Hae; Kong, Yan; Balimane, Praveen; Marino, Anthony; Gao, Mian; Wu, Sophie; Xie, Dianlin; Soars, Matthew G; O'Connell, Jonathan C; Rodrigues, A David; Zhang, Litao; Cvijic, Mary Ellen

    2013-10-01

    Transporter proteins are known to play a critical role in affecting the overall absorption, distribution, metabolism, and excretion characteristics of drug candidates. In addition to efflux transporters (P-gp, BCRP, MRP2, etc.) that limit absorption, there has been a renewed interest in influx transporters at the renal (OATs, OCTs) and hepatic (OATPs, BSEP, NTCP, etc.) organ level that can cause significant clinical drug-drug interactions (DDIs). Several of these transporters are also critical for hepatobiliary disposition of bilirubin and bile acid/salts, and their inhibition is directly implicated in hepatic toxicities. Regulatory agencies took action to address transporter-mediated DDI with the goal of ensuring drug safety in the clinic and on the market. To meet regulatory requirements, advanced bioassay technology and automation solutions were implemented for high-throughput transporter screening to provide structure-activity relationship within lead optimization. To enhance capacity, several functional assay formats were miniaturized to 384-well throughput including novel fluorescence-based uptake and efflux inhibition assays using high-content image analysis as well as cell-based radioactive uptake and vesicle-based efflux inhibition assays. This high-throughput capability enabled a paradigm shift from studying transporter-related issues in the development space to identifying and dialing out these concerns early on in discovery for enhanced mechanism-based efficacy while circumventing DDIs and transporter toxicities.

  12. Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Chaparro, M; Verreth, A; Lobaton, T

    2018-01-01

    OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs...... in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non......-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox...

  13. Regulatory Expectations for Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-05-15

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

  14. Regulatory Expectations for Safety Culture

    International Nuclear Information System (INIS)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

    2014-01-01

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety

  15. Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

    Science.gov (United States)

    Tyczynski, Jerzy E; Oleske, Denise M; Klingman, David; Ferrufino, Cheryl P; Lee, Won Chan

    2012-08-01

    the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.

  16. 78 FR 49988 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules on Foreign Supplier...

    Science.gov (United States)

    2013-08-16

    ... help manage the safety of their global food supply chains. The purpose of the public meeting is to... electronic or written comments to FDA's Division of Dockets Management. ADDRESSES: See section II, ``How to... protect public health by helping to ensure the safety and security of the food supply. FSMA amends the...

  17. 78 FR 57320 - Food and Drug Administration Food Safety Modernization Act: Proposed Rules on Foreign Supplier...

    Science.gov (United States)

    2013-09-18

    ... help manage the safety of their global food supply chains. The purpose of these public meetings is to... submitting either electronic or written comments to FDA's Division of Dockets Management. ADDRESSES: See..., to better protect public health by helping to ensure the safety and security of the food supply. FSMA...

  18. Home closure as a weapon in the Dutch war on drugs: Does judicial review function as a safety net?

    Science.gov (United States)

    Bruijn, L Michelle; Vols, Michel; Brouwer, Jan G

    2018-01-01

    A widespread sense of a failing criminal justice system and increased feelings of insecurity changed the response to crime into a culture of control, which is characterized by policies that punish and exclude. In the Netherlands, these influences can be witnessed in the war on drugs where local authorities use their administrative power to close homes involved in drug-related crime. Citizens can invoke judicial review over these administrative interferences by claiming that such closure results in an unfair balance between purposes, means and consequences. This paper assesses whether judicial review functions as a safety net against losing one's home due to drug-related crime. We used doctrinal legal research methods to examine the "law in the books" and empirical legal research methods to analyse the "law in action". We used a survey to investigate how often the drug-related closure power was used in 2015, and we statistically analysed all published case law of Dutch lower courts between 2007 and 2016. The scope of the closure power broadened over the years and our data show that local authorities fiercely make use of this instrument. In 41.4% of the cases, citizens are successful in fighting the closure. While scholarly literature indicates that judicial courts function as safeguards by questioning the proportionality of administrative action, raising a proportionality defence does not necessarily result in a more favourable outcome for citizens. In fact, raising a proportionality defence makes it more likely to result in dismissal of the appeal. The stretched scope of the drug-related closure power together with the relatively low success rate of citizens who fight the loss of their home and a seemingly meaningless proportionality check show no sign of a safety net against the loss of one's home at the suit of a local authority. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Clinical Relation Extraction Toward Drug Safety Surveillance Using Electronic Health Record Narratives: Classical Learning Versus Deep Learning.

    Science.gov (United States)

    Munkhdalai, Tsendsuren; Liu, Feifan; Yu, Hong

    2018-04-25

    Medication and adverse drug event (ADE) information extracted from electronic health record (EHR) notes can be a rich resource for drug safety surveillance. Existing observational studies have mainly relied on structured EHR data to obtain ADE information; however, ADEs are often buried in the EHR narratives and not recorded in structured data. To unlock ADE-related information from EHR narratives, there is a need to extract relevant entities and identify relations among them. In this study, we focus on relation identification. This study aimed to evaluate natural language processing and machine learning approaches using the expert-annotated medical entities and relations in the context of drug safety surveillance, and investigate how different learning approaches perform under different configurations. We have manually annotated 791 EHR notes with 9 named entities (eg, medication, indication, severity, and ADEs) and 7 different types of relations (eg, medication-dosage, medication-ADE, and severity-ADE). Then, we explored 3 supervised machine learning systems for relation identification: (1) a support vector machines (SVM) system, (2) an end-to-end deep neural network system, and (3) a supervised descriptive rule induction baseline system. For the neural network system, we exploited the state-of-the-art recurrent neural network (RNN) and attention models. We report the performance by macro-averaged precision, recall, and F1-score across the relation types. Our results show that the SVM model achieved the best average F1-score of 89.1% on test data, outperforming the long short-term memory (LSTM) model with attention (F1-score of 65.72%) as well as the rule induction baseline system (F1-score of 7.47%) by a large margin. The bidirectional LSTM model with attention achieved the best performance among different RNN models. With the inclusion of additional features in the LSTM model, its performance can be boosted to an average F1-score of 77.35%. It shows that

  20. Documentation of pediatric drug safety in manufacturers' product monographs: a cross-sectional evaluation of the canadian compendium of pharmaceuticals and specialities.

    Science.gov (United States)

    Uppal, Navjeet K; Dupuis, Lee L; Parshuram, Christopher S

    2008-01-01

    To describe the provision of pediatric drug safety information in a national formulary of manufacturers' drug product monographs. We performed a cross-sectional evaluation of comprehensive product monographs contained in the 2005 Canadian Compendium of Pharmaceuticals and Specialities (CPS). We abstracted data describing indications for prescription, statements about pediatric safety, available preparations, and provision of dosing guidelines. For each monograph we classified pediatric safety data as either present, present but limited or absent. We then described the pediatric safety data in CPS monographs for drugs listed in the published formulary of the Hospital for Sick Children, Toronto, Ontario, Canada. A total of 2232 product monographs were screened; 684 were excluded and 1548 (66%) were further analyzed. 1462 (94%) had indications that did not exclude children. Pediatric safety information was present in 592 (38%), present but limited in 148 (10%), and absent in 808 (52%) drug monographs. Safety statements were absent in 224 (14%) drug monographs that provided both dosing guidelines and formulations suitable for administration to children, and in 214 (52%) of 411 drugs in the pediatric hospital formulary. We evaluated a widely available national source of pediatric prescribing information. Safety data for children was not mentioned in more than half of the product monographs. Moreover, the provision of safety data was discordant with indications for prescription, the availability of pediatric formulations, and dosing guidelines within the monographs, and with inclusion in a pediatric hospital formulary. Our study suggests that the presentation of pediatric safety data in drug product monographs can be improved to better inform prescribing and to optimize pharmacotherapy in children.

  1. Regulatory Oversight of the Legacy Gunner Uranium Mine and Mill Site in Northern Saskatchewan, Canada - 13434

    Energy Technology Data Exchange (ETDEWEB)

    Stenson, Ron; Howard, Don [Canadian Nuclear Safety Commission, P.O. Box 1046, Station B, 280 Slater Street, Ottawa ON K1P 5S9 (Canada)

    2013-07-01

    As Canada's nuclear regulator, the Canadian Nuclear Safety Commission (CNSC) is responsible for licensing all aspects of uranium mining, including remediation activities at legacy sites. Since these sites already existed when the current legislation came into force in 2000, and the previous legislation did not apply, they present a special case. The Nuclear Safety and Control Act (NSCA), was written with cradle-to- grave oversight in mind. Applying the NSCA at the end of a 'facilities' life-cycle poses some challenges to both the regulator and the proponent. When the proponent is the public sector, even more challenges can present themselves. Although the licensing process for legacy sites is no different than for any other CNSC license, assuring regulatory compliance can be more complicated. To demonstrate how the CNSC has approached the oversight of legacy sites the history of the Commission's involvement with the Gunnar uranium mine and mill site provides a good case study. The lessons learned from the CNSC's experience regulating the Gunnar site will benefit those in the future who will need to regulate legacy sites under existing or new legislation. (authors)

  2. The US Food and Drug Administration’s drug safety recommendations and long-acting beta2-agonist dispensing pattern changes in adult asthma patients: 2003–2012

    Directory of Open Access Journals (Sweden)

    Zhou EH

    2017-03-01

    Full Text Available Esther H Zhou,1 Sally Seymour,2 Margie R Goulding,1 Elizabeth M Kang,1 Jacqueline M Major,1 Solomon Iyasu1 1Division of Epidemiology, Office of Surveillance and Epidemiology, 2Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA Background: Emerging safety issues associated with long-acting beta2-agonist (LABA have led to multiple regulatory activities by the US Food and Drug Administration (FDA since 2003, including Drug Safety Communications (DSCs in 2010. These DSCs had three specific recommendations for the safe use of LABA products in adult asthma treatment. Methods: We examined the initiation of LABA-containing products for adult asthma treatment using an intermittent time series approach in a claims database from 2003 to 2012. We assessed the alignment of dispensing patterns with the following 2010 FDA recommendations: 1 contraindicated use of single-ingredient (SI-LABA without an asthma controller medication (ACM; 2 a LABA should only be used when asthma is not adequately controlled on inhaled corticosteroids (ICSs or ACM; and 3 step-down asthma therapy (e.g., discontinue LABA when asthma control is achieved. Results: There were 477,922 adults (18–64 years old dispensed a new LABA during 2003–2012. Among LABA initiators, patients who initiated an SI-LABA and who did “not” have an ACM dispensed on the same date decreased from >9% in 2003 (the initial labeling change to <2% post 2010 DSCs (p-value <0.0001 in the segmented regression model. The proportion of asthma patients dispensed an ICS in 6 months prior to initiating LABA treatment did not increase. The proportion of patients with longer than 4 months of continuous treatment did not decrease over the study period. Conclusion: Although the decrease in SI-LABA initiation is consistent with FDA’s recommendations, low ICS dispensing before initiating a LABA and LABA continuation practices require further efforts

  3. Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

    Science.gov (United States)

    Kirtane, Ameya R; Rothenberger, Meghan K; Frieberg, Abby; Nephew, Karla; Schultz-Darken, Nancy; Schmidt, Thomas; Reimann, Thomas; Haase, Ashley T; Panyam, Jayanth

    2017-07-01

    The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. Nuclear safety in perspective

    DEFF Research Database (Denmark)

    Andersson, K.; Sjöberg, B.M.D.; Lauridsen, Kurt

    2003-01-01

    The aim of the NKS/SOS-1 project has been to enhance common understanding about requirements for nuclear safety by finding improved means of communicat-ing on the subject in society. The project, which has been built around a number of seminars, wassupported by limited research in three sub......-projects: Risk assessment Safety analysis Strategies for safety management The report describes an industry in change due to societal factors. The concepts of risk and safety, safety management and systems forregulatory oversight are de-scribed in the nuclear area and also, to widen the perspective, for other...

  5. Effect of Safety Issues with HIV Drugs on the Approval Process of Other Drugs in the Same Class An Analysis of European Public Assessment Reports : an analysis of European public assessment reports

    NARCIS (Netherlands)

    Arnardottir, Arna H.; Haaijer-Ruskamp, Flora M.; Straus, Sabine M. J.; de Graeff, Pieter A.; Mol, Peter G. M.

    2011-01-01

    Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required >= 1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. Objective:

  6. Illicit Internet availability of drugs subject to recall and patient safety consequences.

    Science.gov (United States)

    Mackey, Tim K; Aung, Phyo; Liang, Bryan A

    2015-12-01

    Permanently recalled drugs are a public health concern if they remain accessible in violation of applicable regulation. Illicit online pharmacies act as an alternative form of access and have been associated with the sale to patients of counterfeit/falsified/fraudulent/substandard drugs. We wished to determine if permanently recalled and significantly restricted drugs were illegally marketed for sale online. The study was conducted in two phases with two objectives. The first phase attempted to identify drugs subject to permanent recall in certain major pharmaceutical markets as well as those listed as recalled or significantly restricted by the United Nations. We also examined the market authorization status of identified drugs in China and India. The second phase used structured searches on the Internet to determine if identified drugs were marketed for sale online. The World Wide Web. After identification of permanently recalled and restricted drugs we conducted Internet searches for illegal "no prescription" marketing events. We assessed the form of marketing, whether a site offered direct-to-patient sale, use of social media marketing, and the site's compliance status with external monitoring bodies. Number of recalled drugs marketed as available for purchase on the Internet. We identified 16 class I equivalent permanently recalled or restricted drugs, 56.3 % (n = 9) of which maintained market authorization in either China or India. Half (n = 8) were marketed for sale online without a prescription direct-to-patient. Use of social media marketing was mixed, with only 18.8 % (n = 3) of recalled drugs having a presence on Facebook, though 50.0 % (n = 8) had content on Twitter. We also found the majority (68.8 %, n = 11) were available and marketed for sale by vendors on the wholesale/business-to-business website alibaba.com primarily as active pharmaceutical ingredient. Despite efforts in several countries to restrict access to these drugs or permanently remove

  7. Leachables and extractables handbook: safety evaluation, qualification, and best practices applied to inhalation drug products

    National Research Council Canada - National Science Library

    Ball, Douglas J

    2012-01-01

    ...). It discusses best practices for evaluation and management of leachables and extractables throughout the pharma product lifecycle by providing practical knowledge about how and why safety thresholds were developed...

  8. EFFICACY AND SAFETY OF LIPID-LOWERING DRUGS IN PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASES IN THE ELDERLY

    Directory of Open Access Journals (Sweden)

    E. A. Ushkalova

    2016-01-01

    Full Text Available Effect of hyperlipidemia on morbidity and mortality in elderly patients is considered. Authors also cover issues of efficacy and safety of lipid-lowering therapy in primary and secondary prevention of cardiovascular diseases in patients ≥80 years of age who are the most quickly growing group of population and have the highest cardiovascular risk. They stress the need to take into account polymorbidity and polypharmacy that increase the risk of adverse reactions due to the use of both statins and their drug-drug interactions, which requires an assessment of risk/benefit ratio. In addition, there is a need for development of reliable prognostic tools to predict relevant outcomes (e.g., stroke, decrease in functionality/independence, quality of life reduction and rationales for lipid-lowering therapy in the elderly and also their adherence to treatment.

  9. Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.

    Science.gov (United States)

    Ferrari, Raffaele; Talamini, Laura; Violatto, Martina Bruna; Giangregorio, Paola; Sponchioni, Mattia; Morbidelli, Massimo; Salmona, Mario; Bigini, Paolo; Moscatelli, Davide

    2017-01-03

    Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.

  10. Efficacy and Safety of Drug-Eluting Stents in the Real World: 8-Year Follow-Up

    Energy Technology Data Exchange (ETDEWEB)

    Pellegrini, Denise Oliveira, E-mail: dennizmo@yahoo.com.br; Gomes, Vitor Osório; Lasevitch, Ricardo; Smidt, Luis; Azeredo, Marco Aurélio; Ledur, Priscila; Bodanese, Rodrigo; Sinnott, Leonardo; Moriguchi, Emílio; Caramori, Paulo [Hospital São Lucas PUC, Porto Alegre, RS (Brazil)

    2014-09-15

    Drug-eluting stents have been used in daily practice since 2002, with the clear advantages of reducing the risk of target vessel revascularization and an impressive reduction in restenosis rate by 50%-70%. However, the occurrence of a late thrombosis can compromise long-term results, particularly if the risks of this event were sustained. In this context, a registry of clinical cases gains special value. To evaluate the efficacy and safety of drug-eluting stents in the real world. We report on the clinical findings and 8-year follow-up parameters of all patients that underwent percutaneous coronary intervention with a drug-eluting stent from January 2002 to April 2007. Drug-eluting stents were used in accordance with the clinical and interventional cardiologist decision and availability of the stent. A total of 611 patients were included, and clinical follow-up of up to 8 years was obtained for 96.2% of the patients. Total mortality was 8.7% and nonfatal infarctions occurred in 4.3% of the cases. Target vessel revascularization occurred in 12.4% of the cases, and target lesion revascularization occurred in 8% of the cases. The rate of stent thrombosis was 2.1%. There were no new episodes of stent thrombosis after the fifth year of follow-up. Comparative subanalysis showed no outcome differences between the different types of stents used, including Cypher®, Taxus®, and Endeavor®. These findings indicate that drug-eluting stents remain safe and effective at very long-term follow-up. Patients in the 'real world' may benefit from drug-eluting stenting with excellent, long-term results.

  11. Patient safety: numerical skills and drug calculation abilities of nursing students and registered nurses.

    Science.gov (United States)

    McMullan, Miriam; Jones, Ray; Lea, Susan

    2010-04-01

    This paper is a report of a correlational study of the relations of age, status, experience and drug calculation ability to numerical ability of nursing students and Registered Nurses. Competent numerical and drug calculation skills are essential for nurses as mistakes can put patients' lives at risk. A cross-sectional study was carried out in 2006 in one United Kingdom university. Validated numerical and drug calculation tests were given to 229 second year nursing students and 44 Registered Nurses attending a non-medical prescribing programme. The numeracy test was failed by 55% of students and 45% of Registered Nurses, while 92% of students and 89% of nurses failed the drug calculation test. Independent of status or experience, older participants (> or = 35 years) were statistically significantly more able to perform numerical calculations. There was no statistically significant difference between nursing students and Registered Nurses in their overall drug calculation ability, but nurses were statistically significantly more able than students to perform basic numerical calculations and calculations for solids, oral liquids and injections. Both nursing students and Registered Nurses were statistically significantly more able to perform calculations for solids, liquid oral and injections than calculations for drug percentages, drip and infusion rates. To prevent deskilling, Registered Nurses should continue to practise and refresh all the different types of drug calculations as often as possible with regular (self)-testing of their ability. Time should be set aside in curricula for nursing students to learn how to perform basic numerical and drug calculations. This learning should be reinforced through regular practice and assessment.

  12. A comparative analysis of drug safety withdrawals in the UK and the US (1971-1992): implications for current regulatory thinking and policy.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2005-09-01

    By going beyond individual case studies and solely quantitative surveys, this paper systematically examines why there were over twice as many new prescription drugs withdrawn from the market on grounds of safety in the UK as there were in the US between 1971 and 1992. Drawing on interviews with regulators, industry scientists and others involved, and on regulatory data never before accessed outside governments and companies, five key hypotheses which might explain this difference in drug safety withdrawals are analysed. These are: (1) simply because the UK approved more new drugs than the US; (2) because of an industrial corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3) because British regulators were more vigilant at spotting post-marketing safety problems than their US counterparts; (4) because the slowness of the US in approving new drugs enabled regulators there to learn from, and avoid, safety problems that had already emerged in the UK or European market; and (5) because more stringent regulation in the US meant that they approved fewer unsafe drugs on to the market in the first place. It is concluded that the main explanation for fewer drug safety withdrawals in the US is that the regulatory agency there applied more stringent pre-market review and/or standards, which took longer than UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering the US market. Contrary to the claims frequently made by the pharmaceutical industry and regulatory agencies on both sides of the Atlantic, these results imply that it is likely that acceleration of regulatory review times in the US and the UK since the early 1990s is compromising drug safety.

  13. 1993 Annual performance report for Environmental Oversight and Monitoring at Department of Energy facilities in New Mexico

    International Nuclear Information System (INIS)

    1993-01-01

    In October of 1990, the New Mexico Environment Department entered into an agreement with the US Department of Energy (DOE) to create the Department of Energy Oversight and Monitoring Program. This program is designed to create an avenue for the State to ensure DOE facilities are in compliance with applicable environmental regulations, to allow the State oversight and monitoring independent of the DOE, to allow the State valuable input into remediation decision making, and to protect the environment and the public health and safety of New Mexicans concerning DOE facility activities. This agreement, called the Agreement in Principle (AIP), includes all four of New Mexico's DOE facilities: Los Alamos National Laboratory in Los Alamos; Sandia National Laboratories and the Inhalation Toxicology Research Institute on Kirtland Air Force Base in Albuquerque; and the Waste Isolation Pilot Plant near Carlsbad

  14. Drug safety in pregnancy: utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services.

    Science.gov (United States)

    Schaefer, Christof

    2011-03-01

    Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology. © 2011 The Author. Congenital Anomalies © 2011 Japanese Teratology Society.

  15. A Cost Analysis of Hospitalizations for Infections Related to Injection Drug Use at a County Safety-Net Hospital in Miami, Florida

    OpenAIRE

    Tookes, Hansel; Diaz, Chanelle; Li, Hua; Khalid, Rafi; Doblecki-Lewis, Susanne

    2015-01-01

    Background Infections related to injection drug use are common. Harm reduction strategies such as syringe exchange programs and skin care clinics aim to prevent these infections in injection drug users (IDUs). Syringe exchange programs are currently prohibited by law in Florida. The goal of this study was to estimate the mortality and cost of injection drug use-related bacterial infections over a 12-month period to the county safety-net hospital in Miami, Florida. Additionally, the prevalence...

  16. 75 FR 10507 - Information Security Oversight Office; National Industrial Security Program Policy Advisory...

    Science.gov (United States)

    2010-03-08

    ... NATIONAL ARCHIVES AND RECORDS ADMINISTRATION Information Security Oversight Office; National Industrial Security Program Policy Advisory Committee (NISPPAC) AGENCY: National Archives and Records... individuals planning to attend must be submitted to the Information Security Oversight Office (ISOO) no later...

  17. Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a brief report.

    Science.gov (United States)

    Meyer, Roger E; Salzman, Carl; Youngstrom, Eric A; Clayton, Paula J; Goodwin, Frederick K; Mann, J John; Alphs, Larry D; Broich, Karl; Goodman, Wayne K; Greden, John F; Meltzer, Herbert Y; Normand, Sharon-Lise T; Posner, Kelly; Shaffer, David; Oquendo, Maria A; Stanley, Barbara; Trivedi, Madhukar H; Turecki, Gustavo; Beasley, Charles M; Beautrais, Annette L; Bridge, Jeffrey A; Brown, Gregory K; Revicki, Dennis A; Ryan, Neal D; Sheehan, David V

    2010-08-01

    disagreement at the conference have been noted in the text. The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's encouragement of standard definitions and definable expectations for investigators and industry sponsors. Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the requirement that all central nervous system clinical drug trials must include a Columbia Classification Algorithm of Suicide Assessment (C-CASA)-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed. Copyright 2010 Physicians Postgraduate Press, Inc.

  18. Suicidality and risk of suicide--definition, drug safety concerns, and a necessary target for drug development: a consensus statement.

    Science.gov (United States)

    Meyer, Roger E; Salzman, Carl; Youngstrom, Eric A; Clayton, Paula J; Goodwin, Frederick K; Mann, J John; Alphs, Larry D; Broich, Karl; Goodman, Wayne K; Greden, John F; Meltzer, Herbert Y; Normand, Sharon-Lise T; Posner, Kelly; Shaffer, David; Oquendo, Maria A; Stanley, Barbara; Trivedi, Madhukar H; Turecki, Gustavo; Beasley, Charles M; Beautrais, Annette L; Bridge, Jeffrey A; Brown, Gregory K; Revicki, Dennis A; Ryan, Neal D; Sheehan, David V

    2010-08-01

    . Any areas of disagreement have been noted. The term suicidality is not as clinically useful as more specific terminology (ideation, behavior, attempts, and suicide). Most participants applauded the FDA's effort to promote standard definitions and definable expectations for investigators and industry sponsors by endorsing the terminology in the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Further research of available assessment instruments is needed to verify their utility, reliability, and validity in identifying suicide-associated treatment-emergent adverse effects and/or a signal of efficacy in suicide prevention trials. The FDA needs to build upon its new authority to systematically monitor postmarketing events by encouraging the development of a validated instrument for postmarketing surveillance of suicidal ideation, behavior, and risk within informative large health care-related databases in the United States and abroad. Over time, the FDA, industry, and clinical researchers should evaluate the impact of the current Agency requirement that all CNS clinical drug trials must include a C-CASA-compatible screening instrument for assessing and documenting the occurrence of treatment-emergent suicidal ideation and behavior. Finally, patients at high risk for suicide can safely be included in clinical trials, if proper precautions are followed, and they need to be included to enable premarket assessments of the risks and benefits of medications related to suicidal ideation, suicidal behavior, and suicide in such patients. Copyright 2010 Physicians Postgraduate Press, Inc.

  19. A New Concept of a Drug Delivery System with Improved Precision and Patient Safety Features

    Directory of Open Access Journals (Sweden)

    Florian Thoma

    2014-12-01

    Full Text Available This paper presents a novel dosing concept for drug delivery based on a peristaltic piezo-electrically actuated micro membrane pump. The design of the silicon micropump itself is straight-forward, using two piezoelectrically actuated membrane valves as inlet and outlet, and a pump chamber with a piezoelectrically actuated pump membrane in-between. To achieve a precise dosing, this micropump is used to fill a metering unit placed at its outlet. In the final design this metering unit will be made from a piezoelectrically actuated inlet valve, a storage chamber with an elastic cover membrane and a piezoelectrically actuated outlet valve, which are connected in series. During a dosing cycle the metering unit is used to adjust the drug volume to be dispensed before delivery and to control the actually dispensed volume. To simulate the new drug delivery concept, a lumped parameter model has been developed to find the decisive design parameters. With the knowledge taken from the model a drug delivery system is designed that includes a silicon micro pump and, in a first step, a silicon chip with the storage chamber and two commercial microvalves as a metering unit. The lumped parameter model is capable to simulate the maximum flow, the frequency response created by the micropump, and also the delivered volume of the drug delivery system.

  20. Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

    Science.gov (United States)

    Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

    2016-12-12

    The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

  1. Regulatory Oversight of Cell and Gene Therapy Products in Canada.

    Science.gov (United States)

    Ridgway, Anthony; Agbanyo, Francisca; Wang, Jian; Rosu-Myles, Michael

    2015-01-01

    Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.

  2. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

    Science.gov (United States)

    Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-01-01

    Objectives To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. Design Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. Setting Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. Main outcome measures Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. Results Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. Conclusions Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are

  3. Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study.

    Science.gov (United States)

    Ye, Xiaobu; Itzoe, MariaLisa; Sarabia-Estrada, Rachel; DeTolla, Louis; Tyler, Betty M; Guarnieri, Michael

    2018-01-01

    Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg) showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.

  4. Suspected Lonely Mouse Syndrome as a Cage Effect in a Drug Safety Study

    Directory of Open Access Journals (Sweden)

    Xiaobu Ye

    2018-01-01

    Full Text Available Studies have demonstrated that buprenorphine, a front line drug for veterinary analgesia, may alleviate symptoms of chronic pain. A cage side observation protocol was used to record behavioral signs in a mouse clinical trial of extended release buprenorphine. A retrospective review of the observations for signs of pain and stress revealed that mice given a fivefold overdose of buprenorphine (16.25 mg/kg showed lethargy and facial signs associated with stress. However, similar signs were observed in the drug-free control mice as early as Day 3 of single-cage housing. This appears to be the first report of cage effects in a clinical trial for a veterinary drug.

  5. Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing

    Directory of Open Access Journals (Sweden)

    Francis A. Ortega

    2018-01-01

    Full Text Available Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

  6. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    International Nuclear Information System (INIS)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y.

    2014-01-01

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  7. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

    2014-09-15

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  8. Safety of antiretroviral drugs in pregnancy and breastfeeding for mother and child

    NARCIS (Netherlands)

    Newell, Marie-Louise; Bunders, Madeleine J.

    2013-01-01

    Purpose of reviewThe introduction of combination ART to prevent mother-to-child-transmission (MTCT) has substantially decreased MTCT rates. However, there are concerns regarding safety of ART exposure for the mother, pregnancy outcome and infant. Changing MTCT prevention guidelines, with expanded

  9. The role of electronic healthcare record databases in paediatric drug safety surveillance: A retrospective cohort study

    NARCIS (Netherlands)

    S. de Bie (Sandra); P.M. Coloma (Preciosa); C. Ferrajolo (Carmen); K.M.C. Verhamme (Katia); G. Trifirò (Gianluca); M.J. Schuemie (Martijn); S.M.J.M. Straus (Sabine); R. Gini (Rosa); R.M.C. Herings (Ron); G. Mazzaglia (Giampiero); G. Picelli (Gino); A. Ghirardi (Arianna); L. Pedersen (Lars); B.H.Ch. Stricker (Bruno); J. van der Lei (Johan); M.C.J.M. Sturkenboom (Miriam)

    2015-01-01

    textabstractAim Electronic healthcare record (EHR)-based surveillance systems are increasingly being developed to support early detection of safety signals. It is unknown what the power of such a system is for surveillance among children and adolescents. In this paper we provide estimates of the

  10. Double pharmacological challenge on repolarization opens new avenues for drug safety research

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard

    2007-01-01

    pointes (TdP) arrhythmia. Both the pharmaceutical industry and the regulatory bodies are neglecting the available proarrhythmia models. In vitro studies have suggested that combined pharmacological hits on repolarization will produce a superior substrate for in vivo proarrhythmia, compared to the single......-drug assessment. By using consecutive pharmacological challenges, a simple model is proposed, in which combinatorial pharmacology is employed to provoke TdP in the conscious dog. The pharmaceutical industry interested in evaluating the proarrhythmic potential of their present and future drugs now has a simple...

  11. The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity

    International Nuclear Information System (INIS)

    Amacher, David E.

    2010-01-01

    Biomarkers are biometric measurements that provide critical quantitative information about the biological condition of the animal or individual being tested. In drug safety studies, established toxicity biomarkers are used along with other conventional study data to determine dose-limiting organ toxicity, and to define species sensitivity for new chemical entities intended for possible use as human medicines. A continuing goal of drug safety scientists in the pharmaceutical industry is to discover and develop better trans-species biomarkers that can be used to determine target organ toxicities for preclinical species in short-term studies at dose levels that are some multiple of the intended human dose and again later in full development for monitoring clinical trials at lower therapeutic doses. Of particular value are early, predictive, noninvasive biomarkers that have in vitro, in vivo, and clinical transferability. Such translational biomarkers bridge animal testing used in preclinical science and human studies that are part of subsequent clinical testing. Although suitable for in vivo preclinical regulatory studies, conventional hepatic safety biomarkers are basically confirmatory markers because they signal organ toxicity after some pathological damage has occurred, and are therefore not well-suited for short-term, predictive screening assays early in the discovery-to-development progression of new chemical entities (NCEs) available in limited quantities. Efforts between regulatory agencies and the pharmaceutical industry are underway for the coordinated discovery, qualification, verification and validation of early predictive toxicity biomarkers. Early predictive safety biomarkers are those that are detectable and quantifiable prior to the onset of irreversible tissue injury and which are associated with a mechanism of action relevant to a specific type of potential hepatic injury. Potential drug toxicity biomarkers are typically endogenous macromolecules in

  12. Essential Aspects in Assessing the Safety Impact of Interactions between a Drug Product and Its Associated Manufacturing System.

    Science.gov (United States)

    Jenke, Dennis

    2012-01-01

    An emerging trend in the biotechnology industry is the utilization of plastic components in manufacturing systems for the production of an active pharmaceutical ingredient (API) or a finished drug product (FDP). If the API, the FDP, or any solution used to generate them (for example, process streams such as media, buffers, and the like) come in contact with a plastic at any time during the manufacturing process, there is the potential that substances leached from the plastic may accumulate in the API or FDP, affecting safety and/or efficacy. In this article the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the article outlines the safety assessment process for manufacturing systems, specifically addressing the topics of risk management and the role of compendial testing. Finally, the proper use of vendor-supplied extractables information is considered. Manufacturing suites used to produce biopharmaceuticals can include components that are made out of plastics. Thus it is possible that substances could leach out of the plastics and into manufacturing solutions, and it is further possible that such leachables could accumulate in the pharmaceutical product. In this article, the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the author proposes a process by which the impact on product safety of such leached substances can be assessed.

  13. 12 CFR 1700.1 - Office of Federal Housing Enterprise Oversight.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Office of Federal Housing Enterprise Oversight. 1700.1 Section 1700.1 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF... of Federal Housing Enterprise Oversight. (a) Scope and authority. The Office of Federal Housing...

  14. Comparative study on drug safety surveillance between medical students of Malaysia and Nigeria.

    Science.gov (United States)

    Abubakar, Abdullahi Rabiu; Ismail, Salwani; Rahman, Nor Iza A; Haque, Mainul

    2015-01-01

    Internationally, there is a remarkable achievement in the areas of drug discovery, drug design, and clinical trials. New and efficient drug formulation techniques are widely available which have led to success in treatment of several diseases. Despite these achievements, large number of patients continue to experience adverse drug reactions (ADRs), and majority of them are yet to be on record. The purpose of this survey is to compare knowledge, attitude, and practice with respect to ADRs and pharmacovigilance (PV) between medical students of Malaysia and Nigeria and to determine if there is a relationship between their knowledge and practice. A cross-sectional, questionnaire-based survey involving year IV and year V medical students of the Department of Medicine, Universiti Sultan Zainal Abidin and Bayero University Kano was carried out. The questionnaire which comprised 25 questions on knowledge, attitude, and practice was adopted, modified, validated, and administered to them. The response was analyzed using SPSS version 20. The response rate from each country was 74%. There was a statistically significant difference in mean knowledge and practice score on ADRs and PV between medical students of Malaysia and Nigeria, both at PMalaysia, although they need improvement. Imparting knowledge of ADRs and PV among medical students will upgrade their practice and enhance health care delivery services in the future.

  15. Targeting outpatient drug safety: recommendations of the Dutch HARM-Wrestling Task Force.

    NARCIS (Netherlands)

    Warle-van Herwaarden, M.F.; Kramers, C.; Sturkenboom, M.C.; Bemt, P.M. van den; Smet, P.A.G.M. de

    2012-01-01

    BACKGROUND: Two Dutch observational studies (HARM [Hospital Admissions Related to Medication] and IPCI [Integrated Primary Care Information]) have shown that approximately 5% of all unplanned hospital admissions are associated with adverse drug events (ADEs), of which 40-46% are potentially

  16. Use and Safety of Non-Steroidal Inflammatory Drugs and Aspirin

    NARCIS (Netherlands)

    V.E. Valkhoff (Vera)

    2012-01-01

    textabstractThe use of acetylsalicylic acid, better known as aspirin, dates back to the Egyptians in 1534 BC. Aspirin-like compounds are naturally derived from willow tree bark and myr-tle. At the end of the 19th century aspirin was patented by Bayer as the world’s first syn-thetic drug. The

  17. Safety information on QT-interval prolongation : comparison of European Union and United States drug labeling

    NARCIS (Netherlands)

    Warnier, Miriam J.; Holtkamp, Frank A.; Rutten, Frans H.; Hoes, Arno W.; de Boer, Anthonius; Mol, Peter G M; De Bruin, Marie L.

    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approved

  18. Safety information on QT-interval prolongation : Comparison of European Union and United States drug labeling

    NARCIS (Netherlands)

    Warnier, Miriam J.; Holtkamp, Frank A.; Rutten, Frans H.; Hoes, Arno W.; de Boer, Anthonius; Mol, Peter G. M.; De Bruin, Marie L.

    Prolongation of the QT interval can predispose to fatal ventricular arrhythmias. Differences in QT-labeling language can result in miscommunication and suboptimal risk mitigation. We systematically compared the phraseology used to communicate on QT-prolonging properties of 144 drugs newly approved

  19. Integrated cardiac safety: assessment methodologies for noncardiac drugs in discovery, development, and postmarketing surveillance

    National Research Council Canada - National Science Library

    Turner, J. Rick; Durham, Todd A

    2009-01-01

    ... PROTEOMICS AND TRANSCRIPTOMICS 2.8 GENE EXPRESSION 2.9 PROTEINS 2.10 CELLS 2.11 CELL MEMBRANES 2.12 PROTEINS IN CELL MEMBRANES 2.13 ION CHANNELS 2.14 RECEPTORS ADVERSE DRUG REACTIONS MELANOGASTER 25 ...

  20. Measuring the impact of pharmacoepidemiologic research using altmetrics: A case study of a CNODES drug-safety article.

    Science.gov (United States)

    Gamble, J M; Traynor, Robyn L; Gruzd, Anatoliy; Mai, Philip; Dormuth, Colin R; Sketris, Ingrid S

    2018-03-24

    To provide an overview of altmetrics, including their potential benefits and limitations, how they may be obtained, and their role in assessing pharmacoepidemiologic research impact. Our review was informed by compiling relevant literature identified through searching multiple health research databases (PubMed, Embase, and CIHNAHL) and grey literature sources (websites, blogs, and reports). We demonstrate how pharmacoepidemiologists, in particular, may use altmetrics to understand scholarly impact and knowledge translation by providing a case study of a drug-safety study conducted by the Canadian Network of Observational Drug Effect Studies. A common approach to measuring research impact is the use of citation-based metrics, such as an article's citation count or a journal's impact factor. "Alternative" metrics, or altmetrics, are increasingly supported as a complementary measure of research uptake in the age of social media. Altmetrics are nontraditional indicators that capture a diverse set of traceable, online research-related artifacts including peer-reviewed publications and other research outputs (software, datasets, blogs, videos, posters, policy documents, presentations, social media posts, wiki entries, etc). Compared with traditional citation-based metrics, altmetrics take a more holistic view of research impact, attempting to capture the activity and engagement of both scholarly and nonscholarly communities. Despite the limited theoretical underpinnings, possible commercial influence, potential for gaming and manipulation, and numerous data quality-related issues, altmetrics are promising as a supplement to more traditional citation-based metrics because they can ingest and process a larger set of data points related to the flow and reach of scholarly communication from an expanded pool of stakeholders. Unlike citation-based metrics, altmetrics are not inherently rooted in the research publication process, which includes peer review; it is unclear to

  1. Nanotechnology, voluntary oversight, and corporate social performance: does company size matter?

    Science.gov (United States)

    Kuzma, Jennifer; Kuzhabekova, Aliya

    2011-04-01

    In this article, we examine voluntary oversight programs for nanotechnology in the context of corporate social performance (CSP) in order to better understand the drivers, barriers, and forms of company participation in such programs. At the theoretical level, we use the management framework of CSP to understand the voluntary behavior of companies. At the empirical level, we investigate nanotech industry participation in the Environmental Protection Agency's Nanoscale Materials Stewardship Program (NMSP) as an example of CSP, in order to examine the effects of company characteristics on CSP outcomes. The analysis demonstrates that, on the average, older and larger companies for which nanotech is one of the many business activities demonstrate greater CSP as judged by company actions, declarations, and self-evaluations. Such companies tended to submit more of the requested information to the NMSP, including specific information about health and safety, and to claim fewer of the submitted items as confidential business information. They were also more likely to have on-line statements of generic and nano-specific corporate social responsibility principles, policies, and achievements. The article suggests a need to encourage smaller and younger companies to participate in voluntary oversight programs for nanotechnology and presents options for better design of these programs.

  2. Nanotechnology, voluntary oversight, and corporate social performance: does company size matter?

    International Nuclear Information System (INIS)

    Kuzma, Jennifer; Kuzhabekova, Aliya

    2011-01-01

    In this article, we examine voluntary oversight programs for nanotechnology in the context of corporate social performance (CSP) in order to better understand the drivers, barriers, and forms of company participation in such programs. At the theoretical level, we use the management framework of CSP to understand the voluntary behavior of companies. At the empirical level, we investigate nanotech industry participation in the Environmental Protection Agency’s Nanoscale Materials Stewardship Program (NMSP) as an example of CSP, in order to examine the effects of company characteristics on CSP outcomes. The analysis demonstrates that, on the average, older and larger companies for which nanotech is one of the many business activities demonstrate greater CSP as judged by company actions, declarations, and self-evaluations. Such companies tended to submit more of the requested information to the NMSP, including specific information about health and safety, and to claim fewer of the submitted items as confidential business information. They were also more likely to have on-line statements of generic and nano-specific corporate social responsibility principles, policies, and achievements. The article suggests a need to encourage smaller and younger companies to participate in voluntary oversight programs for nanotechnology and presents options for better design of these programs.

  3. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Science.gov (United States)

    2010-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products...). Dexfenfluramine hydrochloride: All drug products containing dexfenfluramine hydrochloride. Diamthazole... dihydrostreptomycin sulfate. Dipyrone: All drug products containing dipyrone. Encainide hydrochloride: All drug...

  4. The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

    Science.gov (United States)

    da Silva, Ricardo Eccard; Amato, Angélica Amorim; Sousa, Thiago do Rego; de Carvalho, Marta Rodrigues; Novaes, Maria Rita Carvalho Garbi

    2018-05-12

    Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

  5. Trends in qualifying biomarkers in drug safety. Consensus of the 2011 meeting of the spanish society of clinical pharmacology.

    Science.gov (United States)

    Agúndez, José A G; Del Barrio, Jaime; Padró, Teresa; Stephens, Camilla; Farré, Magí; Andrade, Raúl J; Badimon, Lina; García-Martín, Elena; Vilahur, Gemma; Lucena, M Isabel

    2012-01-01

    In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field.

  6. 13 CFR 120.1070 - Lender oversight fees.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Lender oversight fees. 120.1070 Section 120.1070 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based... Lender” means a Small Business Lending Company or a Non-Federally Regulated Lender. (2) On-site reviews...

  7. Oversight of Department of Defense Reconstruction Projects in Afghanistan

    Science.gov (United States)

    2016-03-16

    had to reschedule some of our site visits multiple times due to security conditions. As an alternative means for conducting oversight, due to a limited...employed less than 20 percent of the staff it was expected to employ. According to the doctors and nurses on site during our inspection, the limited

  8. 15 CFR 2008.18 - Information Security Oversight Committee.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Information Security Oversight Committee. 2008.18 Section 2008.18 Commerce and Foreign Trade Regulations Relating to Foreign Trade Agreements OFFICE OF THE UNITED STATES TRADE REPRESENTATIVE REGULATIONS TO IMPLEMENT E.O. 12065; OFFICE OF...

  9. Notification: Oversight of Clean Water State Revolving Loan Funds

    Science.gov (United States)

    Project #OA-FY15-0153, April 6, 2015. The Office of Inspector General (OIG) for the U.S. Environmental Protection Agency (EPA) is beginning preliminary research on the EPA oversight of the Clean Water State Revolving Fund (CWSRF).

  10. 40 CFR 51.362 - Motorist compliance enforcement program oversight.

    Science.gov (United States)

    2010-07-01

    ... deviate from established requirements, or in the case of non-government entities that process... registrations; and (10) The prevention of fraudulent procurement or use of inspection documents by controlling... measurements. (c) SIP requirements. The SIP shall include a description of enforcement program oversight and...

  11. Strategic planning of an integrated program for state oversight agreements

    International Nuclear Information System (INIS)

    Walzer, A.E.; Cothron, T.K.

    1991-01-01

    Among the barrage of agreements faced by federal facilities are the State Oversight Agreements (known as Agreements in Principle in many states). These agreements between the Department of Energy (DOE) and the states fund the states to conduct independent environmental monitoring and oversight which requires plans, studies, inventories, models, and reports from DOE and its management and operating contractors. Many states have signed such agreements, including Tennessee, Kentucky, Washington, Idaho, Colorado, California, and Florida. This type of oversight agreement originated in Colorado as a result of environmental concerns at the Rocky Flats Plant. The 5-year State Oversight Agreements for Tennessee and Kentucky became effective on May 13, 1991, and fund these states nearly $21 million and $7 million, respectively. Implementation of these open-quotes comprehensive and integratedclose quotes agreements is particularly complex in Tennessee where the DOE Oak Ridge Reservation houses three installations with distinctly different missions. The program development and strategic planning required for coordinating and integrating a program of this magnitude is discussed. Included are the organizational structure and interfaces required to define and coordinate program elements across plants and to also effectively negotiate scope and schedules with the state. The planned Program Management Plan, which will contain implementation and procedural guidelines, and the management control system for detailed tracking of activities and costs are outlined. Additionally, issues inherent in the nature of the agreements and implementation of a program of this magnitude are discussed. Finally, a comparison of the agreements for Tennessee, Kentucky, Colorado, and Idaho is made to gain a better understanding of the similarities and differences in State Oversight Agreements to aid in implementation of these agreements

  12. A modular, prospective, semi-automated drug safety monitoring system for use in a distributed data environment.

    Science.gov (United States)

    Gagne, Joshua J; Wang, Shirley V; Rassen, Jeremy A; Schneeweiss, Sebastian

    2014-06-01

    The aim of this study was to develop and test a semi-automated process for conducting routine active safety monitoring for new drugs in a network of electronic healthcare databases. We built a modular program that semi-automatically performs cohort identification, confounding adjustment, diagnostic checks, aggregation and effect estimation across multiple databases, and application of a sequential alerting algorithm. During beta-testing, we applied the system to five databases to evaluate nine examples emulating prospective monitoring with retrospective data (five pairs for which we expected signals, two negative controls, and two examples for which it was uncertain whether a signal would be expected): cerivastatin versus atorvastatin and rhabdomyolysis; paroxetine versus tricyclic antidepressants and gastrointestinal bleed; lisinopril versus angiotensin receptor blockers and angioedema; ciprofloxacin versus macrolide antibiotics and Achilles tendon rupture; rofecoxib versus non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs) and myocardial infarction; telithromycin versus azithromycin and hepatotoxicity; rosuvastatin versus atorvastatin and diabetes and rhabdomyolysis; and celecoxib versus ns-NSAIDs and myocardial infarction. We describe the program, the necessary inputs, and the assumed data environment. In beta-testing, the system generated four alerts, all among positive control examples (i.e., lisinopril and angioedema; rofecoxib and myocardial infarction; ciprofloxacin and tendon rupture; and cerivastatin and rhabdomyolysis). Sequential effect estimates for each example were consistent in direction and magnitude with existing literature. Beta-testing across nine drug-outcome examples demonstrated the feasibility of the proposed semi-automated prospective monitoring approach. In retrospective assessments, the system identified an increased risk of myocardial infarction with rofecoxib and an increased risk of rhabdomyolysis with cerivastatin years

  13. Illegal "no prescription" internet access to narrow therapeutic index drugs.

    Science.gov (United States)

    Liang, Bryan A; Mackey, Tim K; Lovett, Kimberly M

    2013-05-01

    Narrow therapeutic index (NTI) drugs, because of proximity of therapeutic amounts to toxic amounts, require close professional oversight, particularly when switching formulations. However, safe use may be compromised by unsupervised switching through access to online "no prescription" Web sites. We assessed no prescription online availability of NTI drugs, using an academically published list (core NTI drugs). Using the Google search term "buy DRUG no prescription," we reviewed the first 5 search result pages for marketing of no prescription NTI drugs. We further assessed if National Association of Boards of Pharmacy (NABP) Not Recommended vendors were marketing NTI drugs. Searches were conducted from November 3, 2012 to January 3, 2013. For core NTI drugs, we found 13 of 14 NTI drugs (92%) marketed as available without prescription, all from NABP Not Recommended vendors. On the basis of these initial findings, we expanded our core list to 12 additional NTI drugs; 11 of 12 of these drugs (92%) were available from no prescription Web sites. Overall, 24 of 26 NTI drugs (92%) were illegally marketed as available online without the need for a prescription. Suspect online NTI drug access from no prescription vendors represents a significant patient safety risk because of potential patient drug switching and risk of counterfeit versions. Further, state health care exchanges with coverage limitations may drive patients to seek formulations online. Food and Drug Administration harmonization with tighter international NTI drug standards should be considered, and aggressive action against suspect online marketers should be a regulatory and public health priority. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  14. 1992 Annual performance report for Environmental Monitoring and Oversight at Department of Energy facilities in New Mexico

    Energy Technology Data Exchange (ETDEWEB)

    1992-12-31

    In October 1990 an Agreement-in-Principle (AIP) was entered into between the US Department of Energy (DOE) and the State of New Mexico for the purpose of supporting State oversight activities at DOE facilities in New Mexico. The State`s lead agency for the Agreement is the New Mexico Environment Department (NMED). DOE has agreed to provide the State with resources over a five year period to support State activities in environmental oversight, monitoring, access and emergency response to ensure compliance with applicable federal, state, and local laws at Los Alamos National Laboratory (LANL), Sandia National Laboratories (SNL), the Waste Isolation Pilot Plant (WIPP), and the Inhalation Toxicology Research Institute (ITRI). The Agreement is designed to assure the citizens of New Mexico that public health, safety and the environment are being protected through existing programs; DOE is in compliance with applicable laws and regulations; DOE has made substantial new commitments; cleanup and compliance activities have been prioritized; and a vigorous program of independent monitoring and oversight by the State is underway. This report relates the quality and effectiveness of the facilities` environmental monitoring and surveillance programs. This report satisfies that requirement for the January--December 1992 time frame.

  15. 1992 Annual performance report for Environmental Monitoring and Oversight at Department of Energy facilities in New Mexico

    International Nuclear Information System (INIS)

    1992-01-01

    In October 1990 an Agreement-in-Principle (AIP) was entered into between the US Department of Energy (DOE) and the State of New Mexico for the purpose of supporting State oversight activities at DOE facilities in New Mexico. The State's lead agency for the Agreement is the New Mexico Environment Department (NMED). DOE has agreed to provide the State with resources over a five year period to support State activities in environmental oversight, monitoring, access and emergency response to ensure compliance with applicable federal, state, and local laws at Los Alamos National Laboratory (LANL), Sandia National Laboratories (SNL), the Waste Isolation Pilot Plant (WIPP), and the Inhalation Toxicology Research Institute (ITRI). The Agreement is designed to assure the citizens of New Mexico that public health, safety and the environment are being protected through existing programs; DOE is in compliance with applicable laws and regulations; DOE has made substantial new commitments; cleanup and compliance activities have been prioritized; and a vigorous program of independent monitoring and oversight by the State is underway. This report relates the quality and effectiveness of the facilities' environmental monitoring and surveillance programs. This report satisfies that requirement for the January--December 1992 time frame

  16. SAFETY

    CERN Multimedia

    M. Plagge, C. Schaefer and N. Dupont

    2013-01-01

    Fire Safety – Essential for a particle detector The CMS detector is a marvel of high technology, one of the most precise particle measurement devices we have built until now. Of course it has to be protected from external and internal incidents like the ones that can occur from fires. Due to the fire load, the permanent availability of oxygen and the presence of various ignition sources mostly based on electricity this has to be addressed. Starting from the beam pipe towards the magnet coil, the detector is protected by flooding it with pure gaseous nitrogen during operation. The outer shell of CMS, namely the yoke and the muon chambers are then covered by an emergency inertion system also based on nitrogen. To ensure maximum fire safety, all materials used comply with the CERN regulations IS 23 and IS 41 with only a few exceptions. Every piece of the 30-tonne polyethylene shielding is high-density material, borated, boxed within steel and coated with intumescent (a paint that creates a thick co...

  17. SAFETY

    CERN Multimedia

    C. Schaefer and N. Dupont

    2013-01-01

      “Safety is the highest priority”: this statement from CERN is endorsed by the CMS management. An interpretation of this statement may bring you to the conclusion that you should stop working in order to avoid risks. If the safety is the priority, work is not! This would be a misunderstanding and misinterpretation. One should understand that “working safely” or “operating safely” is the priority at CERN. CERN personnel are exposed to different hazards on many levels on a daily basis. However, risk analyses and assessments are done in order to limit the number and the gravity of accidents. For example, this process takes place each time you cross the road. The hazard is the moving vehicle, the stake is you and the risk might be the risk of collision between both. The same principle has to be applied during our daily work. In particular, keeping in mind the general principles of prevention defined in the late 1980s. These principles wer...

  18. [HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

    Science.gov (United States)

    Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

    2017-04-01

    In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands

  19. Safety

    International Nuclear Information System (INIS)

    Jones, P.M.S.

    1987-01-01

    Aspects of fission reactors are considered - control, heat removal and containment. Brief descriptions of the reactor accidents at the SL-1 reactor (1961), Windscale (1957), Browns Ferry (1975), Three Mile Island (1979) and Chernobyl (1986) are given. The idea of inherently safe reactor designs is discussed. Safety assessment is considered under the headings of preliminary hazard analysis, failure mode analysis, event trees, fault trees, common mode failure and probabalistic risk assessments. These latter can result in a series of risk distributions linked to specific groups of fault sequences and specific consequences. A frequency-consequence diagram is shown. Fatal accident incidence rates in different countries including the United Kingdom for various industries are quoted. The incidence of fatal cancers from occupational exposure to chemicals is tabulated. Human factors and the acceptability of risk are considered. (U.K.)

  20. Schistosoma haematobium treatment in 1-5 year old children: safety and efficacy of the antihelminthic drug praziquantel.

    Directory of Open Access Journals (Sweden)

    Francisca Mutapi

    2011-05-01

    Full Text Available Morbidity due to schistosomiasis is currently controlled by treatment of schistosome infected people with the antihelminthic drug praziquantel (PZQ. Children aged up to 5 years are currently excluded from schistosome control programmes largely due to the lack of PZQ safety data in this age group. This study investigated the safety and efficacy of PZQ treatment in such children.Zimbabwean children aged 1-5 years (n = 104 were treated with PZQ tablets and side effects were assessed by questionnaire administered to their caregivers within 24 hours of taking PZQ. Treatment efficacy was determined 6 weeks after PZQ administration through schistosome egg counts in urine. The change in infection levels in the children 1-5 years old (n = 100 was compared to that in 6-10 year old children (n = 435.Pre-treatment S. haematobium infection intensity in 1-5 year olds was 14.6 eggs/10 ml urine and prevalence was 21%. Of the 104 children, 3.8% reported side effects within 24 hours of taking PZQ treatment. These were stomach ache, loss of appetite, lethargy and inflammation of the face and body. PZQ treatment significantly reduced schistosome infection levels in 1-5 year olds with an egg reduction rate (ERR of 99% and cure rate (CR of 92%. This was comparable to the efficacy of praziquantel in 6-10 year olds where ERR was 96% and CR was 67%. INTERPRETATION/SIGNIFICANCE: PZQ treatment is as safe and efficacious in children aged 1-5 years as it is in older children aged 6-10 years in whom PZQ is the drug of choice for control of schistosome infections.

  1. [Drug management of prisoners: Role of the pharmaceutical staff to ensure patient safety].

    Science.gov (United States)

    Lalande, L; Bertin, C; Rioufol, C; Boleor, P; Cabelguenne, D

    2016-03-01

    In the prisons of Lyon, drug management of inmates implies cooperation between general practitioners, psychiatrists and pharmacists. All the medical prescriptions are reviewed by the pharmacists of the medical unit. The aim of this work was to synthesize the pharmaceutical interventions performed and show the implication of the pharmaceutical staff in detecting and handling prescribing errors. Pharmaceutical interventions performed between the 1st of June 2012 and the 31st December 2014 and entered in the Act-IP(®) database (SFPC) were retrospectively analyzed. Among the 18,205 prescriptions reviewed, 4064 (22.3%) had a prescription error. The main problems encountered were by decreasing order of frequency: missing monitoring (15% of the interventions), lack of compliance (13%), over dosage (10%), lack of conformity with recommendations or consensus (8%). Interventions were accepted in 78% cases. Most prescribing errors implied medications of the central nervous system. Among the interventions, 8% were initiated by pharmacy technicians, mainly lack of compliance. The pharmaceutical interventions reported reflected actions of securisation initiated by the pharmacists in cooperation with physicians: monitoring of patients taking antipsychotic medications or benzodiazepines maximal dosages. Besides, in this population with a high prevalence of psychiatric comorbidities and important suicide rate, detection of patients with default of compliance is one of the keys for drug optimization among these patients as it is an explanation for therapeutic failure. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  2. Mathematical calculation skills required for drug administration in undergraduate nursing students to ensure patient safety: A descriptive study: Drug calculation skills in nursing students.

    Science.gov (United States)

    Bagnasco, Annamaria; Galaverna, Lucia; Aleo, Giuseppe; Grugnetti, Anna Maria; Rosa, Francesca; Sasso, Loredana

    2016-01-01

    In the literature we found many studies that confirmed our concerns about nursing students' poor maths skills that directly impact on their ability to correctly calculate drug dosages with very serious consequences for patient safety. The aim of our study was to explore where students had most difficulty and identify appropriate educational interventions to bridge their mathematical knowledge gaps. This was a quali-quantitative descriptive study that included a sample of 726 undergraduate nursing students. We identified exactly where students had most difficulty and identified appropriate educational interventions to bridge their mathematical knowledge gaps. We found that the undergraduate nursing students mainly had difficulty with basic maths principles. Specific learning interventions are needed to improve their basic maths skills and their dosage calculation skills. For this purpose, we identified safeMedicate and eDose (Authentic World Ltd.), only that they are only available in English. In the near future we hope to set up a partnership to work together on the Italian version of these tools. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells

    International Nuclear Information System (INIS)

    Noor, Fozia; Niklas, Jens; Mueller-Vieira, Ursula; Heinzle, Elmar

    2009-01-01

    Efficient and accurate safety assessment of compounds is extremely important in the preclinical development of drugs especially when hepatotoxicty is in question. Multiparameter and time resolved assays are expected to greatly improve the prediction of toxicity by assessing complex mechanisms of toxicity. An integrated approach is presented in which Hep G2 cells and primary rat hepatocytes are compared in frequently used cytotoxicity assays for parent compound toxicity. The interassay variability was determined. The cytotoxicity assays were also compared with a reliable alternative time resolved respirometric assay. The set of training compounds consisted of well known hepatotoxins; amiodarone, carbamazepine, clozapine, diclofenac, tacrine, troglitazone and verapamil. The sensitivity of both cell systems in each tested assay was determined. Results show that careful selection of assay parameters and inclusion of a kinetic time resolved assay improves prediction for non-metabolism mediated toxicity using Hep G2 cells as indicated by a sensitivity ratio of 1. The drugs with EC 50 values 100 μM or lower were considered toxic. The difference in the sensitivity of the two cell systems to carbamazepine which causes toxicity via reactive metabolites emphasizes the importance of human cell based in-vitro assays. Using the described system, primary rat hepatocytes do not offer advantage over the Hep G2 cells in parent compound toxicity evaluation. Moreover, respiration method is non invasive, highly sensitive and allows following the time course of toxicity. Respiration assay could serve as early indicator of changes that subsequently lead to toxicity.

  4. Workplace violence among female sex workers who use drugs in Vancouver, Canada: does client-targeted policing increase safety?

    Science.gov (United States)

    Prangnell, Amy; Shannon, Kate; Nosova, Ekaterina; DeBeck, Kora; Milloy, M-J; Kerr, Thomas; Hayashi, Kanna

    2018-02-01

    Workplace violence, by clients or predators, poses serious negative health consequences for sex workers. In 2013, the Vancouver (British Columbia), Canada Police Department changed their guidelines with the goal of increasing safety for sex workers by focusing law enforcement on clients and third parties, but not sex workers. We sought to examine the trends and correlates of workplace violence among female sex workers (FSW) before and after the guideline change, using data collected from prospective cohorts of persons who use illicit drugs in Vancouver, Canada. Among 259 FSW, 21.0% reported workplace violence at least once during the study period between 2008 and 2014. There was no statistically significant change in rates of workplace violence after the guideline change. In our multivariable analysis, daily heroin use was independently associated with workplace violence. The 2013 policing guideline change did not appear to have resulted in decreased reports of workplace violence. Increased access to opioid agonist therapies may reduce workplace violence among drug-using FSW.

  5. Performing Drug Safety Research During Pregnancy and Lactation: Biomedical HIV Prevention Research as a Template.

    Science.gov (United States)

    Beigi, Richard H; Noguchi, Lisa; Brown, Gina; Piper, Jeanna; Watts, D Heather

    2016-07-01

    Evidence-based guidance regarding use of nearly all pharmaceuticals by pregnant and lactating women is limited. Models for performing research may assist in filling these knowledge gaps. Internationally, reproductive age women are at high risk of human immunodeficiency virus (HIV) acquisition. Susceptibility to HIV infection may be increased during pregnancy, and risk of maternal-child transmission is increased with incident HIV infection during pregnancy and lactation. A multidisciplinary meeting of experts was convened at the United States National Institutes of Health to consider paradigms for drug research in pregnancy and lactation applicable to HIV prevention. This report summarizes the meeting proceedings and describes a framework for research on candidate HIV prevention agent use during pregnancy and lactation that may also have broader applications to other pharmaceutical products.

  6. Enhancing board oversight on quality of hospital care: an agency theory perspective.

    Science.gov (United States)

    Jiang, H Joanna; Lockee, Carlin; Fraser, Irene

    2012-01-01

    Community hospitals in the United States are almost all governed by a governing board that is legally accountable for the quality of care provided. Increasing pressures for better quality and safety are prompting boards to strengthen their oversight function on quality. In this study, we aimed to provide an update to prior research by exploring the role and practices of governing boards in quality oversight through the lens of agency theory and comparing hospital quality performance in relation to the adoption of those practices. Data on board practices from a survey conducted by The Governance Institute in 2007 were merged with data on hospital quality drawn from two federal sources that measured processes of care and mortality. The study sample includes 445 public and private not-for-profit hospitals. We used factor analysis to explore the underlying dimensions of board practices. We further compared hospital quality performance by the adoption of each individual board practice. Consistent with the agency theory, the 13 board practices included in the survey appear to center around enhancing accountability of the board, management, and the medical staff. Reviewing the hospital's quality performance on a regular basis was the most common practice. A number of board practices, not examined in prior research, showed significant association with better performance on process of care and/or risk-adjusted mortality: requiring major new clinical programs to meet quality-related criteria, setting some quality goals at the "theoretical ideal" level, requiring both the board and the medical staff to be as involved as management in setting the agenda for discussion on quality, and requiring the hospital to report its quality/safety performance to the general public. Hospital governing boards should examine their current practices and consider adopting those that would enhance the accountability of the board itself, management, and the medical staff.

  7. Novel designed polyoxyethylene nonionic surfactant with improved safety and efficiency for anticancer drug delivery

    Directory of Open Access Journals (Sweden)

    Li C

    2014-04-01

    Full Text Available Chang Li,1 Chunmeng Sun,1 Shasha Li,1 Peng Han,2 Huimin Sun,3 Ammar Ouahab,1 Yan Shen,1 Yourui Xu,1 Yerong Xiong,1 Jiasheng Tu11State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 2Chinese Pharmacopoeia Commission, Beijing, 3National Institute for Food and Drug Control, Beijing, People's Republic of ChinaAbstract: In order to limit the adverse reactions caused by polysorbate 80 in Taxotere®, a widely used formulation of docetaxel, a safe and effective nanocarrier for this drug has been developed based on micelles formed by a new class of well-defined polyoxyethylene sorbitol oleate (PSO with sorbitol as the matrix in aqueous solution. The physicochemical properties of the amphiphilic surfactant and the resulting micelles can be easily fine-tuned by the homogeneous sorbitol matrix and pure oleic acid. Composition, critical micelle concentration, and entrapment efficiency were investigated by ultraviolet visible spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, fluorospectrophotometry, and high-performance liquid chromatography. In vitro and in vivo evaluation revealed that PSO had exceptionally low hemolysis and histamine release rates compared with commercial polysorbate 80. Moreover, the tumor targeting delivery of PSO was investigated by in vivo imaging in S180 tumor-bearing mice. The results suggest that this novel delivery system, PSO, provides an acceptable alternative to polysorbate 80 for delivery of docetaxel. Further, due to the hypoallergenic nature of PSO, the mechanism of pseudoallergy caused by the polyoxyethylene nonionic surfactant was investigated. Based on in vitro cell analysis, it was assumed that the initial contact of polyoxyethylene nonionic surfactant with mast cells provoked pseudoallergy via polyamine receptor-mediated endocytosis.Keywords: polyoxyethylene nonionic surfactant, sorbitol, isosorbide, pseudoallergy

  8. Drug development strategies for the treatment of obesity: how to ensure efficacy, safety, and sustainable weight loss

    Directory of Open Access Journals (Sweden)

    Barja-Fernandez S

    2014-12-01

    Full Text Available S Barja-Fernandez,1–3 R Leis,2 FF Casanueva,3,4 LM Seoane1,3 1Grupo Fisiopatología Endocrina, 2Departamento de Pediatría, Universidad de Santiago de Compostela (USC, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS, Santiago de Compostela, Spain; 3CIBER Fisiopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Santiago de Compostela, Spain; 4Laboratorio de Endocrinología Molecular y Celular, Universidad de Santiago de Compostela (USC Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS, Complexo Hospitalario Universitario de Santiago (CHUS/SERGAS, Santiago de Compostela, Spain Abstract: The prevalence of obesity has increased worldwide, and approximately 25%–35% of the adult population is obese in some countries. The excess of body fat is associated with adverse health consequences. Considering the limited efficacy of diet and exercise in the current obese population and the use of bariatric surgery only for morbid obesity, it appears that drug therapy is the only available method to address the problem on a large scale. Currently, pharmacological obesity treatment options are limited. However, new antiobesity drugs acting through central nervous system pathways or the peripheral adiposity signals and gastrointestinal tract are under clinical development. One of the most promising approaches is the use of peptides that influence the peripheral satiety signals and brain–gut axis such as GLP-1 analogs. However, considering that any antiobesity drug may affect one or several of the systems that control food intake and energy expenditure, it is unlikely that a single pharmacological agent will be effective as a striking obesity treatment. Thus, future strategies to treat obesity will need to be directed at sustainable weight loss to ensure maximal safety. This strategy will probably require the coadministration of medications

  9. Safety concerns and hidden agenda behind HPV vaccines: another generation of drug-dependent society?

    Science.gov (United States)

    Khatami, Mahin

    2016-12-01

    Analyses of data and hidden agenda behind repeated failed outcomes of cancer research and therapy, status of American health, safety concerns for HPV vaccines and future research considerations are summarized in this commentary. A closer look at cancer science reveals that highly power structure (system) in medical establishment vs. anti-system and chaos in cancer research ('medical/scientific ponzi schemes') is potent recipe for failed therapeutics that kills patients but generates huge corporate profit. American health status ranks last among other developed nations despite the highest amount that USA invests in healthcare. This is a wake-up call to make sure that the evil part of human being does not prevent the health services that the public deserves. Otherwise, 'it does not matter how many resources you have, if you don't know, or don't want to know, how to use them, they will never be enough'. Answer to cancer and improved public health is possible only by switching the current corruptive and abusive culture of 'who you know' to a culture of 'what you know'. Policy makers and professionals in decision making roles are urged to return to common sense and logics that our Forefathers used to serve the public.

  10. Methotrexate: Revisited efficiency and safety of drug administration in psoriasis patients

    Directory of Open Access Journals (Sweden)

    A. L. Bakulev

    2017-01-01

    Full Text Available The article presents the current data of the literature on methotrexate, which is now one of the most commonly used preparation for the systemic treatment of patients with moderate to severe psoriasis. The following problems are under consideration: estimation by specialists of response to systemic psoriasis therapy and possible therapeutic strategies; selecting initial doses of methotrexate for the treatment of patients with psoriasis; the possibilities of combined use with genetically engineered biological agents and monitoring of therapy. The data from randomized clinical trials on the long-term continuous treatment with methotrexate (efficacy, safety; methods of its administration to patients and time and criteria for long-term effecasy are reported. There are presented the data on the mechanisms of methotrexate action and the new data about the impact on the adenosine metabolism and the ability of the preparation to modulate the inflammatory response in the skin of patients by inhibiting the cellular components of the inflammatory infiltrate in the skin (dendritic antigen-producing cells and T-lymphocytes, as well as the suppression of expression of some proinflammatory cytokines (IFN-y and IL17A.

  11. PARTICULARITIES OF PARLIAMENTARY OVERSIGHT IN DIFFERENT POLITICAL REGIMES

    Directory of Open Access Journals (Sweden)

    Silvia-Claudia CĂLIN-MIHALCEA

    2015-07-01

    Full Text Available The quality and intensity of the parliamentary oversight performed over the Government are shaped by several major criteria: political regime, electoral system, structure of the Parliament (unicameral/bicameral, parliamentary culture and tradition. This paper emphasizes some distinctive elements and particular mechanisms of the control exercised over the activities of the executive power, from the point of view of the political regime established in states with modern democracies.

  12. Technical oversight for installation of TNX piezometers, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Pidcoe, W.W. Jr. [Westinghouse Savannah River Company, Aiken, SC (United States)

    1997-06-05

    Science Applications International Corporation was tasked under subcontract C002025P to provide technical oversight for the drilling of one pilot borehole, and the drilling and installation of five piezometers in the TNX Area Swamp. The work was performed in accordance with the Statement of Work in Task Order Proposal No. ER39-129 dated August 6, 1996. This report describes the activities associated with the performance of the task.

  13. Oil and gas site contamination risks : improved oversight needed

    International Nuclear Information System (INIS)

    2010-02-01

    British Columbia has seen record levels of activities in the oil and gas sector. Upstream petroleum processes include exploration, well completion and production. Site contamination can occur during all of these activities, resulting in potential environmental and human health impacts. Although well operators are responsible by law for site restoration, there is a potential risk that some operators will not fulfill their responsibilities, thereby leaving the province liable for the site restoration costs. In British Columbia, the BC Oil and Gas Commission (OGC) is responsible for managing these risks through oversight activities designed to ensure that industry meets its obligations. The OGC also manages the orphan sites reclamation fund. This report presented an audit of the OGC in order to determine if it is providing adequate oversight of upstream oil and gas site contamination risks. The audit examined whether the agency responsibilities are clear and whether the OGC is fully aware of the environmental and financial risks associated with upstream oil and gas site contamination. The audit also examined if the OGC has established appropriate procedures to oversee the risks and to inform the public of how effectively site contamination risks are being managed. The report presented the audit background, audit expectations, findings, conclusions and recommendations. It was concluded that the OGC's oversight of the environmental and financial risks associated with oil and gas site contamination needs improving. tabs., figs.

  14. Pediatric Drug Safety Signal Detection: A New Drug–Event Reference Set for Performance Testing of Data-Mining Methods and Systems

    NARCIS (Netherlands)

    O.U. Osokogu (Osemeke); F. Fregonese (Federica); C. Ferrajolo (Carmen); K.M.C. Verhamme (Katia); S. de Bie (Sandra); G. Jong (Geert’t); M. Catapano (Mariana); D. Weibel (Daniel); F. Kaguelidou (Florentia); W.M. Bramer (Wichor); Y. Hsia (Yingfen); I. Wong (Ian); M. Gazarian (Madlen); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2015-01-01

    textabstractBackground: Better evidence regarding drug safety in the pediatric population might be generated from existing data sources such as spontaneous reporting systems and electronic healthcare records. The Global Research in Paediatrics (GRiP)–Network of Excellence aims to develop

  15. The Role of Knowledge Brokers: Lessons from a Community Based Research Study of Cultural Safety in Relation to People Who Use Drugs

    Science.gov (United States)

    McCall, Jane; Mollison, Ashley; Browne, Annette; Parker, Joanne; Pauly, Bernie

    2017-01-01

    The study explored cultural safety as a strategy to address the stigma of substance use in acute care settings. Two research team members took on the role of knowledge brokers (KBs) in order to liaise between the research team and two distinct research advisory groups: one with people who use drugs and the other nurses. The KBs were instrumental…

  16. 78 FR 14912 - International Aviation Safety Assessment (IASA) Program Change

    Science.gov (United States)

    2013-03-08

    ... Aviation Safety Assessment (IASA) Program Change AGENCY: Federal Aviation Administration (FAA), DOT. ACTION..., into the U.S., or codeshare with a U.S. air carrier, complies with international aviation safety... subject to that country's aviation safety oversight can serve the United States using its own aircraft or...

  17. Do Published Data in Trials Assessing Cancer Drugs Reflect the Real Picture of Efficacy and Safety?

    Science.gov (United States)

    Lv, Jia-Wei; Chen, Yu-Pei; Zhou, Guan-Qun; Liu, Xu; Guo, Ying; Mao, Yan-Ping; Ma, Jun; Sun, Ying

    2017-11-01

    Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14-28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications. Copyright © 2017 by the National Comprehensive Cancer Network.

  18. Statins and daptomycin: safety assessment of concurrent use and evaluation of drug interaction liability.

    Science.gov (United States)

    Golightly, Larry K; Barber, Gerard R; Barron, Michelle A; Page, Robert L

    2013-01-01

    Acute muscle injury and potentially fatal rhabdomyolysis may occur with use of statins and certain interacting medications. This investigation assessed risk for myopathy in patients receiving treatment with a statin in combination with daptomycin, a medication also associated with muscle injury. Patients hospitalized from July 1, 2005, through June 30, 2010, who received simvastatin or rosuvastatin concurrently with daptomycin were identified and their medical records were examined. Patients were judged to have treatment-related muscle injury if their records contained evidence of myalgia with or without weakness and secondarily impaired mobility together with elevated creatine kinase (CK) levels. These assessments were compared with similar data from hospitalized patients who received a statin alone. A total of 52 patients received 66 courses of concurrent treatment with simvastatin or rosuvastatin and daptomycin. Of these, no patient (0%) met evidentiary requirements for diagnosis of myopathy or related complications. No patient (0%) developed muscle pain or discomfort and none developed markedly elevated CK levels. The incidence of asymptomatic elevations of CK in these simvastatin or rosuvastatin plus daptomycin recipients (9%) was statistically indistinguishable from the incidence of CK elevations found in a cohort of 105 inpatients who received simvastatin or rosuvastatin alone (21%; p=0.135). In patients receiving treatment with simvastatin or rosuvastatin and daptomycin, no symptoms or objective evidence of muscle injury attributable to a drug interaction were identified. These findings are consistent with data indicating that the myopathic effects of statins and daptomycin are incited by disparate and perhaps unique pharmacological mechanisms. Risk of muscle injury therefore appears to be no greater when a statin is administered with daptomycin than when either medication is used alone.

  19. The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs

    Directory of Open Access Journals (Sweden)

    Russell Barrett Van Dyke

    2016-05-01

    Full Text Available The Surveillance Monitoring for ART Toxicities (SMARTT cohort of the Pediatric HIV/AIDS Cohort Study (PHACS includes over 3500 HIV-exposed but uninfected (HEU infants and children at 22 sites in the U.S. including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARV and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental, behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain with exposure to combination ARVs (cARV, any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a neurodevelopmental case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With neurodevelopmental testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir were associated with lower performance, although all groups were within the normal range. No ARVs or classes were

  20. Efficacy and safety of 120w greenlight photoselective vaporisation of prostate in patients receiving anticoagulant drugs

    International Nuclear Information System (INIS)

    Cakiroglu, B.; Gozukucuk, R.; Sinanoglu, O.

    2013-01-01

    Objective: To evaluate the efficacy and safety of photoselective prostate vapourisation with 120w potassium titanyl phosphate laser in benign prostate hyperplasia patients receiving oral anti-coagulant therapy. Methods: The retrospective study was conducted at Istanbul Hisar International Hosptial and comprised 63 male patients who were on anti-coagulant therapy for comorbidities and who underwent prostate vapourisation for benign prostate hyperplasia with 120 Watts potassium titanyl phosphate from November 2007 to December 2010. International Prostate Symptoms Score, Quality of Life scores, uroflowmetry pre-operatively and 3 months post-operatively were obtained. Ultrasound examination was performed for each patient to evaluate prostate and residual urine in the bladder. Plasma haemoglobin, haematocrit and International Normalised Ratio levels were also checked for patients in the pre- and post-operative period. Results: The age range of the patients was from 65-89 years with a mean of 72.3+-8 years. The mean prostate weight was 45+-17ml (range: 40-120). Mean operation time was 54+-16 minutes (25-90). The removal of urinary catheter took place 1-3 days post-operatively. None of the patients required transfusion. The International Prostate Symptoms Score was reduced (23+-6 vs 14+-3) at third month after the operation. Quality of Life scores were improved from 2.2+-1.1 to 4.7+-1.2, and maximal urine flow rate increased from 7.8+-2.3 to 16+-1 in the same period. Urinary obstruction due to clot retention was observed in 1 (1.58%) patient in post-operative 3 days. Urinary retention occurred in 5 (7.98%) patients after the removal of the urinary catheter. Permanent urinary retention, per-operative bleeding and post-operative incontinence were not observed. Conclusion: Treatment of benign prostate hyperplasia with photoselective prostate vapourisation is effective and safe in patients receiving anti-coaguant therapy. However, patients should be monitored in early post

  1. Experience with Regulatory Strategies in Nuclear Power Oversight. Part 1: An International Exploratory Study. Part 2: Workshop Discussions and Conclusions

    Energy Technology Data Exchange (ETDEWEB)

    Melber, Barbara [Melber Consulting, Seattle, WA (United States); Durbin, Nancy E. [Nancy E. Durbin Consulting, Kirkland, WA (United States); Tael, Irene (ed.) [Swedish Nuclear Power Inspectorate, Stockholm (Sweden)

    2005-03-01

    This report presents the results of a study which explored the use of six different regulatory strategies for oversight of commercial nuclear power facilities: prescriptive, case-based, outcome-based, risk-based, process-based, and self-assessment strategies. Information was collected on experiences with the use of these different regulatory strategies from experts from nuclear regulatory agencies in Canada, Finland, Spain, Sweden, the United Kingdom and the United States. Systematic, structured open-ended interviews with expert regulators with extensive experience were used in order to understand how regulatory strategies are applied in practice. Common patterns were identified regarding: Experts' perspectives on the major benefits and difficulties of using specific regulatory strategies; Experts' experiences with using regulatory strategies for three areas of oversight-design and modifications, quality systems, and training and qualifications; Expert views of the consequences of different regulatory strategies; Issues that emerged in the interviews regarding regulatory strategies. The major benefit of a prescriptive strategy was that it is clear about requirements and expectations. The major difficulties were that it takes responsibility away from the licensee, it requires a high use of regulator resources and is rigid and difficult to change. A case-based strategy had the key benefit of flexibility for adapting regulatory responses to unique situations, but the difficulties of being considered arbitrary, inconsistent, and unfair and requiring heavy resource use. An outcome-based strategy had the main benefit of allowing licensees to decide the best way to operate m order to meet safety goals, but the major difficulty of identifying appropriate ways to measure safety performance. The major benefit of a risk strategy was its use co prioritize safety issues and allocate resources. However, it was considered inappropriate to use as a stand alone strategy

  2. Experience with Regulatory Strategies in Nuclear Power Oversight. Part 1: An International Exploratory Study. Part 2: Workshop Discussions and Conclusions

    International Nuclear Information System (INIS)

    Melber, Barbara; Durbin, Nancy E.; Tael, Irene

    2005-03-01

    This report presents the results of a study which explored the use of six different regulatory strategies for oversight of commercial nuclear power facilities: prescriptive, case-based, outcome-based, risk-based, process-based, and self-assessment strategies. Information was collected on experiences with the use of these different regulatory strategies from experts from nuclear regulatory agencies in Canada, Finland, Spain, Sweden, the United Kingdom and the United States. Systematic, structured open-ended interviews with expert regulators with extensive experience were used in order to understand how regulatory strategies are applied in practice. Common patterns were identified regarding: Experts' perspectives on the major benefits and difficulties of using specific regulatory strategies; Experts' experiences with using regulatory strategies for three areas of oversight-design and modifications, quality systems, and training and qualifications; Expert views of the consequences of different regulatory strategies; Issues that emerged in the interviews regarding regulatory strategies. The major benefit of a prescriptive strategy was that it is clear about requirements and expectations. The major difficulties were that it takes responsibility away from the licensee, it requires a high use of regulator resources and is rigid and difficult to change. A case-based strategy had the key benefit of flexibility for adapting regulatory responses to unique situations, but the difficulties of being considered arbitrary, inconsistent, and unfair and requiring heavy resource use. An outcome-based strategy had the main benefit of allowing licensees to decide the best way to operate m order to meet safety goals, but the major difficulty of identifying appropriate ways to measure safety performance. The major benefit of a risk strategy was its use co prioritize safety issues and allocate resources. However, it was considered inappropriate to use as a stand alone strategy and a

  3. Regional aviation safety organisations : enhancing air transport safety through regional cooperation

    NARCIS (Netherlands)

    Ratajczyk, Mikołaj Andrzej

    2014-01-01

    Aviation safety is of global concern. Yet 43% of countries worldwide lack the expertise and administrative capacity to ensure effective safety oversight of the aviation activities for which they are responsible under international law. With air traffic predicted to double in the next 15 years and

  4. Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory drug-induced mucosal toxicity.

    Science.gov (United States)

    Kim, Jeong Ho; Park, Soo-Heon; Cho, Chul-Soo; Lee, Soo Teik; Yoo, Wan-Hee; Kim, Sung Kook; Kang, Young Mo; Rew, Jong Sun; Park, Yong-Wook; Lee, Soo Kon; Lee, Yong Chan; Park, Won; Lee, Don-Haeng

    2014-07-01

    The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 μg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide

  5. Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses

    Science.gov (United States)

    Gentili, Marta; Pozzi, Marco; Peeters, Gabrielle; Radice, Sonia; Carnovale, Carla

    2018-02-06

    Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio. In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis. Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Efficacy and safety of oral antidiabetic drugs in comparison to insulin in treating gestational diabetes mellitus: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Nalinee Poolsup

    Full Text Available OBJECTIVE: To assess the efficacy and safety of oral antidiabetic drugs (OADs in gestational diabetes mellitus (GDM in comparison to insulin. METHODS: A meta-analysis of randomized controlled trials was conducted. The efficacy and safety of OADs in comparison to insulin in GDM patients were explored. Studies were identified by conducting a literature search using the electronic databases of Medline, CENTRAL, CINAHL, LILACS, Scopus and Web of Science in addition to conducting hand search of relevant journals from inception until October 2013. RESULTS: Thirteen studies involving 2,151 patients met the inclusion criteria. These studies were randomized controlled trials of metformin and glyburide in comparison to insulin therapy. Our results indicated a significant increase in the risk for preterm births (RR, 1.51; 95% CI, 1.04-2.19, p = 0.03 with metformin compared to insulin. However, a significant decrease in the risk for gestational hypertension (RR, 0.54; 95% CI, 0.31-0.91, p = 0.02 was found. Postprandial glucose levels also decreased significantly in patients receiving metformin (MD, -2.47 mg/dL; 95% CI, -4.00, -0.94, p = 0.002. There was no significant difference between the two groups for the remaining outcomes. There were significant increases in the risks of macrosomia (RR, 2.34; 95% CI, 1.18-4.63, p = 0.03 and neonatal hypoglycemia (RR, 2.06; 95% CI, 1.27-3.34, p = 0.005 in the glyburide group compared to insulin whereas results for the other analyzed outcomes remained non-significant. CONCLUSION: The available evidence suggests favorable effects of metformin in treating GDM patients. Metformin seems to be an efficacious alternative to insulin and a better choice than glyburide especially those with mild form of disease.

  7. The efficacy and safety of the targeted drug combined with adriamycin liposome solution for HER-2-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Zi-Ping Zhou

    2017-05-01

    Full Text Available Objective: To study the efficacy and safety of the targeted drug trastuzumab combined with adriamycin liposome solution for HER-2-positive breast cancer. Methods: A total of 112 patients with breast cancer who received chemotherapy in Department of Cardiothoracic Breast Surgery, Guangdong TongJiang Hospital between May 2014 and April 2016 were selected as the research subjects and divided into two groups by random number table, liposome group received trastuzumab + adriamycin liposome chemotherapy, and the control group received trastuzumab + adriamycin chemotherapy. Before chemotherapy as well as 4 weeks and 8 weeks after chemotherapy, serum levels of tumor markers, cytokines and myocardial injury indexes were detected, the electrocardiography was conducted and the degree of myocardial injury was determined. Results: 4 weeks and 8 weeks after chemotherapy, serum CEA, CA15-3, TPS, CTGF, TGF-β, TSGF, VEGF and MK levels of both groups were significantly lower than those before chemotherapy, serum CK-MB and cTnI levels were significantly higher than those before chemotherapy, limb leads QRS amplitudes and chest leads QRS amplitudes were significantly lower than those before chemotherapy, serum CEA, CA15-3, TPS, CTGF, TGF-β, TSGF, VEGF, MK, CK-MB and cTnI levels of liposome group were significantly lower than those of control group, and the limb leads QRS amplitudes and chest lead QRS amplitudes were significantly higher than those of control group. Conclusion: Targeted drug combined with adriamycin liposome therapy for HER-2-positive breast cancer can improve the curative effect and reduce the cardiotoxicity.

  8. Risk patterns in drug safety study using relative times by accelerated failure time models when proportional hazards assumption is questionable : an illustrative case study of cancer risk of patients on glucose-lowering therapies

    NARCIS (Netherlands)

    Ng, Edmond S-W; Klungel, Olaf H; Groenwold, Rolf H H; van Staa, Tjeerd-Pieter

    2015-01-01

    Observational drug safety studies may be susceptible to confounding or protopathic bias. This bias may cause a spurious relationship between drug exposure and adverse side effect when none exists and may lead to unwarranted safety alerts. The spurious relationship may manifest itself through

  9. Tennessee Oversight Agreement annual report, May 13, 1993 - May 12, 1994

    International Nuclear Information System (INIS)

    1994-01-01

    This report discusses the activities of the Division of DOE Oversight in the areas of coordination with other State Agencies with regard to environmental restoration, corrective action, and waste management activities on the Oak Ridge Reservation; and the Division's efforts to keep the public informed of those DOE activities that may impact their health and the environment. This report includes the status of the Division's efforts in implementing the Tennessee Oversight Agreement (TOA). Each Program Section provides information concerning the status of its activities. The Administrative Section has been instrumental in achieving access to the ORR without prior notification to DOE and in obtaining documents and environmental, waste management, safety, and health information in a timely manner. The Environmental Restoration Program has provided in-depth document reviews and on-site coordination and monitoring of field activities required under the Federal Facility Agreement. Most notable of the activities are the investigations and planned remediation of the Lower East Fork Poplar Creek and the Watts Bar Reservoir. The Waste Management Program has audited DOE's compliance with air, water, solid, hazardous, and mixed waste storage, treatment, and disposal regulations. Effort was focused on all three DOE Facilities on the ORR. The final portion of this report discusses the Division's findings and recommendations. Most significant of these issues is the Division's request to be an active participant in DOE's prioritization of its TOA commitments. Other issues discussed include long term storage of radioactive waste and the use of environmental restoration funds. A discussion of those findings and recommendations provided in last year's annual report and addressed by DOE are included in this report as well. All documents, logs, files, etc. supporting this report are available for review during routine business hours at the Division's office

  10. MEDICAID FINANCIAL MANAGEMENT: Better Oversight of State Claims for Federal Reimbursement Needed

    National Research Council Canada - National Science Library

    Calbom, Linda

    2002-01-01

    .... Developing baseline information on Medicaid issues at greatest risk for improper payments and measuring improvements in program management against that baseline is key to achieving effective financial oversight...

  11. Political and Budgetary Oversight of the Ukrainian Intelligence Community: Processes, Problems and Prospects for Reform

    National Research Council Canada - National Science Library

    Petrov, Oleksii

    2007-01-01

    This thesis addresses the problem of providing policy and budget oversight of Ukrainian intelligence organizations in accordance with norms and practices developed in contemporary Western democracies...

  12. Current good manufacturing practice and investigational new drugs intended for use in clinical trials. Final rule.

    Science.gov (United States)

    2008-07-15

    The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most phase 1 investigational drugs from complying with the regulatory CGMP requirements. FDA will continue to exercise oversight of the manufacture of these drugs under FDA's general statutory CGMP authority and through review of the investigational new drug applications (IND). In addition, elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance document entitled "Guidance for Industry: CGMP for Phase 1 Investigational Drugs" dated November 2007 (the companion guidance). This guidance document sets forth recommendations on approaches to compliance with statutory CGMP for the exempted phase 1 investigational drugs. FDA is taking this action to focus a manufacturer's effort on applying CGMP that is appropriate and meaningful for the manufacture of the earliest stage investigational drug products intended for use in phase 1 clinical trials while ensuring safety and quality. This action will also streamline and promote the drug development process.

  13. Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

    Science.gov (United States)

    Chang, Lin-Chau; Mahmood, Riaz; Qureshi, Samina; Breder, Christopher D

    2017-01-01

    Standardised MedDRA Queries (SMQs) have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA) and Biologics License Application (BLA) submissions to the United States Food and Drug Administration (USFDA). We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs) of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed. A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59%) of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18%) of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated). Most searches (75% of 227 searches) with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process. SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

  14. Patterns of use and impact of standardised MedDRA query analyses on the safety evaluation and review of new drug and biologics license applications.

    Directory of Open Access Journals (Sweden)

    Lin-Chau Chang

    Full Text Available Standardised MedDRA Queries (SMQs have been developed since the early 2000's and used by academia, industry, public health, and government sectors for detecting safety signals in adverse event safety databases. The purpose of the present study is to characterize how SMQs are used and the impact in safety analyses for New Drug Application (NDA and Biologics License Application (BLA submissions to the United States Food and Drug Administration (USFDA.We used the PharmaPendium database to capture SMQ use in Summary Basis of Approvals (SBoAs of drugs and biologics approved by the USFDA. Characteristics of the drugs and the SMQ use were employed to evaluate the role of SMQ safety analyses in regulatory decisions and the veracity of signals they revealed.A comprehensive search of the SBoAs yielded 184 regulatory submissions approved from 2006 to 2015. Search strategies more frequently utilized restrictive searches with "narrow terms" to enhance specificity over strategies using "broad terms" to increase sensitivity, while some involved modification of search terms. A majority (59% of 1290 searches used descriptive statistics, however inferential statistics were utilized in 35% of them. Commentary from reviewers and supervisory staff suggested that a small, yet notable percentage (18% of 1290 searches supported regulatory decisions. The searches with regulatory impact were found in 73 submissions (40% of the submissions investigated. Most searches (75% of 227 searches with regulatory implications described how the searches were confirmed, indicating prudence in the decision-making process.SMQs have an increasing role in the presentation and review of safety analysis for NDAs/BLAs and their regulatory reviews. This study suggests that SMQs are best used for screening process, with descriptive statistics, description of SMQ modifications, and systematic verification of cases which is crucial for drawing regulatory conclusions.

  15. Regulatory Activities for Licensee's Safety Culture

    International Nuclear Information System (INIS)

    Choi, Young Sung; Choi, Kwang Sik

    2008-01-01

    Weaknesses in safety culture have contributed to a number of incidents/accidents in the nuclear and other high hazard sectors worldwide in the past. These events have fostered an increasing awareness of the need for licensees to develop a strong safety culture to support successful and sustainable nuclear safety performance. Regulatory bodies are taking a growing interest in this issue, and several are actively working to develop and implement approaches to maintaining regulatory oversight of licensee safety culture. However, these approaches are not yet well-established, and it was considered prudent to share experiences and developing methodologies in order to disseminate good practices and avoid potential pitfalls. This paper presents the findings, conclusions and recommendations of international meetings and other countries' activities on safety culture and gives some suggestions for regulators to consider when planning regulatory oversight for licensee's safety culture

  16. Integrating GIS and GPS in environmental remediation oversight

    International Nuclear Information System (INIS)

    Kaletsky, K.; Earle, J.R.; Schneider, T.A.

    1996-01-01

    This paper presents findings on Ohio EPA Office of Federal Facilities Oversight's (OFFO) use of GIS and GPS for environmental remediation oversight at the U.S. Department of Energy's (DOE) Fernald Site. The Fernald site is a former uranium metal production facility within DOE's nuclear weapons complex. Significant uranium contamination of soil and groundwater is being remediated under state and federal regulations. OFFO uses GIS/GPS to enhance environmental monitoring and remediation oversight. These technologies are utilized within OFFO's environmental monitoring program for sample location and parameter selection, data interpretation and presentation. GPS is used to integrate sample data into OFFO's GIS and for permanently linking precise and accurate geographic data to samples and waste units. It is important to identify contamination geographically as all visual references (e.g., buildings, infrastructure) will be removed during remediation. Availability of the GIS allows OFFO to perform independent analysis and review of DOE contractor generated data, models, maps, and designs. This ability helps alleviate concerns associated with open-quotes black boxclose quotes models and data interpretation. OFFO's independent analysis has increased regulatory confidence and the efficiency of design reviews. GIS/GPS technology allows OFFO to record and present complex data in a visual format aiding in stakeholder education and awareness. Presented are OFFO's achievements within the aforementioned activities and some reasons learned in implementing the GIS/GPS program. OFFO's two years of GIS/GPS development have resulted in numerous lessons learned and ideas for increasing effectiveness through the use of GIS/GPS

  17. Role of the Regulatory Body in Implementing Defence in Depth in Nuclear Installations - Regulatory Oversight in Egypt

    Energy Technology Data Exchange (ETDEWEB)

    El-Sheikh, B. M., E-mail: badawymel@yahoo.com [Egyptian Nuclear and Radiological Regulatory Authority Cairo (Egypt)

    2014-10-15

    The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are operated at all times in an acceptably safe manner including the safe conduct of decommissioning activities. Defence in depth is recognized as one of the fundamental safety principles that underlie the safety of nuclear power plants. Defence in depth is implemented to provide a graded protection against a wide variety of transients, incidents and accidents, including equipment failures and human errors within nuclear power plants and events initiated outside plants. The Regulator Body plays an important role in implementing defence in depth in nuclear installations in the context of a clear allocation of responsibilities with an operating organization. This role starting with setting safety objectives and by its own independent review and technical assessment of the safety justifications provided by the operating organization in addition to safety culture investigating within relevant organizations. This paper briefly reviews this role in normal operation and post accidents, and its effects on overall nuclear safety in nuclear installations with reference to Egyptian regulatory oversight. (author)

  18. 77 FR 72905 - Pipeline Safety: Random Drug Testing Rate; Contractor MIS Reporting; and Obtaining DAMIS Sign-In...

    Science.gov (United States)

    2012-12-06

    ... DEPARTMENT OF TRANSPORTATION Pipeline and Hazardous Materials Safety Administration [Docket ID... DAMIS Sign-In Information AGENCY: Pipeline and Hazardous Materials Safety Administration (PHMSA), DOT..., hazardous liquid, and carbon dioxide pipelines and operators of liquefied natural gas facilities must...

  19. Evaluating the Impact of Drug Dispensing Systems on the Safety and Efficiency in a Singapore Outpatient Pharmacy

    Directory of Open Access Journals (Sweden)

    Peter Ong Yong Sheng

    2014-01-01

    Full Text Available Purpose: Automation of pharmacy workflow can reduce medication errors as well as improve efficiency of the medication picking, packing and labeling process. Since September 2012, two drug dispensing systems (DDS began operations in the Singapore General Hospital Specialist Outpatient Clinic Pharmacy. This study sought to evaluate the impact of the DDS on safety and efficiency in the pharmacy. Methods: The primary outcome was the rate of prevented dispensing incidents contributed by DDS or manual picking of medications defined as the number of prevented dispensing incidents per 1000 medications picked. The secondary outcome was the productivity of each full time equivalent (FTE when assigned to either the DDS or manual picking stations. Data pertaining to the primary and secondary outcomes between January and December 2013 were collected and analyzed. The rate of prevented dispensing incidents was expressed in median (interquartile range and compared using Mann-Whitney U test. Other continuous variables were expressed in mean ± standard deviation and compared using independent samples t-test. Results: An average of 59494 medications was picked every month in the pharmacy. DDS accounted for 21.1 percent while manual picking accounted for 78.9 percent of all the medications picked. The median rate of prevented dispensing incidents per month committed by manual picking (2.73 was significantly higher than the DDS (0.00. DDS had greater productivity with each FTE in the DDS having an average of 6175 picks per month which was significantly higher than each FTE in the manual picking stations which had an average of 4867 picks per month. Conclusion: Installation of DDS in an outpatient pharmacy improved safety of the pharmacy workflow by automating the medication picking, packing and labeling process and minimizing human errors. Efficiency of the medication picking, packing and labeling process was also improved by the DDS as there were continuous

  20. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs.

    Science.gov (United States)

    Charles-Schoeman, Christina; Burmester, Gerd; Nash, Peter; Zerbini, Cristiano A F; Soma, Koshika; Kwok, Kenneth; Hendrikx, Thijs; Bananis, Eustratios; Fleischmann, Roy

    2016-07-01

    Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR). Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed. 2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs). Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. (NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385). Published by the BMJ Publishing Group Limited

  1. A Cost Analysis of Hospitalizations for Infections Related to Injection Drug Use at a County Safety-Net Hospital in Miami, Florida.

    Directory of Open Access Journals (Sweden)

    Hansel Tookes

    Full Text Available Infections related to injection drug use are common. Harm reduction strategies such as syringe exchange programs and skin care clinics aim to prevent these infections in injection drug users (IDUs. Syringe exchange programs are currently prohibited by law in Florida. The goal of this study was to estimate the mortality and cost of injection drug use-related bacterial infections over a 12-month period to the county safety-net hospital in Miami, Florida. Additionally, the prevalence of HIV and hepatitis C virus among this cohort of hospitalized IDUs was estimated.IDUs discharged from Jackson Memorial Hospital were identified using the International Classification of Diseases, Ninth Revision, codes for illicit drug abuse and endocarditis, bacteremia or sepsis, osteomyelitis and skin and soft tissue infections (SSTIs. 349 IDUs were identified for chart abstraction and 92% were either uninsured or had publicly funded insurance. SSTIs, the most common infection, were reported in 64% of IDUs. HIV seroprevalence was 17%. Seventeen patients (4.9% died during their hospitalization. The total cost for treatment for injection drug use-related infections to Jackson Memorial Hospital over the 12-month period was $11.4 million.Injection drug use-related bacterial infections represent a significant morbidity for IDUs in Miami-Dade County and a substantial financial cost to the county hospital. Strategies aimed at reducing risk of infections associated with injection drug use could decrease morbidity and the cost associated with these common, yet preventable infections.

  2. Drug Safety - Multiple Languages

    Science.gov (United States)

    ... to Over the Counter Medications - Amarɨñña / አማርኛ (Amharic) MP3 Global Health Center Division of Infectious Diseases University ... to Over the Counter Medications - myanma bhasa (Burmese) MP3 Global Health Center Division of Infectious Diseases University ...

  3. Diverging Conclusions from the Same Meta-Analysis in Drug Safety: Source of Data (Primary Versus Secondary) Takes a Toll.

    Science.gov (United States)

    Prada-Ramallal, Guillermo; Takkouche, Bahi; Figueiras, Adolfo

    2017-04-01

    Meta-analyses of observational studies represent an important tool for assessing efficacy and safety in the pharmacoepidemiologic field. The data from the individual studies are either primary (i.e., collected through interviews or self-administered questionnaires) or secondary (i.e., collected from databases that were established for other purposes). So far, the origin of the data (primary vs. secondary) has not been systematically assessed as a source of heterogeneity in pharmacoepidemiologic meta-analyses. The aim was to assess the impact of considering the source of exposure data as a criterion in sensitivity and subgroup analysis on the conclusions of drug safety meta-analyses. We selected meta-analyses published between 2013 and 2015 in which the intake of frequently used over-the-counter medicines was either the main exposure or a concomitant treatment and the outcome had short latency and induction periods. We stratified the results by origin of data (primary vs. secondary) and compared the new results to those presented originally in the meta-analyses. We used four meta-analyses that fulfilled our criteria of inclusion. The results were selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: original estimate odds ratio (OR) = 1.71 [95% confidence interval (CI) 1.44-2.04], OR primary data = 1.19 (95% CI 0.90-1.58), OR secondary data = 1.81 (95% CI 1.50-2.17); proton pump inhibitors and cardiac events: original estimate hazard ratio (HR) = 1.35 (95% CI 1.18-1.54), HR primary data = 1.05 (95% CI 0.87-1.26), HR secondary data = 1.43 (95% CI 1.23-1.66); non-aspirin non-steroidal anti-inflammatory drugs and myocardial infarction: original estimate risk ratio (RR) = 1.08 (95% CI 0.95-1.22), RR primary data = 0.57 (95% CI 0.34-0.96), RR secondary data = 1.15 (95% CI 1.03-1.28); paracetamol during pregnancy and childhood asthma: original estimate OR = 1.32 (95% CI 1.14-1.52), OR primary data = 1.23 (95% CI 1.06-1.42), OR

  4. Methods and pitfalls in searching drug safety databases utilising the Medical Dictionary for Regulatory Activities (MedDRA).

    Science.gov (United States)

    Brown, Elliot G

    2003-01-01

    The Medical Dictionary for Regulatory Activities (MedDRA) is a unified standard terminology for recording and reporting adverse drug event data. Its introduction is widely seen as a significant improvement on the previous situation, where a multitude of terminologies of widely varying scope and quality were in use. However, there are some complexities that may cause difficulties, and these will form the focus for this paper. Two methods of searching MedDRA-coded databases are described: searching based on term selection from all of MedDRA and searching based on terms in the safety database. There are several potential traps for the unwary in safety searches. There may be multiple locations of relevant terms within a system organ class (SOC) and lack of recognition of appropriate group terms; the user may think that group terms are more inclusive than is the case. MedDRA may distribute terms relevant to one medical condition across several primary SOCs. If the database supports the MedDRA model, it is possible to perform multiaxial searching: while this may help find terms that might have been missed, it is still necessary to consider the entire contents of the SOCs to find all relevant terms and there are many instances of incomplete secondary linkages. It is important to adjust for multiaxiality if data are presented using primary and secondary locations. Other sources for errors in searching are non-intuitive placement and the selection of terms as preferred terms (PTs) that may not be widely recognised. Some MedDRA rules could also result in errors in data retrieval if the individual is unaware of these: in particular, the lack of multiaxial linkages for the Investigations SOC, Social circumstances SOC and Surgical and medical procedures SOC and the requirement that a PT may only be present under one High Level Term (HLT) and one High Level Group Term (HLGT) within any single SOC. Special Search Categories (collections of PTs assembled from various SOCs by

  5. Considerations for the analysis of longitudinal electronic health records linked to claims data to study the effectiveness and safety of drugs.

    Science.gov (United States)

    Lin, K J; Schneeweiss, S

    2016-08-01

    Health insurance claims and electronic health records (EHR) databases have been considered the preferred data sources with which to study drug safety and effectiveness in routine care. Linking claims data to EHR allows researchers to leverage the complementary advantages of each data source to enhance study validity. We propose a framework to evaluate the need for supplementing claims data with EHR and vice versa to optimize outcome ascertainment, exposure assessment, and confounding adjustment. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  6. Real-time Responsiveness for Ethics Oversight During Disaster Research.

    Science.gov (United States)

    Eckenwiler, Lisa; Pringle, John; Boulanger, Renaud; Hunt, Matthew

    2015-11-01

    Disaster research has grown in scope and frequency. Research in the wake of disasters and during humanitarian crises--particularly in resource-poor settings--is likely to raise profound and unique ethical challenges for local communities, crisis responders, researchers, and research ethics committees (RECs). Given the ethical challenges, many have questioned how best to provide research ethics review and oversight. We contribute to the conversation concerning how best to ensure appropriate ethical oversight in disaster research and argue that ethical disaster research requires of researchers and RECs a particular sort of ongoing, critical engagement which may not be warranted in less exceptional research. We present two cases that typify the concerns disaster researchers and RECs may confront, and elaborate upon what this ongoing engagement might look like--how it might be conceptualized and utilized--using the concept of real-time responsiveness (RTR). The central aim of RTR, understood here as both an ethical ideal and practice, is to lessen the potential for research conducted in the wake of disasters to create, perpetuate, or exacerbate vulnerabilities and contribute to injustices suffered by disaster-affected populations. Well cultivated and deployed, we believe that RTR may enhance the moral capacities of researchers and REC members, and RECs as institutions where moral agency is nurtured and sustained. © 2015 John Wiley & Sons Ltd.

  7. 17 CFR 201.440 - Appeal of determinations by the Public Company Accounting Oversight Board.

    Science.gov (United States)

    2010-04-01

    ... and Commission Review § 201.440 Appeal of determinations by the Public Company Accounting Oversight... for registration of a public accounting firm, may file an application for review. (b) Procedure. An... the Public Company Accounting Oversight Board. 201.440 Section 201.440 Commodity and Securities...

  8. 32 CFR 2400.19 - Declassification by the Director of the Information Security Oversight Office.

    Science.gov (United States)

    2010-07-01

    ... Information Security Oversight Office. 2400.19 Section 2400.19 National Defense Other Regulations Relating to... SCIENCE AND TECHNOLOGY POLICY INFORMATION SECURITY PROGRAM Declassification and Downgrading § 2400.19 Declassification by the Director of the Information Security Oversight Office. If the Director of the Information...

  9. Creating a Learning Organization in Law Enforcement: Maturity Levels for Police Oversight Agencies

    Science.gov (United States)

    Filstad, Cathrine; Gottschalk, Petter

    2010-01-01

    Purpose: The purpose of this paper is to conceptualize a stage model for maturity levels for police oversight agencies. Design/methodology/approach: The paper is based on a literature review covering police oversight organizations and stages of growth models. Findings: As a conceptual paper, the main findings are related to the appropriateness of…

  10. 48 CFR 52.236-24 - Work Oversight in Architect-Engineer Contracts.

    Science.gov (United States)

    2010-10-01

    ... Architect-Engineer Contracts. 52.236-24 Section 52.236-24 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.236-24 Work Oversight in Architect-Engineer Contracts. As prescribed in 36.609-3, insert the following clause: Work Oversight in Architect-Engineer Contracts (APR 1984) The extent and...

  11. Whistleblower Protection: DOD Needs to Enhance Oversight of Military Whistleblower Reprisal Investigations

    Science.gov (United States)

    2015-05-01

    WHISTLEBLOWER PROTECTION DOD Needs to Enhance Oversight of Military Whistleblower Reprisal Investigations Report...00-2015 to 00-00-2015 4. TITLE AND SUBTITLE Whistleblower Protection: DOD Needs to Enhance Oversight of Military Whistleblower Reprisal...Government Accountability Office Highlights of GAO-15-477, a report to congressional requesters May 2015 WHISTLEBLOWER PROTECTION DOD

  12. Defense Forensics: Additional Planning and Oversight Needed to Establish an Enduring Expeditionary Forensic Capability

    Science.gov (United States)

    2013-06-01

    forensic pathology, forensic anthropology, and forensic toxicology . 13DOD’s forensic directive defines DOD components as the Office of the...DEFENSE FORENSICS Additional Planning and Oversight Needed to Establish an Enduring Expeditionary Forensic ...COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE Defense Forensics : Additional Planning and Oversight Needed to Establish an Enduring

  13. 76 FR 31416 - Federal Acquisition Regulation; Oversight of Contractor Ethics Programs

    Science.gov (United States)

    2011-05-31

    ...-AL92 Federal Acquisition Regulation; Oversight of Contractor Ethics Programs AGENCY: Department of... that contractors have implemented the mandatory contractor business ethics program requirements. DATES... to Improve DoD's Oversight of Contractor Ethics Programs. The ethics program requirement flows from...

  14. 76 FR 52997 - Public Company Accounting Oversight Board; Order Approving Proposed Board Funding Final Rules for...

    Science.gov (United States)

    2011-08-24

    ... Accounting Oversight Board; Order Approving Proposed Board Funding Final Rules for Allocation of the Board's... August 18, 2011. I. Introduction On June 21, 2011, the Public Company Accounting Oversight Board (the... public accounting firm, in amounts that are sufficient to cover the costs of processing and reviewing...

  15. 17 CFR 202.11 - Public Company Accounting Oversight Board budget approval process.

    Science.gov (United States)

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Public Company Accounting Oversight Board budget approval process. 202.11 Section 202.11 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION INFORMAL AND OTHER PROCEDURES § 202.11 Public Company Accounting Oversight...

  16. A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers

    Directory of Open Access Journals (Sweden)

    Oyoo George O

    2011-03-01

    Full Text Available Abstract Background Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. Methods Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. Results The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product were reported. The maximum concentration (Cmax was 160-200 nM and after 6 hours, the effective concentration (Ceff was Conclusion Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable Ceff of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.

  17. 77 FR 70166 - Provisions of the Food and Drug Administration Safety and Innovation Act Related to Medical Gases...

    Science.gov (United States)

    2012-11-23

    ...; Establishment of a Public Docket AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket for information pertaining to FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1090...

  18. Parliamentary Oversight of European Security and Defence Policy: A Matter of Formal Competences or the Will of Parliamentarians?

    OpenAIRE

    Maatsch, A.; Galella, P.

    2016-01-01

    Are parliaments with strong formal powers for the deployment of troops likely to conduct more intensive oversight than their counterparts with weak or no powers? The literature suggests that strong formal powers delineate boundaries of parliamentary oversight. However, this article demonstrates that strong formal powers are not necessary for parliaments in order to conduct oversight. If parliaments with weak formal powers had strong incentives to carry out oversight of the EU NAVFOR Operation...

  19. A qualitative phenomenological study: Enhanced, risk-based FAA oversight on part 145 maintenance practices

    Science.gov (United States)

    Sheehan, Bryan G.

    The purpose of this qualitative phenomenological study was to examine the phenomenon of enhanced, risk-based Federal Aviation Administration (FAA) oversight of Part 145 repair stations that performed aircraft maintenance for Part 121 air carriers between 2007 and 2014 in Oklahoma. Specifically, this research was utilized to explore what operational changes have occurred in the domestic Part 145 repair station industry such as variations in management or hiring practices, training, recordkeeping and technical data, inventory and aircraft parts supply-chain logistics, equipment, and facilities. After interviewing 12 managers from Part 145 repair stations in Oklahoma, six major theme codes emerged from the data: quality of oversight before 2007, quality of oversight after 2007, advantages of oversight, disadvantages of oversight, status quo of oversight, and process improvement . Of those six major theme codes, 17 subthemes appeared from the data that were used to explain the phenomenon of enhanced oversight in the Part 145 repair station industry. Forty-two percent of the participants indicated a weak FAA oversight system that has hindered the continuous process improvement program in their repair stations. Some of them were financially burdened after hiring additional full-time quality assurance inspectors to specifically manage enhanced FAA oversight. Notwithstanding, the participants of the study indicated that the FAA must apply its surveillance on a more standardized and consistent basis. They want to see this standardization in how FAA inspectors interpret regulations and practice the same quality of oversight for all repair stations, particularly those that are repeat violators and fail to comply with federal aviation regulations. They believed that when the FAA enforces standardization on a consistent basis, repair stations can become more efficient and safer in the performance of their scope of work for the U.S. commercial air transportation industry.

  20. Animal Product Safety Information

    Science.gov (United States)

    ... Home Animal & Veterinary Safety & Health Product Safety Information Product Safety Information Share Tweet Linkedin Pin it More ... to report adverse experiences with veterinary drugs. Additional Product Information Questions and Answers: Evanger’s Dog and Cat ...

  1. Patient safety incident reports related to traditional Japanese Kampo medicines: medication errors and adverse drug events in a university hospital for a ten-year period.

    Science.gov (United States)

    Shimada, Yutaka; Fujimoto, Makoto; Nogami, Tatsuya; Watari, Hidetoshi; Kitahara, Hideyuki; Misawa, Hiroki; Kimbara, Yoshiyuki

    2017-12-21

    Kampo medicine is traditional Japanese medicine, which originated in ancient traditional Chinese medicine, but was introduced and developed uniquely in Japan. Today, Kampo medicines are integrated into the Japanese national health care system. Incident reporting systems are currently being widely used to collect information about patient safety incidents that occur in hospitals. However, no investigations have been conducted regarding patient safety incident reports related to Kampo medicines. The aim of this study was to survey and analyse incident reports related to Kampo medicines in a Japanese university hospital to improve future patient safety. We selected incident reports related to Kampo medicines filed in Toyama University Hospital from May 2007 to April 2017, and investigated them in terms of medication errors and adverse drug events. Out of 21,324 total incident reports filed in the 10-year survey period, we discovered 108 Kampo medicine-related incident reports. However, five cases were redundantly reported; thus, the number of actual incidents was 103. Of those, 99 incidents were classified as medication errors (77 administration errors, 15 dispensing errors, and 7 prescribing errors), and four were adverse drug events, namely Kampo medicine-induced interstitial pneumonia. The Kampo medicine (crude drug) that was thought to induce interstitial pneumonia in all four cases was Scutellariae Radix, which is consistent with past reports. According to the incident severity classification system recommended by the National University Hospital Council of Japan, of the 99 medication errors, 10 incidents were classified as level 0 (an error occurred, but the patient was not affected) and 89 incidents were level 1 (an error occurred that affected the patient, but did not cause harm). Of the four adverse drug events, two incidents were classified as level 2 (patient was transiently harmed, but required no treatment), and two incidents were level 3b (patient was

  2. Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): a drug use investigation.

    Science.gov (United States)

    Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

    2014-11-01

    Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. Prospective drug safety monitoring using the UK primary-care General Practice Research Database: theoretical framework, feasibility analysis and extrapolation to future scenarios.

    Science.gov (United States)

    Johansson, Saga; Wallander, Mari-Ann; de Abajo, Francisco J; García Rodríguez, Luis Alberto

    2010-03-01

    Post-launch drug safety monitoring is essential for the detection of adverse drug signals that may be missed during preclinical trials. Traditional methods of postmarketing surveillance such as spontaneous reporting have intrinsic limitations, many of which can be overcome by the additional application of structured pharmacoepidemiological approaches. However, further improvement in drug safety monitoring requires a shift towards more proactive pharmacoepidemiological methods that can detect adverse drug signals as they occur in the population. To assess the feasibility of using proactive monitoring of an electronic medical record system, in combination with an independent endpoint adjudication committee, to detect adverse events among users of selected drugs. UK General Practice Research Database (GPRD) information was used to detect acute liver disorder associated with the use of amoxicillin/clavulanic acid (hepatotoxic) or low-dose aspirin (acetylsalicylic acid [non-hepatotoxic]). Individuals newly prescribed these drugs between 1 October 2005 and 31 March 2006 were identified. Acute liver disorder cases were assessed using GPRD computer records in combination with case validation by an independent endpoint adjudication committee. Signal generation thresholds were based on the background rate of acute liver disorder in the general population. Over a 6-month period, 8148 patients newly prescribed amoxicillin/clavulanic acid and 5577 patients newly prescribed low-dose aspirin were identified. Within this cohort, searches identified 11 potential liver disorder cases from computerized records: six for amoxicillin/clavulanic acid and five for low-dose aspirin. The independent endpoint adjudication committee refined this to four potential acute liver disorder cases for whom paper-based information was requested for final case assessment. Final case assessments confirmed no cases of acute liver disorder. The time taken for this study was 18 months (6 months for

  4. Clinical oversight and the avoidance of repeat induced abortion.

    Science.gov (United States)

    Jacovetty, Erica L; Clare, Camille A; Squire, Mary-Beatrice; Kubal, Keshar P; Liou, Sherry; Inchiosa, Mario A

    2018-06-03

    To evaluate the impact of patient counseling, demographics, and contraceptive methods on repeat induced abortion in women attending family planning clinics. A retrospective chart review of repeat induced abortions was performed. The analysis included patients with an initial induced abortion obtained between January 1, 2001, and March 31, 2014, at New York City Health + Hospitals/Metropolitan. The duration of involvement in the family planning program, the use of contraceptive interventions, and 18 patient factors were analyzed for their correlation with the incidence of repeat induced abortions per year of follow-up. A decreased rate of repeat induced abortions was associated with a longer duration of clinical oversight (r 2 =0.449, Pabortions. By determining the patient characteristics that most influence repeat induced abortion rates, providers can best choose the most efficacious method of contraception available. © 2018 International Federation of Gynecology and Obstetrics.

  5. External Police Oversight in Mexico: Experiences, Challenges, and Lessons Learned

    Directory of Open Access Journals (Sweden)

    Rubén Guzmán Sánchez

    2014-11-01

    Full Text Available After nearly 20 years of ‘reformist’ measures, the police in Mexico continues to be an ineffective, unreliable, and ‘far from citizen’ institution. The efforts made so far have faded amongst political interests and agendas; multidimensional frameworks out-dated at both conceptual and interagency levels; short-sighted competition for resources; evaluation and performance monitors that are handicapped by bureaucratic inaction; and weak transparency and accountability that perpetuate the opacity in which the police operate. In this context, the agenda of external police oversight is still at a rudimentary stage. However, there are several initiatives that have managed to push the issue to the frontier of new knowledge and promising practices. This paper outlines the experiences and challenges of—as well as the lessons learned by—the Institute for Security and Democracy (Insyde A.C., one of the most recognised think tanks in Mexico.

  6. Not to catch but to deter : simple, less intrusive drug and alcohol tests can improve workplace safety

    Energy Technology Data Exchange (ETDEWEB)

    Stastny, P.

    2009-04-15

    Canadian employees who test positive for drug use have access to a wide range of substance counselling and rehabilitation options. As a result of Canadian human right legislation, drug dependence is considered a disability, and Canadian employers are required to accommodate the employee and retain their position when they are deemed fit for work. While Alberta is considered an employee-friendly province, the oil and gas industry has significant hazards that require a lucid and attentive workforce. As a result, Alberta courts approved pre-employment drug testing in a recent court case. The decision involved an employee who tested positive for traces of marijuana. After being fired, the employee filed a complaint. Although the Queen's Bench decided in favour of the employee, the Alberta Court of Appeal stated that the company's pre-employment drug testing policy did not discriminate against the employee on the basis of a disability. Drug use amongst construction workers and employees in the energy industry has now reached upwards of 24 per cent. While urine testing is a commonly used drug testing method, oral fluid testing is now being more widely adopted in industry. Oral fluids can be used to detect recent drug and alcohol use rather than historical use and can be conducted in the presence of a test administrator. It was concluded that the aim of drug and alcohol testing is to deter substance abuse on the job. 3 figs.

  7. Longitudinal monitoring of the safety of drugs by using a web-based system : the case of pregabalin

    NARCIS (Netherlands)

    Harmark, Linda; van Puijenbroek, Eugene; van Grootheest, Kees

    Purpose Information about the time course of adverse drug reactions (ADRs) is often lacking. If this information would be available, it could help increase patient's adherence to drugs when experiencing an ADR. The aim of this study was to demonstrate how a web-based intensive monitoring system

  8. An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

    Science.gov (United States)

    Cerniglia, Carl E; Pineiro, Silvia A; Kotarski, Susan F

    2016-05-01

    The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Tennessee Oversight Agreement combined annual reports, May 13, 1991--May 12, 1993

    International Nuclear Information System (INIS)

    1993-01-01

    The Tennessee Oversight Agreement provides independent oversight and monitoring of the Department of Energy's activities on the Oak Ridge Reservation by the State. The agreement obligates the state to provide an annual report to DOE and for public distribution of the results of the DOE Oversight Division's monitoring and analysis activities and its findings of the quality and effectiveness of the Department of Energy's environmental monitoring and surveillance programs. The DOE Oversight Division's first report will discuss the status of the entire oversight agreement for the first two years of its existence. The 1991--1993 combined annual reports include a short history of the Division, a list of the Tennessee Oversight Agreement commitments and a status report on each of DOE Oversight Division's programs. Each Division program includes a descriptive status of its findings and recommendations. These findings and recommendations were also consolidated into a separate segment of the report (Chapter 7). Findings indicate there have been genuine successes in the areas of site access and data availability. More effort, however, is required in both of these areas before the state can verify that DOE and its contractors are meeting its obligations. Ambient surveillance monitoring by DOE is extensive. The DOE Oversight Division reviews this data to assure the state and its citizens that all areas of the environment are adequately protected by DOE operations. There is a noticeable lack of research and development in the technology for environmental remediation and radiological and mixed waste treatment, storage and disposal. The DOE Oversight Division's recommendations for improvement are provided with each of the findings listed in this report

  10. 76 FR 52231 - Restrictions on Operators Employing Former Flight Standards Service Aviation Safety Inspectors

    Science.gov (United States)

    2011-08-22

    ... its implementation of safety management systems, issued its report titled, ``Managing Risks in Civil... Standards Service Aviation Safety Inspectors AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... responsible for the oversight of, a Flight Standards Service Aviation Safety Inspector, and had direct...

  11. Population-based analysis of non-steroidal anti-inflammatory drug use among children in four European countries in the SOS project: What size of data platforms and which study designs do we need to assess safety issues?

    NARCIS (Netherlands)

    V.E. Valkhoff (Vera); R. Schade (René); G.W. 't Jong (Geert); S.A. Romio (Silvana); M.J. Schuemie (Martijn); A. Arfe (Andrea); C. Garbe (Claus); R.M.C. Herings (Ron); S. Lucchi (Silvia); G. Picelli (Gino); J.C. Schink (Julian); H. Straatman (Huub); M. Villa (Marco); E.J. Kuipers (Ernst); M.C.J.M. Sturkenboom (Miriam)

    2013-01-01

    textabstractBackground: Data on utilization patterns and safety of non-steroidal anti-inflammatory drugs (NSAIDs) in children are scarce. The purpose of this study was to investigate the utilization of NSAIDs among children in four European countries as part of the Safety Of non-Steroidal

  12. Mort User's Manual: For use with the Management Oversight and Risk Tree analytical logic diagram

    Energy Technology Data Exchange (ETDEWEB)

    Knox, N.W.; Eicher, R.W.

    1992-02-01

    This report contains the User's Manual for MORT (Management Oversight and Risk Tree), a logic diagram in the form of a work sheet'' that illustrates a long series of interrelated questions. MORT is a comprehensive analytical procedure that provides a disciplined method for determining the causes and contributing factors of major accidents. Alternatively, it serves as a tool to evaluate the quality of an existing system. While similar in many respects to fault tree analysis, MORT is more generalized and presents over 1500 specific elements of an ideal universal'' management program for optimizing environment, safety and health, and other programs. This User's Manual is intended to be used with the MORT diagram dated February 1992.

  13. Meeting report: Spontaneous lesions and diseases in wild, captive-bred, and zoo-housed nonhuman primates and in nonhuman primate species used in drug safety studies.

    Science.gov (United States)

    Sasseville, V G; Mansfield, K G; Mankowski, J L; Tremblay, C; Terio, K A; Mätz-Rensing, K; Gruber-Dujardin, E; Delaney, M A; Schmidt, L D; Liu, D; Markovits, J E; Owston, M; Harbison, C; Shanmukhappa, S; Miller, A D; Kaliyaperumal, S; Assaf, B T; Kattenhorn, L; Macri, S Cummings; Simmons, H A; Baldessari, A; Sharma, P; Courtney, C; Bradley, A; Cline, J M; Reindel, J F; Hutto, D L; Montali, R J; Lowenstine, L J

    2012-11-01

    The combination of loss of habitat, human population encroachment, and increased demand of select nonhuman primates for biomedical research has significantly affected populations. There remains a need for knowledge and expertise in understanding background findings as related to the age, source, strain, and disease status of nonhuman primates. In particular, for safety/biomedical studies, a broader understanding and documentation of lesions would help clarify background from drug-related findings. A workshop and a minisymposium on spontaneous lesions and diseases in nonhuman primates were sponsored by the concurrent Annual Meetings of the American College of Veterinary Pathologists and the American Society for Veterinary Clinical Pathology held December 3-4, 2011, in Nashville, Tennessee. The first session had presentations from Drs Lowenstine and Montali, pathologists with extensive experience in wild and zoo populations of nonhuman primates, which was followed by presentations of 20 unique case reports of rare or newly observed spontaneous lesions in nonhuman primates (see online files for access to digital whole-slide images corresponding to each case report at http://www.scanscope.com/ACVP%20Slide%20Seminars/2011/Primate%20Pathology/view.apml). The minisymposium was composed of 5 nonhuman-primate researchers (Drs Bradley, Cline, Sasseville, Miller, Hutto) who concentrated on background and spontaneous lesions in nonhuman primates used in drug safety studies. Cynomolgus and rhesus macaques were emphasized, with some material presented on common marmosets. Congenital, acquired, inflammatory, and neoplastic changes were highlighed with a focus on clinical, macroscopic, and histopathologic findings that could confound the interpretation of drug safety studies.

  14. A Summary of the United States Food and Drug Administrations’ Food Safety Program for Imported Seafood; One Country’s Approach

    Directory of Open Access Journals (Sweden)

    Brett Koonse

    2016-04-01

    Full Text Available It is well known that the vast majority of seafood is captured or farmed in emerging countries and exported to developed countries. This has resulted in seafood being the number one traded food commodity in the world. Food safety is essential to this trade. Exporting countries should understand the regulatory food safety programs of the countries they ship to in order to comply with their applicable laws and regulations to avoid violations and disruptions in trade. The United States (U.S. imports more seafood than any individual country in the world but the European Union (E.U. countries, as a block, import significantly more. Each importing country has its own programs and systems in place to ensure the safety of imported seafood. However, most countries that export seafood have regulatory programs in place that comply with the import requirements of the E.U. The purpose of this paper is to describe the United States Food and Drug Administration’s (USFDA imported seafood safety program. The primary audience for the information is foreign government regulators, seafood exporters, and U.S. importers. It can also give consumers confidence that f U.S. seafood is safe no matter which country it originates from.

  15. Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

    Science.gov (United States)

    Meanwell, Nicholas A

    2011-09-19

    The development of small molecule drug candidates from the discovery phase to a marketed product continues to be a challenging enterprise with very low success rates that have fostered the perception of poor productivity by the pharmaceutical industry. Although there have been significant advances in preclinical profiling that have improved compound triaging and altered the underlying reasons for compound attrition, the failure rates have not appreciably changed. As part of an effort to more deeply understand the reasons for candidate failure, there has been considerable interest in analyzing the physicochemical properties of marketed drugs for the purpose of comparing with drugs in discovery and development as a means capturing recent trends in drug design. The scenario that has emerged is one in which contemporary drug discovery is thought to be focused too heavily on advancing candidates with profiles that are most easily satisfied by molecules with increased molecular weight and higher overall lipophilicity. The preponderance of molecules expressing these properties is frequently a function of increased aromatic ring count when compared with that of the drugs launched in the latter half of the 20th century and may reflect a preoccupation with maximizing target affinity rather than taking a more holistic approach to drug design. These attributes not only present challenges for formulation and absorption but also may influence the manifestation of toxicity during development. By providing some definition around the optimal physicochemical properties associated with marketed drugs, guidelines for drug design have been developed that are based largely on calculated parameters and which may readily be applied by medicinal chemists as an aid to understanding candidate quality. The physicochemical properties of a molecule that are consistent with the potential for good oral absorption were initially defined by Lipinski, with additional insights allowing further

  16. The Additional Value of an E-Mail to Inform Healthcare Professionals of a Drug Safety Issue: A Randomized Controlled Trial in the Netherlands.

    Science.gov (United States)

    Piening, Sigrid; de Graeff, Pieter A; Straus, Sabine M J M; Haaijer-Ruskamp, Flora M; Mol, Peter G M

    2013-09-01

    The usefulness and the impact of Direct Healthcare Professional Communications (DHPCs, or 'Dear Doctor letters') in changing the clinical behaviour of physicians have been debated. Changes in the current risk communication methods should preferably be based on the preferences of the healthcare professionals, to optimize the uptake of the message. The aim of this study was to assess whether safety issues are communicated more effectively with an additional e-mail sent by the Dutch Medicines Evaluation Board (MEB) than with the DHPC only. A randomized controlled trial was conducted amongst ophthalmologists and hospital pharmacists in the Netherlands, who were the target group of a DHPC that was issued for pegaptanib, a drug that is administered intra-ocularly in patients with macular degeneration. The intervention group (N = 110) received the pegaptanib DHPC, as well as the MEB e-mail. The control group (N = 105) received the traditional paper-based DHPC only. Two weeks later, the study population received an invitation to fill out an online questionnaire. Questions were asked about the respondents' knowledge and attitude regarding the pegaptanib issue, and any action they had consequently taken. Additional questions were asked about their satisfaction with the DHPC and the e-mail, and their preferred source of such information. Forty respondents (18.6%) completed the questionnaire. Eighty-one percent of the respondents in the intervention group (N = 21) and 47% of the control group (N = 19) correctly indicated that a serious increase in intra-ocular pressure could be caused by pegaptanib injections (Fishers' exact test, p = 0.046). Nine respondents in the intervention group versus none of the control group respondents indicated that they had taken action in response to the pegaptanib safety issue (Fishers' exact test, p = 0.01). The majority of both the intervention group and the control group confirmed that they would like to receive an MEB e-mail with safety

  17. Immunogenicity and safety of high-dose hepatitis B vaccine among drug users: A randomized, open-labeled, blank-controlled trial.

    Science.gov (United States)

    Feng, Yongliang; Shi, Jing; Gao, Linying; Yao, Tian; Feng, Dan; Luo, Dan; Li, Zhansheng; Zhang, Yawei; Wang, Fuzhen; Cui, Fuqiang; Li, Li; Liang, Xiaofeng; Wang, Suping

    2017-06-03

    Due to the low uptake, adherence, and completion of vaccination among drug users, and their compromised immune responses to hepatitis B vaccination, the current practice of hepatitis B vaccination may not provide optimal protection. The aim of this study was to evaluate the immunogenicity and safety of 60 µg and 20 µg hepatitis B vaccines among drug users. A randomized, open-labeled, blank-controlled trial was conducted among drug users at 2 drug rehabilitation centers in China. The eligible participants were drug users who were serologically negative for the hepatitis B surface antigen (HBsAg) and the hepatitis B surface antibody (anti-HBs). Participants were randomized in a ratio of 1:1:1 to receive 20 µg (IM20 group) or 60 µg (IM60 group) of hepatitis B vaccine or blank control at months 0, 1, and 6, and followed at months 6, 7, and 12. Seroconversion rates of 94.7% and 92.6% were observed in IM20 and IM60 groups at month 7, and correspondingly decreased to 89.5% and 91.7% respectively at month 12. The IM60 group showed significantly higher geometric mean concentrations (GMCs) of anti-HBs (2022.5 and 676.7 mIU mL-1) than the IM20 group did (909.6 and 470.5 mIU mL-1) at months 7 and 12 (P B vaccines showed good immunogenicity among the drug users.

  18. Intra?Target Microdosing ? A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans

    OpenAIRE

    Burt, T; MacLeod, D; Lee, K; Santoro, A; DeMasi, DK; Hawk, T; Feinglos, M; Rowland, M; Noveck, RJ

    2017-01-01

    Intra-target microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers receive...

  19. Improving safety-related knowledge, attitude and practices of nurses handling cytotoxic anticancer drug: pharmacists' experience in a general hospital, Malaysia.

    Science.gov (United States)

    Keat, Chan Huan; Sooaid, Nor Suhada; Yun, Cheng Yi; Sriraman, Malathi

    2013-01-01

    An increasing trend of cytotoxic drug use, mainly in cancer treatment, has increased the occupational exposure among the nurses. This study aimed to assess the change of nurses' safety-related knowledge as well as attitude levels and subsequently to assess the change of cytotoxic drug handling practices in wards after a series of pharmacist-based interventions. This prospective interventional study with a before and after design requested a single group of 96 nurses in 15 wards actively providing chemotherapy to answer a self-administered questionnaire. A performance checklist was then used to determine the compliance of all these wards with the recommended safety measures. The first and second assessments took 2 months respectively with a 9-month intervention period. Pharmacist-based interventions included a series of technical, educational and administrative support measures consisting of the initiation of closed-system cytotoxic drug reconstitution (CDR) services, courses, training workshops and guideline updates. The mean age of nurses was 32.2∓6.19 years. Most of them were female (93.8%) and married (72.9%). The mean knowledge score of nurses was significantly increased from 45.5∓10.52 to 73.4∓8.88 out of 100 (p<0.001) at the end of the second assessment. Overall, the mean practice score among the wards was improved from 7.6∓5.51 to 15.3∓2.55 out of 20 (p<0.001). The pharmacist-based interventions improved the knowledge, attitude and safe practices of nurses in cytotoxic drug handling. Further assessment may help to confirm the sustainability of the improved practices.

  20. Systematic Review of Efficacy and Safety of Newer Antidiabetic Drugs Approved from 2013 to 2017 in Controlling HbA1c in Diabetes Patients

    Directory of Open Access Journals (Sweden)

    Sivanandy Palanisamy

    2018-06-01

    Full Text Available Type 2 Diabetes Mellitus (T2DM is the most common form of diabetes mellitus and accounts for about 95% of all diabetes cases. Many newer oral as well as parenteral antidiabetic drugs have been introduced in to the market in recent years to control hyperglycemic conditions in diabetes patients and many of these drugs produce potential side effects in diabetes patients. Hence, this systematic review was aimed to analyze and compare the efficacy and safety of oral antidiabetic agents in controlling HbA1c in T2DM patients, that were approved by the United States-Food and Drug Administration (US-FDA from 2013 to 2017. All randomized controlled, double-blind trials published in English during the search period involving the newer antidiabetic agents were selected. In the outcome assessment comparison, semaglutide demonstrated the highest efficacy in lowering HbA1c, with a 1.6% reduction (p < 0.0001 when given at a dose of 1.0 mg. The safety profile of all the agents as compared to placebo or control were similar, with no or slight increase in the occurrence of adverse events (AEs but no fatal reaction was reported. The most common AEs of all the antidiabetic agents were gastrointestinal in nature, with several cases of hypoglycemic events. However, among all these agents, semaglutide seems to be the most efficacious drug to improve glycemic control in terms of HbA1c. Alogliptin has the least overall frequency of AEs compared to other treatment groups.

  1. Pharmacokinetics and Safety of DW1029M, a Botanical Drug for the Treatment of Diabetic Nephropathy, Following Single Doses in Healthy Subjects.

    Science.gov (United States)

    Kim, Yunjeong; Jeon, Ji-Young; Kim, Eun-Young; Lim, Cheol-Hee; Jang, Hwan Bong; Kim, Min-Gul

    2017-09-01

    DW1029M is a botanical extract of Morus albalinne root bark and Puerariae radix that is used for the treatment of diabetic nephropathy. This study evaluated the safety and pharmacokinetics of DW1029M following its administration in healthy Korean subjects. We conducted a randomized, open-label, single-dose, crossover phase 1 clinical study. During each period, subjects received 300, 600, or 1200 mg oral doses of DW1029M. Plasma concentrations of puerarin, daidzin, and daidzein were analyzed using a liquid chromatography-tandem mass spectrometry. Six healthy male subjects completed the study. The maximum concentration of the drug in the plasma (C max ) and area under the plasma drug concentration-time curve to the last measurable concentration (AUC last ) for puerarin, daidzin, and daidzein were assessed after oral administration of DW1029M. No serious adverse events or clinically or statistically significant adverse events associated with any of the drug levels were observed. The results of the measurement of vital signs, electrocardiogram, laboratory tests, and physical examinations indicated that no clinically significant changes occurred during this study. The DW1029M tablet was safe and well tolerated over a single dose range of 300-1200 mg. This pharmacokinetic study of a botanical drug may aid in the development of DW1029M. © 2017, The American College of Clinical Pharmacology.

  2. Working towards consensus on methods used to elicit participant-reported safety data in uncomplicated malaria clinical drug studies: a Delphi technique study.

    Science.gov (United States)

    Mandimika, Nyaradzo; Barnes, Karen I; Chandler, Clare I R; Pace, Cheryl; Allen, Elizabeth N

    2017-01-28

    Eliciting adverse event (AE) and non-study medication data reports from clinical research participants is integral to evaluating drug safety. However, using different methods to question participants yields inconsistent results, compromising the interpretation, comparison and pooling of data across studies. This is particularly important given the widespread use of anti-malarials in vulnerable populations, and their increasing use in healthy, but at-risk individuals, as preventive treatment or to reduce malaria transmission. Experienced and knowledgeable anti-malarial drug clinical researchers were invited to participate in a Delphi technique study, to facilitate consensus on what are considered optimal (relevant, important and feasible) methods, tools, and approaches for detecting participant-reported AE and non-study medication data in uncomplicated malaria treatment studies. Of 72 invited, 25, 16 and 10 panellists responded to the first, second and third rounds of the Delphi, respectively. Overall, 68% (68/100) of all questioning items presented for rating achieved consensus. When asking general questions about health, panellists agreed on the utility of a question/concept about any change in health, taking care to ensure that such questions/concepts do not imply causality. Eighty-nine percent (39/44) of specific signs and symptoms questions were rated as optimal. For non-study medications, a general question and most structured questioning items were considered an optimal approach. The use of mobile phones, patient diaries, rating scales as well as openly engaging with participants to discuss concerns were also considered optimal complementary data-elicitation tools. This study succeeded in reaching consensus within a section of the anti-malarial drug clinical research community about using a general question concept, and structured questions for eliciting data about AEs and non-study medication reports. The concepts and items considered in this Delphi to be

  3. Rooting out institutional corruption to manage inappropriate off-label drug use.

    Science.gov (United States)

    Rodwin, Marc A

    2013-01-01

    Prescribing drugs for uses that the FDA has not approved - off-label drug use - can sometimes be justified but is typically not supported by substantial evidence of effectiveness. At the root of inappropriate off-label drug use lie perverse incentives for pharmaceutical firms and flawed oversight of prescribing physicians. Typical reform proposals such as increased sanctions for manufacturers might reduce the incidence of unjustified off-label use, but they do not remove the source of the problem. Public policy should address the cause and control the practice. To manage inappropriate off-label drug use, off-label prescriptions must be tracked in order to monitor the risks and benefits and the manufacturers' conduct. Even more important, reimbursement rules should be changed so that manufacturers cannot profit from off-label sales. When off-label sales pass a critical threshold, manufacturers should also be required to pay for independent testing of the safety and effectiveness of off-label drug uses and for the FDA to review the evidence. Manufacturers should also finance, under FDA supervision, programs designed to warn physicians and the public about the risks of off-label drug use. © 2013 American Society of Law, Medicine & Ethics, Inc.

  4. Political and Budgetary Oversight of the Ukrainian Intelligence Community: Processes, Problems and Prospects for Reform

    National Research Council Canada - National Science Library

    Petrov, Oleksii

    2007-01-01

    .... Official government documents, news reports and other literature on the intelligence system in Ukraine, as well as studies of intelligence oversight within democracies are the primary sources of data...

  5. 76 FR 10135 - Public Housing Evaluation and Oversight: Changes to the Public Housing Assessment System (PHAS...

    Science.gov (United States)

    2011-02-23

    ... Vol. 76 Wednesday, No. 36 February 23, 2011 Part III Department of Housing and Urban Development 24 CFR Parts 901, 902, and 907 Public Housing Evaluation and Oversight: Changes to the Public Housing...

  6. A perspective on the safety of cosmetic products: a position paper of the American Council on Science and Health.

    Science.gov (United States)

    Ross, Gilbert

    2006-01-01

    Over the years, some activist groups have targeted cosmetics as possible human health threats, claiming that cosmetic ingredients are not adequately tested for safety and may pose risks to consumers. The groups allege that industry practices related to safety testing are flawed, that there is little government oversight, and that cosmetics contain cancer-causing chemicals and other toxicants. A critical review of the scientific data related to these claims indicates the following: (1) Industry has the primary responsibility to ensure that all ingredients, preservatives, and coformulants used in products are safe for their intended uses. (2) The U.S. Food and Drug Administration (FDA) has regulatory oversight of the cosmetic industry. Its authority includes the banning or restriction of ingredients for safety reasons. (3) The Cosmetic Ingredient Review (CIR), an independent, scientific review board, critically evaluates chemical ingredients used in cosmetics and publishes the results of its findings in the peer-reviewed literature. (4) Health-related allegations about cosmetic ingredients are generally based on the results of high-dose laboratory testing in animals and have little relevance for humans. As true now as when Paracelsus said it in the 16th century, "It is the dose that makes the poison." (5) The health-related allegations involving specific chemicals (e.g., phthalates, parabens, and 1,3-butadiene) fail to consider important scientific studies and recent regulatory conclusions about these chemicals, which have found that they are not hazardous. (6) Animal and human physiology differ in crucial ways, further invalidating simplistic attempts to extrapolate rodent testing to human health risks. The cosmetic industry should be encouraged to publish more of its toxicity studies and safety evaluations, which would aid in dispelling the uncertainty that some consumers have about cosmetic safety.

  7. Does nanobiotechnology oversight present a uniquely complex challenge to interagency cooperation?

    International Nuclear Information System (INIS)

    Karkkainen, Bradley C.

    2011-01-01

    Numerous regulatory and oversight challenges exist in the field of nanobiotechnology. Although these challenges may appear novel and complex, similar issues have plagued environmental regulation since the 1970 s. This article argues that complexity, uncertainty, and regulatory gaps are common problems in environmental regulation, and that the lessons learned and progress made during more than 40 years of environmental regulation can serve as a guidepost for addressing nanobiotechnology regulation and oversight issues.

  8. Poor Government Oversight of Anham and Its Subcontracting Procedures Allowed Questionable Costs To Go Undetected

    Science.gov (United States)

    2011-07-30

    contractor purchasing system review of Anham. Management Comments and Audit Response The Defense Contract Mangement Agency and the U.S. Central... Introduction 1  Background 1  Government Agency Roles and Oversight Responsibilities 4  Objectives 7  Weak Government Oversight Resulted in Significant...Subcontracting Procedures Allowed Questionable Costs To Go Undetected SIGIR 11-022 July 30, 2011 Introduction Since 2003, the United States Government

  9. Ideal Police Oversight and Review: The Next Piece of the Community Policing Puzzle

    Science.gov (United States)

    2015-12-01

    oversight. Included in that malpractice are instances of perceived physical and verbal abuse , perceived harassment, failure to take appropriate action...a kid from south Stockton. 1 I. INTRODUCTION A. PROBLEM STATEMENT—BACKGROUND Independent oversight boards are asked to make the complaint...communities with inclusion and investigative transparency when filing complaints of police misconduct and abuse of police powers. In his article “Race

  10. Reinventing oversight in the twenty-first century: the question of capacity

    International Nuclear Information System (INIS)

    Bosso, Christopher; DeLeo, Rob A.; Kay, W. D.

    2011-01-01

    This article addresses a key question emerging from this project based at the University of Minnesota: the fundamental capacity of government to engage in “dynamic oversight” of emergent technologies. This conception of oversight requires additional or new types of capacity for government agencies that must arbitrate conflicts and endow any outcomes with necessary democratic legitimacy. Rethinking oversight thus also requires consideration of the fundamental design and organizational capacity of the regulatory regime in the democratic state.

  11. Advancing pharmaceuticals and patient safety in Saudi Arabia: A 2030 vision initiative

    Directory of Open Access Journals (Sweden)

    Tariq M. Alhawassi

    2018-01-01

    Full Text Available Low-quality medicines deliver sub-optimal clinical outcomes and waste precious health resources. It is important to ensure that public funds are spent on healthcare technologies that meet national regulatory bodies such as the Saudi Food and Drug Authority (SFDA, quality standards for safety, efficacy, and quality. Medicines quality is a complicated combination of pre-market regulatory specifications, appropriate sourcing of ingredients (active pharmaceutical ingredient (API, excipients, etc., manufacturing processes, healthcare ecosystem communications, and regular and robust pharmacovigilance practices. A recent conference in Riyadh, sponsored by King Saud University, sought to discuss these issues and develop specific policy recommendations for the Saudi 2030 Vision plan. This and other efforts will require more and more creative educational programs for physicians, pharmacists, hospitals, and patients, and, most importantly evolving regulations on quality standards and oversight by Saudi health authorities.

  12. Food and Drug Administration Drug Approval Process: A History and Overview.

    Science.gov (United States)

    Williams, Christopher Ty

    2016-03-01

    In this article, the processing of investigational and new drug applications is described and the standard and expedited review processes are examined. The efforts of the US Food and Drug Administration to ensure greater agency transparency and fiscal responsibility and intensify oversight during the drug development and approval process are reviewed. Often attributed to a decrease in the number of uninsured adults, both the increase in prescription drug sales and the high costs associated with bringing a new drug to market highlight the necessity for a streamlined and cost-effective process to deliver these drugs safely and effectively. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A population-based case-control study of the safety of oral anti-tuberculosis drug treatment during pregnancy

    DEFF Research Database (Denmark)

    Czeizel, A.E.; Rockenbauer, M.; Olsen, J.

    2001-01-01

    OUTCOME MEASURES: Congenital abnormalities in newborn infants and fetuses diagnosed prenatally during the second and third trimesters, and postnatally from birth to the age of one year. RESULTS: Of 38,151 controls, 29 (0.08%) were exposed to anti-tuberculosis drug treatment during pregnancy......OBJECTIVE: To study the human teratogenic potential of isoniazid and other anti-tuberculosis drug treatment during pregnancy. DESIGN AND SETTING: Cases from a large population-based dataset at the Hungarian Case-Control Surveillance of Congenital Abnormalities, and controls from the National Birth...... Registry, between 1980 and 1996. Information on all oral anti-tuberculosis drug treatments during pregnancy was medically recorded. STUDY PARTICIPANTS: Women who had newborns or fetuses with congenital abnormalities (case group), and women who had babies with no congenital abnormality (control group). MAIN...

  14. A Study of Construction Reactor Oversight Process in US

    International Nuclear Information System (INIS)

    Yun, I.; Kim, S. Y.; Jeong, G. Y.; Kim, S. P.

    2015-01-01

    This process provides a risk-informed approach such as construction significance determination process (SDP) and construction program performance index analogous to those used in the Reactor Oversight Process (ROP). The cROP has been applied to Vogtle units 3, 4 and V.C. Summer units 2, 3 under construction for the regulatory inspection. In this paper, the cROP is dissected to present its major contents and characteristics. The main features of the cROP can be summarized as followings: 1) The cROP which adopts the concept of the ROP used for operating NPPs assesses NPP under construction periodically to determine the appropriate level of regulatory response. 2) The cROP consists of three parts: the CIP, the CAP and the CEP. 3) The inspections for NPPs under construction can be categorized into three parts: vendor inspection, baseline inspection and supplemental and plant specific inspections. USNRC's regulatory resources can be used effectively based on baseline inspection, which is using ITAAC inspections. The construction SDP is used to assign the color scheme to categorize the significance of inspection findings. Regulatory actions are taken from CAM to which the significance of inspection findings input. In this paper, major contents and characteristics of USNRC's cROP have been presented

  15. Moving forward responsibly: Oversight for the nanotechnology-biology interface

    International Nuclear Information System (INIS)

    Kuzma, Jennifer

    2007-01-01

    Challenges and opportunities for appropriate oversight of nanotechnology applied to or derived from biological systems (nano-bio interface) were discussed in a public workshop and dialog hosted by the Center for Science, Technology, and Public Policy of the University of Minnesota on September 15, 2005. This paper discusses the themes that emerged from the workshop, including the importance of analyzing potential gaps in current regulatory systems; deciding upon the general approach taken toward regulation; employing non-regulatory mechanisms for governance; making risk and other studies transparent and available to the public; bolstering mechanisms for public participation in risk analysis; creating more opportunities for meaningful discussion of the social and ethical dimensions of the nano-bio interface; increasing funds for implications and problem-solving research in this area; and having independent and reliable sources for communication. The workshop was successful in identifying ways of moving forward responsibly so that ultimately nanotechnology and its products can succeed in developers', researchers', regulators', and the public's eyes

  16. [Comparison of efficacy and safety of treatment with drugs of clopidogrel in patients after coronary artery stenting].

    Science.gov (United States)

    Avdeeva, L V; Shtegman, O A; Mosina, V A

    2011-01-01

    Proof of clinical equivalence of generic and original dugs - the way to lessen cost of therapy of patients while providing comparable clinical effects. We present in this paper results of 1 year follow-up of 115 patients receiving Egithromb or Plavics after coronary artery stenting. Comparable clinical efficacy and safety of Egithromb and Plavics has been established.

  17. 78 FR 52202 - Request for Comments on the Food and Drug Administration Safety and Innovation Act Section 907...

    Science.gov (United States)

    2013-08-22

    ... information submitted to FDA is available to all interested persons in a timely fashion. DATES: Submit... completeness and quality of analyses of data on demographic subgroups in summaries of product safety and... product types and applicability. The action plan is due not later than 1 year after the publication of the...

  18. Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an update of the Oregon Drug  Effectiveness Review Project

    Directory of Open Access Journals (Sweden)

    Kylie Thaler

    2009-11-01

    Full Text Available Kylie Thaler1, Divya V Chandiramani2, Richard A Hansen2, Gerald Gartlehner11Department for Evidence-based Medicine and Clinical Epidemiology, Danube University Krems, Krems, Austria; 2UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAObjective: To systematically review the general and comparative efficacy and safety of anakinra for rheumatoid arthritis.Methods: We searched MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to April 2009. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database. For efficacy we included randomized controlled trials (RCTs comparing anakinra with placebo or other biologics. For safety both experimental and observational studies were eligible. Two persons independently reviewed abstracts and full text articles and extracted relevant data.Results: We included data from 3 RCTs comparing anakinra with placebo for rheumatoid arthritis (RA. The pooled relative risk (RR of an ACR50 (American College of Rheumatology response for anakinra compared with placebo is 2.28 (95% CI 1.41 to 3.67. Adjusted indirect comparisons of ACR50 response rates of anakinra and anti-TNF agents showed a RR of 0.67 (95% CI 0.38 to 1.17 favoring the anti-TNF drugs. This result did not reach statistical significance. For safety, we included 9 experimental and observational studies of 24 weeks to 3 years duration. Up to 30% of patients withdrew from the studies due to adverse events. 67.2% (95% CI 38.7 to 95.7 of patients experienced an injection site reaction.Conclusions: Anakinra is an effective drug for treating RA. Indirect comparisons with adalimumab, etanercept and infliximab, however, showed a trend towards greater efficacy for the anti-TNF drugs. Anakinra also seems to be associated with comparably high rates of injection site reactions. These results should be taken into

  19. Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir. II: a pediatric drug use investigation.

    Science.gov (United States)

    Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

    2015-03-01

    Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. In October 2010, an additional indication for pediatric use was approved. We conducted a pediatric drug use investigation of peramivir from October 2010 to February 2012 and evaluated its real-world safety and effectiveness in pediatric patients. We collected the data of 1254 peramivir-treated pediatric patients from 161 facilities across Japan and examined the safety in 1199 patients and effectiveness in 1188 patients. In total, 245 adverse events were observed with an incidence rate of 14.01% (168/1199). Of these, 115 events were adverse drug reactions (ADRs) with an incidence rate of 7.67% (92/1199). Common ADRs were diarrhea and abnormal behavior, with incidence rates of 2.50% (30/1199) and 2.25% (27/1199), respectively. Fourteen serious ADRs were observed in 12 patients (1.00%), including 5 cases each of abnormal behavior and neutrophil count decreased. While 87.0% (100 events) of ADRs occurred within 3 days after the initiation of peramivir administration, 87.8% (101 events) resolved or improved within 7 days after onset. Multivariate analyses indicated that the presence or absence of underlying diseases/complications was significantly related to ADR incidence. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. Thus, this study confirms the pediatric safety of peramivir without any concerns about effectiveness under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. The basics of preclinical drug development for neurodegenerative disease indications.

    Science.gov (United States)

    Steinmetz, Karen L; Spack, Edward G

    2009-06-12

    Preclinical development encompasses the activities that link drug discovery in the laboratory to initiation of human clinical trials. Preclinical studies can be designed to identify a lead candidate from several hits; develop the best procedure for new drug scale-up; select the best formulation; determine the route, frequency, and duration of exposure; and ultimately support the intended clinical trial design. The details of each preclinical development package can vary, but all have some common features. Rodent and nonrodent mammalian models are used to delineate the pharmacokinetic profile and general safety, as well as to identify toxicity patterns. One or more species may be used to determine the drug's mean residence time in the body, which depends on inherent absorption, distribution, metabolism, and excretion properties. For drugs intended to treat Alzheimer's disease or other brain-targeted diseases, the ability of a drug to cross the blood brain barrier may be a key issue. Toxicology and safety studies identify potential target organs for adverse effects and define the Therapeutic Index to set the initial starting doses in clinical trials. Pivotal preclinical safety studies generally require regulatory oversight as defined by US Food and Drug Administration (FDA) Good Laboratory Practices and international guidelines, including the International Conference on Harmonization. Concurrent preclinical development activities include developing the Clinical Plan and preparing the new drug product, including the associated documentation to meet stringent FDA Good Manufacturing Practices regulatory guidelines. A wide range of commercial and government contract options are available for investigators seeking to advance their candidate(s). Government programs such as the Small Business Innovative Research and Small Business Technology Transfer grants and the National Institutes of Health Rapid Access to Interventional Development Pilot Program provide funding and