A proposition well known to geometers (United States)

This note describes laboratory experiment ?13 in the liberal arts physics course Galileo to Newton and Beyond. The title of these experiment is Newton's Collision Experiments with Pendulums. Newton described these experiments in his Principia (pp. 22-25). He used these experiments to provide experimental confirmation for his action-reaction law. The note focuses on a mathematical proposition which was well known to geometers at the time of Newton, that "the velocity of a pendulum body in the lowest point is as the chord of the arc which it has described in its descent."

Erlichson, Herman



Video Streaming Performance Under Well-Known Packet Scheduling Algorithms  

Directory of Open Access Journals (Sweden)

Full Text Available Video streaming is becoming increasingly popular among the wireless users. However, supporting videostreaming over the wireless networks is not an easy task due to the dynamic radio propagationenvironment, limited radio resources as well as Quality of Service (QoS requirements of the videostreaming that need to be satisfied at acceptable levels. Most studies proposed to support video streamingare computationally expensive to be used in Orthogonal Frequency Division Multiple Access (OFDMAbased wireless IP networks. This paper evaluates video streaming performance under three well-knownalgorithms that are more practical to be used in the OFDMA based wireless IP networks due to theirreduced complexity. It is demonstrated via computer simulation that Proportional Fair (PF algorithmoutperforms other well-known algorithms by providing video streaming QoS at acceptable levels whilstmaximizing cell throughput.

Huda Adibah Mohd Ramli




Digital Repository Infrastructure Vision for European Research (DRIVER)

This study focuses on organizational capabilities for strategic leadership in logistics companies in today’s hectic and dynamic business environment. The main aim of the thesis is to understand and to explore the logistics companies use organizational capabilities for strategic leadership and how they react to the changes. The mini-survey was made by analyzing seven well-known logistics companies in Finland. Organizational capabilities include formulating strategies, learning process, p...

Urb, Liina



Observer-based control design for three well-known chaotic systems  

International Nuclear Information System (INIS)

In this paper, a singularity-free approach is proposed for controlling three well-known chaotic systems namely Lorenz, Chen and Lu. The control design guarantees the regulation of two states and boundedness of the remaining state. The stability of the proposed scheme has been shown using the Lyapunov stability theorem. Implementation of the proposed control technique requires system states, while in most of practical applications only the system output is available. To overcome this problem, a nonlinear observer is coupled with the controller. Simulation results have illustrated the effectiveness and robustness of the proposed schemes. If the control action is applied to the second system equation, all states will be regulated


An investigation on consumer’s behaviors towards well-known luxury brands  

Directory of Open Access Journals (Sweden)

Full Text Available This paper presents an empirical investigation to find the relationship between consumer’s behaviors towards well-known luxury brands in Iranian market. The study designs a questionnaire in Likert scale and distributes it among 250 randomly people who purchase luxury products. The study investigates the effects of three variables including perception value, social normality and need for being exclusive on perception of a brand for motivating customers to purchase luxury products. In addition, the study tries to find out whether customers’ educational backgrounds influence on purchasing luxury products or not. Cronbach alphas are all well above the minimum acceptable level, which validates the survey. Using structural equation modeling, the study confirms all hypotheses of the survey.

Mohammad Javad Ghasemi



Mobile System to Guide Blind People in a Well-Known Environment (United States)

The system aids to low-vision disabled people to move in a well-known environment, at the University of Almeria. So, a 3G mobile phone has been used in order to help blind people to have a better standard of life because they could go from a building to other using his mobile phone. Therefore, audible instructions are used to inform the user, which will have been decided in advance by the computer vision module (the decision will be taken according to the environment). That module captures images in real time (using the camera of the mobile phone, which has to be over the chest of the user, fixed with a string) and recognizes static objects in the middle of the way. Moreover, it tries to avoid the situation in which the user is going out of the way. On the other hand, an application has been developed so as to supervise all the users of the system and even visualize their position.

Domene, Luis M.; Piedra, José A.; Cantón, Manuel


The impact of media coverage of the suicide of a well-known Quebec reporter: the case of Gaëtan Girouard. (United States)

Evidence of a media impact on suicide is mixed and needs further research. The main objective of this article is to document the effects of the media coverage following the suicide of a well-known and popular television reporter in Quebec, Canada. A content analysis of the printed media and an analysis of suicide rates during the following year, of coroners' records and of calls to Suicide Prevention Centres during the following 3 months was conducted. Most guidelines for responsible reporting of a suicide were not applied. The results showed a rise in the suicides rates immediately after the reporter's suicide, especially by hanging as in the original case. A cluster of six suicides by hanging also took place in the small municipality where the reporter's suicide occurred. There was also an indication of direct influence in the coroners' records and a rise in calls to Suicide Prevention Centres. This research indicates that the reporting of the suicide of a popular figure preceded an important rise in the number of suicides. A possible theoretical explanation is that a positive role model appeared to suddenly fail to cope with life, thus creating high distress and cognitive dissonance in the audience. The news media should apply more caution and follow recommended guidelines in reporting this type of news. PMID:15743643

Tousignant, Michel; Mishara, Brian L; Caillaud, Aline; Fortin, Veronique; St-Laurent, Danielle



Can exposure limitations for well-known contact allergens be simplified? An analysis of dose-response patch test data  

DEFF Research Database (Denmark)

Background. Allergic contact dermatitis is triggered by chemicals in the environment. Primary prevention is aimed at minimizing the risk of induction, whereas secondary and tertiary prevention are aimed at reducing elicitation. Objectives. To identify the elicitation doses that will elicit an allergic reaction in 10% of allergic individuals under patch test conditions (ED10 patch test) for different allergens, and to compare the results with those for different allergens and with animal data indicating sensitizing potency from the literature. Materials and methods. The literature was searched for patch test elicitation studies that fulfilled six selected criteria. The elicitation doses were calculated, and fitted dose–response curves were drawn. Results. Sixteen studies with eight different allergens–methylchloroisothiazolinone/ methylisothiazolinone, formaldehyde, nickel, cobalt, chromium, isoeugenol, hydroxyiso hexyl 3-cyclohexene carboxaldehyde, and methyldibromo glutaronitrile–were selected. The median ED10 value was 0.835 µg/cm2. The ED10 patch test values were all within a factor of 7 from the lowest to the highest value, leaving out three outliers. No obvious patterns between the sensitization and elicitation doses for the allergens were found. Conclusions. We found a rather small variation in the ED10 patch test between the allergens, and no clear relationship between induction potency and elicitation threshold of a range of allergens. This knowledge may stimulate thoughts on introducing a generic approach for limitations in exposure to well-known allergens.

Neergaard, Louise Arup; Menné, Torkil



Polychlorinated biphenyl/biphenyl degrading gene clusters in Rhodococcus sp. K37, HA99, and TA431 are different from well-known bph gene clusters of Rhodococci. (United States)

Four kinds of polychlorinated biphenyl (PCB)-degrading Rhodococcus sp. (TA421, TA431, HA99, and K37) have been isolated from termite ecosystem and under alkaline condition. The bph gene cluster involved in the degradation of PCB/biphenyl has been analyzed in strain TA421. This gene cluster was highly homologous to bph gene clusters in R. globerulus P6 and Rhodococcus sp. RHA1. In this study, we cloned and analyzed the bph gene cluster essential to PCB/biphenyl degradation from R. rhodochrous K37. The order of the genes and the sequence were different in K37 than in P6, RHA1, and TA421. The bphC8(K37) gene was more homologous to the meta-cleavage enzyme involved in phenanthrene metabolism than bphC genes involved in biphenyl metabolism. Two other Rhodococcus strains (HA99 and TA431) had PCB/biphenyl degradation gene clusters similar to that in K37. These findings suggest that these bph gene clusters evolved separately from the well-known bph gene clusters of PCB/biphenyl degraders. PMID:17485846

Taguchi, Katsuhiko; Motoyama, Masaki; Iida, Toshiya; Kudo, Toshiaki



Cardiac surgery and hypertension: a dangerous association that must be well known / Cirurgia cardíaca e hipertensão: uma associação perigosa que deve ser bem conhecida  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese É sabido que a hipertensão é uma doença muito comum, e que os acidentes cerebrovasculares graves podem ocorrer se a pressão sanguínea não for apropriadamente controlada. Contudo, as condições associadas à hipertensão não controlada podem ser negligenciadas, e tornarem-se críticas, necessitando, even [...] tualmente, uma intervenção cirúrgica urgente. Doença coronariana, síndrome aórtica aguda, cardiopatias congênitas, valvopatias e arritmias são sob este tópico de discussão. Dentre eles, a doença corornariana, inclusive o infarto do miocárdio e especialmente a ruptura cardíaca pós-infarto e a dissecção aórtica, são as situações críticas principais que os médicos podem encontrar na prática clínica. O papel que a hipertensão desempenha nessas condições pode ser complexo, incluindo fatores hemodinâmicos, eletrofisiológicos e biomoleculares, nos quais o último pode prevalecer atualmente. A doença coronariana pode associar-se com uma redução na síntese de óxido nítrico. Fator de crescimento transformador e nas metaloproteinases da matriz têm sido observados em relação à síndrome aórtica. O Wnt, p38 e a via de sinalização JNK caminho podem estar implicado no desenvolvimento da hipertrofia ventricular responsável por arritmias cardíacas. Vários fenótipos dos genes podem apresentar defeitos cardíacos congênitos diferentes. Este artigo apresenta essas condições, e discute, além disso, possíveis etiologias e as estratégias de tratamento potenciais bem destacar sua importância quanto a prognóstico. Abstract in english It is well-known that hypertension is a very common disease, and severe cerebrovascular accidents might occur if the blood pressure is not properly controlled. However, conditions associated with uncontrolled hypertension may be overlooked, and may become critical and eventually require a surgical i [...] ntervention on an urgent basis. Coronary artery disease, acute aortic syndrome, congenital and valvular heart disease, and arrhythmias are under this topic of discussion. Of them, coronary artery disease including myocardial infarction and especially postinfarction myocardial rupture, and aortic dissection are major critical situations that physicians may encounter in clinical practice. The role that hypertension plays in these conditions can be complex, including hemodynamic, electrophysiological and biomolecular factors, where the latter may prevail in the current era. Coronary artery disease may be associated with a reduced nitric oxide synthesis. Transforming growth factor and matrix metalloproteinases have been observed in relation to aortic syndrome. Wnt, p38 and JNK signaling pathway may be involved in the development of ventricular hypertrophy responsible for cardiac arrythmias. Various gene phynotypes may present in different congenital heart defects. This article is to present these conditions, and to further discuss the possible etiologies and the potential treatment strategies so as to highlight the relevance at a prognostic level.

Shi-Min, Yuan; Hua, Jing.



Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: Spanish Abstract in spanish Las enfermedades cardiovasculares (ECV) son la principal causa de mortalidad en el mundo. Varios de los factores de riesgo de las ECV, como dislipidemias, hipertensión arterial y diabetes mellitus, son influenciados por la alimentación. Es conocido que las frutas y hortalizas contienen antioxidantes [...] , y que su consumo en una cantidad adecuada disminuye el riesgo cardiovascular. Sin embargo, su efecto antitrombótico (antiagregante plaquetario, anticoagulante y fibrinolítico) es poco conocido. En esta revisión se describen brevemente dichos efectos, tanto in vitro como in vivo, y los posibles mecanismos que podrían explicar éstos. En cuanto al efecto antiagregante plaquetario, entre las frutas que poseen dicha característica se incluyen uva negra, piña, frutilla y kiwi. Entre las hortalizas en que se ha descrito efecto antiagregante están el ajo, la cebolla, el cebollín, el tomate y el melón. Por su parte, el efecto anticoagulante, entre las frutas, sólo se ha encontrado en la piña, y entre las hortalizas en ajos y cebollas. El efecto fibrinolítico se ha descrito en frutas como el kiwi y la piña, y hortalizas como el ajo, las cebollas y la soya. Algunas frutas (piña y kiwi) y hortalizas (ajo y cebollas) presentan más de un efecto antitrombótico por lo que seguramente su consumo regular protege de las ECV. Nosotros hemos iniciado el estudio, por lo pronto in vitro, del posible efecto antitrombótico de frutas y hortalizas de la Región del Maule. Siendo necesario aumentar el consumo interno y las exportaciones de frutas y hortalizas, tanto para mejorar la salud de la población como desde el punto de vista económico, parece relevante contribuir al conocimiento de los efectos aquí descritos, los que son menos conocidos que el efecto antioxidante Abstract in english Cardiovascular diseases (CVD) are the leading cause of death in the world. Several risk factors for CVD, such as lipid disorders, hypertension and diabetes mellitus, are influenced by food. It is well known that fruits and vegetables contain antioxidants and its adequate consumption reduces cardiova [...] scular risk. However, its antithrombotic effect (antiplatelet agent, anticoagulant and fibrinolytic) is little known. This review briefly describes these effects, both in vivo and in vitro, and the possible mechanisms that could explain this effect. Fruits such as black grape, pineapple, strawberry and kiwi show this effect. Among the vegetables that have antiaggregatory effect are garlic, onions, welsh onions, tomatoes and melons. On the other hand, the anticoagulant effect has only been found in fruits like pineapple, and among the vegetables in garlic and onions. The fibrinolytic effect has been described in fruits like kiwi and pineapple, and in vegetables such as garlic, onions and soybeans. Some fruits (pineapple and kiwi) and vegetables (onion and garlic) have more than one antithrombotic effect so their regular consumption certainly protects from CVD. We have begun the study, initially in vitro, of the potential antithrombotic effect of fruits and vegetables in the Maule Region. It is necessary to increase our domestic consumption and export of fruits and vegetables, both to improve the health of the population and the economy. The reasons above stated describe the importance of the contribution of knowledge due to the fact that antioxidant effects are less known

Constanza, Torres U; Luis, Guzmán J; Rodrigo, Moore-Carrasco; Iván, Palomo G.



IgG4-related Hashimoto’s thyroiditis – A new variant of a well known disease / Tireoidite de Hashimoto associada a IgG4 – Uma nova variante de uma doença bem conhecida  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese A tireoidite de Hashimoto (TH) foi caracterizada durante muitos anos como uma entidade clinicopatológica bem definida, mas é atualmente considerada uma patologia heterogênea. A TH associada a IgG4 apresenta-se como um novo subtipo, sendo caracterizada por inflamação da tireoide com numerosos plasmóc [...] itos IgG4-positivos e fibrose extensa. É possível que pertença ao espectro da doença sistêmica associada a IgG4. Relatamos o caso de um homem português de 56 anos que se apresentou com aumento progressivo do volume cervical e disfagia, com um mês de evolução. A avaliação laboratorial revelou elevação dos parâmetros inflamatórios, hipotireoidismo subclínico e níveis muito elevados de autoanticorpos tireoidianos. Por ultrassonografia cervical demonstrou-se tireoide aumentada, heterogênea, com dois nódulos hipoecoicos. Foi realizada citologia aspirativa com agulha fina guiada por ultrassom, compatível com tireoidite linfocítica. O doente foi submetido à tireoidectomia total e o exame histológico revelou achados típicos de TH, extensa fibrose localizada dentro da cápsula tireoidiana e infiltrado linfoplasmocitário, com >50 plasmócitos IgG4-positivos por campo de grande ampliação e uma relação IgG4/IgG >40%. Após cirurgia, a concentração sérica de IgG4 encontrava-se no limite superior do normal. Ocorreu melhoria sintomática e redução dos parâmetros inflamatórios. A função tireoidiana foi controlada com levotiroxina. Relatamos o primeiro caso de TH associada a IgG4 num indivíduo não asiático. Além disso, realizamos uma revisão da literatura sobre doença associada a IgG4 e TH associada a IgG4. Este caso destaca uma nova variante da TH e permite aos médicos reconhecerem suas principais características clínicas, proporcionando diagnóstico e tratamento adequados. Abstract in english Hashimoto’s thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part [...] of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment.

Henrique Vara, Luiz; Diogo, Gonçalves; Tiago Nunes da, Silva; Isabel, Nascimento; Ana, Ribeiro; Manuela, Mafra; Isabel, Manita; Jorge, Portugal.



Russian Summerfolk in Estonia: the Well-Known Names  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Šis straipsnis yra dalis kolektyvinio kult?rologinio tyrimo, atlikto Talino universiteto mokslinink? (pagal Aurikos Meimr?s projekt? G0705 „Kult?rin? topografija: rus? vasaroto jai Estijoje“) ir skirto rusišk? vasarnami? (rus. ????) fenomenui Estijos Kasmu (Laane-Viru rajonas), kur 1960–1980 m. ils?davosi Maskvos ir Sankt Peterburgo inteligentijos atstovai, tirti. ?žangin?je dalyje autorius paaiškina termin? da?ia (lygindamas j? su lotyn? kalbos daiktavardžiu da...

K??????, ?????



Public, epicureans celebrate well-known dining guide (United States)

Centuries ago, the experience of âÂÂdining outâ for most travelers would have been a potentially harrowing one. Faced with few options, most persons on the road would have to settle for the unpredictable fare of a local innkeeper. With the arrival of the automobile and the expansion of dining options, travelers often had more choices, but how to choose? One such traveling salesman by the name of Duncan Hines compiled a list of 167 dining establishments in 1935 that he soon began to pass out to friends and acquaintances. Soon, a deluge of dining guides came on the market over the coming decades, and one of these young upstarts recently celebrated its 25th year in existence. The Zagat Survey was first published in 1979 as a guide to restaurants in New York, and has since grown to cover the entire country, and also branched out into other subjects to rate and pick apart at length, including golf, hotels, and nightlife. The guides are the inventions of Tim and Nina Zagat, who originally started the guidebook as a small hobby. Despite the guidebooksâ popularity, they are not without their critics. As anyone can logon to the Zagat website and cast their votes on various aspects of the dining experience at different restaurants, some have claimed that this process results in a widely varying range of opinions, and that some of these opinions undermine the more qualified opining of food critics and professional chefs.The first link leads to a recent piece from on the long-running restaurant guidebook series, and includes a brief interview with Tim Zagat. The second link will whisk visitors away to an article from this WednesdayâÂÂs San Francisco Chronicle that discusses the online voting process utilized by Zagat that some suggest may be compromising the guidebookâÂÂs credibility and accuracy. The third link leads to another article from the Chicago Sun-Times that discusses the results of the annual Zagat survey of the nationâÂÂs top restaurants. Interestingly enough, the survey finds that Philadelphians are the best tippers in the country, and that denizens of the âÂÂSecond Cityâ donâÂÂt tip so poorly either. The fourth link leads to the Zagat homepage, where visitors can offer their own informed opinions on various restaurants from IvarâÂÂs Acres of Clams in Seattle to the legendary Rainbow Room in New York. The fifth link offers some biographical information about that longtime restaurant critic, Mr. Duncan Hines, courtesy of the equally venerable corporate entity that bears his name. The final link leads to a fun story from from several weeks ago that profiles the most expensive restaurants in the United States, including the Ginza Sushiko in Los Angeles, where meals costs over $600 for a mere two persons.


Clinical Trials  

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Full Text Available Clinical Trials Introduction A clinical trial is a research study done to evaluate new treatments in people. ... a Clinical Trial? A clinical trial is a research study conducted to evaluate new treatments in people. ...


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Full Text Available ... ongoing basis. As a clinical trial progresses, researchers report the results of the trial at scientific meetings, ... secret and will not be mentioned in these reports. How to Find Trials Using For ...


Clinical Trials  

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A randomized controlled trial of R-salbutamol for topical treatment of discoid lupus erythematosus  

DEFF Research Database (Denmark)

In a recent open pilot trial, R-salbutamol sulphate, a well-known molecule with anti-inflammatory effects, was tested successfully on patients with therapy-resistant discoid lupus erythematosus (DLE).

Jemec, Gregor; Ullman, Susanne



Clinical Trials  

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Full Text Available ... clinical trials for many reasons. First is the hope that by participating in a trial, they will ... to answer specific research questions. Some clinical trials test one new treatment in one group of participants. ...


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Full Text Available ... work in people. You may be interested in or asked to consider participating in a clinical trial. ... treatment, its risks, and how well it may or may not work. Why are Clinical Trials Important? ...


Clinical Trials  

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Full Text Available ... answer some of the most common questions. What is a Clinical Trial? A clinical trial is a research study conducted to evaluate new treatments in people. Each study is designed to learn about a potential treatment and ...


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Full Text Available ... should provide for monitoring the data and the safety of patients on an ongoing basis. As a clinical trial progresses, researchers report the results of the trial at scientific meetings, ...


Clinical Trials  

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Full Text Available Clinical Trials Introduction A clinical trial is a research study done to evaluate new treatments in people. Carefully conducted clinical trials are the fastest way to find new treatments that work in people. You may be interested in or ...


Types of Clinical Trials (United States)

Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.


Clinical Trials  

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Full Text Available ... clinical trial is reviewed for patient safety and scientific merit by the research institution. Every study should provide for monitoring the data and the safety of patients on an ongoing basis. As a ... the trial at scientific meetings, to medical journals, and to various government ...


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Full Text Available ... reviewed: 09/15/2012 1 Why Should You Be Interested in a Clinical Trial? People volunteer to ... always a chance that a new treatment will be disappointing. However, based on laboratory results, the researchers ...


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Full Text Available ... a group receives is often decided by a process called “randomization.” It's like tossing a coin, only ... and benefits. Informed Consent Informed consent is a process of learning key facts about a clinical trial ...


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Clinical Trials (United States)

... after the clinical trial ends? If I have bipolar disorder, what will happen if the treatment makes me ... wellness for people who live with depression and bipolar disorder. Because DBSA was created for and is led ...


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Full Text Available ... Every clinical trial is designed to answer a set of research questions. The doctors who conduct a ... institution. Every study should provide for monitoring the data and the safety of patients on an ongoing ...


Clinical Trials  

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Full Text Available The clinical practice of resuscitation science is dependent on discoveries generated in the basic science and animal laboratory and then translated into clinical trials for application in humans. The successful implementation of prospective, randomized, controlled, clinical trials in the field of cardiac arrest remains challenging and continues to evolve. Funding for clinical trials of cardiac arrest is limited, and there are significant obstacles to performing such studies because of the inability to obtain informed consent under these emergency circumstances. The absence of reliable national statistics on cardiac arrest, evaluation of neurological outcome, and potential confounders such as post-resuscitation hospital-based care and quality of cardiopulmonary resuscitation (CPR continue to challenge cardiac arrest clinical trials. Nonetheless, the immense public health burden of cardiac arrest is being recognized, appropriate public health initiatives to address the problem are being implemented, and the resuscitation research community is meeting this challenge.




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Stroke Trials Registry (United States)

... News About Neurology Image Library Search The Internet Stroke Center Trials Registry Clinical Trials Interventions Conditions Sponsors ... a clinical trial near you Welcome to the Stroke Trials Registry Our registry of clinical trials in ...


Paying for Clinical Trials (United States)

Learn About Clinical Trials In English En español Updated: 11/02/2012 Learn About Clinical Trials What Are Clinical Trials? Paying ... for Clinical Trials NCI Publications Español Paying for Clinical Trials Senior couple reviewing bills. As you think ...


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Comparing Semi-Automatic Systems for Recruitment of Patients to Clinical Trials | (United States)

The recruitment process is a well-known bottleneck in research and there is considerable evidence that decision support systems can improve this process. Results of a comprehensive literature search identified 28 distinct studies of Clinical Trial Recruitment Support Systems (CTRSS) over 33 publications. The identified papers propose that adopting a formalized way of representing recruitment criteria could dramatically improve their quality, allow indexing or annotation of clinical trials, and open the way to automatic recruitment of patients.


Whose data set is it anyway? Sharing raw data from randomized trials  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. Discussion Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aidi...

Vickers Andrew J



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Search for Clinical Trials (United States)

Search for Clinical Trials Clinical Trial Questions?Get Help:1-800-4-CANCERLiveHelp online chat Popular Resources Help Using the NCI Clinical Trials Search Form How to Find a Cancer Treatment Trial Learn About Clinical Trials About NCI's List of Cancer


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... products regulated by FDA. How does FDA use clinical trials data? FDA uses the information from clinical ... clinical trials. How can I learn more about clinical trials? FDA has a website to help patients ...


Thermodynamic Properties of Rock-Forming Garnets: How Well Known are They? (United States)

Garnet is an important rock-forming mineral whose geological occurrence is widespread. The silicate garnets (E3G2Si3O12) show extensive compositional variability and the various end-members are stable over an enormous range of rock compositions and pressure and temperature conditions. Extensive geothermometry and geobarometry studies involving garnet have been made. Thus, much research has been done to determine garnet's thermodynamic properties. There are now several internally consistent mineralogical thermodynamic databases and their use is widespread. It is common belief in some/many circles that the present databases represent "the final word" on thermodynamic properties at least in terms of most end-member silicates. The question arises - How true is this assumption in the case of garnet? We have been and are presently engaged in investigating the thermodynamic properties of garnet, where volumetric properties and heat-capacity behavior play a central role. The volumes of the various end-member garnets are now known precisely. Only secondary effects arising from extra minor components (e.g., OH-,Fe3+,Mn3+) have yet to be worked out exactly. In terms of heat capacity Cp behavior, new calorimetric data allow improved understanding. Low T calorimetric measurements on spessartine were made recently and show that previous estimates for S° were in error (Dachs et al. 2009). New unpublished calorimetric results on grossular appear to have resolved long-standing uncertainty regarding its precise S° value. S° for silica-free hydrogrossular has also been determined for the first time. Cp measurements are now focusing on almandine and here low T electronic and magnetic properties must be considered. One can conclude that Cp, S°, ?H°f, V and ?G°f for the common silicate garnet end-members are now well determined to about 1000 K. Cp behavior above roughly 1000 K is less certain for some garnets (e.g., almandine, spessartine). What about thermodynamic behavior of garnet solid solutions? Here, there is much less is known (Geiger 1999). The precise mixing behavior of most garnet binaries, for example, is not understood. An exception is the pyrope-grossular binary, which has now been investigated numerous times and some consensus on its mixing properties now exist. In a related area, crystal-chemical investigations are providing good insight on possible macroscopic thermodynamic mixing behavior. Here, for example, low temperature synchrotron measurements on line broadening of powder diffraction lines give the first quantitative lattice-strain determinations on a solid solution (Dapiaggi et al. 20005). The asymmetric nature of the mixing functions ?Hex, ?Sex, and ?Vex can be explained via strain and local Ca/Mg-O bond behavior. Another area needing further investigation is short-range order. 29Si NMR spectroscopic study of synthetic Py-Gr garnets indicates that some short-range Ca-Mg order may be present. Bosenick et al. (1999) estimate that configurational entropy effects of about 2 J/mole.K may result at T > 1000 °C. It remains to be determined, however, what the structural state is at lower temperatures of 600 to 900 °C. The degree of short-range order could be substantial in metamorphic garnet solid solutions.

Geiger, C. A.; Dachs, E.



The well-known unknown photographer Jaan Klõšeiko / Ellu Maar  

Index Scriptorium Estoniae

Graafik ja fotograaf Jaan Klõšeikost, kes on 45 aastat jäädvustanud kunsti- ja kultuurisündmusi. Galerii Vaal kodulehel ilmunud J. Klõšeiko fotoseeriatest (12), fotod valis ja saatesõnad kirjutas J. Klõšeiko

Maar, Ellu, 1982-



Comparing the personality of three well-known sporting brands in Iran  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A significant amount of literature specifies that there are benefits for having a favorable brand personality, such as purchase intentions and enhanced brand attitudes and higher degrees of consumer trust and loyalty. Brand differentiation is one of most important issues to handle competition in the hostile marketplace. A reliable solution for establishing the distinctiveness of a brand is through brand personality. This study analyzes the personality of Adidas, Nike and Puma brands in Iran u...

Mohmood Mohammadian; Hamidreza Asgari Dehabadi



Macro with Pico Cells (HETNETS System Behaviour using Well-Known Scheduling Algorithms  

Directory of Open Access Journals (Sweden)

Full Text Available This paper demonstrates the concept of using Heterogeneous network s ( HetNets to improve Long Term Evolution (LTE system by introducing the LTE A dvance (LTE - A . The type of HetNets that has been chosen for this study is Macro with Pic o cells. Comparing the system performance with and without Pico cells has clearly illustrated using three well - know n scheduling algorithms ( Proportional Fair P F, Maximum Largest Weighted Delay First MLWDF and Exponential/Proportional Fair EXP/PF. The syst em is judged based on throughpu t, Pac ket Loss Ratio PLR , delay and f airness. . A simulation platform called LTE - Sim has been used to collect the data and produce the paper’s outcomes and graphs. The result s prove that adding Pico cells enhances the overall system performance. From the simulation outcomes, the overall system performance is as follows: throughput is duplicated or tripled based on the number of users , the PLR is almost quartered , the delay is nearly reduced ten times (PF case and c hange d to be a half (MLWDF/EXP cases, and the fairness stays closer to value of 1 . It is considered an efficient and cost effective way to increase the throughput, coverage and reduce the latency.

Haider Al Kim



Pimafucort®. New approach to well-known drug Pimafucort®. Nowe spojrzenie na dobrze znany lek  

Directory of Open Access Journals (Sweden)

Full Text Available Pimafucort, which is composed of natamycin, neomycin and hydrocortisone is a valuable drug used in mixed infections caused by bacteria and fungi as well as in the onset of acute inflammation in different dermatoses (e.g. eczema or intertrigo with secondary contamination.

Wojciech Baran



Joseph Daquin, Piedmontese Savoyard physician, a "not well-known chiarugi". (United States)

We present a critical review of La philosophie de la folie, second edition, published in 1804. Joseph Daquin's thoughts and clinical activity in the psychiatric field are described. Daquin's ideas about various forms of madness and the different therapeutic, moral, physical treatments, his anatomical studies, successes and failures are presented. Several clinical cases are described. The author's view of the moon's influence on madness is described. Finally it is shown how very important was the human person and the moral treatment of madness for Daquin, in contrast with the current opinion at the end of 1700. PMID:11623834

Vanni, D; Salomone, B; Pomini, D; Vanni, P; Ottaviani, R



About the activity and selectivity of less well-known metathesis catalysts during ADMET polymerizations  

Directory of Open Access Journals (Sweden)

Full Text Available We report on the catalytic activity of commercially available Ru-indenylidene and “boomerang” complexes C1, C2 and C3 in acyclic diene metathesis (ADMET polymerization of a fully renewable ?,?-diene. A high activity of these catalysts was observed for the synthesis of the desired renewable polyesters with molecular weights of up to 17000 Da, which is considerably higher than molecular weights obtained using the same monomer with previously studied catalysts. Moreover, olefin isomerization side reactions that occur during the ADMET polymerizations were studied in detail. The isomerization reactions were investigated by degradation of the prepared polyesters via transesterification with methanol, yielding diesters. These diesters, representing the repeat units of the polyesters, were then quantified by GC-MS.

Hatice Mutlu



A Quantitative Relation between Modulational Instability and the Well-known Nonlinear Excitations  

CERN Document Server

We study on explicit relations between modulational instability and analytical nonlinear excitations in a self-focusing Kerr nonlinear fiber in anomalous group velocity dispersion regime, such as bright soliton, nonlinear continuous wave, Akhmediev breather, Peregrine rogue wave, and Kuznetsov-Ma breather. We present a quantitative correspondence between them based on the dominant frequency and propagation constant of each perturbation on a continuous wave background. Especially, we find rogue wave comes from modulational instability under the "resonance" perturbation with continuous wave background. These results will deepen our realization on rogue wave excitation and could be helpful for controllable nonlinear waves excitations in nonlinear fiber and other nonlinear systems.

Zhao, Li-Chen



Participating in Clinical Trials  

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Full Text Available ... basic research. Screening Trials In screening trials, researchers study ways of finding a disease before symptoms occur. These methods, often called screening tests, can include imaging tests ...


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Full Text Available ... are not intended to treat or cure a disease. Phases of Clinical Trials Clinical trials of drugs are usually described based on their phase. The U.S. Food and Drug Administration typically requires Phase 1, 2 ...


What Are Clinical Trials? (United States)

Information covering the basics of cancer clinical trials, including what they are, where they take place, and the types of clinical trials. Also, explains phases, randomization, placebo, and members of the research team.


Clinical Trial Information Management (United States)

An interoperable clinical trial information technology platform can facilitate the reporting, analysis, and sharing of clinical trial data across sites. Clinical trials using consistent Common Data Elements and standard Case Report Forms modules will improve study start-up times and facilitate data collection. A widely recognized credentialing system can eliminate the need to reestablish credentials for personnel and sites each time a trial is initiated.


Search NCI Clinical Trials (United States)

Choose one of the following cancer types to view the clinical trials actively enrolling participants in studies to prevent that type of cancer. All studies are supported by NCI, but not all originate from the Division of Cancer Prevention. Not every cancer type will have active trials at all times. For cancer types not listed here, visit NCI's Clinical Trials information webpage.


Skin Cancer - Featured Clinical Trials (United States)

Skin Cancer - Featured Clinical Trials The following list shows Featured Clinical Trials for a specific type of cancer. You may also want to view: Multiple Cancer Types - Featured Clinical Trials Supportive Care - Featured Clinical Trials


Thyroid Cancer - Featured Clinical Trials (United States)

Thyroid Cancer - Featured Clinical Trials The following list shows Featured Clinical Trials for a specific type of cancer. You may also want to view: Multiple Cancer Types - Featured Clinical Trials Supportive Care - Featured Clinical Trials


HIV/AIDS Clinical Trials (United States)

... aren’t infected with HIV. What is a clinical trial? A clinical trial is a research study ... effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers find ...


Clinical Trials and Older People (United States)

... trial is right for you. What is a clinical trial? A clinical trial is a particular type ... support groups. Why would I participate in a clinical trial? There are many reasons why people choose ...


Clinical Trials in Vision Research (United States)

... Research at NEI Education Programs Training and Jobs Clinical Trials in Vision Research Listen Clinical studies depend ... vision research in the United States. Basics of Clinical Trials What is a clinical trial? Clinical trials ...


A multiple imputation strategy for sequential multiple assignment randomized trials. (United States)

Sequential multiple assignment randomized trials (SMARTs) are increasingly being used to inform clinical and intervention science. In a SMART, each patient is repeatedly randomized over time. Each randomization occurs at a critical decision point in the treatment course. These critical decision points often correspond to milestones in the disease process or other changes in a patient's health status. Thus, the timing and number of randomizations may vary across patients and depend on evolving patient-specific information. This presents unique challenges when analyzing data from a SMART in the presence of missing data. This paper presents the first comprehensive discussion of missing data issues typical of SMART studies: we describe five specific challenges and propose a flexible imputation strategy to facilitate valid statistical estimation and inference using incomplete data from a SMART. To illustrate these contributions, we consider data from the Clinical Antipsychotic Trial of Intervention and Effectiveness, one of the most well-known SMARTs to date. PMID:24919867

Shortreed, Susan M; Laber, Eric; Scott Stroup, T; Pineau, Joelle; Murphy, Susan A



Understanding noninferiority trials  

Directory of Open Access Journals (Sweden)

Full Text Available Noninferiority trials test whether a new experimental treatment is not unacceptably less efficacious than an active control treatment already in use. With continuous improvements in health technologies, standard care, and clinical outcomes, the incremental benefits of newly developed treatments may be only marginal over existing treatments. Sometimes assigning patients to a placebo is unethical. In such circumstances, there has been increasing emphasis on the use of noninferiority trial designs. Noninferiority trials are more complex to design, conduct, and interpret than typical superiority trials. This paper reviews the concept of noninferiority trials and discusses some important issues related to them.

Seokyung Hahn



Coding for clinical trials. (United States)

Although CMS reimburses for routine care associated with clinical trials, it is essential that the correct diagnosis code, modifier, and, where necessary, HCPCS Level II procedure code be assigned to accurately report these qualifying trial services. Remember that not all insurance payors will provide reimbursement for services rendered as part of a clinical trial, and individual payor policies should be obtained and followed for these services. PMID:15648218

Parman, Cindy C



Clinical trials in children. (United States)

The imperative to undertake randomised trials in children arises from extraordinary advances in basic biomedical sciences, needing a matching commitment to translational research if child health is to reap the benefits from this new knowledge. Unfortunately, many prescribed treatments for children have not been adequately tested in children, sometimes resulting in harmful treatments being given and beneficial treatments being withheld. Government, industry, funding agencies, and clinicians are responsible for research priorities being adult-focused because of the greater burden of disease in adults, coupled with financial and marketing considerations. This bias has meant that the equal rights of children to participate in trials has not always been recognised. This is changing, however, as the need for clinical trials in children has been increasingly recognised by the scientific community and broader public, leading to new legislation in some countries making trials of interventions mandatory in children as well as adults before drug approval is given. Trials in children are more challenging than those in adults. The pool of eligible children entering trials is often small because many conditions are uncommon in children, and the threshold for gaining consent is often higher and more complex because parents have to make decisions about trial participation on behalf of their child. Uncertain about what is best, despite supporting the notion of trials in principle, parents and paediatricians generally opt for the new intervention or for standard care rather than trial participation. In this review, we explore issues relating to trial participation for children and suggest some strategies for improving the conduct of clinical trials involving children. PMID:15337409

Caldwell, Patrina H Y; Murphy, Sharon B; Butow, Phyllis N; Craig, Jonathan C


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Full Text Available ... people. Most of this early research occurs at universities and medical centers across the country. The National Institutes of Health funds much of this basic research. Screening Trials In screening trials, researchers study ways of finding a disease before symptoms occur. ...


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Full Text Available ... on their phase. The U.S. Food and Drug Administration typically requires Phase 1, 2 and 3 trials ... 000 people. If the U.S. Food and Drug Administration agrees that the trial results are positive, they ...


CLINICAL TRIALS.GOV (United States) provides patients, family members, health care professionals, and members of the public easy access to information on clinical trials for a wide range of diseases and conditions. The U.S. National Institutes of Health (NIH), through its National Library of Medi...


Participating in Clinical Trials  

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Full Text Available ... disease or prevent a disease from returning. Supportive Care Trials In supportive care trials, researchers look for ways to make life ... groups, and various types of social interventions. Supportive care interventions are not intended to treat or cure ...


Participating in Clinical Trials  

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Full Text Available ... care trials, researchers look for ways to make life better for people living with a life threatening disease or chronic health problem. The goal ... be approved for use. A Phase I trial tests an experimental treatment on a small group of ...


How Do Clinical Trials Work? (United States)

... page from the NHLBI on Twitter. How Do Clinical Trials Work? If you take part in a ... protect patients and help produce reliable study results. Clinical Trial Protocol Each clinical trial has a master ...


What Is a Clinical Trial?  

Medline Plus

Full Text Available Announcer: What is a clinical trial? Clinical trials evaluate promising new cancer treatments or methods, from radiation and chemotherapy to new surgical techniques. This process ...


Inept media trials of clinical trials. (United States)

The Indian media in general, with the exception of a few domain expert journalists, have failed to comprehend the complexities involved in the clinical trial process. In the run up to the deadline-based coverage of a story, a majority of them fall short in conveying the right perspective to readers, but nevertheless they have been successful in sensationalizing an event in this arena. Possibly by unintended misrepresentation, or mostly out of ignorance of the nuances involved in the clinical trials process, the media has done more harm than good, and got away with it. On the other side, the industry has been reluctant to engage with the media in a meaningful dialog for too long now. It bears not only the consequences of damage to its professional reputation following such reportage, but also the repercussions of unnecessary clampdowns by the regulators. Science journalism in India has yet to rise as a profession. PMID:22701819

Ramamurthy, N V



National Lung Screening Trial (United States)

Information about the National Lung Screening Trial (NLST), a research study sponsored by the National Cancer Institute that used low-dose helical CT scans or chest X-ray to screen men and women at risk for lung cancer.


Cancer clinical trials  

International Nuclear Information System (INIS)

This book contains the proceedings on Cancer clinical trials: A critical appraisal. Topics covered include: Scientific fundamentals; Heterogeneous treatment effects; On combining information: Historical controls, overviews, and comprehensive cohort studies; and assessment of quality of life


Participating in Clinical Trials  

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Full Text Available ... an experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or tests to those already available or may compare ...


Participating in Clinical Trials  

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Full Text Available ... body tissues genetic tests that look for genes linked to some types of disease. Diagnostic Trials In ... on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who ...


Participating in Clinical Trials  

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Full Text Available ... is to find out if an experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or ...


Participating in Clinical Trials  

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Full Text Available ... of getting a disease or a specific medical problem. These trials find out if lifestyle changes, such ... active, or eating nutritious foods, can prevent a problem taking certain medicines, or vitamins, or getting vaccines ...


Participating in Clinical Trials  

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Full Text Available ... Phase 1, 2 and 3 trials to be conducted to determine if the drug can be approved ... to obtain preliminary data on whether the drug works in people who have a certain disease or ...


Clinical Trial Basics (United States)

... or treatment’s risks, benefits, and optimal use. Some concepts to understand Typically, clinical trials compare a new ... number in the National Library of Medicine's PubMed® database . Up to top 8. How does the outcome ...


Participating in Clinical Trials  

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Full Text Available ... years of experiments in the laboratory and in animals before they even consider testing an experimental treatment ... determine if the drug can be approved for use. A Phase I trial tests an experimental treatment ...


Participating in Clinical Trials  

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Full Text Available ... test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or ... of them, is the best treatment for a disease evaluate treatment methods such as surgical techniques, psychiatric ...


Participating in Clinical Trials  

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Full Text Available ... experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or prevent a disease. A clinical trial may compare experimental products or tests to those already available or may compare existing ...


Clinical Trials Management (United States)

The Division of Cancer Prevention supports clinical trials funded by investigator-initiated grants. Investigators using this funding mechanism need to refer to requirements from NCI's Division of Extramural Activities including their publication The Grants Process Book.


Participating in Clinical Trials  

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Full Text Available ... side effects, and to find the correct drug dosage. A Phase II trial uses more people (100 ... safety and effectiveness, studying different populations and different dosages and using the drug in combination with other ...


Whose data set is it anyway? Sharing raw data from randomized trials  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Sharing of raw research data is common in many areas of medical research, genomics being perhaps the most well-known example. In the clinical trial community investigators routinely refuse to share raw data from a randomized trial without giving a reason. Discussion Data sharing benefits numerous research-related activities: reproducing analyses; testing secondary hypotheses; developing and evaluating novel statistical methods; teaching; aiding design of future trials; meta-analysis; and, possibly, preventing error, fraud and selective reporting. Clinical trialists, however, sometimes appear overly concerned with being scooped and with misrepresentation of their work. Both possibilities can be avoided with simple measures such as inclusion of the original trialists as co-authors on any publication resulting from data sharing. Moreover, if we treat any data set as belonging to the patients who comprise it, rather than the investigators, such concerns fall away. Conclusion Technological developments, particularly the Internet, have made data sharing generally a trivial logistical problem. Data sharing should come to be seen as an inherent part of conducting a randomized trial, similar to the way in which we consider ethical review and publication of study results. Journals and funding bodies should insist that trialists make raw data available, for example, by publishing data on the Web. If the clinical trial community continues to fail with respect to data sharing, we will only strengthen the public perception that we do clinical trials to benefit ourselves, not our patients.

Vickers Andrew J



The challenge of recruiting patients into a placebo-controlled surgical trial  

DEFF Research Database (Denmark)

BACKGROUND: Randomized placebo-controlled trials represent the gold standard in evaluating healthcare interventions but are rarely performed within orthopedics. Ethical concerns or well-known challenges in recruiting patients for surgical trials in general have been expressed and adding a placebo component only adds to this complexity. The purpose of this study was to report the challenges of recruiting patients into an orthopedic placebo-controlled surgical trial, to determine the number of patients needed to be screened and allocated in order to include one participant into the trial, and to identify reasons associated with participation in a placebo-controlled randomized surgical trial. METHODS: Data were extracted from an ongoing placebo-controlled randomized controlled trial (RCT) on meniscectomy versus placebo surgery. We calculated the number of patients needed to be screened in order to include the required number of participants into the RCT. Participating patients were asked about their rationale for joining the study and which type of information was most useful for deciding upon participation. RESULTS: A total of 476 patients entered the screening group, of which 190 patients fulfilled the inclusion and exclusion criteria. 102 patients declined to participate in the study due to various reasons and 46 were later excluded (no meniscus lesion on the magnetic resonance imaging scan or withdrawn consent). A total of 40 patients were finally included in the RCT. To include one patient into the RCT, 11.9 individuals needed to be screened. A total of 69% of participating patients considered the oral information to be the most important and the most common reason for participating was the contribution to research (90%). CONCLUSIONS: Patients are willing to participate in an orthopedic placebo-controlled surgical trial. Oral information given by the surgeon to the patient and the contribution to research are important aspects to enhance patient recruitment. TRIAL REGISTRATION: NCT01264991, registered 21 December 2010.

Hare, Kristoffer B; Lohmander, L Stefan



Not well known and long time been lost sight of. The great accidents of uranium hexafluoride in the world  

International Nuclear Information System (INIS)

This review tackles the accidents of uranium hexafluorides in the world. This study is made in three parts. This first part explains what is uranium hexafluoride, gives its characteristics, the problems of storage, the tests of resistance of the containers before coming to the accidents themselves. (N.C.)


Not well known and long time been lost sight of. The great accidents of uranium hexafluoride in the world  

International Nuclear Information System (INIS)

This issue reports the accident of uranium hexafluoride leak occurred at Pierrelatte on the 1. july 1977. A container with U F6 was handled to be stored before to be shifted. The gate broke and the liquid U F6 was thrown out under the pressure of gaseous U F6. A white very opaque cloud was formed. It was composed of hydrofluoric acid (HF) and crystals of uranium oxyfluoride (UO2F2). The cloud spread on 1800 meters and became invisible after several kilometers. The fallout was followed as far as Avignon with a maximum of HF pollution of 82 micrograms by cubic metre. The measurement of uranium in urines of working personnel showed that for 320 persons (on 420 workers) the results were not null. Three persons were sent at hospital for kidney surveillance but fortunately without consequences. This accident allowed in less than one month to get major improvements that years of administrative procedures did not get. (N.C.)


Pharmacognostical study and establishment of quality parameters of aerial parts of Costus speciosus-a well known tropical folklore medicine (United States)

Objective To evaluate the diagnostic pharmacognostical characters of Costus speciosus (aerial parts) along with their physico-chemical parameters and fluorosence analysis. Method The pharmacognostical characters were determined in terms of macroscopy, microscopy, powder microscopy, leaf constant, fluorescence analysis and preliminary phytochemical investigation. Results The findings of macroscopy revealed that leaves elliptic to oblong or oblong-lancoelate, thick, spirally arranged, with stem clasping sheaths up to 4 cm, flowers large, white, cone-like terminal spikes, with bright red bracts. Transverse section of leaflet showed the presence of cuticularised epidermis with polygonal cells on adaxial surface and bluntly angled cells on abaxial surface of lamina, mesophyll cells differentiated in to single layered palisade cells on each surface and 2-3 layered spongy parenchyma, unicellular and uniseriate multicellular covering trichomes, paracytic stomata and vascular bundles surrounded by sclerenchymatous multicellular sheath. Preliminary phytochemical screening exhibited the presence of various phytochemical groups like alkaloids, glycosides, steroids, phenolic constituents. Further, the leaf constants, powder microscopy and fluorescence characteristics indicated outstanding results from this investigation Conclusions Various pharmacognostical and physico-chemical parameters have pivotal roles in identification, authentication and establishment of quality parameters of the species.

Singh, Pradeep; Khosa, Ratan Lal; Srivastava, Shruti; Mishra, Garima; Jha, Keshri Kishor; Srivastava, Sourabh; Sangeeta; Verma, Ramesh Kumar; Tahseen, Mohd Adil



The Antiretroviral Lectin Cyanovirin-N Targets Well-Known and Novel Targets on the Surface of Entamoeba histolytica Trophozoites ? †  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, has a truncated Asn-linked glycan (N-glycan) precursor composed of seven sugars (Man5GlcNAc2). Here, we show that glycoproteins with unmodified N-glycans are aggregated and capped on the surface of E. histolytica trophozoites by the antiretroviral lectin cyanovirin-N and then replenished from large intracellular pools. Cyanovirin-N cocaps the Gal/GalNAc adherence lectin, as well as glycoproteins containing O-ph...

Carpentieri, Andrea; Ghosh, Sudip K.; Banerjee, Sulagna; Bushkin, G. Guy; Cui, Jike; Lubrano, Michael; Costello, Catherine E.; O Keefe, Barry; Robbins, Phillips W.; Samuelson, John



Aspects of the nutritional value of cooked Egyptian goose (Alopochen aegyptiacus) meat compared with other well-known fowl species. (United States)

There is no scientific research regarding Egyptian goose (Alopochen aegyptiacus) meat; therefore, a chemical analysis to establish the nutritional characteristics of the breast portion is described. Meat from guinea fowl, Pekin duck, ostrich, and broiler chicken were used as a reference. The high intramuscular fat content of Egyptian goose meat (5.6 g/100 g) may be linked to the fact that this species relies on fat for heat insulation and buoyancy. Egyptian goose meat is very high in polyunsaturated fatty acids (39.7%). The polyunsaturated fatty acid/saturated fatty acid ratio is within the recommendations (>0.4), although the n-6/n-3 ratio is higher than the suggested value of 5. The high Fe content of 7.5 mg/100 g is the differentiating factor within the mineral compositions and is related to the physical activity endured by the breast muscle of Egyptian geese. This study provides new insight into the nutritional characteristics of a meat species providing crucial information that is, as of yet, not available in the literature. PMID:24135611

Geldenhuys, Greta; Hoffman, Louwrens C; Muller, Nina



El antígeno carcinoembrionario: a propósito de un viejo conocido / The carcinoembryonic antigen: by the way a well-known friend  

Scientific Electronic Library Online (English)

Full Text Available SciELO Mexico | Language: Spanish Abstract in spanish El antígeno carcinoembrionario (ACE) es una glucoproteína localizada en el polo apical de los enterocitos. Los genes que codifican para el ACE se localizan en el cromosoma 19q13.2. El grupo total está constituido por 29 genes, divididos en tres subgrupos de los cuales se expresan sólo 18. En el indi [...] viduo sano existen múltiples funciones del ACE que han sido ampliamente estudiadas, su función como molécula de adhesión ha sido la más ampliamente difundida. En pacientes sanos además de expresarse a nivel de colon el ACE se expresa en células de la lengua, esófago, estómago, cervix y próstata. Los pacientes que reciben una mayor utilidad clínica son aquellos con cáncer colorrectal (CCR), cáncer gástrico y cáncer de ovario. Su uso más amplio es en el CCR, actualmente se utiliza como marcador pronóstico, estadiaje, marcador de recurrencia, de respuesta al tratamiento y como indicador de metástasis a nivel hepático. Existen algunas patologías no neoplásicas que causan elevación de las cifras séricas de ACE. Actualmente se estudia al ACE como blanco de inmunoterapia dirigida a tumores que contengan células que expresen esta molécula Abstract in english The carcinoembryonic antigen (CEA) is glycoprotein localized in the apical surface of mature enterocytes. The members of the CEA gene family are clustered on chromosome 19q13.2. It is formed by 29 genes, of which 18 are expressed. Many functions of CEA have been known in healthy individuals, however [...] its role as cell adhesion molecule is the most studied. Besides the colon, CEA is expressed in the stomach, tongue, oesophagus, cervix, and prostate. The most important clinical function is in colorectal, gastric and ovary cancer. It is used as prognosis marker, staging system, recurrence, treatment response and liver metastases. There are many no neoplasic-diseases that enhance CEA value. Actually, the CEA is being studying as target of immunotherapy.

Félix Ignacio, Téllez-Ávila; Sandra Minerva, García-Osogobio.



When conducting a trial burn, it is necessary to make a number of measurements in order to adequately define the performance of the incinerator. n addition to flue gas emissions for particulate matter, HCl, and selected organics, it is also necessary to measure selected organics ...


results of the trial  

An average of 2.5 visibly lesioned or culture-positive animals per herd .... \\affecting the proportion of Bovigam positives that were visibly lesioned or whose \\tissue ..... underneath a brief written description of the trial and the conditions \\agreed to.


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Full Text Available ... are usually described based on their phase. The U.S. Food and Drug Administration typically requires Phase 1, ... hundred to about 3,000 people. If the U.S. Food and Drug Administration agrees that the trial ...


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Full Text Available ... judge its safety and side effects, and to find the correct drug dosage. A Phase II trial uses more people (100 to 300). While the emphasis in Phase 1 is on safety, the emphasis in Phase 2 is on effectiveness. This phase aims to obtain preliminary data on whether the drug works in people who ...


Clinical Trials for Wet AMD (United States)

Clinical trials are the final research phase before a treatment is approved for the general public. Once ... is testing in humans through a succession of clinical trials. Research on treatments starts in the laboratory ...


What Is a Clinical Trial?  

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Full Text Available ... a clinical trial? Clinical trials evaluate promising new cancer treatments or methods, from radiation and chemotherapy to ... the effects of research treatmenton various types of cancer. Once researchers are satisfied that the treatment has ...


The Trial of Katherine Harrison. (United States)

Presents a lesson plan in which the teacher and students participate in a mock trial of Katherine Harrison, who was accused of witchcraft in the seventeenth century. Provides background information about the trial, as well as primary sources of the testimonies given by witnesses during the trial. (CMK)

Woodward, Walter W.



Find Alzheimer's Disease and Related Clinical Trials (United States)

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A randomised controlled trial of nurse-managed trial conclusion following early phase cancer trial participation (United States)

The effect of a nurse-managed intervention, for early phase cancer trial participants at trial conclusion, on psychosocial outcomes was evaluated at two cancer centres in the Midlands, England using a randomised controlled trial. It involved 117 patients who were participating in an early phase cancer clinical trial. It was a nurse-managed trial exit, which included a trial exit interview, trial feedback information leaflet and telephone follow-up compared with standard care at trial conclusion. Psychological distress at 1 week and 4–6 weeks post-trial conclusion, patient's knowledge and understanding and patient's satisfaction were assessed. The results showed there was no significant difference between the two groups regarding scores for anxiety and depression at time one and time two. There is some suggestion that the intervention reduced anxiety from trial conclusion to follow-up (P=0.27). Patients in both groups felt they had contributed to cancer research through trial participation. However, intervention patients were more likely to feel that they knew how the trial was going (P<0.001), knew how other people in the trial were doing (P=0.001), had all the feedback they needed about the trial they took part in (P<0.01) and knew how they would be followed up (P=0.02). Patient satisfaction with the intervention was high (median score=4.5 where 5 is greatest satisfaction). In conclusion, nurse-managed trial conclusion led to positive outcomes for patients who had recently completed a clinical trial. PMID:15986032

Cox, K; Wilson, E; Arthur, A; Elkan, R; Armstrong, S



NATO SOCMET trials (United States)

During 1993, Canada, France, Germany and the United Kingdom will be participating in the Smoke and Obscurants Countermeasures Materials Evaluation Tests (SOCMET). The tests will be carried out under the auspices of the NATO Army Armaments Group, AC/225, Panel VI, Sub-Panel 7 whose interests include multispectral smoke screening systems. The tests will comprise two sets of trials; one under cold climate conditions in Quebec, Canada, during February/March 1993 and the other in temperate conditions in Bourges, France during September 1993. This paper provides an insight into the management and aims of SOCMET. The evaluations will be seeking to identify candidate materials which create effective obscurant screens in the visible, infrared and millimetric bands of the electromagnetic spectrum. These materials will be disseminated through a range area dispersal. A key element of the trials will be the evaluation of field test instrumentation which may eventually lead to the development of standardized evaluation techniques. Following the trials, a scientific workshop will be held to review the results. A final report will be presented to NATO which will form the basis of future collaborative developments on multispectral screening systems leading towards standard NATO documentation on smoke and obscurant systems.

Jenden, C. M.



Ongoing activity in the optic tectum is correlated on a trial-by-trial basis with the pupil dilation response. (United States)

The selection of the appropriate stimulus to induce an orienting response is a basic task thought to be partly achieved by tectal circuitry. Here we addressed the relationship between neural activity in the optic tectum (OT) and orienting behavioral responses. We recorded multiunit activity in the intermediate/deep layers of the OT of the barn owl simultaneously with pupil dilation responses (PDR, a well-known orienting response common to birds and mammals). A trial-by-trial analysis of the responses revealed that the PDR generally did not correlate with the evoked neural responses but significantly correlated with the rate of ongoing neural activity measured shortly before the stimulus. Following this finding, we characterized ongoing activity in the OT and showed that in the intermediate/deep layers it tended to fluctuate spontaneously. It is characterized by short periods of high ongoing activity during which the probability of a PDR to an auditory stimulus inside the receptive field is increased. These high-ongoing activity periods were correlated with increase in the power of gamma band local field potential oscillations. Through dual recordings, we showed that the correlation coefficients of ongoing activity decreased as a function of distance between recording sites in the tectal map. Significant correlations were also found between recording sites in the OT and the forebrain entopallium. Our results suggest that an increase of ongoing activity in the OT reflects an internal state during which coupling between sensory stimulation and behavioral responses increases. PMID:24304859

Netser, Shai; Dutta, Arkadeb; Gutfreund, Yoram



Gateways to clinical trials. (United States)

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: 5-Methyltetrahydrofolate, 9-aminocamptothecin; AdPEDF.11, AE-37, albumin interferon alfa, alicaforsen sodium, alvocidib hydrochloride, AMG-706, arginine butyrate, avanafil, axitinib, azimilide hydrochloride; BAY-579352, belagenpumatucel-L, beta-lapachone, BHT-3009, BIBW-2992, bremelanotide, BX-471; Casopitant mesylate, cediranib, certolizumab pegol, CH-1504, ChimeriVax-West Nile, clofazimine, CpG-7909, curcumin, Cypher; Dapoxetine hydrochloride, darusentan, diflomotecan, D-methionine, dnaJP1, D-serine, DTPw-HB Hib-MenAC, DTPw-HepB-Hib; E-7010, ecogramostim, edodekin alfa, EGFRvlll peptide vaccine, elcometrine, elcometrine/ethinylestradiol, elsilimomab, enrasentan, ertumaxomab, etalocib sodium, exisulind; Fenretinide, fesoterodine, fingolimod hydrochloride, fontolizumab; Gefitinib, gemtuzumab ozogamicin, ghrelin (human), GV-1001; HTU-PA, human papillomavirus vaccine; Indacaterol, indiplon, interleukin-21, intranasal insulin, irinotecan hydrochloride/floxuridine, ISIS-301012, ispinesib mesylate, ixabepilone; K562/GM-CSF; Lapatinib, L-BLP-25, linezolid, liposome encapsulated paclitaxel, LY-2124275; MC-1, MC-1/lisinopril, MDX-066, melanoma vaccine, MMR-V, multivalent (ACYW) meningitis vaccine; Nilotinib, nobori, nociceptin; Oblimersen sodium, orbofiban acetate, ospemifene; Paliperidone, panitumumab, PEG-filgrastim, PEGylated interferon alfacon-1, perflubutane, pertuzumab, phenserine tartrate, phVEGF-A165, pleconaril, prasugrel, prednisolone sodium metasulfobenzoate; R-411, recombinant malaria vaccine, rhGM-CSF, roflumilast, romidepsin, ruboxistaurin mesilate hydrate; Sirolimus-eluting stent, SR-4554, St. John's Wort extract; Talabostat, Taxus, TGN-255, tifacogin, tiotropium bromide, tolevamer sodium, trabectedin, tretinoin LF; Vatalanib succinate; Yellow fever vaccine, YM-155. PMID:17235418

Bayes, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil fumarate, Tocilizumab, Tositumomab/iodine (I131) tositumomab, Trabectedin, TransVax™ hepatitis C vaccine; Ustekinumab; V-260, Valspodar, Varenicline tartrate, VCL-IPT1, Vildagliptin, VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, VRC-HIVDNA016-00-VP; Yttrium 90 (90Y) ibritumomab tiuxetan, Yttrium Y90 Epratuzumab; Zibotentan, Zotarolimus-eluting stent. PMID:21225019

Tomillero, A; Moral, M A



Gateways to clinical trials. (United States)

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide, Uracil, Ustekinumab; V-260, Vandetanib, Vatalanib succinate, Vernakalant hydrochloride, Vorinostat; YM-155; Zileuton, Zoledronic acid monohydrate. PMID:18200333

Bayés, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide, testosterone gel, tezosentan disodium, tipifarnib, tolvaptan, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Vardenafil hydrochloride hydrate; Xcellerated T cells, XR-5944; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziconotide. PMID:15349141

Bayes, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine hydrochloride; Sertindole, Sivelestat sodium hydrate, Sorafenib, Sumatriptan succinate/naproxen sodium, Sunitinib malate; Tafluprost, Telithromycin, Temsirolimus, Tenofovir disoproxil fumavate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Ticagrelor, Tigecycline, Tipranavir, Tirapazamine, Trimetrexate; Ulipristal acetate; Valganciclovir hydrochloride, Vicriviroc, Vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan. PMID:21225012

Tomillero, A; Moral, M A



Gateways to clinical trials. (United States)

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000, Pseudostat; R24, rasburicase, RHAMM R3 peptide, rilonacept, rosuvastatin calcium, rotavirus vaccine, rufinamide; Sabarubicin hydrochloride, SHL-749, sirolimus-eluting stent, SLx-2101, sodium butyrate, sorafenib, SU-6668; TachoSil, tadalafil, taxus, tegaserod maleate, telbivudine, tenofovir disoproxil fumarate, teriparatide, tetramethylpyrazine, teverelix, tiotropium bromide, tipifarnib, tirapazamine, tolvaptan, TransvaxTM hepatitis C vaccine, treprostinil sodium; Valganciclovir hydrochloride, valsartan/amlodipine, vandetanib, vardenafil hydrochloride hydrate, vatalanib succinate, veglin, voriconazole; Yttrium 90 (90Y) ibritumomab tiuxetan; Zileuton, zotarolimus, zotarolimus-eluting stent. PMID:17003851

Bayes, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: 131-I-Chlorotoxin, 423557; Abatacept, Ad.Egr.TNF.11D, Adalimumab, AE-941, Ambrisentan, AMR-001, Anacetrapib, Anakinra, Aripiprazole, Atazanavir sulfate; BAY-639044, Bazedoxifene acetate, Belimumab, Bevacizumab, Bortezomib, Botulinum toxin type B, Brivaracetam, Bucindolol hydrochloride; Carfilzomib, Carisbamate, CCX-282, CD20Bi, Ceftobiprole, Certolizumab pegol, CF-101, Cinacalcet hydrochloride, Cypher; Darifenacin hydrobromide, Degarelix acetate, Denosumab, Desvenlafaxine succinate, Dexlansoprazole, Dexverapamil, Drotrecogin alfa (activated), Duloxetine hydrochloride, Dutasteride; Efalizumab, EPs-7630, Escitalopram oxalate, Etoricoxib; Fluticasone furoate, Fondaparinux sodium, Fospropofol disodium; Hexadecyloxypropyl-cidofovir, HIV gp120/NefTat/AS02A, HPV-6/11/16/18; INCB-18424, Incyclinide, Inhalable human insulin, Insulin detemir; KNS-760704, KW-0761; Lacosamide, Lenalidomide, Levetiracetam, Licofelone, Lidocaine/prilocaine; mAb 216, MEDI-528, Men ACWY, Meningococcal C-CRM197 vaccine, Methylnaltrexone bromide; Nemifitide ditriflutate, Nicotine conjugate vaccine, Nilotinib hydrochloride monohydrate; Octaparin; Parathyroid hormone (human recombinant), Pegaptanib octasodium, Pitrakinra, Prasterone, Pregabalin; Ranelic acid distrontium salt, Rasagiline mesilate, Retigabine, Rimonabant, RTS,S/AS02D; Sarcosine, Sitaxentan sodium, Solifenacin succinate, Sunitinib malate; Taranabant, Taxus, Teduglutide, Teriparatide, Ticagrelor, Travoprost, TRU-015; USlipristal acetate, Urocortin 2; Vardenafil hydrochloride hydrate; YM-155, Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, Zoledronic acid monohydrate, Zotarolimus, Zotarolimus-eluting stent. PMID:18560631

Moral, M A; Tomillero, A



Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, This issue focuses on the following selection of drugs: (PE)HRG214, 1E10, 21-Aminoepothilone B; Ad.Egr.TNF.11D, Ad100-B7.1/HLA, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, AMD-070, anhydrovinblastine, aripiprazole, asimadoline, atrasentan, AVE-5883; Bimatoprost, BNP-7787, bosentan, botulinum toxin type B, BR-1; Canfosfamide hydrochloride, ciclesonide, curcumin, cypher; D0401, darbepoetin alfa, darifenacin hydrobromide, D-D4FC, dendritic cell-based vaccine, desloratadine, dextrin sulfate, dolastatin 10, drospirenone drospirenone/estradiol, DS-992, duloxetine hydrochloride, dutasteride; E-7010, efalizumab, eletriptan, EM-1421, enfuvirtide, entecavir, etoricoxib, everolimus, exenatide, ezetimibe; Favid, fidarestat, fingolimod hydrochloride, FK-352; Gefitinib, gemifloxacin mesilate, gepirone hydrochloride, gimatecan; HE-2000; Imatinib mesylate, indisulam, insulin detemir, irofulven, ISIS-5132; Lapatinib, levocetirizine, liraglutide, lumiracoxib; Metformin/Glyburide, methionine enkephalin, MK-0431, morphine hydrochloride, motexafin gadolinium, mycobacterium cell wall complex; Naturasone, neridronic acid, nesiritide; Oblimersen sodium, olanzapine/fluoxetine hydrochloride, omalizumab, oral insulin; Paclitaxel poliglumex, PC-515, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pegvisomant, pexelizumab, picoplatin, pramlintide acetate, prasterone, pregabalin; Quercetin; Ramelteon, ranirestat, RG228, rhGAD65, roflumilast, rubitecan; Sitaxsentan sodium, solifenacin succinate; Tadalafil, taxus, tipifarnib, tolevamer sodium, topixantrone hydrochloride; Valganciclovir hydrochloride, vardenafil hydrochloride hydrate, vildagliptin, voriconazole; XTL-001; Zoledronic acid monohydrate. PMID:15632957

Bayés, M; Rabasseda, X; Prous, J R



The International Stroke Trial database  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background We aimed to make individual patient data from the International Stroke Trial (IST), one of the largest randomised trials ever conducted in acute stroke, available for public use, to facilitate the planning of future trials and to permit additional secondary analyses. Methods For each randomised patient, we have extracted data on the variables assessed at randomisation, at the early outcome point (14-days after randomisation or prior discharge...

Niewada Maciej; Ag, Sandercock Peter; Cz?onkowska Anna



Japan nuclear ship sea trial  

International Nuclear Information System (INIS)

The sea trial of the first Japan nuclear Ship 'MUTSU' was conducted from the end of October to December in 1990. The purpose of the sea trial was to verify the nuclear propulsive performances and maneuverabilities. The present report describes the results of the sea trial. These results are classified into four items: 1. Speed test and engineering performance tests 2. Maneuvering performance tests 3. Vibration tests 4. Other tests. Acceptable performances were demonstrated, as expected in the original design. The experience of the use of the Global Positioning System (GPS), which were newly adopted for the sea trial, is also reported. (author)


Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables can be retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, acarbose, alefacept, alteplase, amisulpride, amoxicillin trihydrate, apomorphine hydrochloride, aprepitant, argatroban monohydrate, aspirin, atenolol; Betamethasone dipropionate, betamethasone valerate, bicalutamide, bleomycin sulfate; Calcium carbonate, candesartan cilexetil, celecoxib, cetirizine hydrochloride, cisplatin, clarithromycin, clavulanate potassium, clomethiazole edisilate, clopidogrel hydrogensulfate, cyclophosphamide, chorionic gonadotropin (human); Dalteparin sodium, desloratadine, dexamethasone, doxorubicin, DPC-083; Efalizumab, efavirenz, enoxaparin sodium, eprosartan mesilate, etanercept, etoposide, ezetimibe; Faropenem daloxate, fenofibrate, fluocinolone acetonide, flutamide, fluvastatin sodium, follitropin beta, fondaparinux sodium; Gabapentin, glibenclamide, goserelin, granisetron hydrochloride; Haloperidol, hydrochlorothiazide; Imiquimod, interferon beta-1a, irbesartan, iseganan hydrochloride; L-758298, lamivudine, lanoteplase, leflunomide, leuprorelin acetate, loratadine, losartan potassium; Melagatran, metformin hydrochloride, methotrexate, metronidazole, micafungin sodium, mitoxantrone hydrochloride; Nelfinavir mesilate, neutral insulin injection, nizatidine; Olopatadine hydrochloride, omeprazole, ondansetron hydrochloride; Pamidronate sodium, paracetamol, paroxetine hydrochloride, perindopril, pimecrolimus, pioglitazone hydrochloride, piroxicam, pleconaril, pralmorelin, pravastatin sodium, prednisolone, prednisone, propofol; Raloxifene hydrochloride, ranpirnase, remifentanil hydrochloride, risedronate sodium, risperidone, rofecoxib, ropinirole hydrochloride, rosuvastatin calcium; Sevoflurane, sildenafil citrate, simvastatin, somatropin; Tacrolimus, tamoxifen citrate, telmisartan, temozolomide, thiopental sodium, tinzaparin sodium, tirofiban hydrochloride, treosulfan, triamcinolone acetonide; Urokinase; Valsartan, vardenafil, vincristine; Warfarin sodium; Ximelagatran; Zidovudine. PMID:12092009

Bayes, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, adalimumab, adefovir dipivoxil, AdGVVEGF121.10, anastrozole, anecortave acetate, aripiprazole, asulacrine isethionate, atazanavir, ATL-962, 16-Aza-epothilone B; Bevacizumab, bicalutamide, blonanserin, BMS-188667, bosentan; Celecoxib, celmoleukin, cetuximab, cilomilast, cinacalcet hydrochloride, CNTF(Ax15), colesevelam hydrochloride; Daclizumab, delavirdine mesilate, desogestrel, desoxyepothilone B, dexmethylphenidate hydrochloride, duloxetine hydrochloride; Ecogramostim, emtricitabine, epalrestat, escitalopram oxalate, examorelin, exendin-4, ezetimibe; Fidarestat, frovatriptan; HIV-1 Immunogen; Iloperidone, insulin detemir, insulin lispro, irinotecan hydrochloride; Keratinocyte growth factor; Lasofoxifene tartrate, levetiracetam, levormeloxifene, levosimendan, lumiracoxib, LY-307161 SR; Memantine hydrochloride, MEN-10755, metformin hydrochloride, metreleptin, motexafin gadolinium; Naratriptan hydrochloride, natalizumab, nesiritide, nicotine, NN-2211, NN-414; Olanzapine, omalizumab; Pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pimecrolimus, pirfenidone, pramlintide acetate prasterone, pregabalin; Quetiapine fumarate; Rabeprazole sodium, raloxifene hydrochloride, raltitrexed, rDNA insulin, rFGF-2, risedronate sodium, rofecoxib, roflumilast, rosiglitazone maleate; SN-22995; Tacrolimus, tadalafil, tegaserod maleate, tiotropium bromide, tomoxetine hydrochloride, trastuzumab, trimegestone; Voglibose, Voriconazole; Ziprasidone hydrochloride. PMID:12616707

Bayés, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: Abacavir sulfate, abciximab, acetylcysteine, adefovir dipivoxil, alfuzosin hydrochloride, aliskiren fumarate, alosetron hydrochloride, amlodipine besilate, apomorphine hydrochloride, atazanavir, atorvastatin, atorvastatin calcium, atrasentan; Basiliximab, beraprost sodium, bevacizumab, bivalirudin, botulinum toxin type A, botulinum toxin type B; Celecoxib, cetuximab, cilansetron, cilomilast; Daclizumab, darbepoetin alfa, docetaxel, duloxetine hydrochloride; Efalizumab, efavirenz, eletriptan,, entecavir, eplerenone, epoetin alfa, eptifibatide, esomeprazole magnesium. ezetimibe; Filgrastim, finasteride, fluvastatin sodium, follitropin alfa; Gemcitabine, gemeprost, ghrelin (human); HE-2000; Infliximab, 111In-Pentetreotide, interferon alfa-2 alpha, interferon alfa-2 beta, interferon beta-1 alpha, irbesartan, irinotecan hydrochloride; Ketamine hydrochloride; L-778123, lafutidine, lamivudine, lamivudine/zidovudine, latanoprost, letrozole, licofelone, lopinavir, losartan potassium, loxiglumide, lubeluzole; Magnesium sulfate, MeGLA, meloxicam, mycophenolate mofetil; NBI-6024, nelfinavir mesilate, nesiritide, nevirapine, niacin, NN-2211; Octreotide, orlistat; PC-515, peginterferon alfa-2 alpha, peginterferon alfa-2b, pemetrexed disodium, pibrozelesin hydrochloride, pimagedine, pirfenidone, pitavastatin calcium, premarin/trimegestone, prucalopride; Rabeprazole sodium; reboxetine, risedronate sodium, ritonavir, rituximab, rofecoxib, roflumilast, rosuvastatin calcium; Sertraline, sibutramine hydrochloride monohydrate, sildenafil citrate, spironolactone, stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride, tenecteplase, thalidomide, travoprost; Valsartan; Zoledronic acid monohydrate. PMID:12500432

Bayés, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: Aciclovir, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alteplase, amifostine hydrate, antithymocyte globulin (equine), aspirin, atorvastatin calcium, azathioprine; Bacillus Calmette-Guérin, basiliximab, bicalutamide, bimatoprost, BMS-214662, brimonidine tartrate, buprenorphine hydrochloride; Cabergoline, carbamazepine, carboplatin, ciclosporine, cisplatin, cyclophosphamide; Daclizumab, desmopressin acetate, dihydroergotamine mesylate, dorzolamide hydrochloride, doxorubicin, dutasteride; Everolimus; Fluocinolone acetonide, frovatriptan, FTY-720, fulvestrant; Gabapentin, galantamine hydrobromide, ganciclovir, gemcitabine, glatiramer acetate; Hydrocodone bitartrate; Interferon beta, interferon beta-1a, interferon beta-1b, ipratropium bromide; Ketotifen; Lamivudine, latanoprost, levodopa, lidocaine hydrochloride, lonafarnib; Metformin hydrochloride, methylprednisolone, metoclopramide hydrochloride, mirtazapine, mitoxantrone hydrochloride, modafinil, muromonab-CD3, mycophenolate mofetil; NS-2330; Olopatadine hydrochloride, omalizumab, oxcarbazepine, oxycodone hydrochloride; Paclitaxel, paracetamol, piribedil, pramipexole hydrochloride, pravastatin sodium, prednisone; Quetiapine fumarate; Raloxifene hydrochloride, rituximab, rizatriptan sulfate, Ro-63-8695, ropinirole hydrochloride, rosiglitazone maleate; Simvastatin, siplizumab, sirolimus; Tacrolimus, tegaserod maleate, timolol maleate, tiotropium bromide, tipifarnib, tizanidine hydrochloride, tolterodine tartrate, topiramate, travoprost; Unoprostone isopropyl ester; Valganciclovir hydrochloride, visilizumab; Zidovudine. PMID:12224444

Bayés, M; Rabasseda, X; Prous, J R



Gateways to clinical trials. (United States)

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, This issues focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; LA-419, lacosamide, landiolol, lanthanum carbonate, lidocaine/prilocaine, liposomal cisplatin, lutropin alfa; Matuzumab, MBP(82-98), mecasermin, MGCD-0103, MMR-V, morphine hydrochloride, mycophenolic acid sodium salt; Natalizumab, NCX-4016, neridronic acid, nesiritide, nilotinib, NSC-330507; O6-benzylguanine, olanzapine/fluoxetine hydrochloride, omalizumab; Panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegvisomant, pemetrexed disodium, perospirone hydrochloride, pexelizumab, phorbol 12-myristate 13-acetate, pneumococcal 7-valent conjugate vaccine, posaconazole, pramiconazole, prasugrel, pregabalin, prilocaine; rAAV-GAD65, raclopride, rasagiline mesilate, retapamulin, rosuvastatin calcium, rotigotine, rufinamide; SarCNU, SB-743921, SHL-749, sirolimus-eluting stent, sitaxsentan sodium, sorafenib; TachoSil, tadalafil, talampanel, Taxus, tegaserod maleate, telithromycin, telmisartan/hydrochlorothiazide, temsirolimus, tenatoprazole, teriflunomide, tetrathiomolybdate, ticilimumab, timcodar dimesilate, tipifarnib, tirapazamine, TPI, tramiprosate, trifluridine/TPI, trimethoprim; Ularitide, Urocortin 2; Valdecoxib, valganciclovir hydrochloride, valproate magnesium, valspodar, vardenafil hydrochloride hydrate, vitespen, vofopitant hydrochloride, volociximab, vorinostat; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, zotarolimus, zotarolimus-eluting stent. PMID:17136234

Bayés, M; Rabasseda, X; Prous, J R



Insurance Coverage and Clinical Trials (United States)

... costs of a clinical trial. Examples of these costs include extra blood tests or scans that are done purely for the sake of the clinical trial. Often, the research sponsor will cover such costs. Plans are also not required to cover the ...


What Is a Clinical Trial?  

Medline Plus

Full Text Available Announcer: What is a clinical trial? Clinical trials evaluate promising new cancer treatments or methods, from radiation and chemotherapy to new ... This process helps determine if the new treatment is an improvement over existing treatments. For patients' safety, ...


Patient Safety in Clinical Trials (United States)

Information for patients, their families and friends, and the general public about how the rights and safety of people who take part in clinical trials are protected. Learn about informed consent, institutional review boards (IRB's), and how trials are closely monitored for safety.


Gateways to clinical trials. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin; Tadalafil, tesmilifene hydrochloride, theratope, tipifarnib, tirapazamine, topixantrone hydrochloride, trabectedin, traxoprodil, Tri-Luma; Valdecoxib, valganciclovir hydrochloride, vinflunine; Ximelagatran; Ziconotide. PMID:15148527

Bayés, M; Rabasseda, X; Prous, J R



Experimental studies: randomized clinical trials. (United States)

There are two major approaches to medical investigations: observational studies and experimental trials. The classical application of the experimental design to studies of human populations is the randomized clinical trial of the efficacy of a new drug or treatment. A further application of the experimental studies is to the testing of hypotheses about the etiology of a disease, already tested and corroborated from various forms of observational studies. Ethical considerations and requirements for consent of the experimental subjects are of primary concern in the clinical trials, and those concerns set the first and final limits for implementing a trial. General moral principles in research with human and animal beings, defined by the "Nuremberg Code," deal with strict criteria for approval, endorsement and evaluation of a clinical trial. PMID:10205986

Gjorgov, A N



Myeloproliferative/Myelodysplastic Disorders - Featured Clinical Trials (United States)

Myeloproliferative/Myelodysplastic Disorders - Featured Clinical Trials The following list shows Featured Clinical Trials for a specific type of cancer. You may also want to view: Multiple Cancer Types - Featured Clinical Trials Supportive Care - Featured


Randomized phase II clinical trials. (United States)

Traditionally, Phase II trials have been conducted as single-arm trials to compare the response probabilities between an experimental therapy and a historical control. Historical control data, however, often have a small sample size, are collected from a different patient population, or use a different response assessment method, so that a direct comparison between a historical control and an experimental therapy may be severely biased. Randomized Phase II trials entering patients prospectively to both experimental and control arms have been proposed to avoid any bias in such cases. The small sample sizes for typical Phase II clinical trials imply that the use of exact statistical methods for their design and analysis is appropriate. In this article, we propose two-stage randomized Phase II trials based on Fisher's exact test, which does not require specification of the response probability of the control arm for testing. Through numerical studies, we observe that the proposed method controls the type I error accurately and maintains a high power. If we specify the response probabilities of the two arms under the alternative hypothesis, we can identify good randomized Phase II trial designs by adopting the Simon's minimax and optimal design concepts that were developed for single-arm Phase II trials. PMID:24697589

Jung, Sin-Ho; Sargent, Daniel J



Frailty Intervention Trial (FIT  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Frailty is a term commonly used to describe the condition of an older person who has chronic health problems, has lost functional abilities and is likely to deteriorate further. However, despite its common use, only a small number of studies have attempted to define the syndrome of frailty and measure its prevalence. The criteria Fried and colleagues used to define the frailty syndrome will be used in this study (i.e. weight loss, fatigue, decreased grip strength, slow gait speed, and low physical activity. Previous studies have shown that clinical outcomes for frail older people can be improved using multi-factorial interventions such as comprehensive geriatric assessment, and single interventions such as exercise programs or nutritional supplementation, but no interventions have been developed to specifically reverse the syndrome of frailty. We have developed a multidisciplinary intervention that specifically targets frailty as defined by Fried et al. We aim to establish the effects of this intervention on frailty, mobility, hospitalisation and institutionalisation in frail older people. Methods and Design A single centre randomised controlled trial comparing a multidisciplinary intervention with usual care. The intervention will target identified characteristics of frailty, functional limitations, nutritional status, falls risk, psychological issues and management of chronic health conditions. Two hundred and thirty people aged 70 and over who meet the Fried definition of frailty will be recruited from clients of the aged care service of a metropolitan hospital. Participants will be followed for a 12-month period. Discussion This research is an important step in the examination of specifically targeted frailty interventions. This project will assess whether an intervention specifically targeting frailty can be implemented, and whether it is effective when compared to usual care. If successful, the study will establish a new approach to the treatment of older people at risk of further functional decline and institutionalisation. The strategies to be examined are readily transferable to routine clinical practice and are applicable broadly in the setting of aged care health services. Trial Registration Australian New Zealand Clinical Trails Registry: ACTRN12608000250336.

Lockwood Keri



Let's face it, from trial to trial: comparing procedures for N170 single-trial estimation. (United States)

The estimation of event-related single trial EEG activity is notoriously difficult but is of growing interest in various areas of cognitive neuroscience, such as multimodal neuroimaging and EEG-based brain computer interfaces. However, an objective evaluation of different approaches is lacking. The present study therefore compared four frequently-used single-trial data filtering procedures: raw sensor amplitudes, regression-based estimation, bandpass filtering, and independent component analysis (ICA). High-density EEG data were recorded from 20 healthy participants in a face recognition task and were analyzed with a focus on the face-selective N170 single-trial event-related potential. Linear discriminant analysis revealed significantly better single-trial estimation for ICA compared to raw sensor amplitudes, whereas the other two approaches did not improve classification accuracy. Further analyses suggested that ICA enabled extraction of a face-sensitive independent component in each participant, which led to the superior performance in single trial estimation. Additionally, we show that the face-sensitive component does not directly represent activity from a neuronal population exclusively involved in face-processing, but rather the activity of a network involved in general visual processing. We conclude that ICA effectively facilitates the separation of physiological trial-by-trial fluctuations from measurement noise, in particular when the process of interest is reliably reflected in components representing the neural signature of interest. PMID:22877577

De Vos, Maarten; Thorne, Jeremy D; Yovel, Galit; Debener, Stefan



A Machine Learning Approach to Identify Clinical Trials Involving Nanodrugs and Nanodevices from (United States)

Background Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry are not easily told apart as to whether they are nano or non-nano CTs—even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. Methods We propose a supervised learning approach for classifying CT summaries from according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. Results and Conclusions The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on might be relevant to a particular nanoparticle or nanodevice, which is essential to discover any precedents for nanotoxicity events or advantages for targeted drug therapy. PMID:25347075

de la Iglesia, Diana; Garcia-Remesal, Miguel; Anguita, Alberto; Munoz-Marmol, Miguel; Kulikowski, Casimir; Maojo, Victor



What Is a Clinical Trial?  

Medline Plus

Full Text Available ... To help you make a decision, the National Cancer Institute offers publications explaining your disease as well as clinical trials. To receive such information, simply dial 1-800-4-CANCER.


What Is a Clinical Trial?  

Medline Plus

Full Text Available ... and the duration of the patient's life, the quality of their life, has changed dramatically. As a ... fact, all clinical trial patients receive the highest quality medical care, with thorough, careful monitoring during the ...


Global warming on trial  

International Nuclear Information System (INIS)

Jim Hansen, a climatologist at NASA's Goddard Space Institute, is convinced that the earth's temperature is rising and places the blame on the buildup of greenhouse gases in the atmosphere. Unconvinced, John Sununu, former White House chief of staff, doubts that the warming will be great enough to produce serious threat and fears that measures to reduce the emissions would throw a wrench into the gears that drive the Unites States' troubled economy. During his three years at the White House, Sununu's view prevailed, and although his role in the debate has diminished, others continue to cast doubt on the reality of global warming. A new lobbying group called the Climate Council has been created to do just this. Burning fossil fuels is not the only problem; a fifth of emissions of carbon dioxide now come from clearing and burning forests. Scientists are also tracking a host of other greenhouse gases that emanate from a variety of human activities; the warming effect of methane, chlorofluorocarbons and nitrous oxide combined equals that of carbon dioxide. Although the current warming from these gases may be difficult to detect against the background noise of natural climate variation, most climatologists are certain that as the gases continue to accumulate, increases in the earth's temperature will become evident even to skeptics. If the reality of global warming were put on trial, each side would have trouble making its case. Jim Hansen's side could not prove beyond a rm Hansen's side could not prove beyond a reasonable doubt that carbon dioxide and other greenhouse gases have warmed the planet. But neither could John Sununu's side prove beyond a reasonable doubt that the warming expected from greenhouse gases has not occurred. To see why each side would have difficulty proving its case, this article reviews the arguments that might be presented in such a hearing


Malaria diagnostics in clinical trials. (United States)

Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

Murphy, Sean C; Shott, Joseph P; Parikh, Sunil; Etter, Paige; Prescott, William R; Stewart, V Ann



Clinical Trials: Information and Options for People with Mood Disorders (United States)

Clinical Trials: Information and Options for People with Mood Disorders What are clinical trials? Clinical trials are research ... during a clinical trial? Clinical trials that test mood disorder treatments are usually conducted on an outpatient basis, ...


NASH: The tribulations of conducting NASH trials. (United States)

Designing clinical trials for the treatment of NASH is challenging. The pathogenesis of this disease is poorly understood and is probably multifactorial. A trial of a phosphodiesterase-4 inhibitor produced negative results, despite promising preclinical data. Examining why this trial failed might help us design better trials of treatments for NASH in the future. PMID:24709815

Neuschwander-Tetri, Brent A



Efficacy and safety of Suanzaoren decoction for primary insomnia: a systematic review of randomized controlled trials  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Insomnia is a widespread human health problem, but there currently are the limitations of conventional therapies available. Suanzaoren decoction (SZRD is a well known classic Chinese herbal prescription for insomnia and has been treating people’s insomnia for more than thousand years. The objective of this study was to evaluate the efficacy and safety of SZRD for insomnia. Methods A systematic literature search was performed for 6 databases up to July of 2012 to identify randomized control trials (RCTs involving SZRD for insomniac patients. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. Results Twelve RCTs with total of 1376 adult participants were identified. The methodological quality of all included trials are no more than 3/8 score. Majority of the RCTs concluded that SZRD was more significantly effective than benzodiazepines for treating insomnia. Despite these positive outcomes, there were many methodological shortcomings in the studies reviewed, including insufficient information about randomization generation and absence of allocation concealment, lack of blinding and no placebo control, absence of intention-to-treat analysis and lack of follow-ups, selective publishing and reporting, and small number of sample sizes. A number of clinical heterogeneity such as diagnosis, intervention, control, and outcome measures were also reviewed. Only 3 trials reported adverse events, whereas the other 9 trials did not provide the safety information. Conclusions Despite the apparent reported positive findings, there is insufficient evidence to support efficacy of SZRD for insomnia due to the poor methodological quality and the small number of trials of the included studies. SZRD seems generally safe, but is insufficient evidence to make conclusions on the safety because fewer studies reported the adverse events. Further large sample-size and well-designed RCTs are needed.

Xie Cheng-long



A review of international clinical trial registration  

Directory of Open Access Journals (Sweden)

Full Text Available ABSTRACT: Clinical trials play a critical role in medical research. However, only a few clinical trials conducted at present have been registered at various clinical trial registries. Clinical trial registration can prevent bias in these registered trials effectively and avoid unnecessary waste of resources due to meaningless repeats. Moreover, it will benefit the development of evidence-based medicine, and promote human welfare. Great attention has been paid to the importance and necessity of clinical trial registration. This review briefly introduced the definition, justification, contents, history, current status of clinical trial registration, and introduced the information regarding important international clinical trial registries in detail. Clinical trial registration should be developed toward a transparent, compulsory and comprehensive stage




How transparent are migraine clinical trials? (United States)

Transparency in research requires public access to unbiased information prior to trial initiation and openly available results upon study completion. The Repository of Registered Migraine Trials is a global snapshot of registered migraine clinical trials and scorecard of results availability via the peer-reviewed literature, registry databases, and gray literature. The 295 unique clinical trials identified employed 447 investigational agents, with 30% of 154 acute migraine trials and 11% of 141 migraine prophylaxis trials testing combinations of agents. The most frequently studied categories in acute migraine trials were triptans, nonsteroidal anti-inflammatory drugs, antiemetics, calcitonin gene-related peptide antagonists, and acetaminophen. Migraine prophylaxis trials frequently studied anticonvulsants, ?-blockers, complementary/alternative therapies, antidepressants, and botulinum toxin. Overall, 237 trials were eligible for a results search. Of 163 trials completed at least 12 months earlier, 57% had peer-reviewed literature results, and registries/gray literature added another 13%. Using logistic regression analysis, studies with a sample size below the median of 141 subjects were significantly less likely to have results, but the dominant factor associated with availability of results was time since study completion. In unadjusted models, trials registered on and trials with industry primary sponsorship were significantly more likely to have results. Recently completed trials rarely have publicly available results; 2 years after completion, the peer-reviewed literature contains results for fewer than 60% of completed migraine trials. To avoid bias, evidence-based therapy algorithms should consider factors affecting results availability. As negative trials are less likely to be published, special caution should be exercised before recommending a therapy with a high proportion of missing trial results. PMID:25194013

Dufka, Faustine L.; Dworkin, Robert H.



What Is a Clinical Trial?  

Medline Plus

Full Text Available ... trial results warrant, the new treatment becomes standard therapy for all patients. Dr. Stanley Watkins provides some examples. Dr. Stanley Watkins: When I first started in practice, there were diseases such as breast cancer, testicular cancer, and Hodgkin's ...


Prostate Cancer Prevention Trial (PCPT) (United States)

A fact sheet about the Prostate Cancer Prevention Trial (PCPT), which found that 25 percent fewer men taking the drug finasteride developed prostate cancer than men not taking the drug but that men who developed prostate cancer while taking finasteride were more likely to have high-grade cancers.



The Diabetes Prevention Trial--Type 1 (DPT-1) is a nationwide study to see if we can prevent or delay type 1 diabetes, also known as insulin-dependent diabetes. Nine medical centers and more than 350 clinics in the United States and Canada are taking part in the study....


[Phase I cancer trials methodology]. (United States)

The main objective of phase I cancer trials is to determine precisely the recommended dose of an anticancer agent as a single agent or in a context of combinations of anticancer agents (including cytotoxic agents, immunotherapy, radiotherapy...), that is administered for the first time in man, to further proceed clinical development with phase II and III trials. The recommended dose must have the greatest efficiency with acceptable toxicity. For the anticancer agents, the ratio risk/benefit is high, since toxicities associated with many cancer therapeutic agents are substantial and because the efficacy is often limited. Thus, phase I cancer trials present unique challenges in comparison to other therapeutic areas. Indeed, it is essential to minimize the numbers of patients treated at subefficient dose levels, and in the same time not to expose the patients to unacceptable toxicity. Historically, the first method that has been used is the Fibonacci escalation. The major problems raised with this method have been the lengths of the trials and the risk to treat substantial numbers of patients at nontherapeutix doses. Thus, novel methods have been then developed modifying the numbers of patients included at each dose level and the rapidity of dose escalation. These methods include pharmacologically guided dose escalation, escalation with overdose control and the continual reassessment method which are both statistically based dose escalation methods, and the accelerated titration designs. Concerning the targeted anticancer therapies, the therapeutic effect on the target, due to their higher specificity, can be obtained using doses that have few toxicity. Using the toxicity to determine the recommended dose for phase II trials, as it is the case for "classical > anticancer agents, does not seem to be sufficient. Alternatives to determine the optimal biological dose include measurement of target inhibition, pharmacokinetic analysis and functional imaging. PMID:18055311

Le Tourneau, Christophe; Faivre, Sandrine; Raymond, Eric; Diéras, Véronique



NIH Clinical Research Trials and You (United States)

... at NIH NIH Director’s Blog NIH Home NIH Clinical Research Trials and You Home The Basics Finding ... You Have a Question In the News NIH Clinical Research Trials and You Highlights Kayla's Story: A ...


Clinical Trials: What You Need to Know (United States)

... saved articles window. My Saved Articles » My ACS » Clinical Trials: What You Need to Know Download Printable ... PDF] » ( En español ) Knowing all you can about clinical trials can help you feel better when deciding ...


Clinical Trials Shed Light on Minority Health (United States)

... Tobacco Products Vaccines, Blood & Biologics Articulos en Espanol Clinical Trials Shed Light on Minority Health Search the ... health disparities The importance of including minorities in clinical trials Research collaborations OMH Director Jonca Bull's perspective ...


Clinical Trials: Key to Medical Progress (United States)

Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: Key to Medical Progress Past Issues / Summer ... this page please turn Javascript on. Photo iStock Clinical trials are research studies that test how well ...


The Design of Cluster Randomized Crossover Trials (United States)

The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own control. In a CR CO trial, clusters of subjects…

Rietbergen, Charlotte; Moerbeek, Mirjam



Is a Clinical Trial Right for Your Child? (United States)

Is a Clinical Trial Right for Your Child? KidsHealth > Parents > Doctors & Hospitals > Caring for a Seriously or Chronically Ill Child > Is ... enrolling your child in a clinical trial. About Clinical Trials A clinical trial is a research study ...


Bayesian Adaptive Methods for Clinical Trials  

CERN Document Server

Already popular in the analysis of medical device trials, adaptive Bayesian designs are increasingly being used in drug development for a wide variety of diseases and conditions, from Alzheimer's disease and multiple sclerosis to obesity, diabetes, hepatitis C, and HIV. Written by leading pioneers of Bayesian clinical trial designs, "Bayesian Adaptive Methods for Clinical Trials" explores the growing role of Bayesian thinking in the rapidly changing world of clinical trial analysis. The book first summarizes the current state of clinical trial design and analysis and introduces the m

Berry, Scott M



Clinical trials in neurosurgical oncology. (United States)

Brain tumors such as diffuse infiltrating gliomas continue to represent a major clinical challenge. Overall survival for patients diagnosed with glioblastoma, the most common primary brain tumor, remains less than 2 years despite intensive multimodal therapy with surgery, radiation, and chemotherapy. However, advances have been made in standard therapies and novel treatments that are showing great potential. These advances reflect careful study performed in the context of clinical trials. Neurosurgeons have played and will continue to play key parts in these studies. In this manuscript, we review clinical trials in neuro-oncology from a neurosurgical point of view and discuss potential roles for neurosurgeons in advancing glioma therapy in the future. PMID:25106866

Murphy, Meghan; Parney, Ian F



Pediatric Obstructive Uropathy: Clinical Trials  

International Nuclear Information System (INIS)

As the powerful tools of molecular biology continue to delineate new concepts of pathogenesis of diseases, new molecular-level therapeutic modalities are certain to emerge. In order to design and execute clinical trials to evaluate outcomes of these new treatment modalities, we will soon need a new supply of investigators with training and experience in clinical research. The slowly-progressive nature of chronic pediatric kidney disease often results in diagnosis being made at a time remote from initial result, and the inherently slow rate of progression makes changes difficult to measure. Thus, development of molecular markers for both diagnosis and rate of progression will be critical to studies of new therapeutic modalities. We will review general aspects of clinical trials and will use current and past studies as examples to illustrate specific points, especially as these apply to chronic kidney disease associated with obstructive uropathy in children. (author)


Basic problems in controlled trials.  

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On the basis of critical discussions which have taken place in recent years in the Federal Republic of Germany, certain methodological, ethical and legal problems arising in relation to controlled trials are discussed. Because of methodological inconsistencies inherent in the experimental approach, the efficacy of a drug must in any case be judged by physicians. This leads to major ethical and even--at least in Germany--legal problems which impose considerable limits on the feasibility of con...

Burkhardt, R.; Kienle, G.



VTT Field Trial Finnish Experiences  

International Nuclear Information System (INIS)

Finland is actively taking part in the actions related to the implementation of the Additional Protocol. AP creates lots of challenges, not only to the IAEA but also to the EURATOM and especially to the states. In the European Union, to implement AP there are three basic boundary conditions: use of Side Letters for to transfer the duties from the States to the European Commission, statements for the Council minutes concerning the internal communication in the EU and the Additional Protocol itself. Finnish Government has made the decision not to use any Side Letters. So, Finland is going to fulfill all the obligations itself except the common duties with the European Commission. For the common duties the practical and fluent communication channels between Finland and EURATOM has to be described. STUK, Radiation and Nuclear Safety Authority, has been chosen to be a 'site representative' for all sites in Finland. There are certain challenges, which must be solved before AP comes into force in the EU. To prepare to these challenges IAEA, EURATOM and Finland started the VTT Field Trial in Otaniemi, Espoo, during the summer 2000. VTT was chosen to be a site for the Field Trial, because it's divided to the several locations all over the Finland, i e. it's complexity in defining the site boundaries, and because it is the main location where possible nuclear R and D is conducted. Thus the objectives of the VTT Field Trial were: a) to define the site, b) to determine the roles efine the site, b) to determine the roles between IAEA, EU and the state, and to create information flow procedure between these organisations and c) to 97 perform a complementary access procedure. Also the R and D declaration was prepared. Finnish experiences of the VTT Field Trial is described in this paper. The most challenging part was to create practical information flow procedure between all the parties dealing with the AP, not only the new and the technical nature of the AP


Market Trials of Irradiated Spices  

International Nuclear Information System (INIS)

Full text: The objectives of the experiment were to disseminate irradiated retail foods to the domestic publics and to test consumer acceptance on irradiated ground chilli and ground pepper. Market trials of irradiated ground chilli and ground pepper were carried out at 2 local markets and 4 in Bangkok and Nontaburi in 2005-2007. Before the start of the experiment, processing room, gamma irradiation room and labels of the products were approved by Food and Drug Administration, Thailand. 50 grams of irradiated products were packaged in plastic bags for the market trials. 688 and 738 bags of ground chilli and ground pepper were sold, respectively. Questionnaires distributed with the products were commented by 59 consumers and statistically analyzed by experimental data pass program. 88.1 and 91.4 percents of the consumers were satisfied with the quality and the price, respectively. 79.7% of the consumers chose to buy irradiated ground chilli and ground pepper because they believed that the quality of irradiated products were better than that of non-irradiated ones. 91.5% of the consumers would certainly buy irradiated chilli and pepper again. Through these market trials, it was found that all of the products were sold out and the majority of the consumers who returned the questionnaires was satisfied with the irradiated ground chilli and ground pepper and also had good attitude toward irradiated foods


Clinical trials: innovation, progress and controversy  

Directory of Open Access Journals (Sweden)

Full Text Available Greg S MartinDepartment of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, Georgia, USAThe Open Access Journal of Clinical Trials began in 2009 with the goal of being an authoritative, open access source for international, peer-reviewed publications in the field of human research and clinical trials. Since then, the Open Access Journal of Clinical Trials has published approximately 30 high-quality articles on original research, innovative reviews, and critical commentaries. These articles have spanned many aspects of clinical trials wonderfully, including trial design and management; legal, ethical and regulatory issues of clinical trials; subject participation and retention in clinical trials; and data collection and data management.

Martin GS



Multicentre trials: a US regulatory perspective. (United States)

Multicentre trials are very common in the field of drug development. In recent years, multicentre trials have taken on a multinational and multiregional aspect. We provide a conceptual framework for the use of multicentre trials in the context of drug development, from the perspective of drug regulation in the United States. In this paper, we review some regulatory history, milestones and standards as they relate to multicentre trials. Special attention is given to the similarities and differences in the approaches to multicentre trials in the following documents; Guideline for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, International Conference on Harmonization, Draft Guideline on Statistical Principles for clinical trials and the Guidance for Industry Providing Clinical Evidence of Effectiveness for Human Drug and Biologic Products. The paper includes a consideration of some of the issues in the analysis of data from multicentre trials. PMID:15969305

Anello, Charles; O'Neill, Robert T; Dubey, Satya



[The danger of unpublished trial results]. (United States)

Unpublished and selectively published trial results may lead to distortion of the effectiveness and the profile of side effects of interventions. This jeopardizes patient safety and leads to unnecessary costs. Between 25 and 50% of all clinical trials remain unpublished. Primary outcomes, as originally defined in study protocols, often differ from those in the final publication. Positive trial results are almost 3 times as likely to be published as negative results. Commercial sponsorship is strongly associated with the publication of results that promote the interests of that sponsor, but non-publication and selective reporting is also frequent among non-commercial trials. Existing solutions, such as the requirement for prospective registration of trial protocols and the mandatory publication of trial results within 1 year after completion of the trial will only be successful if their compliance is more strictly monitored. PMID:24780575

Korevaar, Daniël A; Hooft, Lotty



Credentialing for participation in clinical trials  

Directory of Open Access Journals (Sweden)

Full Text Available The National Cancer Institute (NCI clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence based clinical trial processes for improvements in patient care. The cooperative groups are undergoing a transformation process to launch, conduct, and publish clinical trials more rapidly. Institutional participation in clinical trials can be made more efficient and include the expansion of relationships with international partners. This paper reviews the current processes that are in use in radiation therapy trials and the importance of maintaining effective credentialing strategies to assure the quality of the outcomes of clinical trials. The paper offers strategies to streamline and harmonize credentialing tools and processes moving forward as the NCI undergoes transformative change in the conduct of clinical trials.




Recruitment and retention in a multicentre randomised controlled trial in Bell's palsy: A case study  

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Full Text Available Abstract Background It is notoriously difficult to recruit patients to randomised controlled trials in primary care. This is particularly true when the disease process under investigation occurs relatively infrequently and must be investigated during a brief time window. Bell's palsy, an acute unilateral paralysis of the facial nerve is just such a relatively rare condition. In this case study we describe the organisational issues presented in setting up a large randomised controlled trial of the management of Bell's palsy across primary and secondary care in Scotland and how we managed to successfully recruit and retain patients presenting in the community. Methods Where possible we used existing evidence on recruitment strategies to maximise recruitment and retention. We consider that the key issues in the success of this study were; the fact that the research was seen as clinically important by the clinicians who had initial responsibility for recruitment; employing an experienced trial co-ordinator and dedicated researchers willing to recruit participants seven days per week and to visit them at home at a time convenient to them, hence reducing missed patients and ensuring they were retained in the study; national visibility and repeated publicity at a local level delivered by locally based principal investigators well known to their primary care community; encouraging recruitment by payment to practices and reducing the workload of the referring doctors by providing immediate access to specialist care; good collaboration between primary and secondary care and basing local investigators in the otolarnygology trial centres Results Although the recruitment rate did not meet our initial expectations, enhanced retention meant that we exceeded our planned target of recruiting 550 patients within the planned time-scale. Conclusion While difficult, recruitment to and retention within multi-centre trials from primary care can be successfully achieved through the application of the best available evidence, establishing good relationships with practices, minimising the workload of those involved in recruitment and offering enhanced care to all participants. Primary care trialists should describe their experiences of the methods used to persuade patients to participate in their trials when publishing their results.

Daly Fergus



Physical activity and trial-by-trial adjustments of response conflict. (United States)

The relationship of physical activity to trial-by-trial adjustments of response conflict was assessed using behavioral task performance, the N2 event-related brain potential component, and phase-locking values (PLVs) in a lower gamma band during a perceptual conflict task. Nineteen physically active and 19 inactive young adults (mean age = 21.3 years) performed a Navon task, using a global letter made up of local letters of either the same kind (congruent trials) or a different kind (incongruent trials). Findings revealed that active individuals exhibited smaller N2 amplitudes and greater PLVs on incongruent trials that were preceded by incongruent trials compared with those preceded by congruent trials. Such phenomena were not observed for inactive individuals. These results suggest that greater physical activity is associated with larger trial-by-trial adjustments of response conflict, which we attribute to upregulation of top-down cognitive control and reductions in response conflict. PMID:23966449

Kamijo, Keita; Takeda, Yuji



Dissecting Pamela (and ATIC) with Occam's Razor: existing, well-known Pulsars naturally account for the "anomalous" Cosmic-Ray Electron and Positron Data  

CERN Document Server

We argue that both the positron fraction measured by PAMELA and the peculiar spectral features reported in the total differential electron-positron flux measured by ATIC have a very natural explanation in electron-positron pairs produced by nearby pulsars. We show that the greatly improved quality of current data allow us to reverse-engineer the problem: given the regions of pulsar parameter space favored by PAMELA and by ATIC, are there known pulsars that naturally explain the data? We address this question by (1) outlining simple theoretical models for estimating the energy output, the diffusion setup and the injection spectral index of electron-positron pairs, and by (2) considering all known pulsars (as given in the ATNF catalogue). It appears unlikely that a single pulsar be responsible for both the PAMELA result and for the ATIC excess, although two sources are enough to naturally explain both of the experimental results. We list several candidate pulsars that can individually or coherently contribute t...

Profumo, Stefano



The use of a new approach to prevention and therapy of acute arterial hypertension with complex of well-known drugs with vegetable glycosides (experimental study  

Directory of Open Access Journals (Sweden)

Full Text Available Aim. To evaluate antihypertensive efficacy of nifedipine (N and nifedipine complex (NC in acute test in rats with adrenaline model of arterial hypertension.Material and methods. N is a conventional short acting formulation while NC is a new formulation of nifedipine in complex with glycyrrhizic acid. NC has an active substance 10 times less than N does in the same dose. Adrenaline which results in two times increase in blood pressure (BP during 4 min was administered as a single i.v. dose (0,03 mg/kg to normotensive unconscious male rats (body weight 190-220 g. NC and N were administered in the same dose (3,5 mg/kg before and after adrenaline administration. Systolic BP recovering time was assessed. BP level was measured with direct method in carotid artery.Results. NC and N decreased in systolic BP in normotensive rats by 26 and 30% respectively. NC and N administered before adrenaline administration resulted in systolic BP recovering time reduction to 94,4 and 79,7 s respectively, which are less than this in control (204,8 s, ?<0,001. Difference in time between NC and N is not significant (p<0,1. NC and N administered after adrenaline administration resulted in systolic BP recovering time reduction to 104,7 and 139 s respectively, which are also less than this in control (204,8 s, ?<0,001. Difference in time between NC and N in this model is also not significant (p<0,1.Conclusion. NC with contents of active substance 10 times less than in N showed antihypertensive efficacy similar with this in N. NC can be used for prevention and therapy of acute arterial hypertension.

T. G. Tolstikova



Intracellular Signaling Transduction Pathways Triggered by a Well-Known Anti-GHR Monoclonal Antibody, Mab263, in Vitro and in Vivo  

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Full Text Available A series of studies have reported that monoclonal antibody 263 (Mab263, a monoclonal antibody against the growth hormone receptor (GHR, acts as an agonist in vitro and in vivo. However, the intracellular signaling pathways triggered by Mab263 have not yet been delineated. Therefore, we examined the intracellular signaling pathways induced by Mab263 in vivo and in vitro in the present study. The results show that this antibody activated janus kinase 2 (JAK2, signal transducer and activator of transcription 3 (STAT3, STAT1 and extracellular signal-regulated kinase 1/2 (ERK1/2, but not STAT5. The phosphorylation kinetics of JAK2, STAT3/1 and ERK1/2 induced by Mab263 were subsequently analyzed in dose-response and time course experiments. Our observations indicate that Mab263 induced different intracellular signaling pathways than GH, which indicates that Mab263 is a signal-specific molecule and that Mab263 may be a valuable biological reagent to study the mechanism(s of GHR-mediated intracellular signaling pathways.

Hainan Lan



Left ventricular assist devices in patients with end-stage heart failure: suggestion of an alternative treatment based on clinically well-known concepts. (United States)

Encouraging results were obtained by using left ventricular assist devices (LVADs) in patients with end-stage heart failure (HF) that exhibits extremely high mortality and who were not candidates for heart transplantation. By using this so-called destination therapy (DT), a substantial percentage of these patients achieved sufficient improvement in cardiac function to permit the explantation of the device. The combination of mechanical and pharmacological therapy increased the frequency and durability of myocardial recovery as compared with other therapeutic approaches. Although cardiac transplantation, LVADs, and cardiac resynchronization therapy have provided a major advance in DT, their limitations stimulate the search for alternative therapies. We discuss the limitations of these 3 treatment options for end-stage HF. Also, we propose and discuss the possible advantages of a new intracorporeal procedure that works continuously as intraaortic balloon counterpulsation without an extracorporeal or intracorporeal computer-controlled mechanism. PMID:24482491

Fantidis, Panayotis; Sánchez, Eladio; Tarhini, Ibrahim; Khan, Ijaz; Pineda, Tomas; Corrales, Juan Antonio; González, José Ramón



Assessing the suitability and safety of a well-known bud-galling wasp, Trichilogaster acaciaelongifoliae, for biological control of Acacia longifolia in Portugal  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Acacia longifolia is a widespread invasive plant species in Portugal. In South Africa, it is controlled by a bud-galling wasp, Trichilogaster acaciaelongifoliae, which could also be used in Portugal. Biological control of invasive alien plants has received little consideration anywhere in Europe and has never been attempted in Portugal. The lack of a suitably-large quarantine facility necessitated the use of a novel approach to test non-target species in Portugal. Mature T. acaciaelongifoliae...

Marchante, H.; Freitas, H.; Hoffmann, J. H.



A Well-Known Lesion in An Unusual Location: Infantile Myofibroma of the Eyelid:A Case Report and Review of Literature  

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Full Text Available "nMyofibroma is a neoplasia of myofibroblasts that can be solitary or multiple and it is found most commonly in the head & neck region including scalp, forehead, parotid region and oral cavity. In the eyelid it is rarely reported. It has a benign course in the solitary form and fatal in its multiple form. A 4 month male infant referred to Farabi hospital -the referral center for eye diseases- with a 2 month history of a mass in his eyelid with gradual enlargement with no other complaints. The only abnormal physical finding was a 2.5 cm mass in the eyelid. This mass was excised and sent to the hospital pathology laboratory. When confronting a spindle cell lesion with a nodular or multinodular growth pattern which appears biphasic due to alteration of light and dark staining areas, the surgical pathologist should think to the possibility of myofibroma. Its pattern of growth and architecture rules out the other differential diagnoses like nodular fasciitis, fibrous histiocytoma, infantile fibromatosis, and peripheral primitive neuroectodermal tumor, mesenchymal chondrosarcoma, malignant hemangiopericytoma, juvenile fibrosarcoma and poorly differentiated synovial sarcoma. In difficult cases immunohistochemical staining is helpful that is Vimentin & Actin positivity & Desmin, CK, EMA & S100 negativity.

Fahimeh Asadi Amoli



Síndrome de Rett: 50 años de historia de un trastorno aun no bien conocido Rett syndrome: 50 years' history of a still not well known condition  

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Desde que fue descrito por primera vez por Andreas Rett hace 50 años, el síndrome de Rett (SR) ha sido objeto de muchas investigaciones, sin embargo continúa siendo un trastorno aún no bien conocido. Presentamos nuestra propia experiencia y una revisión de la literatura sobre el SR. Se trata de un trastorno del neurodesarrollo, dominante ligado a X, que afecta casi siempre a mujeres, la mayoría de los casos de forma esporádica. El diagnóstico de SR debe hacerse en base a la observaci?...

Jaime Campos-Castello; Fernandez-mayoralas, Daniel M.; Nuria Muñoz-Jareño; Victoria San Antonio-Arce



Review of the chronic exposure pathways models in MACCS (MELCOR Accident Consequence Code System) and several other well-known probabilistic risk assessment models  

Energy Technology Data Exchange (ETDEWEB)

The purpose of this report is to document the results of the work performed by the author in connection with the following task, performed for US Nuclear Regulatory Commission, (USNRC) Office of Nuclear Regulatory Research, Division of Systems Research: MACCS Chronic Exposure Pathway Models: Review the chronic exposure pathway models implemented in the MELCOR Accident Consequence Code System (MACCS) and compare those models to the chronic exposure pathway models implemented in similar codes developed in countries that are members of the OECD. The chronic exposures concerned are via: the terrestrial food pathways, the water pathways, the long-term groundshine pathway, and the inhalation of resuspended radionuclides pathway. The USNRC has indicated during discussions of the task that the major effort should be spent on the terrestrial food pathways. There is one chapter for each of the categories of chronic exposure pathways listed above.

Tveten, U. (Institutt for Energiteknikk, Kjeller (Norway))



The use of a new approach to prevention and therapy of acute arterial hypertension with complex of well-known drugs with vegetable glycosides (experimental study)  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Aim. To evaluate antihypertensive efficacy of nifedipine (N) and nifedipine complex (NC) in acute test in rats with adrenaline model of arterial hypertension.Material and methods. N is a conventional short acting formulation while NC is a new formulation of nifedipine in complex with glycyrrhizic acid. NC has an active substance 10 times less than N does in the same dose. Adrenaline which results in two times increase in blood pressure (BP) during 4 min was administered as a single i.v. dose ...

Tolstikova, T. G.; Sorokina, I. V.; Brisgalov, A. O.; Dolgich, M. P.; Lifshitz, G. I.; Chvostov, M. V.



Ontolojik Çözümleme Yöntemi Ve “Kanla Kirlenmi? Evrak” ?iiri Üzerine Bir Çözümleme Denemesi Ontologial Evaluation Validation Method And An Evaluation Essay Upon Well Known Poem “Kanla Kirlenmi? Evrak”  

Directory of Open Access Journals (Sweden)

Full Text Available Art is a value that gives to individuals a new chance forreestablishing their own characteristically environments. The paintings,music and poetry are many reflections of individual characters. Theontology is an individual field that examines the structural analysesbetween an art object and other fine art products. What kind of art wehave that has been studied from the beginning of first era? At thebeginning the question was, whether the art for the community or forthe individual one, and this question replaced it with to the examiningthe layers of an art object and by the way the art ontology appeared thatreflects itself as a modern philosophical discipline. The art ontologyseparates the ideas of Roman Ingarden and Nicolai Hartmann from eachother and evaluates the layers of the art objects. The relationshipbetween subject and object has been surfaced by art ontology, and theart ontology also has been a new method for the literary textsvalidations. Besides the literary text evaluations, the front-yard andback-yard structure evaluations of a poem have been possible by thesame art ontology method. In this perspective the art ontology that hasbeen used to understand the ontological structure of literary texts is anew method for these purposes nowadays. The ontological methods hasbeen surfaced by the Sanat Ontolojisi, work of Ismail Tunali, the layersof the existence and specially the understanding the real meaningshidden in a poetry surfaced by the same method. We may say that theontological method have been used in Turkish literature by Dursun AliTokel and Yavuz Bayram for the explanation gazels in Divan literature.This academic paper aims the introduction of the ontological methodand the evaluation of the poem of Ismet Ozel named “Kanla Kirlenmi?Evrak”. Sanat bireyin kendini ve çevresini yeniden kurmas?na olanak sa?layan bir de?erdir. Resim, müzik, ?iir yarat?c? bir mizac?n yans?malar?d?r. Ontoloji ise sanat eserinin varl??? ile öbür varl?klar?n yap?lar?n? inceleyen bir aland?r. ?lk ça?dan beri üzerinde en çok kafa yorulan sorunsal olan sanat nedir? Toplum için mi yoksa birey için midir sorular? yerini sanat yap?t?n?n tabakalar?n?n incelenmesine b?rakm?? modern bir felsefi disiplin olan sanat ontolojisi do?mu?tur. Sanat ontolojisi, varl?k tabakalar?n? Roman ?ngarden ve Nicolai Hartmann’?n görü?leri ile ay?rarak tabakalar? aç?mlar. Yarat?c? suje ile özne aras?ndaki ili?kiyi gün yüzüne ç?karan sanat ontolojisi edebiyat metinlerin çözümlenmesinde de kullan?lan bir yöntem olmu?tur. Bu yöntem vas?tas?yla edebiyat metinlerini özellikle de ?iiri Ön yap? ve Arka yap? ?eklinde aç?mlamak ve kapal? anlam katmanlar?na ula?mak mümkündür.Bu perspektifte, edebi metinlerin çözümlenmesinde kullan?lan bir yöntem olan ontoloji yöntemi sanat eserinin ontik yap?s?n?n anla??l?r k?l?nmas?nda son zamanlarda kullan?lan bir yöntem olmu?tur. ?lk kez ?smail Tunal?’n?n Sanat Ontolojisi ba?l?kl? çal??mas?yla duyurdu?u ontolojik yöntemle varl???n katmanlar?n?n aç?mlanmas? ve özellikle ?iirin anla??l?r k?l?nmas? sa?lan?r. Türk edebiyat?nda Dursun Ali Tökel ve Yavuz Bayram’?n özellikle divan ?iiri metinlerine farkl? gözle bakmay? amaç edinen gazel çözümlemelerinde bu yöntemden faydalan?p yöntemin yayg?nla?mas?nda öncülük ettikleri söylenebilir. Bu çal??ma ontolojik yöntemin tan?t?lmas? ve ?smet Özel’in “Kanla Kirlenmi? Evrak” ?iirinin çözümlenmesi üzerine kurulmu?tur.

Samet AZAP



Exposing the secrets of two well-known Lactobacillus casei phages, J-1 and PL-1, by genomic and structural analysis. (United States)

Bacteriophage J-1 was isolated in 1965 from an abnormal fermentation of Yakult using Lactobacillus casei strain Shirota, and a related phage, PL-1, was subsequently recovered from a strain resistant to J-1. Complete genome sequencing shows that J-1 and PL-1 are almost identical, but PL-1 has a deletion of 1.9 kbp relative to J-1, resulting in the loss of four predicted gene products involved in immunity regulation. The structural proteins were identified by mass spectrometry analysis. Similarly to phage A2, two capsid proteins are generated by a translational frameshift and undergo proteolytic processing. The structure of gene product 16 (gp16), a putative tail protein, was modeled based on the crystal structure of baseplate distal tail proteins (Dit) that form the baseplate hub in other Siphoviridae. However, two regions of the C terminus of gp16 could not be modeled using this template. The first region accounts for the differences between J-1 and PL-1 gp16 and showed sequence similarity to carbohydrate-binding modules (CBMs). J-1 and PL-1 GFP-gp16 fusions bind specifically to Lactobacillus casei/paracasei cells, and the addition of l-rhamnose inhibits binding. J-1 gp16 exhibited a higher affinity than PL-1 gp16 for cell walls of L. casei ATCC 27139 in phage adsorption inhibition assays, in agreement with differential adsorption kinetics observed for both phages in this strain. The data presented here provide insights into how Lactobacillus phages interact with their hosts at the first steps of infection. PMID:25217012

Dieterle, Maria Eugenia; Bowman, Charles; Batthyany, Carlos; Lanzarotti, Esteban; Turjanski, Adrián; Hatfull, Graham; Piuri, Mariana



Clinical trial to assess the effect of physical exercise on endothelial function and insulin resistance in pregnant women  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Preeclampsia (PE is a common maternal disease that complicates 5 to 10% of pregnancies and remains as the major cause of maternal and neonatal mortality. Cost-effective interventions aimed at preventing the development of preeclampsia are urgently needed. However, the pathogenesis of PE is not well known. Multiple mechanisms such as oxidative stress, endothelial dysfunction and insulin resistance may contribute to its development. Regular aerobic exercise recovers endothelial function; improves insulin resistance and decreases oxidative stress. Therefore the purpose of this clinical trial is to determine the effect of regular aerobic exercise on endothelial function, on insulin resistance and on pregnancy outcome. Methods and design 64 pregnant women will be included in a blind, randomized clinical trial, and parallel assignment. The exercise group will do regular aerobic physical exercise: walking (10 minutes, aerobic exercise (30 minutes, stretching (10 minutes and relaxation exercise (10 minutes in three sessions per week. Control group will do the activities of daily living (bathing, dressing, eating, and walking without counselling from a physical therapist. Trial registration NCT00741312.

Reyes Laura M



Maximizing scientific knowledge from randomized clinical trials  

DEFF Research Database (Denmark)

Trialists have an ethical and financial responsibility to plan and conduct clinical trials in a manner that will maximize the scientific knowledge gained from the trial. However, the amount of scientific information generated by randomized clinical trials in cardiovascular medicine is highly variable. Generation of trial databases and/or biobanks originating in large randomized clinical trials has successfully increased the knowledge obtained from those trials. At the 10th Cardiovascular Trialist Workshop, possibilities and pitfalls in designing and accessing clinical trial databases were discussed by a group of trialists. This review focuses on the arguments for conducting posttrial database studies and presents examples of studies in which posttrial knowledge generation has been substantial. Possible strategies to ensure successful trial database or biobank generation are discussed, in particular with respect to collaboration with the trial sponsor and to analytic pitfalls. The advantages of creating screening databases in conjunction with a given clinical trial are described; and finally, the potential for posttrial database studies to become a platform for training young scientists is outlined.

Gustafsson, Finn; Atar, Dan



Lessons learned from radiation oncology clinical trials. (United States)

A workshop entitled "Lessons Learned from Radiation Oncology Trials" was held on December 7-8, 2011, in Bethesda, MD, to present and discuss some of the recently conducted radiation oncology clinical trials with a focus on those that failed to refute the null hypothesis. The objectives of this workshop were to summarize and examine the questions that these trials provoked, to assess the quality and limitations of the preclinical data that supported the hypotheses underlying these trials, and to consider possible solutions to these challenges for the design of future clinical trials. Several themes emerged from the discussions: (i) opportunities to learn from null-hypothesis trials through tissue and imaging studies; (ii) value of preclinical data supporting the design of combinatorial therapies; (iii) significance of validated biomarkers; (iv) necessity of quality assurance in radiotherapy delivery; (v) conduct of sufficiently powered studies to address the central hypotheses; and (vi) importance of publishing results of the trials regardless of the outcome. The fact that well-designed hypothesis-driven clinical trials produce null or negative results is expected given the limitations of trial design and complexities of cancer biology. It is important to understand the reasons underlying such null results, however, to effectively merge the technologic innovations with the rapidly evolving biology for maximal patient benefit through the design of future clinical trials. PMID:24043463

Liu, Fei-Fei; Okunieff, Paul; Bernhard, Eric J; Stone, Helen B; Yoo, Stephen; Coleman, C Norman; Vikram, Bhadrasain; Brown, Martin; Buatti, John; Guha, Chandan



Microbicide clinical trial adherence: insights for introduction  

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Full Text Available After two decades of microbicide clinical trials it remains uncertain if vaginally- delivered products will be clearly shown to reduce the risk of HIV infection in women and girls. Furthermore, a microbicide product with demonstrated clinical efficacy must be used correctly and consistently if it is to prevent infection. Information on adherence that can be gleaned from microbicide trials is relevant for future microbicide safety and efficacy trials, pre-licensure implementation trials, Phase IV post-marketing research, and microbicide introduction and delivery. Drawing primarily from data and experience that has emerged from the large-scale microbicide efficacy trials completed to-date, the paper identifies six broad areas of adherence lessons learned: (1 Adherence measurement in clinical trials, (2 Comprehension of use instructions/Instructions for use, (3 Unknown efficacy and its effect on adherence/Messages regarding effectiveness, (4 Partner influence on use, (5 Retention and continuation and (6 Generalizability of trial participants' adherence behavior. Each is discussed, with examples provided from microbicide trials. For each of these adherence topics, recommendations are provided for using trial findings to prepare for future microbicide safety and efficacy trials, Phase IV post-marketing research, and microbicide introduction and delivery programs.

Cynthia Woodsong



Registration of noncommercial randomised clinical trials: the feasibility of using trial registries to monitor the number of trials  

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Full Text Available Abstract Background A 2003 survey suggested the number of noncommercial trials in the UK was declining. Formation of the NIHR in 2006 and increased research spending by the Department of Health may have increased the number of noncommercial trials but no data are available. Methods Available data on UK noncommercial trials (were obtained from the two relevant registries: ISRCTN register for the UK, and US Data on each trial were sorted by start year, and compared with the: 2003 survey, and UKCRN portfolio database from 2007. Results The number of UK noncommercial trials registered rose from 25 in 1990 to 188 in 1999, peaked at 533 in 2003, and fell back to 334 in 2009. Total trials registered was similar to but slightly above those in the 2003 survey up to 1998, then rose sharply to 2002 before falling to 2007. From 2007 to 2009 the number registered to start each year was similar to but slightly above the UKCRN database. Less than 10% of UK noncommercial trials registered with ClinGov for most years before 2005, but this rose to 35% by 2009. Conclusions For the periods of overlap, trial registration data provide fairly similar totals to other sources on the number of noncommercial trials starting each year. The rise and fall in the number of trials registered between 1999 and 2007 was due to those registered in the ISRCTN database as funded by NHS Trusts. After 2007, the number of trials registered as funded by NHS Trusts has fallen in the ISRCTN register but these trials may have migrated to the US ClinGov register. The total number of noncommercial trial starts, excluding those funded by NHS Trusts, has been upward since around 2002. By 2009 the two main funders were NIHR and charities. Feasibility of using registration data to monitor the number of noncommercial trials has been demonstrated but is complicated by the use of two registers and difficulties in accessing the data. We recommend an annual report on the number of noncommercial trials registering each year.

Raftery James



Melanoma vaccines: trials and tribulations  

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Full Text Available Robert O Dillman1,21Hoag Cancer Institute and Hoag Institute for Research and Education, Newport Beach, CA, USA; 2University of California Irvine, Irvine, CA, USAAbstract: Metastatic melanoma has been a target of immunotherapy for more than 4 decades. Three immunotherapeutics have received regulatory approval for treating melanoma: interferon-alpha, interleukin-2, and ipilimumab. The antitumor mechanisms of these products depend on enhancing existing immune responses, including autoimmune effects. The combination of autologous, cytotoxic T-lymphocytes plus high-dose interleukin-2 is a promising patient-specific therapy, but has limited clinical application. Other approaches include vaccines targeting melanoma-associated antigens, and patient-specific vaccines that utilize autologous tumor. Non-patient-specific vaccine approaches target melanocyte differentiation antigens (eg, tyrosinase, Melan-A, gp100, antigens identified by cytotoxic T-lymphocytes (eg, NY-Eso-1, Melan-A/Mart-1, Mage-3, and antigens originally identified by murine monoclonal antibodies (gangliosides, gp97, gp225. Self-renewing cells in tumor cell lines may represent tumor stem cells, but vaccines derived from allogeneic tumor cell lines have yielded disappointing results in randomized trials. Patient-specific vaccines can be derived from bulk autologous tumor or autologous tumor cell lines, and intratumoral injections of immunostimulatory fusion products have shown promise. While technically more complex to manufacture, patient-specific vaccines derived from autologous tumor cell lines have the potential to target tumor stem cells and overcome interpatient tumor cell heterogeneity. This article reviews sources of melanoma-associated antigens, costimulatory agents, and clinical trial results for various melanoma vaccines. Comparing Phase II trials is difficult because of the wide range of vaccine strategies and the differences in study patient populations; therefore, randomized trials are necessary to prove the efficacy of such products. Therapeutic vaccines are more likely to enhance, rather than replace, other anti-melanoma immune therapies. In particular, effective vaccines may be synergistic with products that block T-cell immune checkpoint molecules such as ipilimumab and monoclonal antibodies that interfere with programmed death ligand-receptor interactions.Keywords: melanoma, vaccines, melanoma-associated antigens, melanoma stem cells, dendritic cells, GM-CSF, checkpoint molecules

Dillman RO



Statistical aspects of clinical trials  

International Nuclear Information System (INIS)

A basic understanding of the various disciplines involved in the planning and conducting of a clinical trial is a prerequisite for a fruitful result. This paper explains some of the statistical ideas and vocabulary used in the process of documenting the X-ray contrast medium iopentol Nycomed AS, Oslo, Norway). Topics discussed include the concepts of the significance level, the null-value, and the corresponding confidence interval, in controlled situations and in exploratory analysis; and a discussion of parametric vs. non-parametric methods. (author). 8 refs.; 2 figs.; 1 tab


Civil society perspectives on negative biomedical HIV prevention trial results and implications for future trials. (United States)

Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building. PMID:22360605

Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A



Congruency sequence effects are driven by previous-trial congruency, not previous-trial response conflict.  

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Full Text Available Congruency effects in distracter interference tasks are often smaller after incongruent trials than after congruent trials. However, the sources of such congruency sequence effects (CSEs are controversial. The conflict monitoring model of cognitive control links CSEs to the detection and resolution of response conflict. In contrast, competing theories attribute CSEs to attentional or affective processes that vary with previous-trial congruency (incongruent vs. congruent. The present study sought to distinguish between conflict and non-conflict accounts of CSEs. To this end, we determined whether CSEs are driven by previous-trial reaction time (RT--a putative measure of response conflict--or by previous-trial congruency. In two experiments using a face-word Stroop task (n=49, we found that current-trial congruency effects did not vary with previous-trial RT independent of previous-trial congruency. In contrast, current-trial congruency effects were influenced by previous-trial congruency independent of previous-trial RT. These findings appear more consistent with theories that attribute CSEs to non-conflict processes that vary with previous-trial congruency than with theories that link CSEs to previous-trial response conflict.




Legislation for trial registration and data transparency  

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Full Text Available Abstract Public confidence in clinical trials has been eroded by data suppression, misrepresentation and manipulation. Although various attempts have been made to achieve universal trial registration- e.g., Declaration of Helsinki, WHO clinical Trial Registry Platform (WHO ICTRP, the International Committee of Medical Journal Editors requirement- they have not succeeded, probably because they lack the enough power of enforcement. Legislation appears to be the most efficient and effective means to ensure that all researchers register their trials and disseminate their data accurately and in a timely manner. We propose that a global network be established. This could be accomplished in two steps. The first step is to legislate about trial registration and data transparency, such as USA's FDAAA Act 2007; and the second step to establish a global network to ensure uniform, international consistency in policy and enforcement of trial registration and data transparency.

Wu Tai-Xiang



Pharmaceutical clinical trial supply chain management  

Digital Repository Infrastructure Vision for European Research (DRIVER)

New drug development follows an extended sequence of steps (discovery, animal trials, FDA application (IND), product and process development, three phases of clinical trials, FDA filing and approval and launch) as a result of which it takes many years and considerable expense (upwards of $1 Billion) to bring a new drug to market. The clinical trials constitute a critically important and very expensive part of the development process as it involves producing, distributing and administering the...

Chen, Ye



"Wish bias" in antidepressant drug trials?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The present study investigated whether the outcome of randomized clinical trials studying fluoxetine favored fluoxetine, where this was the experimental agent, and favored comparator antidepressants in trials where fluoxetine was the reference agent. A systematic review of all double-blind, randomized clinical trials comparing fluoxetine with any other antidepressant drug in patients suffering from depression was carried out. Thirty-seven studies meeting the inclusion criteria were analyzed. ...

Barbui, C.; Cipriani, A.; Brambilla, P.; Hotopf, M.



Registro dos ensaios clínicos / Clinical trials register  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese [...] Abstract in english The International Committee of Medical Journal Editors (ICMJE) proposed trials registration in a public trials registry, as a condition for publication. This policy started after July 1, 2005, and was supported by the World Association of Medical Editors (WAME). In May 19, 2006, the WHO urged resear [...] ch institutions and companies to register all medical studies that test treatments on human beings, whether they involve patients or healthy volunteers. The WHO also started the International Clinical Trials Registry Platform (ICTRP), aimed at standardizing the way information of studies is made available to the public. The following registers contribute data directly to the Who Search Portal: Australian Clinical Trials Registry,, and International Standard Randomized Controlled Trial Number Register. In May 15, 2007, the Latin American and Caribbean Center on Health Sciences Information (BIREME) published a recommendation for editors of health journals indexed in Latin American and Caribbean Literature on Health Sciences (LILACS) and Scientific Library Electronic Online (ScieLO) about registration of clinical trials. In addition to the UMIN Clinical Trial Registry and the Nederlands Trial Register, the ICMJE is now accepting registration in any of the primary registers that participate in the WHO ICTRP. The ICMJE is also adopting the WHO's definition of clinical trial. Three years ago, trials registration was the exception; now it is the rule. Registration facilitates the dissemination of information, and it helps to assure trial participants that the information that accrues as a result of their altruism will become part of the public record.

Carlos Alberto, Guimarães.


Prudent precaution in clinical trials of nanomedicines. (United States)

Clinical trials of nanotechnology medical products present complex risk management challenges that involve many uncertainties and important risk-risk trade-offs. This paper inquires whether the precautionary principle can help to inform risk management approaches to nanomedicine clinical trials. It concludes that prudent precaution may be appropriate for ensuring the safety of such trials, but that the precautionary principle itself, especially in its more extreme forms, does not provide useful guidance for specific safety measures. PMID:23289685

Marchant, Gary E; Lindor, Rachel A



Methodological bias in cluster randomised trials  

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Abstract Background Cluster randomised trials can be susceptible to a range of methodological problems. These problems are not commonly recognised by many researchers. In this paper we discuss the issues that can lead to bias in cluster trials. Methods We used a sample of cluster randomised trials from a recent review and from a systematic review of hip protectors. We compared the mean age of participants between intervention groups in a sample of 'good' cluster...

Torgerson David J; Puffer Suezann; Hahn Seokyung; Watson Judith



Potential bias in ophthalmic pharmaceutical clinical trials  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Paul VarnerJohn J Pershing Veterans’ Administration Medical Center, Poplar Bluff, Missouri, USAAbstract: To make clinicians aware of potential sources of error in ophthalmic pharmaceutical clinical trials that can lead to erroneous interpretation of results, a critical review of the study design of various pharmaceutical ophthalmic clinical trials was completed. Discrepancies as a result of study shortcomings may explain observed differences between reported ophthalmic trial data an...

Paul Varner



Registro dos ensaios clínicos / Clinical trials register  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese [...] Abstract in english The International Committee of Medical Journal Editors (ICMJE) proposed trials registration in a public trials registry, as a condition for publication. This policy started after July 1, 2005, and was supported by the World Association of Medical Editors (WAME). In May 19, 2006, the WHO urged resear [...] ch institutions and companies to register all medical studies that test treatments on human beings, whether they involve patients or healthy volunteers. The WHO also started the International Clinical Trials Registry Platform (ICTRP), aimed at standardizing the way information of studies is made available to the public. The following registers contribute data directly to the Who Search Portal: Australian Clinical Trials Registry,, and International Standard Randomized Controlled Trial Number Register. In May 15, 2007, the Latin American and Caribbean Center on Health Sciences Information (BIREME) published a recommendation for editors of health journals indexed in Latin American and Caribbean Literature on Health Sciences (LILACS) and Scientific Library Electronic Online (ScieLO) about registration of clinical trials. In addition to the UMIN Clinical Trial Registry and the Nederlands Trial Register, the ICMJE is now accepting registration in any of the primary registers that participate in the WHO ICTRP. The ICMJE is also adopting the WHO's definition of clinical trial. Three years ago, trials registration was the exception; now it is the rule. Registration facilitates the dissemination of information, and it helps to assure trial participants that the information that accrues as a result of their altruism will become part of the public record.

Carlos Alberto, Guimarães.



Clinical Trials for Supportive and Palliative Care (United States)

Clinical trials for supportive and palliative care explore ways to improve the comfort and quality of life of cancer patients and cancer survivors. These trials study ways to help people who are experiencing symptoms related to cancer and its treatment, such as nausea, pain, weight loss, sleep disorders, and depression. Some of these trials also look at nutrition, group therapy, and other interventions to help cancer patients and survivors.


Experience from clinical trials in cancer prevention. (United States)

Conduct of randomized, controlled, large-scale prevention trials is fundamental to the full assessment of the efficacy of interventions to prevent cancer. Clinical trials in cancer prevention, which include dietary modification and chemoprevention, are based on leads from epidemiological and laboratory studies. Dietary intervention trials involve the modification of overall eating patterns, whereas chemoprevention trials involve the administration of natural or synthetic substances reported to have anticarcinogenic properties, e.g. vitamins, minerals, and pharmaceuticals. Clinical/metabolic studies can help advance knowledge of the role of diet in the etiology and prevention of cancer by investigating the metabolism of factors thought to influence cancer risk; thus, these studies have the potential to provide a stronger scientific base for progression to randomized, controlled clinical trials. Cancer prevention trials supported by the National Cancer Institute include the Polyp Prevention Trial, which is testing a low-fat, high-fibre, and vegetable- and fruit-enriched eating pattern on the prevention of polyp recurrence, and the Nutrition Intervention Trials of Oesophageal Cancer in Linxian, China, which are testing the efficacy of vitamin-mineral supplements in the prevention of oesophageal cancer in high-risk populations. Results from clinical cancer prevention trials will enable investigators to establish more firmly the relationships between diet and cancer and to translate the information effectively into significant reductions in cancer incidence and mortality. PMID:8166993

Greenwald, P



Generalisability of results from randomised drug trials. A trial on antimanic treatment  

DEFF Research Database (Denmark)

Exemplified by a randomised trial on antimanic treatment, this paper addresses the question of whether selection of patients for drug trials may limit the applicability of study results from the randomised patients to a wider population.

Licht, R W; Gouliaev, G



Pragmatic trials can be designed as optimal medical care: principles and methods of care trials.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

OBJECTIVES: The way clinical research and care are currently separated encourages the practice of unverifiable medicine. Some pragmatic trials can be designed (1) to guide proper medical conduct in the presence of uncertainty and (2) to govern the distinction between unvalidated and validated care. METHODS: Care trials are simple randomized trials integrated into a practice they regulate in the interest of present patients. The fundamental principle guiding the design of a care trial is the p...

Raymond, J.; Darsaut, Te; Altman, Dg



Can we rely on the best trial? A comparison of individual trials and systematic reviews  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background The ideal evidence to answer a question about the effectiveness of treatment is a systematic review. However, for many clinical questions a systematic review will not be available, or may not be up to date. One option could be to use the evidence from an individual trial to answer the question? Methods We assessed how often (a the estimated effect and (b the p-value in the most precise single trial in a meta-analysis agreed with the whole meta-analysis. For a random sample of 200 completed Cochrane Reviews (January, 2005 we identified a primary outcome and extracted: the number of trials, the statistical weight of the most precise trial, the estimate and confidence interval for both the highest weighted trial and the meta-analysis overall. We calculated the p-value for the most precise trial and meta-analysis. Results Of 200 reviews, only 132 provided a meta-analysis of 2 or more trials, with a further 35 effect estimates based on single trials. The average number of trials was 7.3, with the most precise trial contributing, on average, 51% of the statistical weight to the summary estimate from the whole meta-analysis. The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated (rank correlation of 0.90. There was an 81% agreement in statistical conclusions. Results from the most precise trial were statistically significant in 60 of the 167 evaluable reviews, with 55 of the corresponding systematic reviews also being statistically significant. The five discrepant results were not strikingly different with respect to their estimates of effect, but showed considerable statistical heterogeneity between trials in these meta-analyses. However, among the 101 cases in which the most precise trial was not statistically significant, the corresponding meta-analyses yielded 31 statistically significant results. Conclusions Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed, and statistically significant results are generally in agreement. However, "negative" results were less reliable, as may be expected from single underpowered trials. For systematic reviewers we suggest that: (1 key trial(s in a review deserve greater attention (2 systematic reviewers should check agreement of the most precise trial and the meta analysis. For clinicians using trials we suggest that when a meta-analysis is not available, a focus on the most precise trial is reasonable provided it is adequately powered.

Shepperd Sasha



Safety Monitoring in Clinical Trials  

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Full Text Available Monitoring patient safety during clinical trials is a critical component throughout the drug development life-cycle. Pharmaceutical sponsors must work proactively and collaboratively with all stakeholders to ensure a systematic approach to safety monitoring. The regulatory landscape has evolved with increased requirements for risk management plans, risk evaluation and minimization strategies. As the industry transitions from passive to active safety surveillance activities, there will be greater demand for more comprehensive and innovative approaches that apply quantitative methods to accumulating data from all sources, ranging from the discovery and preclinical through clinical and post-approval stages. Statistical methods, especially those based on the Bayesian framework, are important tools to help provide objectivity and rigor to the safety monitoring process.

H. Amy Xia



The Eichmann Trial on East German Television  

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Full Text Available The trial against Adolf Eichmann was one of the first transnational media events on television. Its world-wide coverage required transnational cooperation. Using East German television reports about the trial this article argues that although the event transcended national borders it maintained at the same time ideological boundaries.

Judith Keilbach



Carotene and Retinol Efficacy Trial (CARET) (United States)

The Carotene and Retinol Efficacy Trial (CARET) was a randomized, double-blind, placebo-controlled trial of the cancer prevention efficacy and safety of a daily combination of 30 milligrams (mg) of beta-carotene and 25,000 IU of retinyl palmitate in 18,314 persons who were at high risk for lung cancer.


Planning Clinical Trials and Navigating Regulatory Requirements (United States)

National and regional regulatory authorities have heightened the level of oversight and regulation required for clinical trials in recent years. So, when trials are conducted in more than one country, the differing regulations can be complicated and difficult to navigate. This checklist explains the requirements for collaborating with U.S.-based groups.


Comments: Statistical Analysis for Multisite Trials (United States)

In this article, the author shares his comments on statistical analysis for multisite trials, and focuses on the contribution of Stephen Raudenbush, Sean Reardon, and Takako Nomi to future research. Raudenbush, Reardon, and Nomi provide a major contribution to future research on variation in program impacts by showing how to use multisite trials

Bloom, Howard S.



The Mycotic Ulcer Treatment Trial (United States)

Objective To compare topical natamycin vs voriconazole in the treatment of filamentous fungal keratitis. Methods This phase 3, double-masked, multicenter trial was designed to randomize 368 patients to voriconazole (1%) or natamycin (5%), applied topically every hour while awake until reepithelialization, then 4 times daily for at least 3 weeks. Eligibility included smear-positive filamentous fungal ulcer and visual acuity of 20/40 to 20/400. Main Outcome Measures The primary outcome was best spectacle-corrected visual acuity at 3 months; secondary outcomes included corneal perforation and/or therapeutic penetrating keratoplasty. Results A total of 940 patients were screened and 323 were enrolled. Causative organisms included Fusarium (128 patients [40%]), Aspergillus (54 patients [17%]), and other filamentous fungi (141 patients [43%]). Natamycin-treated cases had significantly better 3-month best spectacle-corrected visual acuity than voriconazole-treated cases (regression coefficient=?0.18 logMAR; 95% CI, ?0.30 to ?0.05; P=.006). Natamycin-treated cases were less likely to have perforation or require therapeutic penetrating keratoplasty (odds ratio=0.42; 95% CI, 0.22 to 0.80; P=.009). Fusarium cases fared better with natamycin than with voriconazole (regression coefficient=?0.41 logMAR; 95% CI, ?0.61 to ?0.20; PNatamycin treatment was associated with significantly better clinical and microbiological outcomes than voriconazole treatment for smear-positive filamentous fungal keratitis, with much of the difference attributable to improved results in Fusarium cases. Application to Clinical Practice Voriconazole should not be used as monotherapy in filamentous keratitis. Trial Registration Identifier: NCT00996736 PMID:23710492

Prajna, N. Venkatesh; Krishnan, Tiruvengada; Mascarenhas, Jeena; Rajaraman, Revathi; Prajna, Lalitha; Srinivasan, Muthiah; Raghavan, Anita; Oldenburg, Catherine E.; Ray, Kathryn J.; Zegans, Michael E.; McLeod, Stephen D.; Porco, Travis C.; Acharya, Nisha R.; Lietman, Thomas M.



Single-Trial Inference on Visual Attention  

DEFF Research Database (Denmark)

In this paper we take a step towards single-trial behavioral modeling within a Theory of Visual Attention (TVA). In selective attention tasks, such as the Partial Report paradigm, the subject is asked to ignore distractors and only report stimuli that belong to the target class. Nothing about a distractor is observed directly in the subject’s overt behavior, hence behavioral modeling of such trials involves out-marginalizing the variables that represent the distractors’ influence on behavior. In this paper we derive equations for inferring a latent representation of the distractors on a Partial Report trial. This result retrodicts a latent attentional state of the subject using the observed response from that particular trial and thus differs from other predictions made with TVA which are based on expected values of observed variables. We show an example of the result in single-trial analysis of an occipital EEG component.

Dyrholm, Mads; Kyllingsbæk, SØren



Marketing and clinical trials: a case study  

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Full Text Available Abstract Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

Entwistle Vikki A



Ethics of clinical trials in Nigeria. (United States)

The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247

Okonta, Patrick I



Inadequate Dissemination of Phase I Trials: A Retrospective Cohort Study  

Digital Repository Infrastructure Vision for European Research (DRIVER)

François Chapuis and colleagues examine a cohort of clinical trial protocols approved by French ethics committees, and show that Phase I trials are less frequently published than other types of trials.

Decullier, Evelyne; Chan, An-wen; Chapuis, Franc?ois



Randomized Phase II Cancer Clinical Trials (United States)

SUMMARY Traditionally, phase II trials have been conducted as single-arm trials to compare the response probabilities between an experimental therapy and a historical control. Historical control data, however, often have a small sample size, are collected from a different patient population, or use a different response assessment method, so that a direct comparison between a historical control and an experimental therapy may be severely biased. Randomized phase II trials entering patients prospectively to both experimental and control arms have been proposed to avoid any bias in such cases. The small sample sizes for typical phase II clinical trials imply that the use of exact statistical methods for their design and analysis is appropriate. In this paper, we propose two-stage randomized phase II trials based on Fisher’s exact test which does not require specification of the response probability of the control arm for testing. Through numerical studies, we observe that the proposed method controls the type I error accurately and maintains a high power. If we specify the response probabilities of the two arms under the alternative hypothesis, we can identify good randomized phase II trial designs by adopting the Simon’s minimax and optimal design concepts that were developed for single-arm phase II trials. PMID:24697589

Jung, Sin-Ho; Sargent, Daniel J.



Biomarkers for Alzheimer's disease therapeutic trials. (United States)

The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuropathology, including amyloidogenic processing and aggregation, hyperphosphorylation, accumulation of tau and neurofibrillary tangles, progressive functional, metabolic and structural decline, leading to neurodegeneration, loss of brain tissue and cognitive symptoms. Biomarkers should be used throughout clinical trial phases I-III of AD drug development. They can be used to enhance inclusion and exclusion criteria, or as baseline predictors to increase the statistical power of trials. Validated and qualified biomarkers may be used as outcome measures to detect treatment effects in pivotal clinical trials. Finally, biomarkers can be used to identify adverse effects. Questions regarding which biomarkers should be used in clinical trials, and how, are currently far from resolved. The Oxford Task Force continues and expands the work of our previous international expert task forces on disease-modifying trials and on endpoints for Alzheimer's disease clinical trials. The aim of this initiative was to bring together a selected number of key international opinion leaders and experts from academia, regulatory agencies and industry to condense the current knowledge and state of the art regarding the best use of biological markers in Alzheimer's disease therapy trials and to propose practical recommendations for the planning of future AD trials. PMID:21130138

Hampel, Harald; Wilcock, Gordon; Andrieu, Sandrine; Aisen, Paul; Blennow, Kaj; Broich, K; Carrillo, Maria; Fox, Nick C; Frisoni, Giovanni B; Isaac, Maria; Lovestone, Simon; Nordberg, Agneta; Prvulovic, David; Sampaio, Christina; Scheltens, Philip; Weiner, Michael; Winblad, Bengt; Coley, Nicola; Vellas, Bruno



Provenance trials of larch in Siberia  

Energy Technology Data Exchange (ETDEWEB)

Some results of provenance trials of larch in Siberia are given. These provenance trials were established in the last thirty years by efforts of V.N. Sukaczev Inst. of Forest. Provenances and species of larch were tested in some field trials distributed over Siberia between Lat. N 52 deg and 66 deg, Long. E 88 deg and 113 deg: near Krasnoyarsk, in Republic Khakasia (an altitudes of 800 and 1200 metres), in the Lower Yenisei near Turukhansk, in the west and south regions of Krasnoyarsk territory, in the Upper Lena, near Chita. 2 refs

Milyutin, L.I. [V.N. Sukachev Inst. of Forest SB RAS, Krasnoyarsk (Russian Federation)



Potential bias in ophthalmic pharmaceutical clinical trials  

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Full Text Available Paul VarnerJohn J Pershing Veterans’ Administration Medical Center, Poplar Bluff, Missouri, USAAbstract: To make clinicians aware of potential sources of error in ophthalmic pharmaceutical clinical trials that can lead to erroneous interpretation of results, a critical review of the study design of various pharmaceutical ophthalmic clinical trials was completed. Discrepancies as a result of study shortcomings may explain observed differences between reported ophthalmic trial data and observed clinical results.Keywords: evidence-based medicine, validity, bias, gold standard

Paul Varner



Genomic sequencing in clinical trials  

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Full Text Available Abstract Human genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 human chromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing is rapidly becoming a major part of our translational research efforts to understand and improve human health and disease. This article reviews the current and future directions of clinical research with respect to genomic sequencing, a technology that is just beginning to find its way into clinical trials both nationally and worldwide. We highlight the currently available types of genomic sequencing platforms, outline the advantages and disadvantages of each, and compare first- and next-generation techniques with respect to capabilities, quality, and cost. We describe the current geographical distributions and types of disease conditions in which these technologies are used, and how next-generation sequencing is strategically being incorporated into new and existing studies. Lastly, recent major breakthroughs and the ongoing challenges of using genomic sequencing in clinical research are discussed.

Mestan Karen K



Field trials at Bikini Atoll  

International Nuclear Information System (INIS)

Last year's report summarized the status of both the long on-going soil and plant sampling programs (initiated by LLNL in 1978) and the field experiments aimed at reducing radionuclide levels in food plants to acceptable levels. In the current report the two are combined into a single summary table, indicating for each field trial or survey the results to date, information expected by the spring of 1988, and projection, if any, for continuation beyond FY1988. This table is therefore a comprehensive survey of the program and accordingly the individual items in it have been coded to facilitate reference to them. Analytical results from field studies installed in 1985 and 1986 are now providing much new information, briefly described below. In part, these results bear out or enlarge the hypotheses that prompted the studies. They also suggest how some treatments may be modified or combined for greater effectiveness. We shall discuss here certain groups of studies of immediate interest that deal with the blocking effects of potassium and other ions on cesium-137 uptake by plants, the effect of removing topsoil (excavation), cultural studies which involve the manipulation of the subsoil, plus some others


A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial  

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Full Text Available Abstract Background Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. Methods A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days. II A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included. Conclusion A clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach. Trial registration Trial registration number: NCT01111253

Fockens Paul



Efficacy, effectiveness, and behavior change trials in exercise research  

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Full Text Available Abstract Background The widespread incorporation of behavioral support interventions into exercise trials has sometimes caused confusion concerning the primary purpose of a trial. The purpose of the present paper is to offer some conceptual and methodological distinctions among three types of exercise trials with a view towards improving their design, conduct, reporting, and interpretation. Discussion Exercise trials can be divided into "health outcome trials" or "behavior change trials" based on their primary outcome. Health outcome trials can be further divided into efficacy and effectiveness trials based on their potential for dissemination into practice. Exercise efficacy trials may achieve high levels of exercise adherence by supervising the exercise over a short intervention period ("traditional" exercise efficacy trials or by the adoption of an extensive behavioral support intervention designed to accommodate unsupervised exercise and/or an extended intervention period ("contemporary" exercise efficacy trials. Exercise effectiveness trials may emanate from the desire to test exercise interventions with proven efficacy ("traditional" exercise effectiveness trials or the desire to test behavioral support interventions with proven feasibility ("contemporary" exercise effectiveness trials. Efficacy, effectiveness, and behavior change trials often differ in terms of their primary and secondary outcomes, theoretical models adopted, selection of participants, nature of the exercise and comparison interventions, nature of the behavioral support intervention, sample size calculation, and interpretation of trial results. Summary Exercise researchers are encouraged to clarify the primary purpose of their trial to facilitate its design, conduct, and interpretation.

Courneya Kerry S



Stimulation of the autonomic nervous system in colorectal surgery: a study protocol for a randomized controlled trial  

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Full Text Available Abstract Background Postoperative ileus (POI is a well-known complication of abdominal surgery and is considered to be caused by a local inflammation in the gut. Previously it has been shown that both local and systemic inflammation can be reduced by stimulation of the autonomic nervous system via lipid rich nutrition. Stimulation of the autonomic nervous system releases acetylcholine from efferent vagal nerve endings that binds to nicotinic receptors located on the inflammatory cells leading to a decrease of pro-inflammatory mediators. Besides administration of nutrition there are other ways of stimulating the autonomic nervous system such as gum chewing. Methods/design This prospective, placebo-controlled randomized trial will include 120 patients undergoing colorectal surgery which are randomized for gum chewing preoperatively and in the direct postoperative phase or a placebo. Postoperative ileus will be assessed both clinically by time to first flatus and time to first defecation and by determination of gastric motility using ultrasound to measure dimensions of the antrum. Furthermore the inflammatory response is quantified by analyzing pro-inflammatory mediators. Finally, markers of gut barrier integrity will be measured as well as occurrence of postoperative complications. Discussion We hypothesize that chewing gum preoperatively and in the direct postoperative phase in patients undergoing colorectal surgery dampens local and systematic inflammation, via activation of the autonomic nervous system. Down-regulation of the inflammatory cascade via stimulation of the vagus nerve will ameleriote POI and enhance postoperative recovery. Trial registration NTR2867

Berghmans Tim MP



Preventive effect of Korean red ginseng for acute respiratory illness: a randomized and double-blind clinical trial. (United States)

Korean Red Ginseng (KRG) is a functional food and has been well known for keeping good health due to its anti-fatigue and immunomodulating activities. However, there is no data on Korean red ginseng for its preventive activity against acute respiratory illness (ARI). The study was conducted in a randomized, double-blinded, placebo-controlled trial in healthy volunteers (Clinical Trial Number: NCT01478009). Our primary efficacy end point was the number of ARI reported and secondary efficacy end point was severity of symptoms, number of symptoms, and duration of ARI. A total of 100 volunteers were enrolled in the study. Fewer subjects in the KRG group reported contracting at least 1 ARI than in the placebo group (12 [24.5%] vs 22 [44.9%], P = 0.034), the difference was statistically significant between the two groups. The symptom duration of the subjects who experienced the ARI, was similar between the two groups (KRG vs placebo; 5.2 ± 2.3 vs 6.3 ± 5.0, P = 0.475). The symptom scores were low tendency in KRG group (KRG vs placebo; 9.5 ± 4.5 vs 17.6 ± 23.1, P = 0.241). The study suggests that KRG may be effective in protecting subjects from contracting ARI, and may have the tendency to decrease the duration and scores of ARI symptoms. PMID:23255845

Lee, Chang-Seop; Lee, Ju-Hyung; Oh, Mira; Choi, Kyung-Min; Jeong, Mi Ran; Park, Jong-Dae; Kwon, Dae Young; Ha, Ki-Chan; Park, Eun-Ock; Lee, Nuri; Kim, Sun-Young; Choi, Eun-Kyung; Kim, Min-Gul; Chae, Soo-Wan



Single-trial normalization for event-related spectral decomposition reduces sensitivity to noisy trials  

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These spectral methods do not have strong consensus for comparing pre and post-stimulus activity. When computing ERSP, pre-stimulus baseline removal is usually performed after averaging the spectral estimate of multiple trials. Correcting the baseline of each single-trial prior to averaging spectral estimates is an alternative baseline correction method. However, we show that this method leads to positively skewed post-stimulus ERSP values. We eventually present new single-trial based ERSP baseline correction methods that perform trial normalization or centering prior to applying classical baseline correction methods. We show that single-trial correction methods minimize the contribution of artifactual data trials with high-amplitude spectral estimates and are robust to outliers when performing statistical inference testing. We then characterize these methods in terms of their time-frequency responses and behavior when performing statistical inference testing compared to classical ERSP methods.




Population activity changes during a trial-to-trial adaptation of bullfrog retinal ganglion cells. (United States)

A 'trial-to-trial adaptation' of bullfrog retinal ganglion cells in response to a repetitive light stimulus was investigated in the present study. Using the multielectrode recording technique, we studied the trial-to-trial adaptive properties of ganglion cells and explored the activity of population neurons during this adaptation process. It was found that the ganglion cells adapted with different degrees: their firing rates were decreased in different extents from early-adaptation to late-adaptation stage, and this was accompanied by a decrease in cross-correlation strength. In addition, adaptation behavior was different for ON-response and OFF-response, which implied that the mechanism of the trial-to-trial adaptation might involve bipolar cells and/or their synapses with other neurons and the stronger adaptation in the ganglion cells' OFF-responses might reflect the requirement to avoid possible saturation in the OFF circuit. PMID:24848616

Ding, Wei; Xiao, Lei; Jing, Wei; Zhang, Pu-Ming; Liang, Pei-Ji



Characterisation of lung tumour under dosage for interpretation of clinical trial data  

International Nuclear Information System (INIS)

Full text: It is well known that the periphery of lung tumours is under-dosed in radiotherapy as a result of electronic disequilibrium at the interface of lung and tumour tissue. Clinical trials often employ dose calculation algorithms which poorly approximate the dose to peripheral regions of tumour volumes. The aim of this study was to develop a set of systematic under-dosage estimates corresponding to various clinical parameters. High resolution Monte Carlo radiation transport calculations were undertaken for a systematic set of generic lung tumours irradiated with an external photon beam. Varied parameters include beam energy, field size, tumour size and distance to chest wall. Calculations were undertaken using both EGSnrc and GEAI T4. A 'Dose Reduction Factor' is defined which describes the dose to the peripheral 'shell' 01 the tumour, as relevant for multiple-field and arc therapy. For a 6 MV beam, under-dosage is typically between 2 and 5% for the different arrangements investigated, and for a 15 MV beam it is between 5 and 8% (relative to the central dose). Good agreement between EGSnrc and GEANT4 was demonstrated. Comparisons with pencil beam convolution calculations indicate that the treatment planning system does not identify this under-dosage. A systematic set of data has been obtained that characterises the extent of peripheral under-dosage in lung tumours for the retrospective evaluation of clinical trial data. The data presented i: also informative for clinics using less sophisticated planning algorithms, particularly when dose is being prescribed to covering isodoses. (author)



The Treatment of Lead-exposed Children (TLC) clinical trial compared the effect of lead chelation with succimer to placebo therapy. Outcomes included IQ, neuropsychological function, behavior, physical growth and blood pressure three years after initiation of treatment. Residenti...


Children's Assent to Clinical Trial Participation (United States)

... this way, they can make a fully informed decision about whether or not to give "informed permission" for their child's participation in the clinical trial. Tip for Parents and Guardians -- Informed Consent: Be sure to check ...


Oltipraz chemoprevention trial in Qidong, People's Republic of China: unaltered oxidative biomarkers. (United States)

Aflatoxin, which leads to formation of carcinogen-DNA adducts as well as oxidized DNA, is a well-known risk factor for development of hepatocellular carcinoma. The aim of the present study was to investigate if the chemopreventive agent oltipraz had an effect on DNA oxidation measured as oxidized guanine derivatives in urine among healthy individuals living in a region of China at high risk of exposure to aflatoxin and development of hepatocellular carcinoma. Two hundred thirty-three healthy residents of Qidong, PRC, were randomized to 8 weeks treatment with placebo, oltipraz 125 mg daily, or oltipraz 500 mg weekly, with a subsequent 8-week follow-up period. Urine samples were collected as overnight voids. Samples collected 4 weeks into the treatment period and 6 weeks into the follow-up period were analyzed for oxidized guanine derivatives with a HPLC-MS/MS method. A repeated-measures analysis of variance showed no significant differences between the randomization groups regarding changes in oxidized guanine derivatives. In the present double-blind, randomized, placebo-controlled trial performed among healthy individuals, oltipraz had no major effect on oxidative DNA damage. Mechanisms other than prevention of oxidative DNA damage may be of higher importance when oltipraz is used as a chemopreventive agent in humans. PMID:16934685

Glintborg, Bente; Weimann, Allan; Kensler, Thomas W; Poulsen, Henrik E



On Some Aspects of Conditional Power Evaluation In Two-phase Clinical Trials Under Linear Regression  

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Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman","serif";} We investigate the conditional power under the framework of linear regression models so that it can be applied to most actual clinical trials in which multiple treatment effects and covariate effects are included. It is well known that the standard power of a regular test for a treatment contrast depends on unknown parameters only through the contrast itself. However it is not true in general for conditional power. Conditions for this to happen are established here and some instances are illustrated. We also show that similar arguments can be made about the sufficient statistics for the conditional power.

A. S. Hedayat



Clinical trials in systemic lupus erythematosus: a status report on ongoing trials. (United States)

To describe the characteristics of trials in systemic lupus erythematous (SLE) listed in such as study design, funding sources and aspects of the disease and drugs under investigation. We conducted a survey of ongoing clinical trials that were registered in the website. We used the advanced search option and applied the following inclusion criteria, "SLE," "open studies," "interventional," and "adults 18 years or older." Of 97 eligible studies, 34.0 % were phase 3 or 4, 49.5 % were phase 1, 2 or 2/3 and in 16.5 %, we could not determine the study phase. Most trials were randomized (69.0 %) and 48.4 % were double blinded; 34 % of the trials were placebo controlled, 19.6 % had an active agent comparator and 46.4 % had no comparator. Universities and pharmaceutical industries were the primary sponsors for 45.3 and 39.1 % of the trials, respectively, and government agencies for 10.3 %. Multi-center trials based in the USA (US) accounted for 40.2 % of the trials, 46.4 % were outside of the US and 13.4 % were in the US as well as other countries. The most frequently used endpoint was drug efficacy (30.9 %) followed by disease severity indices (25.7 %), drug safety (14.4 %), remission rates and times to remission (7.2 %), and inflammatory markers and antibody titers (7.2 %). The majority of ongoing clinical trials in SLE are university or industry-funded, randomized phase 1, 2, or 2/3 trials, focused on drug efficacy. Federal funding for trials in SLE within and outside the US remains low. PMID:24752544

Gumber, Divya; Paul, Jisna; Ranganathan, Prabha



Phase 1 trials in pancreatic cancer. (United States)

Despite many clinical trials over the last two decades since the approval of gemcitabine, the survival of patients with pancreatic cancer has improved by a few only months. This disappointing reality underlines an urgent need to develop more effective drugs or better combinations. A variety of phase I trials were presented at the annual meeting of ASCO 2014 focusing on locally advanced and metastatic pancreatic cancer. We summarize four abstracts (abstracts #4116, #4123, #4026, #4138). PMID:25076334

Yu, Esther; Saif, Muhammad Wasif; Huber, Kathryn



Psoriatic arthritis assessment tools in clinical trials  

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In order to measure disease activity, progression, and change with therapy in psoriatic arthritis (PsA), it is important to use accurate, reliable, and feasible outcome measures that can ideally be employed in longitudinal cohorts, clinical trials, and clinical practice. Until recently, there has been little focus on this methodology in PsA. Clinical trials and long term clinical registries have used disparate outcome measures. With emerging therapies, the focus on the methodology of outcome ...

Mease, P.; Antoni, C.; Gladman, D.; Taylor, W.



Bayesian sequential analysis of clinical trials feedback  

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Full Text Available The paper deals with the Bayesian sequential analysis of clinical trials and the related predictive approach in a particularly innovative fashion. We propose a unified methodology for sequential clinical trials under a Bayesian paradigm. The idea is to make predictive inference based on the data accrued so far together with future data. We apply a prevision based approach to Gaussian data and end up with some numerical illustrations.

Hayet Merabet



Controlled trial of psychotherapy for bulimia nervosa  

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In a randomised controlled trial of different types of psychotherapy for bulimia 92 women were assigned to receive cognitive-behaviour therapy (n=32), behaviour therapy (30), or group therapy (30) for 15 weeks and a further 20 (controls) assigned to remain on a waiting list for 15 weeks. Eating behaviour and psychopathology were assessed by standard methods. At the end of the trial the controls had significantly higher scores than the treated groups on all measures of bulimic behaviour. In te...

Freeman, C. P. L.; Barry, F.; Dunkeld-turnbull, J.; Henderson, A.



Trials within trials? Researcher, funder and ethical perspectives on the practicality and acceptability of nesting trials of recruitment methods in existing primary care trials  

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Full Text Available Abstract Background Trials frequently encounter difficulties in recruitment, but evidence on effective recruitment methods in primary care is sparse. A robust test of recruitment methods involves comparing alternative methods using a randomized trial, 'nested' in an ongoing 'host' trial. There are potential scientific, logistical and ethical obstacles to such studies. Methods Telephone interviews were undertaken with four groups of stakeholders (funders, principal investigators, trial managers and ethics committee chairs to explore their views on the practicality and acceptability of undertaking nested trials of recruitment methods. These semi-structured interviews were transcribed and analysed thematically. Results Twenty people were interviewed. Respondents were familiar with recruitment difficulties in primary care and recognised the case for 'nested' studies to build an evidence base on effective recruitment strategies. However, enthusiasm for this global aim was tempered by the challenges of implementation. Challenges for host studies included increasing complexity and management burden; compatibility between the host and nested study; and the impact of the nested study on trial design and relationships with collaborators. For nested recruitment studies, there were concerns that host study investigators might have strong preferences, limiting the nested study investigators' control over their research, and also concerns about sample size which might limit statistical power. Nested studies needed to be compatible with the main trial and should be planned from the outset. Good communication and adequate resources were seen as important. Conclusions Although research on recruitment was welcomed in principle, the issue of which study had control of key decisions emerged as critical. To address this concern, it appeared important to align the interests of both host and nested studies and to reduce the burden of hosting a recruitment trial. These findings should prove useful in devising a programme of research involving nested studies of recruitment interventions.

Delaney Brendan



Quality of clinical trials: A moving target  

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Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common defic...

Bhatt, Arun



Consumers’ Trial Buying Process of Service Innovation.  

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The aim of this thesis was to investigate and give a deeper understanding of consumers’ trial buying process of a service innovation in an online environment. More specifically, this thesis tries to clarify the connection between consumers’ adoption decisions, external influences and the service experience of an innovation in an online environment. A trial buying process was studied in order to increase the case company HOK-Elanto’s knowledge of how their customers make adoption decisio...

Peltonen, Laura



Better therapeutic trials in ovarian cancer. (United States)

The Ovarian Task Force of the Gynecologic Cancer Steering Committee convened a clinical trials planning meeting on October 28-29, 2011, with the goals to identify key tumor types, associated molecular pathways, and biomarkers for targeted drug intervention; review strategies to improve early-phase screening, therapeutic evaluation, and comparison of new agents; and optimize design of randomized trials in response to an evolving landscape of scientific, regulatory, and funding priorities. The meeting was attended by international clinical and translational investigators, pharmaceutical industry representatives, government regulators, and patient advocates. Panel discussions focused on disease types, early-phase trials, and randomized trials. A manuscript team summarized the discussions and assisted with formulating key recommendations. A more integrated and efficient approach for screening new agents using smaller selective randomized trials in specific disease-type settings was endorsed, together with collaborative funding models between industry and the evolving national clinical trials network, as well as efforts to enhance public awareness and study enrollment through advocacy. PMID:24627272

Bookman, Michael A; Gilks, C Blake; Kohn, Elise C; Kaplan, Karen O; Huntsman, David; Aghajanian, Carol; Birrer, Michael J; Ledermann, Jonathan A; Oza, Amit M; Swenerton, Kenneth D



Clinical trials design: protocols and endpoints. (United States)

Over the last decade there has been a proliferation in clinical trials to test agents for the treatment of erectile dysfunction (ED). Many aspects of clinical trials design and conduct and guidelines for future conduct have been the subject of a recent comprehensive review (Rosen R et al. In: Proceedings of the 1st International Consultation on Erectile Dysfunction 1999). The present article attempts to extend that analysis from trials that focus purely on symptomatic improvement of ED to trials relevant to the management of the ED patient in the community. Although the regulatory approval process accounts for the bulk of the clinical trials undertaken, studies are also initiated for concept testing, post-marketing surveillance and for promotional and/or pricing reasons. The trial design can be dependent on which of the above objectives is being served. However, there are also many common features that are summarized below; the major focus is placed on regulatory-standard or 'pivotal' studies. International Journal of Impotence Research (2000) 12, Suppl 4, S53-S58. PMID:11035387

Wyllie, M G



Clinical trial networks in orthopaedic surgery (United States)

The aim of this study was to review the role of clinical trial networks in orthopaedic surgery. A total of two electronic databases (MEDLINE and EMBASE) were searched from inception to September 2013 with no language restrictions. Articles related to randomised controlled trials (RCTs), research networks and orthopaedic research, were identified and reviewed. The usefulness of trainee-led research collaborations is reported and our knowledge of current clinical trial infrastructure further supplements the review. Searching yielded 818 titles and abstracts, of which 12 were suitable for this review. Results are summarised and presented narratively under the following headings: 1) identifying clinically relevant research questions; 2) education and training; 3) conduct of multicentre RCTs and 4) dissemination and adoption of trial results. This review confirms growing international awareness of the important role research networks play in supporting trials in orthopaedic surgery. Multidisciplinary collaboration and adequate investment in trial infrastructure are crucial for successful delivery of RCTs. Cite this article: Bone Joint Res 2014;3:169–74. PMID:24869466

Rangan, A.; Jefferson, L.; Baker, P.; Cook, L.



Placebo response and antidepressant clinical trial outcome. (United States)

Placebo response magnitude is suspected to affect the outcome of antidepressant clinical trials. To evaluate this, 52 randomized, double-blind, placebo-controlled clinical trials obtained from the FDA were examined to correlate placebo response magnitude with trial outcome. The magnitude of symptom reduction, percentage mean change from baseline in the Hamilton Depression Rating Scale (HAM-D), was assessed for patients assigned to placebo or an antidepressant. Correlation coefficients between symptom reduction with placebo and antidepressants and between symptom reduction with placebo and magnitude of advantage of antidepressants over placebo were assessed. A statistically significant positive correlation was seen between placebo and antidepressant response magnitude (r =.40, p 30% mean change from baseline) showed statistical superiority over placebo compared with 74.2% in trials with a low placebo response (< or =30). Response magnitude varies and has an important effect on antidepressant clinical trials, illustrating the need for a placebo arm to determine if the trial was sensitive to treatment differences and highlighting the dangers of cross-study comparisons. PMID:12695731

Khan, Arif; Detke, Michael; Khan, Shirin R F; Mallinckrodt, Craig



Implementation of the NCI’s National Clinical Trials Network (United States)

NCI is launching a new clinical trials research network intended to improve treatment for the more than 1.6 million Americans diagnosed with cancer each year. The new system, NCI’s National Clinical Trials Network (NCTN), will facilitate the rapid initiation and completion of cancer clinical trials at over 3,000 clinical trials sites.


Talking About Trials: Overcoming Bottlenecks in Clinical Communication (United States)

Participation in clinical trials by adult patients is dismally low. No one knows how many patients are offered the opportunity to enroll in trials. NCI researchers are studying how patients hear about trials, whether they discuss enrollment with their providers, and the roles they play in deciding to participate in a trial.


Internet trials: participant experiences and perspectives  

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Full Text Available Abstract Background Use of the Internet to conduct randomised controlled trials is increasing, and provides potential to increase equity of access to medical research, increase the generalisability of trial results and decrease the costs involved in conducting large scale trials. Several studies have compared response rates, completeness of data, and reliability of surveys using the Internet and traditional methods, but very little is known about participants’ attitudes towards Internet-based randomised trials or their experience of participating in an Internet-based trial. Objective To obtain insights into the experiences and perspectives of participants in an Internet-based randomised controlled trial, their attitudes to the use of the Internet to conduct medical research, and their intentions regarding future participation in Internet research. Methods All English speaking participants in a recently completed Internet randomised controlled trial were invited to participate in an online survey. Results 1246 invitations were emailed. 416 participants completed the survey between May and October 2009 (33% response rate. Reasons given for participating in the Internet RCT fell into 4 main areas: personal interest in the research question and outcome, ease of participation, an appreciation of the importance of research and altruistic reasons. Participants’ comments and reflections on their experience of participating in a fully online trial were positive and less than half of participants would have participated in the trial had it been conducted using other means of data collection. However participants identified trade-offs between the benefits and downsides of participating in Internet-based trials. The main trade-off was between flexibility and convenience – a perceived benefit – and a lack connectedness and understanding – a perceived disadvantage. The other tradeoffs were in the areas of: ease or difficulty in use of the Internet; security, privacy and confidentiality issues; perceived benefits and disadvantages for researchers; technical aspects of using the Internet; and the impact of Internet data collection on information quality. Overall, more advantages were noted by participants, consistent with their preference for this mode of research over others. The majority of participants (69% would prefer to participate in Internet-based research compared to other modes of data collection in the future. Conclusion Participants in our survey would prefer to participate in Internet-based trials in the future compared to other ways of conducting trials. From the participants’ perspective, participating in Internet-based trials involves trade-offs. The central trade-off is between flexibility and convenience – a perceived benefit – and lack of connectedness and understanding – a perceived disadvantage. Strategies to maintain the convenience of the Internet while increasing opportunities for participants to feel supported, well-informed and well-understood would seem likely to increase the acceptability of Internet-based trials.

Mathieu Erin



The Illawarra Coordinated Care Trial: better outcomes with existing resources? (United States)

The Illawarra Coordinated Care Trial was one of nine Australian trials undertaken to see whether different models of coordinated care could improve the health of people with multiple service needs within existing resources. This paper summarises the findings of an extensive local evaluation and discusses the impact of the trial on clients and service providers. It examines the main findings related to the principal trial hypothesis and points to lessons that might inform the next round of trials. PMID:11496459

Perkins, D; Owen, A; Cromwell, D; Adamson, L; Eagar, K; Quinsey, K; Green, J



To fail or not to fail : clinical trials in depression  

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To fail or not to fail – Clinical trials in depression investigates the causes of the high failure rate of clinical trials in depression research. Apart from the difficulties in the search for new antidepressants during drug discovery, faulty clinical trial designs hinder their evaluation during drug development. This thesis focuses on three important aspects of clinical trials in depression: clinical endpoints, data analysis and trial design-related factors.

Santen, Gijs Willem Eduard



Recent trials to verify quantum mechanics  

International Nuclear Information System (INIS)

An account of the experiments which deal with the verification of Quantum Mechanics and the hidden variable problem is made. First, the well-known EPR paradox is recalled which, in spite of its refutation by Bohr, was the starting point of the questionning on the completeness of Quantum Mechanics and of hidden variable theories; and then Bell's theorem, which shows that the two approaches, Quantum Mechanics and hidden variables, can be put in contradiction. Thereafter the various types of experiments which have been carried out on that subject, mostly concerning the correlation measurements between two photons emitted by a quantum system are described. The most recent experimental results are diverging, some of them to confirm and some others to contradict quantum mechanics. A review of these is given; and a discussion is presented about their possible implications


Factors influencing the participation of older people in clinical trials - data analysis from the MAVIS trial. | (United States)

Older people are less likely to be included in clinical trials. This study explores factors that influence older people’s decisions to participate in randomized clinical trials. The strongest motivator for participation was altruism. Participants valued simple trial designs, which minimize burden on participants, are well organized, and include regular and friendly communication with trial staff. The findings of this survey could be used to plan and design trials in a manner that would maximize recruitment and retention of the elderly.


Ongoing EEG phase as a trial-by-trial predictor of perceptual and attentional variability  

Directory of Open Access Journals (Sweden)

Full Text Available Even in well-controlled laboratory environments, apparently identical repetitions of an experimental trial can give rise to highly variable perceptual outcomes and behavioral responses. This variability is generally discarded as a reflection of intrinsic noise in neuronal systems. However, part of this variability may be accounted for by trial-by-trial fluctuations of the phase of ongoing oscillations at the moment of stimulus presentation. For example, the phase of an EEG oscillation reflecting the rapid waxing and waning of sustained attention can predict the perception of a subsequent visual stimulus at threshold. Similar ongoing periodicities account for a portion of the trial-by-trial variability of visual reaction times. We review the available experimental evidence linking ongoing EEG phase to perceptual and attentional variability, and the corresponding methodology. We propose future tests of this relation, and discuss the theoretical implications for understanding the neuronal dynamics of sensory perception.




Quality of clinical trials: A moving target. (United States)

Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

Bhatt, Arun



Biomarkers in T cell therapy clinical trials  

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Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

Kalos Michael



SPIRIT 2013 Statement : Defining Standard Protocol Items for Clinical Trials  

DEFF Research Database (Denmark)

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Chan, An-Wen; Tetzlaff, Jennifer M



Developments in statistical evaluation of clinical trials  

CERN Document Server

This book describes various ways of approaching and interpreting the data produced by clinical trial studies, with a special emphasis on the essential role that biostatistics plays in clinical trials. Over the past few decades the role of statistics in the evaluation and interpretation of clinical data has become of paramount importance. As a result the standards of clinical study design, conduct and interpretation have undergone substantial improvement. The book includes 18 carefully reviewed chapters on recent developments in clinical trials and their statistical evaluation, with each chapter providing one or more examples involving typical data sets, enabling readers to apply the proposed procedures. The chapters employ a uniform style to enhance comparability between the approaches.

Oud, Johan; Ghidey, Wendimagegn



Problems and alternatives to classical randomized trials  

International Nuclear Information System (INIS)

Randomized clinical trials are regarded as the most credible way of generating scientific data comparing the benefits of different therapies. However, randomized studies present difficulties in their execution. Often physicians are unwilling to participate in such studies because they do not wish to inform the patient that the treatment program will be chosen by a chance mechanism. They feel such a discussion may compromise the physician-patient relationship. In this chapter alternatives to classical randomized trials are discussed, both the advantages and the pitfalls. Also discussed are some aspects of the strategy of clinical experimentation. It is pointed out that the initiation of the definitive Phase III trials made on the basis of little prior expectation of success (''trying something out'') tends to generate false-positive results


Advances in cardiology: clinical trial update. (United States)

Multiple key cardiology trials have been presented or published over recent months, several with the potential to change clinical practice. In this article, we summarize and place in clinical context new trial findings regarding anticoagulation in the cardiac catheterization laboratory (enoxaparin, fondaparinux and unfractionated heparin), the implications of genetic polymorphisms and functional testing for antiplatelet therapy (clopidogrel and ticagrelor), new oral anticoagulants for use in atrial fibrillation (apixiban and rivaroxaban), optimal pacing strategies and pharmacological agents in heart failure (ivabradine, eplerenone, cardiac resynchronization therapy, telemonitoring and intracoronary bone marrow stem cell infusion). Clinical trials in percutaneous structural intervention (transcatheter aortic valve implantation, MONARC™ mitral annular implant, STARFlex(®) patent foramen ovale device) and advanced percutaneous coronary intervention (everolimus-eluting stents, biodegradable polymer/polymer-free technologies and contemporary use of intravascular ultrasound) are also discussed. PMID:21627472

Howe, Andrew J; Shand, James A; Menown, Ian B A



The Hawthorne Effect: a randomised, controlled trial  

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Full Text Available Abstract Background The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia. Methods Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months. Our primary outcomes were cognitive functioning (ADAS-Cog and participant and carer-rated quality of life (QOL-AD. Results We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT, with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group, and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group. There was no significant difference on carer quality of life. Conclusion We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning. Trial registration Current controlled trials: ISRCTN45577048

van Haselen Robbert



Bamboo as Soil Reinforcement: A Laboratory Trial  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A lateritic soil classified as A-6 under AASHTO soil classification system was reinforced with 0, 1, 2 and 3 bamboo specimens at laboratory trial level to evaluate its unconfined compressive strength (UCS) and modulus of rigidity. The soil specimens were molded in cylindrical form of 38mm diameter and 76mm height while the bamboo specimens were trimmed in to circular plates of 34mm diameter and 3mm thickness. The trial soil specimens are: soil specimen without bamboo specimen (0 bamboo), soil...

Mustapha, Alhaji Mohammed



Neuroendocrine cancer vaccines in clinical trials. (United States)

This article focuses on neuroendocrine cancer vaccines that have been evaluated in human clinical trials within the last 5 years. The definition of what constitutes a neuroendocrine tumor requires clarification. Strategies and barriers common to cancer vaccines are highlighted. In general, neuroendocrine cancer is rare; however, special attention will be paid to neuroblastoma and small-cell-lung cancer owing to their relatively higher prevalence. A variety of other neuroendocrine tumor vaccine trials will also be addressed. The common problem of generating only sporadic tumor-specific immune responses that are of low-magnitude will be discussed in detail, with recommendations for future directions. PMID:21692702

Bridle, Byram W



Analysis of the PISC II trials results  

International Nuclear Information System (INIS)

The paper presents the analysis scheme of the Programme for the Inspection of Steel Components PISC II trial results. The objective of the PISC II exercise is to evaluate the effectiveness of current and advanced NDT techniques for inspection of reactor pressure vessel components. The analysis scheme takes data from the Round Robin Trial (RRT) and Destructive Examination, then reduces it to a manageable form in order to present useful conclusions on the effectiveness of NDT. A description is given of the data provided by RRT, the data analysis scheme, the definition of analysis parameters, and the main methods of data presentation. (U.K.)


Photovoltaic domestic field trial. Third annual report  

Energy Technology Data Exchange (ETDEWEB)

An update on a photovoltaics field trial that has been running for four years is presented. The PV Domestic Field Trial was set up to use the design, construction, performance and monitoring of PV units to generate data for utilities, builders and other current and potential users of PVs. Subjects covered were appearance of the systems, architectural integration, fixing methods, cost effectiveness, opinions of users, monitoring and results. During the past 12 months, most of the human effort has gone into collation of data from 22 of the 28 projects. The study was sponsored by Great Britain's DTI.




Randomized Clinical Stroke Trials in 2007  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This article reviews the randomized control trials (RCT’s) that were published in 2007 of emerging pharmacotherapies in patients with acute (? 2 weeks), sub-acute (2 to 12 weeks) and chronic (? 12 weeks) stroke. A Medline search generated 22 RCT’s in stroke in the year 2007 in the English language. These trials were primarily efficacy studies. These included the role of statins (an anti-lipid agent) in reducing post-stroke morbidity and mortality, and decreasing the carotid atheroscle...

Rabadi, Meheroz H.; Blass, John P.



FDA guidance for ABSSSI trials: implications for conducting and interpreting clinical trials. (United States)

Recent guidance from the US Food and Drug Administration (FDA) on the conduct of clinical trials for acute bacterial skin and skin structure infection (ABSSSI) has changed the framework for clinical trial design and conduct. Notable changes included new disease state definitions, new primary endpoint definitions and the timing of assessments at these endpoints, and updated guidance on patient inclusion/exclusion criteria. Supportive evidence and statistical justification for the proposed noninferiority margins were described in detail. Although the updated guidelines are still considered drafts and have been adopted in some trials, they serve as the basis for study protocol discussions between pharmaceutical companies and the FDA in advancing the development of promising new agents. Not only will the new trial designs impact researchers and sponsors responsible for drug development programs, but they will also affect healthcare providers participating in clinical trials and the ways in which clinicians develop patient treatment plans based on the results of those trials. This review provides a summary of key changes that will impact future clinical trial design and outcomes. PMID:24343831

Itani, Kamal M F; Shorr, Andrew F



Trial-to-Trial Reoptimization of Motor Behavior Due to Changes in Task Demands Is Limited (United States)

Each task requires a specific motor behavior that is tuned to task demands. For instance, writing requires a lot of accuracy while clapping does not. It is known that the brain adjusts the motor behavior to different task demands as predicted by optimal control theory. In this study, the mechanism of this reoptimization process is investigated by varying the accuracy demands of a reaching task. In this task, the width of the reaching target (0.5 or 8 cm) was varied either on a trial-to-trial basis (random schedule) or in blocks (blocked schedule). On some trials, the hand of the subjects was clamped to a rectilinear trajectory that ended 2 cm on the left or right of the target center. The rejection of this perturbation largely varied with target width in the blocked schedule but not in the random schedule. That is, subjects exhibited different motor behavior in the different schedules despite identical accuracy demands. Therefore, while reoptimization has been considered immediate and automatic, the differences in motor behavior observed across schedules suggest that the reoptimization of the motor behavior is neither happening on a trial-by-trial basis nor obligatory. The absence of trial-to-trial mechanisms, the inability of the brain to adapt to two conflicting task demands and the existence of a switching cost are discussed as possible sources of the non-optimality of motor behavior during the random schedule. PMID:23776593

de Xivry, Jean-Jacques Orban



Clinical trial registration system and evidence-based medicine  

Directory of Open Access Journals (Sweden)

Full Text Available ABSTRACT: The authors briefly introduced the management of clinical test for new drug development, clinical trials for drugs prepared in hospital and post-market drugs, and other types of clinical trials. The mechanism of WHO International Clinical Trial Register Platform (WHO ICTRP, Chinese Clinical Trial Register (ChiCTR and Chinese Clinical Trial Registration and Publishing Collaboration (ChiCTRPC were also introduced. The authors suggested the trialists to practice the basic philosophy of evidence-based medicine as the rules of their thought and action, and considered that this is the inner guarantee system for the validity of clinical trials.

Tai-xiang WU



EEG activity reveals a trial-by-trial representation of the correctness of decisions  

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Full Text Available Performance monitoring is an executive function, which we depend on for detecting and evaluating the consequences of our behavior. Although event related potentials (ERPs have revealed the existence of differences after correct and incorrect decisions, it is not known whether there is a trial-by-trial representation of the accuracy of the decision. We recorded the electroencephalographic activity (EEG while participants performed a perceptual discrimination task, with two levels of difficulty, in which they received immediate feedback. Receiver Operating Characteristic (ROC analyses were used to reveal two components that convey trial-by-trial representations of the correctness of the decisions. Firstly, the performance monitoring-related negativity (PM-N, a negative deflection whose amplitude is higher (more negative after incorrect trials. Secondly, the performance monitoring-related positivity (PM-P, a positive deflection whose amplitude is higher after incorrect trials. During the time periods corresponding to these components, trials can be accurately categorized as correct or incorrect by looking at the EEG activity; this categorization is more accurate when based on the PM-P. We further show that the difficulty of the discrimination task has a different effect on each component: after easy trials the latency of the PM-N is shorter and the amplitude of the PM-P is higher than after difficult trials. Consistent with previous interpretations of performance-related ERPs, these results suggest a functional differentiation between these components. The PM-N could be related to an automatic error detection system, responsible for fast behavioral corrections of ongoing actions, while the PM-P could reflect the difference between expected and actual outcomes and be related to long-term changes in the decision process.




Trial Marriage: Harnessing the Trend Constructively (United States)

The concept of trial marriage is traced historically and anthropologically. To harness the trend constructively the author recommends that young people who have had a living together experience, evaluate it with a counselor in order to gain insight about their potentialities as mates. (Author)

Berger, Miriam E.



Winding trials for ITER toroidal filed coils  

International Nuclear Information System (INIS)

Cable-in-conduit (CIC) conductors using Nb3Sn strands are used in ITER toroidal fields (TF) coils. The wound TF conductor must be inserted in the groove of the radial plate (RP), which is part of the mechanical structure supporting the large electromagnetic force. Since the available gap between the conductor and RP groove is 0.5 - 3 mm, the tolerance of the circumferences of the winding and RP groove are +/- 0.023%. Since a tolerance of approximately +/-0.01% is needed for the RP machining, the conductor length of the winding must be controlled with an accuracy of +/- 0.01%. In this study, in order to resolve the above technical issues, the authors performed several trials on winding as the part of the activities in Phase II of TF coil manufacture. In these trials, the accuracy of the conductor length measurement system using the optical equipment was evaluated, and winding trials were performed on a 1/3-scale double-pancake (DP) winding to demonstrate use of the winding system. In addition, the conductor length of the 1/3-scale DP trial winding was evaluated, and the elongation of the conductor due to bending was clarified. (author)


Rothamsted Research: GM trial: Part B  

bar gene gives the plant resistance to glufosinate herbicides and was used in the \\selection of ... The location of the field trial is an agricultural area forming part of \\an ... event of horizontal gene transfer to bacteria, neither the trait genes nor the \\selectable marker ... In addition, enzymatic degradation of free plant DNA in the.


Trial access to Cambridge University Press ebooks  

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From 1 August till 31 October, CERN users are invited to enjoy a trial access to all Cambridge University Press electronic books: Please don't hesitate to send feedback to

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Unit: Petroleum, Inspection Pack, National Trial Print. (United States)

This is a National Trial Print of a unit on petroleum developed for the Australian Science Education Project. The package contains the teacher's edition of the written material and a script for a film entitled "The Extraordinary Experience of Nicholas Nodwell" emphasizing the uses of petroleum and petroleum products in daily life and designed to…

Australian Science Education Project, Toorak, Victoria.


Applied Behavior Analysis: Beyond Discrete Trial Teaching (United States)

We discuss the problem of autism-specific special education programs representing themselves as Applied Behavior Analysis (ABA) programs when the only ABA intervention employed is Discrete Trial Teaching (DTT), and often for limited portions of the school day. Although DTT has many advantages to recommend its use, it is not well suited to teach…

Steege, Mark W.; Mace, F. Charles; Perry, Lora; Longenecker, Harold



Contact the Coordinating Center for Clinical Trials (United States)

Contact the Coordinating Center for Clinical Trials Office of the DirectorNational Cancer Institute9609 Medical Center DriveBethesda, MD 20892-9774Phone: 240-276-6160Fax: 240-276-7876Email: NCICCCT@mail.nih.govInternet: CCCT


Assessing laboratory performance in Trichinella ring trials. (United States)

Trichinosis (Trichinellosis) is a zoonotic disease acquired by eating raw or not adequately processed pork or wild game infected with the larvae of the roundworm genus Trichinella. According to European regulations, animals susceptible to Trichinella have to be examined for infestation. To evaluate the performance of laboratories in Germany, inter-laboratory comparisons known as "ring trials" were introduced by the Federal Institute for Risk Assessment in 2004. The current method of analysis makes use of tolerance zones based on the number of larvae in the sample, but does not permit one to determine if a given lab can detect an infested sample reliably, as required by the quality assurance recommendations of the International Commission on Trichinellosis (ICT). A new way of analysing the ring trial data is presented here, which is based on Bayesian hierarchical models. The model implements the ICT requirement by providing an estimate for the probability that a given lab would fail to detect a sample containing, say, five larvae. When applied to the 87 labs that participated in Germany's 2009 ring trials, it turns out this probability is greater than 10% for 21 of them, although only 10 of these in fact returned a false negative result. Such a new method is required to abide by the ICT requirements and make ring trials effective. PMID:24838905

Petroff, David; Hasenclever, Dirk; Makrutzki, Gregor; Riehn, Katharina; Lücker, Ernst



Biorepositories for the Breast Cancer Prevention Trial (United States)

The National Surgical Adjuvant Breast and Bowel Project (NSABP) has a serum and lymphocyte bank with specimens on more than 90% of the 33,000 women in the Breast Cancer Prevention Trial (BCPT) and Study of Tamoxifen and Raloxifene (STAR). They also have tumor blocks on the majority of the breast cancers that have occurred in women on these studies.


India's growing participation in global clinical trials. (United States)

Lower operational costs, recent regulatory reforms and several logistic advantages make India an attractive destination for conducting clinical trials. Efforts for maintaining stringent ethical standards and the launch of Pharmacovigilance Program of India are expected to maximize the potential of the country for clinical research. PMID:21489644

Gupta, Yogendra K; Padhy, Biswa M



Pipeline Decommissioning Trial AWE Berkshire UK - 13619  

Energy Technology Data Exchange (ETDEWEB)

This Paper details the implementation of a 'Decommissioning Trial' to assess the feasibility of decommissioning the redundant pipeline operated by AWE located in Berkshire UK. The paper also presents the tool box of decommissioning techniques that were developed during the decommissioning trial. Constructed in the 1950's and operated until 2005, AWE used a pipeline for the authorised discharge of treated effluent. Now redundant, the pipeline is under a care and surveillance regime awaiting decommissioning. The pipeline is some 18.5 km in length and extends from AWE site to the River Thames. Along its route the pipeline passes along and under several major roads, railway lines and rivers as well as travelling through woodland, agricultural land and residential areas. Currently under care and surveillance AWE is considering a number of options for decommissioning the pipeline. One option is to remove the pipeline. In order to assist option evaluation and assess the feasibility of removing the pipeline a decommissioning trial was undertaken and sections of the pipeline were removed within the AWE site. The objectives of the decommissioning trial were to: - Demonstrate to stakeholders that the pipeline can be removed safely, securely and cleanly - Develop a 'tool box' of methods that could be deployed to remove the pipeline - Replicate the conditions and environments encountered along the route of the pipeline The onsite trial was also designed to replicate the physical prevailing conditions and constraints encountered along the remainder of its route i.e. working along a narrow corridor, working in close proximity to roads, working in proximity to above ground and underground services (e.g. Gas, Water, Electricity). By undertaking the decommissioning trial AWE have successfully demonstrated the pipeline can be decommissioned in a safe, secure and clean manor and have developed a tool box of decommissioning techniques. The tool box of includes; - Hot tapping - a method of breaching the pipe while maintaining containment to remove residual liquids, - Crimp and shear - remote crimping, cutting and handling of pipe using the excavator - Pipe jacking - a way of removing pipes avoiding excavations and causing minimal disturbance and disruption. The details of the decommissioning trial design, the techniques employed, their application and effectiveness are discussed and evaluated here in. (authors)

Agnew, Kieran [AWE, Aldermaston, Reading, RG7 4PR (United Kingdom)



Early participant attrition from clinical trials: role of trial design and logistics. | (United States)

Researchers determined that to help reduce attrition in early phases of a trial, the time between consent to be screened and screening should be minimized. Additionally, duration of screening, especially for minority patients, should be minimized.


SAAB IRST: the system and flight trials (United States)

Saab Bofors Dynamics has developed an IRST-system (Infra Red Search and Track) named IR-OTIS (Optical Tracking and Identification System) and flight trials have been carried out with the system mounted on a Saab JA37 Viggen fighter aircraft. This paper consists of three major parts. First an overview of Saab's IRST-programs. The second part describes the system ( IR-OTIS(Viggen) ) that made flight trials during 1998 and 1999 and finally a report from the flight trials. IR-OTIS has mainly three operating modes: 1) IRST-mode where the system covers several different FOS (Field Of Search). 2) FLIR-mode (Forward Looking IR) where the systems LOS (Line Of Sight) is directed from the aircraft. 3) Track-mode where the built-in-tracker controls the LOS. It is also possible to switch from IRST-mode to track-mode automatically. Physically the IR-OTIS(Viggen) consists of the SU (Sensor Unit) and the SPU (Signal Processing Unit). The SU is operating in the longwave IR-band with a 288*4 detector. In all modes the Sensor Unit generates images in 25 Hz and it is also possible to choose one of three FOV. The SPU consists of a Saab designed image processing hardware and several DSPs. Functions in the SPU includes a scene-based NUC (Non Uniformity Correction), anti-Narcissus, a point-target detector including estimation of SNR and a clutter classifier for CFAR, target association, a correlation target tracker and an AGC for image presentation. We carried out over 50 flight trials during 1998 and 1999 in three different rounds. The functionality of the system has increased during the rounds and at the end of the trials all major goals were achieved.

Andersson, Ingmar A.; Haglund, Leif



ADEPT - Abnormal Doppler Enteral Prescription Trial  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Pregnancies complicated by abnormal umbilical artery Doppler blood flow patterns often result in the baby being born both preterm and growth-restricted. These babies are at high risk of milk intolerance and necrotising enterocolitis, as well as post-natal growth failure, and there is no clinical consensus about how best to feed them. Policies of both early milk feeding and late milk feeding are widely used. This randomised controlled trial aims to determine whether a policy of early initiation of milk feeds is beneficial compared with late initiation. Optimising neonatal feeding for this group of babies may have long-term health implications and if either of these policies is shown to be beneficial it can be immediately adopted into clinical practice. Methods and Design Babies with gestational age below 35 weeks, and with birth weight below 10th centile for gestational age, will be randomly allocated to an "early" or "late" enteral feeding regimen, commencing milk feeds on day 2 and day 6 after birth, respectively. Feeds will be gradually increased over 9-13 days (depending on gestational age using a schedule derived from those used in hospitals in the Eastern and South Western Regions of England, based on surveys of feeding practice. Primary outcome measures are time to establish full enteral feeding and necrotising enterocolitis; secondary outcomes include sepsis and growth. The target sample size is 400 babies. This sample size is large enough to detect a clinically meaningful difference of 3 days in time to establish full enteral feeds between the two feeding policies, with 90% power and a 5% 2-sided significance level. Initial recruitment period was 24 months, subsequently extended to 38 months. Discussion There is limited evidence from randomised controlled trials on which to base decisions regarding feeding policy in high risk preterm infants. This multicentre trial will help to guide clinical practice and may also provide pointers for future research. Trial registration Current Controlled Trials ISRCTN: 87351483

McCormick Kenny



Patient Protection in Clinical Trials in India: Some Concerns  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Clinical trial participants should not be influenced by undue inducement. Clinical trial investigators should be guided by ethical principles, and patient protection should be a top priority. This does not seem to be the case in India.

Srinivasan, Sandhya



What Are the Possible Benefits and Risks of Clinical Trials? (United States)

... the NHLBI on Twitter. What Are the Possible Benefits and Risks of Clinical Trials? Possible Benefits Taking part in a clinical trial can have many benefits. For example, you may gain access to new ...


DW - Trials Goals by Year 6-14.xls (United States)

NCCCP: Clinical Trials Components and Goals by Year # Area Clinical Trial Component Year 1 Year 2 Year 3 1 Community Input Local advisory board to advise & assist pilot w/ varied membership, assist to increase awareness of importance of CTs Convene


Clinical Trials: A Crucial Key to Human Health Research (United States)

Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: A Crucial Key to Human Health Research ... the forefront of human health research today are clinical trials—studies that use human volunteers to help ...


Use of crowdsourcing for cancer clinical trial development. (United States)

Patient and physician awareness and acceptance of trials and patient ineligibility are major cancer clinical trial accrual barriers. Yet, trials are typically conceived and designed by small teams of researchers with limited patient input. We hypothesized that through crowdsourcing, the intellectual and creative capacity of a large number of researchers, clinicians, and patients could be harnessed to improve the clinical trial design process. In this study, we evaluated the feasibility and utility of using an internet-based crowdsourcing platform to inform the design of a clinical trial exploring an antidiabetic drug, metformin, in prostate cancer. Over a six-week period, crowd-sourced input was collected from 60 physicians/researchers and 42 patients/advocates leading to several major (eg, eligibility) and minor modifications to the clinical trial protocol as originally designed. Crowdsourcing clinical trial design is feasible, adds value to the protocol development process, and may ultimately improve the efficiency of trial conduct. PMID:25217580

Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D



Can we identify non-stationary dynamics of trial-to-trial variability? (United States)

Identifying sources of the apparent variability in non-stationary scenarios is a fundamental problem in many biological data analysis settings. For instance, neurophysiological responses to the same task often vary from each repetition of the same experiment (trial) to the next. The origin and functional role of this observed variability is one of the fundamental questions in neuroscience. The nature of such trial-to-trial dynamics however remains largely elusive to current data analysis approaches. A range of strategies have been proposed in modalities such as electro-encephalography but gaining a fundamental insight into latent sources of trial-to-trial variability in neural recordings is still a major challenge. In this paper, we present a proof-of-concept study to the analysis of trial-to-trial variability dynamics founded on non-autonomous dynamical systems. At this initial stage, we evaluate the capacity of a simple statistic based on the behaviour of trajectories in classification settings, the trajectory coherence, in order to identify trial-to-trial dynamics. First, we derive the conditions leading to observable changes in datasets generated by a compact dynamical system (the Duffing equation). This canonical system plays the role of a ubiquitous model of non-stationary supervised classification problems. Second, we estimate the coherence of class-trajectories in empirically reconstructed space of system states. We show how this analysis can discern variations attributable to non-autonomous deterministic processes from stochastic fluctuations. The analyses are benchmarked using simulated and two different real datasets which have been shown to exhibit attractor dynamics. As an illustrative example, we focused on the analysis of the rat's frontal cortex ensemble dynamics during a decision-making task. Results suggest that, in line with recent hypotheses, rather than internal noise, it is the deterministic trend which most likely underlies the observed trial-to-trial variability. Thus, the empirical tool developed within this study potentially allows us to infer the source of variability in in-vivo neural recordings. PMID:24769735

Balaguer-Ballester, Emili; Tabas-Diaz, Alejandro; Budka, Marcin



EU Parliament, ministers agree to more clinical trial transparency in clinical trials | EurActiv  

... Those accusations were epitomised in a book, Bad Pharma by Ben Goldacre, a research fellow of epidemiology at the London School of ... More on this topic News Pharma industry tries to mobilise patient groups in clinical trials battleHealth NGO pushes for more transparency in clinical ...trialsHealth experts critical of pharma industry's new transparency rulesInterview Pharma chief: Governments must stop thinking short-term More in this section Ukrainian leadership vote ...


Managing Injuries of the Neck Trial (MINT): a randomised controlled trial of treatments for whiplash injuries.  

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OBJECTIVES: To examine the clinical effectiveness of a stepped care approach over a 12-month period after an acute whiplash injury; to estimate the costs and cost-effectiveness of each strategy including treatments and subsequent health-care costs; and to gain participants' perspective on experiencing whiplash injury, NHS treatment, and recovery within the context of the Managing Injuries of the Neck Trial (MINT). DESIGN: Two linked, pragmatic, randomised controlled trials. In Step 1, emergen...

Lamb, Se; Williams, Ma; Williamson, Em; Gates, S.; Withers, Ej; Mt-isa, S.; Ashby, D.; Castelnuovo, E.; Underwood, M.; Cooke, Mw



Trial effects in single-trial ERP components and autonomic responses at very long ISIs. (United States)

Single-trial data from autonomic and ERP measures were used to capture the rapidly decreasing initial responses characteristic of the orienting reflex (OR) to repeated stimuli. Stimulus-response patterns were compared to determine central analogues of autonomic indices of processes leading to the OR, and the OR itself. Participants were presented with 12 indifferent tones in an auditory dishabituation paradigm. Temporal principal component analysis (PCA) decomposed EOG-corrected ERP data for 16 subjects. Response patterns of ERPs, cardiac, and respiratory responses were compared to the phasic skin conductance response (SCR). SCR decremented over trials, recovered on the change trial, and dishabituated to the representation of the standard, meeting the formal definition of habituation required of the OR. The evoked cardiac response showed no trial effects. Respiratory pause (RP) decreased linearly over trials, recovering marginally on the change trial. Nine identifiable ERP components were extracted: P1, N1-3, N1-1, processing negativity (PN), P2, P3a, P3b, a novelty-sensitive P3 component (labelled HabP3), and the slow wave (SW). P3b and SW showed decrement over trials, but with no recovery, HabP3 showed decrement and increased response on the change trial, while the P1, N1 subcomponents, P2 and P3a were insensitive to novelty. Stimulus-response patterns of the RP and HabP3 suggest sensitivity to novelty processing, while the P1, N1-3, N-1, PN, P2, P3a and cardiac deceleration appear to mark processing prior to novelty, such as stimulus transient detection (cardiac deceleration) and/or intensity processing. This study supports predictions of preliminary process theory, demonstrating fractionation of 3 autonomic and 9 ERP components to novelty, and disconfirming the unitary nature of the OR. PMID:24681245

MacDonald, Brett; Barry, Robert J



Use of ordinal outcomes in vascular prevention trials: comparison with binary outcomes in published trials  

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Background and Purpose—Vascular prevention trials mostly count “yes/no” (binary) outcome events, eg, stroke/no stroke. Analysis of ordered categorical vascular events (eg, fatal stroke/nonfatal stroke/no stroke) is clinically relevant and could be more powerful statistically. Although this is not a novel idea in the statistical community, ordinal outcomes have not been applied to stroke prevention trials in the past. Methods—Summary data on stroke, myocardial infarction, c...

Bath, Philip M. W.; Geeganage, Chamila; Gray, Laura J.; Collier, T.; Pocock, S.



Assessing risk of bias in randomized controlled trials.  

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Even though randomised controlled trials are the design of choice for evaluating the efficacy of health care interventions, they are not immune to bias that may affect research process and validity of results. In the present paper we discussed how trial quality may be appraised considering both whether a clinical trial is reported in a comprehensive and complete way (consistently with what had been declared in the study protocol), and whether the characteristics of the trial itself are associ...

Purgato, M.; Barbui, C.; Cipriani, A.



LinkedCT: A Linked Data Space for Clinical Trials  

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The Linked Clinical Trials (LinkedCT) project aims at publishing the first open semantic web data source for clinical trials data. The database exposed by LinkedCT is generated by (1) transforming existing data sources of clinical trials into RDF, and (2) discovering semantic links between the records in the trials data and several other data sources. In this paper, we discuss several challenges involved in these two steps and present the methodology used in LinkedCT to over...

Hassanzadeh, Oktie; Kementsietsidis, Anastasios; Lim, Lipyeow; Miller, Renee J.; Wang, Min



The Beta Agonist Lung Injury TrIal (BALTI - prevention trial protocol  

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Full Text Available Abstract Background Acute lung injury complicates approximately 25-30% of subjects undergoing oesophagectomy. Experimental studies suggest that treatment with beta agonists may prevent the development of acute lung injury by decreasing inflammatory cell infiltration, activation and inflammatory cytokine release, enhancing basal alveolar fluid clearance and improving alveolar capillary barrier function. Methods/Design The Beta Agonist Lung Injury TrIal (prevention is a multi-centre, randomised, double blind, placebo-controlled trial. The aim of the trial is to determine in patients undergoing elective transthoracic oesphagectomy, if treatment with inhaled salmeterol 100 mcg twice daily started at induction of anaesthesia and continued for 72 hours thereafter compared to placebo affect the incidence of early acute lung injury and other clinical, resource and patient focused outcomes. The primary outcome will be the development of acute lung injury within 72 hours of oesophagectomy. The trial secondary outcomes are the development of acute lung injury during the first 28 days post operatively; PaO2: FiO2 ratio; the number of ventilator and organ failure free days, 28 and 90 day survival; health related quality of life and resource utilisation. The study aims to recruit 360 patients from 10 UK centres. Trial registration number Current Controlled Trials ISRCTN47481946

Gates Simon



The therapeutic effect of clinical trials: understanding placebo response rates in clinical trials – A secondary analysis  

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Full Text Available Abstract Background and purpose Placebo response rates in clinical trials vary considerably and are observed frequently. For new drugs it can be difficult to prove effectiveness superior to placebo. It is unclear what contributes to improvement in the placebo groups. We wanted to clarify, what elements of clinical trials determine placebo variability. Methods We analysed a representative sample of 141 published long-term trials (randomized, double-blind, placebo-controlled; duration > 12 weeks to find out what study characteristics predict placebo response rates in various diseases. Correlational and regression analyses with study characteristics and placebo response rates were carried out. Results We found a high and significant correlation between placebo and treatment response rate across diseases (r = .78; p Conclusion Medication response rates and placebo response rates in clinical trials are highly correlated. Trial characteristics can explain some portion of the variance in placebo healing rates in RCTs. Placebo response in trials is only partially due to methodological artefacts and only partially dependent on the diagnoses treated.

Walach Harald



Dynamic neural correlates of motor error monitoring and adaptation during trial-to-trial learning. (United States)

A basic EEG feature upon voluntary movements in healthy human subjects is a ? (13-30 Hz) band desynchronization followed by a postmovement event-related synchronization (ERS) over contralateral sensorimotor cortex. The functional implications of these changes remain unclear. We hypothesized that, because ? ERS follows movement, it may reflect the degree of error in that movement, and the salience of that error to the task at hand. As such, the signal might underpin trial-to-trial modifications of the internal model that informs future movements. To test this hypothesis, EEG was recorded in healthy subjects while they moved a joystick-controlled cursor to visual targets on a computer screen, with different rotational perturbations applied between the joystick and cursor. We observed consistently lower ? ERS in trials with large error, even when other possible motor confounds, such as reaction time, movement duration, and path length, were controlled, regardless of whether the perturbation was random or constant. There was a negative trial-to-trial correlation between the size of the absolute initial angular error and the amplitude of the ? ERS, and this negative correlation was enhanced when other contextual information about the behavioral salience of the angular error, namely, the bias and variance of errors in previous trials, was additionally considered. These same features also had an impact on the behavioral performance. The findings suggest that the ? ERS reflects neural processes that evaluate motor error and do so in the context of the prior history of errors. PMID:24741058

Tan, Huiling; Jenkinson, Ned; Brown, Peter



Bayesian methods in clinical trials: a Bayesian analysis of ECOG trials E1684 and E1690  

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Full Text Available Abstract Background E1684 was the pivotal adjuvant melanoma trial for establishment of high-dose interferon (IFN as effective therapy of high-risk melanoma patients. E1690 was an intriguing effort to corroborate E1684, and the differences between the outcomes of these trials have embroiled the field in controversy over the past several years. The analyses of E1684 and E1690 were carried out separately when the results were published, and there were no further analyses trying to perform a single analysis of the combined trials. Method In this paper, we consider such a joint analysis by carrying out a Bayesian analysis of these two trials, thus providing us with a consistent and coherent methodology for combining the results from these two trials. Results The Bayesian analysis using power priors provided a more coherent flexible and potentially more accurate analysis than a separate analysis of these data or a frequentist analysis of these data. The methodology provides a consistent framework for carrying out a single unified analysis by combining data from two or more studies. Conclusions Such Bayesian analyses can be crucial in situations where the results from two theoretically identical trials yield somewhat conflicting or inconsistent results.

Ibrahim Joseph G



21 CFR 886.1405 - Ophthalmic trial lens set. (United States)

...2010-04-01 false Ophthalmic trial lens set. 886.1405 Section 886.1405 Food...Devices § 886.1405 Ophthalmic trial lens set. (a) Identification. An ophthalmic trial lens set is a device that is a set of lenses of...



Randomization in substance abuse clinical trials  

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Full Text Available Abstract Background A well designed randomized clinical trial rates as the highest level of evidence for a particular intervention's efficacy. Randomization, a fundamental feature of clinical trials design, is a process invoking the use of probability to assign treatment interventions to patients. In general, randomization techniques pursue the goal of providing objectivity to the assignment of treatments, while at the same time balancing for treatment assignment totals and covariate distributions. Numerous randomization techniques, each with varying properties of randomness and balance, are suggested in the statistical literature. This paper reviews common randomization techniques often used in substance abuse research and an application from a National Institute on Drug Abuse (NIDA-funded clinical trial in substance abuse is used to illustrate several choices an investigator faces when designing a clinical trial. Results Comparisons and contrasts of randomization schemes are provided with respect to deterministic and balancing properties. Specifically, Monte Carlo simulation is used to explore the balancing nature of randomization techniques for moderately sized clinical trials. Results demonstrate large treatment imbalance for complete randomization with less imbalance for the urn or adaptive scheme. The urn and adaptive randomization methods display smaller treatment imbalance as demonstrated by the low variability of treatment allocation imbalance. For all randomization schemes, covariate imbalance between treatment arms was small with little variation between adaptive schemes, stratified schemes and unstratified schemes given that sample sizes were moderate to large. Conclusion We develop this paper with the goal of reminding substance abuse researchers of the broad array of randomization options available for clinical trial designs. There may be too quick a tendency for substance abuse researchers to implement the fashionable urn randomization schemes and other highly adaptive designs. In many instances, simple or blocked randomization with stratification on a major covariate or two will accomplish the same objectives as an urn or adaptive design, and it can do so with more simply implemented schedules and without the dangers of overmatching. Furthermore, the proper analysis, fully accounting for the stratified design, can be conducted.

Woolson Robert F



Media reporting of tenofovir trials in Cambodia and Cameroon  

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Full Text Available Abstract Background Two planned trials of pre-exposure prophylaxis tenofovir in Cambodia and Cameroon to prevent HIV infection in high-risk populations were closed due to activist pressure on host country governments. The international news media contributed substantially as the primary source of knowledge transfer regarding the trials. We aimed to characterize the nature of reporting, specifically focusing on the issues identified by media reports regarding each trial. Methods With the aid of an information specialist, we searched 3 electronic media databases, 5 electronic medical databases and extensively searched the Internet. In addition we contacted stakeholder groups. We included media reports addressing the trial closures, the reasons for the trial closures, and who was interviewed. We extracted data using content analysis independently, in duplicate. Results We included 24 reports on the Cambodian trial closure and 13 reports on the Cameroon trial closure. One academic news account incorrectly reported that it was an HIV vaccine trial that closed early. The primary reasons cited for the Cambodian trial closure were: a lack of medical insurance for trial related injuries (71%; human rights considerations (71%; study protocol concerns (46%; general suspicions regarding trial location (37% and inadequate prevention counseling (29%. The primary reasons cited for the Cameroon trial closure were: inadequate access to care for seroconverters (69%; participants not sufficiently informed of risks (69%; inadequate number of staff (46%; participants being exploited (46% and an unethical study design (38%. Only 3/23 (13% reports acknowledged interviewing research personnel regarding the Cambodian trial, while 4/13 (30.8% reports interviewed researchers involved in the Cameroon trial. Conclusion Our review indicates that the issues addressed and validity of the media reports of these trials is highly variable. Given the potential impact of the media in formulation of health policy related to HIV, efforts are needed to effectively engage the media during periods of controversy in the HIV/AIDS epidemic.

Wong Elaine



The WHO Global Programme for Vaccines and Immunization Vaccine Trial Registry.  

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In 1995, the WHO Global Programme for Vaccines and Immunization established a Vaccine Trial Registry. As of September 1996, this registry included 50 WHO-supported vaccine trials, of which 25 (50%) were completed studies. The vaccines most frequently tested have been against measles (9 trials), poliovirus (8 trials), cholera (8 trials), enterotoxigenic Escherichia coli (4 trials), and pneumococcus (4 trials). Nearly 80% of these trials have been conducted in developing countries, with the lar...

Robertson, S. E.; Mayans, M. V.; Horsfall, S.; Wright, P. F.; Clemens, J.; Ivanoff, B.; Lambert, P. H.



Oropharyngeal dysphagia, free water protocol and quality of life: an update from a prospective clinical trial. (United States)

Oropharyngeal dysphagia, typically associated with older adults, represents a spectrum of swallowing disorders with potentially serious complications and a negative impact on quality of life. A major complication of dysphagia is caused by aspiration, predominantly of thin liquids, which may cause aspiration pneumonia. Given that thin liquids are typically aspirated, the conventional therapy involves altering the diet to one consisting of modified solid consistencies and thickened fluids. While it is well known that this approach is appropriate for aspiration, it does represent difficulties with compliancy and quality of life. We have undertaken a relatively large scale clinical trial to investigate the relationships between the effects of free access to water and the development of aspiration, aspects of hydration and issues related to quality in people with dysphagia. Along with clinical observations and findings from others we have previously stratified people with dysphagia, namely those that are immobile or who have low mobility and severe degenerative neurological dysfunction, at highest risk of developing aspiration pneumonia following intake of water. In the present study, we have extended our previous clinical results. Our findings indicate that following purposeful selection of people with dysphagia with their own mobility and relatively healthy cognitive function, free access to water did not result in aspiration pneumonia, improved measures of hydration and in particular, significantly increased quality of life when compared to a diet consisting of thickened fluids only. Overall, we conclude that in people with good mobility and cognitive ability, there is no need to deviate from the Frazier Rehabilitation Centre free water protocol, which allows for the provision of water to people with dysphagia with strict guidelines particularly in relation to good physical ability. PMID:24392465

Karagiannis, Martha; Karagiannis, Tom C



Supportive treatment with megestrol acetate during radio-(chemo-)therapy. A randomized trial  

International Nuclear Information System (INIS)

Background: The value of megestrol acetate in treating tumor anorexia and cachexia of terminal patients is well known. However, the supportive effect of megestrol acetate during intensive radio-(chemo-)therapy was not investigated up to now. Therefore a randomized trial was performed including patients with advanced tumors in the head and neck region. Patients and Methods: From June 1991 to December 1993 a total of 64 patients were admitted to a randomized, double-blind placebo-controlled study. During and up to 6 weeks following radiotherapy patients received 160 mg/d megestrol acetate or placebo. The nutritional status (anthropometric and laboratory parameters) and the quality-of-life index according to Padilla et al. were determined prior to therapy, 1, 4, 6 weeks later during radiotherapy and 12, 18 weeks after completion. Results: Sixty-one out of 64 patients were evaluable (control group: n=30; megestrol acetate patients: n=31). One patients refused further participation after randomization. One patient in each arm was excluded due to side effects (impotence, diarrhoea). Further side effects were not observed. In the control group the nutrititional parameters (body weight, triceps skinfold) and the subjective feeling of the patients deteriorated during radiotherapy and did not restore following radiotherapy. By contrast, the patients of the megestrol acetate group were able to stabilize these parameters. This difference was most prominent in the orally nourished patients (weight loss during therapy: Control group: -4.1 kg; megestrol acetate group: -0.8 kg; p=0.004); but not in the patients fed by percutaneous endoscopically guided gastrostomy (weight loss control group: -2.4 kg; megestrol acetate group: -0.8 kg; p=0.14). Conclusion: In patients on radiochemotherapy megestrol acetate prevents patients from further deterioration of the nutritional status and quality of life. (orig.)


Dronedarone in atrial fibrillation: the aftermath of the PALLAS trial. (United States)

Dronedarone is a new antiarrhythmic currently approved for use among patients with nonpermanent atrial fibrillation (AF) based on the positive results of the ATHENA trial. Dronedarone was recently investigated in the PALLAS (Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy) trial, a landmark trial that evaluated treatment with dronedarone compared with placebo among older patients with permanent AF. The trial was terminated early due to a significant increase in adverse cardiovascular events among dronedarone-treated patients. In this article, the trial is presented and the significance and practical implications of the results in the management of older patients with AF briefly discussed. PMID:23244355

Salam, Amar M



Prevention of abdominal wound infection (PROUD trial, DRKS00000390: study protocol for a randomized controlled trial  

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Full Text Available Abstract Background Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus® such a suture has now been made available with triclosan antibacterial coating. Methods/Design The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n = 750 is sufficient to ensure alpha = 5% and power = 80%, an interim analysis will be carried out after data of 375 patients are available. Discussion The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity. Trial Registration The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390.

Heger Ulrike



Coping with Trial-to-Trial Variability of Event Related Signals: A Bayesian Inference Approach (United States)

In electro-neurophysiology, single-trial brain responses to a sensory stimulus or a motor act are commonly assumed to result from the linear superposition of a stereotypic event-related signal (e.g. the event-related potential or ERP) that is invariant across trials and some ongoing brain activity often referred to as noise. To extract the signal, one performs an ensemble average of the brain responses over many identical trials to attenuate the noise. To date, h s simple signal-plus-noise (SPN) model has been the dominant approach in cognitive neuroscience. Mounting empirical evidence has shown that the assumptions underlying this model may be overly simplistic. More realistic models have been proposed that account for the trial-to-trial variability of the event-related signal as well as the possibility of multiple differentially varying components within a given ERP waveform. The variable-signal-plus-noise (VSPN) model, which has been demonstrated to provide the foundation for separation and characterization of multiple differentially varying components, has the potential to provide a rich source of information for questions related to neural functions that complement the SPN model. Thus, being able to estimate the amplitude and latency of each ERP component on a trial-by-trial basis provides a critical link between the perceived benefits of the VSPN model and its many concrete applications. In this paper we describe a Bayesian approach to deal with this issue and the resulting strategy is referred to as the differentially Variable Component Analysis (dVCA). We compare the performance of dVCA on simulated data with Independent Component Analysis (ICA) and analyze neurobiological recordings from monkeys performing cognitive tasks.

Ding, Mingzhou; Chen, Youghong; Knuth, Kevin H.; Bressler, Steven L.; Schroeder, Charles E.



On the Complexity of Trial and Error  

CERN Document Server

Motivated by certain applications from physics, biochemistry, economics, and computer science, in which the objects under investigation are not accessible because of various limitations, we propose a trial-and-error model to examine algorithmic issues in such situations. Given a search problem with a hidden input, we are asked to find a valid solution, to find which we can propose candidate solutions (trials), and use observed violations (errors), to prepare future proposals. In accordance with our motivating applications, we consider the fairly broad class of constraint satisfaction problems, and assume that errors are signaled by a verification oracle in the format of the index of a violated constraint (with the content of the constraint still hidden). Our discoveries are summarized as follows. On one hand, despite the seemingly very little information provided by the verification oracle, efficient algorithms do exist for a number of important problems. For the Nash, Core, Stable Matching, and SAT problems,...

Bei, Xiaohui; Zhang, Shengyu



First clinical trial with iohexol in myelography  

International Nuclear Information System (INIS)

This is a report of the first clinical trial with iohexol in lumbar myelography. The investigation was carried out as an open, non-comparative study in 30 patients and was part of a mulicentre trial. Iohexol doses of 10 to 15 ml (180 mg I/ml) were used and clinical and laboratory tests were performed before and during 48 h after myelography. Spinal repuncture 6 or 24 h after myelography was done in all patients. Only minor side effects of temporary duration were recorded in 8 patients. No seizures or spikes on EEG were seen. There was no significant increase in CSF parameters such as white cell counts, protein or IgG. (Auth.)



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Full Text Available Among the general rights of the citizen on finds the free access to justice, the rights to defense and the right to legal security. The jurisprudence based on principles of law and on international treaties, caused the appearance, along the constitutional protection provided by default by a lawyer, of the need of fair and equitable procedures to ensure a balance in the rights of the parties. Today the right to a fair trial is a fundamental right most frequently invoked in front of Romanian courts, as in complaints to the European Court of Human Rights. This study is intended as a guide of the most important solutions that have been promoted to ensure the protection of the right to a fair trial with all the guarantees that are involved, starting with the right of access to justice and ending with the right to adversarial proceedings.




Annual technical report. PV domestic field trial  

Energy Technology Data Exchange (ETDEWEB)

This report describes progress at the first five sites of the UK photovoltaic (PV) domestic field trial. All five sites are generating electricity, but one has not yet been commissioned and two sites are not yet monitoring performance. The BedZED development has roof-mounted PV modules and PV cells installed in sealed double-glazing. Solar slates/tiles have been installed at the Laing Homes development in Montagu Road, where the designer has sought to minimise the visual impact of the PV system on the roofs. At Hunters Moon, PV modules have been retrofitted and some unforeseen difficulties have arisen. PV is an integral part of the roof design at the state-of-the-art low energy development by Integer Houses at Greenfields. Corn Croft uses a British mounting system to facilitate integration of the modules flush with the roof. Installation issues and the progress of the trial are discussed.




Malaria vaccines: lessons from field trials  

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Full Text Available Malaria vaccine candidates have already been tested and new trials are being carried out. We present a brief description of specific issues of validity that are relevant when assessing vaccine efficacy in the field and illustrate how the application of these principles might improve our interpretation of the data being gathered in actual malaria vaccine field trials. Our discussion assumes that vaccine evaluation shares the same general principles of validity with epidemiologic causal inference, i.e., the process of drawing inferences from epidemiologic data aiming at the identification of causes of diseases. Judicious exercise of these principles indicates that, for meaningful interpretation, measures of vaccine efficacy require definitions based upon arguments conditional on the amount of exposure to infection, and specification of the initial and final states in which one believes the effect of interest takes place.

Struchiner Claudio J.



Randomised controlled trials: important but overrated?  

LENUS (Irish Health Repository)

Practising physicians individualise treatments, hoping to achieve optimal outcomes by tackling relevant patient variables. The randomised controlled trial (RCT) is universally accepted as the best means of comparison. Yet doctors sometimes wonder if particular patients might benefit more from treatments that fared worse in the RCT comparisons. Such clinicians may even feel ostracised by their peers for stepping outside treatments based on RCTs and guidelines. Are RCTs the only acceptable evaluations of how patient care can be assessed and delivered? In this controversy we explore the interpretation of RCT data for practising clinicians facing individualised patient choices. First, critical care anaesthetists John Boylan and Brian Kavanagh emphasise the dangers of bias and show how Bayesian approaches utilise prior probabilities to improve posterior (combined) probability estimates. Secondly, Jane Armitage, of the Clinical Trial Service Unit in Oxford, argues why RCTs remain essential and explores how the quality of randomisation can be improved through systematic reviews and by avoiding selective reporting.

Boylan, J F



Randomized clinical trials in hepatocellular carcinoma. (United States)

Hepatocellular carcinoma is among the most common solid tumors, ranking behind only lung and gastric for cancer-related deaths worldwide. Despite improved surveillance programs in many countries, most patients present with advanced-stage cancer and chronic hepatic dysfunction limiting the available treatment options. This article reviews the most pertinent randomized controlled trials with respect to surgical and adjuvant interventions that shape the current treatment algorithm for hepatocellular carcinoma. PMID:19914564

Yopp, Adam C; Jarnagin, William R



Clinical and Therapeutic Trials of Nigella Sativa  

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Seeds of Nigella sativa (N. sativa) have been used for thousands of years as a spice and food preservative. The oil and seed constituents have shown potential medicinal properties in traditional medicine. This review lists and discusses different therapeutic trials of N. sativa seeds and its active ingredients in many diseases affecting body systems. It has anti?oxidant effects through enhancing the oxidant scavenger system that leads to antitoxic effects induced by several insults. Its ...

Salama, Ragaa H. M.



Psoriasis assessment tools in clinical trials  

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In clinical practice, broad global assessments of psoriasis disease activity and its effect on patients' quality of life are used to assess the severity of patients' disease and their response to treatment. In clinical trials, more objective, validated instruments are required. Several such instruments have been developed and continue to be developed to provide an assessment of the severity of the skin lesions. Because a lesion's impact on patients' lives varies widely among patients, there h...

Feldman, S.; Krueger, G.



Clinical trials in acute ischemic stroke. (United States)

Acute ischemic stroke (AIS) is a major cause of mortality and disability and remains a serious and significant global health problem. The development of neurovascular protectants to treat AIS successfully has been beset by disappointments and setbacks. Many promising candidates have lacked significant pleiotropic protective activity for brain tissue and cerebral blood vessels in clinical trials, while those with protective activity have had poor bioavailability or high toxicity. Moreover, the majority of agents did not confer significant neurovascular protection or clinical efficacy, as measured by standard behavioral endpoints in clinical trials of heterogeneous populations of patients with AIS. The recombinant tissue plasminogen activator alteplase is approved in many countries for the treatment of AIS in the first 3 h after symptom onset. Many drug candidates have been subject to clinical trials, including those with anti-excitotoxic, anti-inflammatory, antioxidant, antiapoptotic/regenerative, calcium/adrenergic-modulating/antihypertensive, thrombolytic, nootropic/stimulant, fluid regulatory, or oxygen-delivering mechanisms of action. Some agents, such as tenecteplase, edaravone and minocycline, may be approved for global use in the future. This review evaluates almost all neurovascular protectants subject to clinical trial evaluation for the treatment of AIS, and includes 241 studies conducted between 1978 and 2014. The development of agents that reduce brain injury after AIS will require new and different approaches based on a deeper understanding of the pathophysiology of AIS. Moreover, the future treatment for AIS is likely to lie in combination therapy rather than monotherapy. Additional approaches to the testing and use of neurovascular protectants should be considered. PMID:25160686

Kikuchi, Kiyoshi; Tanaka, Eiichiro; Murai, Yoshinaka; Tancharoen, Salunya



Biomarkers for Alzheimer's disease therapeutic trials  

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The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuropathology, including amyloidogenic processing and aggregation, hyperphosphorylation...

Hampel, H.; Wilcock, G.; Andrieu, S.; Aisen, P.; Blennow, K.; Broich, K.; Carrillo, M.; Fox, Nc; Frisoni, Gb; Isaac, M.; Lovestone, S.; Nordberg, A.; Prvulovic, D.; Sampaio, C.; Scheltens, P.



Delaying the oocyte maturation trigger by one day leads to a higher metaphase II oocyte yield in IVF/ICSI: a randomised controlled trial (United States)

Background The negative impact of rising progesterone levels on pregnancy rates is well known, but data on mature oocyte yield are conflicting. We examined whether delaying the oocyte maturation trigger in IVF/ICSI affected the number of mature oocytes and investigated the potential influence of serum progesterone levels in this process. Methods Between January 31, 2011, and December 31, 2011, 262 consecutive patients were monitored using ultrasound plus hormonal evaluation. Those with?>?=3 follicles with a mean diameter of?>?=18 mm were divided into 2 groups depending on their serum progesterone levels. In cases with a progesterone level?progesterone levels?>?1 ng/ml were randomised in the same manner, irrespective of the percentage of larger follicles (>?=?18 mm). The number of metaphase II oocytes was our primary outcome variable. Because some patients were included more than once, correction for duplicate patients was performed. Results In the study arm with low progesterone (progesterone (>1 ng/ml), the mean numbers of metaphase II oocytes (+/-SD) were 11.81 (+/-9.91) and 12.03 (+/-7.09) for the delayed and control groups, respectively. After adjusting for PCOS (polycystic ovary syndrome) and female pathology, the mean difference was -0.44 (95% CI: -3.65-2.78; p?=?0.79). Conclusions Delaying oocyte maturation in patients with low progesterone levels yields greater numbers of mature oocytes. Trial registration B67020108975 (Belgian registration) and NCT01980563 ( PMID:24758641



Extremity dosimetry trial: Devonport royal dockyard  

International Nuclear Information System (INIS)

This trial was undertaken to assess extremity dosemeters, which were made available to Devonport Royal Dockyard and determine the most suitable to the site. The trial included operational and laboratory-based exposures. Operational exposures were within a submarine reactor compartment and a waste storage area. Laboratory exposures were undertaken using 241Am, 137Cs and 60Co sources to compare and contrast the dosemeters energy response. In addition, the low dose response and the response if placed in the incorrect orientation were also assessed. Ten passive and two active dosemeters were tested, with three highlighted as the most technically suitable, DSTL Harshaw DXT-RAD, HPA Harshaw EXT-RAD and the AMEC Panasonic UD-807A. The most technically suitable dosemeter was the DSTL Harshaw DXT-RAD, due to good responses within all aspects of the trial and the user's preference for the ring type design. The John Caunt ED2 electronic dosemeter 2 (ED2) also performed well, but suffered radio frequency interference. (authors)


Extremity dosimetry trial: Devonport Royal Dockyard. (United States)

This trial was undertaken to assess extremity dosemeters, which were made available to Devonport Royal Dockyard and determine the most suitable to the site. The trial included operational and laboratory-based exposures. Operational exposures were within a submarine reactor compartment and a waste storage area. Laboratory exposures were undertaken using (241)Am, (137)Cs and (60)Co sources to compare and contrast the dosemeters energy response. In addition, the low dose response and the response if placed in the incorrect orientation were also assessed. Ten passive and two active dosemeters were tested, with three highlighted as the most technically suitable, DSTL Harshaw DXT-RAD, HPA Harshaw EXT-RAD and the AMEC Panasonic UD-807A. The most technically suitable dosemeter was the DSTL Harshaw DXT-RAD, due to good responses within all aspects of the trial and the user's preference for the ring type design. The John Caunt ED2 electronic dosemeter 2 (ED2) also performed well, but suffered radio frequency interference. PMID:18319280

Kenyon, Rob; Collison, Roger



Clinical trials: discerning hype from substance. (United States)

The interest in being able to interpret and report results in clinical trials as being favorable is pervasive throughout health care research. This important source of bias needs to be recognized, and approaches need to be implemented to effectively address it. The prespecified primary analyses of the primary and secondary end points of a clinical trial should be clearly specified when disseminating results in press releases and journal publications. There should be a focus on these analyses when interpreting the results. A substantial risk for biased conclusions is produced by conducting exploratory analyses with an intention to establish that the benefit-to-risk profile of the experimental intervention is favorable, rather than to determine whether it is. In exploratory analyses, P values will be misleading when the actual sampling context is not presented to allow for proper interpretation, and the effect sizes of outcomes having particularly favorable estimates are probably overestimated because of "random high" bias. Performing exploratory analyses should be viewed as generating hypotheses that usually require reassessment in prospectively conducted confirmatory trials. Awareness of these issues will meaningfully improve our ability to be guided by substance, not hype, in making evidence-based decisions about medical care. PMID:20855804

Fleming, Thomas R



Treat-to-target trials in diabetes. (United States)

Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols. PMID:24741511

Wangnoo, Subhash K; Sethi, Bipin; Sahay, Rakesh K; John, Mathew; Ghosal, Samit; Sharma, Surendra K



Optimizing biologically targeted clinical trials for neurofibromatosis (United States)

Introduction The neurofibromatoses (neurofibromatosis type 1, NF1 and neurofibromatosis type 2, NF2) comprise the most common inherited conditions in which affected children and adults develop tumors of the central and peripheral nervous system. In this review, the authors discuss how the establishment of the Neurofibromatosis Clinical Trials Consortium (NFCTC) has positively impacted on the design and execution of treatment studies for individuals with NF1 and NF2. Areas covered Using an extensive PUBMED search in collaboration with select NFCTC members expert in distinct NF topics, the authors discuss the clinical features of NF1 and NF2, the molecular biology of the NF1 and NF2 genes, the development and application of clinically relevant Nf1 and Nf2 genetically engineered mouse models and the formation of the NFCTC to enable efficient clinical trial design and execution. Expert opinion The NFCTC has resulted in a more seamless integration of mouse preclinical and human clinical trials efforts. Leveraging emerging enabling resources, current research is focused on identifying subtypes of tumors in NF1 and NF2 to deliver the most active compounds to the patients most likely to respond to the targeted therapy. PMID:23425047

Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J



Gateways to clinical trials. December 2008. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: AAV1/SERCA2a; Abatacept, ABT-263, Adalimumab, Aflibercept, Afobazole, Aliskiren fumarate, Anakinra, Atazanavir/ritonavir, Aviscumine, Axitinib, Azacitidine; Bevacizumab, Biphasic insulin aspart, Bortezomib, Briobacept; Carmoterol hydrochloride, CCX-282, Ceftobiprole medocaril, Certolizumab pegol, Cetuximab; Darifenacin hydrobromide, Dasatinib, Denosumab, Doripenem, Duloxetine hydrochloride; E-7080, Epratuzumab, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe/simvastatin; Gefitinib, Golimumab; gamma-Hydroxybutyrate sodium; Imatinib mesylate, Insulin detemir, Insulin glulisine, IVX-0142; Laquinimod sodium, Linezolid, Lopinavir/ritonavir; Ocrelizumab, Omalizumab; Parecoxib sodium, Pemetrexed disodium, Pregabalin; Rosuvastatin calcium, Rotigotine; Sorafenib, Sugammadex sodium; Tapentadol hydrochloride, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ularitide, Ustekinumab; Valsartan/amlodipine besylate, Varenicline tartrate, Vatalanib succinate, Vildagliptin, Vorinostat. PMID:19271026

Tomillero, A; Moral, M A



Atrial fibrillation: overview of therapeutic trials. (United States)

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia treated by physicians, and a plethora of therapeutic trials deal with selected aspects of its management. This overview attempts to categorize and summarize the available studies. A key to management of AF is a clinical classification schema that provides a framework for application of the available treatment modalities. Such a classification is provided. Antithrombotic trials have demonstrated the remarkable efficacy of warfarin and more modest effect of acetylsalicylic acid for prevention of stroke; these data are summarized. Cardioversion to restore sinus rhythm is an important aspect of management of AF, particularly of persistent and new onset AF. In this review pharmacological cardioversion is emphasized. The data concerning the use of various drugs for pharmacological cardioversion are reviewed. Many, but not all, agents have been shown to have efficacy in this regard, but efficacy with drugs is lower than that with electrical cardioversion and, in the case of amiodarone, may be delayed. For recurrent AF, the two major rhythm management approaches are maintenance of rhythm and heart rate control. Trials of pharmacological and nonpharmacological therapies for these purposes are reviewed and summarized. Management of AF is an active area of research, and the present review is intended as a foundation upon which new information can be added. PMID:9852938

Sharif, M N; Wyse, D G



Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures. Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139 in the Netherlands to 232 days (P25-P75 98-423 in Canada (p = 0.027. The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21 per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28, representing 3.9% of eligible patients (p Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration NCT00761813

Zielinski Stephanie M



Adolescent experiences in a vaccine trial: a pilot study  

Scientific Electronic Library Online (English)

Full Text Available SciELO South Africa | Language: English Abstract in english ABSTRACT Little is known about how adolescents experience clinical trials. We assessed the experiences of South African adolescent participants in a clinical trial, employing semi-structured interviews to gather qualitative data on the experiences and effects of trial participation. Despite misunder [...] standing certain concepts regarding assent and trial processes subsequent to enrolment, participants reported positive experiences overall. Subjects' motivations for participation included: an ability to help others; receipt of healthcare; and free blood screening. Participants expressed fears associated with trial procedures, such as phlebotomy; however, these apprehensions diminished as the trial progressed. We found that conducting qualitative research within a trial site is feasible, and can provide insight into the uptake and acceptability of interventions.

Amber, Abrams; Nandi, Siegfried; Hennie, Geldenhuys.



Adolescent experiences in a vaccine trial: a pilot study  

Scientific Electronic Library Online (English)

Full Text Available SciELO South Africa | Language: English Abstract in english ABSTRACT Little is known about how adolescents experience clinical trials. We assessed the experiences of South African adolescent participants in a clinical trial, employing semi-structured interviews to gather qualitative data on the experiences and effects of trial participation. Despite misunder [...] standing certain concepts regarding assent and trial processes subsequent to enrolment, participants reported positive experiences overall. Subjects' motivations for participation included: an ability to help others; receipt of healthcare; and free blood screening. Participants expressed fears associated with trial procedures, such as phlebotomy; however, these apprehensions diminished as the trial progressed. We found that conducting qualitative research within a trial site is feasible, and can provide insight into the uptake and acceptability of interventions.

Amber, Abrams; Nandi, Siegfried; Hennie, Geldenhuys.


Randomized controlled trials in schizophrenia: opportunities, limitations, and trial design alternatives (United States)

State-of-the art clinical trial design and methodology are enormously important for the advancement of the field. In contrast, the critical relevance of trial conduct and implementation have only more recently been the focus of discussion and research. Although randomized controlled trials are generally considered the gold standard for the assessment of pharmacologic and nonpharmacologic interventions in medicine, trials are vulnerable to complications and influences that can seriously compromise their success, Like interventions, trial design and conduct are also contextual. They need to be individualized and adapted to a number of relevant variables, such as setting, population, illness phase, interventions, patient and rater expectations and biases, and the overall aims of the investigation. While this means that there is no unified approach possible, certain general principles and guidelines require careful consideration. Knowledge of basic solutions and alternatives, and the recognition of the complex challenges that need to be addressed proactively can help to minimize unwanted outcomes, including trial failure and uninformative or falsely negative outcomes. Moreover, novel design alternatives need to be explored that target sample enrichment according to the study question and enhancement of precision in the measurement of relevant outcomes. We propose two novel design strategies that take advantage of the recently validated early antipsychotic response paradigm (that has also been observed with antidepressants and mood stabilizers). In the “early responder randomized discontinuation design” all patients are assigned to the active drug, and only those who had at least a minimal response at 2 weeks are enrolled in a double-blind, placebo-controlled discontinuation trial, enriching the placebo controlled trial portion with true drug responders. In the mirror image “early nonresponder randomized dose increase or augmentation design,” early nonresponders at 2 weeks are assigned to staying on the medication or going either to a higher dose or an augmentation agent. It is hoped that through increased attention to the issues raised in this article and further refinement of trial methodology and conduct, the field will make much needed additional progress in the prevention and treatment of schizophrenia. PMID:21842613

Correll, Christoph U.; Kishimoto, Taishiro; Kane, John M.



A multivariate approach linking reported side effects of clinical antidepressant and antipsychotic trials to in vitro binding affinities. (United States)

The vast majority of approved antidepressants and antipsychotics exhibit a complex pharmacology. The mechanistic understanding of how these psychotropic medications are related to adverse drug reactions (ADRs) is crucial for the development of novel drug candidates and patient adherence. This study aims to associate in vitro assessed binding affinity profiles (39 compounds, 24 molecular drug targets) and ADRs (n=22) reported in clinical trials of antidepressants and antipsychotics (n>59.000 patients) by the use of robust multivariate statistics. Orthogonal projection to latent structures (O-PLS) regression models with reasonable predictability were found for several frequent ADRs such as nausea, diarrhea, hypotension, dizziness, headache, insomnia, sedation, sleepiness, increased sweating, and weight gain. Results of the present study support many well-known pharmacological principles such as the association of hypotension and dizziness with ?1-receptor or sedation with H1-receptor antagonism. Moreover, the analyses revealed novel or hardly investigated mechanisms for common ADRs including the potential involvement of 5-HT6-antagonism in weight gain, muscarinic receptor antagonism in dizziness, or 5-HT7-antagonism in sedation. To summarize, the presented study underlines the feasibility and value of a multivariate data mining approach in psychopharmacological development of antidepressants and antipsychotics. PMID:25044049

Michl, Johanna; Scharinger, Christian; Zauner, Miriam; Kasper, Siegfried; Freissmuth, Michael; Sitte, Harald H; Ecker, Gerhard F; Pezawas, Lukas



A model–based approach to trial–by–trial P300 amplitude fluctuations  

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Full Text Available It has long been recognized that the amplitude of the P300 component of event–related brain potentials is sensitive to the degree to which eliciting stimuli are surprising to the observers (Donchin, 1981. While Squires et al. (1976 showed and modeled dependencies of P300 amplitudes from observed stimuli on various time scales, Mars et al. (2008 proposed a computational model keeping track of stimulus probabilities on a long–term time scale. We suggest here a computational model which integrates prior information with short–term, long–term, and alternation–based experiential influences on P300 amplitude fluctuations. To evaluate the new model, we measured trial–by–trial P300 amplitude fluctuations in a simple two–choice response time task, and tested the computational models of trial–by–trial P300 amplitudes using Bayesian model evaluation. The results reveal that the new digital filtering (DIF model provides a superior account of the trial–by–trial P300 amplitudes when compared to both, Squires et al.’s (1976 model, and Mars et al.’s (2008 model. We show that the P300–generating system can be described as two parallel first–order infinite impulse response (IIR low–pass filters and an additional fourth–order finite impulse response (FIR high–pass filter. Implications of the acquired data are discussed with regard to the neurobiological distinction between short–term, long–term, and working memory as well as from the point of view of predictive coding models and Bayesian learning theories of cortical function.




De "corpos" a "pessoas": a atuação das pacientes através do julgamento da Dra. Mary Dixon Jones de 1892 From "bodies" to "persons": female patient agency as revealed in the 1892 trial of Dr. Mary Dixon Jones  

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Full Text Available Este artigo discute o sensacional processo de 1892 entre o jornal Eagle, Do Brooklin, Nova Iorque, e uma conhecida cirurgiã ginecologista, Dra. Mary Amanda Dixon Jones. Sugiro que o evento confirmou e ajudou a mudar a compreensão sobre o corpo feminino e as doenças ginecológicas para as pacientes, os espectadores do julgamento e o público mais amplo. O desenvolvimento da cirurgia ginecológica alterou as relações entre médico e paciente, permitindo que mulheres pobres e de classe média falassem no tribunal sobre sua penosa experiência da doença. O julgamento proporcionou um canal público incomum para a divulgação das reclamações quanto à condição feminina, assim como para discussão sobre a prática médica.This article examines a sensational public libel trial that took place in 1892 between the Brooklyn, New York, Eagle newspaper and a well-known female gynecological surgeon, Dr. Mary Amanda Dixon Jones. I suggest that the event both affirmed and helped authorized changing understandings of women's bodies and gynecological disease for female patients, trial spectators, and the larger public. It suggests that the development of gynecological surgery altered doctor-patient relationships which enabled middle class and even some poor women to speak in the courtroom about the burdensome experience of illness. The trial provided an unusual public venue for airing disappointments and complaints about the female condition, as well as the discussion about medical practices.

Regina Morantz-Sanchez



De "corpos" a "pessoas": a atuação das pacientes através do julgamento da Dra. Mary Dixon Jones de 1892 / From "bodies" to "persons": female patient agency as revealed in the 1892 trial of Dr. Mary Dixon Jones  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese Este artigo discute o sensacional processo de 1892 entre o jornal Eagle, Do Brooklin, Nova Iorque, e uma conhecida cirurgiã ginecologista, Dra. Mary Amanda Dixon Jones. Sugiro que o evento confirmou e ajudou a mudar a compreensão sobre o corpo feminino e as doenças ginecológicas para as pacientes, o [...] s espectadores do julgamento e o público mais amplo. O desenvolvimento da cirurgia ginecológica alterou as relações entre médico e paciente, permitindo que mulheres pobres e de classe média falassem no tribunal sobre sua penosa experiência da doença. O julgamento proporcionou um canal público incomum para a divulgação das reclamações quanto à condição feminina, assim como para discussão sobre a prática médica. Abstract in english This article examines a sensational public libel trial that took place in 1892 between the Brooklyn, New York, Eagle newspaper and a well-known female gynecological surgeon, Dr. Mary Amanda Dixon Jones. I suggest that the event both affirmed and helped authorized changing understandings of women's b [...] odies and gynecological disease for female patients, trial spectators, and the larger public. It suggests that the development of gynecological surgery altered doctor-patient relationships which enabled middle class and even some poor women to speak in the courtroom about the burdensome experience of illness. The trial provided an unusual public venue for airing disappointments and complaints about the female condition, as well as the discussion about medical practices.

Regina, Morantz-Sanchez.



Communication of Clinical Trial: Beyond PubMed: Searching the "Grey Literature" for Clinical Trial Results. (United States)

Clinical trial results have been traditionally communicated through the publication of scholarly reports and reviews in biomedical journals. However, this dissemination of information can be delayed or incomplete, making it difficult to appraise new treatments, or in the case of missing data, evaluate older interventions. Going beyond the routine search of PubMed, it is possible to discover additional information in the "grey literature." Examples of the grey literature include clinical trial registries, patent databases, company and industrywide repositories, regulatory agency digital archives, abstracts of paper and poster presentations on meeting/congress websites, industry investor reports and press releases, and institutional and personal websites. PMID:25337445

Citrome, Leslie



Can we rely on the best trial? A comparison of individual trials and systematic reviews  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background The ideal evidence to answer a question about the effectiveness of treatment is a systematic review. However, for many clinical questions a systematic review will not be available, or may not be up to date. One option could be to use the evidence from an individual trial to answer the question? Methods We assessed how often (a) the estimated effect and (b) the p-value in the most precise single trial in a meta-analysis agreed with the whole m...

Shepperd Sasha; Glasziou Paul P; Brassey Jon



Designing implant trials in 2010: a recipe for success. (United States)

In a recent evaluation of 1017 device trials listed on a clinical trials register ( between 2005 and 2009, only 84 (8.2%) represented orthopedic device evaluations. These device trials notably had few numbers of patients and few centers and represented approximately 7% of drug trials on the same registry. The relatively small proportion of device trials in orthopedics may represent a lack of interest; however, given the device focus of the field, the answer is more likely to be a lack of necessity?historically, regulatory pathways to implant approvals have not required clinical trials and have largely focused on preclinical and early case-series evaluations. The changing landscape of the regulatory environment necessitates a renewed interest in high-quality clinical research. Specifically, randomized trials of implants in orthopedics are poised to become major designs in the future. Given the general uncertainty in knowledge of regulatory pathways among researchers and health care providers, the current symposium was developed to clarify the design and execution of device trials in a changing regulatory environment. We focus our papers on the Food and Drug Administration (FDA) device classes and regulatory pathways (510K), design challenges in regulatory trials, site audits, and standard operating procedures. In over a decade of conducting trials, we have also realized the critical importance of data-management systems and contract research organizations. Not every clinician, device manufacturer, or researcher planning a randomized trial will have the infrastructure or experience to meet the strict regulatory compliance guidelines for the proper conduct of the trial. Understanding what to look for in a contract research organization is extremely helpful, especially in an environment of limited funding and high expectations. We hope that the current symposium will provide a broad context to clinical trials of orthopedic devices. Despite the challenges of the current regulatory arena, there has never been a more exciting time to conduct research in our field. PMID:20939776

Bhandari, Mohit



Clinical trials in crisis: Four simple methodologic fixes. (United States)

There is growing consensus that the US clinical trials system is broken, with trial costs and complexity increasing exponentially, and many trials failing to accrue. Yet, concerns about the expense and failure rate of randomized trials are only the tip of the iceberg; perhaps what should worry us most is the number of trials that are not even considered because of projected costs and poor accrual. Several initiatives, including the Clinical Trials Transformation Initiative and the "Sensible Guidelines Group" seek to push back against current trends in clinical trials, arguing that all aspects of trials-including design, approval, conduct, monitoring, analysis, and dissemination-should be based on evidence rather than contemporary norms. Proposed here are four methodologic fixes for current clinical trials. The first two aim to simplify trials, reducing costs, and increasing patient acceptability by dramatically reducing eligibility criteria-often to the single criterion that the consenting physician is uncertain which of the two randomized arms is optimal-and by clinical integration, investment in data infrastructure to bring routinely collected data up to research grade to be used as endpoints in trials. The second two methodologic fixes aim to shed barriers to accrual, either by cluster randomization of clinicians (in the case of modifications to existing treatment) or by early consent, where patients are offered the chance of being randomly selected to be offered a novel intervention if disease progresses at a subsequent point. Such solutions may be partial, or result in a new set of problems of their own. Yet, the current crisis in clinical trials mandates innovative approaches: randomized trials have resulted in enormous benefits for patients, and we need to ensure that they continue to do so. PMID:25278228

Vickers, Andrew J



Queensland Mines plant trials with Caro's acid  

International Nuclear Information System (INIS)

Laboratory leach tests have been carried out to compare the effectiveness of Caro's acid (permonosulphuric acid) as an alternative oxidant to pyrolusite in the leaching of uranium ores. Results demonstrated that Caro's acid reduced acid consumption in leaching and the time required for neutralisation of tailings liquor. The uranium extraction was unaffected by choice of oxidant. A plant trial confirmed that significant savings in acid and lime usage can be achieved under plant conditions. Plant operations also demonstrated that Caro's acid has a number of significant operating advantages over pyrolusite. Queensland Mines Ltd. have recently decided to convert their leaching process from pyrolusite to Caro's acid


Randomized clinical stroke trials in 2004. (United States)

Randomized clinical stroke trials published during 2004 dealt primarily with prevention of strokes by reducing risk factors. The usefulness of innovative versions of widely known treatment modalities was documented. These included angiotensin-converting enzyme inhibitors against hypertension, acarabose against diabetes, and the antiplatelet agent triflusal instead of aspirin. A large British study confirmed the value of treatment with simvastatin. Appropriately powered studies found no benefit for stroke prevention of either vitamin treatment to lower homocysteine or hormonal replacement in post-menopausal women. The circumstances under which antithrombotic, anticoagulant and surgical treatments of acute ischemic stroke are appropriate were further specified. PMID:15975326

Rabadi, Meheroz H; Blass, John



Inactive trials of transport systems: phase II  

International Nuclear Information System (INIS)

Progress made during 1984-85 is reviewed in four sections: the design and installation of a stainless steel working floor in the mock-up of a crate handling and size reduction facility; the detailed evaluation of a single air pad of the type used on commercial air-transporter; an experimental programme designed to examine the problems associated with the operation of a commercial air-transporter; the design, manufacture and commissioning trials of two powered conveyor units which when combined complete a remotely operated transfer system for transporting crated waste into and within the mock-up facility. (author)


Good clinical practice: International quality standard for clinical trials  

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Full Text Available A clinical trial is one of the most important examples of experimental studies. Clinical trials represent an indispensable tool for testing, in a rigorous scientific manner, the efficacy of new therapies. Good Clinical Practice is an international ethical and scientific quality standard for clinical trials, concerning the design, conduct, performance, monitoring auditing, recording, analysis and reporting. This is an assurance to the public that the rights, safety and well-being of trial subjects are protected, and that clinical trial data is credible. The above definitions are consistent with the principles that have their origin in the declaration of Helsinki. The objectives of Good Clinical Practice are to protect the rights of trial subjects, to enhance credibility of data and to improve the quality of science.

Radulovi? Siniša S.



Practical considerations for adaptive trial design and implementation  

CERN Document Server

This edited volume is a definitive text on adaptive clinical trial designs from creation and customization to utilization. As this book covers the full spectrum of topics involved in the adaptive designs arena, it will serve as a valuable reference for researchers working in industry, government and academia. The target audience is anyone involved in the planning and execution of clinical trials, in particular, statisticians, clinicians, pharmacometricians, clinical operation specialists, drug supply managers, and infrastructure providers.  In spite of the increased efficiency of adaptive trials in saving costs and time, ultimately getting drugs to patients sooner, their adoption in clinical development is still relatively low.  One of the chief reasons is the higher complexity of adaptive design trials as compared to traditional trials. Barriers to the use of clinical trials with adaptive features include the concerns about the integrity of study design and conduct, the risk of regulatory non-acceptance, t...

Pinheiro, José; Kuznetsova, Olga



Clinical trial design in the era of comparative effectiveness research  

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Full Text Available Anke C Winter, Graham A Colditz Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO, USA Abstract: Clinical trials are one of the key study designs in the evolving field of comparative effectiveness research. Evaluating the effectiveness of interventions in real-world settings is complex and demands a rethinking of the traditional clinical trial approach as well as transformation of the clinical trial landscape. Novel strategies and refinement of existing approaches have been proposed to generate evidence that can guide health care stakeholders in their decision process. The purpose of this review is to discuss clinical trial design approaches in the era of comparative effectiveness research. We will focus on aspects relevant to the type of clinical trial, study population and recruitment, randomization process, outcome measures, and data collection. Keywords: review, clinical trial, comparative effectiveness research

Winter AC



Methods for therapeutic trials in COPD: lessons from the TORCH trial  

DEFF Research Database (Denmark)

The TORCH (Towards a Revolution in COPD Health) trial has highlighted some important issues in the design and analysis of long term trials in chronic obstructive pulmonary disease. These include collection of off-treatment exacerbation data, analysis of exacerbation rates and the effect of inclusion of patients receiving inhaled corticosteroids (ICS) prior to randomisation. When effective medications are available to patients who withdraw, inclusion of off-treatment data can mask important treatment effects on exacerbation rates. Analysis of on-treatment data avoids this bias but it needs to be combined with careful analysis of withdrawal patterns across treatments. The negative binomial model is currently the best approach to statistical analysis of exacerbation rates, while analysis of time to exacerbation can supplement this approach. In the TORCH trial, exacerbation rates were higher among patients with previous use of ICS compared to those with no prior use on all study treatments. Retrospective subgroup analysis suggests ICS reduced exacerbation rates compared with placebo, regardless of prior use of ICS before entry to the study. Factorial analysis provides an alternative analysis for trials with combinations of treatments, but assumes no interaction between treatments, an assumption which cannot be verified by a significance test. No definitive conclusions can yet be drawn on whether ICS treatment has an effect on mortality.

Keene, O N; Vestbo, J



Application of remote sensing to agricultural field trials.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Remote sensing techniques enable quantitative information about a field trial to be obtained instantaneously and non-destructively. The aim of this study was to identify a method that can reduce inaccuracies in field trial analysis, and to identify how remote sensing can support and/or replace conventional field measurements in field trials.In the literature there is a certain consensus that the best bands from which characteristic spectral information about vegetation can be extracted are th...

Clevers, J. G. P. W.



Targeting targeted agents: open issues for clinical trial design  

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Abstract Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demon...

Giannarelli Diana; Cuppone Federica; Carlini Paolo; Di Maio Massimo; Bria Emilio; Cognetti Francesco; Milella Michele



Cancer screening trials: nuts and bolts. | (United States)

In the United States, new screening tests can become widely used often without valid scientific evidence of benefit or proper assessment of harm. Consequently, it is important for new tests to undergo rigorous trials as quickly as possible before widespread community use precludes establishment of a proper control arm. As exemplified by the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, it is possible to evaluate several screening tests and cancers in the same trial to preserve resources.


A surplus of positive trials: weighing biases and reconsidering equipoise  

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In this issue, Fries and Krishnan raise provocative new ideas to explain the surfeit of positive industry sponsored trials evaluating new drugs. They suggest that these trials were designed after so much preliminary work that they were bound to be positive (design bias) and that this violates clinical equipoise, which they characterize as an antiquated concept that should be replaced by a focus on subject autonomy in decision making and expected value for all treatments in a trial. We contend...

Felson, David T.; Glantz, Leonard



The Cessation in Pregnancy Incentives Trial (CPIT: study protocol for a randomized controlled trial  

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Full Text Available Abstract Background Seventy percent of women in Scotland have at least one baby, making pregnancy an opportunity to help most young women quit smoking before their own health is irreparably compromised. By quitting during pregnancy their infants will be protected from miscarriage and still birth as well as low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. In the UK, the NICE guidelines: ‘How to stop smoking in pregnancy and following childbirth’ (June 2010 highlighted that little evidence exists in the literature to confirm the efficacy of financial incentives to help pregnant smokers to quit. Its first research recommendation was to determine: Within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? Design and methods This study is a phase II exploratory individually randomized controlled trial comparing standard care for pregnant smokers with standard care plus the additional offer of financial voucher incentives to engage with specialist cessation services and/or to quit smoking during pregnancy. Participants (n?=?600 will be pregnant smokers identified at maternity booking who, when contacted by specialist cessation services, agree to having their details passed to the NHS Smokefree Pregnancy Study Helpline to discuss the trial. The NHS Smokefree Pregnancy Study Helpline will be responsible for telephone consent and follow-up in late pregnancy. The primary outcome will be self reported smoking in late pregnancy verified by cotinine measurement. An economic evaluation will refine cost data collection and assess potential cost-effectiveness while qualitative research interviews with clients and health professionals will assess the level of acceptance of this form of incentive payment. The research questions are: What is the likely therapeutic efficacy? Are incentives potentially cost-effective? Is individual randomization an efficient trial design without introducing outcome bias? Can incentives be introduced in a way that is feasible and acceptable? Discussion This phase II trial will establish a workable design to reduce the risks associated with a future definitive phase III multicenter randomized controlled trial and establish a framework to assess the costs and benefits of financial incentives to help pregnant smokers to quit. Trial registration Current Controlled Trials ISRCTN87508788

Tappin David M



Contribution of clinical trials to gross domestic product in Hungary. (United States)

Aim. To determine the contribution of clinical trials to the gross domestic product (GDP) in Hungary. Methods. An anonymous survey of pharmaceutical companies and clinical research organizations (CROs) was conducted to estimate their clinical trial-related employment and revenues. Clinical trial documents at the National Institute of Pharmacy (NIP) were analyzed to estimate trial-related revenues at health care institutions and the value of investigational medical products (IMPs) based on avoided drug costs. Financial benefits were calculated as 2010 US $ purchasing power parity (PPP) values. Results. Clinical trials increased the revenue of Hungarian health care providers by 1 US $65.6 million. The value of IMPs was US $67.0 million. Clinical trial operation and management activities generated 900 jobs and US $166.9 million in revenue among CROs and pharmaceutical companies. Conclusions. The contribution of clinical trials to the Hungarian GDP in 2010 amounted to 0.2%. Participation in international clinical trials may result in health, financial, and intangible benefits that contribute to the sustainability of health care systems, especially in countries with severe resource constraints. Although a conservative approach was employed to estimate the economic benefits of clinical trials, further research is necessary to improve the generalizability of our findings. PMID:25358877

Kaló, Zoltán; Antal, János; Pénzes, Miklós; Pozsgay, Csilla; Szepezdi, Zsuzsanna; Nagyjánosi, László



Open-access clinical trial registries: the Italian scenario  

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Full Text Available Abstract Background Citizens, patients and their representatives are increasingly insisting on working with health professionals to organize and discuss research protocols. The International Committee of Medical Journal Editors recommended setting up a public clinical trial registry where anyone can find key information about a trial. Around the world, governments have, in fact, now begun to legislate mandatory disclosure of all clinical trials. The aims of the present survey were to assess the availability of clinical trial registries for Italian citizens and to examine the transparency of the data items reported. Methods The availability of open-access clinical trial registries was surveyed on a sample of 182 websites, including research institutes and centers of excellence (IRCCS-teaching hospitals, hospitals and associations. For each registry we downloaded a sample of two trials to assess the correspondence of the data items reported. Results from the Italian and international registries were compared. Results Fifteen percent of the sample had an open-access registry of clinical trials. Comparison of the data items available, in terms of completeness and transparency, from institutional and international registries indicated wide variability. Conclusions Italian citizens, patients and their associations have scant access to local registries of clinical trials, and international registries are generally more informative. On the European level, advocacy and lobby actions are needed among citizens and patients to boost the diffusion of open-access clinical trial registries without language barriers, thereby facilitating participation, access to information, and the coordination of clinical research.

Mosconi Paola



The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS trial  

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Full Text Available Abstract Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II have demonstrated a mortality benefit of ?-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of ?-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction.

Bristow Michael R



A review of prospective Clinical Trials for neurogenic bladder: Pharmaceuticals (United States)

Introduction The neurogenic urinary bladder is defined as a dysfunctional bladder associated with a known neurological injury. We review the data from good quality clinical trials looking at drug therapy for the neurogenic bladder. Materials and methods In order to identify as many prospective trials as possible, we performed Internet searches, using the same search string: Urinary Bladder, neurogenic (MESH). In each case, the search was limited to clinical trial, prospective trial, subjects were human and the language was English. There was no year limit for our search. The next step was duplicate removal, which led to a final number of 580 papers. We defined clear inclusion criteria for the papers. Results A total of 82 full text papers were reviewed and analyzed according to the previously mentioned algorithm. The oldest two prospective clinical trials date back to 1976, with an obvious increase in number of trials each year, reaching more than five trials per year after 2001, which demonstrates increased interest toward the subject. The total number of patients included in the trials is 3904, 888 of which are children. The male: female ratio is close to 1, although there were 9 studies where no information regarding the sex of the patients was available. Conclusions Our analysis stresses the acute need for good quality trials looking at the drugs used for the management of the patients with neurogenic bladders, with adequate statistical power to support the data they present.

Braschi, Emmanuel; Lavelle, John



Angiographic outcomes contradict platelet data in the PLATO trial: confusion over official trial substudies. (United States)

Major indication-seeking phase 3 clinical trials usually include numerous subanalyses and substudies designed to facilitate the interpretation of results, often providing putative mechanisms that might explain clinical outcomes. Such subanalyses and/or substudies may focus on socioeconomic implications, cost-effectiveness, biomarker applicability, subgroup analyses, etc. Novel antiplatelet agents may benefit from substudies aimed at elucidating the effects on platelets, while angiographic data are also essential for the adequate assessment of coronary flow. Ideally, the data yielded from substudies should correlate well with the main results of the trial. However, in the PLATO (PLATelet Inhibition and Clinical Outcomes) trial, official angiographic data (PLATO-A) contradict platelet (PLATO-P) substudy results. While the large (n = 2,616) PLATO-A concluded that coronary flow and myocardial perfusion were almost identical after ticagrelor or clopidogrel, the small (n = 24) single-center PLATO-P suggested that ticagrelor achieved a highly significantly greater antiplatelet effect compared to clopidogrel after loading in patients enrolled in the same trial and at similar time points. In contrast to PLATO-P, PLATO-A corresponds well with clinical outcomes including the early percutaneous coronary intervention 'ticagrelor death paradox' in PLATO-USA patients and the lack of an early ticagrelor benefit in the overall invasive PLATO cohort reported by the FDA. The discrepancy between PLATO-A and PLATO-P is obvious and lacks a reasonable explanation: platelet activity and coronary flow are generally inversely related, as consistently shown for other antiplatelet regimens, and should be particularly matched when assessed in the frame of the same trial. PMID:24457905

Serebruany, Victor L



The Home-Based Older People's Exercise (HOPE trial: study protocol for a randomised controlled trial  

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Full Text Available Abstract Background Frailty is common in older age, and is associated with important adverse health outcomes including increased risk of disability and admission to hospital or long-term care. Exercise interventions for frail older people have the potential to reduce the risk of these adverse outcomes by increasing muscle strength and improving mobility. Methods/Design The Home-Based Older People's Exercise (HOPE trial is a two arm, assessor blind pilot randomised controlled trial (RCT to assess the effectiveness of a 12 week exercise intervention (the HOPE programme designed to improve the mobility and functional abilities of frail older people living at home, compared with usual care. The primary outcome is the timed-up-and-go test (TUGT, measured at baseline and 14 weeks post-randomisation. Secondary outcomes include the Barthel Index of activities of daily living (ADL, EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D quality of life measure and the geriatric depression scale (GDS, measured at baseline and 14 weeks post-randomisation. We will record baseline frailty using the Edmonton Frail Scale (EFS, record falls and document muscle/joint pain. We will test the feasibility of collection of data to identify therapy resources required for delivery of the intervention. Discussion The HOPE trial will explore and evaluate a home-based exercise intervention for frail older people. Although previous RCTs have used operationalised, non-validated methods of measuring frailty, the HOPE trial is, to our knowledge, the first RCT of an exercise intervention for frail older people that includes a validated method of frailty assessment at baseline. Trial registration ISRCTN: ISRCTN57066881

Forster Anne



Effectiveness of continuous glucose monitoring during diabetic pregnancy (GlucoMOMS trial; a randomised controlled trial  

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Full Text Available Abstract Background Hyperglycemia in pregnancy is associated with poor perinatal outcome. Even if pregnant women with diabetes are monitored according to current guidelines, they do much worse than their normoglycaemic counterparts, marked by increased risks of pre-eclampsia, macrosomia, and caesarean section amongst others. Continuous Glucose Monitoring (CGM is a new method providing detailed information on daily fluctuations, used to optimize glucose control. Whether this tool improves pregnancy outcome remains unclear. In the present protocol, we aim to assess the effect of CGM use in diabetic pregnancies on pregnancy outcome. Methods/design The GlucoMOMS trial is a multicenter open label randomized clinical trial with a decision and cost-effectiveness study alongside. Pregnant women aged 18 and over with either diabetes mellitus type 1 or 2 on insulin therapy or with gestational diabetes requiring insulin therapy before 30 weeks of gestation will be asked to participate. Consenting women will be randomly allocated to either usual care or complementary CGM. All women will determine their glycaemic control by self-monitoring of blood glucose levels and HbA1c. In addition, women allocated to CGM will use it for 5–7 days every six weeks. Based on their CGM profiles they receive dietary advice and insulin therapy adjustments if necessary. The primary outcome measure is rate of macrosomia, defined as a birth weight above the 90th centile. Secondary outcome measures will be birth weight, composite neonatal morbidity, maternal outcome and costs. The analyses will be according to the intention to treat principle. Discussion With this trial we aim at clarifying whether the CGM improves pregnancy outcome when used during diabetic pregnancies. Trial registration Nederlands Trial Register: NTR2996

Voormolen Daphne N



Phase 0 clinical trial- an overview  

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Full Text Available Drug discovery begins in the laboratory with target identification and validation followed by pre-clinical and clinical development. The entire process takes around 10 to 15 years. It is associated with high costs and a high rate of failure. The probability of a drug going beyond Phase I testing is quite low. The quest for discovering anti-cancer agents has shifted from non-specific chemotherapeutic agents to a specific molecular target-based approach. Drug development processes for various drugs need to be re-evaluated. Phase 0 clinical trials act as a novel tool to hasten and improve the drug development from laboratory to clinic. Phase 0 studies enable go versus no-go decisions for a new drug early in its development process. The administration of a single sub-therapeutic dose provides preliminary data on the pharmacokinetics of the drug. It helps in confirming whether the drug behaves in humans as was predicted by pre-clinical studies. Notwithstanding, Phase 0 clinical studies are associated with some disadvantages. This article describes about Phase 0- its rationale, conduct, potential benefits and limitations. Key Words: Drug development, phase 0, clinical trial

Aanchal Satija



Gateways to clinical trials. March 2003. (United States)

Gateways to clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and devlopment protal, This issue focuses on the following selection of drugs: AAV-CF, adalimumab, ademetionine, afeletecan hydrochloride, agomelatine, alemtuzumab, almotriptan, amdoxovir, aplidine, aranose, arsenic sulfide, atazanavir, atlizumab; Bimatoprost, BMS-181176, BMS-188667, bortezomib, bryostatin 1; Combretastatin A-4 phosphate; Darbepoetin alfa, darusentan, deferasirox, desloratadine, DTaP-HBV-IPV/Hib-vaccine, DTI-0009; Eculizumab, edodekin alfa, emtricitabine, enfuvirtide, epoetin, esomeprazole magnesium etoricoxib; Fampridine, fenretinide, FR-146687; Galiximab, gamma-Hydroxybutyrate sodium, ganirelix acetate, gefitinib, Gemtuzumab ozogamicin, gimatecan; HEA125xOKT3, hIL-13-PE38QQR, HSV-2 theracine, Hu14.18-IL-2, human gammaglobulin; Idraparinux sodium, imatinib mesylate, IMiD3, insulin detemir, interleukin-4, irofulven, ISAtx-247; JT-1001; Levetiracetam, levosimendan, liposomal doxorubicin, liposomal vincristine sulfate, lixivaptan, lopinavir, lumiracoxib; Maxacalcitol, melatonin, midostaurin, MLN-518; Neridronic acid, nesiritide, nitronaproxen; Oblimersen sodium, oregovomab; PEG-filgrastim polyglutamate paclitaxel, prasterone, pregabalin; Rosuvastatin calcium, rotigotine hydrochloride; SGN-30; T-1249, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipranavir, TMC-114, trabectedin, transdermal selegiline; UK-427857; Valdecoxib, valganciclovir hydrochloride, vardenafil, vatalanib succinate, vincristine sulfate TCS; Zofenopril calcium. PMID:12731460

Bayés, M; Rabasseda, X; Prous, J R



Treatment of blepharitis: recent clinical trials. (United States)

Blepharitis is a chronic inflammatory disease of the eyelids that is frequently encountered in clinical practice. The etiology of the disorder is complex and not fully understood, but the general consensus is that bacteria and inflammation contribute to the pathology. Blepharitis can be classified into anterior blepharitis, involving the anterior lid margin and eyelashes, and posterior blepharitis, characterized by dysfunction of the meibomian glands. Long-term management of symptoms may include daily eyelid cleansing routines and the use of therapeutic agents that reduce infection and inflammation. A cure is not possible in most cases, and subjective symptoms may persist even when a clinical assessment of signs indicates that the condition has improved. There are no established guidelines regarding therapeutic regimens, but recent clinical trials have shown that antibiotics and topical corticosteroids can produce significant improvement in signs and symptoms of blepharitis. Fixed combinations of a topical antibiotic and a corticosteroid offer an effective and convenient treatment modality that addresses both infectious and inflammatory components of the disease. Further clinical trials are needed to determine optimal therapies for managing blepharitis. PMID:25284773

Pflugfelder, Stephen C; Karpecki, Paul M; Perez, Victor L



Ethical pitfalls in neonatal comparative effectiveness trials. (United States)

Evidence-based medicine has been embraced wholeheartedly, and rightly so, as the best approach for reducing clinical uncertainty and ensuring that patients receive treatment and care that are efficacious (i.e. they work) and effective (i.e. they work in real life). High-quality evidence comes from high-quality clinical research. It would hence be reasonable to assume that these two would form a closely integrated partnership. Alas, this is not yet the case. So many uncertainties in medical care relate to treatments and practices already widely in use. In neonatal medicine, for example, some of us use protein-carbohydrate fortification of human milk and some of us do not, some of us stop enteral feeds during blood transfusions whereas some of us do not, some of us reach for dopamine when blood pressure falls while some of us use dobutamine. For our patients, these uncertainties represent a lottery, the throw of the dice that determines whether they receive the treatment advocated by Dr. A or Dr. B. They deserve better than this. Randomization is considered the gold standard approach to eliminating the clinician bias that very often dominates the choice of treatments. Randomization reduces the influence on outcomes of confounding by unknown factors, and ensures that every patient has a fair and equal chance of receiving the best possible treatment when this is, in fact, not known. In an ideal world, every medical uncertainty would be addressed in this way. The evaluation of treatments that are in accepted use has been termed 'comparative effectiveness research', i.e. the comparison of existing healthcare interventions to determine which works best, for whom and under which circumstances. Recently a long-standing uncertainty, the optimum saturation target for preterm babies receiving oxygen was put to the test of randomization. The accepted standard-of-care saturation range of 85-95% has been used for a considerable time and its use is intended to avoid both levels of oxygen that are too low or too high. Investigators in the UK, Australia, New Zealand and the USA designed randomized controlled trials to provide more precise guidance, by determining whether targeting the lower end of the accepted range (85-89%) resulted in reduced retinopathy of prematurity when compared with the upper end of the accepted range (91-95%). Between 2004 and 2009, the US SUPPORT trial (Surfactant, Positive Pressure and Oxygenation Randomized Trial) recruited approximately 1,300 infants and showed that babies at the higher end of the recommended oxygen saturation range had a greater incidence of retinopathy of prematurity, but that, unexpectedly, babies at the lower end had a higher risk of death [1]. The data monitoring committees of the BOOST II (Oxygen Saturation and Outcomes in Preterm Infants) trials in the UK, Australia and New Zealand reviewed their interim data, confirmed the higher risk of death in babies randomized to the lower saturation range, and halted further recruitment [2]. Without the trials, the lower saturation target would have continued to be applied to many babies, and many would have died as a result. Though many uncertainties remain, the trials facilitated advances in care. However, in March 2013, the lead investigators for the SUPPORT trial were informed by the US 'Office for Human Research Protections' that they were 'in violation of the regulatory requirements for informed consent, stemming from the failure to describe the reasonably foreseeable risks of blindness, neurological damage and death' [3]. This extraordinary conclusion indicates that the US regulators considered the researchers to be at fault for failing to foresee an unexpected trial result, and for randomizing babies to receive oxygen within the accepted standard-of-care limits. The ruling further implies that the regulators consider that clinicians are acting ethically when they deliver an accepted but non-evidence-based treatment based upon their personal bias, but are acting unethically when they make the selection by randomization. Clearly, there is a

Modi, Neena



Prevention and intervention trials for colorectal cancer. (United States)

There have been a number of candidates for chemopreventive agents from synthetic drugs and natural compounds suggested to prevent colorectal cancer. However, they have shown modest efficacy in humans. The reason for this could be partly explained by the use of inappropriate models in vitro and in vivo, and the limitation of chemoprevention trials. In Japan, there are no cancer chemopreventive medicines, and few cancer chemoprevention trials to date. In contrast, an increase in the prevalence of colorectal cancer in Japan has forced us to develop more efficient chemopreventive strategies. It is now a good time to review in detail the current status and future prospects for chemoprevention of colorectal cancer with respect to the future development of chemopreventive medicines, particularly using synthetic drugs and natural compounds in Asian populations. The role and mode of action of available synthetic drugs, mainly aspirin and metformin, are reviewed. In addition, the possible impact of natural compounds with anti-inflammatory/immunosuppressive properties, such as ?3 polyunsaturated fatty acid and lactoferrin, are also reviewed. PMID:23613189

Komiya, Masami; Fujii, Gen; Takahashi, Mami; Iigo, Masaaki; Mutoh, Michihiro



Alberta government trial of VSAT technology (United States)

Very small aperture terminal (VSAT) satellite systems offer the capability to quickly establish a data communications network without the necessity of installing terrestrial lines. Current VSAT systems also allow local management of the network, have excellent error rate performance, and can simultaneously support several different communications protocols. This paper describes the Government of Alberta's field trial of VSAT technology undertaken to investigate (1) the use of band-edge capacity of the Ku-band television channel transmitted over the Anik C3 satellite to transmit text and data, (2) the data protocol handling capabilities of the system, and (3) the application of VSAT technology to education and oil industry communications requirements. The system consists of a hub which handles transmission to and from the satellite, and multiple remote VSAT terminals in a star network. As a result of this trial, it was recommended that the VSAT system be configured to permit minor configuration changes online, to allow parallel downloading of common protocol software components, to allow configuration changes to be prepared and verified in advance of downloading remote terminals, that nonvolatile read/write memory capabilities be added to the remote terminals, and that remote diagnostics capabilities for VSAT be implemented. Finally, it was recommended that usage statistics be reported and a high speed X.25 computer interface capability be provided.

Allan, A. Rodney; Young, Goodwin K.


Improving the quality of randomized controlled trials in Chinese herbal medicine, Part ?: clinical trial design and methodology  

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Full Text Available Objective: To discuss the quality of randomized controlled trials (RCTs in Chinese herbal medicine (CHM with respect to design and methodology, and provide suggestions for further improvement in future clinical trials. Methods: A search of the Cochrane Library was conducted to identify RCTs of CHM on line in July 2005. Quality of the RCTs was assessed using a 11-item checklist modified from the revised CONSORT statement, with 2 items specific to CHM (i.e. herb preparation form and quality control of herbs. Results: The search yielded 167 RCTs that were selected for assessment. All trials included statements about the interventions, objectives, primary outcome design, statistical methods, and herb preparation form. Although 163 (97.6% trials reported inclusion criteria, exclusion criteria were only reported in 26 (15.6% trials. Fewer than 10% of trials clearly stated the random allocation sequence generation methods, and only 2.4% mentioned allocation concealment. The vast majority (86.8% of trials were open-label, while only 13.2% used blinding. Almost half (45.5% administered the CHM intervention as a tea or decoction. Only one trial (0.6% reported a sample size calculation, and a single trial (0.6% discussed quality control of the CHM intervention. Conclusion: The overall methodologic quality of RCTs in CHM was poor. It is essential to improve the design of future RCTs in this clinical area. Recommendations: (1 Investigator conducting RCTs should have formal training about clinical trial design; (2 A flow chart is recommended to ensure that all essential steps of clinical trial design are included. (3 Conducting pilot studies prior to RCTs may help improve their design; (4 Registration of clinical trials and publishing their protocols prior to enrolment may reduce publication bias and solicit peer reviews of the proposed design; (5 Collaboration between CHM investigators and traditional medicine academic research centers interested in integrative medicine may lead to quality improvement of RCTs of CHM.

Zhao-Xiang BIAN



RReACT goes global: perils and pitfalls of constructing a global open-access database of registered analgesic clinical trials and trial results. (United States)

Eliminating publication bias requires ensuring public awareness of studies and access to results. Clinical trial registries provide basic trial information, but access to unbiased trial results is inadequate. Nearly all studies of trial registration and results reporting have been limited to the registry. We analyzed trial registration, registry functionality, cross-registry harmonization, and results reporting on all 15 primary registries in the World Health Organization International Clinical Trials Registry Platform (ICTRP) for postherpetic neuralgia, painful diabetic neuropathy, and fibromyalgia. A total of 447 unique trials were identified, with 86 trials listed on more than one registry. A comprehensive search algorithm was used to find trial results in the peer-reviewed literature and the grey literature. Creating a global database of registered trials and trial results proved surprisingly difficult for several reasons: (1) ICTRP does not reliably identify trials listed on multiple registries, manual searches are necessary; (2) Searching ICTRP yields different results than searching individual registries; (3) Outcome measure descriptions for multiply registered trials vary between registries; (4) Registry-publication pairings are often inaccurate or incomplete; (5) Grey literature results are not permanent. Overall, only 46% of all trials had results available. Trials registered on were significantly more likely to have results (52% vs. 18%, Pmeeting abstracts and peer-reviewed papers, specific strategies are offered to facilitate identifying multiply registered studies and ensuring accurate pairing of results and publications. PMID:24726925

Munch, Troels; Dufka, Faustine L; Greene, Kaitlin; Smith, Shannon M; Dworkin, Robert H; Rowbotham, Michael C



Review of clinical trials for mitochondrial disorders: 1997-2012. (United States)

Over the last 15 years, some 16 open and controlled clinical trials for potential treatments of mitochondrial diseases have been reported or are in progress, and are summarized and reviewed herein. These include trials of administering dichloroacetate (an activator of pyruvate dehydrogenase complex), arginine or citrulline (precursors of nitric oxide), coenzyme Q10 (CoQ10; part of the electron transport chain and an antioxidant), idebenone (a synthetic analogue of CoQ10), EPI-743 (a novel oral potent 2-electron redox cycling agent), creatine (a precursor of phosphocreatine), combined administration (of creatine, ?-lipoate, and CoQ10), and exercise training (to increase muscle mitochondria). These trials have included patients with various mitochondrial disorders, a selected subcategory of mitochondrial disorders, or specific mitochondrial disorders (Leber hereditary optic neuropathy or mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes). The trial designs have varied from open-label/uncontrolled, open-label/controlled, or double-blind/placebo-controlled/crossover. Primary outcomes have ranged from single, clinically-relevant scores to multiple measures. Eight of these trials have been well-controlled, completed trials. Of these only 1 (treatment with creatine) showed a significant change in primary outcomes, but this was not reproduced in 2 subsequent trials with creatine with different patients. One trial (idebenone treatment of Leber hereditary optic neuropathy) did not show significant improvement in the primary outcome, but there was significant improvement in a subgroup of patients. Despite the paucity of benefits found so far, well-controlled clinical trials are essential building blocks in the continuing search for more effective treatment of mitochondrial disease, and current trials based on information gained from these prior experiences are in progress. Because of difficulties in recruiting sufficient mitochondrial disease patients and the relatively large expense of conducting such trials, advantageous strategies include crossover designs (where possible), multicenter collaboration, and the selection of very few, clinically relevant, primary outcomes. PMID:23361264

Kerr, Douglas S



Regulatory Scientific Advice on Non-Inferiority Drug Trials (United States)

The active-controlled trial with a non-inferiority design has gained popularity in recent years. However, non-inferiority trials present some methodological challenges, especially in determining the non-inferiority margin. Regulatory guidelines provide some general statements on how a non-inferiority trial should be conducted. Moreover, in a scientific advice procedure, regulators give companies the opportunity to discuss critical trial issues prior to the start of the trial. The aim of this study was to identify potential issues that may benefit from more explicit guidance by regulators. To achieve this, we collected and analyzed questions about non-inferiority trials posed by applicants for scientific advice in Europe in 2008 and 2009, as well as the responses given by the European Medicines Agency (EMA). In our analysis we included 156 final letters of advice from 2008 and 2009, addressed to 94 different applicants (manufacturers). Our analysis yielded two major findings: (1) applicants frequently asked questions ‘whether’ and ‘how’ to conduct a non-inferiority trial, 26% and 74%, respectively, and (2) the EMA regulators seem mainly concerned about the choice of the non-inferiority margin in non-inferiority trials (36% of total regulatory answers). In 40% of the answers, the EMA recommended using a stricter margin, and in 10% of the answers regarding non-inferiority margins, the EMA questioned the justification of the proposed non-inferiority margin. We conclude that there are still difficulties in selecting the appropriate methodology for non-inferiority trials. Straightforward and harmonized guidance regarding non-inferiority trials is required, for example on whether it is necessary to conduct such a trial and how the non-inferiority margin is determined. It is unlikely that regulatory guidelines can cover all therapeutic areas; therefore, in some cases regulatory scientific advice may be used as an opportunity for tailored advice. PMID:24040346

Knol, Mirjam J.; Klungel, Olaf H.; Gispen-De Wied, Christine C.; de Boer, Antonius; Hoes, Arno W.; Leufkens, Hubert G.; Mantel-Teeuwisse, Aukje K.



Impact of Payment Policy on Enrollment and Retention in Clinical Trials | (United States)

To avoid financial loss, clinical trial sites are analyzing a trial's financial impact and may decide not to initiate a trial if financial implications are negative. This abstract may be useful for those designing trials as well as institutions considering participating in a trial.


Potential pitfalls in the design and reporting of clinical trials. | (United States)

Factors that can lead to insufficient recruitment to a clinical trial include overestimation of support for the trial, failure to engage the target population in trial design, and inaccurate estimates of appropriate sample size and trial duration. Improved public acceptance of a trial can be a major factor in ensuring participation.


The Hidden Economic Impact of Non-enrolling Clinical Trials from the Academic Medical Center Perspective | (United States)

This study compares oncology and nononcology clinical trial accrual performance and assesses the economic impact of these trials at a single institution. For this assessment, terminated trials resulting in 0 or 1 accruals were defined as nonenrolling trials. The number of nonenrolling sites was stratified by oncology and nononcology trials and summarized across funding mechanisms categorized by industry, institutional, federal, and nonfunded trials. The percentage of nonenrolling trials was significantly greater for oncology trials (around 41%) compared with nononcology trials (around 25%).


DIRECT trial. Diverticulitis recurrences or continuing symptoms: Operative versus conservative Treatment. A MULTICENTER RANDOMISED CLINICAL TRIAL  

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Full Text Available Abstract Background Persisting abdominal complaints are common after an episode of diverticulitis treated conservatively. Furthermore, some patients develop frequent recurrences. These two groups of patients suffer greatly from their disease, as shown by impaired health related quality of life and increased costs due to multiple specialist consultations, pain medication and productivity losses. Both conservative and operative management of patients with persisting abdominal complaints after an episode of diverticulitis and/or frequently recurring diverticulitis are applied. However, direct comparison by a randomised controlled trial is necessary to determine which is superior in relieving symptoms, optimising health related quality of life, minimising costs and preventing diverticulitis recurrences against acceptable morbidity and mortality associated with surgery or the occurrence of a complicated recurrence after conservative management. We, therefore, constructed a randomised clinical trial comparing these two treatment strategies. Methods/design The DIRECT trial is a multicenter randomised clinical trial. Patients (18-75 years presenting themselves with persisting abdominal complaints after an episode of diverticulitis and/or three or more recurrences within 2 years will be included and randomised. Patients randomised for conservative treatment are treated according to the current daily practice (antibiotics, analgetics and/or expectant management. Patients randomised for elective resection will undergo an elective resection of the affected colon segment. Preferably, a laparoscopic approach is used. The primary outcome is health related quality of life measured by the Gastro-intestinal Quality of Life Index, Short-Form 36, EQ-5D and a visual analogue scale for pain quantification. Secondary endpoints are morbidity, mortality and total costs. The total follow-up will be three years. Discussion Considering the high incidence and the multicenter design of this study, it may be assumed that the number of patients needed for this study (n = 214, may be gathered within one and a half year. Depending on the expertise and available equipment, we prefer to perform a laparoscopic resection on patients randomised for elective surgery. Should this be impossible, an open technique may be used as this also reflects the current situation. Trial Registration (Trial register number: NTR1478

van de Wall Bryan JM



The CORONIS Trial. International study of caesarean section surgical techniques: a randomised fractional, factorial trial  

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Full Text Available Abstract Background Caesarean section is one of the most commonly performed operations on women throughout the world. Rates have increased in recent years – about 20–25% in many developed countries. Rates in other parts of the world vary widely. A variety of surgical techniques for all elements of the caesarean section operation are in use. Many have not yet been rigorously evaluated in randomised controlled trials, and it is not known whether any are associated with better outcomes for women and babies. Because huge numbers of women undergo caesarean section, even small differences in post-operative morbidity rates between techniques could translate into improved health for substantial numbers of women, and significant cost savings. Design CORONIS is a multicentre, fractional, factorial randomised controlled trial and will be conducted in centres in Argentina, Ghana, India, Kenya, Pakistan and Sudan. Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision. Five comparisons will be carried out in one trial, using a 2 × 2 × 2 × 2 × 2 fractional factorial design. This design has rarely been used, but is appropriate for the evaluation of several procedures which will be used together in clinical practice. The interventions are: • Blunt versus sharp abdominal entry • Exteriorisation of the uterus for repair versus intra-abdominal repair • Single versus double layer closure of the uterus • Closure versus non-closure of the peritoneum (pelvic and parietal • Chromic catgut versus Polyglactin-910 for uterine repair The primary outcome is death or maternal infectious morbidity (one or more of the following: antibiotic use for maternal febrile morbidity during postnatal hospital stay, antibiotic use for endometritis, wound infection or peritonitis or further operative procedures; or blood transfusion. The sample size required is 15,000 women in total; at least 7,586 women in each comparison. Discussion Improvements in health from optimising caesarean section techniques are likely to be more significant in developing countries, because the rates of postoperative morbidity in these countries tend to be higher. More women could therefore benefit from improvements in techniques. Trial registration The CORONIS Trial is registered in the Current Controlled Trials registry. ISCRTN31089967.



Randomized trial of achieving healthy lifestyles in psychiatric rehabilitation: the ACHIEVE trial  

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Full Text Available Abstract Background Overweight and obesity are highly prevalent among persons with serious mental illness. These conditions likely contribute to premature cardiovascular disease and a 20 to 30 percent shortened life expectancy in this vulnerable population. Persons with serious mental illness need effective, appropriately tailored behavioral interventions to achieve and maintain weight loss. Psychiatric rehabilitation day programs provide logical intervention settings because mental health consumers often attend regularly and exercise can take place on-site. This paper describes the Randomized Trial of Achieving Healthy Lifestyles in Psychiatric Rehabilitation (ACHIEVE. The goal of the study is to determine the effectiveness of a behavioral weight loss intervention among persons with serious mental illness that attend psychiatric rehabilitation programs. Participants randomized to the intervention arm of the study are hypothesized to have greater weight loss than the control group. Methods/Design A targeted 320 men and women with serious mental illness and overweight or obesity (body mass index ? 25.0 kg/m2 will be recruited from 10 psychiatric rehabilitation programs across Maryland. The core design is a randomized, two-arm, parallel, multi-site clinical trial to compare the effectiveness of an 18-month behavioral weight loss intervention to usual care. Active intervention participants receive weight management sessions and physical activity classes on-site led by study interventionists. The intervention incorporates cognitive adaptations for persons with serious mental illness attending psychiatric rehabilitation programs. The initial intensive intervention period is six months, followed by a twelve-month maintenance period in which trained rehabilitation program staff assume responsibility for delivering parts of the intervention. Primary outcomes are weight loss at six and 18 months. Discussion Evidence-based approaches to the high burden of obesity and cardiovascular disease risk in person with serious mental illness are urgently needed. The ACHIEVE Trial is tailored to persons with serious mental illness in community settings. This multi-site randomized clinical trial will provide a rigorous evaluation of a practical behavioral intervention designed to accomplish and sustain weight loss in persons with serious mental illness. Trial Registration Clinical NCT00902694

Guallar Eliseo



Individual nutrition therapy and exercise regime: A controlled trial of injured, vulnerable elderly (INTERACTIVE trial  

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Full Text Available Abstract Background Proximal femoral fractures are amongst the most devastating consequences of osteoporosis and injurious accidental falls with 25–35% of patients dying in the first year post-fracture. Effective rehabilitation strategies are evolving however, despite established associations between nutrition, mobility, strength and strength-related functional outcomes; there has been only one small study with older adults immediately following fragility fracture where a combination of both exercise and nutrition have been provided. The aim of the INTERACTIVE trial is to establish whether a six month, individualised exercise and nutrition program commencing within fourteen days of surgery for proximal femur fracture, results in clinically and statistically significant improvements in physical function, body composition and quality of life at an acceptable level of cost and resource use and without increasing the burden of caregivers. Methods and Design This randomised controlled trial will be performed across two sites, a 500 bed acute hospital in Adelaide, South Australia and a 250 bed acute hospital in Sydney, New South Wales. Four hundred and sixty community-dwelling older adults aged > 70 will be recruited after suffering a proximal femoral fracture and followed into the community over a 12-month period. Participants allocated to the intervention group will receive a six month individualised care plan combining resistance training and nutrition therapy commencing within 14 days post-surgery. Outcomes will be assessed by an individual masked to treatment allocation at six and 12 months. To determine differences between the groups at the primary end-point (six months, ANCOVA or logistic regression will be used with models adjusted according to potential confounders. Discussion The INTERACTIVE trial is among the first to combine nutrition and exercise therapy as an early intervention to address the serious consequence of rapid deconditioning and weight loss and subsequent ability to regain pre-morbid function in older patients post proximal femoral fracture. The results of this trial will guide the development of more effective rehabilitation programs, which may ultimately lead to reduced health care costs, and improvements in mobility, independence and quality of life for proximal femoral fracture sufferers. Trial registration Australian Clinical Trials Registry: ACTRN12607000017426.

Whitehead Craig



European user trial of paging by satellite (United States)

British Telecom conceived the idea of adapting their existing paging service, together with the use of existing terrestrial pagers, to yield a one way data (i.e., paging) satellite service to mobiles. The user trial of paging by satellites was successful. It demonstrated that services could be provided over a wide geographical area to low priced terminals. Many lessons were learned in unexpected areas. These include the need for extensive liaison with all users involved, especially the drivers, to ensure they understood the potential benefits. There was a significant desire for a return acknowledgement channel or even a return data channel. Above all there is a need to ensure that the equipment can be taken across European borders and legitimately used in all European countries. The next step in a marketing assessment would be to consider the impact of two way data messaging such as INMARSAT-C.

Fudge, R. E.; Fenton, C. J.



Commentary: Pursuing justice in death penalty trials. (United States)

The capital trial, by its nature, is fraught with emotionally disturbing elements that jurors must face when deciding the ultimate fate of a guilty defendant. A confluence of mitigating and aggravating factors influences a capital jury's decision to impose a sentence of death. The presence or absence of defendant remorse in these cases may make all the difference in whether a capital defendant's life is spared. This commentary examines the onerous emotional toll encountered by capital jurors in light of the findings of Corwin and colleagues regarding defendant remorse and juror's need for affect. The commentary also presents practical and ethics-related considerations that should be kept in mind when reflecting on their study. PMID:22396341

Watson, Clarence; Eth, Spencer; Leong, Gregory B



Quality assurance in the CHART clinical trial  

International Nuclear Information System (INIS)

As part of the clinical trial of CHART (continuous hyperfractionated accelerated radiotherapy) a quality assurance programme was included. The technical part of this -- which is reported in this paper -- is a series of tests designed to check all aspects of treatment planning and delivery. The results of visits to the 13 participating centres -- and repeat visits to some of these centres -- are discussed. The main areas tested were as follows. The linear accelerator: mechanical, and optical, scales and indicators; radiation field size; flatness and symmetry. Dosimetry: output; wedge factor; beam energy; phantom measurements against a plan calculated by the centre. Simulator: mechanical, optical scales and indicators. The results show these centres work within the tolerances chosen for most parameters. Flatness, wedge factor and energy were areas of weakness in some centres. This must be partly the cause of the spread of phantom measurements which, after removal of variations in output, still range from -7 to +6% between calculated and measured values


Outcomes research: clinical trials in the elderly. (United States)

Very few clinical trials have been done in the elderly. This report reviews results of two completed studies and describes one in progress. The largest published study was a United States Veterans Affairs Administration study in newly diagnosed patients with epilepsy. It compared carbamazepine to gabapentin and lamotrigine, and found that, although equivalent in efficacy, the newer antiepileptic drugs (AEDs) were better tolerated. This study also highlighted many of the difficulties in recruiting and retaining elderly patients in studies, the large number of comorbidities, and the problems of distinguishing seizures in the elderly from other symptoms. Another study of new-onset epilepsy suggested that a large percentage of elderly patients respond to initial AED therapy, but side effect profiles differ. More studies are needed to better define the risk/benefit relationships in elderly patients. PMID:16413171

Leppik, Ilo E; Brodie, Martin J; Saetre, Erik R; Rowan, A James; Ramsay, R Eugene; Macias, Flavia; Jacobs, Margaret P



The Svalbard shoreline oilspill field trials  

International Nuclear Information System (INIS)

The 1997 Svalbard shoreline oil spill field experiment was conducted to quantify the effectiveness of different in situ shoreline treatment options that are commonly used to accelerate natural oil removal processes on mixed coarse sediment beaches. Three experimental sites were chosen near the mining town of Sveagruva on Spitsbergen, the largest island in Svalbard, Norway. 5,500 litres of an intermediate fuel oil, was applied directly to a 3 m wide area of the upper intertidal zone sediment surface in a controlled and uniform manner. Full scale treatments began one week after oiling to allow for wave and tidal washing and stabilization of the oiled zone. Five treatment options were used: (1) sediment relocation, (2) tilling (or aeration); (3) bioremediation, (4) tilling combined with bioremediation, and (5) natural recovery. The sediment was treated in the same way as in an actual response operation. The trials were successful from both an operational and experimental point of view. 14 refs., 2 tabs., 9 figs


Diagnostic trials using CT scanning in urology  

Energy Technology Data Exchange (ETDEWEB)

We attempted various new diagnostic trials using CT scanning. The results obtained were: 1) Twelve transplanted kidneys were scanned after bolus contrast administration. Enhancing indices (EI) calculated from the formula: EI = (CT numbers 10 minutes after injection) / (CT numbers before injection) were inversely proportional to serum creatinine. 2) CT guided puncture was successful in percutaneous nephrostomy in 3 of 5 cases of obstructive uropathy and in 5 cases of renal cystic disease. 3) Emergent CT scans were diagnostically useful in 9 cases of urinary tract injury to indicate surgery. 4) CT scans after perivesical pneumography in 5 cases of vesical tumor diclosed perivesical invasion. 5) Cervical CT scans were performed as a localization study of parathyroid gland in 3 cases of secondary hyperparathyroidism in chronic renal insufficiency. More than 1400 mg of parathyroid gland in the neck was clearly visualized on cervical CT scans.

Fujita, T. (Fujita Gakuen Univ., Toyoake, Aichi (Japan). School of Medicine)



Mechanical ventilation: lessons from the ARDSNet trial  

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Full Text Available Abstract The acute respiratory distress syndrome (ARDS is an inflammatory disease of the lungs characterized clinically by bilateral pulmonary infiltrates, decreased pulmonary compliance and hypoxemia. Although supportive care for ARDS seems to have improved over the past few decades, few studies have shown that any treatment can decrease mortality for this deadly syndrome. In the 4 May 2000 issue of New England Journal of Medicine, the results of an NIH-sponsored trial were presented; they demonstrated that the use of a ventilatory strategy that minimizes ventilator-induced lung injury leads to a 22% decrease in mortality. The implications of this study with respect to clinical practice, further ARDS studies and clinical research in the critical care setting are discussed.

Marco Ranieri V



The Svalbard shoreline oilspill field trials  

Energy Technology Data Exchange (ETDEWEB)

The 1997 Svalbard shoreline oil spill field experiment was conducted to quantify the effectiveness of different in situ shoreline treatment options that are commonly used to accelerate natural oil removal processes on mixed coarse sediment beaches. Three experimental sites were chosen near the mining town of Sveagruva on Spitsbergen, the largest island in Svalbard, Norway. 5,500 litres of an intermediate fuel oil, was applied directly to a 3 m wide area of the upper intertidal zone sediment surface in a controlled and uniform manner. Full scale treatments began one week after oiling to allow for wave and tidal washing and stabilization of the oiled zone. Five treatment options were used: (1) sediment relocation, (2) tilling (or aeration); (3) bioremediation, (4) tilling combined with bioremediation, and (5) natural recovery. The sediment was treated in the same way as in an actual response operation. The trials were successful from both an operational and experimental point of view. 14 refs., 2 tabs., 9 figs.

Sergy, G.A. [Environment Canada, Edmonton, AB (Canada); Guenette, C.C. [SINTEF Applied Chemistry Environmental Engineering, Trondheim (Norway); Owens, E.H. [Owens Coastal Consultants, Bainbridge Island, WA (United States); Prince, R.C. [Exxon Research and Engineering Co., Annandale, NJ (United States)



Training Residential Staff to Conduct Trial-Based Functional Analyses (United States)

We taught 6 supervisors of a residential service provider for adults with developmental disabilities to train 9 house managers to conduct trial-based functional analyses. Effects of the training were evaluated with a nonconcurrent multiple baseline. Results suggest that house managers can be trained to conduct trial-based functional analyses with…

Lambert, Joseph M.; Bloom, Sarah E.; Kunnavatana, S. Shanun; Collins, Shawnee D.; Clay, Casey J.



Problems encountered in recruiting patients to an ophthalmic drug trial. (United States)

Two clinical trials to assess the efficacy of two topical beta-blocker preparations involved the recruitment of 60 and 40 patients respectively. The greatest obstacle encountered in carrying out the trials was recruiting patients. This difficulty is reported in detail and comparisons are made with the experience of others who have met similar problems. PMID:2751975

Quick, A. M.; Khaw, P. T.; Elkington, A. R.




The manual concentrates on those aspects of a trial burn that are the most important and those that are potentially troublesome. The manual contains practical explanations based on experience of Midwest Research Institute (MRI) and others in conducting trial burns and related tes...


Review on clinical trials of targeted treatments in malignant mesothelioma  

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Abstract Purpose Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all clinical trials evaluating the effect of targeted treatments in MM. Methods An extensive litera...



An Overview of NCI’s National Clinical Trials Network (United States)

Information about the National Clinical Trial Network’s (NCTN) structure, a summary of the changes taking place as a result of the NCTN launch, and a synopsis of how these changes build on the success of the Cooperative Group program and will improve the speed and efficiency of cancer clinical trials.


Cluster randomised trials in the medical literature: two bibliometric surveys  

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Full Text Available Abstract Background Several reviews of published cluster randomised trials have reported that about half did not take clustering into account in the analysis, which was thus incorrect and potentially misleading. In this paper I ask whether cluster randomised trials are increasing in both number and quality of reporting. Methods Computer search for papers on cluster randomised trials since 1980, hand search of trial reports published in selected volumes of the British Medical Journal over 20 years. Results There has been a large increase in the numbers of methodological papers and of trial reports using the term 'cluster random' in recent years, with about equal numbers of each type of paper. The British Medical Journal contained more such reports than any other journal. In this journal there was a corresponding increase over time in the number of trials where subjects were randomised in clusters. In 2003 all reports showed awareness of the need to allow for clustering in the analysis. In 1993 and before clustering was ignored in most such trials. Conclusion Cluster trials are becoming more frequent and reporting is of higher quality. Perhaps statistician pressure works.

Bland J Martin



Invasion of the Zebra Mussels: A Mock Trial Activity (United States)

In this activity, students learn about the important topic of invasive species, specifically Zebra Mussels. Students role-play different characters in a real-life situation: the trial of the Zebra Mussel for unlawful disruption of the Great Lakes ecosystem. Students will also learn about jurisprudential inquiry by examining the trial process. This…

Beck, Judy A.; Czerniak, Charlene M.



Review on clinical trials of targeted treatments in malignant mesothelioma  

DEFF Research Database (Denmark)

Malignant mesothelioma (MM) is an aggressive tumor of the serosal surfaces with a poor prognosis. Advances in the understanding of tumor biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. This article is a comprehensive review of all clinical trials evaluating the effect of targeted treatments in MM.

Jakobsen, Jan Nyrop; SØrensen, Jens Benn



Neurokinin-1 receptor antagonists as novel antidepressants: trials and tribulations. (United States)

Based upon animal experiments and early clinical trials, neurokinin-1 receptor antagonists showed promise as novel antidepressants. Subsequently, however, more extensive clinical trials did not reveal evidence of efficacy in depression. The development of novel antidepressants will require a better understanding of the neural basis of antidepressant action in humans. PMID:17906236

Hafizi, Sepehr; Chandra, Prakash; Cowen, J



Future vision for the quality assurance of oncology clinical trials  

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Full Text Available The National Cancer Institute clinical cooperative groups have been instrumental over the past 50 years in developing clinical trials and evidence based process improvements for clinical oncology patient care. The cooperative groups are undergoing a transformation process as we further integrate molecular biology into personalized patient care and move to incorporate international partners in clinical trials. To support this vision, data acquisition and data management informatics tools must become both nimble and robust to support transformational research at an enterprise level. Information, including imaging, pathology, molecular biology, radiation oncology, surgery, systemic therapy and patient outcome data needs to be integrated into the clinical trial charter using adaptive clinical trial mechanisms for design of the trial. This information needs to be made available to investigators using digital processes for real time data analysis. Future clinical trials will need to be designed and completed in a timely manner facilitated by nimble informatics processes for data management. This paper discusses both past experience and future vision for clinical trials as we move to develop data management and quality assurance processes to meet the needs of the modern trial.

ThomasFitzGerald, MD



Reforms speed initiation of NCI-sponsored clinical trials (United States)

The process of opening a cancer clinical trial for patient accrual often takes years, and research has shown that trials which are slow to register patients often fail to finish. Following a thorough review, NCI’s Operational Efficiency Working Group produced a series of recommendations that are now being implemented.


Towards a framework of success factors for clinical trials  

DEFF Research Database (Denmark)

Clinical trials in the pharmaceutical industry are the most critical part of the drug development process with respect to obtaining the market approval from the authorities. Clinical trials are highly expensive, time-consuming and often unsuccessful. While new product development (NPD) literature has extensively investigated success factors in R&D projects, it has not directly addressed success factors in clinical trials, as the late testing stage of a NPD yet. The aim of this paper is to enhance our understanding of the clinical trial management by creating a new conceptual framework of success factors. This paper creates the new framework by combining success factors from NPD literature and from empirical evidence collected through 11 semi-structured interviews with experts in clinical trials. The framework of success factors provides managerial guidelines for practitioners to optimize clinical trials reducing failures and increasing profits. The framework directs managerial focus on the most important factors for success and helps managers in decision-making of operational tasks. The framework can also be applied as a checklist for assessing the status of a clinical trial and later as a benchmarking tool to compare clinical trial processes. Dependencies among the identified factors seem to exist, thus a set of propositions, can be developed from the success factors and be the basis for future empirical testing.

Buonansegna, Erika; Salomo, SØren



Trial-by-Trial Changes in a Priori Informational Value of External Cues and Subjective Expectancies in Human Auditory Attention (United States)

Background Preparatory activity based on a priori probabilities generated in previous trials and subjective expectancies would produce an attentional bias. However, preparation can be correct (valid) or incorrect (invalid) depending on the actual target stimulus. The alternation effect refers to the subjective expectancy that a target will not be repeated in the same position, causing RTs to increase if the target location is repeated. The present experiment, using the Posner's central cue paradigm, tries to demonstrate that not only the credibility of the cue, but also the expectancy about the next position of the target are changedin a trial by trial basis. Sequences of trials were analyzed. Results The results indicated an increase in RT benefits when sequences of two and three valid trials occurred. The analysis of errors indicated an increase in anticipatory behavior which grows as the number of valid trials is increased. On the other hand, there was also an RT benefit when a trial was preceded by trials in which the position of the target changed with respect to the current trial (alternation effect). Sequences of two alternations or two repetitions were faster than sequences of trials in which a pattern of repetition or alternation is broken. Conclusions Taken together, these results suggest that in Posner's central cue paradigm, and with regard to the anticipatory activity, the credibility of the external cue and of the endogenously anticipated patterns of target location are constantly updated. The results suggest that Bayesian rules are operating in the generation of anticipatory activity as a function of the previous trial's outcome, but also on biases or prior beliefs like the “gambler fallacy”. PMID:21698164

Arjona, Antonio; Gomez, Carlos M.



Gateways to Clinical Trials. June 2002. (United States)

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, alicaforsen sodium, almotriptan, alteplase, amlodipine, amoxicillin trihydrate, amprenavir, argatroban monohydrate, aspirin, atorvastatin calcium, azathioprine; Baclofen, benidipine hydrochloride, benserazide, BMS-214662, bosentan, botulinum toxin type B; Candesartan cilexetil, carbamazepine, carbidopa, carboplatin, ceftriaxone sodium, celecoxib, cetirizine hydrochloride, clarithromycin, clavulanate potassium, clopidogrel hydrogensulfate, clozapine, CPI-1189, cyclophosphamide, cytarabine; Darbepoetin alfa, denileukin diftitox, dexamethasone, dipyridamole, droperidol, DW-166HC; Ebastine, efalizumab, efavirenz, eletriptan, enalapril maleate, enfuvirtide, enoxaparin sodium, enrasentan, entacapone, epoetin, eprosartan mesilate, etanercept, etoricoxib; Fenofibratefexofenadine hydrochloride, filgrastim, fludarabine phosphate, fluoxetine hydrochloride fluvoxamine maleate, frovatriptan, furosemide; Gabapentin, galantamine hydrobromide, gatifloxacin, gefitinib, ghrelin (human), glatiramer acetate; Haloperidol; Ibuprofen, ibuprofen, guaiacol ester, idarubicin hydrochloride, imipramine hydrochloride, imiquimod, interferon beta, interferon beta-1a, interferon beta-1b, interferon omega, irbesartan, itraconazole; Ketorolac, ketorolac tromethamine; Lamifiban, lamotrigine, lanoteplase, lansoprazole, leflunomide, leuprorelin acetate, levetiracetam, levocetirizine, levodopa, lisinopril, loratadine; Manidipine, methylprednisolone, metronidazole, mirtazapine, mizolastine, modafinil, morphine sulfate; Naproxen sodium, naratriptan hydrochloride, nifedipine, NSC-683864; Ofloxacin, olanzapine, omalizumab, omapatrilat, ondansetron hydrochloride, oxcarbazepine; Paclitaxel, parecoxib sodium, paroxetine hydrochloride, phenytoin sodium, pimecrolimus, pramipexole hydrochloride, pravastatin, prednisone, pregabalin; Quetiapine fumarate; Ranitidine hydrochloride, rasburicase, ritonavir, rivastigmine tartrate, rizatriptan benzoate, rofecoxib; Saquinavir mesilate, sertraline, sildenafil citrate, simvastatin, sumatriptan succinate; Tacrolimus, tiagabine hydrochloride, ticlopidine hydrochloride, tirofiban hydrochloride, tolvaptan, topiramate, tretinoin; Valproic acid, valsartan, venlafaxine hydrochloride, verapamil; Warfarin sodium; Ximelagatran; Zanamivir, ziconotide, zolmitriptan, zonisamide. PMID:12168506

Bayes, M; Rabasseda, X; Prous, J R



Contemporary issues in clinical trials for medulloblastoma  

International Nuclear Information System (INIS)

Medulloblastoma is the seminal pediatric brain tumor providing opportunities for clinical investigation to define improved treatment strategies for both disease control and ultimate functional integrity. Recent studies addressing neuraxis radiation dose provide a 'standard' for conventional therapy while establishing 5-year disease control rates for 'favorable' or 'low risk' presentations approximating 60% following surgery and irradiation. A highly visible recent report of combined post-operative irradiation and chemotherapy incorporating a platinum- and alkylator-based regimen indicates 5-year disease control approaching 90% in localized medulloblastoma. Despite unfavorable outcome with reduced-dose neuraxis irradiation in earlier trials, further data from recent studies suggest the addition of post-operative chemotherapy to similarly reduced-dose neuraxis irradiation (23.4 Gy) in 'favorable' presentations may result in progression-free survival rates at least equivalent to those achieved with full-dose neuraxis irradiation (36 Gy) absent chemotherapy. The panel will (1) provide updated information regarding the major clinical trials that form the basis for current and planned protocols and (2) debate the therapeutic modifications appropriate for contemporary clinical investigations. Critical in planning future studies in the analysis of risk factors that may identify 'favorable' patients versus 'high risk' patients. Risk-related studies appropriately address maintalated studies appropriately address maintaining or improving current disease control rates in the context of diminishing late treatment sequelae for 'favorable' presentations. For those identified as 'high risk' (e.g., patients with disease beyond the primary site), studies are in development that increase the intensity of chemotherapy and explore modifications of radiation delivery. Study designs that permit assessment of innovations in surgical, radiotherapeutic, and chemotherapeutic approaches will be presented and debated by the panelists representing the two cooperative/competing modalities and neuro-oncology biostatistics


Clinical trials in zirconia: a systematic review. (United States)

Zirconia is unique in its polymorphic crystalline makeup, reported to be sensitive to manufacturing and handling processes, and there is debate about which processing method is least harmful to the final product. Currently, zirconia restorations are manufactured by either soft or hard-milling processes, with the manufacturer of each claiming advantages over the other. Chipping of the veneering porcelain is reported as a common problem and has been labelled as its main clinical setback. The objective of this systematic review is to report on the clinical success of zirconia-based restorations fabricated by both milling processes, in regard to framework fractures and veneering porcelain chipping. A comprehensive review of the literature was completed for in vivo trials on zirconia restorations in MEDLINE and PubMed between 1950 and 2009. A manual hand search of relevant dental journals was also completed. Seventeen clinical trials involving zirconia-based restorations were found, 13 were conducted on fixed partial dentures, two on single crowns and two on zirconia implant abutments, of which 11 were based on soft-milled zirconia and six on hard-milled zirconia. Chipping of the veneering porcelain was a common occurrence, and framework fracture was only observed in soft-milled zirconia. Based on the limited number of short-term in vivo studies, zirconia appears to be suitable for the fabrication of single crowns, and fixed partial dentures and implant abutments providing strict protocols during the manufacturing and delivery process are adhered to. Further long-term prospective studies are necessary to establish the best manufacturing process for zirconia-based restorations. PMID:20406352

Al-Amleh, B; Lyons, K; Swain, M



Student Participation in Rover Field Trials (United States)

The LAPIS program was developed in 1999 as part of the Athena Science Payload education and public outreach, funded by the JPL Mars Program Office. For the past three years, the Athena Science Team has been preparing for 2003 Mars Exploration Rover Mission operations using the JPL prototype Field Integrated Design and Operations (FIDO) rover in extended rover field trials. Students and teachers participating in LAPIS work with them each year to develop a complementary mission plan and implement an actual portion of the annual tests using FIDO and its instruments. LAPIS is designed to mirror an end-to-end mission: Small, geographically distributed groups of students form an integrated mission team, working together with Athena Science Team members and FIDO engineers to plan, implement, and archive a two-day test mission, controlling FIDO remotely over the Internet using the Web Interface for Telescience (WITS) and communicating with each other by email, the web, and teleconferences. The overarching goal of LAPIS is to get students excited about science and related fields. The program provides students with the opportunity to apply knowledge learned in school, such as geometry and geology, to a "real world" situation and to explore careers in science and engineering through continuous one-on-one interactions with teachers, Athena Science Team mentors, and FIDO engineers. A secondary goal is to help students develop improved communication skills and appreciation of teamwork, enhanced problem-solving skills, and increased self-confidence. The LAPIS program will provide a model for outreach associated with future FIDO field trials and the 2003 Mars mission operations. The base of participation will be broadened beyond the original four sites by taking advantage of the wide geographic distribution of Athena team member locations. This will provide greater numbers of students with the opportunity to actively engage in rover testing and to explore the possibilities of science, engineering, and technology.

Bowman, C. D.; Arvidson, R. E.; Nelson, S. V.; Sherman, D. M.; Squyres, S. W.



Clinical outcomes in clinical trials of anti-HIV treatment  

DEFF Research Database (Denmark)

Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding and knowledge of HIV led to short-term trials using surrogate outcomes such as viral load and CD4 count. This established a faster drug approval process that complimented the rapid need to evaluate and provide access to drugs based on short-term trials. However, no treatment has yet been found that eradicates the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?

Reekie, J; Mocroft, A



The status of clinical trials: Cause for concern  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Americans see clinical research as important, with over 15 million American residents participating in NIH-sponsored studies in 2008 and growing yearly. Methods Documents reporting NIH supported Clinical Research projects were reviewed. Results When compared with other studies, the number of interventional Phase III and Phase IV trials have decreased from 20% to 4.4% from 1994-2008. Conclusions This finding most likely has occurred for several reasons. One reason is that the physician lacks an infrastructure for designing and carrying out trials. This lack is because of an absence of a coordinated effort to train clinical trialists. It is clear that the Nation needs a more purposeful approach to developing and maintaining the infrastructure for designing and conducting clinical trials. Building it de novo trial by trial is profoundly inefficient, to say nothing about time consuming and error prone.

Meinert Curtis L



Clinical trial design: increasing efficiency in evaluating new healthcare interventions. (United States)

Professor Shaun Treweek speaks to Adam Born, Assistant Comissioning Editor: Professor Shaun Treweek is Chair in Health Services Research at the University of Aberdeen (UK) and has over 18 years experience as a health services researcher specializing in trial methodology. He is active in the field of pragmatic trial design, the design and pretrial testing of complex interventions, interventions to improve recruitment to trials, and theory-based methods to assess the implementation potential of interventions. Professor Treweek previously helped create the Tayside Clinical Trials Unit at the University of Dundee (UK) and served as the Assistant Director 2010-2013. His interest in trial methodology began before his time in Dundee when he spent 6 years in Oslo (Norway) working at the Norwegian Knowledge Centre for the Health Services. PMID:24969149

Treweek, Shaun; Born, Adam



Placebo control and clinical trial of Chinese medicine  

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Full Text Available World Health Organization aims to develop safe, effective and practical traditional medicine. Traditional Chinese medicine (TCM and other complementary and alternative medicine are being recognized in the whole world nowadays. However, the definite effect of Chinese medicine is still in need of scientific research proof. Placebo control is of equal importance to active control and blank control in clinical trial of TCM. This article briefly reviewed the importance of placebo control and commented on its present situation in clinical trial of TCM. This article also brought up the preliminary proposals of placebo application in TCM clinical trial. We should emphasize scientific placebo preparation and good design of placebo-controlled trial, which are directed by International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. A good clinical trial project will avoid unnecessary wastes and provide safe and effective treatment for people.

Jing Wu



Automatic denoising of single-trial evoked potentials. (United States)

We present an automatic denoising method based on the wavelet transform to obtain single trial evoked potentials. The method is based on the inter- and intra-scale variability of the wavelet coefficients and their deviations from baseline values. The performance of the method is tested with simulated event related potentials (ERPs) and with real visual and auditory ERPs. For the simulated data the presented method gives a significant improvement in the observation of single trial ERPs as well as in the estimation of their amplitudes and latencies, in comparison with a standard denoising technique (Donoho's thresholding) and in comparison with the noisy single trials. For the real data, the proposed method largely filters the spontaneous EEG activity, thus helping the identification of single trial visual and auditory ERPs. The proposed method provides a simple, automatic and fast tool that allows the study of single trial responses and their correlations with behavior. PMID:23142653

Ahmadi, Maryam; Quian Quiroga, Rodrigo



Randomized controlled trials of malaria intervention trials in Africa, 1948 to 2007: a descriptive analysis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Nine out of ten deaths from malaria occur in sub-Saharan Africa. Various control measures have achieved some progress in the control of the disease, but malaria is still a major public health problem in Africa. Randomized controlled trials (RCTs) are universally considered the best study type to rigorously assess whether an intervention is effective. The study reported here provides a descriptive analysis of RCTs reporting interventions for the prevention ...

Gerritsen Annette; Lutje Vittoria; Siegfried Nandi



Juveniles' competence to stand trial: a comparison of adolescents' and adults' capacities as trial defendants. (United States)

Abilities associated with adjudicative competence were assessed among 927 adolescents in juvenile detention facilities and community settings. Adolescents' abilities were compared to those of 466 young adults in jails and in the community. Participants at 4 locations across the United States completed a standardized measure of abilities relevant for competence to stand trial (the MacArthur Competence Assessment Tool--Criminal Adjudication) as well as a new procedure for assessing psychosocial influences on legal decisions often required of defendants (MacArthur Judgment Evaluation). Youths aged 15 and younger performed more poorly than young adults, with a greater proportion manifesting a level of impairment consistent with that of persons found incompetent to stand trial. Adolescents also tended more often than young adults to make choices (e.g., about plea agreements) that reflected compliance with authority, as well as influences of psychosocial immaturity. Implications of these results for policy and practice are discussed, with an emphasis on the development of legal standards that recognize immaturity as a potential predicate of incompetence to stand trial. PMID:12916225

Grisso, Thomas; Steinberg, Laurence; Woolard, Jennifer; Cauffman, Elizabeth; Scott, Elizabeth; Graham, Sandra; Lexcen, Fran; Reppucci, N Dickon; Schwartz, Robert



Chelation therapy after the Trial to Assess Chelation Therapy: results of a unique trial (United States)

Purpose of review EDTA chelation therapy has been in off-label use for the treatment of atherosclerosis. We review the results of the first large-scale randomized trial of this treatment. Recent findings The trial to assess chelation therapy was a $30 million National Institutes of Health-funded study of the safety and efficacy of EDTA-based chelation infusions in 1708 post-myocardial infarction (MI) patients. The trial to assess chelation therapy demonstrated a significant (P?=?0.035) 18% reduction in a combined primary endpoint of death, MI, stroke, coronary revascularization, or hospitalization for angina. In diabetic patients the benefit was more extreme, with a 41% relative reduction in risk (P?=?0.0002) and a 43% reduction in total mortality (P?=?0.011). Safety data were favorable. A reduction of oxidative stress by chelation of toxic metals has been proposed as a possible mechanism of action. Summary Recent research suggests that EDTA chelation may be a well-tolerated and effective treatment for post-MI patients. Future replication and mechanistic studies are important prior to implementation in all post-MI patients. PMID:25023079

Avila, Maria D.; Escolar, Esteban; Lamas, Gervasio A.



Minehound TM trials in Cambodia, Bosnia, and Angola (United States)

This paper describes the trials of the MINEHOUND TM dual sensor, land mine detector carried out in Cambodia, Bosnia and Angola. MINEHOUND TM has been developed for use in humanitarian demining as a means of improving the efficiency of clearance operations. The trials were sponsored by the UK Department for International Development (DFID). ERA Technology Ltd conducted the trials, which were monitored by staff drawn from the countries participating in the International Test and Evaluation Programme (ITEP) for humanitarian de-mining. Experienced deminers from the Mines Advisory Group (MAG) and Norwegian Peoples Aid (NPA) used the pre-production units in live minefields. The objectives of the trial were: 1. To record information on the performance of MINEHOUND TM when used in a live minefield. 2. To determine the reduction in False Alarm Rate (FAR) that could be achieved using a dual sensor mine detector. The trials were conducted in three mine-affected countries for a period of eight weeks per country; the programme of trials ran from July 2005 to December 2005, with an additional smaller trial in late February 2006. The results of the trials showed that MINEHOUND TM achieved 100% detection of the mines encountered and an improvement in FAR of better than 5:1 compared with a basic metal detector. The trials enabled optimisation of the production design and clearly demonstrated that new technology can be brought to humanitarian clearance operations in a safe and controlled manner. As a result of the highly successful trials, Vallon and ERA will produce the MINEHOUND TM (Type number VMR1) starting in Q3 of 2006.

Daniels, David J.; Curtis, Paul



What constitutes a "clinical trial"?: A survey of oncology professionals  

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Full Text Available Abstract Background What constitutes a "clinical trial" is inconsistently defined in the medical literature. With an initiative by Cancer Care Ontario (CCO to report institutional clinical trials activity across the province of Ontario, Canada, we sought to investigate the variability in the interpretation of the term by local oncology professionals. Methods A survey amongst the physicians and nurses at the Juravinski Cancer Centre at Hamilton Health Sciences, Ontario was conducted. The survey included 12 summaries of local clinical research studies, and respondents were asked which they believed represented a clinical trial. Subsequently, they were asked which of the same 12 studies they believed should be labeled as clinical trials when considering separate definitions provided by CCO and by the Ontario Cancer Research Network (OCRN. Results A total of 66 (54% of 123 surveys were completed; 32/46 (70% by physicians, 21/59 (36% by primary care nurses, and 13/18 (72% by clinical trial nurses. Without a standardized definition, all studies, 12/12, were considered to be clinical trials by at least 50% of respondents. When provided with the CCO definition only 6/12 studies were considered to be clinical trials by the majority of respondents, while with the OCRN definition it was 9/12 studies. Studies evaluating natural health products, non-traditional medical interventions, and non-randomized studies with standard interventions consistently ranked the lowest, regardless of the definition used. Conclusion Oncology professionals appear to have a broadly inclusive baseline definition of what constitutes a clinical trial. Establishing rigor and consistency in the definition of a clinical trial is important for any program, institutional or jurisdictional based comparisons of clinical trials activity, especially when used as a quality indicator of patient care.

Kowaleski Brenda



Do current clinical trials meet society's needs?: a critical review of recent evidence. (United States)

This paper describes some important controversies regarding the current state of clinical trials research in cardiology. Topics covered include the inadequacy of trial research on medical devices, problems with industry-sponsored trials, the lack of head-to-head trials of new effective treatments, the need for wiser handling of drug safety issues, the credibility (or lack thereof) of trial reports in medical journals, problems with globalization of trials, the role of personalized (stratified) medicine in trials, the need for new trials of old drugs, the need for trials of treatment withdrawal, the importance of pragmatic trials of treatment strategies, and the limitations of observational comparative effectiveness studies. All issues are illustrated by recent topical trials in cardiology. Overall, we explore the extent to which clinical trials, as currently practiced, are successful in meeting society's expectations. PMID:25301467

Pocock, Stuart J; Gersh, Bernard J



Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine (United States)

... of this page please turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research ... very emotional." Should You Be Interested in a Clinical Trial People volunteer to take part in clinical ...


Surgical trial in traumatic intracerebral hemorrhage (STITCH(Trauma: study protocol for a randomized controlled trial  

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Full Text Available Abstract Background Intracranial hemorrhage occurs in over 60% of severe head injuries in one of three types: extradural (EDH; subdural (SDH; and intraparenchymal (TICH. Prompt surgical removal of significant SDH and EDH is established and widely accepted. However, TICH is more common and is found in more than 40% of severe head injuries. It is associated with a worse outcome but the role for surgical removal remains undefined. Surgical practice in the treatment of TICHs differs widely around the world. The aim of early surgery in TICH removal is to prevent secondary brain injury. There have been trials of surgery for spontaneous ICH (including the STICH II trial, but none so far of surgery for TICH. Methods/Design The UK National Institutes of Health Research has funded STITCH(Trauma to determine whether a policy of early surgery in patients with TICH improves outcome compared to a policy of initial conservative treatment. It will include a health economics component and carry out a subgroup analysis of patients undergoing invasive monitoring. This is an international multicenter pragmatic randomized controlled trial. Patients are eligible if: they are within 48 h of injury; they have evidence of TICH on CT scan with a confluent volume of attenuation significantly raised above that of the background white and grey matter that has a total volume >10 mL; and their treating neurosurgeon is in equipoise. Patients will be ineligible if they have: a significant surface hematoma (EDH or SDH requiring surgery; a hemorrhage/contusion located in the cerebellum; three or more separate hematomas fulfilling inclusion criteria; or severe pre-existing physical or mental disability or severe co-morbidity which would lead to poor outcome even if the patient made a full recovery from the head injury. Patients will be randomized via an independent service. Patients randomized to surgery receive surgery within 12 h. Both groups will be monitored according to standard neurosurgical practice. All patients have a CT scan at 5 days (+/?2 days to assess changes in hematoma size. Follow-up is by postal questionnaire at 6 and 12 months. The recruitment target is 840 patients. Trial registration Current Controlled Trials ISRCTN19321911

Gregson Barbara A



Sternal and vertebral fractures, a well-known association, usually overlooked: review of six clinical cases / Fracturas vertebrales y fracturas concomitantes del esternón: revisión de seis casos / Fraturas vertebrais e fraturas concomitantes do esterno: revisão de seis casos  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese OBJETIVO: a associação de fraturas do esterno e vertebral tem sido previamente descrita na literatura. Essas lesões são frequentemente negligenciadas na avaliação inicial. O objetivo deste estudo foi analisar e discutir os métodos diagnósticos utilizados para essas lesões e salientar a importância d [...] o reconhecimento precoce dessas fraturas. MÉTODOS: foi realizada uma análise retrospectiva de seis pacientes que sofreram, concomitantemente, fraturas do esterno e vertebrais, por meio da análise de prontuários e exames de imagem. RESULTADOS: todos os pacientes foram diagnosticados com fraturas do esterno na avaliação inicial, mas somente dois foram diagnosticados com fraturas vertebrais. CONCLUSÃO: o não-reconhecimento dessas fraturas na avaliação inicial pode ser associado à dificuldade de explorar a região torácica superior. Na presença de fraturas do esterno, uma fratura vertebral deve ser descartada, embora lesões maiores não sejam presentes. A tomografia computadorizada (TC) e a ressonância magnética (RM) devem ser obtidas se houver suspeita clínica, apesar de os raios-X serem negativos. Abstract in spanish OBJETIVO: la asociación de las fracturas del esternón y vertebrales ha sido descrita previamente en la literatura. Estas lesiones son frecuentemente descuidadas en la evaluación inicial. El objetivo de este estudio fue analizar y discutir los métodos diagnósticos utilizados para estas lesiones y res [...] altar la importancia del reconocimiento precoz de estas fracturas. MÉTODOS: fue realizado un análisis retrospectivo de seis pacientes que sufrieron concomitantemente fracturas del esternón y vertebrales, por medio del análisis de las historias clínicas y exámenes de imagen. RESULTADOS: todos los pacientes fueron diagnosticados con fracturas del esternón en la evaluación inicial, pero solamente dos fueron diagnosticados con fracturas vertebrales. CONCLUSIONES: el hecho de no reconocer estas fracturas en la evaluación inicial puede estar asociado a la dificultad de explorar la región torácica superior. En la presencia de fracturas del esternón, una fractura vertebral debe ser descartada, así no estén presentes lesiones mayores. La tomografía computarizada y la resonancia magnética deben ser obtenidas en el momento de sospecha clínica, aunque el rayo-X sea negativo. Abstract in english OBJECTIVE: the association of sternal and vertebral fractures has previously been described in the literature. These lesions are frequently overlooked at the initial evaluation. The purpose of this study was to review and discuss the diagnostic methods used to diagnose these lesions and to highlight [...] the importance of early recognition of these fractures. METHODS: we performed a retrospective analysis of six patients who suffered sternal and concomitant vertebral fractures. Clinical charts and imaging studies were reviewed. RESULTS: all patients were diagnosed with sternal fractures at the initial evaluation, but only two were diagnosed with vertebral fractures. CONCLUSION: failure to recognize these fractures at initial evaluation may be associated with the fact that the upper thoracic region is difficult to explore. In the presence of sternal fractures, a vertebral fracture must be ruled out even though major injuries are not present. A computer tomography (CT) scan and magnetic resonance imaging (MRI) should be obtained despite negative X-rays if clinical suspicion is present.

Alvaro, Silva G.; Paulina de, la Fuente D; Andrés, Schmidt-Hebbel N; Manuel, Valencia C.; José, Antonio Riera M; Javier del Río, A; Bernardo, Merello T; Carlos, Thibaut L..


Pharmacologically active: Clinical trials and the pharmaceutical industry  

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Full Text Available SciELO South Africa | Language: English Abstract in english Multinational pharmaceutical companies ('pharmas') import and produce pharmaceuticals and also conduct clinical trials which are an important aspect of research and development (R&D). This may raise the question: Is South Africa a guinea pig for the pharmas? The Department of Trade and Industry Nati [...] onal Industrial Policy Framework¹ designates chemicals, plastic fabrication and pharmaceuticals as a key value chain. So a second question could be: Can South Africa be a manufacturer for the pharmas, or can it leverage strengths in medical research and the conducting of clinical trials so as to develop a discovery-led industry? This paper analyses and quantifies the state of the clinical trials industry in South Africa, and concludes that: (i) a sizeable clinical trials industry exists, and that these trials are predominantly phase 3 and global in scope; (ii) South Africa is not a specific or unique guinea pig - a range of conditions is studied as part of global trials; and (iii) while South Africa has excellent prospects for increased clinical trials activity, R&D investment is too low to make it a major pharmaceutical contender.

Michael, Kahn; Michael, Gastrow.


Health literacy and usability of clinical trial search engines. (United States)

Several web-based search engines have been developed to assist individuals to find clinical trials for which they may be interested in volunteering. However, these search engines may be difficult for individuals with low health and computer literacy to navigate. The authors present findings from a usability evaluation of clinical trial search tools with 41 participants across the health and computer literacy spectrum. The study consisted of 3 parts: (a) a usability study of an existing web-based clinical trial search tool; (b) a usability study of a keyword-based clinical trial search tool; and (c) an exploratory study investigating users' information needs when deciding among 2 or more candidate clinical trials. From the first 2 studies, the authors found that users with low health literacy have difficulty forming queries using keywords and have significantly more difficulty using a standard web-based clinical trial search tool compared with users with adequate health literacy. From the third study, the authors identified the search factors most important to individuals searching for clinical trials and how these varied by health literacy level. PMID:25315593

Utami, Dina; Bickmore, Timothy W; Barry, Barbara; Paasche-Orlow, Michael K



Construction of ethics in clinical research: clinical trials registration  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english Scientific development that has been achieved through decades finds in clinical research a great possibility of translating findings to human health application. Evidence given by clinical trials allows everyone to have access to the best health services. However, the millionaire world of pharmaceut [...] ical industries has stained clinical research with doubt and improbability. Study results (fruits of controlled clinical trials) and scientific publications (selective, manipulated and with wrong conclusions) led to an inappropriate clinical practice, favoring the involved economic aspect. In 2005, the International Committee of Medical Journal Editors (ICMJE), supported by the World Association of Medical Editors, started demanding as a requisite for publication that all clinical trials be registered at the database In 2006, the World Health Organization (WHO) created the International Clinical Trial Registry Platform (ICTRP), which gathers several registry centers from all over the world, and required that all researchers and pharmaceutical industries register clinical trials. Such obligatory registration has progressed and will extend to all scientific journals indexed in all worldwide databases. Registration of clinical trials means another step of clinical research towards transparency, ethics and impartiality, resulting in real evidence to the forthcoming changes in clinical practice as well as in the health situation.

C. A., Caramori.


Pharmacologically active: clinical trials and the pharmaceutical industry. (United States)

Multinational pharmaceutical companies ( 'pharmas') import and produce pharmaceuticals and also conduct clinical trials which are an important aspect of research and development (R&D). This may raise the question: Is South Africa a guinea pig for the pharmas? The Department of Trade and Industry National Industrial Policy Framework(1) designates chemicals, plastic fabrication and pharmaceuticals as a key value chain. So a second question could be: Can South Africa be a manufacturer for the pharmas, or can it leverage strengths in medical research and the conducting of clinical trials so as to develop a discovery-led industry? This paper analyses and quantifies the state of the clinical trials industry in South Africa, and concludes that: (i) a sizeable clinical trials industry exists, and that these trials are predominantly phase 3 and global in scope; (ii) South Africa is not a specific or unique guinea pig--a range of conditions is studied as part of global trials; and (iii) while South Africa has excellent prospects for increased clinical trials activity, R&D investment is too low to make it a major pharmaceutical contender. PMID:18350205

Kahn, Michael; Gastrow, Michael



Pharmacologically active: Clinical trials and the pharmaceutical industry  

Scientific Electronic Library Online (English)

Full Text Available SciELO South Africa | Language: English Abstract in english Multinational pharmaceutical companies ('pharmas') import and produce pharmaceuticals and also conduct clinical trials which are an important aspect of research and development (R&D). This may raise the question: Is South Africa a guinea pig for the pharmas? The Department of Trade and Industry Nati [...] onal Industrial Policy Framework¹ designates chemicals, plastic fabrication and pharmaceuticals as a key value chain. So a second question could be: Can South Africa be a manufacturer for the pharmas, or can it leverage strengths in medical research and the conducting of clinical trials so as to develop a discovery-led industry? This paper analyses and quantifies the state of the clinical trials industry in South Africa, and concludes that: (i) a sizeable clinical trials industry exists, and that these trials are predominantly phase 3 and global in scope; (ii) South Africa is not a specific or unique guinea pig - a range of conditions is studied as part of global trials; and (iii) while South Africa has excellent prospects for increased clinical trials activity, R&D investment is too low to make it a major pharmaceutical contender.

Michael, Kahn; Michael, Gastrow.



Vasopressors and the search for the optimal trial design. (United States)

Despite several advances in the care of critically ill patients, sepsis and septic shock continue to carry the largest burden of mortality and morbidity. Trials comparing vasopressors in shock have been disappointing and several key issues in methodology may need to be explored. There has been substantial progress in evolving adaptive trial methodology, however these have seldom been translated to clinical trials. This paper discusses some of the issues relevant to critical illness. To illustrate the potential contribution of adaptive trials we discuss fixed sample size design including event and time to event studies. We then explore group sequential and adaptive trial design, enrichment strategies and sample size re-estimation. An attractive feature of responsive adaptive designs is the flexibility to deal with unanticipated treatment effect size. If the observed effect size is larger than expected, early stopping is permitted. If the effect size is smaller than expected, sample size recalculation would be a reasonable choice in the face of an underpowered study. This allows for optimal efficiency in trial design. Reservations about adaptive trial design centre on issues of validity, feasibility and integrity of the study and are discussed in this paper. PMID:21807122

Maharaj, Ritesh



Does Milk Cause Constipation? A Crossover Dietary Trial  

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Full Text Available The aims of this study were to: (1 determine whether replacement of cow’s milk protein with soy resolves Chronic Functional Constipation (CFC; and (2 investigate the effects of cow’s milk ? casein A1 and cow’s milk ? casein A2 on CFC. Children diagnosed with CFC were recruited to one of two crossover trials: Trial 1 compared the effects of cow’s milk and soy milk; Trial 2 compared the effects of cow’s milk ? casein A1 and cow’s milk ? casein A2. Resolution of constipation was defined as greater than eight bowel motions during a two week intervention. Thirteen children (18 to 144 months participated in Trial 1 (6 boys, 7 girls. Nine participants who completed the soy epoch all experienced resolution (p < 0.05. Thirty-nine children (21 to 144 months participated in Trial 2 (25 boys, 14 girls. Resolution of constipation was highest during the washout epoch, 81%; followed by cow’s milk ? casein A2, 79%; and cow’s milk ? casein A1, 57%; however, the proportions did not differ statistically. The results of Trial 1 demonstrate an association between CFC and cow’s milk consumption but Trial 2 failed to show an effect from type of casein. Some other component in cow’s milk common to both A1 and A2 milk may be causing a problem in these susceptible children.

Peter D. Jones



Global randomized trials: the promise of India and China. (United States)

Although modern clinical trials are traditionally conducted in Western countries, currently there is a shift to involve developing countries, particularly China and India. For these trials, the large population size of India and China means that substantial numbers of individuals affected by rare diseases may be found, increasing the likelihood of successfully completing enrollment in a clinical trial. Furthermore, the increasing involvement of Asian countries in global clinical trials is likely to lead to greater appreciation of the value of evidence-based treatment decisions in the region. These sites are more cost-effective, although this advantage is being eroded over time. Asian participants in clinical trials are also typically more likely to complete study follow-up and procedures, and to adhere to their randomized treatment allocation than individuals from Western countries. Challenges include relevance of the proposed trial to the region, capacity limitations because of undeveloped training, and ensuring research implementation quality and different intellectual property practices. There are specific challenges to conducting clinical trials in India, such as the status of ethics committees, health insurance and coverage for participants, and variability in languages and record-keeping. Challenges in both countries are substantial but are able to be managed with appropriate planning. PMID:22810456

Perkovic, Vlado; Patil, Vinodvenkatesh; Wei, Liu; Lv, Jicheng; Petersen, Marisa; Patel, Anushka



Patients' Motivation about Clinical Trials: A Local Perspective from Turkey  

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Full Text Available Objective: To investigate attitudes concerning clinical trials amongst potential Turkish research participants.Patients and Methods: This is a survey of 504 Turkish patients who applied to 4 research and education hospitals in Istanbul, Turkey in March and April 2008. Attitudes and knowledge of the patients concerning clinical trials were measured.Results: Of the 504 patients, 62.3% were male and the mean ± SD age was 36.8±14.0 years. Most of the respondents (88.3% believed that the new drugs should not be used directly on human beings without being tested on human subjects and 52.2% thought that clinical trials were being performed in Turkey. 97.8% of the patients believed that new drugs should be developed, 71.4% specified that the new drugs should be tested on human subjects durring the research period, 84.5% mentioned that apart from clinical trials they could not use a drug that had never been tested on human beings. Only 28.6% of the respondents believed that clinical trials could be performed on healthy human subjects. The educational status was an affecting factor for the patients' attitudes toward clinical trials. Only 7 (1.4% patients in the survey participated in a clinical trial previously, but 33.7% of the survey group indicates that they may agree with participating in a clinical trial.Conclusion: This survey presents first and valuable information about Turkish patients' attitudes for clinical trials. The results of this survey provide an understanding of Turkish patients' motivations, and supply information concerning recruitment and retention strategies. (Marmara Medical Journal 2011;24:179-84




On the methodology of drug trials in migraine with aura  

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INTRODUCTION: Specific problems occur in clinical treatment trials for migraine with aura that differ from those encountered in treatment trials for migraine without aura. DISCUSSION: Based on our experience with four such trials, we point to a number of possible solutions and outline areas for future inquiry. We make recommendations about subject selection; the choice, definition and assessment of outcome measures; optimal treatments in relation to aura and headache; and we provide samples of study report forms used to record occurrence of aura and headache in this population.

Hauge, Anne Werner; Hougaard, Anders



Clinical trials - from anecdotes to evidence based medicine  

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Full Text Available Treatments based on theory and anecdote with extravagant public claims without being properly tested has become past time in medical practice. Only valid unbiased and relevant evidence obtained by methodology of clinical trials should be adopted in medical practice and practice guidelines. In such way clinical decisions are based on evidence rather than on authority. Inevitable part of clinical trials is medical ethics formally defined within the Nuremberg Code, World Medical Association Declaration of Helsinki and guidelines issued by the U.S. Department of Health, Education and Welfare. This paper presents in short history of clinical trials and current status worldwide.

Baji? Nada



The METEOR trial: no rush to repair a torn meniscus. (United States)

It is uncertain whether arthroscopic partial meniscectomy is better than physical therapy in patients who have a symptomatic torn meniscus on top of osteoarthritis of the knee. The Meniscal Repair in Osteoarthritis Research (METEOR) trial concluded that physical therapy is acceptable at first, and that surgery is not routinely needed. In patients assigned to physical therapy who eventually needed surgery, the delay resulting from a trial of conservative management did not impair outcomes at 12 months from the initial presentation. Here, we analyze the background, design, findings, and clinical implications of the METEOR trial. PMID:24692441

Hwang, Yong Gil; Kwoh, C Kent



Design of Early Validation Trials of Biomarkers  

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Full Text Available Abstract: The design of early-phase studies of putative screening markers in clinical populations is discussed. Biological, epidemiological, statistical and computational issues all affect the design of early-phase studies of these markers, but there are frequently little or no data in hand to facilitate the design. Early-phase studies must be designed as part of a development program, considering the final use of the marker, directly informing the decision to made at the study's conclusion. Therefore, they should test for sensitivity and specificity that would be minimally acceptable to proceed to the next stage of development. Designing such trials requires explicit assumptions about prevalence and false positive and negative costs in the ultimate target population. Early discussion of these issues strengthens the development process, since enthusiasm for developing technologies is balanced by realism about the requirements of a valid population screen. Receiver operating characteristic (ROC curves, which are useful descriptive tools, may be misleading when evaluating tests in low-prevalence populations, because they emphasize the relationship between specificity and sensitivity in the range of specificity likely to be too low to be useful in mass screening applications.

Daniel Normollea, Mack T. Ruffin IVb and Dean Brennerc



Imaging in early phase childhood cancer trials  

International Nuclear Information System (INIS)

Advances made in the treatment of childhood malignancies during the last four decades have resulted in overall cure rates of approximately 80%, but progress has slowed significantly during the last 10 years, underscoring the need for more effective and less toxic agents. Current research is focused on development of molecularly targeted agents, an era ushered in with the discovery of imatinib mesylate for the treatment of chronic myelogenous leukemia. Since imatinib's introduction into the clinic, an increasing number of tyrosine kinase inhibitors have been developed and entered into clinical trials and practice. Parallel to the initial advances made in molecularly targeted agents has been the development of a spectrum of novel imaging modalities. Future goals for imaging in childhood cancer research thus include (1) patient identification based on target identification or other biologic characteristics of the tumor, (2) assessing pharmacokinetic-pharmacodynamic (PK-PD) effects, and (3) predictive value with an early indication of patient benefit. Development and application of novel imaging modalities for children with cancer can serve to streamline development of molecularly targeted agents. (orig.)


Clinical Trial: Marine Lipid Suppositories as Laxatives  

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Full Text Available Cod-liver oil and other marine products containing polyunsaturated fatty acids have anti-inflammatory, anti-bacterial and anti-viral effects and may be useful in the treatment of various inflammatory and infectious diseases. We developed suppositories and ointment with 30% free fatty acid (FFA extract from omega-3 fish oil. Our purpose was to evaluate the safety of marine lipid suppositories and ointment in healthy volunteers and to explore the laxative effect of the suppositories. Thirty healthy volunteers were randomized either to a study group administrating 30% FFA suppositories and applying 30% FFA ointment to the perianal region twice per day for two weeks, or to a control group using placebo suppositories and ointment in a double blinded manner. Results: No serious toxic effects or irritation were observed. In the study group 93% felt the urge to defecate after administration of the suppositories as compared to 37% in the control group (P = 0.001. Subsequently 90% in the study group defecated, compared to 33% in the control group (P = 0.001. Conclusion: The marine lipid suppositories and ointment were well tolerated with no significant toxic side effects observed during the study period. The suppositories have a distinct laxative effect and we aim to explore this effect in further clinical trials.

Orri Thor Ormarsson



Physiological determinants of the cycling time trial. (United States)

The purpose of this study was to examine the physiological determinants of endurance cycling time trial (TT) performance in a heterogeneous group of competitive male road cyclists. About 15 male cyclists who had all competed in cycling the preceding season were tested for the anthropometric variables height, body weight, leg length, ankle circumference, and body fat percentage. They were also tested for maximal oxygen consumption (VO2max), lactate threshold (LT), metabolic cost of cycling (CC), peak power output and average power output during a 30-second Wingate test, 1 repetition maximum and peak power in half squats, and a TT test on an ergometer. Heart rate and cadence (rounds per minute, RPM) were continuously measured during all cycle tests. Pearson Bivariate correlation tests and single linear regression tests were performed to obtain correlation coefficients (r), effect size (F), standard error of estimate (SEE), and 95% confidence interval. The single variable that correlated best with TT performance was power output at LT (r = 0.86, p anaerobic endurance capacity TT(w) = 0.95 ([VO2max/CC] TT%VO2max) + 0.05 (Wingate average) correlated strongly with TT laboratory performance (r = 0.93, p power, or anthropometric variables correlated significantly with TT laboratory performance. PMID:23238091

Støren, Øyvind; Ulevåg, Kåre; Larsen, Morten H; Støa, Eva M; Helgerud, Jan



Clinical and Therapeutic Trials of Nigella Sativa  

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Full Text Available Seeds of Nigella sativa (N. sativa have been used for thousands of years as a spice and food preservative. The oil and seed constituents have shown potential medicinal properties in traditional medicine. This review lists and discusses different therapeutic trials of N. sativa seeds and its active ingredients in many diseases affecting body systems. It has anti?oxidant effects through enhancing the oxidant scavenger system that leads to antitoxic effects induced by several insults. Its anti?inflammatory effects conduct through suppression of the inflammatory mediators? prostaglandins and leukotriens. Its immunomodulatory properties were proved by augmenting the T cell and natural killer cell?mediated immune responses. It expresses antimicrobial and anti?tumor properties toward different microbes and cancers. It decreases DNA damage and thereby prevents initiation of carcinogenesis in colonic tissue secondary to exposure to toxic agents. N. sativa is of immense therapeutic benefit in DM. It stimulates glucose?induced secretion of insulin besides having a negative impact on glucose absorption from the intestinal mucosa. N. sativa administration protects hepatic tissue from deleterious effects of toxic substances and attenuates hepatic lipid peroxidation. N. sativa provides a promising strategy that combines anti?inflammatory, antioxidants, and antineoplastics modes of action. [TAF Prev Med Bull 2010; 9(5.000: 513-522

Ragaa H.M. Salama



Decision-Making Trial and Evaluation Laboratory  

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Full Text Available The aim of this study is introducing a technique to illuminate composite issue, aspects or system factors, the complicated problems need to be structured with graphical illustration and analyzed casual interdependence and influences throughout the organization. Decision-Making Trial and Evaluation Laboratory (DEMATEL methodology is proposed to for researching and solving complex and intertwined problem groups because of its capability in verifying interdependence between variables and try to improve them by offering a specific chart to reflect interrelationships between variables. In this technique experts plays complementary and approval role in all steps and sections. , key factors will be clarified by using the direct-influenced matrix and then it specifies priorities of each factor. The end product of the DEMATEL process is a visual demonstration-the Impact-Relations Map (IRM-by which respondents organize their own actions in the world. First In this study, DEMATEL methodology in explained and then kind of different problems which can be solved by DEMATEL, will discussed and finally the method of DEMATEL is detailed completely.

Elham Falatoonitoosi



Interpretation of Subgroup Effects in Published Trials  

DEFF Research Database (Denmark)

With the rapidly expanding number of studies reporting on treatment subgroups come new challenges in analyzing and interpreting this sometimes complex area of the literature. This article discusses 3 important issues regarding the analysis and interpretation of existing trials or systematic reviews that report on treatment effect modifiers (subgroups) for specific physical therapy interventions. The key messages are: (1) point estimates of treatment modifier effect size (interaction effect) and their confidence intervals can be calculated using group-level data when individual patient-level data are not available; (2) interaction effects do not define the total effect size of the intervention in the subgroup but rather how much more effective it is in the subgroup than in those not in the subgroup; (3) recommendations regarding the use of an intervention in a subgroup need to consider the size and direction of the main effect and the interaction effect; and (4) rather than simply judging whether a treatment modifier effect is clinically important based only on the interaction effect size, a better criterion is to determine whether the combined effect of the interaction effect and main effect makes the difference between an overall effect that is clinically important and one that is not clinically important.

Hancock, Mark J; Kjær, Per



Clinical trials of hypoxic cell sensitizer misonidazole  

International Nuclear Information System (INIS)

Misonidazole is the first hypoxic cell sensitizer which is introdused into the world-wide clinical trials. More than 500 patients have been treated with misonidazole in Japan. Phase I study, involved 106 patients, established its pharmacology, toxicities and safe dose regimens to Japanese. Total amount of 10.0g/m2, 1.5g/m2 once, 1.0g/m2 twice and 0.5g/m2 5 times a week, can be administered with acceptable toxicities and give plasma levels of the sensitizer enough to expect sensitizing effect to a certain degree. Several preliminary studies demonstrated the effect of the drug by factor about 1.3 in tumor regression, however the results of most Phase II studies were controversial. Final determination of its efficacy should be postponed until the completion of randomized Phase III studies with large number of patients, which are ongoing in the United States, Japan and so on. Considering the neurotoxicity of misonidazole, it is not the ideal sensitizer, but should be regarded as the first generation drug for hypoxic cells. Since a number of less toxic sensitizers are under development at present, more effective and safe drugs will appear in the near future. (author)


Analyzing Incomplete Discrete Longitudinal Clinical Trial Data  

CERN Document Server

Commonly used methods to analyze incomplete longitudinal clinical trial data include complete case analysis (CC) and last observation carried forward (LOCF). However, such methods rest on strong assumptions, including missing completely at random (MCAR) for CC and unchanging profile after dropout for LOCF. Such assumptions are too strong to generally hold. Over the last decades, a number of full longitudinal data analysis methods have become available, such as the linear mixed model for Gaussian outcomes, that are valid under the much weaker missing at random (MAR) assumption. Such a method is useful, even if the scientific question is in terms of a single time point, for example, the last planned measurement occasion, and it is generally consistent with the intention-to-treat principle. The validity of such a method rests on the use of maximum likelihood, under which the missing data mechanism is ignorable as soon as it is MAR. In this paper, we will focus on non-Gaussian outcomes, such as binary, categorica...

Jansen, I; Molenberghs, G; Verbeke,