Evans, Alicia; Shaw, Geoffrey M; Le Compte, Aaron; Tan, Chia*-Siong; Ward, Logan; Steel, James,; Pretty, Christopher G; Pfeifer, Leesa; Penning, Sophie; Suhaimi, Fatanah; Signal, Matthew; Desaive, Thomas; Chase, J. Geoffrey
ABSTRACT: INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly accounting for intra- and inter- patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) < 4.0 mmol/L. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in pilot trials. METHODS: Seven...
Deborah E Barnes
Full Text Available Current dementia medications have small effect sizes, many adverse effects and do not change the disease course. Therefore, it is critically important to study alternative treatment strategies. The goal of this study was to pilot-test a novel, integrative group exercise program for individuals with mild-to-moderate dementia called Preventing Loss of Independence through Exercise (PLIÉ, which focuses on training procedural memory for basic functional movements (e.g., sit-to-stand while increasing mindful body awareness and facilitating social connection.We performed a 36-week cross-over pilot clinical trial to compare PLIÉ with usual care (UC at an adult day program for individuals with dementia in San Francisco, CA. Assessments of physical performance, cognitive function, physical function, dementia-related behaviors, quality of life and caregiver burden were performed by blinded assessors at baseline, 18 weeks (cross-over and 36 weeks. Our primary outcomes were effect sizes based on between-group comparisons of change from baseline to 18 weeks; secondary outcomes were within-group comparisons of change before and after cross-over.Twelve individuals enrolled (7 PLIÉ, 5 UC and 2 withdrew (1 PLIÉ, 18 weeks; 1 UC, 36 weeks. Participants were 82% women (mean age, 84 ± 4 years; caregivers were 82% daughters (mean age, 56 ± 13 years. Effect sizes were not statistically significant but suggested potentially clinically meaningful (≥ 0.25 SDs improvement with PLIÉ versus UC for physical performance (Cohen's D: 0.34 SDs, cognitive function (0.76 SDs and quality of life (0.83 SDs as well as for caregiver measures of participant's quality of life (0.33 SDs and caregiver burden (0.49 SDs. Results were similar when within-group comparisons were made before and after cross-over.PLIÉ is a novel, integrative exercise program that shows promise for improving physical function, cognitive function, quality of life and caregiver burden in individuals with
showed a clinically relevant difference between groups that was also supported by a small distribution based effect size, i.e. vitality (-7.3 points, Cohen's d -0.34 which was in favour of IM. There was a clinical trend between groups showing that IM contributed to less use of prescription and non-prescription analgesics (-11.7 and - 9.7 percent units respectively compared to conventional care. Exploring clinically relevant differences and the SF-36 as the basis for a main outcome measure showed that the sample sizes needed per arm to adequately power a full-scale trial depended on the target domain, i.e. ranging from 60 (vitality to 339 (role emotion. Conclusion This pilot study investigated the implementation of IM in the primary care management of non-specific back and neck pain. Recruiting patients and implementing IM in routine clinical practice was feasible. The results warrant further exploration into different perspectives and relevant combinations of outcome measures including the use of health resources, drugs and cost-effectiveness to help understand the relevance of IM in primary care. Future research should prioritise larger scale studies considering variability, pain duration and small to moderate treatment effects. Trial registration Clinical trials NCT00565942
Kathleen B. Cartmell
Conclusions: In this formative single-arm pilot project, initial evidence was found for the potential effect of a lay navigation intervention on CT understanding and enrollment. A randomized controlled trial is needed to examine the efficacy of the intervention for improving CT education and enrollment.
Clinical trials are research studies that test how well new medical approaches work in people. Each study answers ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to a ...
Akin, Yigit; Gulmez, Hakan; Ates, Mutlu; Bozkurt, Aliseydi; Nuhoglu, Baris
Background: Premature ejaculation (PE) is the most common sexual disorder in men and studies reported prevalence up to 30% (1, 2). PE is not a life-threatening medical condition but it influences the quality of life (QoL). Objectives: The aim of this study was to compare the efficiency, and safety of alpha blocker drugs in the treatment of patients with premature ejaculation (PE). Additionally we investigated the quality of life (QoL) in patients with PE who were treated with alpha blocker drugs. Materials and Methods: This study was a pilot clinical trial. Prospectively documented 108 patients with PE were treated and were followed-up in urology outpatient clinic. All patients were divided into 5 groups according to used alpha blocker agents which were determined by simple randomization. Silodosin 4mg (Group 1, n = 21), tamsulosin hydrochloride 0.4mg (Group 2, n = 23), alfuzosin 10mg (Group 3, n = 22), terazosin 5mg (Group 4, n = 21), doksazosin mesylate 4mg (Group5, n = 21), were used for treatment. The demographic parameters of patients, pre and post treatment intravaginal ejaculation latency time (IELT), PE Profile (PEP), and QoL index were recorded and evaluated. Effectiveness of treatment was evaluated by measuring IELT. Additionally, side effects of drugs were recorded. P IELT and decrease in PEP were provided more in Group 1 than other groups (P IELT), PE Profile (PEP), and QoL index were recorded and evaluated. Effectiveness of treatment was evaluated by measuring IELT. Additionally, side effects of drugs were recorded. P < 0.05 was considered statistically significant. PMID:24693363
Samuel Oliveira de Afonseca
Full Text Available CONTEXT AND OBJECTIVEOxaliplatin is one of the chemotherapy regimens most used for treating colorectal cancer. One of the main limitations to its use is induction of peripheral neuropathy. Previous studies have shown that vitamin E can reduce the incidence of peripheral neuropathy by 50%. This study aimed to assess the effectiveness of vitamin E for prevention of oxaliplatin-induced peripheral neuropathy.DESIGN AND SETTINGProspective, phase II, randomized pilot study developed at a university hospital in the Greater ABC region.METHODSPatients were randomized five days before starting oxaliplatin treatment, to receive either vitamin E or placebo until the end of the chemotherapy regimen. The outcome was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE, version 3, and specific gradation scales for oxaliplatin-induced peripheral neuropathy. Patients with colorectal and gastric cancer who had been scheduled to receive oxaliplatin-based chemotherapy were included. Both groups received calcium and magnesium supplementation before and after oxaliplatin infusions.RESULTSEighteen patients were randomized to the vitamin E group and 16 to the placebo group. Cumulative incidence of 83% with peripheral neuropathy grades 1/2 was observed in the vitamin E group, versus 68% in the placebo group (P = 0.45. A trend towards more diarrhea was observed among patients who received vitamin E (55.6% vs. 18.8%; P = 0.06. There were no other significant differences in toxicity between the groups.CONCLUSIONSNo significant decrease in the incidence of acute oxaliplatin-induced peripheral neuropathy was demonstrated through vitamin E use.CLINICAL TRIAL REGISTRATIONNCT01523574.
Luchsinger, José A; Perez, Thania; Chang, Helena; Mehta, Pankaj; Steffener, Jason; Pradabhan, Gnanavalli; Ichise, Masanori; Manly, Jennifer; Devanand, Davangere P; Bagiella, Emilia
Diabetes and hyperinsulinemia may be risk factors for Alzheimer's disease (AD). We conducted a pilot study of metformin, a medication efficacious in treating and preventing diabetes while reducing hyperinsulinemia, among persons with amnestic mild cognitive impairment (aMCI) with the goal of collecting preliminary data on feasibility, safety, and efficacy. Participants were 80 men and women aged 55 to 90 years with aMCI, overweight or obese, without treated diabetes. We randomized participants to metformin 1000 mg twice a day or matching placebo for 12 months. The co-primary clinical outcomes were changes from baseline to 12 months in total recall of the Selective Reminding Test (SRT) and the score of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcome was change in relative glucose uptake in the posterior cingulate-precuneus in brain fluorodeoxyglucose positron emission tomography. Change in plasma Aβ42 was an exploratory outcome. The mean age of participants was 65 years. Fifty percent of participants were women. The only baseline variable that was different between the arms was the ADAS-Cog. Metformin could not be tolerated by 7.5% of participants; 15% tolerated 500 mg/day, 35% tolerated 1000 mg/day, 32.5% tolerated 1500 mg/day, and only 10% tolerated the maximum dose. There were no serious adverse events related to metformin. The 7.5% of persons who did not tolerate metformin reported gastrointestinal symptoms. After adjusting for baseline ADAS-cog, changes in total recall of the SRT favored the metformin group (9.7±8.5 versus 5.3±8.5; p = 0.02). Differences for other outcomes were not significant. A larger trial seems warranted to evaluate the efficacy and cognitive safety of metformin in prodromal AD.
Full Text Available Background & Objectives: Honey has been used as a nutraceutical in many traditional and ancient remedies. Considering well documented benefits of honey to accelerate wound healing, for the first time we aimed to assess intra oral surgical wound healing process with honey. Methods: We designed a pilot randomized placebo controlled cross-over clinical trial. Patients who required bilateral Modified Widman Flap (MWF surgery randomly assigned to receive either 15 cc topical Persian Thymus Vulgaris concentrated honey three times a day or normal saline as placebo with the same amount at the site of the surgery for seven consecutive days. After a 35-day wash-out period the study groups were crossed. The primary efficacy outcome was changes in healing index (Landry index and the secondary efficacy outcome were changes in gingival and plaque indices (Loe & Sillness, Sillness & Loe indices. It also includes safety issues consisting of any allergic reaction, delayed healing or wound dehiscence. Results: Ten patients enrolled with the mean age of 36 (±1.5 ranged between 35-40 yrs. There was a significant improvement in wound healing considering time and treatment effects in both groups, although faster wound healing observed in honey treated patients (P<0.001. In both groups gingival indices were noticed to be improved by the time during the first phase of the study. Both groups displayed aggravated Plaque formation; nevertheless it was merely statistically significant in the control group [F (3, 27 =12.88, P value < 0.001]. All wounds healed normally and no adverse events recorded. Conclusion: Our study established the safety, efficacy and feasibility of topical honey to promote periodontal surgical wound healing.
Krieger, Janice L; Parrott, Roxanne L; Nussbaum, Jon F
Patients often have difficulty understanding what randomization is and why it is needed in Phase III clinical trials. Physicians commonly report using metaphorical language to convey the role of chance in being assignment to treatment; however, the effectiveness of this strategy as an educational tool has not been explored. Guided by W. McGuire's (1972) information-processing model, the purpose of this pilot study was to explore effects of metaphors to explain randomization on message acceptance and behavioral intention to participate in a Phase III clinical trial among a sample of low-income, rural women (N = 64). Participants were randomly assigned to watch a video that explained randomization using 1 of 3 message strategies: a low-literacy definition, standard metaphor (i.e., flip of a coin), or a culturally derived metaphor (i.e., sex of a baby). The influence of attention on behavioral intentions to participate in clinical trials was partially moderated by message strategy. Under conditions of low attention, participants in the culturally derived metaphor condition experienced significantly higher intentions to participate in clinical trials compared with participants in the standard metaphor condition. However, as attention increased, differences in intentions among the conditions diminished. Having a positive affective response to the randomization message was a strong, positive predictor of behavioral intentions to participate in clinical trials. The authors discuss the theoretical and practical implications of these findings.
Full Text Available Objectives: A vertebral compression fracture (VCF is characterized by back pain and fracture of a vertebral body on spinal radiography. VCFs of the thoraco lumbar spine are common in the elderly. In general, appropriate analgesics should be prescribed to reduce pain and, thus, promote early mobilization. The ideal treatment approach for VCFs has not been determined. In Korea, acupuncture and herbal medication have been used to treat VCFs for many years. There is empirical evidence that acupuncture might benefit patients with a VCF. However, no randomized, controlled, clinical trials evaluating the efficacy and the safety of acupuncture for treating a VCF have been published. Therefore, we designed a randomized, controlled, pilot, clinical trial to obtain information for the design of a further full scale trial. Methods: A five week protocol for a randomized, controlled, pilot, clinical trial is presented. Fourteen patients will be recruited and randomly allocated to two groups: a control group receiving interlaminar epidural steroid injections once a week for three weeks, and an experimental group receiving interlaminar epidural steroid injections plus acupuncture treatment (three acupuncture sessions per week for three weeks, nine sessions in total. The primary outcomes will be the pain intensity (visual analogue scale and PainVisionTM system. The secondary outcome measurements will be the answers on the short form McGill pain questionnaire and the oswestry disability index. Assessments will be made at baseline and at one, three, and five weeks. The last assessment (week five will take place two weeks after treatment cessation. This study will provide both an indication of feasibility and a clinical foundation for a future large scale trial. The outcomes will provide additional resources for incorporating acupuncture into existing treatments, such as nonsteroidal anti-inflammatory medications, narcotics and vertebral augmentation. This article
Full Text Available Nia Thompson1, Niaman Nazir1, Lisa Sanderson Cox1,2, Babalola Faseru1,2, Kathy Goggin3, Jasjit S Ahluwalia4, Nicole L Nollen1,21University of Kansas School of Medicine, Department of Preventive Medicine and Public Health, Kansas City, KS, USA; 2University of Kansas Cancer Center, Kansas City, KS, USA; 3University of Missouri-Kansas City, Department of Psychology, Kansas City, MO, USA; 4University of Minnesota Medical School, Department of Medicine and Center for Health Equity, Minneapolis, MN, USABackground: Despite consistent evidence linking smoking cessation pharmacotherapy adherence to better outcomes, knowledge about objective adherence measures is lacking and little attention is given to monitoring pharmacotherapy use in smoking cessation clinical trials.Objectives: To examine unannounced telephone pill counts as a method for assessing adherence to smoking cessation pharmacotherapy.Research design: Secondary data analysis of a randomized pilot study.Participants: 46 moderate-to-heavy (>10 cigarettes per day African-American smokers.Main measures: Smokers received 1 month of varenicline (Pfizer Global Pharmaceuticals, New York, NY in a pill box at baseline. Unannounced pill counts were completed by telephone 4 days prior to an in-person pill count conducted at Month 1. At both counts, each compartment of the pill box was opened and the number of remaining pills was recorded.Results: Participants were a mean age of 48 years (SD = 13, predominately female (59%, low income (60% < $1800 monthly family income, and smoked an average of 17 (SD = 7 cigarettes per day. A high degree of concordance was observed between the number of pills counted by phone and in-person (rs = 0.94, P < 0.001. Participants with discordant counts (n = 7 had lower varenicline adherence (mean [SD] = 77% [18%] vs 95% [9%], P < 0.0005, but reported better medication adherence in the past (1.0 [0.8] vs 2.8 [1.0], P < 0.0004 than participants with matching phone and in
Abstract Background A model for integrative medicine (IM) adapted to Swedish primary care was previously developed. The aim of this study was to explore the feasibility of a pragmatic randomised clinical trial to investigate the effectiveness of the IM model versus conventional primary care in the management of patients with non-specific back/neck pain. Specific objectives included the exploration of recruitment and retention rates, patient and care characteristics, clinical differences and e...
McCloskey, Michael S.; Noblett, Kurtis L.; Deffenbacher, Jerry L.; Gollan, Jackie K.; Coccaro, Emil F.
No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized…
McCloskey, Michael S.; Noblett, Kurtis L.; Deffenbacher, Jerry L.; Gollan, Jackie K.; Coccaro, Emil F.
No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized…
Sipponen, Arno; Kuokkanen, Opri; Tiihonen, Raine; Kauppinen, Harri; Jokinen, Janne J
Resin is a natural product of coniferous trees. Salves manufactured from spruce resin (Picea abies) have been used for centuries to treat wounds and skin infections. We report a pilot clinical trial designed to investigate healing rates, factors that contribute to delayed wound healing, cost-effectiveness, and incidence of allergic reactions when resin salve is used to treat complicated surgical wounds. The trial involved 23 patients in whom wound healing after surgery was delayed. These patients were assigned to resin salve treatment. The primary outcome measure was the number of days to complete wound healing. Secondary objectives included an assessment of factors contributing to delayed wound healing, an estimation of associated costs, and an investigation into the occurrence of allergic reactions related to resin salve therapy. The study achieved a healing rate of 100%. The mean ± SD healing time was 43 ± 24 days. The mean ± SD wound size (length × width × depth) was (29 ± 19) × (12 ± 7) × (4 ± 3) mm. Wound size, use of corticosteroids or other immunosuppressants, and immobilization were statistically significant (P < 0.05) contributors to delayed wound healing and impaired re-epithelialization. The total mean ± SD costs of the resin salve treatment were €45.0 ± 26.0 per patient during the entire treatment period and €1.2 ± 0.5 per treatment day. The rate of allergic reactions was 0%. The results of this pilot trial indicate that complicated surgical wounds may be treated successfully with resin salve. The treatment method is clinically effective and cost-effective, and the rate of allergic reactions is low. © 2012 The International Society of Dermatology.
Beinlich, I; Bokemeyer, C; Räth, U; Walter-Kirst, R; Hartlapp, J; Muschiol, J; Fraass, U; Schneider, H T
This study assesses the feasibility of pen-based remote data entry and measures the acceptance of such systems by patients and physicians. Three clinical investigators participated in a phase-I/II clinical trial of escalated doses of chemotherapy followed by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). The study included 20 patients with testicular cancer who were treated at three university hospitals. The patients' data obtained in this trial were recorded and stored on a pen-based computer system. A total of 798 data points were recorded for each patient using 33 electronic forms resembling the paper forms used during an earlier phase of the study. The data recorded include the past medical history, inclusion/exclusion criteria, disease staging, therapy documentation, laboratory values and side effects. Both physicians and patients were interviewed directly after using the pen-based remote data entry system. Patients accepted that their physician was taking notes on an electronic form rather than on paper. All patients noted that a pen-based system is superior to a desktop computer when used during an interview. For the investigators electronic data entry takes additional effort, but time savings are realized later with less data clearing and increased data quality. These benefits are important for the study sponsor as well. In conclusion, pen-based remote data entry is a feasible new mode of recording clinical data with concrete benefits to both investigators and sponsors.
Rahul A. Sheth
Full Text Available White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15–25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1 the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2 the ability of this system to identify polyps as small as 1 mm, and (3 the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps.
Schortinghuis, J; Bronckers, ALLJ; Stegenga, B; Raghoebar, GM; de Bont, LGM
Objective: In a double blind randomised clinical pilot trial, it was investigated whether tow intensity pulsed ultrasound therapy stimulates early bone formation in a distraction gap created in a severely resorbed mandible. Design: Eight patients underwent a mandibular vertical distraction over an a
O. Yu. Leplina
Full Text Available Chronic recurrent infections caused by herpes simplex virus (HSV types 1 and 2 represent a serious medical and social challenge. Given an important role of immune system in surveillance of viral infections, an induced enhancement of antigen-specific immune response seems to be a promising approach to treatment of recurrent HSV infections, in particular, using dendritic cell (DCs vaccines. The present paper contains results of an open pilot study evaluating efficacy and safety of dendritic-cell vaccines in the patients with recurrent HSV infections. Twenty-nine patients including 14 persons with labial herpes, and 15, with genital herpes have been enrolled in this study. DCs were generated in presence of GM-CSF and IFNα and then loaded with recombinant viral proteins (HSV1gD or HSV2gD. These cells were applied in 2 rounds of vaccination performed within 9 months. Immunotherapy with DCs did not induce sufficient side effects, and was accompanied by more than two-fold decrease in relapse rate and increased length of remissions during the 9-month period of treatment. Later on, we revealed a reduced frequency of relapses, and a 3-fold increase in remission duration over the subsequent 6-month follow up. The clinical effect during the treatment and at later terms (a half-year observation was noted with both labial and genital herpes, as registered in the majority of patients, being associated with induction of antigen-specific proliferative response and normalization of reduced mitogenic responsiveness of mononuclear cells towards ConA. The patients’ survey at longer terms (more than 24 months has shown that the beneficial effect of immunotherapy, in terms of reduced relapse rates, was maintained in 77.8% of the respondents by 48 months (a median follow-up term. At this time, the antigen specific proliferative response was maintained in 66.7% of patients. The data obtained suggest that the dendritic-cell vaccines may be a promising approach to the
Lu, Weidong; Matulonis, Ursula A.; Doherty-Gilman, Anne; Lee, Hang; Dean-Clower, Elizabeth; Rosulek, Andrew; Gibson, Carolyn; Goodman, Annekathryn; Davis, Roger B.; Buring, Julie E.; Wayne, Peter M.; Rosenthal, David S.; Penson, Richard T.
Abstract Objectives The objective of this study was to investigate the effect of acupuncture administered during myelosuppressive chemotherapy on white blood cell (WBC) count and absolute neutrophil count (ANC) in patients with ovarian cancer. Design This study is a pilot, randomized, sham-controlled clinical trial. Patients received active acupuncture versus sham acupuncture while undergoing chemotherapy. A standardized acupuncture protocol was employed with manual and electrostimulation. The frequency of treatment was 2–3 times per week for a total of 10 sessions, starting 1 week before the second cycle of chemotherapy. Setting The setting was two outpatient academic centers for patients with cancer. Subjects Twenty-one (21) newly diagnosed and recurrent ovarian cancer patients were the subjects. Outcome measures WBC count, ANC, and plasma granulocyte colony-stimulating factor (G-CSF) were assessed weekly. Results The median leukocyte value in the acupuncture arm at the first day of the third cycle of chemotherapy was significantly higher than in the control arm after adjusting for baseline value (8600 cells/μL, range: 4800–12,000 versus 4400 cell/μL, range: 2300–10,000) (p = 0.046). The incidence of grade 2–4 leukopenia was less in the acupuncture arm than in the sham arm (30% versus 90%; p = 0.02). However, the median leukocyte nadir, neutrophil nadir, and recovering ANC were all higher but not statistically significantly different (p = 0.116–0.16), after adjusting for baseline differences. There were no statistically significant differences in plasma G-CSF between the two groups. Conclusions We observed clinically relevant trends of higher WBC values during one cycle of chemotherapy in patients with ovarian cancer, which suggests a potential myeloprotective effect of acupuncture. A larger trial is warranted to more definitively determine the efficacy of acupuncture on clinically important outcomes of chemotherapy-induced neutropenia. PMID:19552597
Berman, Marvin H; Halper, James P; Nichols, Trent W; Jarrett, H; Lundy, Alan; Huang, Jason H
Alzheimer’s disease (AD) is a common, chronic expensive debilitating neurodegenerative disease with no current treatments to prevent the physical deterioration of the brain and the consequent cognitive deficits. The current pathophysiology of Alzheimer’s disease is the accumulation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein and amyloid-beta (Aβ) plaques. Antibody therapy of Tau and Amyloid beta, vaccines and other methods to decrease Tau and or Amyloid have not been successful after considerable pharmaceutical and biotech efforts. For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer’s drug solanezumab which failed to reach statistical significance. Recently, a report on animal models using photomodulation with near infrared light to treat AD pathology in K369I tau transgenic model (K3) l engineered to develop neurofibrillary tangles, and the APPs/PSEN1dE9 transgenic model (APP/PS1) to develop amyloid plaques. Mice were treated with NIR 20 times over a four-week period and NIR treatment (600–1000 nm) was associated with a reduction in the size and number of amyloid-β plaques in the neocortex and hippocampus. We now report a small pilot double blind, placebo-controlled trial (n=11) 6 active, 3 controls and 2 dropouts assessing the effect of 28 consecutive, sixminute transcranial sessions of near infrared (NIR) stimulation using 1060–1080 nm light emitting diodes. Subjects were independently diagnosed with dementia conducted in an outpatient behavioral healthcare clinic. IRB approval was obtained through the Quietmind Foundation’s institutional review Board (IRB). Results showed changes in executive functioning; clock drawing, immediate recall, praxis memory, visual attention and task switching (Trails A&B) as well as a trend of improved EEG amplitude and connectivity measures. Neuroplasticity has also been reported with NIR light stimulation and mitochondrial enhancement. PMID
Full Text Available Background. From the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR, autism is considered a pervasive developmental disorder. It manifests as a behavioral syndrome characterised by impairment in social interaction and communication, restricted interests and activities, as well as repetitive and stereotyped patterns. Such profile renders prevention measures and dental care seriously compromised so that usually autistic children are treated and cared following general anesthesia. Aims. We aimed at developing a target-specific educational approach allowing to avoid general anesthesia in autistic patients subjected to dental care treatments (e.g. sealing, plaque ablation, minimal carious lesions etc.; such protocol should also facilitate the implementation of prevention measures. Design. It is proposed a target-specific educational research protocol adopting individual strategies and methodologies, including Augmentative and Alternative Communication (AAC for patients with speech and language impairments. The dentists are trained by the educator, who acts as a filter between the patient and the medical team. The team is required until a relationship of trust with the patient is built and the dentist is able to continue independently. Results. We present a pilot clinical trial in which out of 34 patients between 6 and 12 years old showed a positive response to the application of the protocol, allowing the execution of dental therapies together with a long-term prevention programme and in 32 of them the general anesthesia was avoided. Negative results regarded two patients who had not undergone any behavioral, psychomotor or speech rehabilitation therapy. Conclusions. Though the results should be considered as preliminary, the application of the method with the synergistic action of the people in the team allowed the execution of dental therapies. Given the positive outcomes, the Pediatric Dentistry Unit of the Umberto I Hospital
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Schumacher, Andrew; Sikov, William M.; Quesenberry, Matthew I.; Safran, Howard; Khurshid, Humera; Mitchell, Kristen M.
Background Informed consent forms (ICFs) for oncology clinical trials have grown increasingly longer and more complex. We evaluated objective understanding of critical components of informed consent among patients enrolling in contemporary trials of conventional or novel biologic/targeted therapies. Methods We evaluated ICFs for cancer clinical trials for length and readability, and patients registered on those studies were asked to complete a validated 14-question survey assessing their understanding of key characteristics of the trial. Mean scores were compared in groups defined by trial and patient characteristics. Results Fifty patients, of whom half participated in trials of immunotherapy or biologic/targeted agents and half in trials of conventional therapy, completed the survey. On average, ICFs for industry-originated trials (N = 9 trials) were significantly longer (P < .0001) and had lower Flesch ease-of-reading scores (P = .003) than investigator-initiated trials (N = 11). At least 80% of patients incorrectly responded to three key questions which addressed the experimental nature of their trial therapy, its purported efficacy and potential risks relative to alternative treatments. The mean objective understanding score was 76.9±8.8, but it was statistically significantly lower for patients who had not completed high school (P = .011). The scores did not differ significantly by type of cancer therapy (P = .12) or trial sponsor (P = .38). Conclusions Many participants enrolled on cancer trials had poor understanding of essential elements of their trial. In order to ensure true informed consent, innovative approaches, such as expanded in-person counseling adapted to the patient’s education level or cultural characteristics should be evaluated across socio-demographic groups. Trial registration Clinicaltrials.gov NCT01772511 PMID:28235011
Full Text Available Abstract Background Moxibustion is an ancient traditional medicine using burning mugworts to stimulate acupuncture points. The aim of this study was to investigate the safety and efficacy of moxibustion for the treatment of constipation using a randomized, sham-controlled, participant-blinded, pilot trial. Methods Twenty-six participants (identified with either qi (vital energy deficiency or qi excess syndrome were randomly divided into either a moxibustion or sham group. Participants were treated with real or sham moxibustion at 4 acupuncture points, ST23 and ST27, bilaterally, 3 times per week for four weeks. The primary outcome was the frequency of defecations; secondary outcomes were the Bristol stool form scale (BSS and the constipation assessment scale (CAS. Results Of the 26 participants that were randomized, 24 completed the study. Defecation frequency, BSS, and CAS showed no difference between the moxibustion and sham groups. The differences were -0.25 (95% CI: -2.08, 1.58, p = 0.78, -1.22 (95% CI: -2.7, 0.26, p = 0.1, 0.91 (95% CI: -1.46, 3.28, p = 0.44 in defecation frequency, BSS, CAS, respectively. The defecation frequency increased from an average of 3.3 to 4.6 times per week in the moxibustion group (1.5[-0.5, 2], p = 0.06 and from 2.7 to 3.7 stools per week in the sham group (1[-1, 2], p = 0.15 after four weeks of treatment. The difference between participants with a deficiency or an excess syndrome, determined based on assessment of sweat, facial features, pain, body energy, and pulse type, was significant in only defecation frequency. The difference was 3.3 (95% CI: 0.41, 6.19, p = 0.03. Conclusion Moxibustion treatment appears safe, but showed no positive effect on constipation. The effectiveness of moxibustion treatment may depend on the syndrome pattern, and further long-term studies with a larger number of subjects are warranted. Trial registration Clinical Research Information Service, KCT0000168
Douglas de Oliveira, Dhelfeson Willya; Oliveira, Evandro Silveira de; Mota, André Felipe Miranda; Pereira, Victor Hugo Urzedo; Bastos, Vinícius Oliveira; Glória, José Cristiano Ramos; Gonçalves, Patricia Furtado; Flecha, Olga Dumont
Cervical dentin hypersensitivity (CDH) is defined as an acute pain of short duration that occurs in dentin exposed to the oral environment. The aim of this study was to evaluate the effi cacy of three desensitizing toothpastes (Sensodyne® Rapid-Relief, Colgate® Sensitive Pro-Relief, Nano P®) for immediate and intermediate-term relief of CDH, when compared with a control toothpaste (Cocoricó®). Eight patients were enrolled in this clinical study. One hundred thirty-eight hypersensitive teeth were randomized into four groups according to the com- position of the desensitizing toothpaste tested: Group I) strontium acetate and calcium carbonate; II) calcium carbonate and arginine 8%; III) calcium phosphate nanoparticles; and IV) a control toothpaste. A split mouth design was used for one application each of the desensitizing dentifrices. Assessment of CDH was done by evaporative and cold stimuli at baseline, immediately, 24 hours and 30 days after the treatment. The toothpastes presented similar effectiveness and statistically significant improvement in 30 days compared to baseline. Group III showed statistically significant relief for cervical dentin hypersensitivity immediately after the treatment. The only toothpaste that presented immediate relief effect was the paste containing calcium phosphate nanoparticles in the form of hydroxyapatite. Copyright© by the International Academy of Periodontology.
Singab, Abdel-Naser B; El-Hefnawy, Hala M; Esmat, Ahmed; Gad, Haidy A; Nazeam, Jilan A
Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in the last few decades has verified several such claims. Aloe arborescens Miller, belonging to the Aloe genus (Family Asphodelaceae), is one of the main varieties of Aloe used worldwide. The popularity of the plant in traditional medicine for several ailments (antitumor, immunomodulatory, antiinflammatory, antiulcer, antimicrobial and antifungal activity) focused the investigator's interest on this plant. Most importantly, the reported studies have shown the plant effectiveness on various cancer types such as liver, colon, duodenal, skin, pancreatic, intestinal, lung and kidney types. These multiple biological actions make Aloe an important resource for developing new natural therapies. However, the biological activities of isolated compounds such as glycoprotein, polysaccharides, enzyme and phenolics were insufficient. Considering all these, this contribution provides a systematic review outlining the evidence on the biological efficacy of the plant including the pharmacology and the related mechanisms of action, with specific attention to the various safety precautions, and preclinical and clinical studies, indicating the future research prospects of this plant.
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Full Text Available BACKGROUND: The severity and longevity of inflammation is controlled by endogenous counter-regulatory signals. Among them are long-chain polyunsaturated fatty acid (PUFA-derived lipid mediators, which promote the resolution of inflammation, an active process for returning to tissue homeostasis. OBJECTIVE: To determine whether endogenous production of lipid-derived resolution agonists is regulated differentially in patients with highly active and less active multiple sclerosis (MS. DESIGN: Matched-pairs study in University hospital Neurology department. PATIENTS: Based on clinical (relapse frequency and paraclinical (MRI lesions, contrast enhancement criteria, 10 pairs of age- and sex-matched patients with relapsing-remitting MS were assigned either to a group with highly active or less active MS. Lipid mediators were quantified in serum and cerebrospinal fluid using LC-MS/MS-based lipidomics. RESULTS: Levels of the key arachidonic (ω-6 and docosahexaenoic acid (ω-6-derived mediators prostaglandins (PG, leukotrienes, hydroxyeicosatetraenoic acids (HETE and resolution agonists lipoxin A(4 (LXA(4, resolvin D1 (RvD1 and neuroprotectin D1 (NPD1 were quantified. In the patient group with highly active MS, 15-HETE and PGE(2 were increased, which are products of the 15-lipoxygenase and cyclooxygenase pathways. The proresolution mediator RvD1 was significantly upregulated and NPD1 was detected in the highly active group only. LXA(4 levels were not increased in patients with highly active MS. CONCLUSIONS: Lipid mediator pathways are regulated differentially in the cerebrospinal fluid of MS patients, depending on disease severity. Non-exhaustive or possibly 'delayed' resolution pathways may suggest a defective resolution program in patients with highly active MS. Longitudinal analyses are required to hetero-typify this differential resolution capacity, which may be associated with disease progression, longevity and eventual termination.
Steiner, Hans; Saxena, Kirti S.; Carrion, Victor; Khanzode, Leena A.; Silverman, Melissa; Chang, Kiki
We examined the efficacy of divalproex sodium (DVP) for the treatment of PTSD in conduct disorder, utilizing a previous study in which 71 youth were enrolled in a randomized controlled clinical trial. Twelve had PTSD. Subjects (all males, mean age 16, SD 1.0) were randomized into high and low dose conditions. Clinical Global Impression (CGI)…
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Højskov, Ida E; Moons, Philip; Hansen, Niels V; Greve, Helle; Olsen, Dorte Bæk; Cour, Søren La; Glud, Christian; Winkel, Per; Lindschou, Jane; Egerod, Ingrid; Christensen, Anne Vinggaard; Berg, Selina Kikkenborg
Patients undergoing coronary artery bypass graft surgery often experience a range of problems and symptoms such as immobility, pain and insufficient sleep. Results from trials investigating testing in-hospital physical exercise or psychological intervention have been promising. However, no randomized clinical trials have tested a comprehensive rehabilitation programme consisting of both physical exercise and psycho-education in the early rehabilitation phase. The aims of the present SheppHeart pilot randomized clinical trial were to evaluate the feasibility of patient recruitment, patient acceptance of the intervention, safety and tolerability of the intervention. Sixty patients admitted for coronary artery bypass graft were randomized 1:1:1:1 to: 1) physical exercise plus usual care, or 2) psycho-educational intervention plus usual care, or 3) physical exercise and psycho-educational plus usual care, or 4) usual care alone during a four week period after surgery. The acceptability of trial participation was 67% during the three month recruitment period. In the physical exercise groups, patients complied with 59% of the total expected training sessions during hospitalization. Nine patients (30%) complied with >75% and nine patients (30%) complied with 50% of the planned exercise sessions. Eleven patients (42%) participated in ⩾75% of the four consultations and six patients (23%) participated in 50% of the psycho-educational programme. Comprehensive phase one rehabilitation combining physical exercise and psycho-education in coronary artery bypass graft patients shows reasonably high inclusion, feasibility and safety. © The European Society of Cardiology 2015.
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Naumann, Johannes; Grebe, Julian; Kaifel, Sonja; Weinert, Tomas; Sadaghiani, Catharina; Huber, Roman
Despite advances in the treatment of depression, one-third of depressed patients fail to respond to conventional antidepressant medication. There is a need for more effective treatments with fewer side effects. The primary aim of this study was to determine whether hyperthermic baths reduce depressive symptoms in adults with depressive disorder. Randomized, two-arm placebo-controlled, 8-week pilot trial. Medically stable outpatients with confirmed depressive disorder (ICD-10: F32/F33) who were moderately depressed as determined by the 17-item Hamilton Scale for Depression (HAM-D) score ≥18 were randomly assigned to 2 hyperthermic baths (40 °C) per week for 4 weeks or a sham intervention with green light and follow-up after 4 weeks. Main outcome measure was the change in HAM-Dtotal score from baseline (T0) to the 2-week time point (T1). A total of 36 patients were randomized (hyperthermic baths, n = 17; sham condition, n = 19). The intention-to-treat analysis showed a significant (P = .037) difference in the change in HAM-Dtotal score with 3.14 points after 4 interventions (T1) in favour of the hyperthermic bath group compared to the placebo group. This pilot study suggests that hyperthermic baths do have generalized efficacy in depressed patients. DRKS00004803 at drks-neu.uniklinik-freiburg.de, German Clinical Trials Register (registration date 2016-02-02), retrospectively registered.
Schneider, Kristin L; Pagoto, Sherry L; Handschin, Barbara; Panza, Emily; Bakke, Susan; Liu, Qin; Blendea, Mihaela; Ockene, Ira S; Ma, Yunsheng
BACKGROUND: The comorbidity of type 2 diabetes mellitus (T2DM) and depression is associated with poor glycemic control. Exercise has been shown to improve mood and glycemic control, but individuals with comorbid T2DM and depression are disproportionately sedentary compared to the general population and report more difficulty with exercise. Behavioral activation, an evidence-based depression psychotherapy, was designed to help people with depression make gradual behavior changes, and may be helpful to build exercise adherence in sedentary populations. This pilot randomized clinical trial will test the feasibility of a group exercise program enhanced with behavioral activation strategies among women with comorbid T2DM and depression. METHODS/DESIGN: Sedentary women with inadequately controlled T2DM and depression (N=60) will be randomly assigned to one of two conditions: exercise or usual care. Participants randomized to the exercise condition will attend 38 behavioral activation-enhanced group exercise classes over 24 weeks in addition to usual care. Participants randomized to the usual care condition will receive depression treatment referrals and print information on diabetes management via diet and physical activity. Assessments will occur at baseline and 3-, 6-, and 9-months following randomization. The goals of this pilot study are to demonstrate feasibility and intervention acceptability, estimate the resources and costs required to deliver the intervention and to estimate the standard deviation of continuous outcomes (e.g., depressive symptoms and glycosylated hemoglobin) in preparation for a fully-powered randomized clinical trial. DISCUSSION: A novel intervention that combines exercise and behavioral activation strategies could potentially improve glycemic control and mood in women with comorbid type 2 diabetes and depression. TRIAL REGISTRATION: NCT01024790.
Paul J Novotny
Full Text Available Paul J Novotny1, Denise J Smith1, Lorna Guse2, Teresa A Rummans3, Lynn Hartmann4, Steven Alberts4, Richard Goldberg5, David Gregory6, Mary Johnson7, Jeff A Sloan11Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 2Faculty of Nursing, University of Manitoba, Winnipeg, Manitoba, Canada; 3Psychiatry, Mayo Clinic, Rochester, MN, USA; 4Medical Oncology, Mayo Clinic, Rochester, MN, USA; 5Oncology Services, University of North Carolina, Chapel Hill, NC, USA; 6Faculty of Health Sciences Nursing, University of Lethbridge, Lethbridge, Alberta, Canada; 7Chaplain Services, Mayo Clinic, Rochester, MN, USAPurpose: This study tested the logistical feasibility of obtaining data on social support systems from cancer patients enrolled on clinical trials and compared the social support of older adults (age ≥65 and younger adults (<50 years of age with cancer.Methods: Patients had to be eligible for a phase II or phase III oncology clinical trial and enter the study prior to treatment. Patients filled out the Lubben Social Network Scale (LSNS at baseline. The Symptom Distress Scale (SDS and single-item overall quality of life (QOL Uniscale were assessed at baseline and weekly for 4 weeks.Results: There was no significant difference in overall mean Lubben social support levels by age. Older patients had more relatives they felt close to (85% versus 53% with 5 or more relatives, P = 0.02, heard from more friends monthly (84% versus 53% with 3 or more friends, P = 0.02, less overall symptom distress (P = 0.03, less insomnia (P = 0.003, better concentration (P = 0.005, better outlook (P = 0.01, and less depression (P = 0.005 than younger patients.Conclusions: Younger subjects reported worse symptoms, a smaller social support network, and fewer close friends and relatives than older subjects. Having someone to discuss decisions and seeing friends or relatives often was associated with longer survival. Keywords: social support, Lubben scale, QOL, elderly
Fulda, Kimberly G; Slicho, Turner; Stoll, Scott T
Placebo treatments should be believable to ensure expectation of benefit, yet not provide a true treatment effect. One obstacle to conducting clinical trials with osteopathic manipulative treatment (OMT) is choosing an appropriate placebo. Various placebo treatments have been used in OMT clinical trials. The purpose of this study was to determine expectations of 3 treatments (HVLA, placebo light touch, placebo sub-therapeutic ultrasound) commonly used in OMT clinical research trials. A randomized, cross-over design was utilized. Subjects were recruited from the Family Medicine Clinic, Texas College of Osteopathic Medicine. Participants watched a video with 2 minute demonstrations of a High Velocity Low Amplitude (HVLA), placebo light touch (LT), and placebo sub-therapeutic ultrasound (ULTRA) treatment for low back pain. The order of presentations was randomized to control for order effect bias. Subjects indicated the extent of their agreement (using a 4 point Likert scale) with 4 statements that were presented after each treatment was viewed: 1)I believe this treatment would allow me to get better quicker; 2)I believe this treatment would decrease my low back pain; 3)I believe this treatment would make me more able to do the things I want to do; 4)This seems like a logical way to treat low back pain. Repeated measures analysis of variance was performed, and a partial Eta squared was calculated for each statement. Effect sizes (Cohen's d) were calculated where appropriate. Thirty of 40 eligible subjects participated. Twenty-two (73%) were female, 16 (53%) were Caucasian, and 11 (37%) had completed college. The mean age was 43 (SD = 15.). Repeated measures ANOVA revealed no significant differences for statements 2 and 4. For both statements 1 (p = 0.025) and 3 (p = 0.039), post hoc analysis revealed a difference between HVLA and LT. The partial Eta squared (etap2) was 0.105, 0.072, 0.107, and 0.024 for each statement, respectively. There is a difference in treatment
Hejazi, Mohammad Esmaeil; Modarresi-Ghazani, Faezeh; Hamishehkar, Hadi; Mesgari-Abbasi, Mehran; Dousti, Samaneh; Entezari-Maleki, Taher
Despite the known role of vitamin D deficiency in development of thrombosis, no studies have evaluated the impact of treating of vitamin D deficiency on the markers of thrombosis. A pilot randomized clinical trial was done on 40 vitamin D-deficient patients with deep vein thrombosis (DVT) or pulmonary embolism (PE). The intervention group received an oral dose of 50,000 IU vitamin D3 every week for 8 weeks, followed by 1 pearl every 2 weeks for 4 weeks (a total of 3 months), while the control group did not receive vitamin D. Then, P-selectin and hs-CRP were measured at baseline and 1 and 3 months after the intervention. There was no significant decrease in hs-CRP in either group after 1 month (P = .955) or after 3 months (P = .525). Likewise, there was no significant decrease in P-selectin between the 2 groups after 1 month (P = .921) or 3 months (P = .795). The results indicated that treatment of vitamin D deficiency had no significant effect on hs-CRP or P-selectin after 3 months among DVT/PE patients. However, treatment of vitamin D deficiency in these patients resulted in the control of the international normalized ratio (INR) with the lower doses of warfarin. This observation is the first clinical report of enhancement of the anticoagulant effect of warfarin by the supplementing of vitamin D. Larger trials are needed to clearly show the effect of treating of vitamin D deficiency on thrombosis.
-test and ANCOVA (P <0.05). Discussion The results of this study will allow evaluation of contralateral acupuncture from two aspects. First, if the contralateral acupuncture shows the effects similar to ipsilateral acupuncture, this will establish clinical basis for contralateral acupuncture. Second, if the effects of contralateral acupuncture are not comparable to the effects of ipsilateral acupuncture, but are shown to be similar to the effects of the sham acupuncture, we can establish the basis for using the same acupoints of the unaffected side as a control in acupuncture clinical studies. Trial registration This trial has been registered with the ‘Clinical Research Information Service (CRIS)’, Republic of Korea: KCT0000628. PMID:23768129
. Conclusions Our results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV patients, worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results. Trial Registration WHO Clinical Trial Registration ID: ACTRN12610000958088 http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000958088
results could suggest a therapeutically feasible potential for Spirulina platensis in chronic HCV patients, worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results. Trial Registration WHO Clinical Trial Registration ID: ACTRN12610000958088 http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000958088 PMID:22497849
Dimbwadyo-Terrer, I; Gil-Agudo, A; Segura-Fragoso, A; de los Reyes-Guzmán, A; Trincado-Alonso, F; Piazza, S; Polonio-López, B
The aim of this study was to investigate the effects of a virtual reality program combined with conventional therapy in upper limb function in people with tetraplegia and to provide data about patients' satisfaction with the virtual reality system. Thirty-one people with subacute complete cervical tetraplegia participated in the study. Experimental group received 15 sessions with Toyra(®) virtual reality system for 5 weeks, 30 minutes/day, 3 days/week in addition to conventional therapy, while control group only received conventional therapy. All patients were assessed at baseline, after intervention, and at three-month follow-up with a battery of clinical, functional, and satisfaction scales. Control group showed significant improvements in the manual muscle test (p = 0,043, partial η (2) = 0,22) in the follow-up evaluation. Both groups demonstrated clinical, but nonsignificant, changes to their arm function in 4 of the 5 scales used. All patients showed a high level of satisfaction with the virtual reality system. This study showed that virtual reality added to conventional therapy produces similar results in upper limb function compared to only conventional therapy. Moreover, the gaming aspects incorporated in conventional rehabilitation appear to produce high motivation during execution of the assigned tasks. This trial is registered with EudraCT number 2015-002157-35.
Full Text Available The aim of this study was to investigate the effects of a virtual reality program combined with conventional therapy in upper limb function in people with tetraplegia and to provide data about patients’ satisfaction with the virtual reality system. Thirty-one people with subacute complete cervical tetraplegia participated in the study. Experimental group received 15 sessions with Toyra® virtual reality system for 5 weeks, 30 minutes/day, 3 days/week in addition to conventional therapy, while control group only received conventional therapy. All patients were assessed at baseline, after intervention, and at three-month follow-up with a battery of clinical, functional, and satisfaction scales. Control group showed significant improvements in the manual muscle test (p = 0,043, partial η2 = 0,22 in the follow-up evaluation. Both groups demonstrated clinical, but nonsignificant, changes to their arm function in 4 of the 5 scales used. All patients showed a high level of satisfaction with the virtual reality system. This study showed that virtual reality added to conventional therapy produces similar results in upper limb function compared to only conventional therapy. Moreover, the gaming aspects incorporated in conventional rehabilitation appear to produce high motivation during execution of the assigned tasks. This trial is registered with EudraCT number 2015-002157-35.
Dimbwadyo-Terrer, I.; Gil-Agudo, A.; Segura-Fragoso, A.; de los Reyes-Guzmán, A.; Trincado-Alonso, F.; Piazza, S.; Polonio-López, B.
The aim of this study was to investigate the effects of a virtual reality program combined with conventional therapy in upper limb function in people with tetraplegia and to provide data about patients' satisfaction with the virtual reality system. Thirty-one people with subacute complete cervical tetraplegia participated in the study. Experimental group received 15 sessions with Toyra® virtual reality system for 5 weeks, 30 minutes/day, 3 days/week in addition to conventional therapy, while control group only received conventional therapy. All patients were assessed at baseline, after intervention, and at three-month follow-up with a battery of clinical, functional, and satisfaction scales. Control group showed significant improvements in the manual muscle test (p = 0,043, partial η2 = 0,22) in the follow-up evaluation. Both groups demonstrated clinical, but nonsignificant, changes to their arm function in 4 of the 5 scales used. All patients showed a high level of satisfaction with the virtual reality system. This study showed that virtual reality added to conventional therapy produces similar results in upper limb function compared to only conventional therapy. Moreover, the gaming aspects incorporated in conventional rehabilitation appear to produce high motivation during execution of the assigned tasks. This trial is registered with EudraCT number 2015-002157-35. PMID:26885511
Full Text Available Hassan Adalatkhah1, Farhad Pourfarzi2, Homayoun Sadeghi-Bazargani31Department of Dermatology, 2Department of Social Medicine, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil; 3Statistics and Epidemiology Department, Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, IranBackground: The use of oral flutamide is rarely investigated in acne therapy. The aim of this study was to compare the efficacy of oral flutamide with that of a cyproterone-estradiol combination in treating acne lesions.Methods: A randomized clinical trial enrolled patients with moderate acne into two equal groups to receive either oral flutamide or the cyproterone-estradiol combination for 6 months. Lesion count, Acne Severity Index, and Global Acne Grading system (GAGS scores were used to assess improvement in acne lesions. The dichotomous measurement scale for primary endpoint assessment was defined as improvement from moderate to mild acne based on GAGS score. Patient satisfaction and dermal fat were also assessed. Intention to treat and per protocol analyses were done, reporting related effect sizes.Results: Both treatments resulted in substantial improvement in acne lesions. Although flutamide seemed to have higher efficacy, an intention to treat analysis did not find the two treatment protocols to be different. The relative risk in intention to treat analysis was 1.8 (95% confidence interval [CI] 0.89–1.6, and was 1.33 (95% CI 1.03–1.72 for the per protocol analysis. The number needed to treat for flutamide compared with the cyproterone-estradiol combination was 7.7 and 4.2 in the intention to treat and per protocol analyses, respectively.Conclusion: Flutamide appears to be more effective than a cyproterone-estradiol combination in some aspects of acne treatment, but this requires confirmation in a larger trial.Keywords: acne vulgaris, flutamide, cyproterone acetate, ethinyl estradiol, androgen antagonists
Tramontina, Silzá; Zeni, Cristian P; Ketzer, Carla R; Pheula, Gabriel F; Narvaez, Joana; Rohde, Luis Augusto
To assess response to treatment with aripiprazole in children and adolescents with bipolar disorder comorbid with attention-deficit/hyperactivity disorder (ADHD). Children and adolescents were extensively assessed according to DSM-IV criteria for bipolar disorder comorbid with ADHD (n = 710). Those with this comorbidity who were acutely manic or in mixed states were randomly assigned in a 6-week double-blind, placebo-controlled trial to aripiprazole (n = 18) or placebo (n = 25). Primary outcome measures were assessed weekly and included the Young Mania Rating Scale; the Swanson, Nolan, and Pelham Scale-Version IV; and weight. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale, the Child Mania Rating Scale-Parental Version (CMRS-P), the Children's Depression Rating Scale-Revised, the Kutcher Adolescent Depression Scale, and adverse events. The trial was conducted at the Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil, from January 2005 to November 2007. The group receiving aripiprazole showed a significantly greater reduction in YMRS scores (P = .02, effect size [ES] = 0.80), CMRS-P scores (P = .02; ES = 0.54), and CGI-S scores (P = .04; ES = 0.28) from baseline to endpoint than the placebo group. In addition, higher rates of response (P = .02) and remission (P = .01) were found for the aripiprazole group. No significant between-group differences were found in weight, ADHD symptoms, and depressive symptoms. Adverse events significantly more frequent in the aripiprazole group were somnolence and sialorrhea. Aripiprazole was effective in reducing manic symptoms and improving global functioning without promoting severe adverse events or weight gain. No significant treatment effect in ADHD symptoms was observed. Studies are needed to assess psychopharmacologic interventions for improving ADHD symptoms in juvenile bipolar disorder comorbid with ADHD. clinicaltrials.gov Identifier: NCT00116259. Copyright 2009
Yakoot, Mostafa; Salem, Amel
feasible potential for Spirulina platensis in chronic HCV patients, worthy to conduct a larger sized and longer study to confirm these safety and efficacy encouraging results. WHO Clinical Trial Registration ID: ACTRN12610000958088http://apps.who.int/trialsearch/trial.aspx?trialid=ACTRN12610000958088.
Gadi Lalazar; Tomer Adar; Yaron Ilan
AIM: To assess the role of the 13C-methacetin breath test (MBT) in patients with acute liver disease. METHODS: Fifteen patients with severe acute liver disease from diverse etiologies were followed-up with 13C-MBT during the acute phase of their illnesses (range 3-116 d after treatment). Patients fasted for 8 h and ingested 75 mg of methacetin prior to the MBT. We compared results from standard clinical assessment, serum liver enzymes, synthetic function, and breath test scores. RESULTS: Thirteen patients recovered and two patients died. In patients that recovered, MBT parameters improved in parallel with improvements in lab results. Evidence of consistent improvement began on day 3 for MBT parameters and between days 7 and 9 for blood tests. Later convergence to normality occurred at an average of 9 d for MBT parameters and from 13 to 28 d for blood tests. In both patients that died, MBT parameters remained low despite fluctuating laboratory values. CONCLUSION: The 13C-MBT provides a rapid, noninvasive assessment of liver function in acute severe liver disease of diverse etiologies. The results of this pilot clinical trial suggest that the MBT may offer greater sensitivity than standard clinical tests for managing patients with severe acute liver disease.
Plaugher, Gregory; Long, Cynthia R; Alcantara, Joel; Silveus, Alyssa D; Wood, Herbert; Lotun, Kapildeo; Menke, J Michael; Meeker, William C; Rowe, Stephen H
To determine the feasibility of conducting a randomized clinical trial in the private practice setting examining short- and long-term effects of chiropractic adjustments for subjects with essential hypertension compared with a brief soft tissue massage, as well as a nontreatment control group. Randomized controlled-comparison trial with 3 parallel groups. Private practice outpatient chiropractic clinic. Twenty-three subjects, aged 24 to 50 years with systolic or diastolic essential hypertension. Two months of full-spine chiropractic care (ie, Gonstead) consisting primarily of specific-contact, short-lever-arm adjustments delivered at motion segments exhibiting signs of subluxation. The massage group had a brief effleurage procedure delivered at localized regions of the spine believed to be exhibiting signs of subluxation. The nontreatment control group rested alone for a period of approximately 5 minutes in an adjustment room. Cost per enrolled subject, as well as systolic and diastolic blood pressure (BP) measured with a random-0 sphygmomanometer and patient reported health status (SF-36). Pilot study outcome measures also included an assessment of cooperation of subjects to randomization procedures and drop-out rates, recruitment effectiveness, analysis of temporal stability of BPs at the beginning of care, and the effects of inclusion/exclusion criteria on the subject pool. Thirty subjects enrolled, yielding a cost of $161 per enrolled subject. One subject was later determined to be ineligible, and 6 others dropped out. In both the chiropractic and massage therapy groups, all subjects were classified as either overweight or obese; in the control group there were only 2 classified as such. SF-36 profiles for the groups were similar to that of a normal population. The mean change in diastolic BP was -4 (95% confidence interval [CI]: -8.6, 0.5) in the chiropractic care group, 0.5 (95% CI: -3.5, 4.5) in the brief massage treatment group, and -4.9 (95% CI: -9.7, -0
Friedman, Lawrence M; DeMets, David L; Reboussin, David M; Granger, Christopher B
This is the fifth edition of a very successful textbook on clinical trials methodology, written by recognized leaders who have long and extensive experience in all areas of clinical trials. The three authors of the first four editions have been joined by two others who add great expertise. Most chapters have been revised considerably from the fourth edition. A chapter on regulatory issues has been included and the chapter on data monitoring has been split into two and expanded. Many contemporary clinical trial examples have been added. There is much new material on adverse events, adherence, issues in analysis, electronic data, data sharing, and international trials. This book is intended for the clinical researcher who is interested in designing a clinical trial and developing a protocol. It is also of value to researchers and practitioners who must critically evaluate the literature of published clinical trials and assess the merits of each trial and the implications for the care and treatment of ...
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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 ...
Senn, S J
The relevance of the philosophy of Sir Karl Popper to the planning, conduct and analysis of clinical trials is examined. It is shown that blinding and randomization can only be regarded as valuable for the purpose of refuting universal hypotheses. The purpose of inclusion criteria is also examined. It is concluded that a misplaced belief in induction is responsible for many false notions regarding clinical trials.
Álvarez, Evelyn A; Garrido, Maricel A; Tobar, Eduardo A; Prieto, Stephanie A; Vergara, Sebastian O; Briceño, Constanza D; González, Francisco J
Delirium has negative consequences such as increased mortality, hospital expenses and decreased cognitive and functional status. This research aims to determine the impact of occupational therapy intervention in duration, incidence and severity of delirium in elderly patients in the intensive care unit; secondary outcome was to assess functionality at hospital discharge. This is a pilot randomized clinical trial of patients without mechanical ventilation for 60 years. Patients were assigned to a control group that received standard strategies of prevention (n=70) or to an experimental group that received standard strategies plus occupational therapy twice a day for 5 days (n=70). Delirium was valued with Confusion Assessment Method and Delirium Rating Scale, and functional outcomes at discharge with Functional Independence Measure, Hand Dynamometer, and Mini-Mental State Examination. A total of 140 participants were recruited. The experimental group had lower duration (risk incidence ratios, 0.15 [P=.000; 95% confidence interval, 0.12-0.19] vs 6.6 [P=.000, 95% confidence interval, 5.23-8.3]) and incidence of delirium (3% vs 20%, P=.001), and had higher scores in Motor Functional Independence Measure (59 vs 40 points, POccupational therapy is effective in decreasing duration and incidence of delirium in nonventilated elderly patients in the intensive care unit and improved functionality at discharge. Copyright © 2016 Elsevier Inc. All rights reserved.
... How Am I Protected? Mark Bowden / iStock Ethical guidelines The goal of clinical research is to develop knowledge that improves human ... data and decide whether the results have medical importance. Results from clinical trials are often published in peer-reviewed scientific ...
Kraus, V B; Blanco, F J; Englund, M
The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from...... of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute...... both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials...
Full Text Available BACKGROUND/OBJECTIVES: Pain-related misbeliefs among health care professionals (HCPs are common and contribute to ineffective postoperative pain assessment. While standardized patients (SPs have been effectively used to improve HCPs’ assessment skills, not all centres have SP programs. The present equivalence randomized controlled pilot trial examined the efficacy of an alternative simulation method – deteriorating patient-based simulation (DPS – versus SPs for improving HCPs’ pain knowledge and assessment skills.
McAlindon, T. E.; Driban, J. B.; Henrotin, Y.;
The goal of this document is to update the original OARSI recommendations specifically for the design, conduct, and reporting of clinical trials that target symptom or structure modification among individuals with knee osteoarthritis (OA). To develop recommendations for the design, conduct...... and index knee, describing interventions, patient-reported and physical performance measures, structural outcome measures, biochemical biomarkers, and reporting recommendations. In summary, the working group identified 25 recommendations that represent the current best practices regarding clinical trials...... that target symptom or structure modification among individuals with knee OA. These updated recommendations incorporate novel technologies (e.g., magnetic resonance imaging (MRI)) and strategies to address the heterogeneity of knee OA....
Sruthima N. V. S. Gottumukkala
Full Text Available Aim: The aim of this study is to evaluate the efficacy of 1% curcumin (CU solution and compare it with conventional irrigant i.e., 0.2% chlorhexidine (CHX gluconate and a positive control (saline as an adjunct to thorough scaling and root planing. Materials and Methods: A total of 23 patients with non-adjacent probing pocket depths (PPDs ≥5mm were randomly assigned to CHX, CU and positive control irrigation groups and subjected to randomized single blinded clinical control trial. The clinical parameters bleeding on probing, redness, plaque index, PPD and microbiological parameter N-benzoyl-DL-arginine-2-naphthylamide (BANA test were evaluated at baseline, 1, 3 and 6 months interval. Results: At 1 month evaluation, CU group showed better results compared with the other groups. However, by the end of the study period CHX group showed the best results with as light recurrence in the CU group. The results of BANA test showed similar results for both CU and CHX group throughout the study period. Conclusion: The results of this study show a mild to moderate beneficiary effect of CU irrigation when used as an adjunct to Scaling and root planing. Further studies may be required using varied concentrations of the drug to improve the substantivity of the drug and also to prevent early re-colonization of periodontal pathogens.
Henderson, John C.; Neradilek, Moni B.; Moyer, Nicolas A.; Ashcraft, Kristine C.; Thirumaran, Ranjit K.
Background In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients. Methods and findings This prospective, open-label, randomized controlled trial was conducted at one hospital-based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32–1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27–0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31–1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34–0.99; P = 0.045). Differences in composite outcomes at
Full Text Available Gait disorder, a key contributor to fall and poor quality of life, represents a major therapeutic challenge in Parkinson's disease (PD. The efficacy of acupuncture for PD remains unclear, largely due to methodological flaws and lack of studies using objective outcome measures.To objectively assess the efficacy of electroacupuncture (EA for gait disorders using body-worn sensor technology in patients with PD.In this randomized pilot study, both the patients and assessors were masked. Fifteen PD patients were randomly assigned to an experimental group (n = 10 or to a control group (n = 5. Outcomes were assessed at baseline and after completion of three weekly EA treatments. Measurements included gait analysis during single-task habitual walking (STHW, dual-task habitual walking (DTHW, single-task fast walking (STFW, dual-task fast walking (DTFW. In addition, Unified Parkinson's Disease Rating Scale (UPDRS, SF-12 health survey, short Falls Efficacy Scale-International (FES-I, and visual analog scale (VAS for pain were utilized.All gait parameters were improved in the experimental group in response to EA treatment. After adjustment by age and BMI, the improvement achieved statistical significant level for gait speed under STHW, STFW, and DTFW (9%-19%, p0.110. The highest correlation between gait parameters and UPRDS scores at baseline was observed between gait speed during STFW and UPDRS II (r = -0.888, p = 0.004. The change in this gait parameter in response to active intervention was positively correlated with baseline UPDRS (r = 0.595, p = 0.057. Finally, comparison of responses to treatment between groups showed significant improvement, prominently in gait speed (effect size 0.32-1.16, p = 0.001.This study provides the objective proof of concept for potential benefits of non-pharmaceutical based EA therapy on enhancing gait in patients with PD.ClinicalTrials.gov NCT02556164.
Pacheco-da-Costa, Soraya; Hita-Herranz, Edgar
Background: Nonspecific shoulder pain has a high prevalence in older adults and causes functional alterations. Furthermore, there are difficulties in establishing a clinical diagnosis, effective treatments are lacking, and little evidence has been found regarding the use of invasive physical therapy techniques in this age group. Purpose: To determine the efficacy of a single physical therapy intervention with deep dry needling (DDN) on latent and active myofascial trigger points (MTrPs) in older adults with nonspecific shoulder pain. Methods: This pilot study is a single-blind, randomized, controlled clinical trial that included 20 participants, aged 65 years and older, who were diagnosed with nonspecific shoulder pain. The study was approved by the Clinical Research Ethics Committee of the area. Participants were recruited at their homes or at a care center and were randomly assigned into either an experimental group (n = 10), which received a session of DDN on 1 active and 1 latent MTrP of the infraspinatus muscle, or a control group (n = 10), which received a session of DDN on only 1 active MTrP. A blind examiner assessed the pain intensity, pain pressure threshold on the anterior deltoid, and extensor carpi radialis brevis muscles and grip strength before, immediately after, and 1 week after the intervention. Results: Statistically significant differences (P < .05) in the pressure pain thresholds (PPTs) of the extensor carpi radialis brevis were found in the experimental group in both posttreatment assessments. Moreover, the effect size values (d Cohen) varied from small for grip strength (0.017-0.36) to moderate for the pain intensity (0.46-0.78) and PPT in the anterior deltoid (0.49-0.66) and to large for the PPT in the extensor carpi radialis brevis (1.06-1.58). Conclusions: A single physical therapy intervention with DDN on 1 latent MTrP, in conjunction with 1 active MTrP, in the infraspinatus muscle may increase the PPT of the extensor carpi radialis
Calvo-Lobo, César; Pacheco-da-Costa, Soraya; Hita-Herranz, Edgar
Nonspecific shoulder pain has a high prevalence in older adults and causes functional alterations. Furthermore, there are difficulties in establishing a clinical diagnosis, effective treatments are lacking, and little evidence has been found regarding the use of invasive physical therapy techniques in this age group. To determine the efficacy of a single physical therapy intervention with deep dry needling (DDN) on latent and active myofascial trigger points (MTrPs) in older adults with nonspecific shoulder pain. This pilot study is a single-blind, randomized, controlled clinical trial that included 20 participants, aged 65 years and older, who were diagnosed with nonspecific shoulder pain. The study was approved by the Clinical Research Ethics Committee of the area. Participants were recruited at their homes or at a care center and were randomly assigned into either an experimental group (n = 10), which received a session of DDN on 1 active and 1 latent MTrP of the infraspinatus muscle, or a control group (n = 10), which received a session of DDN on only 1 active MTrP. A blind examiner assessed the pain intensity, pain pressure threshold on the anterior deltoid, and extensor carpi radialis brevis muscles and grip strength before, immediately after, and 1 week after the intervention. Statistically significant differences (P < .05) in the pressure pain thresholds (PPTs) of the extensor carpi radialis brevis were found in the experimental group in both posttreatment assessments. Moreover, the effect size values (d Cohen) varied from small for grip strength (0.017-0.36) to moderate for the pain intensity (0.46-0.78) and PPT in the anterior deltoid (0.49-0.66) and to large for the PPT in the extensor carpi radialis brevis (1.06-1.58). A single physical therapy intervention with DDN on 1 latent MTrP, in conjunction with 1 active MTrP, in the infraspinatus muscle may increase the PPT of the extensor carpi radialis brevis muscle area immediately following and 1 week after
Full Text Available skip navigation Help Search home health topics A-Z Videos A-Z about us Customer Support NIH SeniorHealth Built with You in Mind Resize Text: A A A Change Contrast print sign up Share Home > Health topics A-Z > Participating in Clinical Trials: About ...
... will not know if you are taking the medicine or the placebo until the clinical trial is over. How do ... can already get by prescription ) or sugar pills ( placebos ) with the new medicine may last longer than Phases I and II ...
Chassany, O; Duracinský, M
The current reference guideline about ethics in clinical trials is the Declaration of Helsinki of human rights in medical research. Three major principles are emphasised: respect of the patient to accept or not to participate in a trial, the constraints and the presumed risks must be acceptable for patients included in a study, and vulnerable subjects should not participate in studies. The investigator is responsible for obtaining a free and well-informed consent from patients before their inclusion in a study. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. Else, a small-sized trial comparing a new drug versus a reference treatment can lead to an erroneous conclusion of absence of difference. Moreover, good results or improvement are obtained in at least 30% of cases with placebo, whatever the disease. The use of placebo is unethical in life-threatening diseases and when an effective proved drug exists. The use of placebo is ethical in severe diseases with no efficient drug, in some severe diseases even when an active reference treatment is available, and in all moderate and functional diseases. In order to detect flawed studies, most journals now ask for any manuscript submitted and reporting results of a randomised clinical trial to join a checklist in order to verify the quality of the trial. Finally, it remains the responsibility of the doctor to decide whether or not a protocol is ethical, to participate or not and to include patients or not.
Full Text Available ... Trials Insurance Coverage and Clinical Trials How to Work With Your Health Insurance Plan Federal Government Programs Patient Safety Informed Consent Children's Assent Scientific Review Ending Trials Early Deciding to Take Part ...
Bayés, M; Rabasseda, X; Prous, J R
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, http://integrity.prous.com. This issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5-methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA-794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155.
Muqit, Mahiul M K; Young, Lorna B; McKenzie, Rod; John, Binu; Marcellino, George R; Henson, David B; Turner, George S; Stanga, Paulo E
To investigate the short-term effects of high-density 20-ms laser on macular thickness using Pascal-targeted retinal photocoagulation (TRP) and reduced fluence/minimally-traumatic panretinal photocoagulation (MT-PRP) compared to standard-intensity PRP (SI-PRP) in proliferative diabetic retinopathy (PDR). Prospective randomised clinical trial. Treatment-naive PDR was treated with single-session 20-ms Pascal 2500 burns photocoagulation randomised to one of three treatment arms (TRP:MT-PRP:SI-PRP). Primary outcome measure was change in central retinal thickness (CRT) on OCT. Secondary outcomes at 4 and 12 weeks post-laser included: OCT peripapillary nerve fibre layer (NFL) thickness; PDR disease regression on Optos angiography; SITA-Std visual fields (VF); and, visual acuity (VA). 30 eyes of 24 patients were studied, ten eyes/arm. At 12 weeks, there were significant reductions in CRT after TRP (9.6 µm; 95% CI, 1.84 to 17.36; p=0.021) and MT-PRP (17.1 µm; 95% CI, 11 to 23.2; p=0.001), versus SI-PRP (+5.9 µm; 95% CI, -6.75 to 18.55; p=0.32). PDR regression was similar between groups (TRP 70%; MT-PRP 70%; SI-PRP 90%; κ=0.76). No significant changes in VA and NFL thickness developed between groups. The VF mean deviation scores increased significantly in all groups at 12 weeks ([TRP, +0.70dB; 95% CI, 0.07 to 1.48; p=0.07], [MT-PRP, +0.63dB; 95% CI, 0.12 to 1.15; p=0.02], [SI-PRP, +1.0dB; 95% CI, 0.19 to 1.74; p=0.02]). There were no laser-related ocular complications. This pilot study reports that high-density 20-ms Pascal TRP and MT-PRP using 2500 burns did not produce increased macular thickness or any ocular adverse events during the short-term.
Frias, Juan; Raja, Praveen; Kim, Yoona; Savage, George; Osterberg, Lars
Background Hypertension and type 2 diabetes mellitus are major modifiable risk factors for cardiac, cerebrovascular, and kidney diseases. Reasons for poor disease control include nonadherence, lack of patient engagement, and therapeutic inertia. Objective The aim of this study was to assess the impact on clinic-measured blood pressure (BP) and glycated hemoglobin (HbA1c) using a digital medicine offering (DMO) that measures medication ingestion adherence, physical activity, and rest using digital medicines (medication taken with ingestible sensor), wearable sensor patches, and a mobile device app. Methods Participants with elevated systolic BP (SBP ≥140 mm Hg) and HbA1c (≥7%) failing antihypertensive (≥2 medications) and oral diabetes therapy were enrolled in this three-arm, 12-week, cluster-randomized study. Participants used DMO (includes digital medicines, the wearable sensor patch, and the mobile device app) for 4 or 12 weeks or received usual care based on site randomization. Providers in the DMO arms could review the DMO data via a Web portal. In all three arms, providers were instructed to make medical decisions (medication titration, adherence counseling, education, and lifestyle coaching) on all available clinical information at each visit. Primary outcome was change in SBP at week 4. Other outcomes included change in SBP and HbA1c at week 12, and low-density lipoprotein cholesterol (LDL-C) and diastolic blood pressure (DBP) at weeks 4 and 12, as well as proportion of patients at BP goal (<140/90 mm Hg) at weeks 4 and 12, medical decisions, and medication adherence patterns. Results Final analysis included 109 participants (12 sites; age: mean 58.7, SD years; female: 49.5%, 54/109; Hispanic: 45.9%, 50/109; income ≤ US $20,000: 56.9%, 62/109; and ≤ high school education: 52.3%, 57/109). The DMO groups had 80 participants (7 sites) and usual care had 29 participants (5 sites). At week 4, DMO resulted in a statistically greater SBP reduction than
Full Text Available ... treatment, screening, diagnostic, prevention, and supportive care trials. Treatment Trials In treatment trials, researchers may gather information about experimental treatments, ...
The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 6: Patient selection for pilot clinical trials of islet xenotransplantation.
O'Connell, Philip J
Several clinical scenarios would justify trials of islet xenotransplantation, including islet after kidney (IAK) transplantation and islet xenotransplantation for hypoglycemia unawareness. In selecting a patient cohort, several factors unique to xenotransplant trials must be considered, including the potential for unique infective complications, the risks of immunosuppression, and the requirement for life-long monitoring. These factors need to be balanced against the benefits of improved glycemic control and ability to deliver large numbers of high-quality islets, something more difficult to achieve in islet allotransplantation. The importance of these risks varies depending on the patient cohort selected and proposed therapy to be undertaken. In islet xenotransplantation for hypoglycemia unawareness, immunosuppressive risks, and problems with life-long monitoring need special attention in trial design. Whereas in IAK xenotransplantation, consideration must be given to ensure that the procedure does not impact on renal allograft outcomes and patient co-morbidity, which is already significant in renal transplant recipients. This review outlines the rationale for undertaking islet xenotransplantation in highly select patients with type 1 diabetes and addresses some of the unique challenges. At present, no clear consensus exists as to the most appropriate patient group for the first trials of islet xenotransplantation. Rather, this will depend on the type of treatment being proposed, the potential infective risks and the overall burden of immunosuppression.
Full Text Available ... Usually, trial participants must show signs of the disease or condition before they can join this type of trial. Prevention Trials Click for more information In prevention trials, ...
Bayés, M; Rabasseda, X; Prous, J R
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, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort
Conchillo, M; de Knegt, RJ; Payeras, M; Quiroga, J; Sangro, B; Herrero, JI; Castilla-Cortazar, [No Value; Frystyk, J; Flyvbjerg, A; Yoshizawa, C; Jansen, PLM; Scharschmidt, B; Prieto, J
Background/Aims: Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesized in the liver whose levels decrease sharply in liver cirrhosis. Methods: We conducted a randomized double-blind placebo-controlled clinical trial to evaluate the effect of subcutaneous administration of IGF-I (20
Conchillo, M; de Knegt, RJ; Payeras, M; Quiroga, J; Sangro, B; Herrero, JI; Castilla-Cortazar, [No Value; Frystyk, J; Flyvbjerg, A; Yoshizawa, C; Jansen, PLM; Scharschmidt, B; Prieto, J
Background/Aims: Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesized in the liver whose levels decrease sharply in liver cirrhosis. Methods: We conducted a randomized double-blind placebo-controlled clinical trial to evaluate the effect of subcutaneous administration of IGF-I (20
Full Text Available ... Trials Information A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about ... Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to ...
Full Text Available ... Unusual Cancers of Childhood Treatment Childhood Cancer Genomics Study Findings Metastatic Cancer Metastatic Cancer Research Common Cancer ... Trials Insurance Coverage and Clinical Trials How to Work With Your Health Insurance Plan Federal Government Programs ...
Full Text Available ... Trials Information A to Z List of Cancer Drugs Complementary & Alternative Medicine (CAM) Questions to Ask about ... Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & Cancer Adjusting to ...
Subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder manual therapy plus exercise intervention in individuals with subacromial impingement syndrome: a prospective, randomized controlled clinical trial pilot study.
Wright, Alexis A; Donaldson, Megan; Wassinger, Craig A; Emerson-Kavchak, Alicia J
To determine the subacute effects of cervicothoracic spinal thrust/non-thrust in addition to shoulder non-thrust plus exercise in patients with subacromial pathology. This was a randomized, single blinded controlled trial pilot study. This trial was registered at ClinicalTrials.gov (NCT01753271) and reported according to Consolidated Standards of Reporting Trials requirements. Patients were randomly assigned to either shoulder treatment plus cervicothoracic spinal thrust/non-thrust or shoulder treatment-only group. Primary outcomes were average pain intensity (Numeric Pain Rating Scale) and physical function (Shoulder Pain and Disability Index) at 2 weeks, 4 weeks, and patient discharge. 18 patients, mean age 43.1(15.8) years satisfied the eligibility criteria and were analyzed for follow-up data. Both groups showed statistically significant improvements in both pain and function at 2 weeks, 4 weeks, and discharge. The between-group differences for changes in pain or physical function were not significant at any time point. The addition of cervicothoracic spinal thrust/non-thrust to the shoulder treatment-only group did not significantly alter improvement in pain or function in patients with subacromial pathology. Both approaches appeared to provide an equally notable benefit. Both groups improved on all outcomes and met the criteria for clinical relevance for both pain and function. 2b.
Full Text Available ... trial. Prevention Trials Click for more information In prevention trials, researchers study ways to reduce the risk of getting a disease or a specific medical problem. These trials find out if lifestyle changes, such as exercising more, getting more sleep, ...
Aptel, F; Cucherat, M; Blumen-Ohana, E; Denis, P
Clinical trials are playing an increasingly crucial role in modern evidence based medicine, allowing for rigorous scientific evaluation of treatment strategies and validation of patient care. The results of clinical trials often form the rational basis from which physicians draw information used to adapt their therapeutic practices. Critical reading and analysis of trials involves the assessment of whether the available data provide enough credible evidence that the treatment will result in a clinically significant and relevant improvement. Evaluating the quality of a clinical trial is a process that draws upon sometimes complex methodological and statistical concepts, with which the reader should nonetheless be familiar in order to come to impartial conclusions regarding the raw data presented in the clinical trials. The goal of the current article is to review the methodological and statistical concepts required for the design and interpretation of clinical trials, so as to allow for a critical analysis of publications or presentations of clinical trials. The first section describes the major methodological principles of clinical trial design required for a rigorous evaluation of the treatment benefit, as well as the various pitfalls or biases that could lead to erroneous conclusions. The second section briefly describes the main statistical tests used in clinical trials, as well as certain situations that may increase the risk of false positive findings (type 1 error), such as multiple, subgroup, intermediate and non-inferiority analysis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Full Text Available ... Phases of Clinical Trials Cancer Treatment Types of Cancer Treatment Surgery Radiation Therapy Chemotherapy Immunotherapy Targeted Therapy Hormone Therapy Stem Cell Transplant Precision ...
... this page: //medlineplus.gov/ency/patientinstructions/000823.htm A guide to clinical trials for cancer To use ... trial and where to find one. What is a Clinical Trial for Cancer? Clinical trials for cancer ...
Full Text Available ... Institutes of Health funds much of this 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 ...
Avraham, Feazadeh; Aviv, Saposhnik; Ya'akobi, Pnina; Faran, Hava; Fisher, Zilla; Goldman, Yael; Neeman, Guy; Carmeli, Eli
Patello-femoral pain syndrome (PFPS) is a common knee joint disability. The integration of hip soft tissue regimens are not always emphasized, although current literature implies that there is a significant relationship between the two and there is a lack of randomized clinical trials to substantiate this relationship in clinical practice. A randomized controlled assessor blinded trial was designed to explore different rehabilitation programs related to PFPS. The study was conducted at RAZIEL institute of physical therapy, Netania, Israel with a total of 30 consecutive patients (mean age 35y), diagnosed with PFPS. All patients were randomly allocated into 3 groups. Group I conventional knee rehabilitation program. Included quadriceps strengthening and Trans Electric Neuromuscular Stimulation (TENS). Group II hip oriented rehabilitation program. included stretching, Hip external rotators strengthening and TENS. Group III a combination of the two above programs. Pain and function were documented on initial of the program and again 3 weeks later, on the completion. Pain was assessed by a numeric visual analogue scale (VAS); function was assessed by Patello-femoral joint evaluation scale (PFJES) (0-100 points). At end of trial, all groups showed significant improvements in VAS and PFJES (p<0.0001); these improvements did not vary significantly between the 3 groups. The conclusions were that the explored different rehabilitation programs showed a similar beneficial effect.
Full Text Available Patello-femoral pain syndrome (PFPS is a common knee joint disability. The integration of hip soft tissue regimens are not always emphasized, although current literature implies that there is a significant relationship between the two and there is a lack of randomized clinical trials to substantiate this relationship in clinical practice. A randomized controlled assessor blinded trial was designed to explore different rehabilitation programs related to PFPS. The study was conducted at RAZIEL institute of physical therapy, Netania, Israel with a total of 30 consecutive patients (mean age 35y, diagnosed with PFPS. All patients were randomly allocated into 3 groups. Group I conventional knee rehabilitation program. Included quadriceps strengthening and Trans Electric Neuromuscular Stimulation (TENS. Group II hip oriented rehabilitation program. included stretching, Hip external rotators strengthening and TENS. Group III a combination of the two above programs. Pain and function were documented on initial of the program and again 3 weeks later, on the completion. Pain was assessed by a numeric visual analogue scale (VAS; function was assessed by Patello-femoral joint evaluation scale (PFJES (0-100 points. At end of trial, all groups showed significant improvements in VAS and PFJES (p<0.0001; these improvements did not vary significantly between the 3 groups. The conclusions were that the explored different rehabilitation programs showed a similar beneficial effect.
Ayres, Thomas R.
The Dynamo Clinical Trial evaluates long-term stellar magnetic health through periodic X-ray examinations (by the Chandra Observatory). So far, there are only three subjects enrolled in the DTC: Alpha Centauri A (a solar-like G dwarf), Alpha Cen B (an early K dwarf, more active than the Sun), and Alpha Canis Majoris A (Procyon, a mid-F subgiant similar in activity to the Sun). Of these, Procyon is a new candidate, so it is too early to judge how it will fare. Of the other two, Alpha Cen B has responded well, with a steady magnetic heartbeat of about 8 years duration. The sickest of the bunch, Alpha Cen A, was in magnetic cardiac arrest during 2005-2010, but has begun responding to treatment in recent years, and seems to be successfully cycling again, perhaps achieving a new peak of magnetic health in the 2016 time frame. If this is the case, it has been 20 years since A's last healthful peak, significantly longer than the middle-aged Sun's 11-year magnetic heartbeat, but perhaps in line with Alpha Cen A's more senescent state (in terms of "relative evolutionary age," apparently an important driver of activity). (By the way, don't miss the exciting movie of the Alpha Cen stars' 20-year X-ray dance.)
First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--Chapter 6: patient selection for pilot clinical trials of islet xenotransplantation.
Hering, Bernhard J; O'Connell, Philip J
Patients in whom type 1 diabetes is complicated by impaired awareness of hypoglycemia and recurrent episodes of severe hypoglycemia are candidates for islet or pancreas transplantation if severe hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run-in period that provides access to hypoglycemia-specific education including behavioral therapies, insulin analogs, and diabetes technologies under the close supervision of a specialist hypoglycemia service. Patients with type 1 diabetes and end-stage renal failure who cannot meet clinically appropriate glycemic goals or continue to experience severe hypoglycemia after completion of a formalized medical optimization program under the guidance of an expert diabetes care team are candidates for islet or pancreas transplantation either simultaneously with or after a previous kidney transplant. Similarly, patients with type 2 diabetes and problematic hypoglycemia or renal failure who meet these criteria are considered candidates for islet replacement. Likewise, patients with pancreatectomy-induced diabetes in whom an islet autograft was not available or deemed inappropriate are candidates for islet or pancreas transplantation if extreme glycemic lability persists despite best medical therapy. To justify participation of these transplant candidates in early-phase trials of porcine islet cell products, lack of timely access to islet or pancreas allotransplantation due to allosensitization, high islet dose requirements, or other factors, or alternatively, a more favorable benefit-risk determination associated with the xenoislet than the alloislet or allopancreas transplant must be demonstrated. Additionally, in non-uremic xenoislet recipients, the risks associated with diabetes must be perceived to be more serious than the risks associated with the xenoislet product and the rejection prophylaxis, and in xenoislet recipients with renal failure, the xenoislet product
Madero, Magdalena; Rodríguez Castellanos, Francisco E; Jalal, Diana; Villalobos-Martín, Maria; Salazar, Jonathan; Vazquez-Rangel, Armando; Johnson, Richard J; Sanchez-Lozada, L Gabriela
Fructose and sodium intake have been associated with hypertension and metabolic syndrome. Although various mechanisms are involved, fructose causes hypertension partly through rising intracellular and serum uric acid. To date, there are no studies in adults that have evaluated the impact of low fructose diets and allopurinol on prehypertensive and overweight subjects. The objective of this study was to compare the effect of low fructose diet and allopurinol or placebo on blood pressure (BP) and metabolic syndrome components The study was a controlled clinical trial and consisted of two phases; in the first phase of intervention (4 weeks), patients were randomized to either low fructose diet (34 patients) or control diet (38 patients). In the second phase of intervention (weeks 4-8), the same groups continued with the same diet prescriptions but were further randomized to receive placebo or allopurinol (300 mg/d). Clinic and 24-hour ambulatory BP, anthropometric measures, and laboratory data were determined at baseline, weeks 4 and 8. Seventy-two patients were included in the trial. At the end of the dietary phase, both diet groups significantly reduced their BP, but there were no between-group differences. Compared to placebo, at the end of follow-up, subjects in the allopurinol group had a lower clinic systolic blood pressure and this was significant within- and between-group comparisons. The percentage of dippers was higher in the allopurinol group, and weight was reduced significantly despite the absence of caloric restriction Allopurinol was associated with a significant reduction in clinic BP, an increase in the percentage of dippers, and significant weight loss. Larger studies with longer follow-up are needed to confirm our findings. Copyright © 2015 American Society of Hypertension. All rights reserved.
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 ...
Erica C. Borresen MPH
Full Text Available Background: Navy beans and rice bran demonstrate efficacy to regulate serum cholesterol in hypercholesterolemic adults; however, the cardiovascular disease (CVD protective properties of these foods in children are unknown and merit investigation. Objective: The objectives were to determine whether cooked navy bean powder (NBP and/or heat-stabilized rice bran (RB supplementation is tolerable, improves dietary fiber intake in children, and modulates lipid profiles. Methods: Children aged 8 to 13 years at risk for CVD due to abnormal lipids were recruited. Elevated cholesterol levels were defined as total cholesterol ≥180 mg/dL and high-density lipoprotein (HDL 100 mg/dL and HDL <60 mg/dL. Participants completed a pilot 4-week, randomized controlled, 4-arm dietary intervention. They consumed study-provided muffins or a smoothie daily that included 0 g NBP or RB (control, 17.5 g NBP, 15 g RB, or a combination 9 g NBP + 8 g RB. Fasting blood was collected at baseline and week 4. Participants also completed 3-day food logs and gastrointestinal health questionnaires. Results: Thirty-eight children completed the trial (n = 9 control, n = 10 NBP, n = 9 RB, and n = 10 NBP + RB groups. Only 3 participants withdrew due to noncompliance of required food consumption. Participants in the intervention groups significantly increased intake of NBP and RB at week 4 (p≤.01. The NBP and NBP + RB groups increased total fiber intake from baseline to week 4 (p=.02 and p=<.01, respectively. HDL-cholesterol was higher in NBP-group participants compared to control at week 4 (P = .02. Conclusion: Increasing NBP and/or RB intake is tolerable for children, and our findings suggest higher daily intakes are needed for a longer duration to induce favorable changes across multiple serum lipid parameters.
Seyedeh Neda Mousavi
Full Text Available Background: Parenteral nutrition (PN is a valuable life saving intervention, which can improve the nutritional status of hospitalized malnourished patients. PN is associated with complications including hyperglycemia. This study was conducted to compare two methods of blood glucose control in traumatic brain injury patients on PN. Materials and Methods: A randomized, open-label, controlled trial with blinded end point assessment was designed. Traumatic brain injury patients (GCS = 4-9 on PN, without diabetes, pancreatitis, liver disease, kidney complication, were participated. Patients were randomly assigned to receive continuous insulin infusion to maintain glucose levels between 4.4 mmol/l (80 mg/dl and 6.6 mmol/l (120 mg/dl (n = 13 or conventional treatment (n = 13. Patients in the conventional group were not received insulin unless glucose levels were greater than 10 mmol/l (>180 mg/dl. These methods were done to maintain normoglycemia in ICU. The primary outcome was hypo/hyperglycemic episodes. Other factors such as C-reactive protein, blood electrolytes, liver function tests, lipid profile and mid-arm circumference were compared. Results: Mean glucose concentration were significantly lower in IIT group (118 ± 28 mg/dl vs conventional group (210 ± 31 mg/dl (P < 0.01. No hypoglycemic episode occurred in two groups. Triglyceride (P = 0.02 and C-reactive protein (P = 0.001 was decreased in the IIT group, significantly. There were also significant differences in the electrolytes, with magnesium and phosphorus being lower in the IIT group (P = 0.05. Conclusion: In this pilot study, blood glucose level, CRP and TG were lower in IIT group. Further data collection is warranted to reach definitive conclusions.
Schwartz Howard I
Full Text Available Abstract Background Recent research has established correlations between stress, anxiety, insomnia and excess body weight and these correlations have significant implications for health. This study measured the effects of a proprietary blend of extracts of Magnolia officinalis and Phellodendron amurense (Relora® on anxiety, stress and sleep in healthy premenopausal women. Methods This randomized, parallel, placebo controlled clinical study was conducted with healthy, overweight (BMI 25 to 34.9, premenopausal female adults, between the ages of 20 and 50 years, who typically eat more in response to stressful situations and scores above the national mean for women on self-reporting anxiety. The intervention was Relora (250 mg capsules or identical placebo 3 times daily for 6 weeks. Anxiety as measured by the Spielberger STATE-TRAIT questionnaires, salivary amylase and cortisol levels, Likert Scales/Visual Analog Scores for sleep quality and latency, appetite, and clinical markers of safety. The study was conducted by Miami Research Associates, a clinical research organization in Miami, FL. Results The intent-to-treat population consisted of 40 subjects with 26 participants completing the study. There were no significant adverse events. Relora was effective, in comparison to placebo, in reducing temporary, transitory anxiety as measured by the Spielberger STATE anxiety questionnaire. It was not effective in reducing long-standing feelings of anxiety or depression as measured using the Spielberger TRAIT questionnaire. Other assessments conducted in this study including salivary cortisol and amylase levels, appetite, body morphology and sleep quality/latency were not significantly changed by Relora in comparison to placebo. Conclusion This pilot study indicates that Relora may offer some relief for premenopausal women experiencing mild transitory anxiety. There were no safety concerns or significant adverse events observed in this study.
Thompson, Michael A
Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.
Reparative therapy for acute ischemic stroke with allogeneic mesenchymal stem cells from adipose tissue: a safety assessment: a phase II randomized, double-blind, placebo-controlled, single-center, pilot clinical trial.
Díez-Tejedor, Exuperio; Gutiérrez-Fernández, María; Martínez-Sánchez, Patricia; Rodríguez-Frutos, Berta; Ruiz-Ares, Gerardo; Lara, Manuel Lara; Gimeno, Blanca Fuentes
Few studies have evaluated the possible beneficial effect of the administration of stem cells in the early stages of stroke. Intravenous administration of allogeneic mesenchymal stem cells (MSCs) from adipose tissue in patients with acute stroke could be a safe therapy for promoting neurovascular unit repair, consequently supporting better functional recovery. We aim to assess the safety and efficacy of MSC administration and evaluate its potential as a treatment for cerebral protection and repair. A Phase IIa, prospective, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Twenty patients presenting acute ischemic stroke will be randomized in a 1:1 proportion to treatment with allogeneic MSCs from adipose tissue or to placebo (or vehicle) administered as a single intravenous dose within the first 2 weeks after the onset of stroke symptoms. The patients will be followed up for 2 years. Primary outcomes for safety analysis: adverse events (AEs) and serious AEs; neurologic and systemic complications, and tumor development. Secondary outcomes for efficacy analysis: modified Rankin Scale; NIHSS; infarct size; and biochemical markers of brain repair (vascular endothelial growth factor, brain-derived neurotrophic factor, and matrix metalloproteinases 9). To our knowledge, this is the first, phase II, pilot clinical trial to investigate the safety and efficacy of intravenous administration of allogeneic MSCs from adipose tissue within the first 2 weeks of stroke. In addition, its results will help us define the best criteria for a future phase III study. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Holmes, Jonathan M
Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. Copyright © 2015 Elsevier Ltd. All rights reserved.
George, Stephen L; Buyse, Marc
Highly publicized cases of fabrication or falsification of data in clinical trials have occurred in recent years and it is likely that there are additional undetected or unreported cases. We review the available evidence on the incidence of data fraud in clinical trials, describe several prominent cases, present information on motivation and contributing factors and discuss cost-effective ways of early detection of data fraud as part of routine central statistical monitoring of data quality. Adoption of these clinical trial monitoring procedures can identify potential data fraud not detected by conventional on-site monitoring and can improve overall data quality. PMID:25729561
Full Text Available ... to obtain preliminary data on whether the drug works in people who have a certain disease or condition. These trials also continue to study safety, including short-term side effects. This phase ...
Full Text Available ... out if an experimental drug, therapy, medical device, lifestyle change, or test will help treat, find, or ... specific medical problem. These trials find out if lifestyle changes, such as exercising more, getting more sleep, ...
Katz, J N; Losina, E; Lohmander, L S
To highlight methodological challenges in the design and conduct of randomized trials of surgical interventions and to propose strategies for addressing these challenges. This paper focuses on three broad areas: enrollment; intervention; and assessment including implications for analysis. For eac...
Full Text Available ... new tests that could identify a disease in its early stages. Usually, trial participants must show signs ... often healthy people (20 to 80), to judge its safety and side effects, and to find the ...
Full Text Available Abstract Background It is known that repetitive, skilled, functional movement is beneficial in driving functional reorganisation of the brain early after stroke. This study will investigate a whether pedalling an upright, static exercise cycle, to provide such beneficial activity, will enhance recovery and b which stroke survivors might be able to participate in pedalling. Methods/Design Participants (n = 24 will be up to 30 days since stroke onset, with unilateral weakness and unable to walk without assistance. This study will use a modified exercise bicycle fitted with a UniCam crank. All participants will give informed consent, then undergo baseline measurements, and then attempt to pedal. Those able to pedal will be entered into a single-centre, observer-blinded randomised controlled trial (RCT. All participants will receive routine rehabilitation. The experimental group will, in addition, pedal daily for up to ten minutes, for up to ten working days. Prognostic indicators, measured at baseline, will be: site of stroke lesion, trunk control, ability to ambulate, and severity of lower limb paresis. The primary outcome for the RCT is ability to voluntarily contract paretic lower limb muscle, measured by the Motricity Index. Secondary outcomes include ability to ambulate and timing of onset and offset of activity in antagonist muscle groups during pedalling, measured by EMG. Discussion This protocol is for a trial of a novel therapy intervention. Findings will establish whether there is sufficient evidence of benefit to justify proceeding with further research into clinical efficacy of upright pedalling exercise early after stroke. Information on potential prognostic indicators will suggest which stroke survivors could benefit from the intervention. Trial Registration ISRCTN: ISRCTN45392701
... and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers ... to HIV Can anyone participate in an HIV/AIDS clinical trial? It depends on the study. Some ...
N V Ramamurthy
Full Text Available 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.
Full Text Available ... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Contacts Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training ...
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Full Text Available ... Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Lung Cancer Lymphoma Pancreatic Cancer ... Therapy Chemotherapy Immunotherapy Targeted Therapy Hormone Therapy Stem Cell Transplant Precision Medicine Side Effects Clinical Trials Information ...
Full Text Available ... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Report (RPPR) Grant Closeout Grant Resources NCI Grants Management Legal Requirements NCI Grant Policies Grants Management Contacts ...
... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... Report (RPPR) Grant Closeout Grant Resources NCI Grants Management Legal Requirements NCI Grant Policies Grants Management Contacts ...
Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.
The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398
Emery, C. A.; Roos, Ewa M.; Verhagen, E.;
The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform...
The Conducting Clinical Trials in Europe meeting, held in London, included topics covering new developments in the field of clinical trials and recommendations on how to best conduct a trial. This conference report highlights selected presentations on the state of affairs of trials in Europe, conducting trials in emerging markets, strategies for improving trials, trial design options, peri-approval and pediatric trials, and the role of key players, such as physicians. Company perspectives from Pfizer Inc and Nycomed are also included.
Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |
Full Text Available Hiroshi Kikuchi,1,2 Nobuyoshi Shiozawa,1 Shingo Takata,1 Kozo Ashida,1 Fumihiro Mitsunobu11Division of Medicine, Misasa Medical Center, Okayama University Hospital, Misasa, Tottori, Japan; 2Division of Internal Medicine, Takamatsu Hospital KKR, Takamatsu, JapanPurpose: Controlled clinical trials evaluating the efficacy of repeated Waon therapy for patients with chronic obstructive pulmonary disease (COPD have yet to be conducted. The purpose of the present study was to evaluate whether repeated Waon therapy exhibits an adjuvant effect on conventional therapy for COPD patients.Patients and methods: This prospective trial comprised 20 consecutive COPD patients who satisfied the criteria of the Global initiative for chronic Obstructive Lung Disease (GOLD guidelines, stages 1–4. They were assigned to either a Waon or control group. The patients in the Waon group received both repeated Waon therapy and conventional therapy, including medications, such as long-acting inhaled β2 agonists, long-acting anticholinergics and xanthine derivatives, and pulmonary rehabilitation. The Waon therapy consisted of sitting in a 60°C sauna room for 15 minutes, followed by 30 minutes of being warmed with blankets once a day, 5 days a week, for a total of 20 times. The patients in the control group received only conventional therapy. Pulmonary function and the 6-minute walk test were assessed before and at 4 weeks after the program.Results: The change in vital capacity (0.30 ± 0.4 L and in peak expiratory flow (0.48 ± 0.79 L/s in the Waon group was larger than the change in the vital capacity (0.02 ± 0.21 L (P=0.077 and peak expiratory flow (−0.11 ± 0.72 L/s (P=0.095 in the control group. The change in forced expiratory flow after 50% of expired forced vital capacity in the Waon group, 0.08 (0.01–0.212 L/s, was larger than that in the control group, −0.01 (−0.075–0.04 L/s (P=0.019. Significant differences were not observed in the change in any
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Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D
Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Knutson Keith L
induced and boosted Her2-specific antibodies that could be detected for several years after the last vaccine administration in a subgroup of patients. Conclusion This pilot clinical trial demonstrates that Her2-pDNA vaccination in conjunction with GM-CSF and IL-2 administration is safe, well tolerated and can induce long-lasting cellular and humoral immune responses against Her2 in patients with advanced breast cancer. Trial registration The trial registration number at the Swedish Medical Products Agency for this trial is Dnr151:785/2001.
Reimer, C; Lødrup, A B; Smith, G;
BACKGROUND: Many reflux patients remain symptomatic on a standard dose of proton pump inhibitor (PPI). Alginates decrease the number of reflux events by forming a raft on top of the stomach content and thus offer a supplemental mechanism of action to acid suppression. AIM: To assess the efficacy...... of an alginate (Gaviscon Advance, Reckitt Benckiser, Slough, UK) on reflux symptoms in patients with persistent symptoms despite once daily PPI. METHODS: This was a multicentre, randomised, placebo-controlled, 7-day double-blind trial preceded by a 7-day run-in period. Reflux symptoms were assessed using......: In patients with residual reflux symptoms despite PPI treatment, adding an alginate offers additional decrease in the burden of reflux symptoms (EudraCT/IND Number: 2011-005486-21)....
Full Text Available Background: Type II diabetes mellitus (T2DM is the prevalent type of diabetes in the world. Prediabetic patients are the most probable group to get diabetes. Several studies have mentioned the role of inflammation in the incidence of diabetes. The origin of inflammation can be infection such as Helicobacter pylori (HP infection. This study was designed to explore the effect of HP eradication on insulin resistance. Materials and Methods: This single-blind randomized controlled clinical trial was conducted in 2014-2015. The sample size consisted of 49 individuals who were in prediabetes stage with HP infection. Patients with positive stool antigen were allocated randomly into two groups. The treatment group took medication to eradicate HP infection by the routine method of four-drug eradication. However, placebo capsules and tablets were given to the patients in the placebo group. Then fasting plasma glucose (FPG, fasting plasma insulin (FPI, and quantitative C-reactive protein (CRP levels were measured and homeostatic model assessment of insulin resistance (HOMA-IR, homeostatic model assessment of beta-cell function (HOMA-B, Matsuda index, insulinogenic index, and disposition index were calculated. Results: Results of this study showed that FPI and HOMA-IR increased significantly (P value of FPI = 0.023 and P value of HOMA-IR = 0.019 after HP eradication in the treatment group. On the other hand, comparison of differences at the baseline and after 6 weeks in FPG (P value = 0.045, FPI (P value = 0.013, and HOMA-B (P value = 0.038 revealed significant differences between the placebo group and treatment group. Conclusion: Results showed that HP eradication by a 2-week antibiotic medication did not decrease insulin resistance and even increased FPI and insulin resistance indices. So HP eradication among prediabetic patients is not recommended for the decrease of insulin resistance and postponement of the development of diabetes mellitus.
Kachuei, Ali; Amini, Masoud; Sebghatollahi, Vahid; Feizi, Awat; Hamedani, Pooria; Iraj, Bijan
Background: Type II diabetes mellitus (T2DM) is the prevalent type of diabetes in the world. Prediabetic patients are the most probable group to get diabetes. Several studies have mentioned the role of inflammation in the incidence of diabetes. The origin of inflammation can be infection such as Helicobacter pylori (HP) infection. This study was designed to explore the effect of HP eradication on insulin resistance. Materials and Methods: This single-blind randomized controlled clinical trial was conducted in 2014-2015. The sample size consisted of 49 individuals who were in prediabetes stage with HP infection. Patients with positive stool antigen were allocated randomly into two groups. The treatment group took medication to eradicate HP infection by the routine method of four-drug eradication. However, placebo capsules and tablets were given to the patients in the placebo group. Then fasting plasma glucose (FPG), fasting plasma insulin (FPI), and quantitative C-reactive protein (CRP) levels were measured and homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta-cell function (HOMA-B), Matsuda index, insulinogenic index, and disposition index were calculated. Results: Results of this study showed that FPI and HOMA-IR increased significantly (P value of FPI = 0.023 and P value of HOMA-IR = 0.019) after HP eradication in the treatment group. On the other hand, comparison of differences at the baseline and after 6 weeks in FPG (P value = 0.045), FPI (P value = 0.013), and HOMA-B (P value = 0.038) revealed significant differences between the placebo group and treatment group. Conclusion: Results showed that HP eradication by a 2-week antibiotic medication did not decrease insulin resistance and even increased FPI and insulin resistance indices. So HP eradication among prediabetic patients is not recommended for the decrease of insulin resistance and postponement of the development of diabetes mellitus. PMID:27904554
Full Text Available Data generated in all clinical trial are recorded on the data collection instrument Case report Form / Electronic Case Report Form by investigators located at various sites in various countries. In multicentric clinical trials since different investigator or medically qualified experts are from different sites / centers recording the medical term(s uniformly is a big challenge. Medical coders from clinical data management team process these terms and perform medical coding. Medical coding is performed to categorize the medical terms reported appropriately so that they can be analyzed/reviewed. This article describes process which is used for medical coding in clinical data management and two most commonly used medical dictionaries MedDRA and WHO-DDE in brief. It is expected to help medical coders to understand the process of medical coding in clinical data management. Few common issues which the medical coder faces while performing medical coding, are also highlighted.
Bergmann, J F; Chassany, O
To improve medical knowledge by reading clinical trial reports it is necessary to check for the respect of the methodological rules, and to analyze and criticize the results. A control group and a randomisation are always necessary. Double blind assessment, sample size calculation, intention to treat analysis, a unique primary end point are also important. The conclusions of the trial are valid only for the population included and the clinical signification of the results, depending on the control treatment, has to be evaluated. Respect of the reading rules is necessary to assess the reliability of the conclusions, in order to promote evidence-based practice.
Summers, Ron; Vyas, Hiten; Dudhal, Nilesh; Doherty, Neil F; Coombs, Crispin R; Hepworth, Mark
This paper will investigate innovations in information management for use in clinical trials. The application typifies a complex, adaptive, distributed and information-rich environment for which continuous innovation is necessary. Organisational innovation is highlighted as well as the technical innovations in workflow processes and their representation as an integrated set of web services. Benefits realization uncovers further innovations in the business strand of the work undertaken. Following the description of the development of this information management system, the semantic web is postulated as a possible solution to tame the complexity related to information management issues found within clinical trials support systems.
The NCI Community Oncology Research Program (NCORP) is a national network of investigators, cancer care providers, academic institutions, and other organizations. NCORP conducts multi-site cancer clinical trials and studies in diverse populations in community-based healthcare systems across the United States and Puerto Rico.
... National Institutes of Health grant numbers. (See also Secondary IDs data element on ClinicalTrials.gov.) OUTCOME MEASURE A planned ... and Secondary Outcome Measure . (See also Primary and Secondary Outcome Measures data element and Outcome Measure results data element on ...
Full Text Available ... Questions to Ask about Your Diagnosis Research Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z ... Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping with Cancer Feelings and Cancer Adjusting ...
Full Text Available ... Questions to Ask about Your Diagnosis Research Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z ... Alternative Medicine (CAM) Questions to Ask about Your Treatment Research Coping with Cancer Feelings and Cancer Adjusting ...
López-Carrero, Carmen; Arriaza, Elena; Bolaños, Elena; Ciudad, Antonio; Municio, Marco; Ramos, José; Hesen, Wout
Computing has become an integral part of many disciplines nowadays, turning it into an evermore necessary working tool. Internet provides a fast and easy way to collect scientific data and is becoming a more and more effective and safe way to transmit data. It is also an efficient means for interaction and information sharing within a work group that provides the necessary flexibility. A pilot project was conducted replacing the traditional hardcopy version of the case report form for an electronic one (e-CRF) and with access to Internet within the Naturalistic Randomized Clinical Trial of the Effectiveness of Olanzapine and Risperidone in the Treatment of Schizophrenia. Carrying out this pilot project has given us the opportunity to determine the advantages electronic data collection (EDC) by Internet has to offer both researchers and sponsors. The results have optimized time management, since it is easier to work in real time; data quality is improved, since intermediates are eliminated, and it facilitates communication amongst the different parties involved in the project. The use of this technology requires updated Internet connections and adequate personal computers, since the possibilities offered by the computer system and high-speed connection are critical in conducting the project. Obviously, this may involve a higher initial investment, but the results have revealed to us that these start-up costs are later offset by lowering personnel costs or by decreasing the number of monitoring visits. On the basis of our experience and that of the participating investigators, certain recommendations for future clinical trials using e-CRF can be made. We will go into these recommendations in greater depth throughout this paper. In short, EDC can dramatically improve the clinical trial process, opening the door to new technologies in the world of clinical research, not only for sponsors, but also for clinicians.
Paramasivan, S; Rogers, C A; Welbourn, R; Byrne, J P; Salter, N; Mahon, D; Noble, H; Kelly, J; Mazza, G; Whybrow, P; Andrews, R C; Wilson, C; Blazeby, J M; Donovan, J L
Randomized controlled trials (RCTs) involving surgical procedures are challenging for recruitment and infrequent in the specialty of bariatrics. The pilot phase of the By-Band-Sleeve study (gastric bypass versus gastric band versus sleeve gastrectomy) provided the opportunity for an investigation of recruitment using a qualitative research integrated in trials (QuinteT) recruitment intervention (QRI). The QRI investigated recruitment in two centers in the pilot phase comparing bypass and banding, through the analysis of 12 in-depth staff interviews, 84 audio recordings of patient consultations, 19 non-participant observations of consultations and patient screening data. QRI findings were developed into a plan of action and fed back to centers to improve information provision and recruitment organization. Recruitment proved to be extremely difficult with only two patients recruited during the first 2 months. The pivotal issue in Center A was that an effective and established clinical service could not easily adapt to the needs of the RCT. There was little scope to present RCT details or ensure efficient eligibility assessment, and recruiters struggled to convey equipoise. Following presentation of QRI findings, recruitment in Center A increased from 9% in the first 2 months (2/22) to 40% (26/65) in the 4 months thereafter. Center B, commencing recruitment 3 months after Center A, learnt from the emerging issues in Center A and set up a special clinic for trial recruitment. The trial successfully completed pilot recruitment and progressed to the main phase across 11 centers. The QRI identified key issues that enabled the integration of the trial into the clinical setting. This contributed to successful recruitment in the By-Band-Sleeve trial-currently the largest in bariatric practice-and offers opportunities to optimize recruitment in other trials in bariatrics.International Journal of Obesity advance online publication, 15 August 2017; doi:10.1038/ijo.2017.153.
A 6-month clinical trial in the Philippines sought to determine the efficacy of coconut oil and of "monolaurin," a coconut oil byproduct, in killing HIV by breaking down its coating. This research is based on the theory that medium-chain fatty acids, like monolaurin, can have this effect on certain viruses. The trial involves 12 women and 3 men in the early stage of HIV infection. 10 patients will take different doses of monolaurin, and 5 will consume coconut oil. It is hypothesized that the regimen will lead to higher CD4 counts and a lower viral load. The trial was almost abandoned because it received only lukewarm approval from the Health Secretary.
Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida
The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763
Healy, D A; Boyle, E; McCartan, D; Bourke, M; Medani, M; Ferguson, J; Yagoub, H; Bashar, K; O'Donnell, M; Newell, J; Canning, C; McMonagle, M; Dowdall, J; Cross, S; O'Daly, S; Manning, B; Fulton, G; Kavanagh, E G; Burke, P; Grace, P A; Moloney, M Clarke; Walsh, S R
A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed. © The Author(s) 2015.
Mohammad Reza Fattahi
Full Text Available Background: The aim of this study was to compare the efficacy and side effects of lactulose plus traditional Persian medicine with only lactulose on the functional chronic constipation. Methods: Participants included 20 patients (10 in each group aged 18–80 years, with major inclusion criteria of ROME III. They were assigned into two parallel therapeutic groups, including the intervention group (lactulose plus traditional Persian medicine [TPM] advices and control group (only lactulose through a block randomization. Weekly follow-up was done for 1 month for both groups. Results: After the intervention, the frequency of bowel habit increased significantly in patients of both groups (P = 0.001, and the frequency of hard stool defecation, sensation of painful defecation, sensation of incomplete evacuation, sensation of anorectal obstruction, and manual maneuver for evacuation were decreased significantly in patients of both groups (P < 0.001 for all comparisons and 0.025 for manual maneuver. However, the only significant difference between the two groups was more reduction in the sensation of painful defecation in the lactulose group versus lactulose plus TPM advices (P = 0.014. Conclusions: Based on the pilot study, no significant difference was shown between TPM with lactulose and lactulose only in the management of chronic functional constipation. However, the easy recommendations of TPM can be useful in improving chronic constipation.
Over the past decades, randomised controlled trials (RCTs) have prevailed over clinical judgement, case reports, and observational studies and became the gold evidential standard in medicine. Furthermore, during the same time frame, RCTs became a crucial part of the regulatory process whereby a new therapeutic can gain access to the drug market. Today, clinical trials are large and tightly regulated enterprises that have to comply with ethical requirements while maintaining high epistemic standards, a balance that becomes increasingly difficult as the research questions become more sophisticated. In this review, the author will discuss some of the most important ethical issues surrounding RCTs, with an eye to the most recent debates and the context of oncological research in particular. PMID:24482672
.... Clinical Trials in Neurology aims to improve the efficiency of clinical trials and the development of interventions in order to enhance the development of new treatments for neurologic diseases...
Christian S. Kessler
Full Text Available Background. Fibromyalgia (FMS is a challenging condition for health care systems worldwide. Only limited trial data is available for FMS for outcomes of complex treatment interventions of complementary and integrative (CIM approaches. Methods. We conducted a controlled, nonrandomized feasibility study that compared outcomes in 21 patients treated with Ayurveda with those of 11 patients treated with a conventional approach at the end of a two-week inpatient hospital stay. Primary outcome was the impact of fibromyalgia on patients as assessed by the FIQ. Secondary outcomes included scores of pain intensity, pain perception, depression, anxiety, and quality of sleep. Follow-up assessments were done after 6 months. Results. At 2 weeks, there were comparable and significant improvements in the FIQ and for most of secondary outcomes in both groups with no significant in-between-group differences. The beneficial effects for both treatment groups were partly maintained for the main outcome and a number of secondary outcomes at the 6-month followup, again with no significant in-between-group differences. Discussion. The findings of this feasibility study suggest that Ayurvedic therapy is noninferior to conventional treatment in patients with severe FMS. Since Ayurveda was only used as add-on treatment, RCTs on Ayurveda alone are warranted to increase model validity. This trial is registered with NCT01389336.
Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven
To successfully implement a pragmatic clinical trial, investigators need access to numerous resources, including financial support, institutional infrastructure (e.g. clinics, facilities, staff), eligible patients, and patient data. Gatekeepers are people or entities who have the ability to allow or deny access to the resources required to support the conduct of clinical research. Based on this definition, gatekeepers relevant to the US clinical research enterprise include research sponsors, regulatory agencies, payers, health system and other organizational leadership, research team leadership, human research protections programs, advocacy and community groups, and clinicians. This article provides a framework to help guide gatekeepers' decision-making related to the use of resources for pragmatic clinical trials. Relevant ethical considerations for gatekeepers include (1) concern for the interests of individuals, groups, and communities affected by the gatekeepers' decisions, including protection from harm and maximization of benefits; (2) advancement of organizational mission and values; and (3) stewardship of financial, human, and other organizational resources. Separate from these ethical considerations, gatekeepers' actions will be guided by relevant federal, state, and local regulations. This framework also suggests that to further enhance the legitimacy of their decision-making, gatekeepers should adopt transparent processes that engage relevant stakeholders when feasible and appropriate. We apply this framework to the set of gatekeepers responsible for making decisions about resources necessary for pragmatic clinical trials in the United States, describing the relevance of the criteria in different situations and pointing out where conflicts among the criteria and relevant regulations may affect decision-making. Recognition of the complex set of considerations that should inform decision-making will guide gatekeepers in making justifiable choices regarding
Background Negative pressure wound therapy (NPWT) is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial. Methods This was a two-centre (acute and community), pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC) (spun hydrocolloid, alginate or foam dressings). Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up. Results Three hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8%) were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group) during follow-up (time to healing 79 days). The mean number of treatment visits per week was 3.1 (NPWT) and 5.7 (SC); 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT) and 5.0 (SC) months. Conclusions This pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial. Trial registration Current Controlled Trials ISRCTN69032034. PMID:22839453
Ashby Rebecca L
Full Text Available Abstract Background Negative pressure wound therapy (NPWT is widely promoted as a treatment for full thickness wounds; however, there is a lack of high-quality research evidence regarding its clinical and cost effectiveness. A trial of NPWT for the treatment of grade III/IV pressure ulcers would be worthwhile but premature without assessing whether such a trial is feasible. The aim of this pilot randomised controlled trial was to assess the feasibility of conducting a future full trial of NPWT for the treatment of grade III and IV pressure ulcers and to pilot all aspects of the trial. Methods This was a two-centre (acute and community, pilot randomised controlled trial. Eligible participants were randomised to receive either NPWT or standard care (SC (spun hydrocolloid, alginate or foam dressings. Outcome measures were time to healing of the reference pressure ulcer, recruitment rates, frequency of treatment visits, resources used and duration of follow-up. Results Three hundred and twelve patients were screened for eligibility into this trial over a 12-month recruitment period and 12/312 participants (3.8% were randomised: 6 to NPWT and 6 to SC. Only one reference pressure ulcer healed (NPWT group during follow-up (time to healing 79 days. The mean number of treatment visits per week was 3.1 (NPWT and 5.7 (SC; 6/6 NPWT and 1/6 SC participants withdrew from their allocated trial treatment. The mean duration of follow-up was 3.8 (NPWT and 5.0 (SC months. Conclusions This pilot trial yielded vital information for the planning of a future full study including projected recruitment rate, required duration of follow-up and extent of research nurse support required. Data were also used to inform the cost-effectiveness and value of information analyses, which were conducted alongside the pilot trial. Trial registration Current Controlled Trials ISRCTN69032034.
This study was not able to document statistically significant clinical effect of iCBT with minimal therapist contact compared to a waiting list control group in a specialised anxiety clinic in routine care. However, a large and significant effect was seen on self-reported quality of life. Although these results offer an interesting perspective on iCBT in specialised care, they should be interpreted with caution, due to the limitations of the study. A large scale fully powered RCT is recommended.
Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials.
Effects on heart function of neoadjuvant chemotherapy and chemoradiotherapy in patients with cancer in the esophagus or gastroesophageal junction - a prospective cohort pilot study within a randomized clinical trial.
Lund, Mikael; Alexandersson von Döbeln, Gabriella; Nilsson, Magnus; Winter, Reidar; Lundell, Lars; Tsai, Jon A; Kalman, Sigridur
Neoadjuvant therapy for cancer of the esophagus or gastroesophageal (GE)-junction is well established. The pros and cons of chemoradiotherapy and chemotherapy are debated. Chemoradiotherapy might impair cardiac function eliciting postoperative morbidity. The aim of this pilot study was to describe acute changes in left ventricular function following chemoradiotherapy or chemotherapy. Patients with esophageal and (GE)-junction cancer enrolled at our center into a multicenter trial comparing neoadjuvant chemoradiotherapy and chemotherapy were eligible. Patients were randomized to receive cisplatin and 5-fluorouracil with or without the addition of 40 Gy radiotherapy prior to surgery. Left ventricular function was evaluated using echocardiography and plasma N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) before and after neoadjuvant treatment. The primary outcome measure was left ventricular global strain (GS). Clinical effects were assessed using repeated exercise tests. Linear mixed models were used to analyze the effects of treatment group, and the interaction between groups. 40 patients participated (chemoradiotherapy, n=17; chemotherapy, n=23). In the chemoradiotherapy group there was no change in left ventricular global strain but mitral annular plane systolic excursion (MAPSE) of the ventricular septum, early diastolic filling velocity (E-velocity), and the ratio of early to late ventricular filling velocities (E/A ratio) decreased significantly (p=0.02, p=0.01, and p=0.03, respectively). No changes were observed in the chemotherapy group. There was a trend towards an interaction effect for MAPSE sept and E (p=0.09 and p=0.09). NT-proBNP increased following chemoradiotherapy (p=0.05) but not after chemotherapy (p>0.99), and there was a trend towards an interaction effect (p=0.07). Working capacity decreased following neoadjuvant treatment (chemoradiotherapy p = 0.001, chemotherapy p=0.03) and was more pronounced after chemoradiotherapy with a trend
Gustafsson, Finn; Atar, Dan; Pitt, Bertram;
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......, 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...
Tobin, Karin; Kuramoto, Satoko J; German, Danielle; Fields, Errol; Spikes, Pilgrim S; Patterson, Jocelyn; Latkin, Carl
Unity in Diversity was a randomized controlled trial of a culturally tailored HIV prevention intervention for African American men who have sex with men. The intervention condition was six group-based sessions and one individual session. The control condition was a single-session HIV prevention review. Participants were aged 18 years or older, identified as African American/Black race, reported having at least two sex partners in the prior 90 days (at least one of whom must be a male partner), unprotected anal sex with male partner in the prior 90 days, and willing to test for HIV. Retention exceeded 95% at 3-month follow-up. Results of multivariate logistic regression analysis adjusting for baseline risk, HIV status, and health insurance indicate intervention efficacy in decreasing the number of male sex partners and marginal effects on condom use with male partners and HIV-negative/unknown partners. Specifically, intervention condition was associated with increased odds of zero male sex partners (adjusted odds ratio [AOR] = 3.03, 95% confidence interval [CI] = 1.26-7.28), condom use with male partners (AOR = 2.64, 95% CI = 0.95-7.36), and HIV-negative/unknown status partners (AOR = 3.19, 95% CI = 0.98-10.38) at follow-up. These results contribute to the limited number of culturally appropriate models of HIV prevention intervention that are urgently needed for African American men who have sex with men to address their persistently high rates of HIV.
Accrual to cancer clinical trials (CCT) is imperative to safeguard continued improvement in cancer outcomes. A retrospective chart review was performed of patients (n=140) starting a new anti-cancer agent in a north Dublin cancer centre. This review was performed over a four-month period, beginning in November 2015. Only 29% (n=41) had a CCT option. The overall accrual rate to CCT was 5% (n=7), which is comparable to internationally reported figures. The main reasons for failure to recruit to CCT included the lack of a CCT option for cancer type (n=30, 23%), stage (n=25, 19%), and line of treatment (n=23, 17%). Over the last decade, the rate of accrual to CCTs has in fact doubled and the number of trials open to recruitment has tripled. Ongoing governmental and philanthropic support is necessary to continue this trend to further expand CCT patient options with a target accrual rate of 10%.
Full Text Available Abstract Background Despite multiple antidepressant options, major depressive disorder (MDD still faces high non-response rates, eventually requiring anticonvulsant augmentation strategies too. The aim of this study was to explore such a potential role for zonisamide. Methods A total of 40 MDD outpatients diagnosed using the Diagnostic and Statistical Manual for Mental Disorders, fourth edition criteria entered a 24 week open trial receiving duloxetine 60 mg/day for the first 12 weeks and subsequently (weeks 12 to 24 augmentation with zonisamide 75 mg/day if they did not respond to the initial monotherapy. Efficacy and tolerability were assessed using the Hamilton Scales for Anxiety and Depression (a 12 week score ≥50% vs baseline defined 'non-response', the Arizona Sexual Experience Scale, the Patient Rated Inventory of Side Effects and the Young Mania Rating Scale. Results At week 12, 15 patients out of 39 (38.5% were responders, and 1 had dropped out; remarkably, 14 patients out of 24 (58.3% had achieved response by week 24. Poor concentration and general malaise were associated with non-response both at week 12 and 24 (P = 0.001, while loss of libido and reduced energy were prominent among final timepoint non-responders. Patients receiving zonisamide also experienced weight reduction (2.09 ± 12.14 kg; P = 0.001 independently of the outcome. Conclusions Although only a preliminary study due to strong methodological limitations, and thus requiring confirmation by further controlled investigations, the current results indicate zonisamide may be a potential augmentation option for some depressed patients receiving low doses of duloxetine.
In this study we aimed to evaluate the effectiveness of Iyengar yoga in chronic neck pain by means of a randomized clinical trial. 77 with chronic neck pain who scored > 40 mm on a 100-mm visual analog scale (VAS) were randomized to a nine week Iyengar yoga program with weekly 90-minute classes or to a self-care/exercise program. The primary outcome measure was change of mean pain at rest (VAS) from baseline to week ten. Secondary outcomes included pain at motion, functional disabilit...
Anthony V Nguyen
Full Text Available Anthony V Nguyen1, Micaela Martinez1, Michael J Stamos2, Mary P Moyer3, Kestutis Planutis1, Christopher Hope1 Randall F Holcombe11Division of Hematology/Oncology and Chao Family Comprehensive Cancer Center, 2Department of Surgery, University of California, Irvine CA, USA; 3Incell Corporation, San Antonio, TX USAContext: Resveratrol exhibits colon cancer prevention activity in animal models; it is purported to have this activity in humans and inhibit a key signaling pathway involved in colon cancer initiation, the Wnt pathway, in vitro.Design: A phase I pilot study in patients with colon cancer was performed to evaluate the effects of a low dose of plant-derived resveratrol formulation and resveratrol-containing freeze-dried grape powder (GP on Wnt signaling in the colon. Eight patients were enrolled and normal colonic mucosa and colon cancer tissue were evaluated by Wnt pathway-specific microarray and quantitative real-time polymerase chain reaction (qRT-PCR pre- and post-exposure to resveratrol/GP.Results: Based on the expression of a panel of Wnt target genes, resveratrol/GP did not inhibit the Wnt pathway in colon cancer but had significant (p < 0.03 activity in inhibiting Wnt target gene expression in normal colonic mucosa. The greatest effect on Wnt target gene expression was seen following ingestion of 80 g of GP per day (p < 0.001. These results were confirmed with qRT-PCR of cyclinD1 and axinII. The inhibitory effect of GP on Wnt signal throughput was confirmed in vitro with a normal colonic mucosa-derived cell line.Conclusions: These data suggest that GP, which contains low dosages of resveratrol in combination with other bioactive components, can inhibit the Wnt pathway in vivo and that this effect is confined to the normal colonic mucosa. Further study of dietary supplementation with resveratrol-containing foods such as whole grapes or GP as a potential colon cancer preventive strategy is warranted.Trial registration: NCT00256334
Full Text Available Women use more medicines than men because they fall ill more often and suffer more from chronic diseases, but also because women pay more attention to their health and have more consciousness and care about themselves. Although medicines can have different effects on women and men, women still represent a small percentage in the first phases of trials (22% which are essential to verify drugs dosage, side effects, and safety. Even though women are more present in trials, studies results are not presented with a gender approach. This situation is due to educational, social, ethical and economical factors. The scientific research must increase feminine presence in clinical trials in order to be equal and correct, and all the key stakeholder should be involved in this process. We still have a long way to cover and it doesn't concern only women but also children and old people. The aim is to have a medicine not only illness-focused but patient-focused: a medicine able to take into consideration all the patient characteristics and so to produce a really personalized therapy. What above described is part of the reasons why in 2005 was founded the National Observatory for Women's Health (Osservatorio Nazionale sulla Salute della Donna, ONDa which promotes a gender health awareness and culture in Italy, at all the levels of the civil and scientific society.
Gustafsson, Finn; Atar, Dan; Pitt, Bertram
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...
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.
Berry, Scott M; Muller, Peter
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 main ideas and potential benefits of a Bayesian alternative. It then gives an overview of basic Bayesian methodological and computational tools needed for Bayesian clinical trials. With a focus on Bayesian designs that achieve good power and Type I error, the next chapters present Bayesian tools useful in early (Phase I) and middle (Phase II) clinical trials as well as two recent Bayesian adaptive Phase II studies: the BATTLE and ISP...
Full Text Available Abstract Background High blood pressure during acute stroke is associated with poorer stroke outcome. Previous trials have failed to show benefit from lowering blood pressure but treatment may have been commenced too late to be effective. The earliest that acute stroke treatments could be initiated is during contact with the emergency medical services (paramedics. However, experience of pre-hospital clinical trials is limited and logistical challenges are likely to be greater than for trials performed in other settings. We report the protocol for a pilot randomised controlled trial of paramedic initiated blood pressure lowering treatment for hypertension in acute stroke. Methods Trial Design: Double blind parallel group external pilot randomised controlled trial. Setting: Participant recruitment and initial treatment by North East Ambulance Service research trained paramedics responding to the emergency call. Continued treatment in three study hospitals. Participants: Target is recruitment of 60 adults with acute arm weakness due to suspected stroke (within 3 hours of symptom onset and hypertension (systolic BP>160 mmHg. Intervention: Lisinopril 5-10 mg (intervention group, matched placebo (control group, daily for 7 days. Randomisation: Study medication contained within identical pre-randomised "trial packs" carried by research trained paramedics. Outcomes: Study feasibility (recruitment rate, compliance with data collection and clinical data to inform the design of a definitive randomised controlled trial (blood pressure monitoring, National Institute of Health Stroke Scale, Barthel ADL Index, Modified Rankin Scale, renal function. Discussion This pilot study is assessing the feasibility of a randomised controlled trial of paramedic initiated lisinopril for hypertension early after the onset of acute stroke. The results will inform the design of a definitive RCT to evaluate the effects of very early blood pressure lowering in acute stroke
Juraskova, Ilona; Butow, Phyllis; Fisher, Alana; Bonner, Carissa; Anderson, Caroline; Bu, Stella; Scarlet, Jenni; Stockler, Martin R; Wetzig, Neil; Ung, Owen; Campbell, Ian
This study aimed to (1) develop a decision aid for women considering participation in the Sentinel Node Biopsy versus Axillary Clearance 2 (SNAC-2) breast cancer surgical trial and (2) obtain evidence on its acceptability, feasibility, and potential efficacy in routine trial clinical practice via a two-stage pilot. The decision aid was developed according to International Patient Decision Aid Standards. Study 1: an initial pilot involved 25 members of the consumer advocacy group, Breast Cancer Network Australia. Study 2: the main pilot involved 20 women eligible to participate in the SNAC-2 trial in New Zealand. In both pilots, a questionnaire assessed: information and involvement preferences, decisional conflict, SNAC-2 trial-related understanding and attitudes, psychological distress, and general decision aid feedback. A follow-up telephone interview elicited more detailed feedback on the decision aid design and content. In both pilots, participants indicated good subjective and objective understanding of SNAC-2 trial and reported low decisional conflict and anxiety. The decision aid was found helpful when deciding about trial participation and provided additional, useful information to the standard trial information sheet. The development and two-stage piloting process for this decision aid resulted in a resource that women found very acceptable and helpful in assisting decision-making about SNAC-2 trial participation. The process and findings provide a guide for developing other trial decision aids. © The Author(s) 2015.
Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L
There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.
Vieira, Jean Mendes de Lucena; Lima, Elisangela da Costa; Land, Marcelo Gerardin Poirot; Ventura, Miriam; Coelho, Helena Lutescia Luna
This study aimed to characterize the clinical trials with medicines enrolling Brazilian children and adolescents, registered in the databases of Clinical Trials and the Brazilian Clinical Trials Network (ReBEC) from 1994 to 2014. Only 462 clinical trials enrolled Brazilian children and adolescents. There was an increase in registrations beginning in 2003, with an important drop in 2011. Among these trials, 35.5% were hosted in Brazil. The international clinical trials were mostly conducted by North American companies. In both cases, multinational industry was the principal source of funding. The clinical trials were predominantly phase III with injectable and solid oral pharmaceutical forms of antiviral drugs. Domestic clinical trials showed wider variation in the pharmaceutical forms and higher percentage of liquid formulations, when compared to the international trials. In addition to heavy external dependence for conducting clinical trials, the study emphasized the challenge for pediatric care in Brazil, which presents epidemiological peculiarities in an environment prone to the use of unlicensed medicines for children.
A pilot randomised trial to assess the methods and procedures for evaluating the clinical effectiveness and cost-effectiveness of Exercise Assisted Reduction then Stop (EARS) among disadvantaged smokers.
Taylor, Adrian H; Thompson, Tom P; Greaves, Colin J; Taylor, Rod S; Green, Colin; Warren, Fiona C; Kandiyali, Rebecca; Aveyard, Paul; Ayres, Richard; Byng, Richard; Campbell, John L; Ussher, Michael H; Michie, Susan; West, Robert
There have been few rigorous studies on the effects of behavioural support for helping smokers to reduce who do not immediately wish to quit. While reduction may not have the health benefits of quitting, it may lead smokers to want to quit. Physical activity (PA) helps to reduce cravings and withdrawal symptoms, and also reduces weight gain after quitting, but smokers may be less inclined to exercise. There is scope to develop and determine the effectiveness of interventions to support smoking reduction and increase physical activity, for those not ready to quit. To conduct a pilot randomised controlled trial (RCT) [Exercise Assisted Reduction then Stop (EARS) smoking study] to (1) design and evaluate the feasibility and acceptability of a PA and smoking-reduction counselling intervention [for disadvantaged smokers who do not wish to quit but do want to reduce their smoking (to increase the likelihood of quitting)], and (2) to inform the design of a large RCT to determine the clinical effectiveness and cost-effectiveness of the intervention. A single-centre, pragmatic, pilot trial with follow-up up to 16 weeks. A mixed methods approach assessed the acceptability and feasibility of the intervention and trial methods. Smokers were individually randomised to intervention or control arms. General practices, NHS buildings, community venues, and the Stop Smoking Service (SSS) within Plymouth, UK. Aged > 18 years, smoking ≥ 10 cigarettes per day (for ≥ 2 years) who wished to cut down. We excluded individuals who were contraindicated for moderate PA, posed a safety risk to the research team, wished to quit immediately or use Nicotine Replacement Therapy, not registered with a general practitioner, or did not converse in English. We designed a client-centred, counselling-based intervention designed to support smoking reduction and increases in PA. Support sessions were delivered by trained counsellors either face to face or by telephone. Both intervention
Hansson, Sven Ove
A probabilistic explication is offered of equipoise and uncertainty in clinical trials. In order to be useful in the justification of clinical trials, equipoise has to be interpreted in terms of overlapping probability distributions of possible treatment outcomes, rather than point estimates representing expectation values. Uncertainty about treatment outcomes is shown to be a necessary but insufficient condition for the ethical defensibility of clinical trials. Additional requirements are proposed for the nature of that uncertainty. The indecisiveness of our criteria for cautious decision-making under uncertainty creates the leeway that makes clinical trials defensible.
Chen, Yin-Ying; Wu, Ping; Wang, Jie
Drug clinical trial is an important link in the chain of new drug research and development. The results of drug discovery and development directly depend on the extent of standardization of clinical trials. Therefore, improving the quality of drug clinical trials is of great importance, and drug clinical trial institutions play a crucial role in the quality management of drug clinical trials. After years of development, the overall level of drug clinical trials has advanced rapidly in China, and a large number of clinical trials of traditional Chinese medicine have also been carried out. However, there is still a big gap between our country and developed countries. Therefore, for the construction and management of Chinese drug clinical trial institutions, there is still a long way to go. This study aims to analyze the current development of drug clinical trial institutions in China and explore the existing problems from three aspects, including current situations of institutional organization and management, regional and professional distributions, and quality control. And some suggestions are put forward finally, including support of traditional Chinese medicine, introduction of drug-risk management system, and construction of information management.
Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina
Background To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. Methods The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, p...
Cihoric, Nikola; Tsikkinis, Alexandros; Gutierrez Miguelez, Cristina; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina
Background To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. Methods The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type,...
The purpose of this work is to use simulated trials to study how pilot trials can be implemented in relation to bioequivalence testing, and how the use of the information obtained at the pilot stage can influence the overall chance of showing bioequivalence (power) or the chance of approving a truly bioinequivalent product (type I error). The work also covers the use of repeat pivotal trials since the difference between a pilot trial followed by a pivotal trial and a pivotal trial followed by a repeat trial is mainly a question of whether a conclusion of bioequivalence can be allowed after the first trial. Repeating a pivotal trial after a failed trial involves dual or serial testing of the bioequivalence null hypothesis, and the paper illustrates how this may inflate the type I error up to almost 10%. Hence, it is questioned if such practice is in the interest of patients. Tables for power, type I error, and sample sizes are provided for a total of six different decision trees which allow the developer to use either the observed geometric mean ratio (GMR) from the first or trial or to assume that the GMR is 0.95. In cases when the true GMR can be controlled so as not to deviate more from unity than 0.95, sequential design methods ad modum Potvin may be superior to pilot trials. The tables provide a quantitative basis for choosing between sequential designs and pivotal trials preceded by pilot trials.
Bose, Anindya; Das, Suman
Prolonged timelines and large expenses associated with clinical trials have prompted a new focus on improving the operational efficiency of clinical trials by use of Clinical Trial Management Systems (CTMS) in order to improve managerial control in trial conduct. However, current CTMS systems are not able to meet the expectations due to various shortcomings like inability of timely reporting and trend visualization within/beyond an organization. To overcome these shortcomings of CTMS, clinical researchers can apply a business intelligence (BI) framework to create Clinical Research Intelligence (CLRI) for optimization of data collection and analytics. This paper proposes the usage of an innovative and collaborative visualization tool (CTA) as CTMS "add-on" to help overwhelm these deficiencies of traditional CTMS, with suitable examples.
Bricker, Jonathan B; Mull, Kristin E; Kientz, Julie A; Vilardaga, Roger; Mercer, Laina D; Akioka, Katrina J; Heffner, Jaimee L
There is a dual need for (1) innovative theory-based smartphone applications for smoking cessation and (2) controlled trials to evaluate their efficacy. Accordingly, this study tested the feasibility, acceptability, preliminary efficacy, and mechanism of behavioral change of an innovative smartphone-delivered acceptance and commitment therapy (ACT) application for smoking cessation vs. an application following US Clinical Practice Guidelines. Adult participants were recruited nationally into the double-blind randomized controlled pilot trial (n=196) that compared smartphone-delivered ACT for smoking cessation application (SmartQuit) with the National Cancer Institute's application for smoking cessation (QuitGuide). We recruited 196 participants in two months. SmartQuit participants opened their application an average of 37.2 times, as compared to 15.2 times for QuitGuide participants (pacceptance of cravings at baseline (n=88), the quit rates were 15% in SmartQuit vs. 8% in QuitGuide (OR=2.9; 95% CI=0.6-20.7). ACT is feasible to deliver by smartphone application and shows higher engagement and promising quit rates compared to an application that follows US Clinical Practice Guidelines. As results were limited by the pilot design (e.g., small sample), a full-scale efficacy trial is now needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Ellenberg, Susan S; Culbertson, Richard; Gillen, Daniel L; Goodman, Steven; Schrandt, Suzanne; Zirkle, Maryan
In any clinical trial, it is essential to monitor the accumulating data to be sure that the trial continues to be safe for participants and that the trial is being conducted properly. Data monitoring committees, independent expert panels who undertake regular reviews of the data as the trial progresses, serve an important role in safeguarding the interests of research participants and ensuring trial integrity in many trials. Many pragmatic clinical trials, which aim to inform healthcare decisions by comparing alternate interventions in heterogeneous healthcare delivery settings, will warrant review by an independent data monitoring committee due to their potential impact on clinical practice. However, the very features that make a trial "pragmatic" may pose challenges in terms of which aspects of a trial to monitor and when it is appropriate for a data monitoring committee to intervene. Using the Pragmatic-Explanatory Continuum Indicator Summary tool that draws distinctions between pragmatic and explanatory clinical trials, we review characteristics of pragmatic clinical trials that may have implications for data monitoring committees and interim monitoring plans. These include broad eligibility criteria, a focus on subjective patient-centered outcomes, and in some cases a lack of standardized follow-up procedures across study sites. Additionally, protocol adherence is often purposefully not addressed in pragmatic trials in order to accurately represent the clinical practice setting and maintain practicability of implementation; there are differing viewpoints as to whether adherence should be assessed and acted upon by data monitoring committees in these trials. Some other issues not specifically related to the Pragmatic-Explanatory Continuum Indicator Summary criteria may also merit special consideration in pragmatic trials. Thresholds for early termination of a pragmatic clinical trial might be controversial. The distinguishing features of pragmatic clinical
Anand, Vibha; Cahan, Amos; Ghosh, Soumya
ClinicalTrials.gov was established as a web-based registry for clinical trials of human participants in 2000. Mandatory registration started in 2008. Given more than a decade of registered trials, it's important to understand the "topic" areas and their evolution over time from this resource. This information may help in identifying current knowledge gaps. We use dynamic topic model (DTM) methods to discover topics and their evolution over last 17 years. Our model suggests that there are disease or organ specific trials such as 'Cardiovascular disorders', Heart & Brain conditions', or 'Breast & Prostate cancer' as well as trials registered for general health. General health trials are less likely to be FDA regulated, but both health and pain management, as well as surgical, heart, and brain trials have upward trend in recent years while advanced cancer trials have downward trended. Our model derives unique insights from metadata associated with each topic area.
Full Text Available Clinical trials are emerging as an important activity in India as it is an essential component of the drug discovery and development program to which India is committed. The only robust way to evaluate a new medicine is by doing properly designed clinical trials. In addition to advancing science, clinical trials offer myriad benefits to the participants. The recent hue that created in India about clinical trials is probably an exaggeration of facts. However, these points to the need for ensuring proper compliance with the regulatory norms and proper training of concerned personnel in good clinical practice (GCP. This will ensure that India continues to reap the benefits of clinical trials and also become a world leader in this field.
Patrick I Okonta
Full Text Available 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.
Okonta, Patrick I
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.
Palevsky, Paul M; Molitoris, Bruce A; Okusa, Mark D; Levin, Adeera; Waikar, Sushrut S; Wald, Ron; Chertow, Glenn M; Murray, Patrick T; Parikh, Chirag R; Shaw, Andrew D; Go, Alan S; Faubel, Sarah G; Kellum, John A; Chinchilli, Vernon M; Liu, Kathleen D; Cheung, Alfred K; Weisbord, Steven D; Chawla, Lakhmir S; Kaufman, James S; Devarajan, Prasad; Toto, Robert M; Hsu, Chi-yuan; Greene, Tom; Mehta, Ravindra L; Stokes, John B; Thompson, Aliza M; Thompson, B Taylor; Westenfelder, Christof S; Tumlin, James A; Warnock, David G; Shah, Sudhir V; Xie, Yining; Duggan, Emily G; Kimmel, Paul L; Star, Robert A
Acute kidney injury (AKI) remains a complex clinical problem associated with significant short-term morbidity and mortality and lacking effective pharmacologic interventions. Patients with AKI experience longer-term risks for progressive chronic ESRD, which diminish patients' health-related quality of life and create a larger burden on the healthcare system. Although experimental models have yielded numerous promising agents, translation into clinical practice has been unsuccessful, possibly because of issues in clinical trial design, such as delayed drug administration, masking of therapeutic benefit by adverse events, and inadequate sample size. To address issues of clinical trial design, the National Institute of Diabetes and Digestive and Kidney Diseases sponsored a workshop titled "Clinical Trials in Acute Kidney Injury: Current Opportunities and Barriers" in December 2010. Workshop participants included representatives from academia, industry, and government agencies whose areas of expertise spanned basic science, clinical nephrology, critical care medicine, biostatistics, pharmacology, and drug development. This document summarizes the discussions of collaborative workgroups that addressed issues related to patient selection, study endpoints, the role of novel biomarkers, sample size and power calculations, and adverse events and pilot/feasibility studies in prevention and treatment of AKI. Companion articles outline the discussions of workgroups for model trials related to prevention or treatment of established AKI in different clinical settings, such as in patients with sepsis.
Alex D McMahon
Full Text Available Alex McMahon and colleagues critique the International Conference on Harmonisation (ICH guidance on good clinical practice (GCP, arguing that it is having a disastrous effect on noncommerical randomized clinical trials in Europe.
Alex D McMahon; Conway, David I; MacDonald, Tom M; McInnes, Gordon T
Alex McMahon and colleagues critique the International Conference on Harmonisation (ICH) guidance on good clinical practice (GCP), arguing that it is having a disastrous effect on noncommerical randomized clinical trials in Europe.
Prins, J.C.M.; Stubbe, J.H.; Meeteren, N.L.U. van; Scheffers, F.A.; Dongen, M.C.J.M. van
Objective: To investigate the feasibility of a randomized controlled trial and the preliminary effectiveness of ice therapy in the acute phase of a gastrocnemius tear for the quality of functional recovery. Design: A pilot version of an intended prospective randomized controlled clinical trial was
Shakuri Seyed Kazem
Full Text Available Introduction: Prevention of pulmonary complications after coronary artery bypass graft is attended as a very important issue. The aim of this study was to evaluate the role of pulmonary rehabilitation before surgery for reducing the risk of pulmonary complications after surgery. Methods: In a randomized clinical trial, 60 patients undergoing heart surgery were randomly divided into two groups A and B. Chest physiotherapy was performed before and after surgery on group A patients however it was done on group B’s, only after surgery. Effects of preoperative pulmonary rehabilitation were compared between two groups, using spirometry and arterial blood gas (ABG. Results: Thirty nine males (65% and 21 females (35% with mean age of 8.10 ± 9.56 were analyzed.The mean differences were statistically significant for predicted forced vital capacity (FVC (CI95%:1.3 to 8.7 and Predicted Peak Flow indices (PEF (CI 95%: 1.9 to 9.4 of spirometry indicator,PCO2 index (of ABG parameter (CI 95%: 1.4 to 8.9 and mean oxygen saturation (mean Spo2 (CI 95%: 0.6 to 1.7 of ABG index in two groups. Conclusion: The performance of pulmonary rehabilitation program before surgery is recommended, as it may result in the reduction of complications of heart surgery.
Bland Martin J
Full Text Available Abstract Background Acupuncture is increasingly being used for many conditions including chronic neck pain. However the evidence remains inconclusive, indicating the need for further well-designed research. The aim of this study was to conduct a pilot randomised controlled parallel arm trial, to establish key features required for the design and implementation of a large-scale trial on acupuncture for chronic neck pain. Methods Patients whose GPs had diagnosed neck pain were recruited from one general practice, and randomised to receive usual GP care only, or acupuncture (up to 10 treatments over 3 months as an adjunctive treatment to usual GP care. The primary outcome measure was the Northwick Park Neck Pain Questionnaire (NPQ at 3 months. The primary analysis was to determine the sample size for the full scale study. Results Of the 227 patients with neck pain identified from the GP database, 28 (12.3% consenting patients were eligible to participate in the pilot and 24 (10.5% were recruited to the trial. Ten patients were randomised to acupuncture, receiving an average of eight treatments from one of four acupuncturists, and 14 were randomised to usual GP care alone. The sample size for the full scale trial was calculated from a clinically meaningful difference of 5% on the NPQ and, from this pilot, an adjusted standard deviation of 15.3%. Assuming 90% power at the 5% significance level, a sample size of 229 would be required in each arm in a large-scale trial when allowing for a loss to follow-up rate of 14%. In order to achieve this sample, one would need to identify patients from databases of GP practices with a total population of 230,000 patients, or approximately 15 GP practices roughly equal in size to the one involved in this study (i.e. 15,694 patients. Conclusion This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence
Ondersma, Steven J.; Beatty, Jessica R.; Svikis, Dace S.; Strickler, Ronald C.; Tzilos, Golfo K.; Chang, Grace; Divine, W.; Taylor, Andrew R.; Sokol, Robert J.
Background Although screening and brief intervention (SBI) for unhealthy alcohol use has demonstrated efficacy in some trials, its implementation has been limited. Technology-delivered approaches are a promising alternative, particularly during pregnancy when the importance of alcohol use is amplified. The present trial evaluated the feasibility and acceptability of an interactive, empathic, video-enhanced, and computer-delivered SBI (e-SBI) plus three separate tailored mailings, and estimated intervention effects. Methods We recruited 48 pregnant women who screened positive for alcohol risk at an urban prenatal care clinic. Participants were randomly assigned to the e-SBI plus mailings or to a control session on infant nutrition, and were reevaluated during their postpartum hospitalization. The primary outcome was 90-day period-prevalence abstinence as measured by timeline follow-back interview. Results Participants rated the intervention as easy to use and helpful (4.7-5.0 on a 5-point scale). Blinded follow-up evaluation at childbirth revealed medium-size intervention effects on 90-day period prevalence abstinence (OR = 3.4); similarly, intervention effects on a combined healthy pregnancy outcome variable (live birth, normal birthweight, and no NICU stay) were also of moderate magnitude in favor of e-SBI participants (OR=3.3). As expected in this intentionally under-powered pilot trial, these effects were non-significant (p = .19 and .09, respectively). Conclusions This pilot trial demonstrated the acceptability and preliminary efficacy of a computer-delivered screening and brief intervention (e-SBI) plus tailored mailings for alcohol use in pregnancy. These findings mirror the promising results of other trials using a similar approach, and should be confirmed in a fully-powered trial. PMID:26010235
C. A. Caramori
Full Text Available 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 pharmaceutical 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 ClinicalTrials.gov. 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.
Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy
The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs.
Lund, Henrik Hautop; Jessen, Jari Due
We used the modular playware in the form of modular interactive tiles for playful training of community-dwelling elderly with balancing problem. During short-term play on the modular interactive tiles, the elderly were playing physical, interactive games that were challenging their dynamic balance......, agility, endurance, and sensor-motoric reaction. A population of 12 elderly (average age: 79) with balancing problems (DGI average score: 18.7) was randomly assigned to control group or tiles training group, and tested before and after intervention. The tiles training group had statistical significant...... increase in balancing performance (DGI score: 21.3) after short-term playful training with the modular interactive tiles, whereas the control group remained with a score indicating balancing problems and risk of falling (DGI score: 16.6). The small pilot randomized controlled trial suggests...
Klimt, C R
The subject of varied acceptance of clinical trial results is discussed in the context of review of trials with which I have been involved and my subjective evaluation of their impact on the practice of clinical medicine. My experience goes back to 1949 and a World Health Organization trial of hyperimmune gamma globulin against rabies. This was followed by a large trial of secondary prevention of poliomyelitis. I participated in the planning and initiation of the first chronic disease trial, the University Group Diabetes Program (UGDP). The latter lasted for 15 years and its ramifications continue to this day. My next trial was the Coronary Drug Project (CDP), a complex trial with more than 8,000 patients. The trials of aspirin and aspirin combined with persantine (the CDPA, AMIS, PARIS I, and PARIS II) followed. My last three trials were a trial of photocoagulation in diabetic retinopathy (DRS), a six-country trial of the antiarrhythmic drug mexiletine (IMPACT), and a study involving two diagnostic procedures for pulmonary embolism (PIOPED). When one considers, in retrospect, the plethora of trials one is struck by the uniform absence of a priori considerations of the impact on medical practice, or likely lack thereof, of possible outcomes.
Full Text Available n(s) being investigated Acute Stroke MedDRA Classification E.1.3Condition being s... General Information on the Trial E.1 Medical condition or disease under investigation E.1.1Medical conditio
Krarup, L.H.; Gluud, C.; Truelsen, T.
of increasing stroke patients' level of physical activity and secondarily to associate the level of physical activity to the risk of recurrent stroke, myocardial infarction, and all-cause mortality in the two groups. We describe the rationale, design, and baseline data of the ExStroke Pilot Trial. METHODS......INTRODUCTION: A high level of physical activity is associated with a decreased risk of first stroke and physical activity modifies recognized stroke risk factors and is recommended for stroke survivors. Available research shows that stroke patients can increase their level of physical performance...... over a short period. When the intervention period is over, physical performance often declines towards baseline level. Currently, there is no evidence on the association between physical activity and the risk of recurrent stroke. The ExStroke Pilot Trial is a randomized clinical trial with the aim...
Gupta, Sandeep K.
There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464
Sandeep K Gupta
Full Text Available There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process.
Gupta, Sandeep K
There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process.
Klimt, C R
Long-term clinical trials often include more than one active treatment group. These may be discontinued independently if found to be ineffective or possibly harmful. Certain subgroups of patients may be discovered, in the course of a clinical trial, who do not respond satisfactorily and are, therefore, excluded during the course of a trial. Yet another kind of termination comes when we have a therapeutic breakthrough or when hope has to be abandoned for demonstrating beneficial effects for one, several, or all treatments included in a trial. Examples from the authors' experience are presented, as are successful and unsuccessful techniques in managing terminations of various types.
An evaluation of knowledge, attitude, and practice of institutional ethics committee members from eastern India regarding ethics committee functioning and pharmacovigilance activities conducted during clinical trials: A pilot study
Full Text Available Purpose of study: The vital responsibility of Institutional Ethics Committee (IEC members is to ensure the safety of the subjects participating in clinical trials. Hence, it is essential for IEC members to be aware of the common pharmacovigilance strategies followed during clinical trials. However, the information about the knowledge, attitude, and practice of IEC members regarding the pharmacovigilance activities followed during clinical trials is scarce worldwide, especially in India. Hence, this cross-sectional study was designed to assess the knowledge, attitude, and practice of IEC members of 10 hospitals of Kolkata, India. Materials and Methods: A cross-sectional study using a self-administered, validated questionnaire was conducted among 10 hospitals (five government and five corporate hospitals in Kolkata conducting active clinical research and having functional Ethics Committees (ECs in the month of September-November, 2012. An IEC approval was taken for this study. Two reminders were given to all EC members through telephone/e-mail for completion and returning of the forms. The filled in forms were returned to their respective Member Secretaries, from whom authors′ collected the forms. Data were analyzed using SPSS version 16.0 software and MS-Excel 2007. Categorical data were analyzed using Chi-square test and a P < 0.05 was considered statistically significant. Results: Out of the 100 distributed questionnaires, 40 were returned of which 10 were not filled properly. Overall awareness regarding different pharmacovigilance terminologies and activities among EC members from nonmedical background (71.43% was found to be more than that of the medical members (68.75%, though the figure was not statistically significant. Majority of the members (75% felt that EC should decide compensation in case of a serious adverse event. Conclusion: The present study signifies that there is a low level of awareness in IEC members of Kolkata regarding
The effect of changing movement and posture using motion-sensor biofeedback, versus guidelines-based care, on the clinical outcomes of people with sub-acute or chronic low back pain-a multicentre, cluster-randomised, placebo-controlled, pilot trial.
Kent, Peter; Laird, Robert; Haines, Terry
The aims of this pilot trial were to (i) test the hypothesis that modifying patterns of painful lumbo-pelvic movement using motion-sensor biofeedback in people with low back pain would lead to reduced pain and activity limitation compared with guidelines-based care, and (ii) facilitate sample size calculations for a fully powered trial. A multicentre (8 clinics), cluster-randomised, placebo-controlled pilot trial compared two groups of patients seeking medical or physiotherapy primary care for sub-acute and chronic back pain. It was powered for longitudinal analysis, but not for adjusted single-time point comparisons. The intervention group (n = 58) received modification of movement patterns augmented by motion-sensor movement biofeedback (ViMove, dorsaVi.com) plus guidelines-based medical or physiotherapy care. The control group (n = 54) received a placebo (wearing the motion-sensors without biofeedback) plus guidelines-based medical or physiotherapy care. Primary outcomes were self-reported pain intensity (VAS) and activity limitation (Roland Morris Disability Questionnaire (RMDQ), Patient Specific Functional Scale (PSFS)), all on 0-100 scales. Both groups received 6-8 treatment sessions. Outcomes were measured seven times during 10-weeks of treatment and at 12, 26 and 52 week follow-up, with 17.0 % dropout. Patients were not informed of group allocation or the study hypothesis. Across one-year, there were significant between-group differences favouring the intervention group [generalized linear model coefficient (95 % CI): group effect RMDQ -7.1 (95 % CI-12.6;-1.6), PSFS -10.3 (-16.6; -3.9), QVAS -7.7 (-13.0; -2.4); and group by time effect differences (per 100 days) RMDQ -3.5 (-5.2; -2.2), PSFS -4.7 (-7.0; -2.5), QVAS -4.8 (-6.1; -3.5)], all p 30 % at 12-months = RMDQ 2.4 (95 % CI 1.5; 4.1), PSFS 2.5 (1.5; 4.0), QVAS 3.3 (1.8; 5.9). The only device-related side-effects involved transient skin irritation from tape used to mount motion sensors. Individualised
C. A. Caramori
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 pharmaceutical industries has stained clinical research with doubt and improbability. Study results (fruits of controlled clinical trials) and scientific publications (selective, manipulated and with wrong c...
Full Text Available The Clinical Trials Transformation Initiative (CTTI is a public-private partnership created in 2007 between the United States Food and Drug Administration (FDA and Duke University for the purpose of identifying practices that will increase the quality and efficiency of clinical trials. The initiative was generated from the realization that the clinical trials system in the United States has been suffering as a result of increasingly longer study start-up times, slowing enrollment of patients into trials, increasing clinical trial costs, and declining investigator interest in participating in clinical trials. Although CTTI was created to address a crisis for US clinical research, it seeks to identify practice improvements that can be applied internationally, and is therefore engaging international collaborators with international efforts that have similar objectives. CTTI's approach is to involve all sectors in the selection, conduct, and interpretation of its projects; to keep the dialogue open across sectors; to provide evidence that can influence regulatory guidance, and to attempt to create a "level playing field" when recommending change. The hope is that a broad and diverse data-driven discussion of the important issues in clinical trials will lead to meaningful change for the benefit of all concerned, and importantly for patients.
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.
Clark, William F; Sontrop, Jessica M; Huang, Shih-Han; Gallo, Kerri; Moist, Louise; House, Andrew A; Weir, Matthew A; Garg, Amit X
Background and objectives Increased water intake may benefit kidney function. Prior to initiating a larger randomised controlled trial (RCT), we examined the safety and feasibility of asking adults with chronic kidney disease (CKD) to increase their water intake. Design, setting, participants and measurements Beginning in October 2012, we randomly assigned 29 adults with stage 3 CKD (estimated glomerular filtration rate (eGFR) 30–60 mL/min/1.73 m2 and albuminuria) to one of the two groups of water intake: hydration (n=18) or standard (n=11). We asked the hydration group to increase their water intake by 1.0–1.5 L/day (in addition to usual intake, depending on sex and weight) for 6 weeks, while the control group carried on with their usual intake. Participants collected a 24 h urine sample at baseline and at 2 and 6 weeks after randomisation. Our primary outcome was the between-group difference in change in 24 h urine volume from baseline to 6 weeks. Results (63%)of participants were men, 81% were Caucasians and the average age was 61 years (SD 14 years). The average baseline eGFR was 40 mL/min/1.73 m2 (SD 11 mL/min/1.73 m2); the median albumin to creatinine ratio was 19 mg/mmol (IQR 6–74 mg/mmol). Between baseline and 6-week follow-up, the hydration group's average 24 h urine volume increased by 0.7 L/day (from 2.3 to 3.0 L/day) and the control group's 24 h urine decreased by 0.3 L/day (from 2.0 to 1.7 L/day; between-group difference in change: 0.9 L/day (95% CI 0.4 to 1.5; p=0.002)). We found no significant changes in urine, serum osmolality or electrolyte concentrations, or eGFR. No serious adverse events or changes in quality of life were reported. Conclusions A pilot RCT indicates adults with stage 3 CKD can successfully and safely increase water intake by up to 0.7 L/day in addition to usual fluid intake. Trial registration Registered with Clinical Trials—government identifier NCT01753466. PMID:24362012
Martin Schencking; Stefan Wilm; Marcus Redaelli
An increasingly aging population implies an increasing prevalence of osteoarthritis (OA) of hip or knee.It has been ascertained that unspecific hydrotherapy of OA according to Sebastian Kneipp not only improves the range of mobility but also reduces pain significantly and increases the quality of life of the patients affected.OBJECTIVE:The main aim of this pilot study was to determine the effects of hydrotherapy in comparison to conventional physiotherapy,and to analyze the feasibility of the study design under clinical circumstances.DESIGN,SETTING,PARTICIPANTS AND INTERVENTIONS:The study design is a prospective randomized controlled three-arm clinical pilot trial,carried out at a specialist clinic for integrative medicine.Thirty patients diagnosed with symptomatic OA of hip or knee and radiologic findings were randomly assigned to one of two intervention groups and a control group:hydrotherapy (group 1),physiotherapy (group 2),and both physiotherapy and hydrotherapy (group 3,control group) of the affected joint.MAIN OUTCOME MEASURES:Primary outcome:pain intensity of the affected joint in the course of inpatient treatment; secondary outcome:health-related quality of life,joint-specific pain and mobility in the course of the study.RESULTS:Concerning the main outcome,intervention group 1 showed most beneficial effects in the course of inpatient treatment,followed by groups 3 and 2,and also the indirect flexion ability of hip or knee together with the general patient mobility through the "timed up and go" test were mainly improved within group 1 followed by groups 3 and 2.CONCLUSION:The results of this pilot study demonstrate beneficial effects of hydrotherapy.The study design is feasible.For statistically significant evidence and a robust conclusion of efficacy of Kneipp's hydrotherapy,a larger sample size is necessary.TRIAL REGISTRATION NUMBER:NCT 00950326.
Lirio Romero, Cristina; Torres Lacomba, María; Castilla Montoro, Yurema; Prieto Merino, David; Pacheco da Costa, Soraya; Velasco Marchante, María Jesús; Bodes Pardo, Gema
The purpose of this study was to evaluate the feasibility of the methods proposed to conduct a full randomized clinical trial to assess the effectiveness of mobilization with movement on shoulder functionality in older adults with shoulder dysfunction. A pilot, randomized, single-blinded clinical trial was carried out with 44 older adults (83.9±8.2 years) with shoulder dysfunction in 3 nursing homes in Toledo, Spain. Participants were recruited through information sessions and were randomly allocated into 2 groups. The control group (n = 22) intervention consisted of a physical therapy standard protocol proposed by the Spanish Rheumatology Society. Techniques based on Mulligan's concepts of mobilization with movement were added to the standard protocol for the experimental group (n = 22) intervention. Interventions took place 3 times a week for 2 consecutive weeks and were performed by 2 experienced therapists. Main outcomes were recruitment rates, participation and adherence to interventions, assessment procedures, and the implementation of mobilization with movement. Clinical outcomes were shoulder functionality, active glenohumeral range of motion, and pain intensity. Data were collected at baseline, after each group intervention, and at 1 and 3 months after finishing interventions. All the participants accepted to be randomized. Participation rates were 97.7% for the experimental group and 95.5% for the control group. The analysis of variance did not show any statistically significant difference between treatment groups for any of the variables (all P values for the group effect were greater than .36) or a change of the difference between groups over time (all P values for the time-treatment interactions were greater than .3). The research methods tested in this pilot study offer a suitable foundation to conduct a full clinical trial.
Lirio Romero, Cristina; Torres Lacomba, María; Castilla Montoro, Yurema; Prieto Merino, David; Pacheco da Costa, Soraya; Velasco Marchante, María Jesús; Bodes Pardo, Gema
Objective The purpose of this study was to evaluate the feasibility of the methods proposed to conduct a full randomized clinical trial to assess the effectiveness of mobilization with movement on shoulder functionality in older adults with shoulder dysfunction. Methods A pilot, randomized, single-blinded clinical trial was carried out with 44 older adults (83.9±8.2 years) with shoulder dysfunction in 3 nursing homes in Toledo, Spain. Participants were recruited through information sessions and were randomly allocated into 2 groups. The control group (n = 22) intervention consisted of a physical therapy standard protocol proposed by the Spanish Rheumatology Society. Techniques based on Mulligan’s concepts of mobilization with movement were added to the standard protocol for the experimental group (n = 22) intervention. Interventions took place 3 times a week for 2 consecutive weeks and were performed by 2 experienced therapists. Main outcomes were recruitment rates, participation and adherence to interventions, assessment procedures, and the implementation of mobilization with movement. Clinical outcomes were shoulder functionality, active glenohumeral range of motion, and pain intensity. Data were collected at baseline, after each group intervention, and at 1 and 3 months after finishing interventions. Results All the participants accepted to be randomized. Participation rates were 97.7% for the experimental group and 95.5% for the control group. The analysis of variance did not show any statistically significant difference between treatment groups for any of the variables (all P values for the group effect were greater than .36) or a change of the difference between groups over time (all P values for the time-treatment interactions were greater than .3). Conclusion The research methods tested in this pilot study offer a suitable foundation to conduct a full clinical trial. PMID:26793036
Østervig, R M; Sonne, A; Rasmussen, L S
BACKGROUND: Registration of interventional studies is necessary according to the Declaration of Helsinki but implementation has been a challenge for many journals. Acta Anaesthesiologica Scandinavica (Acta) requires registration for studies conducted after January 1(st) 2010. We aimed to assess...... registered when it could be verified that patient enrolment was started after registration in a trial registry. RESULTS: We identified 200 RCTs. Dates for patient enrolment were not specified in 51 (25.5%). The proportion of correctly registered trials increased significantly from 17.1% (19/111) for trials...
Ness, Elizabeth A; Royce, Cheryl
Clinical trials are paramount to improving human health. New trial designs and informed consent issues are emerging as a result of genomic profiling and the development of molecularly targeted agents. Many groups and individuals are responsible for ensuring the protection of research participants and the quality of the data produced. The specialty role of the clinical trials nurse (CTN) is critical to clinical trials. Oncology CTNs have competencies that can help guide their practice; however, not all oncology clinical trials are supervised by a nurse. Using the process of engagement, one organization has restructured oncology CTNs under a nurse-supervised model.
Full Text Available Overweight and obesity is prevalent among women of reproductive age (42% BMI > 25 kg/m2 and parity is associated with risk of weight gain. Weight gain greater than that recommended by the Institute of Medicine (IOM is also associated with lower rates of breastfeeding initiation and duration in women. The aim of this pilot randomised controlled trial is to examine the feasibility of recruiting and maintaining a cohort of pregnant women with the view of reducing postpartum weight retention and improving breastfeeding outcomes. Women (BMI of 25–35 kg/m2 (n = 36 were recruited from the John Hunter Hospital antenatal clinic in New South Wales, Australia. Participants were stratified by BMI and randomised to one of three groups with follow-up to six months postpartum. Women received a dietary intervention with or without breastfeeding support from a lactation consultant, or were assigned to a wait-list control group where the dietary intervention was issued at three months postpartum. Feasibility and acceptability was assessed by participation rates and questionnaire. Analysis of variance and covariance was conducted to determine any differences between groups. Sixty-nine per cent of the participants were still enrolled at six months postpartum. This pilot demonstrated some difficulties in recruiting women from antenatal clinics and retaining them in the trial. Although underpowered; the results on weight; biomarkers and breastfeeding outcomes indicated improved metabolic health.
Full Text Available nter, Randomized, Double-blind, Placebo-controlled Trial of Three Fixed Doses of OPC-34712 in the Treatment of Adults With Acute...2 in the Treatment of Adults With Acute Schizophrenia A.4.1Sponsor's protocol code number331-10-231 A.5.2US ... Information on the Trial E.1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute...ition or disease under investigation E.1.2Version 14.1 E.1.2Level LLT E.1.2Classification code 10001064 E.1.2Term Acute
Full Text Available 2, and 1 mg/day) in the Treatment of Adults With Acute Schizophrenia A.3.1Title ...of the trial for lay people, in easily understood, i.e. non-technical, language Efficacy Study of OPC-34712 in Adults With Acute...e Trial E.1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute...nder investigation E.1.2Version 14.0 E.1.2Level LLT E.1.2Classification code 10001064 E.1.2Term Acute schizo
Ellis, Cara E; Korbutt, Gregory S
The development of the Edmonton Protocol encouraged a great deal of optimism that a cell-based cure for type I diabetes could be achieved. However, donor organ shortages prevent islet transplantation from being a widespread solution as the supply cannot possibly equal the demand. Porcine islet xenotransplantation has the potential to address these shortages, and recent preclinical and clinical trials show promising scientific support. Consequently, it is important to consider whether the current science meets the ethical requirements for moving toward clinical trials. Despite the potential risks and the scientific unknowns that remain to be investigated, there is optimism regarding the xenotransplantation of some types of tissue, and enough evidence has been gathered to ethically justify clinical trials for the most safe and advanced area of research, porcine islet transplantation. Researchers must make a concerted effort to maintain a positive image for xenotransplantation, as a few well-publicized failed trials could irrevocably damage public perception of xenotransplantation. Because all of society carries the burden of risk, it is important that the public be involved in the decision to proceed. As new information from preclinical and clinical trials develops, policy decisions should be frequently updated. If at any point evidence shows that islet xenotransplantation is unsafe, then clinical trials will no longer be justified and they should be halted. However, as of now, the expected benefit of an unlimited supply of islets, combined with adequate informed consent, justifies clinical trials for islet xenotransplantation.
Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L
A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well.
Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K
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. 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. 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. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.
Full Text Available lot Trial of Indomethacin in Acute Pancreatitis Ensayo piloto controlado y aleatorizado con indometacina en ....1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute...n criteria Patients ages 18 or above admitted to hospital with a diagnosis of Acute pancreatitis (AP) based
Full Text Available edical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute Rhinosinu....2.3Trial contains a sub-study No E.3Principal inclusion criteria 1. Adult male and female outpatients aged ≥ 18 - 75 years 2. Acute
... Releases & Announcements Public Service Announcements Partnering with DBSA Clinical Trials: Information and Options for People with Mood Disorders What are clinical trials? Clinical trials are research studies involving people, which ...
@@ Introduction The mission of the WHO Intemational Clinical Trials Registry Platform is to ensure that a complete view of research is accessible to all those involved in health care decision making.This will improve research transparency and will ultimately strengthen tha validity and value of the scientific evidence base.The registration of all interventional trials is a scientific, ethical and moral responsibility.
A pilot cluster randomised controlled trial to investigate the addition of direct access to physiotherapy to usual GP-led primary care for adults with musculoskeletal pain: the STEMS pilot trial protocol (ISRCTN23378642).
Bishop, Annette; Tooth, Stephanie; Protheroe, Joanne; Salisbury, Chris; Ogollah, Reuben O; Jowett, Sue; Hay, Elaine M; Foster, Nadine E
Musculoskeletal problems are common, accounting for up to 30 % of general practitioner (GP) consultations and are a major cause of chronic disability worldwide. Demand for health care for musculoskeletal conditions is likely to continue to rise given the ageing population and the increasing impact of these common painful conditions. Physiotherapists are well equipped to deliver evidence-based management for these conditions. Direct access allows patients to access physiotherapy without seeing their GP or another referring practitioner first; however, for most patients in the UK, access to National Health Service physiotherapy is controlled through GP referral. The aim of this pilot, pragmatic, cluster trial is to assess the feasibility of a future large trial to compare the clinical and cost-effectiveness of the additional offer of direct access to physiotherapy versus continuing with usual GP-led primary care alone for adults with common musculoskeletal problems. The pilot will focus on process outcomes to assess feasibility, although performance of the likely outcomes of a main trial will also be assessed. This is a two-arm parallel, cluster RCT where GP practices are the units of randomisation (the clusters), yet data are collected from individual patients with musculoskeletal problems (the participants). A direct access service will be set up in the participating physiotherapy service to provide the option of direct access to patients of the intervention arm practices. Inclusion criteria are broad to reflect the 'real-world' operation of an NHS physiotherapy direct access service for patients with musculoskeletal pain. Data collection will be through patient self-reported questionnaires at baseline, 2, 6 and 12 months and medical record review. No previous trials have been conducted into direct access to physiotherapy for patients with musculoskeletal problems. The strengths of the STEMS pilot trial are its size, the length of follow-up, and collection of
Hróbjartsson, A; Boutron, I
Blinding, or "masking," is a crucial method for reducing bias in randomized clinical trials. In this paper, we review important methodological aspects of blinding, emphasizing terminology, reporting, bias mechanisms, empirical evidence, and the risk of unblinding. Theoretical considerations...
Molloy, Síle F; Henley, Patricia
This article describes the processes and procedures involved in planning, conducting and reporting monitoring activities for large Clinical Trials of Investigational Medicinal Products (CTIMPs), focusing on those conducted in resource-limited settings. © 2016 John Wiley & Sons Ltd.
... altering them as they run to take into account accumulating results. Although Bayesian designs are now widely used in everything from astrophysics to ecology, they've been slower to catch on in medical research, particularly clinical trials...
Geller, Nancy L; Kim, Dong-Yun; Tian, Xin
This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.
Jan 22, 2008 ... Manufacturers Association, on the basis of a survey of its members ... from this information. The US database, on the other hand, clearly identifies 172 ... workforce involved in clinical trials outside the public sector. This figure ...
Williamson, Paula R; Gamble, Carrol; O'Connell Francischetto, Elaine; Metcalfe, Chris; Davidson, Peter; Williams, Hywel; Blazeby, Jane M
Objectives Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or ‘progression’ criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. Design A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. Results There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Conclusions Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials. PMID:28213598
Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba
Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0
Benjamin M Davies
Full Text Available There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.
Full Text Available r investigation E.1.1Medical condition(s) being investigated Acute Heart Failure MedDRA Classification E.1.3...in one hour of admission to ICU.3. Signed informed consent E.4Principal exclusion criteria 1. Age less than 18 years.2. Acute...y with Trimetazidine in Acute heart failure: an open pilot randomized trial (The METTA – PRAGUE 10 Trial) A....e ConcernedCzech Republic - SUKL A.2EudraCT number2007-002893-76 A.3Full title of the trial MEtabolic Therap
Full Text Available E.1 Medical condition or disease under investigation E.1.1Medical condition(s) being investigated Acute Gou...t E.1.1.1Medical condition in easily understood language Acute Gout E.1.1.2Therapeutic area Diseases [C] - M...n the trial (if it is different from the expected normal treatment of that condition) Acute gout is a self l
Kjaergard, L L; Nikolova, D; Gluud, C
. Quality was assessed by means of a validated 5-point scale and separate quality components associated with empirical evidence of bias. Only 26% of all RCTs reported sample size calculations, 52% adequate generation of the allocation sequence, 34% adequate allocation concealment and 34% double......, single-center trials, and trials with no external funding. Quality did not improve with time and was not associated with country of origin. The main conclusions are that the quality of RCTs in HEPATOLOGY needs improvement and that the probability of high quality increased with the number of centers...
Olga Lidia Cuevas Pérez
Full Text Available Today there are countless examples that illustrate the nature of technoscience, including biotechnology and pharmacology. The clinical trial is the appropriate methodology used by clinical pharmacology to test the efficacy and safety of a treatment or intervention in humans. It constitutes the cornerstone of research. Once the preclinical research is completed, one of the biggest challenges currently facing the Cuban Pharmaceutical and Biotechnological Industry is precisely the clinical evaluation. Therefore, this work aims to provide a reflection on the most significant aspects of clinical trials and their impact on society.
Liu, Fei-Fei; Okunieff, Paul; Bernhard, Eric J.; Stone, Helen B.; Yoo, Stephen; Coleman, C. Norman; Vikram, Bhadrasain; Brown, Martin; Buatti, John; Guha, Chandan
A Workshop entitled “Lessons Learned from Radiation Oncology Trials” was held on December 7–8th, 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 pre-clinical data that supported the hypotheses underlying these trials, an...
Oud, Johan; Ghidey, Wendimagegn
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.
Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen
To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.
Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian
The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.
Yankeelov, Thomas E; Mankoff, David A; Schwartz, Lawrence H; Lieberman, Frank S; Buatti, John M; Mountz, James M; Erickson, Bradley J; Fennessy, Fiona M M; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L; Linden, Hannah M; Kinahan, Paul E; Zhao, Binsheng; Hylton, Nola M; Gillies, Robert J; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L
As anticancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. Although traditional, anatomic CT, and MRI examinations are useful in many settings, increasing evidence suggests that these methods cannot answer the fundamental biologic and physiologic questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients and to provide a more efficient path for the development of improved targeted therapies.
Plétan, Yannick; Zannad, Faïez; Jaillon, Patrice
Be it to restore the confused image of clinical research in relation to the lay public, or to develop new ways of accruing healthy volunteers or patients for clinical trials, there is a need to draft some guidance on how best to provide information on research. Although the French legal and regulatory armamentarium in this area is essentially liberal, there is currently little-justified reluctance among study sponsors to advertise publicly. A group of academic and pharmaceutical industry researchers, assembled for a workshop, together with regulators, journalists, representatives from ethics committees, social security, patient and health consumer groups and other French institutional bodies, has suggested the following series of recommendations: there is no need for additional legal or regulatory constraints; sponsors should be aware of and make use of direct public information on trials; a 'good practice charter' on public communication about clinical trials should be developed; all professionals should be involved in this communication platform; communication in the patient's immediate vicinity should be preferred (primary-care physician, local press); clinical databases and websites accessible to professionals, but also to patients and non-professionals, should be developed; genuine instruction on clinical trials for physicians and health professionals unfamiliar with such trials should be developed and disseminated; media groups should receive at least some training in the fundamentals of clinical research.
Full Text Available ion E.1.1Medical condition(s) being investigated Acute cough Akuter Husten E.1.1.1Medical condition in easily understood language Acu...igation E.1.2Version 17.1 E.1.2Level LLT E.1.2Classification code 10066522 E.1.2Term Acute cough E.1.2System...igible for inclusion in this trial must fulfill all of the following criteria:1. Acute cough with symptoms l...based on medical history and physical examination7. CS score of at least 50 mm on a 100 mm VAS at V1 8. Acute...te cough Akuter Husten E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Dis
Biological and clinical evaluation of lanreotide (BIM 23014), a somatostatin analogue, in the treatment of advanced breast cancer. A pilot study by the I.T.M.O. Group. Italian Trials in Medical Oncology.
Di Leo, A; Ferrari, L; Bajetta, E; Bartoli, C; Vicario, G; Moglia, D; Miceli, R; Callegari, M; Bono, A
Biological data support the development of clinical trials designed to evaluate the activity of somatostatin (SMS) analogues in advanced breast cancer (ABC). Although previous clinical trials have failed to show antitumor activity, various factors may have biased their results. In an attempt to improve our understanding of the role of SMS analogues in ABC, 10 patients with favourable prognostic factors and who had not been heavily pretreated for advanced disease were treated with lanreotide 30 mg i.m. fortnightly (depot formulation). Blood samples were periodically taken to evaluate the effect of the drug on growth hormone (GH) and insulin-like growth factor 1 (IGF-1) and to determine drug serum levels. Although the drug was well tolerated, no clinical activity was observed. Serum GH and IGF-1 levels were not properly suppressed over time and drug serum concentrations fluctuated widely. In conclusion, SMS analogues cannot be recommended even as palliative treatment of ABC. Further studies should be undertaken to investigate the effect of higher drug doses, given subcutaneously or by means of continuous infusion, in suppressing GH and IGF-1 serum levels.
Aboulker, J P
Comparative judgement, which is seminal to any kind of science performing measurements, has been applied to clinical reasoning for many centuries. The need for systematizing the observational methods used in medicine in order to draw more reliable inferences about the effects of therapies has been active all along the 19th century. This has resulted in controlled studies which yielded important advances in clinical and therapeutic knowledge, although their designs were not fully satisfactory. Clinical trials have gained their status of "hard science", methodology allowing causal inference, by the end of the 1940s after having adopted the statistical theories developed in the 1930s by Fisher for experimental design in agronomy. A long way has been run since the first controlled randomized trial. However, half a century later, modern clinical trial remains essentially a controlled randomized prospective study using methods to limit potential biases and to establish statistical significance.
Clinical trials are necessary for medical advancement. They must respect legal obligations. Ethical questions related to protection of the human being's rights are yielded by these trials. Joining research to medical core is problematical in consideration of patient's consent to clinical trial. Exclusion by the Tunisian law of persons under age, pregnant or breast-feeding women from medical experimentation in the aim of protecting them against clinical research adverse events or abuses is ethically questionable since it deprives them from a possible medical progress. So why not to involve them in clinical research when there is an expected benefit, after bringing them protection as vulnerable persons like we should do for instance for the elderly, handicapped persons or prisoners. Legal creation of research ethics committees is important for the respect of experimentation rules on human beings.
Hussain-Gambles, M; Leese, B; Atkin, K; Brown, J; Mason, S; Tovey, P
To investigate how South Asian patients conceptualise the notion of clinical trials and to identify key processes that impact on trial participation and the extent to which communication difficulties, perceptions of risk and attitudes to authority influence these decisions. Also to identify whether 'South Asian' patients are homogeneous in these issues, and which factors differ between different South Asian subgroups and finally how professionals regard the involvement of South Asian patients and their views on strategies to increase participation. A review of the literature on minority ethnic participation in clinical trials was followed by three qualitative interview studies. Interviews were taped and transcribed (and translated if required) and subjected to framework analysis. Face-to-face interviews were conducted with 25 health professionals; 60 South Asian lay people who had not taken part in a trial and 15 South Asian trial participants. Motivations for trial participation were identified as follows: to help society, to improve own health or that of family and friends, out of obligation to the doctor and to increase scientific knowledge. Deterrents were concerns about drug side-effects, busy lifestyles, language, previous bad experiences, mistrust and feelings of not belonging to British society. There was no evidence of antipathy amongst South Asians to the concept of clinical trials and, overall, the younger respondents were more knowledgeable than the older ones. Problems are more likely to be associated with service delivery. Lack of being approached was a common response. Lay-reported factors that might affect South Asian participation in clinical trials include age, language, social class, feeling of not belonging/mistrust, culture and religion. Awareness of clinical trials varied between each group. There are more similarities than differences in attitudes towards clinical trial participation between the South Asian and the general population
Full Text Available To assess the feasibility and acceptability of a randomized controlled trial compared auricular acupressure (AA on specific acupoints with AA on non-specific acupoints for treating maintenance hemodialysis (MHD patients with insomnia.Sixty three (63 eligible subjects were randomly assigned into either AA group received AA on specific acupoints (n=32, or sham AA (SAA group received AA on points irrelevant to insomnia treatment (n=31 for eight weeks. All participants were followed up for 12 weeks after treatments. The primary outcome was clinical response at eight weeks after randomization, defined as a reduction of Pittsburgh Sleep Quality Index (PSQI global score by 3 points and more.Fifty-eight (58 participants completed the trial and five dropped out. Twenty participants in AA group (62.5% and ten in SAA group (32.3% responded to the eight-week interventions (χ2 = 5.77, P = 0.02. PSQI global score declined 3.75 ± 4.36 (95%CI -5.32, -2.18 and 2.26 ± 3.89 (95%CI -3.68, -0.83 in AA group and SAA group respectively. Three participants died during the follow-up period. No evidence supported their deaths were related to the AA intervention. No other adverse event was observed.Feasibility and logistics of patient recruitment, randomization procedure, blinding approach, interventions application and outcome assessment had been tested in this pilot trial. The preliminary data appeared to show a favorable result on AA treatment. A full-scale trial is warranted.Chinese Clinical Trial Registry ChiCTR-TRC-12002272.
Milesi, Marie-Anne; Lacan, Dominique; Brosse, Hervé; Desor, Didier; Notin, Claire
Background Recent studies have demonstrated a correlation between perceived stress and oxidative stress. As SOD is the main enzyme of the enzymatic antioxidant defence system of the body, we evaluated the effect of an oral daily intake of a proprietary melon juice concentrate rich in SOD (EXTRAMEL®) on the signs and symptoms of stress and fatigue in healthy volunteers. Methods This randomized, double blind, placebo controlled clinical study was conducted with seventy healthy volunteers aged between 30 and 55 years, who feel daily stress and fatigue. They took the dietary supplement based on the melon juice concentrate (10 mg Extramel® corresponding to 140 IU SOD per capsule) or a placebo one time daily during 4 weeks. Stress and fatigue were measured using four observational psychometric scales: FARD, PSS-14, SF-12 and Epworth scale. The study was conducted by Isoclin, a clinical research organization, located in Poitiers, France. Results No adverse effect was noted. The supplementation with the proprietary melon juice concentrate bringing 140 IU SOD/day significantly improved signs and symptoms of stress and fatigue linked to performance, physical (pain, sleep troubles), cognitive (concentration, weariness, sleep troubles) or behavioural (attitude, irritability, difficulty of contact) compared to the placebo. In the same way, quality of life and perceived stress were significantly improved with SOD supplementation. Conclusion This pilot study showed that an oral supplementation with a proprietary melon juice concentrate rich in SOD may have a positive effect on several signs and symptoms of perceived stress and fatigue. PMID:19754931
Full Text Available 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.
Rahn, Anne C; Backhus, Imke; Fuest, Franz; Riemann-Lorenz, Karin; Köpke, Sascha; van de Roemer, Adrianus; Mühlhauser, Ingrid; Heesen, Christoph
's internal consistency was moderate (Cronbach's alpha = 0.56). The pilot-phase shows promising results concerning acceptability and feasibility. Pilot randomised controlled trial results indicate that the patient information is well understood and that knowledge gain on confidence intervals can be assessed with a set of six questions. German Clinical Trials Register: DRKS00008561 . Registered 8th of June 2015.
Laber, Eric B; Zhao, Ying-Qi; Regh, Todd; Davidian, Marie; Tsiatis, Anastasios; Stanford, Joseph B; Zeng, Donglin; Song, Rui; Kosorok, Michael R
A personalized treatment strategy formalizes evidence-based treatment selection by mapping patient information to a recommended treatment. Personalized treatment strategies can produce better patient outcomes while reducing cost and treatment burden. Thus, among clinical and intervention scientists, there is a growing interest in conducting randomized clinical trials when one of the primary aims is estimation of a personalized treatment strategy. However, at present, there are no appropriate sample size formulae to assist in the design of such a trial. Furthermore, because the sampling distribution of the estimated outcome under an estimated optimal treatment strategy can be highly sensitive to small perturbations in the underlying generative model, sample size calculations based on standard (uncorrected) asymptotic approximations or computer simulations may not be reliable. We offer a simple and robust method for powering a single stage, two-armed randomized clinical trial when the primary aim is estimating the optimal single stage personalized treatment strategy. The proposed method is based on inverting a plugin projection confidence interval and is thereby regular and robust to small perturbations of the underlying generative model. The proposed method requires elicitation of two clinically meaningful parameters from clinical scientists and uses data from a small pilot study to estimate nuisance parameters, which are not easily elicited. The method performs well in simulated experiments and is illustrated using data from a pilot study of time to conception and fertility awareness.
Full Text Available Abstract Background Previous results with the planar robot MIT-MANUS demonstrated positive benefits in trials with over 250 stroke patients. Consistent with motor learning, the positive effects did not generalize to other muscle groups or limb segments. Therefore we are designing a new class of robots to exercise other muscle groups or limb segments. This paper presents basic engineering aspects of a novel robotic module that extends our approach to anti-gravity movements out of the horizontal plane and a pilot study with 10 outpatients. Patients were trained during the initial six-weeks with the planar module (i.e., performance-based training limited to horizontal movements with gravity compensation. This training was followed by six-weeks of robotic therapy that focused on performing vertical arm movements against gravity. The 12-week protocol includes three one-hour robot therapy sessions per week (total 36 robot treatment sessions. Results Pilot study demonstrated that the protocol was safe and well tolerated with no patient presenting any adverse effect. Consistent with our past experience with persons with chronic strokes, there was a statistically significant reduction in tone measurement from admission to discharge of performance-based planar robot therapy and we have not observed increases in muscle tone or spasticity during the anti-gravity training protocol. Pilot results showed also a reduction in shoulder-elbow impairment following planar horizontal training. Furthermore, it suggested an additional reduction in shoulder-elbow impairment following the anti-gravity training. Conclusion Our clinical experiments have focused on a fundamental question of whether task specific robotic training influences brain recovery. To date several studies demonstrate that in mature and damaged nervous systems, nurture indeed has an effect on nature. The improved recovery is most pronounced in the trained limb segments. We have now embarked on
Rangan, A; Jefferson, L; Baker, P; Cook, L
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. ©2014 The British Editorial Society of Bone & Joint Surgery.
Sterba, Katherine Regan; Armeson, Kent; Franco, Regina; Harper, Jennifer; Patten, Rebecca; Kindall, Stacey; Bearden, James; Zapka, Jane
Background Interventions addressing cancer survivors’ post-treatment concerns can be time-intensive and require specialized staff. Research is needed to identify feasible minimal intervention strategies to improve survivors’ quality of life after treatment. Objectives The objectives of this study were to evaluate the feasibility and short-term impact of a minimal clinic intervention on breast cancer survivors’ quality of life, unmet needs, distress and cancer worry. Interventions/Methods In this randomized controlled pilot trial, we enrolled breast cancer survivors at the end of treatment and administered baseline surveys. Participants were randomized to study arm (4-week video plus educational booklet intervention group and usual care group) and completed follow-up surveys at 10 weeks. Linear regression was used to examine intervention effects on quality of life outcomes controlling for clinical and demographic factors. Open-ended questions were used to examine program satisfaction and obtain feedback to improve the intervention. Results We enrolled 92 survivors in the trial. Participants rated the intervention highly and reported feeling less isolated and having more realistic expectations about their recovery after completing the program. Despite positive qualitative findings, no significant intervention effects were observed for quality of life, unmet needs, distress or cancer worry in unadjusted or adjusted analyses. Conclusions Future research is needed to define optimal intervention elements to prepare breast cancer survivors for the post-treatment period. Implications for Practice Effective survivorship interventions may require more intensive components such as clinical input and longer follow-up periods. PMID:24831043
Katz, Deborah G; Dutcher, Gale A; Toigo, Theresa A; Bates, Ruthann; Temple, Freda; Cadden, Cynthia G
The AIDS Clinical Trials Information Service (ACTIS) is a central resource for information about federally and privately funded HIV/AIDS clinical trials. Sponsored by four components of the U.S. Department of Health and Human Services, ACTIS has been a key part of U.S. HIV/AIDS information and education services since 1989. ACTIS offers a toll-free telephone service, through which trained information specialists can provide callers with information about AIDS clinical trials in English or Spanish, and a website that provides access to clinical trials databases and a variety of educational resources. Future priorities include the development of new resources to target diverse and underserved populations. In addition, research needs to be conducted on the use of telephone services vs. Web-based information exchange to ensure the broadest possible dissemination of up-to-date information on HIV infection and clinical trials.
Rosa, Carmen; Campbell, Aimee N C; Miele, Gloria M; Brunner, Meg; Winstanley, Erin L
Clinical trials have been slow to incorporate e-technology (digital and electronic technology that utilizes mobile devices or the Internet) into the design and execution of studies. In the meantime, individuals and corporations are relying more on electronic platforms and most have incorporated such technology into their daily lives. This paper provides a general overview of the use of e-technologies in clinical trials research, specifically within the last decade, marked by rapid growth of mobile and Internet-based tools. Benefits of and challenges to the use of e-technologies in data collection, recruitment and retention, delivery of interventions, and dissemination are provided, as well as a description of the current status of regulatory oversight of e-technologies in clinical trials research. As an example of ways in which e-technologies can be used for intervention delivery, a summary of e-technologies for treatment of substance use disorders is presented. Using e-technologies to design and implement clinical trials has the potential to reach a wide audience, making trials more efficient while also reducing costs; however, researchers should be cautious when adopting these tools given the many challenges in using new technologies, as well as threats to participant privacy/confidentiality. Challenges of using e-technologies can be overcome with careful planning, useful partnerships, and forethought. The role of web- and smartphone-based applications is expanding, and the increasing use of those platforms by scientists and the public alike make them tools that cannot be ignored.
Schüssler-Lenz, M; Schneider, C K
For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.
Schmal, Hagen; Bernstein, Anke; Feucht, Matthias J;
clinical trial and the cytokine composition of effusions (n = 76) was analyzed. Characteristics of epidemiology and disease severity were correlated with levels of cytokines with known roles in cartilage turnover and degradation. Results. Higher synovial IL-1β concentrations were associated with clinical......-2, and BMP-7. Infections with Staphylococcus species induced higher IL-1β expression but less cartilage destruction than other bacteria. Conclusion. Articular infections have bacteria-specific implications on cartilage metabolism. Collagen type II cleavage products reliably mark destruction, which...... is associated with upregulation of typical cartilage turnover cytokines. This trial is registered with DRKS00003536, MISSinG....
Sessler, Daniel I; Imrey, Peter B
Randomized assignment of treatment excludes reverse causation and selection bias and, in sufficiently large studies, effectively prevents confounding. Well-implemented blinding prevents measurement bias. Studies that include these protections are called randomized, blinded clinical trials and, when conducted with sufficient numbers of patients, provide the most valid results. Although conceptually straightforward, design of clinical trials requires thoughtful trade-offs among competing approaches-all of which influence the number of patients required, enrollment time, internal and external validity, ability to evaluate interactions among treatments, and cost.
Full Text Available Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but only in East Asian men can testosterone alone suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians, additional agents are required of which progestins are favored. Clinical trials concentrate on testosterone combined with norethisterone, desogestrel, etonogestrel or depot-medroxyprogesterone acetate. The first randomized, placebo-controlled clinical trial performed by the pharmaceutical industry demonstrated the effectiveness of a combination of testosterone undecanoate and etonogestrel in suppressing spermatogenesis in volunteers.
Chen, Junwen; Liu, Xi; Rapee, Ronald M; Pillay, Pallavi
Transdiagnostic interventions present pragmatic benefits in treatment dissemination and training of mental health professionals when faced with emotional disorders such as anxiety and depression. Excessive worry is a common feature across emotional disorders and represents an ideal candidate target for transdiagnostic intervention. The current pilot trial examined the efficacy of a behavioural activation treatment for worry (BAW) in a community population. 49 individuals experiencing excessive worry were randomised to waitlist or BAW receiving an 8 week group based intervention. Results demonstrated that BAW was successful in reducing excessive worry, depressive symptoms, cognitive avoidance, Intolerance of Uncertainty and improving problem solving orientation. Twice as many individuals showed clinically significant reductions in excessive worry after treatment compared to the waitlist control. Despite limitations to sample size and power, this study presents promising support for BAW as a practical transdiagnostic treatment for worry.
Reekie, J; Mocroft, A; J, Neaton;
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...
Reekie, J; Mocroft, A; J, Neaton;
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 k...
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.
Full Text Available Abstract Background Childhood intermittent exotropia [X(T] is a type of strabismus (squint in which one eye deviates outward at times, usually when the child is tired. It may progress to a permanent squint, loss of stereovision and/or amblyopia (reduced vision. Treatment options for X(T include eye patches, glasses, surgery and active monitoring. There is no consensus regarding how this condition should be managed, and even when surgery is the preferred option clinicians disagree as to the optimal timing. Reports on the natural history of X(T are limited, and there is no randomised controlled trial (RCT evidence on the effectiveness or efficiency of surgery compared with active monitoring. The SamExo (Surgery versus Active Monitoring in Intermittent Exotropia pilot study has been designed to test the feasibility of such a trial in the UK. Methods Design: an external pilot patient randomised controlled trial. Setting: four UK secondary ophthalmology care facilities at Newcastle NHS Hospitals Foundation Trust, Sunderland Eye Infirmary, Moorfields Eye Hospital and York NHS Trust. Participants: children aged between 6 months and 16 years referred with suspected and subsequently diagnosed X(T. Recruitment target is a total of 144 children over a 9-month period, with 120 retained by 9-month outcome visit. Randomisation: permuted blocks stratified by collaborating centre, age and severity of X(T. Interventions: initial clinical assessment; randomisation (eye muscle surgery or active monitoring; 3-, 6- and 9-month (primary outcome clinical assessments; participant/proxy completed questionnaire covering time and travel costs, health services use and quality of life (Intermittent Exotropia Questionnaire; qualitative interviews with parents to establish reasons for agreeing or declining participation in the pilot trial. Outcomes: recruitment and retention rates; nature and extent of participation bias; nature and extent of biases arising from crossover or
Van Sciver, Angela; Mahnken, Jonathan D.; Honea, Robyn A.; Brooks, William M.; Billinger, Sandra A.; Swerdlow, Russell H.; Burns, Jeffrey M.
Background There is increasing interest in the role of physical exercise as a therapeutic strategy for individuals with Alzheimer’s disease (AD). We assessed the effect of 26 weeks (6 months) of a supervised aerobic exercise program on memory, executive function, functional ability and depression in early AD. Methods and findings This study was a 26-week randomized controlled trial comparing the effects of 150 minutes per week of aerobic exercise vs. non-aerobic stretching and toning control intervention in individuals with early AD. A total of 76 well-characterized older adults with probable AD (mean age 72.9 [7.7]) were enrolled and 68 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. Neuropsychological tests and surveys were conducted at baseline,13, and 26 weeks to assess memory and executive function composite scores, functional ability (Disability Assessment for Dementia), and depressive symptoms (Cornell Scale for Depression in Dementia). Cardiorespiratory fitness testing and brain MRI was performed at baseline and 26 weeks. Aerobic exercise was associated with a modest gain in functional ability (Disability Assessment for Dementia) compared to individuals in the ST group (X2 = 8.2, p = 0.02). There was no clear effect of intervention on other primary outcome measures of Memory, Executive Function, or depressive symptoms. However, secondary analyses revealed that change in cardiorespiratory fitness was positively correlated with change in memory performance and bilateral hippocampal volume. Conclusions Aerobic exercise in early AD is associated with benefits in functional ability. Exercise-related gains in cardiorespiratory fitness were associated with improved memory performance and reduced hippocampal atrophy, suggesting cardiorespiratory fitness gains may be important in driving brain benefits. Trial registration ClinicalTrials.gov NCT01128361 PMID:28187125
Ban, T A; Amin, M M
1 In an uncontrolled clinical trial, carried out in 11 psychiatric patients with the clinical diagnoses of anxiety neurosis and depressive neurosis, clobazam, a new benzodiazepine preparation, in the dosage range 10-60 mg daily produced statistically significant improvement in the total and both factor scores of the Hamilton Anxiety Scale (HAM-A). The lowest mean total HAM-A scores occurred with a mean clobazam dosage of 48 mg daily. 2 Results of the uncontrolled clinical trial were further substantiated in a standard-controlled clinical study in which no statistically significant difference between the therapeutic effectiveness of clobazam and diazepam could be revealed. The lowest mean total HAM-A scores occurred with a mean clobazam dosage of 49 mg daily. There was a lower incidence of adverse effects reported in patients receiving clobazam than in those taking the control drug (diazepam).
Full Text Available June Chen1, Stephen A Runyan1, Michael R Robinson21Department of Biological Sciences, 2Ophthalmology Clinical Research, Allergan, Inc, Irvine, CA, USAIntroduction: Glaucoma is a multifactorial disease characterized by progressive optic nerve injury and visual field defects. Elevated intraocular pressure (IOP is the most widely recognized risk factor for the onset and progression of open-angle glaucoma, and IOP-lowering medications comprise the primary treatment strategy. IOP elevation in glaucoma is associated with diminished or obstructed aqueous humor outflow. Pharmacotherapy reduces IOP by suppressing aqueous inflow and/or increasing aqueous outflow.Purpose: This review focuses on novel non-FDA approved ocular antihypertensive compounds being investigated for IOP reduction in ocular hypertensive and glaucoma patients in active clinical trials within approximately the past 2 years.Methods: The mode of IOP reduction, pharmacology, efficacy, and safety of these new agents were assessed. Relevant drug efficacy and safety trials were identified from searches of various scientific literature databases and clinical trial registries. Compounds with no specified drug class, insufficient background information, reformulations, and fixed-combinations of marketed drugs were not considered.Results: The investigational agents identified comprise those that act on the same targets of established drug classes approved by the FDA (ie, prostaglandin analogs and β-adrenergic blockers as well as agents belonging to novel drug classes with unique mechanisms of action. Novel targets and compounds evaluated in clinical trials include an actin polymerization inhibitor (ie, latrunculin, Rho-associated protein kinase inhibitors, adenosine receptor analogs, an angiotensin II type 1 receptor antagonist, cannabinoid receptor agonists, and a serotonin receptor antagonist.Conclusion: The clinical value of novel compounds for the treatment of glaucoma will depend
Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina
Background Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Methods Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. Results All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. Conclusion This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB. PMID:28182700
Ichikawa, Kayoko; Takahashi, Yoshimitsu; Ando, Masahiko; Anme, Tokie; Ishizaki, Tatsuro; Yamaguchi, Hinako; Nakayama, Takeo
Although social skills training programs for people with high-functioning autism (HFA) are widely practiced, the standardization of curricula, the examination of clinical effectiveness, and the evaluation of the feasibility of future trials have yet to be done in Asian countries. To compensate for this problem, a Japanese pilot randomized controlled trial (RCT) of the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH)-based group social skills training for children with HFA and their mothers was conducted. Eleven children with HFA, aged 5-6 years, and their mothers were randomly assigned to the TEACCH program (n=5) or a waiting-list control group (n=6). The program involved comprehensive group intervention and featured weekly 2-hour sessions, totaling 20 sessions over six months. The adaptive behaviors and social reciprocity of the children, parenting stress, and parent-child interactions were assessed using the Strengths and Difficulties Questionnaire (SDQ), Parenting Stress Index (PSI), Beck depression inventory-II (BDI-II), and Interaction Rating Scale (IRS). Through this pilot trial, the intervention and evaluation of the program has been shaped. There were no dropouts from the program and the mothers' satisfaction was high. The outcome measurements improved more in the program group than in the control group, with moderate effect sizes (SDQ, 0.71; PSI, 0.58; BDI-II, 0.40; and IRS, 0.69). This pilot trial also implied that this program is more beneficial for high IQ children and mothers with low stress than for those who are not. We have standardized the TEACCH program, confirmed the feasibility of a future trial, and successfully estimated the positive effect size. These findings will contribute to a larger trial in the future and to forthcoming systematic reviews with meta-analyses. UMIN000004560.
New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.
Viergever Roderik F
Full Text Available Abstract Information on blinding is part of the data that should be provided upon registration of a trial at a clinical trials registry. Reporting of blinding is often absent or of low quality in published articles of clinical trials. This study researched the presence and quality of information on blinding in registered records of clinical trials and highlights the important role of data-recording formats at clinical trial registries in ensuring high-quality registration.
Subherwal, Sumeet; Patel, Manesh R.; Chiswell, Karen; Tidemann-Miller, Beth A.; Jones, W. Schuyler; Conte, Michael S.; White, Christopher J.; Bhatt, Deepak L.; Laird, John R.; Hiatt, William R.; Tasneem, Asba; Califf, Robert M.
Background Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); however, until recently it has not been possible to examine the entire clinical trial portfolio of studies for treatment of PVD (both arterial and venous disease). Methods and Results We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower extremity peripheral artery disease and acute stroke (35% and 24%, respectively), while most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients aged >65 years. Enrollment in at least 1 US site decreased from 51% in 2007 to 41% of trials in 2010. Compared with non-cardiology disciplines, PVD trials were more likely to be double-blinded, investigate use of devices and procedures, and have industry sponsorship and assumed funding source, and less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. Conclusions PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. PMID:25239436
Kloppenburg, M; Maheu, E; Kraus, V B; Cicuttini, F; Doherty, M; Dreiser, R-L; Henrotin, Y; Jiang, G-L; Mandl, L; Martel-Pelletier, J; Nelson, A E; Neogi, T; Pelletier, J-P; Punzi, L; Ramonda, R; Simon, L S; Wang, S
Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.
Lubaroff, David M
This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.
Silverberg, Nanette B
Dermoscopy is a noninvasive technique to assess skin architecture. A pilot study was conducted using polarized dermoscopy as a tool to monitor the pediatric skin barrier. Ten pediatric patients (age range, 1-14 years) with mild to moderate atopic dermatitis (AD), ichthyosis vulgaris (IV), and/or keratosis pilaris (KP) participated in a 4-week clinical trial. After a week of emollient usage alone, a mid-potency topical corticosteroid cream was added twice daily if necessary to treat erythema, dermatitis, or pruritus. The participants were assessed at weeks 0, 1, and 4 using the eczema area and severity index (EASI) for atopic dermatitis, investigator global assessment for atopic dermatitis, children dermatology life quality index (CDLQI), and clinical and dermoscopic photography. Dermoscopic appearance demonstrated dermal vascular ectasia in AD and KP, hyperkeratosis and prominence of the interkeratinocyte space in AD and IV and widening of the follicular orifice in KP. Improvements in these dermoscopic abnormalities were noted after emollient usage, mirroring improvements in clinical appearance, EASI, and CDLQI. Dermoscopy is a promising tool to assess localized improvement in skin architecture in pediatric dermatoses. Further studies and development of scoring systems will be needed to apply this technology to clinical practice.
Gutmann, David H; Blakeley, Jaishri O; Korf, Bruce R; Packer, Roger J
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. 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. 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.
Heise, Barbara A; Gilpin, Laura C
Although debriefing in simulation settings is routine in nursing education, debriefing does not routinely take place in clinical settings with nursing students after a patient has died. This pilot study sought to explore nursing students' perceptions of their first experience with the death of a patient. Students reported emotional distress and feelings of inadequacy with regard to communicating with and supporting the family of the dying patient. Only half the students sampled reported debriefing by their clinical instructor or staff. Nurse educators must include debriefing and student support following a patient death in the clinical setting.
Juul, Rasmus Vestergaard; Nyberg, Joakim; Kreilgaard, Mads
Inconsistent trial design and analysis is a key reason that few advances in postoperative pain management have been made from clinical trials analyzing opioid consumption data. This study aimed to compare four different approaches to analyze opioid consumption data. A repeated time-to-event (RTTE...... of potency was obtained with a RTTE model accounting for both morphine effects and time-varying covariates on opioid consumption. An RTTE analysis approach proved better suited for demonstrating efficacy of opioid sparing analgesics than traditional statistical tests as a lower sample size was required due...
Buck, Deborah; McColl, Elaine; Powell, Christine J; Shen, Jing; Sloper, John; Steen, Nick; Taylor, Robert; Tiffin, Peter; Vale, Luke; Clarke, Michael P
Childhood intermittent exotropia [X(T)] is a type of strabismus (squint) in which one eye deviates outward at times, usually when the child is tired. It may progress to a permanent squint, loss of stereovision and/or amblyopia (reduced vision). Treatment options for X(T) include eye patches, glasses, surgery and active monitoring. There is no consensus regarding how this condition should be managed, and even when surgery is the preferred option clinicians disagree as to the optimal timing. Reports on the natural history of X(T) are limited, and there is no randomised controlled trial (RCT) evidence on the effectiveness or efficiency of surgery compared with active monitoring. The SamExo (Surgery versus Active Monitoring in Intermittent Exotropia) pilot study has been designed to test the feasibility of such a trial in the UK. an external pilot patient randomised controlled trial. four UK secondary ophthalmology care facilities at Newcastle NHS Hospitals Foundation Trust, Sunderland Eye Infirmary, Moorfields Eye Hospital and York NHS Trust. children aged between 6 months and 16 years referred with suspected and subsequently diagnosed X(T). Recruitment target is a total of 144 children over a 9-month period, with 120 retained by 9-month outcome visit.Randomisation: permuted blocks stratified by collaborating centre, age and severity of X(T). initial clinical assessment; randomisation (eye muscle surgery or active monitoring); 3-, 6- and 9-month (primary outcome) clinical assessments; participant/proxy completed questionnaire covering time and travel costs, health services use and quality of life (Intermittent Exotropia Questionnaire); qualitative interviews with parents to establish reasons for agreeing or declining participation in the pilot trial. recruitment and retention rates; nature and extent of participation bias; nature and extent of biases arising from crossover or loss to follow-up; reasons for agreeing/declining participation; variability of cure rates
Lammertse, D; Tuszynski, MH; Steeves, JD; Curt, A; Fawcett, JW; Rask, C; Ditunno, JF; Fehlings, MG; Guest, JD; Ellaway, PH; Kleitman, N; Blight, AR; Dobkin, BH; Grossman, R.; Katoh, H.
The International Campaign for Cures of Spinal Cord Injury Paralysis established a panel tasked with reviewing the methodology for clinical trials for spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the fourth of four papers. Here, we examine the phases of a clinical trial program, the elements, types, and protocols for valid clinical trial design. The most rigorous and valid SCI clinical trial would be a prospective double-blind randomized contro...
Milošević-Georgiev Andrijana; Krajnović Dušanka; Milovanović Srđan; Ignjatović Svetlana; Đurić Dušan; Marinković Valentina
Introduction. Every clinical trial has to meet all ethical criteria in addition to the scientific ones. The basic ethical principles in the clinical trials are the following: nonmaleficence, beneficence, respect for autonomy and the principle of justice. Objective. The aim of the study was to analyze clinical cases with the outcomes leading to the changes in regulatoryethical framework related to the clinical trials, as well as the outcomes of key clinical trials that influenced the in...
Dal-Ré, Rafael; Moher, David; Gluud, Christian;
Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends.......Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends....
Woolson Robert F
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
McGraw, Deven; Greene, Sarah M; Miner, Caroline S; Staman, Karen L; Welch, Mary Jane; Rubel, Alan
With pragmatic clinical trials, an opportunity exists to answer important questions about the relative risks, burdens, and benefits of therapeutic interventions. However, concerns about protecting the privacy of this information are significant and must be balanced with the imperative to learn from the data gathered in routine clinical practice. Traditional privacy protections for research uses of identifiable information rely disproportionately on informed consent or authorizations, based on a presumption that this is necessary to fulfill ethical principles of respect for persons. But frequently, the ideal of informed consent is not realized in its implementation. Moreover, the principle of respect for persons—which encompasses their interests in health information privacy—can be honored through other mechanisms. Data anonymization also plays a role in protecting privacy but is not suitable for all research, particularly pragmatic clinical trials. In this article, we explore both the ethical foundation and regulatory framework intended to protect privacy in pragmatic clinical trials. We then review examples of novel approaches to respecting persons in research that may have the added benefit of honoring patient privacy considerations.
Beach, J E
When contract research organizations (CROs) were first formed, pharmaceutical companies outsourced to them only certain aspects of the conduct of their clinical trials. At first CROs were highly specialized entities, providing, for example, either biostatistical advice, clinical research associates who monitored investigational sites for regulatory compliance, or regulatory support. Gradually, full service CROs emerged, offering a full range of services for clinical trials, including the selection of investigators and investigational sites, assistance with patient recruitment, safety surveillance and reporting, site audits, and data management and biostatistics. This evolving relationship between CROs and the pharmaceutical and medical device industries has resulted in CROs assuming more and more of the regulatory and ethical risks and responsibilities inherent in the conduct of clinical trials. In this full service role, CROs, unlike sponsors, are not interested in the outcome of study, but like sponsors, are subject to heavy regulation by the federal government, must follow applicable state laws, must respect international guidelines, and are obliged to follow their own operating procedures. Moreover, they are judged by the industry on the basis of the scope and quality of services provided, including the degree of adherence to the research protocol, regulatory requirements, and timelines; the quality of the professional working relationships with investigators and institutions, both academic and community-based; and the validity of the data. Further, CROs are subject to comprehensive audits by sponsoring companies, FDA, and other regulatory authorities. For all these reasons, CROs are being tasked with strict vigilance of all stages of the clinical trial process to ensure that the laws, regulations, and industry standards designed for the protection of human subjects and data integrity are maintained.
Holmberg, Christine; Karner, Julia J; Rappenecker, Julia; Witt, Claudia M
Objectives To improve clinical study developments for elderly populations, we aim to understand how they transfer their experiences into validated, standardised self-completed study measurement instruments. We analysed how women (mean 78±8 years of age) participating in a randomised controlled trial (RCT) cognised study instruments used to evaluate outcomes of the intervention. Setting The interview study was nested in an RCT on chronic neck pain using common measurement instruments situated in an elderly community in Berlin, Germany, which comprised of units for independent and assisted-living options. Participants The sample (n=20 women) was selected from the RCT sample (n=117, 95% women, mean age 76 (SD±8) years). Interview participants were selected using a purposive sampling list based on the RCT outcomes. Outcomes We asked participants about their experiences completing the RCT questionnaires. Interviews were analysed thematically, then compared with the questionnaires. Results Interviewees had difficulties in translating complex experiences into a single value on a scale and understanding the relationship of the questionnaires to study aims. Interviewees considered important for the trial that their actual experiences were understood by trial organisers. This information was not transferrable by means of the questionnaires. To rectify these difficulties, interviewees used strategies such as adding notes, adding response categories or skipping an item. Conclusions Elderly interview participants understood the importance of completing questionnaires for trial success. This led to strategies of completing the questionnaires that resulted in ‘missing’ or ambiguous data. To improve data collection in elderly populations, educational materials addressing the differential logics should be developed and tested. Pilot testing validated instruments using cognitive interviews may be particularly important in such populations. Finally, when the target of an
Full Text Available Background and Aims: Withholding findings of clinical trials for publication or presentation to the regulatory authorities is a major concern. We aimed to address the importance of clinical trial registration and whether it is needed or not. Discussion: For ethical conduct of clinical trial, registration is an important but debatable issue due to proprietary interest of the pharmaceutical industry. Over the years, investigating agencies uncovered several instances of misconduct during the clinical trial. The International committee of medical journal editors requires registration of trial methodology, but does not require registration of trial results; however, the U.S. Food and Drug Administration Amendments does require researchers to register results. Conclusion: Prospective registration of clinical trial is mandatory for more transparent research and sustaining the validity of evidence based practice and availability of reliable data. Clinical trials registration has the potential to contribute substantially to improve clinical trial transparency and reducing publication bias and selective reporting.
Eldridge, Sandra M; Lancaster, Gillian A; Campbell, Michael J; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L; Bond, Christine M
We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.
Sandra M Eldridge
Full Text Available We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.
Grankvist, Hannah; Kimmelman, Jonathan
Launch of clinical investigation represents a substantial escalation in commitment to a particular clinical translation trajectory; it also exposes human subjects to poorly understood interventions. Despite these high stakes, there is little to guide decision-makers on the scientific and ethical evaluation of early phase trials. In this article, we review policies and consensus statements on human protections, drug regulation, and research design surrounding trial launch, and conclude that decision-making is largely left to the discretion of research teams and sponsors. We then review what is currently understood about how research teams exercise this discretion, and close by laying out a research agenda for characterizing the way investigators, sponsors, and reviewers approach decision-making in early phase research.
... Consumer Updates FDA Encourages More Participation, Diversity in Clinical Trials Share Tweet Linkedin Pin it More sharing options ... while research is conducted. back to top Do clinical trials have possible risks and benefits? Yes. Sometimes patients ...
Plasma biomarker analysis in pediatric ARDS: generating future framework from a pilot randomized control trial of methylprednisoloneA framework for identifying plasma biomarkers related to clinical outcomes in pediatric ARDS
Full Text Available Objective: Lung injury activates multiple pro-inflammatory pathways, including neutrophils, epithelial and endothelial injury, and coagulation factors leading to acute respiratory distress syndrome (ARDS. Low-dose methylprednisolone therapy (MPT improved oxygenation and ventilation in early pediatric ARDS without altering duration of mechanical ventilation or mortality. We evaluated the effects of MPT on biomarkers of endothelial (Ang-2, sICAM-1 or epithelial (sRAGE injury, neutrophil activation (MMP-8, and coagulation (PAI-1. Design: Double-blind, placebo-controlled randomized trialSetting: Tertiary-care Pediatric Intensive Care Unit Patients: Mechanically ventilated children (0-18 years with early ARDS.Interventions: Blood samples were collected on Days 0 (before MPT, 7, and 14 during low-dose MPT (n=17 vs. placebo (n=18 therapy. The MPT group received a 2mg/kg loading dose followed by 1mg/kg/day continuous infusions from days 1-7, tapered off over 7 days; placebo group received equivalent amounts of 0.9% saline. We analyzed plasma samples using a multiplex assay for 5 biomarkers of ARDS. Multiple regression models were constructed to predict associations between changes in biomarkers and the clinical outcomes reported earlier including: P/F ratio on days 8&9, plateau pressure on days 1&2, PaCO2 on days 2&3, racemic epinephrine following extubation, and supplemental oxygen at ICU discharge.Results: No differences occurred in biomarker concentrations between the groups on Day 0. On Day 7, reduction in MMP-8 levels (p=0.0016 occurred in the MPT group, whereas increases in sICAM-1 levels (p=0.0005 occurred in the placebo group (no increases in sICAM-1 in the MPT group. sRAGE levels decreased in both MPT and placebo groups (p<0.0001 from Day 0 to Day 7. On Day 7, sRAGE levels were positively correlated with MPT group PaO2/FiO2 ratios on Day 8 (r=0.93, p=0.024. O2 requirements at ICU transfer positively correlated with Day 7 MMP-8 (r=0.85, p=0
ZHANG Zhi-jun; LIU Wei
How to design clinical trials for medical devices is a problem plaguing the industry today. As there are many differences in clinical trials of medical devices and drugs. This paper describes the differences of the two points from the perspectivs of defi-nition of medical devices and drugs, scope, phasing, subjects and design of clinical trials in details, aiming to help the related personnel make scientific decisions while conduct-ing clinical trial design for medical devices.
England, Timothy J; Hedstrom, Amanda; O'Sullivan, Saoirse; Donnelly, Richard; Barrett, David A; Sarmad, Sarir; Sprigg, Nikola; Bath, Philip M
Repeated episodes of limb ischemia and reperfusion (remote ischemic conditioning [RIC]) may improve outcome after acute stroke. We performed a pilot blinded placebo-controlled trial in patients with acute ischemic stroke, randomized 1:1 to receive 4 cycles of RIC within 24 hours of ictus. The primary outcome was tolerability and feasibility. Secondary outcomes included safety, clinical efficacy (day 90), putative biomarkers (pre- and post-intervention, day 4), and exploratory hemodynamic measures. Twenty-six patients (13 RIC and 13 sham) were recruited 15.8 hours (SD 6.2) post-onset, age 76.2 years (SD 10.5), blood pressure 159/83 mm Hg (SD 25/11), and National Institutes of Health Stroke Scale (NIHSS) score 5 (interquartile range, 3.75-9.25). RIC was well tolerated with 49 out of 52 cycles completed in full. Three patients experienced vascular events in the sham group: 2 ischemic strokes and 2 myocardial infarcts versus none in the RIC group (P=0.076, log-rank test). Compared with sham, there was a significant decrease in day 90 NIHSS score in the RIC group, median NIHSS score 1 (interquartile range, 0.5-5) versus 3 (interquartile range, 2-9.5; P=0.04); RIC augmented plasma HSP27 (heat shock protein 27; Pacute stroke is well tolerated and appears safe and feasible. RIC may improve neurological outcome, and protective mechanisms may be mediated through HSP27. A larger trial is warranted. URL: http://www.isrctn.com. Unique identifier: ISRCTN86672015. © 2017 American Heart Association, Inc.
Santen, Gijs Willem Eduard
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 dru
Bartoli, E; Sorrentino, D; Trevisi, A
Randomized clinical trials represent the final, essential link between basic medical research and human health. However, their conduction presents very complex ethical problems, since the patient is the actual target of the experiment. Proper randomization, informed consent, and preliminary disclosure of results create deep ethical conflicts between the role of caretaker and that of impartial observer, both played by the same doctor. The dilemma reproduces the conflict between two different ethics. One is based on the inalienable individual rights stemming from the concept of man as an end in himself and not a means to an end. The other, derived from utilitarian philosophies, is based on the benefit for society as a whole. If we agree that randomized clinical trials represent the best method to test the validity of a new treatment, there is no easy solution. The dilemma could be solved by separating the role of the family doctor, committed to the best treatment possible for his patient, from the role of the scientist, committed to the progress of science and humanity. The former is involved in the treatment of individual patients, the latter in clinical and scientific experiments of a therapeutic nature. The patient may trade his rights to the best possible cure for the safety and the efficiency guaranteed by the scientific institution conducting the trial. Trials on relevant issues--expected to produce important results and impeccably designed scientifically--could be endowed with the ethics of science per se and this could be considered equivalent to the individual rights waived by the patient.
Bent, Stephen; Bertoglio, Kiah; Ashwood, Paul; Bostrom, Alan; Hendren, Robert L.
We conducted a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children ages 3-8 with autism spectrum disorder (ASD). After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (plus or minus…
Hillier, Susan; McIntyre, Auburn; Plummer, Leanne
Aquatic therapy is an intervention for children with Developmental Coordination Disorder (DCD) that has not been investigated formally. This was a pilot randomized controlled trial to investigate the feasibility and preliminary effectiveness of an aquatic therapy program to improve motor skills of children with DCD. Thirteen children (mean age 7…
Hillier, Susan; McIntyre, Auburn; Plummer, Leanne
Aquatic therapy is an intervention for children with Developmental Coordination Disorder (DCD) that has not been investigated formally. This was a pilot randomized controlled trial to investigate the feasibility and preliminary effectiveness of an aquatic therapy program to improve motor skills of children with DCD. Thirteen children (mean age 7…
DeBar, Lynn L.; Wilson, G. Terence; Yarborough, Bobbi Jo; Burns, Beryl; Oyler, Barbara; Hildebrandt, Tom; Clarke, Gregory N.; Dickerson, John; Striegel, Ruth H.
There is a need for treatment interventions to address the high prevalence of disordered eating throughout adolescence and early adulthood. We developed an adolescent-specific manualized CBT protocol to treat female adolescents with recurrent binge eating and tested its efficacy in a small, pilot randomized controlled trial. We present lessons…
Kuskowski Michael A
Full Text Available Abstract Background This small, pilot study evaluated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin on walking distance, pain and joint mobility in subjects with moderate to severe osteoarthritis of the knee. Methods Subjects (n = 70 with moderate to severe osteoarthritis of the knee were randomized to four double-blinded treatments for 12 weeks: (a Glucosamine sulfate (1500 mg/d; (b Aquamin (2400 mg/d; (c Combined treatment composed of Glucosamine sulfate (1500 mg/d plus Aquamin (2400 mg/d and (d Placebo. Primary outcome measures were WOMAC scores and 6 Minute Walking Distances (6 MWD. Laboratory based blood tests were used as safety measures. Results Fifty subjects completed the study and analysis of the data showed significant differences between the groups for changes in WOMAC pain scores over time (p = 0.009 ANCOVA; however, these data must be reviewed with caution since significant differences were found between the groups at baseline for WOMAC pain and stiffness scores (p = 0.0039 and p = 0.013, respectively, ANOVA. Only the Aquamin and Glucosamine groups demonstrated significant improvements in symptoms over the course of the study. The combination group (like the placebo group did not show any significant improvements in OA symptoms in this trial. Within group analysis demonstrated significant improvements over time on treatment for the WOMAC pain, activity, composite and stiffness (Aquamin only scores as well as the 6 minute walking distances for subjects in the Aquamin and Glucosamine treatment groups. The Aquamin and Glucosamine groups walked 101 feet (+7% and 56 feet (+3.5% extra respectively. All treatments were well tolerated and the adverse events profiles were not significantly different between the groups. Conclusion This small preliminary study suggested that a multi mineral supplement (Aquamin may reduce the pain and stiffness of osteoarthritis of the knee over 12 weeks of treatment and
Choi, Jeeyae; Choi, Jeungok E
To enhance patient safety from falls, many hospital information systems have been implemented to collect clinical data from the bedside and have used the information to improve fall prevention care. However, most of them use administrative data not clinical nursing data. This necessitated the development of a web-based Nursing Practice and Research Information Management System (NPRIMS) that processes clinical nursing data to measure nurses' delivery of fall prevention care and its impact on patient outcomes. This pilot study developed computer algorithms based on a falls prevention protocol and programmed the prototype NPRIMS. It successfully measured the performance of nursing care delivered and its impact on patient outcomes using clinical nursing data from the study site. Results of the study revealed that NPRIMS has the potential to pinpoint components of nursing processes that are in need of improvement for preventing patient from falls.
Full Text Available ATL is a distinct peripheral T-lymphocytic malignancy associated with human T-cell lymphotropic virus type I (HTLV-1. The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types, defined by organ involvement, and LDH and calcium values. In case of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL, intensive chemotherapy like the LSG15 regimen (VCAP-AMP-VECP is usually recommended if outside of clinical trials, based on the results of a phase 3 trial. In case of favorable chronic or smoldering ATL (indolent ATL, watchful waiting until disease progression has been recommended, although the long-term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT is also promising for the treatment of aggressive ATL possibly reflecting graft versus ATL effect. Several new agent trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody, IL2-fused with diphtheria toxin, histone deacetylase inhibitors, a purine nucleoside phosphorylase inhibitor, a proteasome inhibitor, and lenalidomide.
Holmberg, Christine; Karner, Julia J; Rappenecker, Julia; Witt, Claudia M
To improve clinical study developments for elderly populations, we aim to understand how they transfer their experiences into validated, standardised self-completed study measurement instruments. We analysed how women (mean 78±8 years of age) participating in a randomised controlled trial (RCT) cognised study instruments used to evaluate outcomes of the intervention. The interview study was nested in an RCT on chronic neck pain using common measurement instruments situated in an elderly community in Berlin, Germany, which comprised of units for independent and assisted-living options. The sample (n=20 women) was selected from the RCT sample (n=117, 95% women, mean age 76 (SD±8) years). Interview participants were selected using a purposive sampling list based on the RCT outcomes. We asked participants about their experiences completing the RCT questionnaires. Interviews were analysed thematically, then compared with the questionnaires. Interviewees had difficulties in translating complex experiences into a single value on a scale and understanding the relationship of the questionnaires to study aims. Interviewees considered important for the trial that their actual experiences were understood by trial organisers. This information was not transferrable by means of the questionnaires. To rectify these difficulties, interviewees used strategies such as adding notes, adding response categories or skipping an item. Elderly interview participants understood the importance of completing questionnaires for trial success. This led to strategies of completing the questionnaires that resulted in 'missing' or ambiguous data. To improve data collection in elderly populations, educational materials addressing the differential logics should be developed and tested. Pilot testing validated instruments using cognitive interviews may be particularly important in such populations. Finally, when the target of an intervention is a subjective experience, it seems important to create a
Simon, Laura J; Chinchilli, Vernon M
Two design principles are used frequently in clinical trials: 1) A subject is "matched" or "paired" with a similar subject to reduce the chance that other variables obscure the primary comparison of interest. 2) A subject serves as his/her own control by "crossing over" from one treatment to another during the course of an experiment. There are situations in which it may be advantageous to use the two design principles - crossing over and matching - simultaneously. That is, it may be advantageous to conduct a "paired crossover design," in which each subject, while paired with a similar subject, crosses over and receives each experimental treatment. In this paper, we describe two clinical trials conducted by the National Heart, Lung and Blood Institute's Asthma Clinical Research Network that used a paired 2x2 crossover design. The Beta Adrenergic Response by GEnotype (BARGE) Study compared the effects of regular use of inhaled albuterol on mildly asthmatic patients with different genotypes at the 16th position of the beta-agonist receptor gene. The Smoking Modulates Outcomes of Glucocorticoid (SMOG) Therapy in Asthma Study evaluated the hypothesis that smoking reduces the response to inhaled corticosteroids. For such paired crossover designs, the primary parameter of interest is typically the treatment-by-pairing interaction term. In evaluating the relative efficiency of the paired 2x2 crossover design to two independent crossover designs with respect to this interaction term, we show that the paired 2x2 crossover design is more efficient if the correlations between the paired members on the same treatments are greater than their correlations on different treatments. This condition should hold in most circumstances, and therefore the paired crossover design deserves serious consideration for any clinical trial in which the crossing over and matching of subjects is deemed simultaneously beneficial.
Sridharan, Kannan; Sivaramakrishnan, Gowri
Ayurveda is one of the complementary and alternative systems of medicine requiring generation of high quality evidence for rational practice. Evidence can be generated from study designs and the present study is an attempt to critically assess the registered studies in the field of Ayurveda from clinical trial registry of India. We found low number of trials conducted with more focus required on the quality of these studies to contribute to high quality evidence.
Krarup, L.H.; Gluud, C.; Truelsen, T.
: Patients with ischemic stroke above 39 years were randomized to intervention or control group. The intervention group will, over a 2-year period, receive information on and verbal instruction to exercise by a physiotherapist or a physician. The control group will receive the department's usual care......INTRODUCTION: A high level of physical activity is associated with a decreased risk of first stroke and physical activity modifies recognized stroke risk factors and is recommended for stroke survivors. Available research shows that stroke patients can increase their level of physical performance...... over a short period. When the intervention period is over, physical performance often declines towards baseline level. Currently, there is no evidence on the association between physical activity and the risk of recurrent stroke. The ExStroke Pilot Trial is a randomized clinical trial with the aim...
D'Avolio, Leonard; Ferguson, Ryan; Goryachev, Sergey; Woods, Patricia; Sabin, Thomas; O'Neil, Joseph; Conrad, Chester; Gillon, Joseph; Escalera, Jasmine; Brophy, Mary; Lavori, Phillip; Fiore, Louis
The Massachusetts Veterans Epidemiology Research and Information Center in collaboration with the Stanford Center for Innovative Study Design set out to test the feasibility of a new method of evidence generation. The first pilot of a point-of-care clinical trial (POCCT), adding randomization and other study processes to an electronic medical record (EMR) system, was launched to compare the effectiveness of two insulin regimens. Existing functionalities of the Veterans Affairs (VA) computerized patient record system (CPRS)/veterans health information systems and technology architecture (VISTA) were modified to support the activities of a randomized controlled trial including enrolment, randomization, and longitudinal data collection. The VA's CPRS/VISTA was successfully adapted to support the processes of a clinical trial and longitudinal study data are being collected from the medical record automatically. As of 30 June 2011, 55 of the 67 eligible patients approached received a randomized intervention. The design of CPRS/VISTA made integration of study workflows and data collection possible. Institutions and investigators considering similar designs must carefully map clinical workflows and clinical trial workflows to EMR capabilities. POCCT study teams are necessarily interdisciplinary and interdepartmental. As a result, executive sponsorship is critical. POCCT represent a promising new method for conducting clinical science. Much work is needed to understand better the optimal uses and designs for this new approach. Next steps include focus groups to measure patient and clinician perceptions, multisite deployment of the current pilot, and implementation of additional studies.
Wang, Lei; Qu, Xintao; Yu, Xiuchun
PDCA cycle was applied in special rectification activities for medical instrument clinical trial, with quality criteria of implementation made. Completed medical instrument clinical trial from January 2011 to December 2012 was believed as control group, from January 2013 to December 2014 as PDCA group, the scores of clinical trial and the score rate of items were compared and analyzed. Results show quality scores of clinical trial in PDCA group are higher than that in control group (51 vs. 81, P rectification activities with PDCA applied in our department are feasible and effective. It significantly improves implement quality of medical instrument clinical trial.
Ethics has often been ignored or evaded in clinical trials, and the conditions under which global clinical trials are conducted make this problem likely to persist. Ethics can, however, have an impact at any of several stages of a trial when the individuals involved are committed. This editorial provides historical examples of ignoring, evading or, alternatively, using ethical help to improve clinical trials, and suggests that the actual role of ethics depends on the individuals involved.
... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical trial... Pharmaceutical Clinical Trial; (3) Medical Device Aspects of Clinical Research; (4) Adverse Event...
Robinson, T W
Autism is a condition characterised by impairments of social communication, social interaction and social imagination. The exact aetiology of autism is unknown but some autistic features have been explained by the 'opioid excess theory' in which excess brain peptide levels have a morphine-like activity. Reduction of peptide levels by administration of the duodenal enzyme Secretin has been found to improve social and language skills in autistic patients. Homeopathic Secretin has been said to produce similar effects. A pilot study was undertaken to study these effects by administration of Secretin to a group of autistic patients. Weekly assessment for 12 weeks was performed by the patients' care workers. Statistical analysis of the mean pre-treatment results compared with the mean treatment results suggested a worsening in the autistic symptoms during treatment. Discussion with the care workers revealed changes and some improvements that were not recordable on the scoring system. Further research into Secretin treatment of autism using a more detailed and customized scoring system would be justified. Following this pilot study a randomised controlled trial of Secretin vs placebo would be appropriate.
Hahn, Joyce; Bishop, Geri; Fennell, Lenora
The complex dynamics of the current healthcare environment require healthcare delivery systems to become cost effective and quality driven. Educated healthcare consumers expect superior service and timely responses to their needs. For one healthcare system, customer expectations were an integral part of designing, implementing, and measuring the service components of congestive heart failure pathway outcomes. Service excellence can influence overall clinical outcomes when measured by consumer awareness and patient satisfaction. The inclusion of service excellence as an intrinsic piece of the organizational strategic plan laid the groundwork for this integrated pilot project.
Vaughn, Jacqueline; Lister, Michael; Shaw, Ryan J
We describe a pilot study that incorporated an innovative hybrid simulation designed to increase the perception of realism in a high-fidelity simulation. Prelicensure students (N = 12) cared for a manikin in a simulation lab scenario wearing Google Glass, a wearable head device that projected video into the students' field of vision. Students reported that the simulation gave them confidence that they were developing skills and knowledge to perform necessary tasks in a clinical setting and that they met the learning objectives of the simulation. The video combined visual images and cues seen in a real patient and created a sense of realism the manikin alone could not provide.
Leiter, Amanda; Sablinski, Tomasz; Diefenbach, Michael; Foster, Marc; Greenberg, Alex; Holland, John; Oh, William K; Galsky, Matthew D
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.
George, Melvin; Selvarajan, Sandhiya; S, Suresh-Kumar; Dkhar, Steven A; Chandrasekaran, Adithan
The last decade has witnessed a greater transparency in clinical research with the advent of clinical trial registries. The aim of the study was to describe the trends in the globalization of clinical trials in the last five years. We performed an internet search using the WHO International clinical trials registry platform (WHO ICTRP) to identify the clinical trials conducted from January 2007 to December 31, 2011 among 25 countries. Among the 25 countries, the United States, Japan and Germany occupy the top positions in the total number of clinical trials conducted. Clinical trials in the US (36312) constituted 31.5% of the total number of trials performed during this period. However over a period of five years both US and Western Europe appear to show a decline, while the emerging countries show a rise in clinical trials registered. Among the emerging countries China, India and Republic of Korea are most active regions involved in clinical trials. Cancer, diabetes and respiratory diseases were most widely researched areas overall. Although the study confirms the transition in the clinical trials research towards emerging countries, the developed regions of the world still contribute to more than 70% of the trials registered worldwide.
Van Pham, Phuc
In recent years, both stem cell research and the clinical application of these promising cells have increased rapidly. About 1000 clinical trials using stem cells have to date been performed globally. More importantly, more than 10 stem cell-based products have been approved in some countries. With the rapid growth of stem cell applications, some countries have used clinical trials as a tool to diminish the rate of clinical stem cell applications. However, the point at which stem cell clinical trials are essential remains unclear. This commentary discusses when stem cell clinical trials are essential for stem cell transplantation therapies.
Bernardo de Sampaio Pereira Junior
Full Text Available Background. Bipolar depression (BD is a prevalent condition, with poor therapeutic options and a high degree of refractoriness. This justifies the development of novel treatment strategies, such as transcranial direct current stimulation (tDCS that showed promising results in unipolar depression. Methods. We describe a randomized, sham-controlled, double-blinded trial using tDCS for refractory, acutely symptomatic BD (the bipolar depression electrical treatment trial, BETTER. Sixty patients will be enrolled and assessed with clinical and neuropsychological tests. The primary outcome is change (over time and across groups in the scores of the Hamilton Depression Rating Scale (17 items. Biological markers such as blood neurotrophins and interleukins, genetic polymorphisms, heart rate variability, and motor cortical excitability will be assessed. Twelve anodal-left/cathodal-right 2 mA tDCS sessions over the dorsolateral prefrontal cortex will be performed in 6 weeks. Results. In the pilot phase, five patients received active tDCS and were double-blindly assessed, two presenting clinical response. TDCS was well-tolerated, with no changes in cognitive scores. Conclusion. This upcoming clinical trial will address the efficacy of tDCS for BD on different degrees of refractoriness. The evaluation of biological markers will also help in understanding the pathophysiology of BD and the mechanisms of action of tDCS.
William A. Mattingly
Conclusion: We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are useful for clinical trial management. They can be used in a standalone trial or can be included into a larger management system.
... HUMAN SERVICES Food and Drug Administration Dialogues in Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials AGENCY: Food and Drug Administration, HHS... Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials....
Research in human beings is an important chapter of medical ethics. In recent years, investigation has been taken over by profit driven corporations that must guarantee the medical and commercial application of results. This new model of investigation has generated conflicts of interest in doctor-patient, researcher-subject relationship. The inevitable debate and media reaction has led. These trials of controversial design to regions of the globe where the vulnerability of the populations continues to allow their undertaking. This article includes a historical perspective on experimentation in human beings and the conditions that led to its regulation: the Nuremberg CODE, followed by the Helsinky Declaration in its different versions, and the Belmont Report, that defend the subject according to the ethic of principles used in western medicine. There is then a review of the attempts to change international regulation to reintroduce clinical trials with placebo--which since 1996 is only permitted where there are no therapeutic or diagnostic methods--on populations that would otherwise have no access to treatment. This then leads on to the issue of double standards in medical investigation defended by many investigators and some official entities. The article concludes that it may be prudent to allow local ethical commissions to approve deviation from the established norm if such is necessary to resolve urgent questions of health in the country, but it is unacceptable that any such emergency is used as a reason to reduce the ethical prerequisites, in clinical trials. It also concludes that true urgency is in making available to all who need it the effective products already in existence. Furthermore, that the acceptance of ethical relativism can result in the exploitation of vulnerable third world populations for research programmes that cannot be undertaken in their sponsoring countries due to the ethical restrictions in place.
Phase I of clinical trials is the first stage of clinical pharmacology and body safety evaluation, including body tolerance test and pharmacokinetics test. The aim is providing evidence for dosage regimen and be the cornerstone of the preliminary assessment of efficacy and safety of phase II of clinical trials. This text discussed the technique and requirement of phase I of new drugs' clinical tolerance trials.
Xu, Jun; Zhang, Yaoyun; Wu, Yonghui; Wang, Jingqi; Dong, Xiao; Xu, Hua
In scientific writing, positive credits and negative criticisms can often be seen in the text mentioning the cited papers, providing useful information about whether a study can be reproduced or not. In this study, we focus on citation sentiment analysis, which aims to determine the sentiment polarity that the citation context carries towards the cited paper. A citation sentiment corpus was annotated first on clinical trial papers. The effectiveness of n-gram and sentiment lexicon features, and problem-specified structure features for citation sentiment analysis were then examined using the annotated corpus. The combined features from the word n-grams, the sentiment lexicons and the structure information achieved the highest Micro F-score of 0.860 and Macro-F score of 0.719, indicating that it is feasible to use machine learning methods for citation sentiment analysis in biomedical publications. A comprehensive comparison between citation sentiment analysis of clinical trial papers and other general domains were conducted, which additionally highlights the unique challenges within this domain. PMID:26958274
Kelen, G D; Brown, C G; Ashton, J
Hypothesis testing is based on certain statistical and mathematical principles that allow investigators to evaluate data by making decisions based on the probability or implausibility of observing the results obtained. However, classic hypothesis testing has its limitations, and probabilities mathematically calculated are inextricably linked to sample size. Furthermore, the meaning of the p value frequently is misconstrued as indicating that the findings are also of clinical significance. Finally, hypothesis testing allows for four possible outcomes, two of which are errors that can lead to erroneous adoption of certain hypotheses: 1. The null hypothesis is rejected when, in fact, it is false. 2. The null hypothesis is rejected when, in fact, it is true (type I or alpha error). 3. The null hypothesis is conceded when, in fact, it is true. 4. The null hypothesis is conceded when, in fact, it is false (type II or beta error). The implications of these errors, their relation to sample size, the interpretation of negative trials, and strategies related to the planning of clinical trials will be explored in a future article in this journal.
Xu, Jun; Zhang, Yaoyun; Wu, Yonghui; Wang, Jingqi; Dong, Xiao; Xu, Hua
In scientific writing, positive credits and negative criticisms can often be seen in the text mentioning the cited papers, providing useful information about whether a study can be reproduced or not. In this study, we focus on citation sentiment analysis, which aims to determine the sentiment polarity that the citation context carries towards the cited paper. A citation sentiment corpus was annotated first on clinical trial papers. The effectiveness of n-gram and sentiment lexicon features, and problem-specified structure features for citation sentiment analysis were then examined using the annotated corpus. The combined features from the word n-grams, the sentiment lexicons and the structure information achieved the highest Micro F-score of 0.860 and Macro-F score of 0.719, indicating that it is feasible to use machine learning methods for citation sentiment analysis in biomedical publications. A comprehensive comparison between citation sentiment analysis of clinical trial papers and other general domains were conducted, which additionally highlights the unique challenges within this domain.
Foster, Jared C; Taylor, Jeremy M G; Ruberg, Stephen J
We consider the problem of identifying a subgroup of patients who may have an enhanced treatment effect in a randomized clinical trial, and it is desirable that the subgroup be defined by a limited number of covariates. For this problem, the development of a standard, pre-determined strategy may help to avoid the well-known dangers of subgroup analysis. We present a method developed to find subgroups of enhanced treatment effect. This method, referred to as 'Virtual Twins', involves predicting response probabilities for treatment and control 'twins' for each subject. The difference in these probabilities is then used as the outcome in a classification or regression tree, which can potentially include any set of the covariates. We define a measure Q(Â) to be the difference between the treatment effect in estimated subgroup Â and the marginal treatment effect. We present several methods developed to obtain an estimate of Q(Â), including estimation of Q(Â) using estimated probabilities in the original data, using estimated probabilities in newly simulated data, two cross-validation-based approaches, and a bootstrap-based bias-corrected approach. Results of a simulation study indicate that the Virtual Twins method noticeably outperforms logistic regression with forward selection when a true subgroup of enhanced treatment effect exists. Generally, large sample sizes or strong enhanced treatment effects are needed for subgroup estimation. As an illustration, we apply the proposed methods to data from a randomized clinical trial.
Andres E. Morales La Madrid
Full Text Available In spite of major recent advances in DIPG molecular characterization, this body of knowledge has not yet translated into better treatments.To date,more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy as well as newer biologic agents,have failed to improve the dismal outcome when compared to palliative radiation alone.The biology of DIPG remained unknown until recently when the neurosurgical expertise along with the recognition by the scientific and clinical community of the importance of tissue sampling at diagnosis;ideally in the context of a clinical trial and by trained neurosurgical teams to maximize patient safety.These pre-treatment tumor samples,and others coming from tissue obtained post-mortem,have yielded new insights into DIPG molecular biology.We now know that DIPG comprises a heterogeneous disease with variable molecular phenotypes, different from adult high grade glioma,other non-pontine pediatric high grade gliomas and even between pontine gliomas.The discovery of histone H3.3 or H3.1 mutations has been an important step forward in understanding tumor formation,maintenance and progression.Pharmacologic reversal of DIPG histone demethylation therefore offers an important potential intervention strategy for the treatment of DIPG.To date,clinical trials of newly diagnosed or progressive DIPG with epigenetic modifiers have been unsuccessful.Whether this failure represents limited activity of the agents used,their CNS penetration,redundant pathways within the tumor,or the possibility that histone mutations are necessary only to initiate DIPGs but not maintain their growth,suggest that a great deal still needs to be elucidated in both the underlying biology of these pathways,and the drugs designed to target them.In this review, we discuss the role of both epigenetic and genetic mutations within DIPG and the development of treatment strategies directed against the unique abnormalities
Taylor, William J; Brown, Melanie; William, Levack; McPherson, Kathryn M; Reed, Kirk; Dean, Sarah G; Weatherall, Mark
To determine the feasibility, the cluster design effect and the variance and minimal clinical importance difference in the primary outcome in a pilot study of a structured approach to goal-setting. A cluster randomized controlled trial. Inpatient rehabilitation facilities. People who were admitted to inpatient rehabilitation following stroke who had sufficient cognition to engage in structured goal-setting and complete the primary outcome measure. Structured goal elicitation using the Canadian Occupational Performance Measure. Quality of life at 12 weeks using the Schedule for Individualised Quality of Life (SEIQOL-DW), Functional Independence Measure, Short Form 36 and Patient Perception of Rehabilitation (measuring satisfaction with rehabilitation). Assessors were blinded to the intervention. Four rehabilitation services and 41 patients were randomized. We found high values of the intraclass correlation for the outcome measures (ranging from 0.03 to 0.40) and high variance of the SEIQOL-DW (SD 19.6) in relation to the minimally importance difference of 2.1, leading to impractically large sample size requirements for a cluster randomized design. A cluster randomized design is not a practical means of avoiding contamination effects in studies of inpatient rehabilitation goal-setting. Other techniques for coping with contamination effects are necessary.
Clarke, Greg; McGlinchey, Eleanor L; Hein, Kerrie; Gullion, Christina M; Dickerson, John F; Leo, Michael C; Harvey, Allison G
We tested whether augmenting conventional depression treatment in youth by treating sleep issues with cognitive behavioral therapy for insomnia (CBT-I) improved depression outcomes. We randomized youth 12-20 years of age to 10 weekly sessions of a sleep hygiene control condition (SH) combined with CBT for depression (CBT-D) (n = 20), or an experimental condition consisting of CBT-I combined with CBT-D (n = 21). We assessed outcomes through 26 weeks of follow-up and found medium-large effects favoring the experimental CBT-I arm on some sleep outcomes (actigraphy total sleep time and Insomnia Severity Index "caseness") and depression outcomes (higher percentage recovered, faster time to recovery), but little effect on other measures. Total sleep time improved by 99 min from baseline to week 12 in the CBT-I arm, but not in the SH arm. In addition, our pilot yielded important products to facilitate future studies: the youth-adapted CBT-I program; the study protocol; estimates of recruitment, retention, and attrition; and performance and parameters of candidate outcome measures. ClinicalTrials.gov Identifier NCT00949689.
Mishler, John M.
A pilot program at the University of Missouri-Kansas City included creation of a part-time administrative position to enhance cooperative ventures between the university and the pharmaceutical industry through placement of clinical trials among academic units with interdisciplinary research programs in the health sciences. Sponsored funding levels…
Mishler, John M.
A pilot program at the University of Missouri-Kansas City included creation of a part-time administrative position to enhance cooperative ventures between the university and the pharmaceutical industry through placement of clinical trials among academic units with interdisciplinary research programs in the health sciences. Sponsored funding levels…
Pelto, Debra J.; Sadler, Georgia Robins; Njoku, Ogo; Rodriguez, Maria Carina; Villagra, Cristina; Malcarne, Vanessa L.; Riley, Natasha E.; Behar, Alma I.; Jandorf, Lina
The pilot study reported in this article culturally and linguistically adapted an educational intervention to promote cancer clinical trials (CCTs) participation among Latinas/os and African Americans. The single-session slide presentation with embedded videos, originally developed through a campus-community partnership in Southern California, was…
Ineke Van Der Meulen
Full Text Available AbstractMelodic Intonation Therapy (MIT is a language production therapy for severely non-fluent aphasic patients using melodic intoning and rhythm to restore language. Although many studies have reported its beneficial effects on language production, randomized controlled trials (RCT examining the efficacy of MIT are rare. In an earlier publication, we presented the results of an RCT on MIT in subacute aphasia and found that MIT was effective on trained and untrained items. Further, we observed a clear trend in improved functional language use after MIT. Subacute aphasic patients receiving MIT improved considerably on language tasks measuring connected speech and daily life verbal communication. Here, we present the results of a pilot RCT on MIT in chronic aphasia and compare these to the results observed in subacute aphasia. We used a multicenter waiting-list randomized controlled trial design. Patients with chronic (>1 year post-stroke aphasia were randomly allocated to the experimental group (6 weeks MIT or to the control group (6 weeks no intervention followed by 6 weeks MIT. Assessments were done at baseline (T1, after 6 weeks (T2, and 6 weeks later (T3. Efficacy was evaluated at T2 using univariable linear regression analyses. Outcome measures were chosen to examine several levels of therapy success: improvement on trained items, generalization to untrained items, and generalization to verbal communication. Of 17 included patients, 10 were allocated to the experimental condition and 7 to the control condition. MIT significantly improved repetition of trained items (β=13.32, p=.02. This effect did not remain stable at follow-up assessment. In contrast to earlier studies, we found only a limited and temporary effect of MIT, without generalization to untrained material or to functional communication. The results further suggest that the effect of MIT in chronic aphasia is more restricted than its effect in earlier stages post stroke. This
Full Text Available Abstract Background Hypnosis treatment in general practice is a rather new concept. This pilot study was performed to evaluate the effect of a standardized hypnosis treatment used in general practice for patients with chronic widespread pain (CWP. Methods The study was designed as a randomized control group-controlled study. Sixteen patients were randomized into a treatment group or a control group, each constituting eight patients. Seven patients in the treatment group completed the schedule. After the control period, five of the patients in the control group also received treatment, making a total of 12 patients having completed the treatment sessions. The intervention group went through a standardized hypnosis treatment with ten consecutive therapeutic sessions once a week, each lasting for about 30 minutes, focusing on ego-strengthening, relaxation, releasing muscular tension and increasing self-efficacy. A questionnaire was developed in order to calibrate the symptoms before and after the 10 weeks period, and the results were interpolated into a scale from 0 to 100, increasing numbers representing increasing suffering. Data were analyzed by means of T-tests. Results The treatment group improved from their symptoms, (change from 62.5 to 55.4, while the control group deteriorated, (change from 37.2 to 45.1, (p = 0,045. The 12 patients who completed the treatment showed a mean improvement from 51.5 to 41.6. (p = 0,046. One year later the corresponding result was 41.3, indicating a persisting improvement. Conclusion The study indicates that hypnosis treatment may have a positive effect on pain and quality of life for patients with chronic muscular pain. Considering the limited number of patients, more studies should be conducted to confirm the results. Trial Registration The study was registered in ClinicalTrials.gov and released 27.08.07 Reg nr NCT00521807 Approval Number: 05032001.
Mitschke, Diane B; Cassel, Kevin; Higuchi, Paula
Cancer clinical trials are essential to advancing the prevention and treatment of cancer, yet adult participation rates in clinical trials remain abysmal. Despite the essential contributions of clinical trials to science and medicine, adult participation in clinical trials remains exceedingly low, with only 2%-4% of all adult patients with cancer in the U.S. participating in clinical trials. Clinical trials accrual rates in Hawai'i follow this national trend of less than 3% of eligible patients participating in trials. Recognizing the need to increase awareness about clinical trials, the National Cancer Institute's Cancer Information Service-Pacific Region, through the Hawai'i Clinical Trials Education Coalition, has employed strategic dissemination plans to train and educate key target audiences, including registered nurses, nursing students, and community outreach workers about the availability of over 90 cancer clinical trials in Hawai'i. Previous research suggests that nurses often play a vital role in increasing a patient's understanding of clinical trials and may also act as a patient advocate in regards to participation in a clinical trial. A train-the-trainer model curriculum was developed using the Clinical Trials Education Series (CTES), a collection of multi-level resources designed by the National Cancer Institute, to educate various constituents about clinical trials. The training curriculum and workshop format is adapted based on both formal and informal needs assessments conducted with audiences prior to the planned training, yet key elements remain central to the training model. In addition, an interactive, internet-based case study was developed using local place names and cultural cues to allow training participants to engage in realistic and practical methods for locating and sharing information about clinical trials with patients and the public. This training model has been implemented in a variety of settings including three statewide nursing
Full Text Available Abstract Background Venous thromboembolism (VTE is a common preventable cause of mortality in hospitalized medical patients. Despite rigorous randomized trials generating strong recommendations for anticoagulant use to prevent VTE, nearly 40% of medical patients receive inappropriate thromboprophylaxis. Knowledge-translation strategies are needed to bridge this gap. Methods We conducted a 16-week pilot cluster randomized controlled trial (RCT to determine the proportion of medical patients that were appropriately managed for thromboprophylaxis (according to the American College of Chest Physician guidelines within 24 hours of admission, through the use of a multicomponent knowledge-translation intervention. Our primary goal was to determine the feasibility of conducting this study on a larger scale. The intervention comprised clinician education, a paper-based VTE risk assessment algorithm, printed physicians’ orders, and audit and feedback sessions. Medical wards at six hospitals (representing clusters in Ontario, Canada were included; three were randomized to the multicomponent intervention and three to usual care (i.e., no active strategies for thromboprophylaxis in place. Blinding was not used. Results A total of 2,611 patients (1,154 in the intervention and 1,457 in the control group were eligible and included in the analysis. This multicomponent intervention did not lead to a significant difference in appropriate VTE prophylaxis rates between intervention and control hospitals (appropriate management rate odds ratio = 0.80; 95% confidence interval: 0.50, 1.28; p = 0.36; intra-class correlation coefficient: 0.022, and thus was not considered feasible. Major barriers to effective knowledge translation were poor attendance by clinical staff at education and feedback sessions, difficulty locating preprinted orders, and lack of involvement by clinical and administrative leaders. We identified several factors that may increase uptake of a VTE
Vandenheuvel, Dieter; Lavigne, Rob; Brüssow, Harald
Recently, a number of phage therapy phase I and II safety trials have been concluded, showing no notable safety concerns associated with the use of phage. Though hurdles for efficient treatment remain, these trials hold promise for future phase III clinical trials. Interestingly, most phage formulations used in these clinical trials are straightforward phage suspensions, and not much research has focused on the processing of phage cocktails in specific pharmaceutical dosage forms. Additional research on formulation strategies and the stability of phage-based drugs will be of key importance, especially with phage therapy advancing toward phase III clinical trials.
Campbell-Tofte, Joan I A; Mølgaard, Per; Josefsen, Knud
The aim of this randomized and double blinded pilot clinical trial was to investigate the anti-diabetic efficacy of the Rauvolfia-Citrus (RC) tea in humans. We have earlier shown that a combination of calorie-restriction and chronic administration of the RC tea to the genetic diabetic (BKS-db) mice...
Britton, Willoughby B.; Lepp, Nathaniel E.; Niles, Halsey F.; Rocha, Tomas; Fisher, Nathan; Gold, Jonathan
Children in the United States are at risk for numerous psychological problems, such as anxiety, attention problems, and mood disorders, and are underserved by current mental health provisions. The current study is a pilot trial to examine the effects of a nonelective, classroom-based, teacher-implemented, mindfulness meditation intervention on standard clinical measures of mental health and affect in middle school children. A total of 101 healthy sixth-grade students (55 boys and 46 girls) we...
Freeman, D; Waite, F.; Startup, H; Myers, E; Lister, R.; McInerney, J; Harvey, AG; Geddes, J.; Zaiwalla, Z; Luengo-Fernandez, R.; Foster, R.; Clifton, L; Yu, LM
Summary Background Sleep disturbance occurs in most patients with delusions or hallucinations and should be treated as a clinical problem in its own right. However, cognitive behavioural therapy (CBT)—the best evidence-based treatment for insomnia—has not been tested in this patient population. We aimed to pilot procedures for a randomised trial testing CBT for sleep problems in patients with current psychotic experiences, and to provide a preliminary assessment of potential benefit. Methods ...
Roumiantseva, Dina; Carini, Simona; Sim, Ida; Wagner, Todd H
We examine the extent to which ClinicalTrials.gov is meeting its goal of providing oversight and transparency of clinical trials with human subjects. We analyzed the ClinicalTrials.gov database contents as of June 2011, comparing interventions, medical conditions, and trial characteristics by sponsor type. We also conducted a detailed analysis of incomplete data. Among trials with only government sponsorship (N=9252), 36% were observational and 64% interventional; in contrast, almost all (90%) industry-only sponsored trials were interventional. Industry-only sponsored interventional trials (N=30,036) were most likely to report a drug intervention (81%), followed by biologics (9%) and devices (8%). Government-only interventional trials (N=5886) were significantly more likely to test behavioral interventions (28%) and procedures (13%) than industry-only trials (pgov. Published by Elsevier Inc.
Conclusion: The number of clinical trials done in allied fields of medicine other than the allopathic system has lowered down, and furthermore focus is required regarding the methodological quality of these trials and more support from various organizations.
Penning, Sophie; Le Compte, Aaron J; Moorhead, Katherine T; Desaive, Thomas; Massion, Paul; Preiser, Jean-Charles; Shaw, Geoffrey M; Chase, J Geoffrey
Tight glycemic control (TGC) has shown benefits in ICU patients, but been difficult to achieve consistently due to inter- and intra- patient variability that requires more adaptive, patient-specific solutions. STAR (Stochastic TARgeted) is a flexible model-based TGC framework accounting for patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) below 72 mg/dL. This research describes the first clinical pilot trial of the STAR approach and the post-trial analysis of the models and methods that underpin the protocol. The STAR framework works with clinically specified targets and intervention guidelines. The clinically specified glycemic target was 125 mg/dL. Each trial was 24 h with BG measured 1-2 hourly. Two-hourly measurement was used when BG was between 110-135 mg/dL for 3 h. In the STAR approach, each intervention leads to a predicted BG level and outcome range (5-95th percentile) based on a stochastic model of metabolic patient variability. Carbohydrate intake (all sources) was monitored, but not changed from clinical settings except to prevent BGLiege (Liege, Belgium). Nine patient trials were undertaken after obtaining informed consent. There were 205 measurements over all 9 trials. Median [IQR] per-patient results were: BG: 138.5 [130.6-146.0]mg/dL; carbohydrate administered: 2-11 g/h; median insulin:1.3 [0.9-2.4]U/h with a maximum of 6.0 [4.7-6.0]U/h. Median [IQR] time in the desired 110-140 mg/dL band was: 50.0 [31.2-54.2]%. Median model prediction errors ranged: 10-18%, with larger errors due to small meals and other clinical events. The minimum BG was 63 mg/dL and no other measurement was below 72 mg/dL, so only 1 measurement (0.5%) was below the 5% guaranteed minimum risk level. Post-trial analysis showed that patients were more variable than predicted by the stochastic model used for control, resulting in some of the prediction errors seen. Analysis and (validated) virtual trial re-simulating the clinical trial using
Elad Sharon; Howard Streicher; Priscila Goncalves; Helen XChen
Immunology-based therapy is rapidly developing into an effective treatment option for a surprising range of cancers. We have learned over the last decade that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called“immune checkpoints.” These checkpoints serve to control or turn off the immune response when it is no longer needed to prevent tissue injury and autoimmunity. Cancer cells have learned or evolved to use these mechanisms to evade immune control and elimination. The development of a new therapeutic class of drugs that inhibit these inhibitory pathways has recently emerged as a potent strategy in oncology. Three sets of agents have emerged in clinical trials exploiting this strategy. These agents are antibody-based therapies targeting cytotoxic T-lymphocyte antigen4 (CTLA4), programmed cell death1 (PD-1), and programmed cell death ligand 1 (PD-L1). These inhibitors of immune inhibition have demonstrated extensive activity as single agents and in combinations. Clinical responses have been seen in melanoma, renal cellcarcinoma, non-smal celllung cancer, and several other tumor types. Despite the autoimmune or inflammatory immune-mediated adverse effects which have been seen, the responses and overall survival benefits exhibited thus far warrant further clinical development.
Tandava Krishnan Panakanti
Full Text Available Branch retinal vein occlusion (BRVO is the second most common retinal vascular disorder. The management of macular edema has changed considerably over time. The laser is considered the gold standard treatment for over two decades. However, visual recovery with laser is usually slow and incomplete. The advent of intravitreal agents, specifically anti-vascular endothelial growth factors (VEGF have heralded a new era which promises rapid recovery of vision and quality of vision. Randomized clinical trials have reported optimal results with anti-VEGF agents (ranibizumab, bevacizumab, and aflibercept compared to laser therapy or steroids. However, nearly 50% of the patients require repeat intravitreal anti-VEGF therapy up to 4 years after initiating therapy to sustain the visual gains. The adverse events (systemic and ocular of these agents are minimal. Monotherapy with anti-VEGF agents have been found to provide better results than any combination with laser. This review article summarizes evidence from randomized controlled trials evaluating treatment options for the treatment of macular edema secondary to BRVO with a special focus on anti-VEGF therapy.
Panakanti, Tandava Krishnan; Chhablani, Jay
Branch retinal vein occlusion (BRVO) is the second most common retinal vascular disorder. The management of macular edema has changed considerably over time. The laser is considered the gold standard treatment for over two decades. However, visual recovery with laser is usually slow and incomplete. The advent of intravitreal agents, specifically anti-vascular endothelial growth factors (VEGF) have heralded a new era which promises rapid recovery of vision and quality of vision. Randomized clinical trials have reported optimal results with anti-VEGF agents (ranibizumab, bevacizumab, and aflibercept) compared to laser therapy or steroids. However, nearly 50% of the patients require repeat intravitreal anti-VEGF therapy up to 4 years after initiating therapy to sustain the visual gains. The adverse events (systemic and ocular) of these agents are minimal. Monotherapy with anti-VEGF agents have been found to provide better results than any combination with laser. This review article summarizes evidence from randomized controlled trials evaluating treatment options for the treatment of macular edema secondary to BRVO with a special focus on anti-VEGF therapy. PMID:26957837
Vawdrey, David K; Hripcsak, George
To measure the rate of non-publication and assess possible publication bias in clinical trials of electronic health records. We searched ClinicalTrials.gov to identify registered clinical trials of electronic health records and searched the biomedical literature and contacted trial investigators to determine whether the results of the trials were published. Publications were judged as positive, negative, or neutral according to the primary outcome. Seventy-six percent of trials had publications describing trial results; of these, 74% were positive, 21% were neutral, and 4% were negative (harmful). Of unpublished studies for which the investigator responded, 43% were positive, 57% were neutral, and none were negative; the lower rate of positive results was significant (pelectronic health record studies is similar to that in other biomedical studies. There appears to be a bias toward publication of positive trials in this domain. Copyright © 2012 Elsevier Inc. All rights reserved.
As much information as possible should be obtained in clinical trials to assess possible interactions between test drugs and concomitant medications prescribed for other medical indications. Side effect profiles were compared in patients taking buspirone, mean = 20 mg/day; diazepam, 20 mg/day; clorazepate, 23 mg/day; and placebo, with or without concomitant medications. Approximately 1,000 anxious patients were included in the analysis; 700 received buspirone. The use of a variety of common medications did not affect the side effect profile in the buspirone, clorazepate, and placebo groups, but did increase the incidence of side effects in the diazepam group. The increased incidence of sedation noted with diazepam and clorazepate, however, was not due to concomitant medication.
Cofield,Stacey; Conwit, Robin; Barsan, William; Quinn, James
The emergency medicine and pre-hospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in Emergency Medicine Clinical Trials (EMCT), and provides strategies from emergency medicine and non-emergency medicine trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment...
Lenio Souza Alvarenga; Elisabeth Nogueira Martins
OBJECTIVE: To evaluate biopharmaceutical industry-sponsored clinical trials placed in countries previously described as emerging regions for clinical research, and potential differences for those placed in Brazil. METHODS: Data regarding recruitment of subjects for clinical trials were retrieved from www.clinicaltrials.gov on February 2nd 2009. Proportions of sites in each country were compared among emerging countries. Multiple logistic regressions were performed to evaluate whether trial pl...
Cristina Cavaiuolo; Anna Casani; Gaetano Di Manso; Luigi Orfeo
Objective: The aim of this pilot study was to determine the effect of music by Mozart on heel prick procedural pain in premature infants.Background: Painful procedures are routinely performed in the setting of neonatal intensive care unit (NICU). Pain may exert short- and long-term deleterious effects on premature babies. Many non-pharmacological interventions have been proven efficacious for blunting neonatal pain.Study design: Randomized, controlled trial.Methods: The study was carried out ...
Full Text Available Many chiropractors believe that chiropractic treatments are effective for gastrointestinal disorders. The aim of the present systematic review was to critically evaluate the evidence from controlled clinical trials supporting or not supporting this notion. Six electronic databases were searched for relevant studies. No limits were applied to language or publication date. Prospective, controlled, clinical trials of any type of chiropractic treatment for any type of gastrointestinal problem, except infant colic, were included. Only two trials were found – one was a pilot study, and the other had reached a positive conclusion; however, both had serious methodological flaws. There is no supportive evidence that chiropractic is an effective treatment for gastrointestinal disorders.
Breitkopf, Carmen Radecki; Loza, Melissa; Vincent, Kathleen; Moench, Thomas; Stanberry, Lawrence R; Rosenthal, Susan L
A greater understanding of participant views regarding reimbursement will help investigators plan studies that have better potential for reaching target enrollment, maximize efficient recruitment, maintain scientific integrity, and enhance retention over time. As part of a clinical trial in the area of sexual health, healthy women's perceptions of reimbursement for research participation were investigated. Semi-structured, audio-recorded, qualitative interviews were conducted immediately upon women's completion of the clinical trial to enable a participant-driven understanding of perceptions about monetary reimbursement. Audio-recordings were transcribed and analyzed using framework analysis. Women (N = 30) had a mean age of 29.5 ± 5.7 years (range 22-45 years). Sixty-three percent of participants (n = 19) were non-Hispanic (white n = 13, black n = 4, and Asian n = 2), while the remaining were Hispanic (n = 11). Seventy-three percent (n = 22) reported previous participation in research. In general, women viewed reimbursement as a benefit to research participation, the amount of which should reflect time, the inconvenience to the research subject, and the potential for unknown risks in the short- and long-term. They believed reimbursement should take into account the degree of risk of the study, with investigations of experimental products offering greater reimbursement. Women believed that monetary reimbursement is unlikely to coerce an individual to volunteer for a study involving procedures or requirements that they found unacceptable. The results of this study can be used to provide guidance to those planning and evaluating reimbursement for research participation.
There is a serious interest growing nationally towards the use of PAA at various stages of public waste water treatment facilities; one of such use is secondary waste water treatment. MSDGC is currently interested in improving efficiency and economic aspects of waste water treatment. MSDGC requested for ORD’s support to evaluate alternative cost-effective disinfectants. This report herein is based on the data generated from the field pilot test conducted at the Little Miami Wastewater Treatment Plant. Chlorine assisted disinfection of wastewaters created the concern regarding the formation of high levels of toxic halogenated disinfection byproducts (DBPs) detrimental to aquatic life and public health. Peracetic acid is emerging as a green alternative to chlorine and claimed to have economic and social benefits. In addition, it is a relatively simple retrofit to the existing chlorine treated wastewater treatment facilities. PAA is appealed to possess a much lower aquatic toxicity profile than chlorine and decays rapidly in the environment, even if overdosed. As a result, PAA generally does not need a quenching step, such as dechlorination, reducing process complexity, sodium pollution and cost. PAA treatment does not result in the formation of chlorinated disinfection by-products such as trihalomethanes (THMs), haloacetic acids and other byproducts such as cyanide and n-Nitrosodimethylamine (NDMA).
Cork Michael J
Full Text Available Abstract Background The vulnerability of newborn babies' skin creates the potential for a number of skin problems. Despite this, there remains a dearth of good quality evidence to inform practice. Published studies comparing water with a skin-cleansing product have not provided adequate data to inform an adequately powered trial. Nor have they distinguished between babies with and without a predisposition to atopic eczema. We conducted a pilot study as a prequel to designing an optimum trial to investigate whether bathing with a specific cleansing product is superior to bathing with water alone. The aims were to produce baseline data which would inform decisions for the main trial design (i.e. population, primary outcome, sample size calculation and to optimize the robustness of trial processes within the study setting. Methods 100 healthy, full term neonates aged Results Forty nine babies were randomized to cleansing product, 51 to water. The 95% confidence intervals (CI for the average TEWL measurement at each time point were: whole sample at baseline: 10.8 g/m2/h to 11.7 g/m2/h; CP group 4 weeks: 10.9 g/m2/h to 13.3 g/m2/h; 8 weeks: 11.4 g/m2/h to 12.9 g/m2/h; W group 4 weeks:10.9 g/m2/h to 12.2 g/m2/h; 8 weeks: 11.4 g/m2/h to 12.9 g/m2/h. Conclusion This pilot study provided valuable baseline data and important information on trial processes. The decision to proceed with a superiority trial, for example, was inconsistent with our data; therefore a non-inferiority trial is recommended. Trial registration ISRCTN72285670
Joseph S Ross
Full Text Available BACKGROUND: ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. METHODS AND FINDINGS: We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515, nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46% of trials were published, among which 96 (31% provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357 were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001, but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22. Among trials that reported an end date, 75 of 123 (61% completed prior to 2004, 50 of 96 (52% completed during 2004, and 62 of 149 (42% completed during 2005 were published (p = 0.006. CONCLUSIONS: Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low
Cuc, Andrea V; Locke, Dona E C; Duncan, Noah; Fields, Julie A; Snyder, Charlene Hoffman; Hanna, Sherrie; Lunde, Angela; Smith, Glenn E; Chandler, Melanie
This study aims to provide effect size estimates of the impact of two cognitive rehabilitation interventions provided to patients with mild cognitive impairment: computerized brain fitness exercise and memory support system on support partners' outcomes of depression, anxiety, quality of life, and partner burden. A randomized controlled pilot trial was performed. At 6 months, the partners from both treatment groups showed stable to improved depression scores, while partners in an untreated control group showed worsening depression over 6 months. There were no statistically significant differences on anxiety, quality of life, or burden outcomes in this small pilot trial; however, effect sizes were moderate, suggesting that the sample sizes in this pilot study were not adequate to detect statistical significance. Either form of cognitive rehabilitation may help partners' mood, compared with providing no treatment. However, effect size estimates related to other partner outcomes (i.e., burden, quality of life, and anxiety) suggest that follow-up efficacy trials will need sample sizes of at least 30-100 people per group to accurately determine significance. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Pariera, Katrina L; Murphy, Sheila T; Meng, Jingbo; McLaughlin, Margaret L
African-Americans and Hispanic-Americans are disproportionately affected by cancer, yet underrepresented in cancer clinical trials. Because of this, it is important to understand how attitudes and beliefs about clinical trials vary by ethnicity. A national, random sample of 860 adults was given an online survey about attitudes toward clinical trials. We examined willingness to participate in clinical trials, attitudes toward clinical trials, trust in doctors, attitudes toward alternative and complementary medicine, and preferred information channels. Results indicate that African-American and Hispanic-American participants have more negative attitudes about clinical trials, more distrust toward doctors, more interest in complementary and alternative medicine, and less willingness to participate in clinical trials than white/non-Hispanics, although specific factors affecting willingness to participate vary. The channels people turn to for information on clinical trials also varied by ethnicity. These results help explain the ethnic disparities in cancer clinical trial enrollment by highlighting some potential underlying causes and drawing attention to areas of importance to these groups.
Cofield, Stacey; Conwit, Robin; Barsan, William; Quinn, James
The emergency medicine and pre-hospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in Emergency Medicine Clinical Trials (EMCT), and provides strategies from emergency medicine and non-emergency medicine trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment and retention issues with specific strategies will help researchers deal with these issues in their funding applications and in turn develop the necessary infrastructure to participate in emergency medicine clinical trials. PMID:21040112
Scardino Peter T
Full Text Available Abstract Introduction Randomized controlled trials provide the best method of determining which of two comparable treatments is preferable. Unfortunately, contemporary randomized trials have become increasingly expensive, complex and burdened by regulation, so much so that many trials are of doubtful feasibility. Discussion Here we present a proposal for a novel, streamlined approach to randomized trials: the "clinically-integrated randomized trial". The key aspect of our methodology is that the clinical experience of the patient and doctor is virtually indistinguishable whether or not the patient is randomized, primarily because outcome data are obtained from routine clinical data, or from short, web-based questionnaires. Integration of a randomized trial into routine clinical practice also implies that there should be an attempt to randomize every patient, a corollary of which is that eligibility criteria are minimized. The similar clinical experience of patients on- and off-study also entails that the marginal cost of putting an additional patient on trial is negligible. We propose examples of how the clinically-integrated randomized trial might be applied in four distinct areas of medicine: comparisons of surgical techniques, "me too" drugs, rare diseases and lifestyle interventions. Barriers to implementing clinically-integrated randomized trials are discussed. Conclusion The proposed clinically-integrated randomized trial may allow us to enlarge dramatically the number of clinical questions that can be addressed by randomization.
Hu, Min; Liu, Jian-Ping; Wu, Xiao-Ke
Acupuncture clinical trials are designed to provide reliable evidence of clinical efficacy, and SCI papers is one of the high-quality clinical efficacy of acupuncture research. To analyze these papers published in high impact factor journals on acupuncture clinical trials, we can study clinical trials from design to implementation, the efficacy of prevention and cure, combined with international standard practices to evaluate the effectiveness and safety of acupuncture. That is the core of acupuncture clinical trials, as well as a prerequisite for outstanding academic output. A scientific and complete acupuncture clinical trial should be topically novel, designed innovative, logically clear, linguistically refining, and the most important point lies in a great discovery and solving the pragmatic problem. All of these are critical points of papers to be published in high impact factor journal, and directly affect international evaluation and promotion of acupuncture.
Full Text Available Abstract Background Infection with HIV-1 results in marked immunologic insults and structural damage to the intestinal mucosa, including compromised barrier function. While the development of highly active antiretroviral therapy (HAART has been a major advancement in the treatment of HIV-1 infection, the need for novel complementary interventions to help restore intestinal structural and functional integrity remains unmet. Known properties of pre-, pro-, and synbiotics suggest that they may be useful tools in achieving this goal. Methods This was a 4-week parallel, placebo-controlled, randomized pilot trial in HIV-infected women on antiretroviral therapy. A synbiotic formulation (Synbiotic 2000® containing 4 strains of probiotic bacteria (1010 each plus 4 nondigestible, fermentable dietary fibers (2.5 g each was provided each day, versus a fiber-only placebo formulation. The primary outcome was bacterial translocation. Secondary outcomes included the levels of supplemented bacteria in stool, the activation phenotype of peripheral T-cells and monocytes, and plasma levels of C-reactive protein and soluble CD14. Results Microbial translocation, as measured by plasma bacterial 16S ribosomal DNA concentration, was not altered by synbiotic treatment. In contrast, the synbiotic formulation resulted in significantly elevated levels of supplemented probiotic bacterial strains in stool, including L. plantarum and P. pentosaceus, with the colonization of these two species being positively correlated with each other. T-cell activation phenotype of peripheral blood lymphocytes showed modest changes in response to synbiotic exposure, with HLA-DR expression slightly elevated on a minor population of CD4+ T-cells which lack expression of HLA-DR or PD-1. In addition, CD38 expression on CD8+ T-cells was slightly lower in the fiber-only group. Plasma levels of soluble CD14 and C-reactive protein were unaffected by synbiotic treatment in this study. Conclusions
Hind, Daniel; Parkin, James; Whitworth, Victoria; Rex, Saleema; Young, Tracey; Hampson, Lisa; Sheehan, Jennie; Maguire, Chin; Cantrill, Hannah; Scott, Elaine; Epps, Heather; Main, Marion; Geary, Michelle; McMurchie, Heather; Pallant, Lindsey; Woods, Daniel; Freeman, Jennifer; Lee, Ellen; Eagle, Michelle; Willis, Tracey; Muntoni, Francesco; Baxter, Peter
Standard treatment of Duchenne muscular dystrophy (DMD) includes regular physiotherapy. There are no data to show whether adding aquatic therapy (AT) to land-based exercises helps maintain motor function. We assessed the feasibility of recruiting and collecting data from boys with DMD in a parallel-group pilot randomised trial (primary objective), also assessing how intervention and trial procedures work. Ambulant boys with DMD aged 7-16 years established on steroids, with North Star Ambulatory Assessment (NSAA) score ≥8, who were able to complete a 10-m walk test without aids or assistance, were randomly allocated (1:1) to 6 months of either optimised land-based exercises 4 to 6 days/week, defined by local community physiotherapists, or the same 4 days/week plus AT 2 days/week. Those unable to commit to a programme, with >20% variation between NSAA scores 4 weeks apart, or contraindications to AT were excluded. The main outcome measures included feasibility of recruiting 40 participants in 6 months from six UK centres, clinical outcomes including NSAA, independent assessment of treatment optimisation, participant/therapist views on acceptability of intervention and research protocols, value of information (VoI) analysis and cost-impact analysis. Over 6 months, 348 boys were screened: most lived too far from centres or were enrolled in other trials; 12 (30% of the targets) were randomised to AT (n = 8) or control (n = 4). The mean change in NSAA at 6 months was -5.5 (SD 7.8) in the control arm and -2.8 (SD 4.1) in the AT arm. Harms included fatigue in two boys, pain in one. Physiotherapists and parents valued AT but believed it should be delivered in community settings. Randomisation was unattractive to families, who had already decided that AT was useful and who often preferred to enrol in drug studies. The AT prescription was considered to be optimised for three boys, with other boys given programmes that were too extensive and insufficiently
Manns Michael P
Full Text Available Abstract Background The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD, for which probiotic therapy yielded promising results. Methods Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ, endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial. Results 14 patients presenting ulcerative colitis (UC and 17 patients presenting Crohn's disease (CD, most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04. Conclusion The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials. Trial registration
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.
Winstanley, P; Olliaro, P
Plasmodium falciparum remains one of the World's most prevalent and devastating pathogens. Mainly for economic reasons, the parasite's ability to develop resistance to drugs has not been matched by the rate at which new compounds are developed. Even so, there are new drugs (or new combinations of old drugs) currently under investigation, or in the process of development (at the moment): Pyronaridine, a well-tolerated, synthetic drug that may have utility for multi-resistant falciparum malaria in many parts of the world; however,problems remain over the formulation of this drug (which is a major determinant of its bioavailability) and its eventual cost. Chlorproguanil-dapsone (lap dap) is being studied as a possible low-cost'successor' to pyrimethamine-sulfadoxine; the utility of chlorproguanil-dapsone as 'salvage' therapy for clinical cases of pyrimethamine-sulfadoxine failure has yet to be tested in clinical trials. Atovaquone-proguanil (malarone) has utility against multi-resistant parasites; however, it is likely to be expensive (but is currently being provided free-of-charge in certain areas of Africa). Artemether-benflumetol (coartemether) combines the advantages of artemether (a rapid reduction in parasite load) with a second drug that reduces the risk of recrudescence; the cost of this combination is unclear. Rectal artesunate is being studied as an intervention to reduce the proportion of children with falciparum malaria who deteriorate to severe disease; the formulation is appropriate for use in rural health centres.
Pushpa-Rajah, Angela; Bradshaw, Lucy; Dorling, Jon; Gyte, Gill; Mitchell, Eleanor J; Thornton, Jim; Duley, Lelia
Preterm birth is the most important single determinant of adverse outcome in the United Kingdom; one in every 70 babies (1.4%) is born before 32 weeks (very preterm), yet these births account for over half of infant deaths.Deferring cord clamping allows blood flow between baby and placenta to continue for a short time. This often leads to increased neonatal blood volume at birth and may allow longer for transition to the neonatal circulation. Optimal timing for clamping the cord remains uncertain, however. The Cochrane Review suggests that deferring umbilical cord clamping for preterm births may improve outcome, but larger studies reporting substantive outcomes and with long-term follow-up are needed. Studies of the physiology of placental transfusion suggest that flow in the umbilical cord at very preterm birth may continue for several minutes. This pilot trial aims to assess the feasibility of conducting a large randomised trial comparing immediate and deferred cord clamping in the UK. Women are eligible for the trial if they are expected to have a live birth before 32 weeks gestation. Exclusion criteria are known monochorionic twins or clinical evidence of twin-twin transfusion syndrome, triplet or higher order multiple pregnancy, and known major congenital malformation. The interventions will be cord clamping within 20 seconds compared with cord clamping after at least two minutes. For births with cord clamping after at least two minutes, initial neonatal care is at the bedside. For the pilot trial, outcomes include measures of recruitment, compliance with the intervention, retention of participants and data quality for the clinical outcomes.Information about the trial is available to women during their antenatal care. Women considered likely to have a very preterm birth are approached for informed consent. Randomisation is close to the time of birth. Follow-up for the women is for one year, and for the children to two years of age (corrected for gestation
DePasse, J Mason; Park, Sara; Eltorai, Adam E M; Daniels, Alan H
Treatment options for spinal cord injuries are currently limited, but multiple clinical trials are underway for a variety of interventions, drugs, and devices. The Food and Drug Administration website www.ClinicalTrials.gov catalogues these trials and includes information on the status of the trial, date of initiation and completion, source of funding, and region. This investigation assesses the factors associated with publication and the publication rate of spinal cord injury trials. Retrospective analysis of publically available data on www.ClinicalTrials.gov. The www.ClinicalTrials.gov was queried for all trials on patients with spinal cord injury, and these trials were assessed for status, type of intervention, source of funding, and region. Multiple literature searches were performed on all completed trials to determine publication status. There were 626 studies identified concerning the treatment of patients with spinal cord injury, of which 250 (39.9%) were completed. Of these, only 119 (47.6%) were published. There was no significant difference in the rate of publication between regions (p> 0.16) or by study type (p> 0.29). However, trials that were funded by the NIH were more likely to be published than trials funded by industry (p= 0.01). The current publication rate of spinal cord injury trials is only 47.6%, though this rate is similar to the publication rate for trials in other fields. NIH-funded trials are significantly more likely to become published than industry-funded trials, which could indicate that some trials remain unpublished due to undesirable results. However, it is also likely that many trials on spinal cord injury yield negative results, as treatments are often ineffective.
Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: A Crucial Key to Human Health Research Past ... the forefront of human health research today are clinical trials—studies that use human volunteers to help medical ...
The article analyses the importance of laboratory test methods, namely pathomorfological at conduct of clinical trials. The article focuses on complex laboratory diagnostics at determination of clinical condition of animals, safety and efficacy of tested medicinal product.
Scifres, Christina M; Iams, Jay D; Klebanoff, Mark; Macones, George A
Large, randomized clinical trials have long been considered the gold standard to guide clinical care. Metaanalysis is a type of analysis in which results of a number of randomized clinical trials are combined and a summary measure of effect for a given treatment is ascertained. The clinician in practice often is faced with a dilemma regarding the type of evidence that should be used to guide clinical practice; for many clinical problems, there are both randomized controlled trials and metaanalyses available. The cases of calcium and aspirin therapy for the prevention of preeclampsia afford an opportunity to explore the benefits and limitations of each type of study to guide clinical practice. We conclude that, when available, large randomized clinical trials should be used to guide clinical practice.
Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M
The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
BACKGROUND:Clinical trials are commonly done without blinded outcome assessors despite the risk of bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. METHODS......:We conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two......%). Heterogeneity was moderate (I(2) = 46%, p = 0.02) and unexplained by metaregression. INTERPRETATION:We provide empirical evidence for observer bias in randomized clinical trials with subjective measurement scale outcomes. A failure to blind assessors of outcomes in such trials results in a high risk...
Goldenholz, Daniel M; Tharayil, Joseph J; Kuzniecky, Rubin; Karoly, Philippa; Theodore, William H; Cook, Mark J
It is currently unknown if knowledge of clinically silent (electrographic) seizures improves the statistical efficiency of clinical trials. Using data obtained from 10 patients with chronically implanted subdural electrodes over an average of 1 year, a Monte Carlo bootstrapping simulation study was performed to estimate the statistical power of running a clinical trial based on A) patient reported seizures with intracranial EEG (icEEG) confirmation, B) all patient reported events, or C) all icEEG confirmed seizures. A "drug" was modeled as having 10%, 20%, 30%, 40% and 50% efficacy in 1000 simulated trials each. Outcomes were represented as percentage of trials that achieved pseizures (pseizure detection using chronically implanted icEEG improves statistical power of clinical trials. Newer invasive and noninvasive seizure detection devices may have the potential to provide greater statistical efficiency, accelerate drug discovery and lower trial costs.
Full Text Available First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomized clinical trials and their limitations, discuss the key points in the design of future trials, and depict new directions of research in this fascinating field.
Smed, Marie; Getz, Kenneth A.
in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract...... knowledge gained by physicians in the process of clinical trials. These restrictions to knowledge-transfer between site and sponsor are further challenged if CRO partners are integrated in the trial process. © 2013 Elsevier Inc. All rights reserved....
MANINDER KAUR; AMRITPAL SINGH
Objective: The main objective of this study is to know clinical trials in nutshell and phase 0 clinical trial are to establish at the very earliest opportunity-before large numbers of patients have been accrued and exposed to potential drug-associated toxicity-whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted. We review here the fundamental requirements of clinical studies conducted under an exploratory IND and address som...
Mandel, Jacob J; Yust-Katz, Shlomit; Patel, Akash J; Cachia, David; Liu, Diane; Park, Minjeong; Yuan, Ying; A Kent, Thomas; de Groot, John F
Glioblastoma is the most common primary malignant brain tumor in adults, but effective therapies are lacking. With the scarcity of positive phase III trials, which are increasing in cost, we examined the ability of positive phase II trials to predict statistically significant improvement in clinical outcomes of phase III trials. A PubMed search was conducted to identify phase III clinical trials performed in the past 25 years for patients with newly diagnosed or recurrent glioblastoma. Trials were excluded if they did not examine an investigational chemotherapy or agent, if they were stopped early owing to toxicity, if they lacked prior phase II studies, or if a prior phase II study was negative. Seven phase III clinical trials in newly diagnosed glioblastoma and 4 phase III clinical trials in recurrent glioblastoma met the inclusion criteria. Only 1 (9%) phase III study documented an improvement in overall survival and changed the standard of care. The high failure rate of phase III trials demonstrates the urgent need to increase the reliability of phase II trials of treatments for glioblastoma. Strategies such as the use of adaptive trial designs, Bayesian statistics, biomarkers, volumetric imaging, and mathematical modeling warrant testing. Additionally, it is critical to increase our expectations of phase II trials so that positive findings increase the probability that a phase III trial will be successful.
Grønbech, Bettina Ellen
People with severe mental illness, such as schizophrenia have higher rates of mortality especially due to cardiovascular disease. We have established a clinical trial named “Coronary artery disease and schizophrenia”. However, patients with schizophrenia have cognitive disturbances, which make re...... recruitment of patients challenging. The purpose of this study is to understand which type of recruitment strategy is needed in clinical trials....
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes.......To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes....
Jakobsen, Jan Nyrop; Sørensen, Jens Benn
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....
Lambers Heerspink, Hiddo Jan
Large scale randomized clinical trials are needed to detect small but meaningful effects of new drugs. However, large scale randomized clinical trials are expensive undertakings and they are in imbalance with the scientific output. As a consequence there is a strong voice for more efficacious random
Thomas eFitzGerald, MD
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.
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 initia
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida
To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes.......To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes....
Puterman, Jared; Alter, David A
The utilization of disease management (DM) as a minimum standard of care is believed to facilitate pronounced benefits in overall patient outcome and cost management. Randomized clinical trials remain the gold standard evaluative tool in clinical medicine. However, the extent to which contemporary cardiovascular clinical trials incorporate DM components into their treatment or control arms is unknown. Our study is the first to evaluate the extent to which clinical trials incorporate DM as a minimum standard of care for both the intervention and control groups. In total, 386 clinical trials published in 3 leading medical journals between 2003 and 2006 were evaluated. For each study, elements related to DM care, as defined using the American Heart Association Taxonomy, were abstracted and characterized. Our results demonstrate that while the application of DM has increased over time, only 3.4% of the clinical trials examined incorporated all 8 DM elements (and only 11% of such trials incorporated 4 DM elements). A significant association was found between study year and the inclusion of more than 3 elements of DM (chi(2) = 10.10 (3); p = 0.018). In addition, associations were found between study objective and DM criteria, as well as between cohort type and domains described. Our study serves as a baseline reference for the tracking of DM within, and its application to, randomized clinical trials. Moreover, our results underscore the need for broader implementation and evaluation of DM as a minimum care standard within clinical trial research.
Wisner, Katherine L.; Sit, Dorothy K.Y.; Moses-Kolko, Eydie L.; Driscoll, Kara E.; Prairie, Beth; Stika, Catherine S.; Eng, Heather F.; Dills, John L; Luther, James F.; Wisniewski, Stephen R.
Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609
Gilburt, Helen; Burns, Tom; Copello, Alex; Crawford, Michael; Day, Ed; Deluca, Paolo; Godfrey, Christine; Parrott, Steve; Rose, Abigail; Sinclair, Julia; Coulton, Simon
Abstract Aims A pilot randomized controlled trial (RCT) to assess the feasibility and potential efficacy of assertive community treatment (ACT) in adults with alcohol dependence. Methods Single blind, individually randomized, pilot RCT of 12 months of ACT plus treatment as usual (TAU) versus TAU alone in adults (age 18+ years) with alcohol dependence and a history of previous unsuccessful alcohol treatment attending specialist community alcohol treatment services. ACT aimed to actively engage participants for 12 months with assertive, regular, minimum weekly contact. ACT was combined with TAU. TAU comprised access to the full range of services provided by the community teams. Primary outcome is mean drinks per drinking day and percent days abstinent at 12 months follow up. Analysis of covariance was conducted using 80% confidence intervals, appropriate in the context of a pilot trial. Results A total of 94 participants were randomized, 45 in ACT and 49 in TAU. Follow-up was achieved with 98 and 88%, respectively at 12 months. Those in ACT had better treatment engagement, and were more often seen in their homes or local community than TAU participants. At 12 months the ACT group had more problems related to drinking and lower quality of life than TAU but no differences in drinking measures. The ACT group had a higher percentage of days abstinent but lower quality of life at 6 months. The ACT group had less unplanned healthcare use than TAU. Conclusions An trial of ACT was feasible to implement in an alcohol dependent treatment population. Trial registration ISRCTN22775534 PMID:27940571
革军; 王臻; 刘鹏; 栗向东; 陈国景
目的 针对儿童股骨下段恶性骨肿瘤的诸多治疗方法中存在的问题,本课题组首次提出具有双屈伸运动人工半膝关节(双动半膝关节)的概念,进行其运动轨迹规律及实验性临床研究.方法 以Mimics/Geomagic/Pro-E软件的设计路线为技术路线.基于成人膝关节标本的CT数据,利用数控铣床机加工制作双动半膝关节假体,进行体外实验研究其运动参数特点,最后进行实验性临床研究.结果 离体实验结果:股骨内侧髁屈曲面球心位移在正常膝关节组为(2.59±0.43)mm,双动半膝关节组为(2.22±0.52) mm,全膝关节组为(1.18±0.43) mm；股骨外侧髁屈曲面球心位移在正常膝关节组为(11.95±6.62) mm,双动半膝关节组为(11.25±6.19)mm,全膝关节组为(1.26±0.42) mm；相对胫骨最大旋转角度在正常膝关节组为13.17°±7.58°,双动半膝关节组为11.69°±6.49°,全膝关节组为5.40°±1.29°.完成探索性临床试验,术后患者恢复良好,效果满意.结论 运动参数分析证明双动半膝关节接近正常膝关节运动模式,双动半膝关节为治疗儿童股骨下段恶性肿瘤提供了全新的理念和思路,新型附丽概念和新型韧带附丽装置为膝关节韧带功能重建提出新的解决方案.%Objective Aim at the problems in the treatments of the children malignant bone tumor of distal femur,we put forward the concept of the dual mobility hemi-knee prosthesis and try to perform the motion parameters analysis and the pilot clinical trials.Methods Base on the CT data from samples of knee joint in adult,we adopted the Mimics/Geomagic/Pro-E software and computer numerical control milling machine technology to design and produce the dual mobility hemi-knee artificial prosthesis,and then motion parameters was analyzed in vitro test,and at last pilot clinical trial was performed.Results In vitro experiment showed that the displacement of the internal femoral condyle flexion facet center was (2
Ginn, Samantha L; Alexander, Ian E; Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo
To date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our June 2012 update, we have entries on 1843 trials undertaken in 31 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are available on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in clinical trials of gene therapy approaches around the world and discuss the prospects for the future.
Stensland, Kristian D; McBride, Russell B; Latif, Asma; Wisnivesky, Juan; Hendricks, Ryan; Roper, Nitin; Boffetta, Paolo; Hall, Simon J; Oh, William K; Galsky, Matthew D
The number and diversity of cancer therapeutics in the pipeline has increased over the past decade due to an enhanced understanding of cancer biology and the identification of novel therapeutic targets. At the same time, the cost of bringing new drugs to market and the regulatory burdens associated with clinical drug development have progressively increased. The finite number of eligible patients and limited financial resources available to evaluate promising new therapeutics represent rate-limiting factors in the effort to translate preclinical discoveries into the next generation of standard therapeutic approaches. Optimal use of resources requires understanding and ultimately addressing inefficiencies in the cancer clinical trials system. Prior analyses have demonstrated that a large proportion of trials initiated by the National Cancer Institute (NCI) Cooperative Group system are never completed. While NCI Cooperative Group trials are important, they represent only a small proportion of all cancer clinical trials performed. Herein, we explore the problem of cancer clinical trials that fail to complete within the broader cancer clinical trials enterprise. Among 7776 phase II-III adult cancer clinical trials initiated between 2005-2011, we found a seven-year cumulative incidence of failure to complete of approximately 20% (95% confidence interval = 18% to 22%). Nearly 48000 patients were enrolled in trials that failed to complete. These trials likely contribute little to the scientific knowledge base, divert resources and patients from answering other critical questions, and represent a barrier to progress.
Qi, Guan D; We, Ding A; Chung, Leung P; Fai, Cheng K
One of the important components in randomized Controlled Trial (RCT) is blinding. The gold standard of clinical trials is to achieve a double blind design. However, only a small number of randomized controlled trials in traditional Chinese medicine have been reported, most of them are of poor quality in methodology including placebo preparation and verification. The purpose of the article is to review the validity of placebo used in blinded clinical trials for Chinese herbal medicine (CHM) in recent years and related patents. We searched the Wanfang Database (total of 827 Chinese journals of medicine and/or pharmacy, from 1999 to 2005) and 598 full-length articles related to placebo clinical trials were found. 77 placebo blinded clinical trials for Chinese medicine were extracted by manual search from the 598 articles. After reviewing the 77 full-length articles, we found that nearly half of the clinical trials did not pay attention to the physical quality of the testing drug and placebo and whether they were of comparable physical quality. The rest provided very limited placebo information so that blinding assurance could not be assumed. Only 2 articles (2.6%) specifically validated the comparability between the testing drug and the placebo. Researchers in Chinese medicine commonly ignored the quality of the placebo in comparison to the test drug. This may be causing bias in the clinical trials. Quality specifications and evaluation of the placebo should deserve special attention to reduce bias in randomized controlled trials in TCM study.
As Japan becomes more integrated into the global market, pharmaceutical research and development (R&D) in Japan faces considerable challenges. While global simultaneous development including Asian countries has become a common strategy for multi-national pharmaceutical companies, Japan has been frequently set aside because of its provincial regulatory and clinical trial infrastructure. Meanwhile, many improvement programs in pharmaceutical area have been initiated in Japan. With this increased scrutiny, significant improvements in regulatory process, clinical trial costs, and site performance are anticipated over the next few years. RENAAL is the first multi-national clinical trial involving Japanese patients diabetic nephropathy associated with type II diabetes mellitus. In this article, issues which have been observed in the process of conducting multi-national clinical trial were discussed based on the experience with RENAAL. It is hoped that, as we gain more experiences in multi-national clinical trials, solutions for these issues are found in near future.
Buonansegna, Erika; Salomo, Søren; Maier, Anja
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...... 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; Maier, Anja
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......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...
Ormarsson, Orri Thor; Geirsson, Thormodur; Bjornsson, Einar Stefan; Jonsson, Tomas; Moller, Pall; Loftsson, Thorsteinn; Stefansson, Einar
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. PMID:23118720
Ogawa, Hisao; Kojima, Sunao
"Evidence-based medicine (EBM)" implies effective and high quality practice for patients based on well-grounded medical science. The success of clinical trials in Japan is essential to build original evidence specific for Japanese patients. Based on this concept, we have performed several large-scale clinical trials to provide EBM, including the Japanese Antiplatelets Myocardial Infarction Study [JAMIS; clinical improvement in acute myocardial infarction (AMI) patients with antiplatelet therapy], the Japanese beta-Blockers and Calcium Antagonists Myocardial Infarction (JBCMI; comparison of the effects of beta-blockers and calcium antagonists on cardiovascular events in post-AMI patients), a multicenter study for aggressive lipid-lowering strategy by HMG-CoA reductase inhibitors in patients with AMI (MUSASHI; effects of statin therapy on cardiovascular events in patients with AMI), and the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD trial; efficacy of low-dose aspirin therapy for primary prevention of atherosclerotic events in type 2 diabetic patients). The results of these prospective studies were directly linked with clinical practice. We have acquired the know-how of large-scale clinical trials; an important point is to have passion for "buildup evidence specific for the Japanese" and to recruit subjects for enrollment after explaining the significance of "clinical trials for the Japanese".
Kyte, DG; Draper, H; Ives, J.; Liles, C; Gheorghe, A.; Calvert, M
BACKGROUND: Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this revie...
Berry, Donald A
Clinical trials are the final links in the chains of knowledge and for determining the roles of therapeutic advances. Unfortunately, in an important sense they are the weakest links. This article describes two designs that are being explored today: platform trials and basket trials. Both are attempting to merge clinical research and clinical practice.
Peter T Choi
Full Text Available Early randomized controlled trials have suggested that neuraxial blockade may reduce cardiorespiratory complications after non-cardiothoracic surgery, but recent larger trials have been inconclusive. We conducted a pilot study to assess the feasibility of conducting a large multicentre randomized controlled trial in Canada.After Research Ethics Board approvals from the participating institutions, subjects were recruited if they were > or = 45 years old, had an expected hospital stay > or = 48 hours, were undergoing a noncardiothoracic procedure amenable to epidural analgesia, met one of six risk criteria, and did not have contraindications to neuraxial blockade. After informed consent, subjects were randomly allocated to combined epidural analgesia (epidural group and neuraxial anesthesia, with or without general anesthesia, or intravenous opioid analgesia (IV group and general anesthesia. The primary outcomes were the rate of recruitment and the percents of eligible patients recruited, crossed over, and followed completely. Feasibility targets were defined a priori. A blinded, independent committee adjudicated the secondary clinical outcomes. Subjects were followed daily while in hospital and then at 30 days after surgery. Analysis was intention-to-treat. Over a 15-month period, the recruitment rate was 0.5+/-0.3 (mean+/-SEM subjects per week per centre; 112/494 (22.7% eligible subjects were recruited at four tertiary-care teaching hospitals in Canada. Thirteen (26.5% of 49 subjects in the epidural group crossed over to the IV group; seven (14.3% were due to failed or inadequate analgesia or complications from epidural analgesia. Five (9.8% of 51 subjects in the IV group crossed over to the epidural group but none were due to inadequate analgesia or complications. Ninety-eight (97.0% of 101 subjects were successfully followed up until 30 days after their surgery.Of the criteria we defined for the feasibility of a full-scale trial, only the
Sanderson, Frances; Andrews, Laura; Douglas, Alexander D; Hunt-Cooke, Angela; Bejon, Philip; Hill, Adrian V S
There is increasing interest in malaria vaccines targeting the asexual blood stage of Plasmodium falciparum. Without accepted immunologic correlates of clinical protection, challenge studies are useful for assessing the efficacy of candidate vaccines in vivo in healthy volunteers. We report a pilot study of a safe and robust challenge protocol using a blood-stage inoculum. We have applied well-validated trial endpoints and twice daily real-time quantitative polymerase chain reaction monitoring of parasitemia to blood-stage challenge, which enabled direct comparison with sporozoite challenge. We found that greater accuracy in quantification of blood-stage growth rates can be achieved with blood-stage challenge. This finding may provide greater power to detect partial efficacy of many blood-stage candidate vaccines. We discuss the potential utility of blood-stage challenge studies in accelerating malaria vaccine development.
Brown, Alison; Santilli, Mario; Scott, Belinda
Governing bodies of health services need assurance that major risks to achieving the health service objectives are being controlled. Currently, the main assurance mechanisms generated within the organization are through the review of implementation of policies and procedures and review of clinical audits and quality data. The governing bodies of health services need more robust, objective data to inform their understanding of the control of clinical risks. Internal audit provides a methodological framework that provides independent and objective assurance to the governing body on the control of significant risks. The article describes the pilot of the internal audit methodology in an emergency unit in a health service. An internal auditor was partnered with a clinical expert to assess the application of clinical criteria based on best practice guidelines. The pilot of the internal audit of a clinical area was successful in identifying significant clinical risks that required further management. The application of an internal audit methodology to a clinical area is a promising mechanism to gain robust assurance at the governance level regarding the management of significant clinical risks. This approach needs further exploration and trial in a range of health care settings. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.
Weisskopf, Michael; Bucklar, Guido; Blaser, Jürg
Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research. In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient-trial-assignment-tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures. The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of
Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N
Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.
Menezes, Amber S; Barnes, Alison; Scheer, Adena S; Martel, Guillaume; Moloo, Husein; Boushey, Robin P; Sabri, Elham; Auer, Rebecca C
The objective of this study was to provide a descriptive analysis of registered clinical trials in surgical oncology at ClinicalTrials.gov. Data was extracted from ClinicalTrials.gov using the following search engine criteria: "Cancer" as Condition, "Surgery OR Operation OR Resection" as Intervention, and Non-Industry sponsored. The search was limited to Canada and the United States and included trials registered from January 1, 2001 to January 1, 2011. Of 9,961 oncology trials, 1,049 (10.5%) included any type of surgical intervention. Of these trials, 125 (11.9%, 1.3% of all oncology trials) assessed a surgical variable, 773 (73.7%) assessed adjuvant/neoadjuvant therapies, and 151 (14.4%) were observational studies. Of the trials assessing adjuvant therapies, systemic treatment (362 trials, 46.8%) and multimodal therapy (129 trials, 16.7%) comprised a large focus. Of the 125 trials where surgery was the intervention, 59 trials (47.2%) focused on surgical techniques or devices, 45 trials (36.0%) studied invasive diagnostic methods, and 21 trials (16.8%) evaluated surgery versus no surgery. The majority of the 125 trials were nonrandomized (72, 57.6%). The number of registered surgical oncology trials is small in comparison to oncology trials as a whole. Clinical trials specifically designed to assess surgical interventions are vastly outnumbered by trials focusing on adjuvant therapies. Randomized surgical oncology trials account for <1% of all registered cancer trials. Barriers to the design and implementation of randomized trials in surgical oncology need to be clarified in order to facilitate higher-level evidence in surgical decision-making.
Cooper Cindy L
Full Text Available Abstract Background People with multiple sclerosis (MS are at high risk of depression. We undertook a pilot trial of computerised cognitive behavioural therapy (CCBT for the treatment of depression in people with MS to test the feasibility of undertaking a full trial. Methods Participants with a diagnosis of MS and clinical levels of depression were recruited through out-patient clinics and postal screening questionnaires at two UK centres and randomised to CCBT or usual care. Clinical outcomes included the Beck Depression Inventory (BDI-II and Multiple Sclerosis Impact Scale (MSIS-29 at baseline, 8 and 21 weeks. Feasibility outcomes included: recruitment rate; reasons for refusal, withdrawal and dropout; feasibility and acceptability of the proposed outcome measures; sample size estimation and variation in and preferences for service delivery. Results Twenty-four participants were recruited. The recruitment rate, calculated as the proportion of those invited to fill in a screening questionnaire who were consented into the trial, was 4.1%. Recruitment through out-patient clinics was somewhat slower than through screening questionnaire mail-out but the overall recruitment yield was similar. Of the 12 patients in the CCBT arm, 9 (75% completed at least four, and 6 completed all 8 CCBT sessions. For completers, the median time (IQR to complete all eight CCBT sessions was 15 (13 to 20 weeks. Participants expressed concern about the face validity of the Beck Depression Inventory II for the measurement of self-reported depression in people with MS. The MSIS-29 was the patient-reported outcome measure which participants felt best reflected their concerns. The estimated sample size for a full trial is between 180 and 390 participants. NHS partners were not delivering CCBT in community facilities and participants preferred to access CCBT at home, with no one expressing a preference for use of CCBT in an alternative location. Conclusions A definitive
Shergis Johannah L
Full Text Available Abstract Conducting clinical trials of Chinese medicines (CM in hospitals presents challenges for researchers. The success of hospital-based CM clinical trials may be influenced by the protocol design, including the maintenance of CM theory in compliance with scientific rigour and hospital guidelines and justified treatment approaches with results that can translate into clinical practice. Other influences include personnel and resources such as a dedicated team open to CM with an established research culture and the ability to maximise participant recruitment. This article identifies the key challenges and limitations of conducting CM clinical trials in Australian hospitals.
Alvarenga, Lenio Souza; Martins, Elisabeth Nogueira
To evaluate biopharmaceutical industry-sponsored clinical trials placed in countries previously described as emerging regions for clinical research, and potential differences for those placed in Brazil. Data regarding recruitment of subjects for clinical trials were retrieved from www.clinicaltrials.gov on February 2nd 2009. Proportions of sites in each country were compared among emerging countries. Multiple logistic regressions were performed to evaluate whether trial placement in Brazil could be predicted by trial location in other countries and/or by trial features. A total of 8,501 trials were then active and 1,170 (13.8%) included sites in emerging countries (i.e., Argentina, Brazil, China, Czech Republic, Hungary, India, Mexico, Poland, Russia, South Korea, and South Africa). South Korea and China presented a significantly higher proportion of sites when compared to other countries (plogistic regressions detected no negative correlation between placement in other countries when compared to Brazil. Trials involving subjects with less than 15 years of age, those with targeted recruitment of at least 1,000 subjects, and seven sponsors were identified as significant predictors of trial placement in Brazil. No clear direct competition between Brazil and other emerging countries was detected. South Korea showed the higher proportion of sites and ranked third in total number of trials, appearing as a major player in attractiveness for biopharmaceutical industry-sponsored clinical trials.
Beer, S; Aschbacher, B; Manoglou, D; Gamper, E; Kool, J; Kesselring, J
To evaluate feasibility and perform an explanatory analysis of the efficacy of robot-assisted gait training (RAGT) in MS patients with severe walking disabilities (Expanded Disability Status Scale [EDSS] 6.0-7.5) in a pilot trial. Prospective, randomized, controlled clinical trial comparing RAGT with conventional walking training (CWT) in a group of stable MS patients (n = 35) during an inpatient rehabilitation stay, 15 sessions over three weeks. All patients participated additionally in a multimodal rehabilitation program. The primary outcome measure was walking velocity and secondary measures were 6-min-walking distance, stride length and knee-extensor strength. All tests were performed by an external blinded assessor at baseline after three weeks and at follow-up after six months. Additionally, Extended Barthel Index (EBI) at entry and discharge was assessed (not blinded), and acceptance/convenience of RAGT rated by patients (Visual Analogue Scale [VAS]) was recorded. Nineteen patients were randomly allocated to RAGT and 16 patients to CWT. Groups were comparable at baseline. There were 5 drop-outs (2 related directly to treatment) in the RAGT group and 1 in the CWT group, leaving 14 RAGT patients and 15 CWT patients for final analysis. Acceptance and convenience of RAGT as rated by patients were high. Effect sizes were moderate to large, although not significant, for walking velocity (0.700, 95% CI -0.089 to 1.489), walking distance (0.401, 95% CI - 0.370 to 1.172) and knee-extensor strength (right: 1.105, 95% CI 0.278 to 1.932, left 0.650, 95% CI -0.135 to 1.436) favouring RAGT. Prepost within-group analysis revealed an increase of walking velocity, walking distance and knee-extensor strength in the RAGT group, whereas in CWT group only walking velocity was improved. In both groups outcome values returned to baseline at follow-up after six months (n = 23). Robot-assisted gait training is feasible and may be an effective therapeutic option in MS patients with
psychological well-being. Trial registration ClinicalTrials.gov Identified NCT00090506. PMID:24980650
Recently, the complexity and costs of clinical trials have increased dramatically, especially in the area of new drug development. Risk-based monitoring (RBM) has been attracting attention as an efficient and effective trial monitoring approach, which can be applied irrespectively of the trial sponsor, i.e., academic institution or pharmaceutical company. In the RBM paradigm, it is expected that a statistical approach to central monitoring can help improve the effectiveness of on-site monitoring by prioritizing and guiding site visits according to central statistical data checks, as evidenced by examples of actual trial datasets. In this review, several statistical methods for central monitoring are presented. It is important to share knowledge about the role and performance capabilities of statistical methodology among clinical trial team members (i.e., sponsors, investigators, data managers, monitors, and biostatisticians) in order to adopt central statistical monitoring for assessing data quality in the actual clinical trial.
Cloutier, Francis; Khoury, Naim; Ghostine, Jimmy; Farzin, Behzad; Kotowski, Marc; Weill, Alain; Roy, Daniel; Raymond, Jean
Background and purpose Endovascular coil embolization of cerebral aneurysms is associated with suboptimal angiographic results in up to 20-30% of patients. Coil packing density has been used as an index of the success of the initial procedure. The trial sought to study the effects of using 15-caliber coils, as compared with 10-caliber coils, on packing density. Methods Does Embolization with Larger coils lead to better Treatment of Aneurysms (DELTA) is an investigator-initiated multicenter prospective, randomized, controlled clinical trial. Patients are randomized 1:1 to embolization with either 10-caliber coils exclusively (control group) or the highest safely achievable proportion of 15-caliber coils and 10-caliber coils if necessary (intervention group) in 4-12-mm aneurysms. The endpoint of the pilot phase of the trial was the capacity to increase packing density of the initial procedure, calculated using a mathematical transformation of the dimensions entered into the case report forms. Secondary outcomes included the total number of coils used per aneurysm, total fluoroscopy time, initial angiographic outcomes and any adverse or undesirable event. Results Seventy patients were recruited between June 2014 and November 2015. Compared with 10-caliber coils, the 15-caliber coil group had a higher median packing density (44% vs 24%, p = 0.017). Results of other outcome measures were similar for the two groups. Conclusion Coiling of small and medium aneurysms randomized to 15-caliber coils achieved higher packing densities compared with coiling using 10-caliber coils.
Full Text Available Abstract Background Since siblings of pediatric cancer patients are at risk for emotional, behavioral, and social problems, there is considerable interest in development of early psychological interventions. This paper aimed at evaluating the effectiveness of a two-session psychological intervention for siblings of newly diagnosed pediatric cancer patients. Methods Thirty siblings age 6-17 years were randomly assigned to an intervention group or an active control group with standard psychosocial care. The manualized intervention provided to siblings in the first 2 months after the cancer diagnosis of the ill child included medical information, promotion of coping skills, and a psychoeducational booklet for parents. At 4 to 6 weeks, 4 months, and 7 months after the diagnosis, all siblings and their parents completed measures (from standardized instruments of social support, quality of life, medical knowledge, posttraumatic stress symptoms, and anxiety. Results At follow-up siblings in the intervention group showed better psychological well-being, had better medical knowledge, and reported receiving social support from more people. However, the intervention had no effects on posttraumatic stress symptoms and anxiety. Conclusions The results of this pilot trial suggest that a two-session sibling intervention can improve siblings' adjustment, particularly psychological well-being, in the early stage after a cancer diagnosis. Trial Registration ClinicalTrials.gov NCT00296907
Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.
Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects
Dimitrios Zardavas; Martine Piccart-Gebhart
The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.
Emma L. Healey
Full Text Available Background: Long-term conditions (LTCs are important determinants of quality of life and healthcare expenditure worldwide. Whilst multimorbidity is increasingly the norm in primary care, clinical guidelines and the delivery of care remain focused on single diseases, resulting in poorer clinical outcomes. Osteoarthritis, and anxiety and/or depression frequently co-occur with other LTCs, yet are seldom prioritized by the patient or clinician, resulting in higher levels of disability, poorer prognosis, and increased healthcare costs. Objective: To examine the feasibility and acceptability of an integrated approach to LTC management, tackling the under-diagnosis and under-management of osteoarthritis-related pain and anxiety and/or depression in older adults with other LTCs in primary care. Design: The ENHANCE study is a pilot stepped-wedge cluster randomized controlled trial to test the feasibility and acceptability of a nurse-led ENHANCE LTC review consultation for identifying, assessing, and managing joint pain, and anxiety and/or depression in patients attending LTC reviews. Specific objectives (process evaluation and research outcomes will be achieved through a theoretically informed mixed-methods approach using participant self-reported questionnaires, a medical record review, an ENHANCE EMIS template, qualitative interviews, and audio recordings of the ENHANCE LTC review. Discussion: Success of the pilot trial will be measured against the level of the primary care team engagement, assessment of training delivery, and degree of patient recruitment and retention. Patient satisfaction and treatment fidelity will also be explored. ISRCTN registry number: 12154418. Journal of Comorbidity 2015;5(1:135–149
Umscheid, Craig A.; Margolis, David J.; Grossman, Craig E.
The recent focus of federal funding on comparative effectiveness research underscores the importance of clinical trials in the practice of evidence-based medicine and health care reform. The impact of clinical trials not only extends to the individual patient by establishing a broader selection of effective therapies, but also to society as a whole by enhancing the value of health care provided. However, clinical trials also have the potential to pose unknown risks to their participants, and biased knowledge extracted from flawed clinical trials may lead to the inadvertent harm of patients. Although conducting a well-designed clinical trial may appear straightforward, it is founded on rigorous methodology and oversight governed by key ethical principles. In this review, we provide an overview of the ethical foundations of trial design, trial oversight, and the process of obtaining approval of a therapeutic, from its pre-clinical phase to post-marketing surveillance. This narrative review is based on a course in clinical trials developed by one of the authors (DJM), and is supplemented by a PubMed search predating January 2011 using the keywords “randomized controlled trial,” “patient/clinical research,” “ethics,” “phase IV,” “data and safety monitoring board,” and “surrogate endpoint.” With an understanding of the key principles in designing and implementing clinical trials, health care providers can partner with the pharmaceutical industry and regulatory bodies to effectively compare medical therapies and thereby meet one of the essential goals of health care reform. PMID:21904102
Duan, Naihua; Kravitz, Richard L; Schmid, Christopher H
To raise awareness among clinicians and epidemiologists that single-patient (n-of-1) trials are potentially useful for informing personalized treatment decisions for patients with chronic conditions. We reviewed the clinical and statistical literature on methods and applications of single-patient trials and then critically evaluated the needs for further methodological developments. Existing literature reports application of 2,154 single-patient trials in 108 studies for diverse clinical conditions; various recent commentaries advocate for wider application of such trials in clinical decision making. Preliminary evidence from several recent pilot acceptability studies suggests that single-patient trials have the potential for widespread acceptance by patients and clinicians as an effective modality for increasing the therapeutic precision. Bayesian and adaptive statistical methods hold promise for increasing the informational yield of single-patient trials while reducing participant burden, but are not widely used. Personalized applications of single-patient trials can be enhanced through further development and application of methodologies on adaptive trial design, stopping rules, network meta-analysis, washout methods, and methods for communicating trial findings to patients and clinicians. Single-patient trials may be poised to emerge as an important part of the methodological armamentarium for comparative effectiveness research and patient-centered outcomes research. By permitting direct estimation of individual treatment effects, they can facilitate finely graded individualized care, enhance therapeutic precision, improve patient outcomes, and reduce costs. Copyright © 2013 Elsevier Inc. All rights reserved.
Natale, Enrico; Marsocci, Alfiera
Generally in the clinical practice patients are more complex in comparison with those included in the clinical trials. In this article, we discuss three relevant items, which may implement the transferability of the clinical trial results in the real world. The observational studies have fewer restrictions on the number of patients included, due to more relaxed inclusion and exlusion criteria than in randomized clinical trials. The absence of randomization however may lead to potential for bias. The recurrent event analysis may extend the positive results of clinical trials regarding the reductions of the first primary endpoint event to total events, including those beyond the first event. This analysis is of great interest in the clinical practice, where recurrent events are common. Finally the reliability of subgroup analysis is discussed. Pre-specified subgroup analyses are more credible and valuable than post-hoc analyses.
Full Text Available Abstract Background Although the connection between ascending infection and preterm birth is undisputed, research focused on finding effective treatments has been disappointing. However evidence that eradication of Candida in pregnancy may reduce the risk of preterm birth is emerging. We conducted a pilot study to assess the feasibility of conducting a large randomized controlled trial to determine whether treatment of asymptomatic candidiasis in early pregnancy reduces the incidence of preterm birth. Methods We used a prospective, randomized, open-label, blinded-endpoint (PROBE study design. Pregnant women presenting at Candida were randomized to 6-days of clotrimazole vaginal pessaries (100mg or usual care (screening result is not revealed, no treatment. The primary outcomes were the rate of asymptomatic vaginal candidiasis, participation and follow-up. The proposed primary trial outcome of spontaneous preterm birth Results Of 779 women approached, 500 (64% participated in candidiasis screening, and 98 (19.6% had asymptomatic vaginal candidiasis and were randomized to clotrimazole or usual care. Women were not inconvenienced by participation in the study, laboratory testing and medication dispensing were problem-free, and the follow-up rate was 99%. There was a tendency towards a reduction in spontaneous preterm birth among women with asymptomatic candidiasis who were treated with clotrimazole RR = 0.33, 95%CI 0.04-3.03. Conclusions A large, adequately powered, randomized trial of clotrimazole to prevent preterm birth in women with asymptomatic candidiasis is both feasible and warranted. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12609001052224
Sozu, Takashi; Hamasaki, Toshimitsu; Evans, Scott R
This book integrates recent methodological developments for calculating the sample size and power in trials with more than one endpoint considered as multiple primary or co-primary, offering an important reference work for statisticians working in this area. The determination of sample size and the evaluation of power are fundamental and critical elements in the design of clinical trials. If the sample size is too small, important effects may go unnoticed; if the sample size is too large, it represents a waste of resources and unethically puts more participants at risk than necessary. Recently many clinical trials have been designed with more than one endpoint considered as multiple primary or co-primary, creating a need for new approaches to the design and analysis of these clinical trials. The book focuses on the evaluation of power and sample size determination when comparing the effects of two interventions in superiority clinical trials with multiple endpoints. Methods for sample size calculation in clin...
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.
Klimt, C R
Some of the guiding principles as well as the pitfall of long-term randomized clinical trials are presented. Examples have been chosen from trials in the cardiovascular field. A typical long-term clinical trial is divided into five phases: planning, preparation, recruitment, clinical follow-up and termination, and finally analysis. Administrative, legal, and ethical aspects of a trial are discussed, as well as the cost of clinical trials. Organization patterns are described and some prevalent ones are criticized. Further, practical matters such as recruitment techniques, obtaining informed consent from the patients, determining drug dosage and formulation as well as the problem of interaction with nonstudy drugs are referred to. Adherence testing remains a problem, because of our inability to test for placebo adherence.
Full Text Available Abstract Background In Germany, clinical trials and comparative effectiveness studies in primary care are still very rare, while their usefulness has been recognised in many other countries. A network of researchers from German academic general practice has explored the reasons for this discrepancy. Methods Based on a comprehensive literature review and expert group discussions, problem analyses as well as structural and procedural prerequisites for a better implementation of clinical trials in German primary care are presented. Results In Germany, basic biomedical science and technology is more reputed than clinical or health services research. Clinical trials are funded by industry or a single national programme, which is highly competitive, specialist-dominated, exclusive of pilot studies, and usually favours innovation rather than comparative effectiveness studies. Academic general practice is still not fully implemented, and existing departments are small. Most general practitioners (GPs work in a market-based, competitive setting of small private practices, with a high case load. They have no protected time or funding for research, and mostly no research training or experience. Good Clinical Practice (GCP training is compulsory for participation in clinical trials. The group defined three work packages to be addressed regarding clinical trials in German general practice: (1 problem analysis, and definition of (2 structural prerequisites and (3 procedural prerequisites. Structural prerequisites comprise specific support facilities for general practice-based research networks that could provide practices with a point of contact. Procedural prerequisites consist, for example, of a summary of specific relevant key measures, for example on a web platform. The platform should contain standard operating procedures (SOPs, templates, checklists and other supporting materials for researchers. Conclusion All in all, our problem analyses revealed that
Full Text Available Abstract Background Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. Methods The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists’ clinical judgment and maintaining consistency with a prior pilot study. Results The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. Conclusions The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Trial registration Clinicaltrials.gov NCT00970008 (18 August 2009
Aman, Michael G; Novotny, Sherie; Samango-Sprouse, Carole; Lecavalier, Luc; Leonard, Elizabeth; Gadow, Kenneth D.; King, Bryan H; Pearson, Deborah A.; Gernsbacher, Morton Ann; Chez, Michael
This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs). The Clinical Global Impressions scale was recommended for all randomized clinical trials. At this point, however, there is no “perfect” choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across t...
With the increasing amounts of clinical data required for drug regulatory approval and the fierce competition for patients in the Western countries, the cost of clinical trials continues to rise considerably. This study suggests that outsourcing clinical trials to China is an effective strategy to reduce cost and cycle time of drug development. China offers a high market potential and strong research capacity that can provide long term benefits to pharmaceutical and biotech companies. An inte...
Shergis Johannah L; Parker Shefton; Coyle Meaghan E; Zhang Anthony L; Xue Charlie C
Abstract Conducting clinical trials of Chinese medicines (CM) in hospitals presents challenges for researchers. The success of hospital-based CM clinical trials may be influenced by the protocol design, including the maintenance of CM theory in compliance with scientific rigour and hospital guidelines and justified treatment approaches with results that can translate into clinical practice. Other influences include personnel and resources such as a dedicated team open to CM with an establishe...
gene therapy program with Oxford Biomedica to bring gene therapy for juvenile macular degeneration (Stargardt’s disease). This phase I clinical trial...working with Oxford Biomedica and a separate project with academic investigators on gene therapy for Usher lb syndrome (deaf-blindness due to a gene... Biomedica collaboration will begin no later than 04 2011. 3. NNRI has held multiple clinical investigator meetings to define clinical trial outcomes for
Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi
Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to
Mentz, Robert J; Hernandez, Adrian F; Berdan, Lisa G; Rorick, Tyrus; O'Brien, Emily C; Ibarra, Jenny C; Curtis, Lesley H; Peterson, Eric D
Randomized, clinical trials are commonly regarded as the highest level of evidence to support clinical decisions. Good Clinical Practice guidelines have been constructed to provide an ethical and scientific quality standard for trials that involve human subjects in a manner aligned with the Declaration of Helsinki. Originally designed to provide a unified standard of trial data to support submission to regulatory authorities, the principles may also be applied to other studies of human subjects. Although the application of Good Clinical Practice principles generally led to improvements in the quality and consistency of trial operations, these principles have also contributed to increasing trial complexity and costs. Alternatively, the growing availability of electronic health record data has facilitated the possibility for streamlined pragmatic clinical trials. The central tenets of Good Clinical Practice and pragmatic clinical trials represent potential tensions in trial design (stringent quality and highly efficient operations). In the present article, we highlight potential areas of discordance between Good Clinical Practice guidelines and the principles of pragmatic clinical trials and suggest strategies to streamline study conduct in an ethical manner to optimally perform clinical trials in the electronic age.
Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.
Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo
The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.
Utami, Dina; Bickmore, Timothy W; Barry, Barbara; Paasche-Orlow, Michael K
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.
de Bruijn, Berry; Carini, Simona; Kiritchenko, Svetlana; Martin, Joel; Sim, Ida
Clinical trials are one of the most valuable sources of scientific evidence for improving the practice of medicine. The Trial Bank project aims to improve structured access to trial findings by including formalized trial information into a knowledge base. Manually extracting trial information from published articles is costly, but automated information extraction techniques can assist. The current study highlights a single architecture to extract a wide array of information elements from full-text publications of randomized clinical trials (RCTs). This architecture combines a text classifier with a weak regular expression matcher. We tested this two-stage architecture on 88 RCT reports from 5 leading medical journals, extracting 23 elements of key trial information such as eligibility rules, sample size, intervention, and outcome names. Results prove this to be a promising avenue to help critical appraisers, systematic reviewers, and curators quickly identify key information elements in published RCT articles.
Flight, Laura; Julious, Steven A; Goodacre, Steve
Adaptive design clinical trials use preplanned interim analyses to determine whether studies should be stopped or modified before recruitment is complete. Emergency medicine trials are well suited to these designs as many have a short time to primary outcome relative to the length of recruitment. We hypothesised that the majority of published emergency medicine trials have the potential to use a simple adaptive trial design. We reviewed clinical trials published in three emergency medicine journals between January 2003 and December 2013. We determined the proportion that used an adaptive design as well as the proportion that could have used a simple adaptive design based on the time to primary outcome and length of recruitment. Only 19 of 188 trials included in the review were considered to have used an adaptive trial design. A total of 154/165 trials that were fixed in design had the potential to use an adaptive design. Currently, there seems to be limited uptake in the use of adaptive trial designs in emergency medicine despite their potential benefits to save time and resources. Failing to take advantage of adaptive designs could be costly to patients and research. It is recommended that where practical and logistical considerations allow, adaptive designs should be used for all emergency medicine clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo; Edelstein, Richard M
In 1989, Rosenberg et al. performed the first human gene therapy trial when they used a retrovirus to introduce the gene coding for resistance to neomycin into human tumor-infiltrating lymphocytes before infusing them into five patients with advanced melanoma. This study demonstrated the feasibility of using retroviral gene transduction in humans and set the stage for further studies. Since then, over 900 clinical trials have been completed, are ongoing or have been approved worldwide. These trials have been designed to establish feasibility and safety, to demonstrate the reality of expression of therapeutic protein(s) in vivo by the genes transferred and, in some cases, to show therapeutic benefit. There is no single source of information that presents an overview of all the clinical trials undertaken worldwide. In 1997 we set up a database to bring all the information on clinical trials together as comprehensively and as globally as possible. The data were compiled and are regularly updated from official agency sources, the published literature, presentations at conferences and from information kindly provided by investigators or trial sponsors themselves. As of January 31, 2004, we have identified 918 trials in 24 countries. The USA accounts for two-thirds of these trials. Cancer is by far the most common disease indication, followed by inherited monogenic diseases, and cardiovascular diseases. Viral vectors have been the most frequently used vehicles for transferring genes into human cells, with retroviruses and adenoviruses representing the vast majority. Plasmid (naked) DNA and other non-viral vectors have been used in one-quarter of the trials. Over 100 distinct genes have been transferred. This article aims to provide a descriptive overview of the clinical trials that, to the best of our knowledge, have been or are being performed worldwide. Details of the data presented, including an interactive, searchable database that currently holds information on 918
Silva, Betania Huber; Martinez, Denis; Wender, Maria Celeste Osório
Insomnia is a frequent climacteric symptom. This pilot, double-blind, randomized placebo-controlled trial compared estradiol associated with trimegestone or placebo in 12 women with perimenopausal insomnia. The Pittsburgh Sleep Quality Index (PSQI) was administered, and polysomnography was performed at baseline and after 28 days. Sleep efficiency and median score of the PSQI improved significantly in the hormone therapy group (HT) (p=0.041 and p=0.027, respectively) and not in placebo group. Perimenopausal insomnia improved after short-term HT.
Bent, Stephen; Bertoglio, Kiah; Ashwood, Paul; Bostrom, Alan; Hendren, Robert L.
We conducted a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children ages 3–8 with autism spectrum disorder (ASD). After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (±4.8) points in the omega-3 group compared to 0.3 (±7.2) points in the placebo group (p = 0.40; effect size = 0.38). Correlations were found between decreases in f...
Salsbury, Stacie A; DeVocht, James W; Hondras, Maria;
and study participants regarding treatment group assignment. METHODS: We conducted an observational analysis of digital video-recordings derived from study visits conducted during a pilot randomized trial of conservative therapies for temporomandibular pain. A theory-based, iterative process developed...... aimed to: 1) develop an instrument to assess practitioner-patient interactions; 2) determine the equivalence of a chiropractor's verbal interactions and treatment delivery for participants allocated to active or sham chiropractic groups; and 3) describe the perceptions of a treatment-masked evaluator...
Smaïl-Faugeron, V; Fron-Chabouis, H; Durieux, P
Prospective registration of randomized controlled trials (RCTs) represents the best solution to reporting bias. The extent to which oral health journals have endorsed and complied with RCT registration is unknown. We identified journals publishing RCTs in dentistry, oral surgery, and medicine in the Journal Citation Reports. We classified journals into 3 groups: journals requiring or recommending trial registration, journals referring indirectly to registration, and journals providing no reference to registration. For the 5 journals with the highest 2012 impact factors in each group, we assessed whether RCTs with results published in 2013 had been registered. Of 78 journals examined, 32 (41%) required or recommended trial registration, 19 (24%) referred indirectly to registration, and 27 (35%) provided no reference to registration. We identified 317 RCTs with results published in the 15 selected journals in 2013. Overall, 73 (23%) were registered in a trial registry. Among those, 91% were registered retrospectively and 32% did not report trial registration in the published article. The proportion of trials registered was not significantly associated with editorial policies: 29% with results in journals that required or recommended registration, 15% in those that referred indirectly to registration, and 21% in those providing no reference to registration (P = 0.05). Less than one-quarter of RCTs with results published in a sample of oral health journals were registered with a public registry. Improvements are needed with respect to how journals inform and require their authors to register their trials.
Lessard Martin R
Full Text Available Abstract Background Weaning is the process during which mechanical ventilation is withdrawn and the work of breathing is transferred from the ventilator back to the patient. Prolonged weaning is associated with development of ventilator-related complications and longer stays in the Intensive Care Unit (ICU. Computerized or Automated Weaning is a novel weaning strategy that continuously measures and adapts ventilator support (by frequently measuring and averaging three breathing parameters and automatically conducts Spontaneous Breathing Trials to ascertain whether patients can resume autonomous breathing. Automated Weaning holds promise as a strategy to reduce the time spent on the ventilator, decrease ICU length of stay, and improve clinically important outcomes. Methods/Design A pilot weaning randomized controlled trial (RCT is underway in the ICUs of 8 Canadian hospitals. We will randomize 90 critically ill adults requiring invasive ventilation for at least 24 hours and identified at an early stage of the weaning process to either Automated Weaning (SmartCare™ or Protocolized Weaning. The results of a National Weaning Survey informed the design of the Protocolized Weaning arm. Both weaning protocols are operationalized in Pressure Support mode, include opportunities for Spontaneous Breathing Trials, and share a common sedation protocol, oxygen titration parameters, and extubation and reintubation criteria. The primary outcome of the WEAN study is to evaluate compliance with the proposed weaning and sedation protocols. A key secondary outcome of the pilot RCT is to evaluate clinician acceptance of the weaning and sedation protocols. Prior to initiating the WEAN Study, we conducted a run-in phase, involving two patients per centre (randomizing the first participant to either weaning strategy and assigning the second patient to the alternate strategy to ensure that participating centres could implement the weaning and sedation protocols and
Goertz, Christine M; Salsbury, Stacie A; Vining, Robert D; Long, Cynthia R; Pohlman, Katherine A; Weeks, William B; Lamas, Gervasio A
The purpose of this pilot sham-controlled clinical trial was to estimate the treatment effect and safety of toggle recoil spinal manipulation for blood pressure management. Fifty-one participants with prehypertension or stage 1 hypertension (systolic blood pressure ranging from 135 to 159 mm Hg or diastolic blood pressure ranging from 85 to 99 mm Hg) were allocated by an adaptive design to 2 treatments: toggle recoil spinal manipulation or a sham procedure. Participants were seen by a doctor of chiropractic twice weekly for 6 weeks and remained on their antihypertensive medications, as prescribed, throughout the trial. Blood pressure was assessed at baseline and after study visits 1, 6 (week 3), and 12 (week 6), with the primary end point at week 6. Analysis of covariance was used to compare mean blood pressure changes from baseline between groups at each end point, controlling for sex, age, body mass index, and baseline blood pressure. Adjusted mean change from baseline to week 6 was greater in the sham group (systolic, -4.2 mm Hg; diastolic, -1.6 mm Hg) than in the spinal manipulation group (systolic, 0.6 mm Hg; diastolic, 0.7 mm Hg), but the difference was not statistically significant. No serious and few adverse events were noted. Six weeks of toggle recoil spinal manipulation did not lower systolic or diastolic blood pressure when compared with a sham procedure. No serious adverse events from either treatment were reported. Our results do not support a larger clinical trial. Further research to understand the potential mechanisms of action involving upper cervical manipulation on blood pressure is warranted before additional clinical investigations are conducted. Copyright © 2016. Published by Elsevier Inc.
Raynor, Hollie A; Steeves, Elizabeth Anderson; Bassett, David R; Thompson, Dixie L; Gorin, Amy A; Bond, Dale S
The more time adults spend being sedentary, the greater the risk of obesity. The effect of reducing television (TV) watching, a prominent sedentary behavior, on weight loss has not been tested in an adult standard behavioral obesity intervention, and the mechanisms by which reducing TV watching influences energy balance behaviors are not well understood. Two, 8-week, pilot, randomized controlled trials were conducted examining the effect of a reduced TV watching prescription on energy balance behaviors and weight loss within an adult standard behavioral obesity intervention. In the first study, participants (n=24) were randomized into one of two conditions: (a) reduce energy intake and increase moderate to vigorous physical activity (MVPA) (INCREASE PA); or (b) reduce energy intake and decrease TV watching (DECREASE TV). As findings from the first pilot study did not show an increase in MVPA in the DECREASE TV group, the second study was designed to examine the effect of adding a reduced TV prescription to a standard intervention to optimize outcomes. In Pilot Study 2, participants (n=28) were randomized to INCREASE PA or to INCREASE PA+DECREASE TV. Outcomes included objectively measured TV watching and MVPA, self-reported light physical activity (LPA-Pilot Study 2 only), self-reported dietary intake while watching TV, and weight. Conditions with TV watching prescriptions significantly reduced TV watching. Both studies showed medium to large effect sizes for conditions with TV watching prescriptions to show greater reductions in dietary intake while watching TV. Pilot Study 1 found a trend for an increase in MVPA in INCREASE PA and Pilot Study 2 found significant increases in MVPA in both conditions. Pilot Study 2 found a significant increase in LPA in the INCREASE PA+DECREASE TV. Results indicate adding a TV watching prescription to a standard obesity intervention did not enhance increases in MVPA, but may assist with reducing dietary intake while TV watching and
Full Text Available Abstract Objective Few methodological studies address the prioritization of clinical topics for the development of Clinical Practice Guidelines (CPGs. The aim of this study was to validate a methodology for Priority Determination of Topics (PDT of CPGs. Methods and results Firstly, we developed an instrument for PDT with 41 criteria that were grouped under 10 domains, based on a comprehensive systematic search. Secondly, we performed a survey of stakeholders involved in CPGs development, and end users of guidelines, using the instrument. Thirdly, a pilot testing of the PDT procedure was performed in order to choose 10 guideline topics among 34 proposed projects; using a multi-criteria analysis approach, we validated a mechanism that followed five stages: determination of the composition of groups, item/domain scoring, weights determination, quality of the information used to support judgments, and finally, topic selection. Participants first scored the importance of each domain, after which four different weighting procedures were calculated (including the survey results. The process of weighting was determined by correlating the data between them. We also reported the quality of evidence used for PDT. Finally, we provided a qualitative analysis of the process. The main domains used to support judgement, having higher quality scores and weightings, were feasibility, disease burden, implementation and information needs. Other important domains such as user preferences, adverse events, potential for health promotion, social effects, and economic impact had lower relevance for clinicians. Criteria for prioritization were mainly judged through professional experience, while good quality information was only used in 15% of cases. Conclusion The main advantages of the proposed methodology are supported by the use of a systematic approach to identify, score and weight guideline topics selection, limiting or exposing the influence of personal biases
Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques
Growing use of cloud computing in clinical trials prompted the European Clinical Research Infrastructures Network, a European non-profit organisation established to support multinational clinical research, to organise a one-day workshop on the topic to clarify potential benefits and risks. The issues that arose in that workshop are summarised and include the following: the nature of cloud computing and the cloud computing industry; the risks in using cloud computing services now; the lack of explicit guidance on this subject, both generally and with reference to clinical trials; and some possible ways of reducing risks. There was particular interest in developing and using a European 'community cloud' specifically for academic clinical trial data. It was recognised that the day-long workshop was only the start of an ongoing process. Future discussion needs to include clarification of trial-specific regulatory requirements for cloud computing and involve representatives from the relevant regulatory bodies.
Rashmi Ashish Kadam
Full Text Available Background: Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. Objective: To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. Methods: We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. Results: Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%, lack of awareness about clinical trials in patients (37%, and sociocultural issues related to trial participation (37%. About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%, and designing a recruitment strategy prior to study initiation (46.6% would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6% would enhance recruitment. Experiencing a serious adverse event, subject′s fear for study procedures (47% and side effects (44% were thought to have a moderate effect on subject retention. Conclusion: Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India.
Kadam, Rashmi Ashish; Borde, Sanghratna Umakant; Madas, Sapna Amol; Salvi, Sundeep Santosh; Limaye, Sneha Saurabh
Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%), lack of awareness about clinical trials in patients (37%), and sociocultural issues related to trial participation (37%). About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%), and designing a recruitment strategy prior to study initiation (46.6%) would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6%) would enhance recruitment. Experiencing a serious adverse event, subject's fear for study procedures (47%) and side effects (44%) were thought to have a moderate effect on subject retention. Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India.
Geifman, Nophar; Butte, Atul J
Open clinical trial data offer many opportunities for the scientific community to independently verify published results, evaluate new hypotheses and conduct meta-analyses. These data provide a springboard for scientific advances in precision medicine but the question arises as to how representative clinical trials data are of cancer patients overall. Here we present the integrative analysis of data from several cancer clinical trials and compare these to patient-level data from The Cancer Genome Atlas (TCGA). Comparison of cancer type-specific survival rates reveals that these are overall lower in trial subjects. This effect, at least to some extent, can be explained by the more advanced stages of cancer of trial subjects. This analysis also reveals that for stage IV cancer, colorectal cancer patients have a better chance of survival than breast cancer patients. On the other hand, for all other stages, breast cancer patients have better survival than colorectal cancer patients. Comparison of survival in different stages of disease between the two datasets reveals that subjects with stage IV cancer from the trials dataset have a lower chance of survival than matching stage IV subjects from TCGA. One likely explanation for this observation is that stage IV trial subjects have lower survival rates since their cancer is less likely to respond to treatment. To conclude, we present here a newly available clinical trials dataset which allowed for the integration of patient-level data from many cancer clinical trials. Our comprehensive analysis reveals that cancer-related clinical trials are not representative of general cancer patient populations, mostly due to their focus on the more advanced stages of the disease. These and other limitations of clinical trials data should, perhaps, be taken into consideration in medical research and in the field of precision medicine.
Moustgaard, Helene; Bello, Segun; Miller, Franklin G
providing a classification of clinical trial outcomes and a descriptive study of how outcomes were classified in 200 PubMed indexed clinical trial reports published in 2012. RESULTS: We identified 90 methodological publications with some form of a classification of outcomes. Three distinct definitions were...... "subjective outcome" and "objective outcome" are defined in methodological publications and clinical trial reports. To put this examination into perspective, we also provide an overview of how outcomes are classified more broadly. STUDY DESIGN AND SETTING: A systematic review of methodological publications...
Paganoni, Sabrina; Cudkowicz, Merit; Berry, James D
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an average survival of 3–5 years. While therapies for ALS remain limited, basic and translational ALS research has been host to numerous influential discoveries in recent years. These discoveries have led to a large pipeline of potential therapies that await testing in clinical trials. Until recently, ALS clinical trials have relied on a limited cadre of ‘traditional’ outcome measures, including survival and measures of function. These measures have proven useful, although imperfect, in Phase III ALS trials. However, their utility in early-phase ALS trials is limited. For these early trials, outcome measures focused on target engagement or biological pathway analysis might improve trial outcomes and better support the drug development process.
networks, namely the HIV Vaccine Trials Network (HVTN - www.hvtn.org) and the International ... These include life skills education, sanitation, potable water supply ... and data management centre, central laboratories, a community advisory ...
Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D
Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving
Hauke, C; Meisser, A; Perren, S M
Once development and mechanical and biological laboratory testing have been completed, new technologies to be used in orthopaedic and trauma surgery must be investigated in humans before they can be used routinely. Prospective clinical investigations with or without randomization to standard treatments conducted according to the current standards and guidelines for Good Clinical Practice must be performed to prove the safety and efficacy of the new device. Furthermore, these tests serve to determine the specific indications, contraindications, tips and tricks as well as the pitfalls and how to avoid them. Last, but not least, the study must result in improved teaching of the use of the device and in improved follow-up of patients. The basis of every conclusion drawn from such a study is the complete documentation of each single use of the new device. We present the modalities and methodology for conducting a prospective clinical multicentre investigation in trauma surgery, focusing on the clinical trials carried out on the Point Contact Fixator (PC-Fix), a device for the internal fixation of long bone fractures developed as part of the scientific evolution towards the Less Invasive Stabilization Systems (LISS) now being introduced into clinical practice. Four prospective multicentre clinical investigations with an overall number of 1,229 PC-Fixators implanted from October 1993 to May 1998 were performed. To our knowledge this is the largest prospective series ever reported in orthopaedic trauma surgery to test a new device before market introduction. Due to a special documentation and implant replacement procedure, every PC-Fix implantation was documented. Very few patients were lost to long-term follow-up due to the personal commitment of the study monitors. Regular personal visits of the study monitor to the investigating hospitals and close communication between the surgeons, the engineers responsible for development, the study monitor, and the study sponsor
Bucur, Anca; Van Leeuwen, Jasper; Chen, Njin-Zu; Claerhout, Brecht; De Schepper, Kristof; Perez-Rey, David; Alonso-Calvo, Raul; Pugliano, Lina; Saini, Kamal
To support the efficient execution of post-genomic multi-centric clinical trials in breast cancer we propose a solution that streamlines the assessment of the eligibility of patients for available trials. The assessment of the eligibility of a patient for a trial requires evaluating whether each eligibility criterion is satisfied and is often a time consuming and manual task. The main focus in the literature has been on proposing different methods for modelling and formalizing the eligibility criteria. However the current adoption of these approaches in clinical care is limited. Less effort has been dedicated to the automatic matching of criteria to the patient data managed in clinical care. We address both aspects and propose a scalable, efficient and pragmatic patient screening solution enabling automatic evaluation of eligibility of patients for a relevant set of trials. This covers the flexible formalization of criteria and of other relevant trial metadata and the efficient management of these representations.
Gluud, C; Sørensen, T I
The urgent need for the performance of more, better designed, and better conducted randomised clinical trials is increasingly recognised. Based on structured interviews with leading persons of 43 outstanding organisations and units involved in clinical trials in Europe and North America during 1993......, ways of organising and staffing clinical trial units were investigated. The present proposal is based on this experience from which an attempt to extract a composite set of minimal requirements has been made regarding pertinent objectives and aims, organisational aspects, staffing, and estimated costs...... to a total cost for coordination per trial of about GBP 340,000. However, with a larger staff more studies may be coordinated possibly reducing the cost per trial depending on greater effectiveness in utilisation of the basic facilities....
Mentz, Robert J; Kaski, Juan-Carlos; Dan, Gheorghe-Andrei; Goldstein, Sidney; Stockbridge, Norman; Alonso-Garcia, Angeles; Ruilope, Luis M; Martinez, Felipe A; Zannad, Faiez; Pitt, Bertram; Fiuzat, Mona; O'Connor, Christopher M
Cardiovascular clinical trials are increasingly conducted globally as a means to reduce costs, expedite timelines, provide broad applicability, and satisfy regulatory authorities. Potential problems with trial globalization include regional differences in patient characteristics, medical practice patterns, and health policies which may influence outcomes and limit generalizability. Moreover, concerns have been raised about ethical misconduct and unsatisfactory quality oversight in regions with less trial experience and infrastructure. This article reviews geographical differences in cardiovascular trials in heart failure, acute coronary syndromes, hypertension and atrial fibrillation. It also explores potential explanations for these differences and methods to standardize the presentation of trial results. This review is based on discussions between basic scientists and clinical trialists at the 8th Global Cardio Vascular Clinical Trialists Forum 2011 in Paris, France, from December 2 to 3. Copyright © 2012 Mosby, Inc. All rights reserved.
Nejrup, Kirsten; Olivarius, Niels de Fine; Jacobsen, Judith L.
The primary objective of this double-blind, randomised, controlled trial was to determine if implanting gold beads at five acupuncture points around the knee joint improves 1-year outcomes for patients with osteoarthritis (OA) of the knee. Participants were 43 adults aged 18-80 years with pain...... and stiffness from non-specific OA of the knee for over a year. The intervention was blinded implantation of gold beads at five acupuncture points around the affected knee through a hypodermic needle, or needle insertion alone. Primary outcome measures were knee pain, stiffness and function assessed...... acupuncture had greater relative improvements in self-assessed outcomes. The treatment was well tolerated. This 1-year pilot study indicates that extraarticular gold bead implantation is a promising treatment modality for patients with OA of the knee. The new treatment should be tested in a larger trial...
Merolli, Mark; Gray, Kathleen; Martin-Sanchez, Fernando; Mantopoulos, Steven; Hogg, Malcolm
.... The aim was to conduct a longitudinal pilot study to understand what aspects of research design are key to the success of running a larger-scale study of social media use in the clinical management of chronic pain...
... HUMAN SERVICES Food and Drug Administration Analgesic Clinical Trials Innovation, Opportunities, and... Analgesic Clinical Trials Innovation, Opportunities, and Networks (ACTION) Initiative. The goal of the... major gaps in scientific information, which can slow down analgesic clinical trials and analgesic...
Sánchez-Martín, J; Beltrán-Heredia, J; Solera-Hernández, C
A new tannin-based coagulant-flocculant (Tanfloc) was tested for water treatment at a pilot plant level. Four types of water sample were treated: surface water (collected from a river), and municipal, textile industry (simulated by a 100 mg L(-1) aqueous solution of an acid dye), and laundry (simulated by a 50 mg L(-1) aqueous solution of an anionic surfactant) wastewaters. The pilot plant process consisted of coagulation, sedimentation, and filtration. The experiments were carried out with an average coagulant dosage of 92.2 mg L(-1) (except in the case of the surface water for which the dosage was 2 mg L(-1)). The efficacy of the water purification was notable in every case: total turbidity removal in the surface water and municipal wastewater, about 95% dye removal in the case of the textile industry wastewater, and about 80% surfactant removal in the laundry wastewater. Filtration improved the removal of suspended solids, both flocs and turbidity, and slightly improved the process as a whole. The efficiency of Tanfloc in these pilot studies was similar to or even better than that obtained in batch trials.
Lee Su Jin
Full Text Available Abstract Background In the past few years, the number of clinical trials has increased rapidly in East Asia, especially for gastric and hepatobiliary cancer that are prevalent in Asian populations. However, the actual degree of understanding or perceptions of clinical trials by cancer patients in East Asian countries have seldom been studied. Methods Between July 1st and November 30th of 2011, we conducted a prospective study to survey cancer patients regarding their awareness of, and willingness to participate in, a clinical trial. Patients with gastrointestinal/hepatobiliary cancer who visited the Hematology-Oncology outpatient clinic at Samsung Medical Center (SMC were enrolled. A total of 21 questions were asked including four questions which used the Visual analogue scale (VAS score. Results In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%. The awareness of clinical trials was substantially higher in patients who had a higher level of education (pp=0.004, and had a higher economic status (p=0.001. However, the willingness to participate in a clinical trial was not affected by the level of education or economic status of patients. The most influential factors for patient willingness to participate were a physician recommendation (n=181, 26.8%, limited treatment options (n=178, 26.4%, and expectations of effectiveness of new anti-cancer drugs (n=142, 21.0%. Patients with previous experience in clinical trials had a greater willingness to participate in clinical trials compared to patients without previous experience (p Conclusions This large patient cohort survey study showed that Korean cancer patients are more aware of clinical trials, but awareness did not translate into willingness to participate.
Rosenberg, Jacob; Burcharth, Jakob; Pommergaard, Hans-Christian;
Discussions about authorship often arise in multi-centre clinical trials. Such trials may involve up to hundreds of contributors of whom some will eventually co-author the final publication. It is, however, often impossible to involve all contributors in the manuscript process sufficiently for them...
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 prod
Full Text Available BACKGROUND: The hematopoietic protein Granulocyte-colony stimulating factor (G-CSF has neuroprotective and -regenerative properties. The G-CSF receptor is expressed by motoneurons, and G-CSF protects cultured motoneuronal cells from apoptosis. It therefore appears as an attractive and feasible drug candidate for the treatment of amyotrophic lateral sclerosis (ALS. The current pilot study was performed to determine whether treatment with G-CSF in ALS patients is feasible. METHODS: Ten patients with definite ALS were entered into a double-blind, placebo-controlled, randomized trial. Patients received either 10 µg/kg BW G-CSF or placebo subcutaneously for the first 10 days and from day 20 to 25 of the study. Clinical outcome was assessed by changes in the ALS functional rating scale (ALSFRS, a comprehensive neuropsychological test battery, and by examining hand activities of daily living over the course of the study (100 days. The total number of adverse events (AE and treatment-related AEs, discontinuation due to treatment-related AEs, laboratory parameters including leukocyte, erythrocyte, and platelet count, as well as vital signs were examined as safety endpoints. Furthermore, we explored potential effects of G-CSF on structural cerebral abnormalities on the basis of voxel-wise statistics of Diffusion Tensor Imaging (DTI, brain volumetry, and voxel-based morphometry. RESULTS: Treatment was well-tolerated. No significant differences were found between groups in clinical tests and brain volumetry from baseline to day 100. However, DTI analysis revealed significant reductions of fractional anisotropy (FA encompassing diffuse areas of the brain when patients were compared to controls. On longitudinal analysis, the placebo group showed significant greater and more widespread decline in FA than the ALS patients treated with G-CSF. CONCLUSIONS: Subcutaneous G-CSF treatment in ALS patients appears as feasible approach. Although exploratory analysis of
Full Text Available Abstract Background Randomised controlled clinical (drug trials supply high quality evidence for therapeutic strategies in primary care. Until now, experience with drug trials in German general practice has been sparse. In 2007/2008, the authors conducted an investigator-initiated, non-commercial, double-blind, randomised controlled pilot trial (HWI-01 to assess the clinical equivalence of ibuprofen and ciprofloxacin in the treatment of uncomplicated urinary tract infection (UTI. Here, we report the feasibility of this trial in German general practices and the implementation of Good Clinical Practice (GCP standards as defined by the International Conference on Harmonisation (ICH in mainly inexperienced general practices. Methods This report is based on the experience of the HWI-01 study conducted in 29 German general practices. Feasibility was defined by 1 successful practice recruitment, 2 sufficient patient recruitment, 3 complete and accurate data collection and 4 appropriate protection of patient safety. Results The final practice recruitment rate was 18%. In these practices, 79 of 195 screened UTI patients were enrolled. Recruitment differed strongly between practices (range 0-12, mean 2.8 patients per practice and was below the recruitment goal of approximately 100 patients. As anticipated, practice nurses became the key figures in the screening und recruitment of patients. Clinical trial demands, in particular for completing symptom questionnaires, documentation of source data and reporting of adverse events, did not agree well with GPs' documentation habits and required support from study nurses. In many cases, GPs and practice staff seemed to be overwhelmed by the amount of information and regulations. No sudden unexpected serious adverse reactions (SUSARs were observed during the trial. Conclusions To enable drug trials in general practice, it is necessary to adapt the setup of clinical research infrastructure to the needs of GPs and
Paludan-Müller, Asger Sand; Laursen, David R. T.; Hróbjartsson, Asbjørn
clinical trials. METHODS: Two systematic reviews and a theoretical analysis. We conducted one systematic review of empirical studies of motives/methods for deciphering patient allocation sequences; and another review of methods publications commenting on allocation bias. We theoretically analysed...
Mahesh J. Patel; Cris A. Slentz; William E. Kraus
Randomized clinical trials of exercise training regimens in sedentary individuals have provided a mechanistic understanding of the long-term health benefits and consequences of physical activity and inactivity...
Hanson, Sarah L; Davis, Miriam (Medical writer); Altevogt, Bruce M
"The Food and Drug Administration (FDA) now requires that all clinical trials for drugs that affect the central nervous system--including psychiatric drugs--are assessed for whether that drug might cause suicidal ideation or behavior...
Pedersen, Allan Gorm; Petersen, O B; Wara, P;
BACKGROUND: Laparoscopy in patients with a clinical suspicion of acute appendicitis has not gained wide acceptance, and its use remains controversial. METHODS: In a randomized controlled trial of laparoscopic versus open appendicectomy, 583 of 828 consecutive patients consented to participate...
Kurzrock, Razelle; Stewart, David J
The issue of compliance in a research environment in which investigators are subject to disciplinary action if they fail to ensure that patients adhere precisely to the intense monitoring mandates of a clinical trial is explored.
Mathura, Venkatarajan S; Rangareddy, Mahendiranath; Gupta, Pankaj; Mullan, Michael
Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment. Availability http://www.rfdn.org/bioinfo/CTMS/ctms.html. PMID:21670796
Maecker, Holden T; McCoy, J Philip; Amos, Michael; Elliott, John; Gaigalas, Adolfas; Wang, Lili; Aranda, Richard; Banchereau, Jacques; Boshoff, Chris; Braun, Jonathan; Korin, Yael; Reed, Elaine; Cho, Judy; Hafler, David; Davis, Mark; Fathman, C Garrison; Robinson, William; Denny, Thomas; Weinhold, Kent; Desai, Bela; Diamond, Betty; Gregersen, Peter; Di Meglio, Paola; DiMeglio, Paola; Nestle, Frank O; Nestle, Frank; Peakman, Mark; Villanova, Federica; Villnova, Federica; Ferbas, John; Field, Elizabeth; Kantor, Aaron; Kawabata, Thomas; Komocsar, Wendy; Lotze, Michael; Nepom, Jerry; Ochs, Hans; O'Lone, Raegan; Phippard, Deborah; Plevy, Scott; Rich, Stephen; Roederer, Mario; Rotrosen, Dan; Yeh, Jung-Hua
Complexities in sample handling, instrument setup and data analysis are barriers to the effective use of flow cytometry to monitor immunological parameters in clinical trials. The novel use of a central laboratory may help mitigate these issues.
U.S. Department of Health & Human Services — The National Database for Clinical Trials Related to Mental Illness (NDCT) is an extensible informatics platform for relevant data at all levels of biological and...
A Randomized, Controlled Clinical Trial Comparing Efficacy, Safety and Cost Effectiveness of ... Log in or Register to get access to full text downloads. ... Pharmacological control of pain is the mainstay of management of osteoarthritis.
Research misconduct and fraud in clinical research is an increasing problem facing the scientific community. This problem is expected to increase due to discoveries in central statistical monitoring and with the increase in first-time clinical trial investigators in the increasingly global reach of oncology clinical trials. This paper explores the most common forms of fraud in clinical trials in order to develop offensive and defensive strategies to deal with fraud. The offensive strategies are used when fraud is detected during a trial and the defensive strategies are those design strategies that seek to minimize or eliminate the effect of fraud. This leads to a proposed fraud recovery plan (FRP) that would be specified before the start of a clinical trial and would indicate actions to be taken upon detecting fraud of different types. Statistical/regulatory issues related to fraud include: dropping all patients from a site that committed fraud, or just the fraudulent data (perhaps replacing the latter through imputation); the role of intent-to-treat analysis; effect on a planned interim analysis; effect on stratified analyses and model adjustment when fraud is detected in covariates; effect on trial-wide randomization, etc. The details of a typical defensive strategy are also presented. It is concluded that it is best to follow a defensive strategy and to have an FRP in place to follow if fraud is detected during the trial.
Full Text Available Background. “Fructus Mume or Dark Plum” (pilule form has been used for many years in Traditional Chinese Medicine (TCM and may be a valid treatment for type 2 diabetes mellitus (T2DM. Aim. One aspect toward efficacy validation is the evaluation of the blood glucose-lowering effect of Fructus Mume (FM with T2DM patients in a randomized controlled trial (RCT. Methods. This pilot study uses a RCT procedure to assess efficacy of FM and Metformin. The trial was for 12 weeks, with 80 T2DM subjects. Both groups were standardized in their diet and exercise routine. Comparisons of several variables were analyzed. Results. No significant differences were found between groups in the fasting and postprandial glucose levels although both had significant decreases. The values of glycosylated hemoglobin were significantly reduced in both groups. For patients whose body mass index (BMI was 25, both FM and Metformin significantly reduce the BMI. Conclusions. In this pilot study, it was demonstrated that Fructus Mume formula may reduce the levels of blood glucose in patients with type 2 diabetes.
Soral, P.; Pal, U.; Larson, H. R.; Schroeder, B.
A laboratory-scale galvanic deoxidation technology developed by earlier workers has been improved, with the aim of developing a prototype pilot-scale deoxidation unit. Each deoxidation cell consists of a one end-closed yttria-stabilized zirconia (YSZ) tube coated with a Ni-YSZ cermet anode on the inner walls. The YSZ tube is immersed, with its closed end in the metallic melt, and an oxygen-chemical-potential gradient across the tube is established by passing a reducing gas through the tube. The melt is then deoxidized by short circuiting it with the anode. Through laboratory experimentation, the nature of the anode/electrolyte interface adhesion was identified to be an important factor in obtaining enhanced deoxidation kinetics. The kinetics of oxygen removal from the melt was increased by an order of magnitude with an improved anode/electrolyte interface. A pilot-scale refining unit consisting of 53 cells with the improved anode/electrolyte interface was manufactured, and a field evaluation of the galvanic deoxidation of copper was conducted. The deoxidation-process model was modified to include multiple deoxidation cells, which were required for the pilot-scale trials, and to analyze the effect of electrolyte/electrode adhesion on deoxidation kinetics. Preliminary studies on process component lifetimes were conducted by investigating the thermal cycling, corrosion behavior of the electrolyte, and stability of the cermet anode structure. Based on the results of the field trial and the analyses of the process component lifetime, future work needed toward commercializing the technology is discussed.
Zhang, Xiaoming; Osborn, Thomas; Zhou, Boran; Meixner, Duane; Kinnick, Randall R; Bartholmai, Brian; Greenleaf, James F; Kalra, Sanjay
A lung ultrasound surface wave elastography (LUSWE) technique is developed to measure superficial lung tissue elastic properties. The purpose of this paper was to translate LUSWE into clinical studies for assessing patients with interstitial lung disease (ILD) and present the pilot data from lung measurements on 10 healthy subjects and 10 patients with ILD. ILD includes multiple lung disorders in which the lung tissue is distorted and stiffened by tissue fibrosis. Chest radiography and computed tomography are the most commonly used techniques for assessing lung disease, but they are associated with radiation and cannot directly measure lung elastic properties. LUSWE provides a noninvasive and nonionizing technique to measure the elastic properties of superficial lung tissue. LUSWE was used to measure regions of both lungs through six intercostal spaces for patients and healthy subjects. The data are presented as wave speed at 100, 150, and 200 Hz at the six intercostal spaces. As an example, the surface wave speeds are, respectively, 1.88 ± 0.11 m/s at 100 Hz, 2.74 ± 0.26 m/s at 150 Hz, and 3.62 ± 0.13 m/s at 200 Hz for a healthy subject in the upper right lung; this is in comparison to measurements from an ILD patient of 3.3 ± 0.37 m/s at 100 Hz, 4.38 ± 0.33 m/s at 150 Hz, and 5.24 ± 0.44 m/s at 200 Hz in the same lung space. Significant differences in wave speed between healthy subjects and ILD patients were found. LUSWE is a safe and noninvasive technique which may be useful for assessing ILD.
Ricardo Sanz-Ruiz; Enrique Gutiérrez Ibañes; Adolfo Villa Arranz; María Eugenia Fernández Santos; Pedro L. Sánchez Fernández; Francisco Fernández-Avilés
First randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease. Nevertheless, some trials have shown that conflicting results and uncertainties remain in the case of mechanisms of action and possible ways to improve clinical impact of stem cells in cardiac repair. In this paper we will examine the evidence available, analyze the main phase I and II randomize...
Multi - Agent System for Recruiting Patients for Clinical Trials Samhar Mahmoud King’s College London London, UK firstname.lastname@example.org Gareth Tyson...TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Multi - Agent System for Recruiting Patients for Clinical Trials 5a...methodology  was proposed to guide the process of de- veloping a multi - agent system from analysis to design. For brevity, we focus here on one
Barker, Anna L; Talevski, Jason; Bohensky, Megan A; Brand, Caroline A; Cameron, Peter A; Morello, Renata T
To evaluate the feasibility of Pilates exercise in older people to decrease falls risk and inform a larger trial. Pilot Randomized controlled trial. Community physiotherapy clinic. A total of 53 community-dwelling people aged ⩾60 years (mean age, 69.3 years; age range, 61-84). A 60-minute Pilates class incorporating best practice guidelines for exercise to prevent falls, performed twice weekly for 12 weeks. All participants received a letter to their general practitioner with falls risk information, fall and fracture prevention education and home exercises. Indicators of feasibility included: acceptability (recruitment, retention, intervention adherence and participant experience survey); safety (adverse events); and potential effectiveness (fall, fall injury and injurious fall rates; standing balance; lower limb strength; and flexibility) measured at 12 and 24 weeks. Recruitment was achievable but control group drop-outs were high (23%). Of the 20 participants who completed the intervention, 19 (95%) attended ⩾75% of the classes and reported classes were enjoyable and would recommend them to others. The rate of fall injuries at 24 weeks was 42% lower and injurious fall rates 64% lower in the Pilates group, however, was not statistically significant (P = 0.347 and P = 0.136). Standing balance, lower-limb strength and flexibility improved in the Pilates group relative to the control group (P Pilates in older people would be feasible and is warranted given the acceptability and potential positive effects of Pilates on fall injuries and fall risk factors. The protocol for this study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN1262000224820). © The Author(s) 2015.
Conclusions: Our pilot observation suggests scrub typhus is common in females and in younger age groups. These findings need further exploration in a large, prospective, trial in confirmed cases of scrub typhus. [Int J Res Med Sci 2016; 4(11.000: 4898-4902
Full Text Available BACKGROUND: Cough is listed as an adverse drug reaction (ADR on the labels of angiotensin receptor blockers (ARB. However, a causal association with cough has also been reported for angiotensin converting enzyme inhibitors (ACEI, which have frequently been used as comparator drugs in the registration clinical trials of ARBs. This prompted us to examine the possible influence of using comparator drugs with well-known ADRs on the safety reporting of investigational drugs in blinded randomized clinical trials. METHODS AND FINDINGS: The double-blinded, randomized clinical trials with comparator drugs were identified in the Japanese dossiers for the new drug applications of ARBs. The risk ratios (RR of reporting cough and headache in ARB arms were calculated for each ARB by comparing trials using ACEIs and trials using non-ACEIs, were then combined with a meta-analysis. 23 trials with a total of 6643 patients were identified, consisting 6 trials using an ACEI comparator including 819 ARB patients and 17 trials using a non-ACEI comparator including 5824 ARB patients. The combined RR of cough reporting was significantly elevated (20.77; 95% confidence interval [CI], 7.47 to 57.76, indicating more frequent reporting of cough in clinical trials using an ACEI comparator. In contrast, the combined RR of headache, a negative control, was insignificant (1.45; 95% CI, 0.34 to 6.22. CONCLUSION: The use of comparators with well-known ADRs in blinded randomized trials produces potential bias in the reporting frequency of ADRs for investigational drugs. The selection of appropriate comparator drugs should be critical in unbiased safety assessment in double-blinded, randomized clinical trials and thus have relevance in reviewing the safety results from a regulatory point of view.
Kollmann, Martina; Aldrian, Lisa; Scheuchenegger, Anna; Mautner, Eva; Herzog, Sereina A.; Urlesberger, Berndt; Raggam, Reinhard B.; Lang, Uwe; Obermayer-Pietsch, Barbara; Klaritsch, Philipp
Objective Early bonding by skin-to-skin contact (SSC) has been demonstrated to be beneficial for mothers and newborns following vaginal delivery. The aim of this study was to investigate the impact of intraoperative bonding (early SSC) after cesarean section on neonatal adaptation, maternal pain and stress response. Study design This prospective, randomized-controlled pilot study was performed at a single academic tertiary hospital (Department of Obstetrics and Gynecology, Medical University of Graz, Austria) between September 2013 and January 2014. Women were randomly assigned to intraoperative (“early”) SCC (n = 17) versus postoperative (“late”) SCC (n = 18). Main variables investigated were neonatal transition (Apgar score, arterial oxygen saturation, heart rate and temperature), maternal pain perception and both maternal and neonatal stress response by measuring the stress biomarkers salivary free cortisol and salivary alpha amylase. Results There was no evidence for differences in parameters reflecting neonatal transition or stress response between the ‘Early SSC Group’ and the ‘Late SSC Group’. Maternal salivary cortisol and alpha-amylase levels as well as maternal wellbeing and pain did not differ between the groups. However, the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’ (p = 0.004). Conclusions This study did not reveal significant risks for the newborn in terms of neonatal transition when early SSC is applied in the operating room. Maternal condition and stress marker levels did not differ either, although the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’, which may indicate a stressor sign due to intensive activation of the sympathetic-adreno-medullary-system. This needs to be further evaluated in a larger prospective randomized trial. Trial
Singhal, Richa; Rana, Rakesh
Missing data is frequently encountered in clinical studies. Unfortunately, they are often neglected or not properly handled during data analysis and this may significantly bias the results of the study, reduce study power and lead to invalid conclusions. Substantial instances of missing data are a serious problem that undermines the scientific trustworthiness of causal conclusions from clinical trials. The assumption that statistical analysis methods can compensate for such missing data is not justified. Hence aspects of clinical trial design that limit the probability of missing data should be an important objective, while planning a clinical trial. In addition to specific aspects of trial design, many components of clinical trial conduct can also limit the extent of missing data. The topic of missing data is often not a major concern until it is time for data collection and data analysis. This article discusses some basic issues about missing data as well as prospective "watch outs" which could reduce the occurrence of missing data. It provides some possible design considerations that should be considered in order to alleviate patients from dropping out of a clinical trial. In addition to these the concept of the missing data mechanism has also been discussed. Three types of missing data mechanisms missing completely at random, missing at random and not missing at random have been discussed in detail.
Gonçalves, Giulliano Peixoto; Barbosa, Fabiano Timbó; Barbosa, Luciano Timbó; Duarte, José Lira
A randomized clinical trial is a prospective study that compares the effect and value of interventions in human beings, of one or more groups vs. a control group. The objective of this study was to evaluate the quality of published randomized clinical trials in Intensive care in Brazil. All randomized clinical trials in intensive care found by manual search in Revista Brasileira de Terapia Intensiva from January 2001 to March 2008 were assessed to evaluate their description by the quality scale. Descriptive statistics and a 95 % confidence interval were used for the primary outcome. Our primary outcome was the randomized clinical trial quality. Our search found 185 original articles, of which 14 were randomized clinical trials. Only one original article (7.1%) showed good quality. There was no statistical significance between the collected data and the data shown in the hypothesis of this search. It can be concluded that in the sample of assessed articles 7% of the randomized clinical trials in intensive care published in a single intensive care journal in Brazil, present good methodological quality.
Alemayehu, Demissie; Anziano, Richard J; Levenstein, Marcia
The increased demand for transparency and disclosure of data from clinical trials sponsored by pharmaceutical companies poses considerable challenges and opportunities from a statistical perspective. A central issue is the need to protect patient privacy and adhere to Good Clinical and Statistical Practices, while ensuring access to patient-level data from clinical trials to the wider research community. This paper offers options to navigate this dilemma and balance competing priorities, with emphasis on the role of good clinical and statistical practices as proven safeguards for scientific integrity, the importance of adopting best practices for reporting of data from secondary analyses, and the need for optimal collaboration among stakeholders to facilitate data sharing.
Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.
Photodynamic therapy(PDT) has been demonstrated to effectively kill human periopathogens in vitro. To evaluate the efficacy of PDT in vivo a series of clinical trials was carried out in multiple centers and populations. Clinical parameters including clinical attachment level, pocket probing depth and bleeding on probing were all evaluated. All groups received the standard of care, scaling and root planing, and the treatment group additionally received a single treatment of PDT. Of the total 309 patients and over 40,000 pockets treated in these 5 trials it was determined that photodynamic therapy provided a statistically significant improvement in clinical parameters over scaling and root planing alone.
Background Qualitative research methods are increasingly used within clinical trials to address broader research questions than can be addressed by quantitative methods alone. These methods enable health professionals, service users, and other stakeholders to contribute their views and experiences to evaluation of healthcare treatments, interventions, or policies, and influence the design of trials. Qualitative data often contribute information that is better able to reform policy or influence design. Methods Health services researchers, including trialists, clinicians, and qualitative researchers, worked collaboratively to develop a comprehensive portfolio of standard operating procedures (SOPs) for the West Wales Organisation for Rigorous Trials in Health (WWORTH), a clinical trials unit (CTU) at Swansea University, which has recently achieved registration with the UK Clinical Research Collaboration (UKCRC). Although the UKCRC requires a total of 25 SOPs from registered CTUs, WWORTH chose to add an additional qualitative-methods SOP (QM-SOP). Results The qualitative methods SOP (QM-SOP) defines good practice in designing and implementing qualitative components of trials, while allowing flexibility of approach and method. Its basic principles are that: qualitative researchers should be contributors from the start of trials with qualitative potential; the qualitative component should have clear aims; and the main study publication should report on the qualitative component. Conclusions We recommend that CTUs consider developing a QM-SOP to enhance the conduct of quantitative trials by adding qualitative data and analysis. We judge that this improves the value of quantitative trials, and contributes to the future development of multi-method trials. PMID:23433341
Awerbach, Jordan D; Krasuski, Richard A; Hill, Kevin D
The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n = 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n = 18, 39%). Single group study designs were used in 44% (n = 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n = 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized.
Full Text Available The past 30 years have seen rapid growth in the number of clinical trials in liver disease; due mostly to effective drug discovery programs by the pharmaceutical industry. The advantages associated with therapeutic trials in chronic liver disease, or any other disease for that matter, go far beyond potential benefit to the individual patient, other beneficiaries include the treating physician, the sponsoring agency and their investors, the institution/university and the general public. But there is always a downside to any experiment. The disadvantages and advantages of clinical trials in liver disease are the topics for this discussion.
Muirhead, Robb J
This paper explores an approach to Bayesian sample size determination in clinical trials. The approach falls into the category of what is often called "proper Bayesian", in that it does not mix frequentist concepts with Bayesian ones. A criterion for a "successful trial" is defined in terms of a posterior probability, its probability is assessed using the marginal distribution of the data, and this probability forms the basis for choosing sample sizes. We illustrate with a standard problem in clinical trials, that of establishing superiority of a new drug over a control.
created military Vision Center of Excellence in NEER steering committee meetings and deliberations. References: 1. Cideciyan AV, Aleman TS, Boye SL, et...2008;105:15112-15117. 2. Hauswirth W, Aleman TS, Kaushal S, et al. Phase I Trial of Leber Congenital Amaurosis due to RPE65 Mutations by Ocular
A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom
Smed, Marie; Getz, Kenneth A
Knowledge generated by site representatives through their participation in clinical trials is valuable for testing new products in use and obtaining final market approval. The leverage of this important knowledge is however challenged as the former direct relationships between in-house staff in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract Research Organization) and thereby adding another link in the relationships between site and sponsor. These changes are intended to optimize the time-consuming and costly trial phases; however, there is a need to study whether valuable knowledge and experience is compromised in the process. Limited research exists on the full range of clinical practice insights obtained by investigators during and after clinical trials and how well these insights are transferred to study sponsors. This study explores the important knowledge-transfer processes between sites and sponsors and to what extent sites' knowledge gained in clinical trials is utilized by the industry. Responses from 451 global investigative site representatives are included in the study. The analysis of the extensive dataset reveals that the current processes of collaboration between sites and the industry restrict the leverage of valuable knowledge gained by physicians in the process of clinical trials. These restrictions to knowledge-transfer between site and sponsor are further challenged if CRO partners are integrated in the trial process.
Abdullah, Kawsari; Thorpe, Kevin E; Mamak, Eva; Maguire, Jonathon L; Birken, Catherine S; Fehlings, Darcy; Hanley, Anthony J; Macarthur, Colin; Zlotkin, Stanley H; Parkin, Patricia C
The OptEC trial aims to evaluate the effectiveness of oral iron in young children with non-anemic iron deficiency (NAID). The initial sample size calculated for the OptEC trial ranged from 112-198 subjects. Given the uncertainty regarding the parameters used to calculate the sample, an internal pilot study was conducted. The objectives of this internal pilot study were to obtain reliable estimate of parameters (standard deviation and design factor) to recalculate the sample size and to assess the adherence rate and reasons for non-adherence in children enrolled in the pilot study. The first 30 subjects enrolled into the OptEC trial constituted the internal pilot study. The primary outcome of the OptEC trial is the Early Learning Composite (ELC). For estimation of the SD of the ELC, descriptive statistics of the 4 month follow-up ELC scores were assessed within each intervention group. The observed SD within each group was then pooled to obtain an estimated SD (S2) of the ELC. Correlation (ρ) between the ELC measured at baseline and follow-up was assessed. Recalculation of the sample size was performed using analysis of covariance (ANCOVA) method which uses the design factor (1- ρ(2)). Adherence rate was calculated using a parent reported rate of missed doses of the study intervention. The new estimate of the SD of the ELC was found to be 17.40 (S2). The design factor was (1- ρ2) = 0.21. Using a significance level of 5%, power of 80%, S2 = 17.40 and effect estimate (Δ) ranging from 6-8 points, the new sample size based on ANCOVA method ranged from 32-56 subjects (16-28 per group). Adherence ranged between 14% and 100% with 44% of the children having an adherence rate ≥ 86%. Information generated from our internal pilot study was used to update the design of the full and definitive trial, including recalculation of sample size, determination of the adequacy of adherence, and application of strategies to improve adherence. ClinicalTrials.gov Identifier: NCT
Concannon, Thomas W; Guise, Jeanne-Marie; Dolor, Rowena J; Meissner, Paul; Tunis, Sean; Krishnan, Jerry A; Pace, Wilson D; Saltz, Joel; Hersh, William R; Michener, Lloyd; Carey, Timothy S
An important challenge in comparative effectiveness research is the lack of infrastructure to support pragmatic clinical trials, which compare interventions in usual practice settings and subjects. These trials present challenges that differ from those of classical efficacy trials, which are conducted under ideal circumstances, in patients selected for their suitability, and with highly controlled protocols. In 2012, we launched a 1-year learning network to identify high-priority pragmatic clinical trials and to deploy research infrastructure through the NIH Clinical and Translational Science Awards Consortium that could be used to launch and sustain them. The network and infrastructure were initiated as a learning ground and shared resource for investigators and communities interested in developing pragmatic clinical trials. We followed a three-stage process of developing the network, prioritizing proposed trials, and implementing learning exercises that culminated in a 1-day