Science.gov

Sample records for clinical trials conducted

  1. [Difficulties with conducting clinical trials in France].

    PubMed

    Zannad, F; Plétan, Y

    2001-01-01

    France ranks third among European countries as regards the level of investment in clinical R&D and, overall, accounts for a contributive effort proportional to the size of its population and pharmaceutical market respectively. However, there is a trend for phase II and III studies to become proportionally fewer than in the past, while the number of phase IV studies is increasing. In a growing proportion of the mega-trials, which are instrumental for establishing evidence-based practice, French experts, investigators and, even more seriously, French patients, are insufficiently represented. Though studies in France are initiated relatively fast due to a clear regulatory framework and perform equally well as far as quantitative and qualitative factors are concerned, compared with most European countries involved in clinical research the costs incurred per completed patient are higher than those recorded in the other countries. Academic research shares most of these constraints and suffers from a lack of financial and human resources, while it faces additional delays in implementing studies because of longer administrative processes. Given the stakes in play, specific solutions should be implemented to maintain and further develop French competitiveness in clinical R&D. At the patient level, positive perception and awareness of the usefulness and safety of participating in clinical trials need to be emphasized. Education at the school level and using the lay media should be developed. Intervention of institutional and government officials is much needed. Direct patient recruitment should be developed through advertisement and the Internet, as well as within doctors' offices and through collaboration with patients' organizations. Patient information and consent forms should be made much simpler than those imposed within the framework of global studies because of FDA requirements. The French health system discourages the recruitment of patients by investigators who are

  2. Access to medications and conducting clinical trials in LMICs.

    PubMed

    Okpechi, Ikechi G; Swanepoel, Charles R; Venter, Francois

    2015-03-01

    Access to essential medications is limited in many low-to-middle income countries (LMICs) and those that are available may be prohibitively expensive to the general population. Clinical trials have been suggested as an approach to improve drug access in LMICs but the number of trials conducted in these countries is small because of regulatory issues and a lack of infrastructure. In this article, Nature Reviews Nephrology asks three experts their opinions on how to improve drug access and increase the numbers of clinical trials conducted in LMICs. PMID:25668002

  3. 21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... and evaluation of clinical trials. For drugs covered under this section, the Commissioner and other agency officials will monitor the progress of the conduct and evaluation of clinical trials and...

  4. 21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... and evaluation of clinical trials. For drugs covered under this section, the Commissioner and other agency officials will monitor the progress of the conduct and evaluation of clinical trials and...

  5. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of surgical interventions for osteoarthritis

    PubMed Central

    Katz, J.N.; Losina, E.; Lohmander, L.S.

    2015-01-01

    summary 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 each challenge raised in the paper, we propose potential solutions. Enrollment poses challenges in maintaining investigator equipoise, managing conflict of interest and anticipating that patient preferences for specific treatments may reduce enrollment. Intervention design and implementation pose challenges relating to obsolescence, fidelity of intervention delivery, and adherence and crossover. Assessment and analysis raise questions regarding blinding and clustering of observations. This paper describes methodological problems in the design and conduct of surgical randomized trials and proposes strategies for addressing these challenges. PMID:25952350

  6. Potential Risks and Mitigation Strategies Before the Conduct of a Clinical Trial: An Industry Perspective.

    PubMed

    Bhagat, Seema; Kapatkar, Vaibhavi K; Mourya, Meenakshi; Roy, Sucheta; Jha, Shailendra; Reddy, Rajasekhar; Kadhe, Ganesh; Mane, Amey; Sawant, Sandesh

    2016-01-01

    Conduct of clinical trials has undergone substantial changes over the last two decades. Newer markets, evolving guidelines and documentation and high cost involved in conducting the trials have led pharmaceutical companies to prepare a risk mitigation plan. Extensive monitoring of potential risks is an essential element of clinical trials which helps to ensure quality and integrity of a clinical investigation. Every clinical trial has pre (before the trial), conduct and post phase. This article which has been developed as a result of extensive research at ground level by a reputed pharmaceutical company to identify the potential stages of risks that could affect the overall quality and safety of a trial and its outcome during the pre-phase of trial (the stage of the trial where the study design is being planned before initiation of the clinical trial). It includes risks associated with basic study concept, protocol design, Confidential Disclosure Agreement (CDA) and Clinical Trial Authorization (CTA) application signing, vendors of central drug laboratory, site and investigator selection, Clinical Research Coordinator (CRC) meet, Informed Consent Form (ICF), Case Report Form (CRF)/ Status Report Form (SRF) preparation, Ethics Committee (EC) submission, etc. have been highlighted. The risk based mitigation strategy (to develop an effective risk monitoring plan before staring a clinical trial) has also been suggested by authors. A well-tailored and integrated plan, recognition of potential risks and their mitigation strategy can result in the pre exclusion or end to end solution of all the risks associated with pre- phase of clinical trials. PMID:26435140

  7. The global conduct of cancer clinical trials: challenges and opportunities.

    PubMed

    Barrios, Carlos H; Werutsky, Gustavo; Martinez-Mesa, Jeovany

    2015-01-01

    The nature of clinical research has changed substantially over the last 2 decades, evolving from being centered almost exclusively in developed countries to a more global scenario that is increasingly involving less developed regions of the world. Pharmaceutical companies and some academic cooperative groups have been conducting challenging, large pivotal registration studies with multinational participation. The much more needed globalization of academic research demands particular attention and represents a worthwhile subject for a more profound discussion. The requirement of large sample sizes and the potential for fast recruitment leading to a speedy completion of clinical studies are probably the most important factors that have fueled globalization of studies. Reduced operational costs and the ability to expedite the regulatory approval of drugs in various countries or regions are also important drivers. Globalization of research should be seen as having a much wider effect in the societies involved, in particular, when we consider public health, economic, social, and ethical implications. Most importantly, the process of expanding the network of clinical research sites also fosters the integration and the development of closer relationships among investigators at a global level. We consider this an essential element that should remain a prominent element in the discussion. In this article, we address the underlying reasons for globalization and we highlight some of the scientific and ethical concerns arising as a consequence. Finally, some strategies to address and mitigate the challenges of conducting multinational clinical research are proposed. PMID:25993164

  8. Conducting feasibilities in clinical trials: an investment to ensure a good study.

    PubMed

    Rajadhyaksha, Viraj

    2010-07-01

    Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative. PMID:21814631

  9. 75 FR 37818 - Issues in the Design and Conduct of Clinical Trials for Antibacterial Drug Development; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ... clinical trial design and the types of infectious disease indications for which the NI clinical trial... HUMAN SERVICES Food and Drug Administration Issues in the Design and Conduct of Clinical Trials for... regarding scientific issues in the design and conduct of clinical trials for antibacterial drug...

  10. Justification for conducting neurological clinical trials as part of patient care within private practice.

    PubMed

    Beran, R G; Stepanova, D; Beran, M E

    2016-05-01

    The aim of this review was to assess the benefits and drawbacks of conducting neurological clinical trials and research in private practice for the patients, clinician, Practice Manager, sponsors/Clinical Research Organisations (CROs) and Clinical Trial Coordinator (CTC) to determine if this is justified for all involved. A combination of literature reviews, original research articles and books were selected from 2005 to 2015. Provided that the practice has sufficient number of active trials to prevent financial loss, support staff, adequate facilities and equipment and time, the benefits outweigh the drawbacks. Clinical trials provide patients with more thorough monitoring, re-imbursement of trial-related expenses and the opportunity to try an innovative treatment at no charge when other options have failed. For the clinician, clinical trials provide more information to ensure better care for their patients and improved treatment methods, technical experience and global recognition. Trials collect detailed and up-to-date information on the benefits and risks of drugs, improving society's confidence in clinical research and pharmaceuticals, allow trial sponsors to explore new scientific questions and accelerate innovation. For the CTC, industry-sponsored clinical trials allow potential entry for a career in clinical research giving CTCs the opportunity to become Clinical Research Associates (CRAs), Study Start-Up Managers or Drug Safety Associates. PMID:27040457

  11. A critical appraisal of clinical trials conducted and subsequent drug approvals in India and South Africa

    PubMed Central

    Limaye, Dnyanesh; Langer, Janka Marisa; Rühling, Tjorben; Fortwengel, Gerhard

    2015-01-01

    Objectives To assess the relation between the number of clinical trials conducted and respective new drug approvals in India and South Africa. Design Construction and analysis of a comprehensive database of completed randomised controlled clinical trials based on clinicaltrials.gov from 1 January 2005 to 31 December 2010 and drug approval data from 2006 until 2013 for India and South Africa. Setting USA, the EU, India and South Africa. Main outcome measures Percentage of completed randomised clinical trials for an Investigational Medicinal Product (IMP) leading to new drug approval in India and South Africa. Results A total of 622 eligible randomised controlled trials were identified as per search criteria for India and South Africa. Clustering them for the same sponsor and the same Investigational New Drug (IND) resulted in 453 eligible trials, that is, 224 for India and 229 for South Africa. The distribution of the market application approvals between the EU/USA as well as India and South Africa revealed that out of clinical trials with the participation of test centres in India and/or South Africa, 39.6% (India) clinical trials and 60.1% (South Africa) clinical trials led to market authorisation in the EU/USA without a New Drug Application (NDA) approval in India or South Africa. Conclusions Despite an increase in clinical trial activities, there is a clear gap between the number of trials conducted and market availability of these new drugs in India and South Africa. Drug regulatory authorities, investigators, institutional review boards and patient groups should direct their efforts to ensuring availability of new drugs in the market that have been tested and researched on their population. PMID:26324720

  12. Prevalence and Characteristics of Interventional Trials Conducted Exclusively in Elderly Persons: A Cross-Sectional Analysis of Registered Clinical Trials

    PubMed Central

    Bourgeois, Florence T.; Olson, Karen L.; Tse, Tony; Ioannidis, John P. A.; Mandl, Kenneth D.

    2016-01-01

    Background Elderly patients represent the greatest consumers of healthcare per capita but have historically been underrepresented in clinical trials. It is unknown how many trials are designed to focus exclusively on elderly patients. Objective To define the prevalence of interventional trials that study exclusively elderly persons and describe the characteristics of these trials, including their distribution across conditions most prevalent in the elderly. Design All interventional clinical trials enrolling exclusively elderly patients (≥65 years), conducted primarily in high-income countries, and initiated between 2006 and 2014, identified through ClincialTrials.gov. Main Measures Trials were identified and characterized according to design features and disease categories studied. Across disease categories we examined the burden of disease in the elderly in high-income countries (measured in disability-adjusted life years [DALYs]) and compared to the number of trials conducted exclusively in the elderly. Results Among 80,965 interventional trials, 1,112 (1.4%) focused on elderly patients. Diverse types of interventions were studied in these trials (medications 33%, behavioral interventions 18%, and dietary supplements 10%) and the majority was funded by non-profit organizations (81%). Studies tended to be small (median sample size 122 participants [IQR 58, 305]), single-center studies (67%). Only 43% of 126 disease categories affecting elderly persons were studied in trials focused on the elderly. Among these disease categories, there was a 5162-fold range in the ratio of DALYs per trial. Across 5 conditions where over 80% of DALYs are in the elderly, there were a total of only 117 trials done exclusively in the elderly. Conclusions Very few and mostly small studies are conducted exclusively in elderly persons, even for conditions that affect almost exclusively the elderly. PMID:27196289

  13. Testing ground GDR: Western pharmaceutical firms conducting clinical trials behind the Iron Curtain.

    PubMed

    Erices, Rainer; Frewer, Andreas; Gumz, Antje

    2015-07-01

    Western pharmaceutical companies conducted clinical trials in the Eastern Bloc during the Cold War. Recently, media reports about alleged human experimentation provoked a wave of indignation. However, a scientific and objective account of these trials is lacking. The aim of this study was to describe and evaluate the clinical trials performed in the German Democratic Republic (GDR) based on archival material from the health system and the secret service. We found documents relating to 220 trials involving more than 14,000 patients and 68 Western companies. However, no record of patient information forms or systematic documentation regarding the provision of patient consent was discovered. There was no evidence to suggest that the trials systematically and intentionally damaged patients. The trials were conducted without the knowledge of the public. GDR legislation stipulated that patients must consent to the trials, but no evidence was found to suggest that patients were systematically informed. Documents suggest that at least some of the trials were carried out without patients having a comprehensive understanding of what the trial involved. The GDR agreed to the trials due to impending bankruptcy and Western pharmaceutical companies capitalised on this situation. PMID:25341732

  14. Improving cardiovascular clinical trials conduct in the United States: recommendation from clinicians, researchers, sponsors, and regulators.

    PubMed

    Butler, Javed; Fonarow, Gregg C; O'Connor, Christopher; Adams, Kirkwood; Bonow, Robert O; Cody, Robert J; Collins, Sean P; Dunnmon, Preston; Dinh, Wilfried; Fiuzat, Mona; Georgiopoulou, Vasiliki V; Grant, Stephen; Kim, So-Young; Kupfer, Stuart; Lefkowitz, Martin; Mentz, Robert J; Misselwitz, Frank; Pitt, Bertram; Roessig, Lothar; Schelbert, Erik; Shah, Monica; Solomon, Scott; Stockbridge, Norman; Yancy, Clyde; Gheorghiade, Mihai

    2015-03-01

    Advances in medical therapies leading to improved patient outcomes are in large part related to successful conduct of clinical trials that offer critical information regarding the efficacy and safety of novel interventions. The conduct of clinical trials in the United States, however, continues to face increasing challenges with recruitment and retention. These trends are paralleled by an increasing shift toward more multinational trials where most participants are enrolled in countries outside the United States, bringing into question the generalizability of the results to the American population. This manuscript presents the perspectives and recommendations from clinicians, researchers, sponsors, and regulators who attended a meeting facilitated by the Food and Drug Administration to improve upon the current clinical trial trends in the United States. PMID:25728719

  15. Clinical Trials

    MedlinePlus

    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 ...

  16. Clinical Trials

    MedlinePlus

    Clinical trials are research studies that test how well new medical approaches work in people. Each study ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to ...

  17. OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

    PubMed

    Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

    2015-05-01

    The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. PMID:25952349

  18. Research Areas: Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  19. Research Areas - Clinical Trials

    Cancer.gov

    Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

  20. Use of mifepristone to treat endometriosis: a review of clinical trials and trial-like studies conducted in China.

    PubMed

    Guo, Sun-Wei; Liu, Maohua; Shen, Fanghua; Liu, Xishi

    2011-01-01

    China was the first country in the world that approved mifepristone (RU-486) for abortion. A total of 6 years after the report published in the Western world indicated that mifepristone may also be effective in treating endometriosis, the first paper on the same topic was published in China in 1997. Since then, over 160 studies on this topic have been published in China. We retrieved 104 papers on clinical trials and trial-like studies conducted in China evaluating the use of mifepristone to treat endometriosis that were published in the last 11 years. We found that the quality of these studies is well below an acceptable level, making it difficult to judge whether mifepristone is truly efficacious. There are intriguing signs that these studies, as a whole, have serious anomalies. The areas that are glaringly deficient are informed consent, choice of outcome measures, the evaluation of outcome measures, data analysis and randomization. The uniformly low quality is disquieting, given the large quantity of studies, the enormous amount of resource and energy put into these studies and, above all, the weighty issue of treatment efficacy that concerns each and every patient with endometriosis. Equally disquieting are the low-quality repetition, the absence of a critical, systematic review on the subject, the lack of suggestions for multicenter clinical trials and the seemingly unnecessary duplication of clinical trials without due informed consent. In view of this, it may be time to institute changes in attitude and practice, and to change education and training programs in the methodology of clinical trials in obstetrics and gynecology research in China. PMID:21175391

  1. To conduct clinical trial in China, to go or not to go.

    PubMed

    Kong, Liang

    2014-01-01

    In the last 10 years, more and more clinical trials have come to China because of potential market/easy access of patient and cost-effectiveness, but if we look back, there had been minimum changes on the regulatory requirements, and there is a possibility that China government could further strengthen the regulatory requirements for the global pharma/foreign pharma. In 2013, there was a breaking news that China government would start to investigate the corruption of GSK. So now, should the global pharma/foreign pharma go to China to conduct clinical trial? If the sponsor wants to access China market and provide unmet medical needs to China market, there are still many opportunities and there are ways to get all of these barriers resolved. PMID:25329485

  2. Clinical Trials

    MedlinePlus

    ... of visits, and any adjustments to treatment. (back) Requirements for Participation Admission into a clinical trial is based on a rigid set of requirements. You must be diagnosed with the illness that ...

  3. Readability of informed consent forms in clinical trials conducted in a skin research center

    PubMed Central

    Samadi, Aniseh; Asghari, Fariba

    2016-01-01

    Obtaining informed consents is one of the most fundamental principles in conducting a clinical trial. In order for the consent to be informed, the patient must receive and comprehend the information appropriately. Complexity of the consent form is a common problem that has been shown to be a major barrier to comprehension for many patients. The objective of this study was to assess the readability of different templates of informed consent forms (ICFs) used in clinical trials in the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran, Iran. This study was conducted on ICFs of 45 clinical trials of the CRTSDL affiliated with Tehran University of Medical Sciences. ICFs were tested for reading difficulty, using the readability assessments formula adjusted for the Persian language including the Flesch–Kincaid reading ease score, Flesch–Kincaid grade level, and Gunning fog index. Mean readability score of the whole text of ICFs as well as their 7 main information parts were calculated. The mean ± SD Flesch Reading Ease score for all ICFs was 31.96 ± 5.62 that is in the difficult range. The mean ± SD grade level was calculated as 10.71 ± 1.8 (8.23–14.09) using the Flesch–Kincaid formula and 14.64 ± 1.22 (12.67–18.27) using the Gunning fog index. These results indicate that the text is expected to be understandable for an average student in the 11th grade, while the ethics committee recommend grade level 8 as the standard readability level for ICFs. The results showed that the readability scores of ICFs assessed in our study were not in the acceptable range. This means they were too complex to be understood by the general population. Ethics committees must examine the simplicity and readability of ICFs used in clinical trials. PMID:27471590

  4. Readability of informed consent forms in clinical trials conducted in a skin research center.

    PubMed

    Samadi, Aniseh; Asghari, Fariba

    2016-01-01

    Obtaining informed consents is one of the most fundamental principles in conducting a clinical trial. In order for the consent to be informed, the patient must receive and comprehend the information appropriately. Complexity of the consent form is a common problem that has been shown to be a major barrier to comprehension for many patients. The objective of this study was to assess the readability of different templates of informed consent forms (ICFs) used in clinical trials in the Center for Research and Training in Skin Diseases and Leprosy (CRTSDL), Tehran, Iran. This study was conducted on ICFs of 45 clinical trials of the CRTSDL affiliated with Tehran University of Medical Sciences. ICFs were tested for reading difficulty, using the readability assessments formula adjusted for the Persian language including the Flesch-Kincaid reading ease score, Flesch-Kincaid grade level, and Gunning fog index. Mean readability score of the whole text of ICFs as well as their 7 main information parts were calculated. The mean ± SD Flesch Reading Ease score for all ICFs was 31.96 ± 5.62 that is in the difficult range. The mean ± SD grade level was calculated as 10.71 ± 1.8 (8.23-14.09) using the Flesch-Kincaid formula and 14.64 ± 1.22 (12.67-18.27) using the Gunning fog index. These results indicate that the text is expected to be understandable for an average student in the 11(th) grade, while the ethics committee recommend grade level 8 as the standard readability level for ICFs. The results showed that the readability scores of ICFs assessed in our study were not in the acceptable range. This means they were too complex to be understood by the general population. Ethics committees must examine the simplicity and readability of ICFs used in clinical trials. PMID:27471590

  5. Hepatitis C: Clinical Trials

    MedlinePlus

    ... and Public Home » Hepatitis C » Treatment Decisions Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... can I find out about participating in a hepatitis C clinical trial? Many trials are being conducted ...

  6. Obtaining Valid Laboratory Data in Clinical Trials Conducted in Resource Diverse Settings: Lessons Learned from a Microbicide Phase III Clinical Trial

    PubMed Central

    Crucitti, Tania; Fransen, Katrien; Maharaj, Rashika; Tenywa, Tom; Massinga Loembé, Marguerite; Murugavel, Kailapuri Gangatharan; Mendonca, Kevin; Abdellati, Said; Beelaert, Greet; Van Damme, Lut

    2010-01-01

    Background Over the last decade several phase III microbicides trials have been conducted in developing countries. However, laboratories in resource constrained settings do not always have the experience, infrastructure, and the capacity to deliver laboratory data meeting the high standards of clinical trials. This paper describes the design and outcomes of a laboratory quality assurance program which was implemented during a phase III clinical trial evaluating the efficacy of the candidate microbicide Cellulose Sulfate 6% (CS) [1]. Methodology In order to assess the effectiveness of CS for HIV and STI prevention, a phase III clinical trial was conducted in 5 sites: 3 in Africa and 2 in India. The trial sponsor identified an International Central Reference Laboratory (ICRL), responsible for the design and management of a quality assurance program, which would guarantee the reliability of laboratory data. The ICRL provided advice on the tests, assessed local laboratories, organized trainings, conducted supervision visits, performed re-tests, and prepared control panels. Local laboratories were provided with control panels for HIV rapid tests and Chlamydia trachomatis/Neisseria gonorrhoeae (CT/NG) amplification technique. Aliquots from respective control panels were tested by local laboratories and were compared with results obtained at the ICRL. Results Overall, good results were observed. However, discordances between the ICRL and site laboratories were identified for HIV and CT/NG results. One particular site experienced difficulties with HIV rapid testing shortly after study initiation. At all sites, DNA contamination was identified as a cause of invalid CT/NG results. Both problems were timely detected and solved. Through immediate feedback, guidance and repeated training of laboratory staff, additional inaccuracies were prevented. Conclusions Quality control guidelines when applied in field laboratories ensured the reliability and validity of final study data

  7. Prevalence and Determinants of Physician Participation in Conducting Pharmaceutical-sponsored Clinical Trials and Lectures

    PubMed Central

    Ashar, Bimal H; Miller, Redonda G; Getz, Kelly J; Powe, Nell R

    2004-01-01

    BACKGROUND The relationship between physicians and the pharmaceutical industry is controversial because of the potential for conflicts of interest. However, little empirical evidence exists on the extent of physician participation in activities sponsored by pharmaceutical companies. OBJECTIVES To determine the prevalence of participation of internal medicine physicians in clinical trials and lectures sponsored by pharmaceutical companies and to describe factors that are associated with such participation. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional regional survey of 1,000 Maryland internal medicine physicians between February 2000 and January 2001 in order to measure the prevalence of physician participation in pharmaceutical-sponsored clinical trials and lectures. We also collected economic and demographic information to examine potential associations between physician characteristics and engagement in such activities. RESULTS Of 835 eligible physicians 444 (53%) responded, of whom 37% reported engaging in pharmaceutical-sponsored clinical trials and/or lectures to supplement their incomes. In our multivariable analysis, subspecialists versus generalist physicians (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.14 to 2.99), physicians in private group-single specialty and academic practice versus physicians in solo practice (OR, 2.30; 95% CI, 1.19 to 4.44 and OR, 2.56; 95% CI, 1.17 to 5.61, respectively), and physicians with higher versus lower annual incomes (OR, 1.22; 95% CI, 1.04 to 1.44) had a greater odds of participation in these activities. Additionally, physicians dissatisfied with their income had a 140% greater odds of participation (OR, 2.36; 95% CI, 1.45 to 3.83) than those who were satisfied with their income. CONCLUSIONS A substantial number of internists engage in pharmaceutical industry-sponsored clinical trials and/or lectures in an effort to supplement their incomes. Physician dissatisfaction with income appears to

  8. The challenges and opportunities of conducting a clinical trial in a low resource setting: the case of the Cameroon mobile phone SMS (CAMPS) trial, an investigator initiated trial.

    PubMed

    Mbuagbaw, Lawrence; Thabane, Lehana; Ongolo-Zogo, Pierre; Lang, Trudie

    2011-01-01

    Conducting clinical trials in developing countries often presents significant ethical, organisational, cultural and infrastructural challenges to researchers, pharmaceutical companies, sponsors and regulatory bodies. Globally, these regions are under-represented in research, yet this population stands to gain more from research in these settings as the burdens on health are greater than those in developed resourceful countries. However, developing countries also offer an attractive setting for clinical trials because they often have larger treatment naive populations with higher incidence rates of disease and more advanced stages. These factors can present a reduction in costs and time required to recruit patients. So, balance needs to be found where research can be encouraged and supported in order to bring maximum public health benefits to these communities. The difficulties with such trials arise from problems with obtaining valid informed consent, ethical compensation mechanisms for extremely poor populations, poor health infrastructure and considerable socio-economic and cultural divides. Ethical concerns with trials in developing countries have received attention, even though many other non-ethical issues may arise. Local investigator initiated trials also face a variety of difficulties that have not been adequately reported in literature. This paper uses the example of the Cameroon Mobile Phone SMS trial to describe in detail, the specific difficulties encountered in an investigator-initiated trial in a developing country. It highlights administrative, ethical, financial and staff related issues, proposes solutions and gives a list of additional documentation to ease the organisational process. PMID:21658262

  9. A Review of Clinical Trials Conducted With Oral, Multicomponent Dietary Supplements for Improving Photoaged Skin.

    PubMed

    Birnbaum, Jay; Le Moigne, Anne; Dispensa, Lisa; Buchner, Larry

    2015-12-01

    Although the FDA does not require documentation of efficacy of dietary supplements, prospective clinical studies, including randomized controlled trials, have been conducted with individual micronutrients alone and in combination with other ingredients for promoting skin health. Proposed mechanisms include antioxidation, anti-inflammation, photoprotection, collagen formation, reductions in matrix metalloproteinases, and other effects on photoaging. Literature searches were conducted to identify clinical trials assessing multicomponent dietary supplement formulations on photoaging outcomes. Sixteen studies of various nutrient and non-nutrient ingredients, including essential micronutrients (vitamins, minerals), plant extracts (polyphenols, carotenoids), and marine- or animal-derived ingredients, were identified. Studies were single center, 2-12 months in duration, primarily enrolled women, and evaluated numerous outcomes, including investigator/subject assessments and instrumental/objective measures. Methods to control for potential confounders were implemented in some studies, including limiting sun exposure, cosmetic procedures, and changes in dietary habits/body weight. Given the range of different products, clinical/methodologic heterogeneity, insufficient detail in reporting, and lack of comparable outcome measures, quantitative analysis of results was not possible. Results of individual studies revealed significant improvements from baseline for the dietary supplement group(s) on ≥ 1 endpoint across all studies; significant differences from placebo were observed in 7 of 12 controlled studies (although only 1 study designated a prospectively defined primary endpoint). Most products had only been tested in 1 study; confirmatory studies were rarely conducted per the publicly available literature. Meaningful assessment of dietary supplements, which typically contain nutrients found in the diet, requires unique methodologic considerations and endpoints

  10. Reducing Conduct Problems among Children Exposed to Intimate Partner Violence: A Randomized Clinical Trial Examining Effects of Project Support

    ERIC Educational Resources Information Center

    Jouriles, Ernest N.; McDonald, Renee; Rosenfield, David; Stephens, Nanette; Corbitt-Shindler, Deborah; Miller, Pamela C.

    2009-01-01

    This study was a randomized clinical trial of Project Support, an intervention designed to reduce conduct problems among children exposed to intimate partner violence. Participants were 66 families (mothers and children) with at least 1 child exhibiting clinical levels of conduct problems. Families were recruited from domestic violence shelters.…

  11. Availability and affordability of new medicines in Latin American countries where pivotal clinical trials were conducted

    PubMed Central

    Ugalde, Antonio

    2015-01-01

    Abstract Objective To assess whether new pharmaceutical products approved by the United States Food and Drug Administration (FDA) in 2011 and 2012 were registered, commercialized and sold at affordable prices in the Latin American countries where they were tested. Methods We obtained a list of new molecular entities (new pharmaceutical products) approved by the FDA in 2011 and 2012. FDA medical reviews indicated the countries where pivotal clinical trials had been conducted. The registration status of the products was obtained from pharmaceutical registers; pharmaceutical companies confirmed their availability in national markets and local pricing observatories provided the price of medicines in retail pharmacies. Affordability was assessed as the cost of a course of treatment as a proportion of monthly income. Information on safety and efficacy was gathered from independent drug bulletins. Findings Of an expected 114 registrations, if the 33 products had been registered in all the countries where tested, only 68 (60%) were completed. Eight products were registered and commercialized in all countries but 10 had not been registered in any of the countries. With one exception, products for which we obtained pricing information (n = 18) cost more than the monthly minimum wage in all countries and 12 products cost at least five times the monthly minimum wage. Conclusion Many pharmaceutical products tested in Latin America are unavailable and/or unaffordable to most of the population. Ethical review committees should consider the local affordability and therapeutic relevance of new products as additional criteria for the approval of clinical trials. Finally, clinical trials have opportunity costs that need to be assessed. PMID:26600609

  12. Overcoming Challenges in Conducting Clinical Trials in Minority Populations: Identifying and Testing What Works

    PubMed Central

    Azuine, Romuladus E.; Ekejiuba, Sussan E.

    2015-01-01

    Participation in clinical trials is one of the greatest gifts that humanity can give to the fields of medicine and public health. Clinical trials are central in public health’s mission to advance drug discovery. The enrollment and retention of participants, especially minority populations, is one of the most practical challenges of successfully implementing a clinical trial. In spite of these challenges, there are many reasons why a broader public participation in clinical trials is critical. The ability to generalize the scientific findings and the principles of equity, justice, and beneficence require an equitable distribution of the risks, benefits, and burdens of research for all classes and groups of people. A new methodology article published in this journal presents a promising framework for addressing minority recruitment and retention using what is known and using it innovatively to address a difficult problem facing clinical trials and public health. The innovative application of what is known in addressing a challenging problem, as this article presents, is worth the reading of all those interested in scientifically rigorous and ethically sound clinical trials that substantially comprise of diverse populations.

  13. Ethical standards for clinical trials conducted in third countries: the new strategy of the European Medicines Agency.

    PubMed

    Altavilla, Annagrazia

    2011-01-01

    Clinical trials increasingly occur on a global scale as industry and government sponsors in wealthy countries move trials to low- and middle-income countries. The globalization of clinical research raises important questions about the economical and ethical aspects of clinical research and the translation of trial results to clinical practice: which ethical standards are applied? Are trials results accurate and valid, and can they be extrapolated to other settings? This article provides an overview of the strategy approved by the European Medicines Agency (EMA) to clarify ethical standards for clinical research conducted outside the European Economic Area (EEA) and included in Marketing Authorization Applications. Reference to the EMA Reflection paper is made. PMID:21409974

  14. Conducting a fully mobile and randomised clinical trial for depression: access, engagement and expense

    PubMed Central

    Jordan, Joshua T; Castaneda, Diego; Gazzaley, Adam; Areán, Patricia A

    2016-01-01

    Importance Advances in mobile technology have resulted in federal and industry-level initiatives to facilitate large-scale clinical research using smart devices. Although the benefits of technology to expand data collection are obvious, assumptions about the reach of mobile research methods (access), participant willingness to engage in mobile research protocols (engagement), and the cost of this research (cost) remain untested. Objective To assess the feasibility of a fully mobile randomised controlled trial using assessments and treatments delivered entirely through mobile devices to depressed individuals. Design Using a web-based research portal, adult participants with depression who also owned a smart device were screened, consented and randomised to 1 of 3 mental health apps for treatment. Assessments of self-reported mood and cognitive function were conducted at baseline, 4, 8 and 12 weeks. Physical and social activity was monitored daily using passively collected phone use data. All treatment and assessment tools were housed on each participant's smart phone or tablet. Interventions A cognitive training application, an application based on problem-solving therapy, and a mobile-sensing application promoting daily activities. Results Access: We screened 2923 people and enrolled 1098 participants in 5 months. The sample characteristics were comparable to the 2013 US census data. Recruitment via Craigslist.org yielded the largest sample. Engagement: Study engagement was high during the first 2 weeks of treatment, falling to 44% adherence by the 4th week. Cost: The total amount spent on for this project, including staff costs and β testing, was $314 264 over 2 years. Conclusions and relevance These findings suggest that mobile randomised control trials can recruit large numbers of participants in a short period of time and with minimal cost, but study engagement remains challenging. Trial registration number NCT00540865. PMID:27019745

  15. Divalproex Sodium for the Treatment of PTSD and Conduct Disordered Youth: A Pilot Randomized Controlled Clinical Trial

    ERIC Educational Resources Information Center

    Steiner, Hans; Saxena, Kirti S.; Carrion, Victor; Khanzode, Leena A.; Silverman, Melissa; Chang, Kiki

    2007-01-01

    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)…

  16. Ethical and Legal Aspects of Conducting Clinical Trials in Alcohol Withdrawal Syndrome

    PubMed Central

    R, Harsha

    2014-01-01

    Alcohol Withdrawal Syndrome (AWS) is a condition where the patients will be mentally unstable initially and where later, with therapy, they gradually return to normalcy. As AWS comprises two stages; a mentally unstable state and a normal state of mind, the ethical and legal issues behind recruitment of these subjects become a little ambiguous in a clinical trial. This study was taken up to clarify the uncertainty regarding the biphasic states of minds (i.e. unstable mind and sound mind) of the subjects who were involved in a clinical trial done on AWS. Law and ethics regarding the clinical trials which involve psychiatric subjects need to be strengthened and amended from time to time, in order to protect the interests of both patients and physicians. PMID:24995195

  17. Treatment costs associated with interventional cancer clinical trials conducted at a single UK institution over 2 years (2009–2010)

    PubMed Central

    Liniker, E; Harrison, M; Weaver, J M J; Agrawal, N; Chhabra, A; Kingshott, V; Bailey, S; Eisen, T G G; Corrie, P G

    2013-01-01

    Background: The conduct of clinical trials should be an integral part of routine patient care. Treating patients in trials incurs additional costs over and above standard of care (SOC), but the extent of the cost burden is not known. We undertook a retrospective cost attribution analysis to quantitate the treatment costs associated with cancer clinical trial protocols conducted over a 2 year period. Methods: All patients entered into oncology (non-haematology) clinical trials involving investigational medicinal products in 2009 and 2010 in a single UK institution were identified. The trial protocols on which they were treated were analysed to identify the treatment costs for the experimental arm(s) of the trial and the equivalent SOC had the patient not been entered in the trial. The treatment cost difference was calculated by subtracting the experimental treatment cost from SOC cost. For randomised trials, an average treatment cost was estimated by taking into account the number of arms and randomisation ratio. An estimate of the annual treatment costs was calculated. Results: A total of 357 adult oncology patients were treated on 53 different trial protocols: 40 phase III, 2 randomised II/III and 11 phase II design. A total of 27 trials were academic, non-commercial sponsored trials and 26 were commercial sponsored trials. When compared with SOC, the average treatment cost per patient was an excess of £431 for a non-commercial trial (range £6393 excess to £6005 saving) and a saving of £9294 for a commercial trial (range £0 to £71 480). There was an overall treatment cost saving of £388 719 in 2009 and £496 556 in 2010, largely attributable to pharmaceutical company provision of free drug supplies. Conclusion: On an average, non-commercial trial protocols were associated with a small per patient excess treatment cost, whereas commercial trials were associated with a substantially higher cost saving. Taking into account the total number of patients

  18. Methodological challenges in conducting a multi-site randomized clinical trial of massage therapy in hospice.

    PubMed

    Kutner, Jean; Smith, Marlaine; Mellis, Karen; Felton, Sue; Yamashita, Traci; Corbin, Lisa

    2010-06-01

    Researchers conducting multi-site studies of interventions for end-of-life symptom management face significant challenges with respect to obtaining an adequate sample and training and retaining on-site study teams. The purpose of this paper is to describe the strategies and responses to these challenges in a multi-site randomized clinical trial (RCT) of the efficacy of massage therapy for decreasing pain among patients with advanced cancer in palliative care/hospice settings. Over a period of 36 months, we enrolled 380 participants across 15 sites; 27% of whom withdrew prior to study completion (less than the anticipated 30% rate). We saw an average of 68% turnover amongst study staff. Three key qualities characterized successful on-site study teams: (1) organizational commitment; (2) strong leadership from on-site study coordinators; and (3) effective lines of communication between the on-site study coordinators and both their teams and the university-based research team. Issues of recruitment, retention and training should be accounted for in hospice-based research study design and budgeting. PMID:20597707

  19. Considerations in the rational design and conduct of phase I/II pediatric clinical trials: avoiding the problems and pitfalls.

    PubMed

    Abdel-Rahman, S M; Reed, M D; Wells, T G; Kearns, G L

    2007-04-01

    Over the past decade, there has been a heightened awareness of the need to include children in the drug development process. With this awareness has come an expansion of the infrastructure for conducting studies in children and an increase in the sponsorship of pediatric clinical trials. However, the growth in pediatric research has, in many cases, not been accompanied by an increase in the involvement of trained pediatric investigators when it comes to trial design and/or interpretation. Pediatric phase I/II protocols continue to span a spectrum from those that are carefully constructed to those that are poorly designed. This paper highlights the basic elements of phase I/II protocols that merit unique consideration when the clinical trial involves children. Illustrations are provided from our experience, which highlight problems that may arise when trials are not designed with the pediatric patient in mind. PMID:17329988

  20. Regulatory impediments jeopardizing the conduct of clinical trials in Europe funded by the National Institutes of Health

    PubMed Central

    Neaton, James D; Babiker, Abdel; Bohnhorst, Mark; Darbyshire, Janet; Denning, Eileen; Frishman, Arnie; Grarup, Jesper; Larson, Gregg; Lundgren, Jens

    2011-01-01

    Background A number of reports have highlighted problems of conducting publicly funded trials in Europe as a consequence of the European Union (EU) Clinical Trials Directive. The impact of the EU Directive on multi-national trials, which include sites in Europe that are funded by the US National Institutes of Health (NIH) have not been described. Methods Four problems in the conduct of two international HIV treatment trials funded by NIH in the EU are described: (1) conflicting regulations on the continuing review of protocols by Institutional Review Boards/Research Ethics Committees; (2) US regulations requiring Federalwide Assurances for sites which are only partially funded by NIH; (3) EU guidance on the designation of studies as a trial of an investigational medicinal product; and (4) EU guidance on trial sponsorship and the requirements for insurance and indemnification. Following the description of the problems, recommendations for improving global collaborations are made to the US Office of Human Research Protections, to NIH, and to the EU and its Member States. Results A lack of harmonization of regulations at multiple levels caused enrollment in one study to be interrupted for several months and delayed for one year the initiation of another study aimed at obtaining definitive evidence to guide the timing of the initiation of antiretroviral therapy for individuals infected with HIV. The delays and the purchase of insurance resulted in substantial increases in trial costs and caused substantial disruption at clinical sites among staff and study participants. Limitations The problems cited and recommendations made pertain to trials funded by NIH and conducted by sites in the EU. There are many other challenges in the conduct of international research, public and private, that global harmonization would alleviate. Conclusions Disharmony, at multiple levels, in international regulations and guidelines is stifling publicly funded global research. International

  1. The Perfect Clinical Trial.

    PubMed

    Bril, V

    2016-01-01

    Multiple phase III clinical trials have failed to show disease-modifying benefits for diabetic sensorimotor polyneuropathy (DSP) and this may be due to the design of the clinical trials. The perfect clinical trial in DSP would enroll sufficiently large numbers of patients having early or minimal disease, as demonstrated by nerve conduction studies (NCS). These patients would be treated with an intervention given at an effective and well-tolerated dose for a sufficient duration of time to show change in the end points selected. For objective or surrogate measures such as NCS and for some small fiber measures, the duration needed to show positive change may be as brief as 6-12 months, but subsequently, trials lasting 5-8 years will be required to demonstrate clinical benefits. PMID:27133143

  2. ReCAP: Clinical Trial Assessment of Infrastructure Matrix Tool to Improve the Quality of Research Conduct in the Community

    PubMed Central

    Zon, Robin T.; Weiner, Bryan J.; St. Germain, Diane; Denicoff, Andrea M.; Dempsey, Kandie; Carrigan, Angela C.; Teal, Randall W.; Good, Marjorie J.; McCaskill-Stevens, Worta; Grubbs, Stephen S.

    2016-01-01

    QUESTION ASKED: Is there a tool for sites engaged in cancer clinical research to use to assess their infrastructure and improve their research conduct toward exemplary levels of performance beyond the standard of Good Clinical Practice (GCP)? SUMMARY ANSWER: The NCI Community Cancer Center Program (NCCCP) sites, with NCI Clinical Trial advisor input, created a “Clinical Trials Best Practice Matrix” self-assessment tool to assess research infrastructure. The tool identified nine attributes (eg, physician engagement in clinical trials, accrual activity, clinical trial portfolio diversity), each with three progressive levels (I – III) for sites to score infrastructural elements from less (I) to more (III) exemplary. For example, a level-one site might have active Phase III treatment trials in two to three disease sites and review their portfolio diversity once a year, whereas a level-three site has active Phase II and also Phase I or I/II trials across five or more disease sites and reviews their portfolio quarterly. The tool also provided a road map toward more exemplary practices. METHODS: From 2011 to 2013, 21 NCCCP sites self-assessed their programs with the tool annually. Sites reported significant increases in level III (more exemplary) scores across the original nine attributes combined (P < .001 [see Figure 1]). During 2013 to 2014, NCI collaborators conducted a five-step formative evaluation of the tool resulting in expansion of attributes from nine to 11 and a new name: the Clinical Trials Assessment of Infrastructure Matrix, or CT AIM, tool which is described and fully presented in the manuscript. BIAS, CONFOUNDING FACTOR(S), DRAWBACKS: Tool scores are self-reported which are subject to potential bias. The tool was developed by community hospital based cancer centers and has not been psychometrically validated. Use of scores for ranking between programs is not recommended at this time. The attributes and indicators in the tool may need to be adapted

  3. Challenges of conducting clinical trials of natural products to combat cancer.

    PubMed

    Paller, Channing J; Denmeade, Samuel R; Carducci, Michael A

    2016-06-01

    Numerous drugs that the US Food and Drug Administration (FDA) has approved for use in cancer therapy are derived from plants, including taxanes such as paclitaxel and vinca alkaloids such as vinblastine. Dietary supplements are another category of natural products that are widely used by patients with cancer, but without the FDA-reviewed evidence of safety and efficacy--be it related to survival, palliation, symptom mitigation, and/or immune system enhancement-that is required for therapy approval. Nearly half of patients in the United States with cancer report that they started taking new dietary supplements after being given a diagnosis of cancer. Oncologists are challenged in providing advice to patients about which supplements are safe and effective to use to treat cancer or the side effects of cancer therapy, and which supplements are antagonistic to standard treatment with chemotherapy, radiation, and/or immunotherapy. Despite the large number of trials that have been launched, the FDA has not approved any dietary supplement or food to prevent cancer, halt its growth, or prevent its recurrence. In this article, we review the primary challenges faced by researchers attempting to conduct rigorous trials of natural products, including shortages of funding due to lack of patentability, manufacturing difficulties, contamination, and lack of product consistency. We also highlight the methods used by dietary supplement marketers to persuade patients that a supplement is effective (or at least safe) even without FDA approval, as well as the efforts of the US government to protect the health and safety of its citizens by ensuring that the information used to market natural products is accurate. We close with a summary of the most widely used databases of information about the safety, efficacy, and interactions of dietary supplements. PMID:27379814

  4. ClinicalTrials.gov

    MedlinePlus

    ... Health ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ... This Site ClinicalTrials.gov Background About the Results Database History, Policies, and Laws Media/Press Resources Linking ...

  5. How Do Clinical Trials Work?

    MedlinePlus

    ... Trials Clinical Trial Websites How Do Clinical Trials Work? If you take part in a clinical trial, ... kol). This plan explains how the trial will work. The trial is led by a principal investigator ( ...

  6. Can Clinical Trials Requiring Frequent Participant Contact Be Conducted Over the Internet? Results From an Online Randomized Controlled Trial Evaluating a Topical Ointment for Herpes Labialis

    PubMed Central

    Kabbara, Karim; Clark, Rachael; McAlindon, Tim

    2004-01-01

    Background The Internet has tremendous appeal for conducting randomized clinical trials and may be especially applicable to trials requiring frequent participant contact. Trials of cold sore remedies, for example, often require daily clinic visits during outbreaks, imposing substantial burden on participants. An Internet-based randomized clinical trial design may reduce this burden, permitting frequent symptom reports with considerably less effort. Objective To evaluate the feasibility of a Web-based randomized clinical trial requiring frequent participant interaction, using a 6-month, double-blind, randomized, placebo-controlled pilot trial of a topical ointment containing dioctyl sodium sulfosuccinate (DSS) (Zilex; Meditech Pharmaceuticals, Inc, Scottsdale, Arizona, USA) intended for treatment of recurrent herpes labialis. A secondary objective was to obtain preliminary data on effectiveness outcomes, to assist in planning a fully-powered trial of DSS. Methods Adults with physician-confirmed herpes labialis were recruited to apply to the trial. Eligible applicants were randomized to DSS or placebo, mailed to them upon enrolment with instructions to apply topically every 2 hours for the duration of every cold sore outbreak. Participants were instructed to complete online questionnaires at 2-week intervals and, at the initiation of a cold sore, daily "outbreak questionnaires" until outbreak termination. Feasibility outcome measures included trial participant characteristics, frequency of cold sores, participant retention and adherence (to study medication), and data completeness. Treatment effectiveness outcome measures included outbreak duration, days to crust formation, and pain. Results Of the 292 individuals applying, 182 screened eligible; 32 participants with confirmed herpes labialis enrolled in the trial. 16 were randomized into the verum group and 16 into the placebo group. 29 (91%) participants completed the trial. During the trial, 34 outbreaks were

  7. Conduct, Oversight, and Ethical Considerations of Clinical Trials in Companion Animals with Cancer: Report of a Workshop on Best Practice Recommendations.

    PubMed

    Page, R; Baneux, P; Vail, D; Duda, L; Olson, P; Anestidou, L; Dybdal, N; Golab, G; Shelton, W; Salgaller, M; Hardy, C

    2016-03-01

    Development of effective and safe treatments for companion animals with cancer requires the collaboration of numerous animal health professionals and the full engagement of animal owners. Establishing 'Best Practice Recommendations' for clinical trials in veterinary oncology represents an important step toward meeting the goal of rigorous clinical trial design and conduct that is required to establish valid evidence. Likewise, optimizing patient welfare and owner education and advocacy is crucial to meet the unique ethical obligations to both owners and animals enrolled in these clinical trials and to ensure trust in the team conducting the research. To date, 'Best Practice Recommendations' for clinical trial conduct have not been reported for veterinary oncology. This document summarizes the consensus of a workshop held in November, 2014 to identify relevant ethical principles and to ensure responsible conduct of clinical research in companion animals with cancer. It is intended as a working document that will be updated as advances in science and ethical considerations require. To the extent possible, existing guidelines for the conduct and oversight of clinical trials in humans have been adapted for veterinary trials to avoid duplicative effort and to facilitate integration of clinical trials such that translational research with benefits for both companion animals and humans are encouraged. PMID:26950524

  8. Clinical Trials in Vision Research

    MedlinePlus

    ... Clinical Trials in Vision Research Clinical Trials in Vision Research Clinical studies depend on people who volunteer. ... about the treatment. How are clinical trials in vision different from other clinical trials? Eyes are one ...

  9. What Are Clinical Trials? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Clinical Trials What Are Clinical Trials? Past Issues / Fall 2010 Table of Contents ... conducted all the time. The Different Phases of Clinical Trials Clinical trials related to drugs are classified ...

  10. Conducting experimental research in marginalised populations: clinical and methodological implications from a mixed-methods randomised controlled trial in Kenya.

    PubMed

    Lowther, Keira; Harding, Richard; Ahmed, Aabid; Gikaara, Nancy; Ali, Zippy; Kariuki, Hellen; Sherr, Lorraine; Simms, Victoria; Selman, Lucy

    2016-01-01

    Experimental studies to test interventions for people living with HIV in low- and middle-income countries are essential to ensure appropriate and effective clinical care. The implications of study participation on outcome data in such populations have been discussed theoretically, but rarely empirically examined. We aimed to explore the effects of participating in a randomised controlled trial conducted in an HIV clinic in Mombasa, Kenya. We report qualitative data from the Treatment Outcomes in Palliative Care trial, which evaluated the impact of a nurse-led palliative care intervention for HIV positive adults on antiretroviral therapy compared to standard care. Participants in both arms attended five monthly quantitative data collection appointments. Post-trial exit, 10 control and 20 intervention patients participated in semi-structured qualitative interviews, analysed using thematic analysis. We found benefit attributed to the compassion of the research team, social support, communication, completion of patient reported outcome measures (PROMs) and material support (transport reimbursement). Being treated with compassion and receiving social support enabled participants to build positive relationships with the research team, which improved mental health and well-being. Open and non-judgmental communication made participants feel accepted. Participants described how repeated completion of the PROMs was a prompt for reflection, through which they began to help themselves and self-care. Participant reimbursements relieved financial hardship and enabled them to fulfil their social responsibilities, enhancing self-worth. These findings emphasise the importance of compassion, support and effective communication in the clinical encounter, particularly in stigmatised and isolated populations, and the potential of the integration of simple PROMs to improve patient outcomes. Participation in research has unexpected positive benefits for participants, which should be

  11. Conducting experimental research in marginalised populations: clinical and methodological implications from a mixed-methods randomised controlled trial in Kenya

    PubMed Central

    Lowther, Keira; Harding, Richard; Ahmed, Aabid; Gikaara, Nancy; Ali, Zippy; Kariuki, Hellen; Sherr, Lorraine; Simms, Victoria; Selman, Lucy

    2016-01-01

    ABSTRACT Experimental studies to test interventions for people living with HIV in low- and middle-income countries are essential to ensure appropriate and effective clinical care. The implications of study participation on outcome data in such populations have been discussed theoretically, but rarely empirically examined. We aimed to explore the effects of participating in a randomised controlled trial conducted in an HIV clinic in Mombasa, Kenya. We report qualitative data from the Treatment Outcomes in Palliative Care trial, which evaluated the impact of a nurse-led palliative care intervention for HIV positive adults on antiretroviral therapy compared to standard care. Participants in both arms attended five monthly quantitative data collection appointments. Post-trial exit, 10 control and 20 intervention patients participated in semi-structured qualitative interviews, analysed using thematic analysis. We found benefit attributed to the compassion of the research team, social support, communication, completion of patient reported outcome measures (PROMs) and material support (transport reimbursement). Being treated with compassion and receiving social support enabled participants to build positive relationships with the research team, which improved mental health and well-being. Open and non-judgmental communication made participants feel accepted. Participants described how repeated completion of the PROMs was a prompt for reflection, through which they began to help themselves and self-care. Participant reimbursements relieved financial hardship and enabled them to fulfil their social responsibilities, enhancing self-worth. These findings emphasise the importance of compassion, support and effective communication in the clinical encounter, particularly in stigmatised and isolated populations, and the potential of the integration of simple PROMs to improve patient outcomes. Participation in research has unexpected positive benefits for participants, which

  12. Reflections One Year into the 22 Center NIH-funded WRIST Study. A Primer on Conducting a Multicenter Clinical Trial

    PubMed Central

    2013-01-01

    The Wrist and Radius Surgery Trial (WRIST) study group is a collaboration of 22 hand surgery centers in the US, Canada, and Singapore to showcase the interest and capability of hand surgeons to conduct a multicenter clinical trial. The WRIST study group was formed in response to the seminal systematic review by Margaliot et al. and the Cochrane report that indicated marked deficiency in the quality of evidence in the distal radius fracture literature. Since the initial description of this fracture by Colles in 1814, over 2,000 studies have been published on this subject, yet high level studies based on the principles of evidence-based medicine are lacking. As we continue to embrace evidence-based medicine to raise the quality of research, the lessons learned during the organization and conduct of WRIST can serve as a template for others contemplating similar efforts. This paper will trace the course of WRIST by sharing the triumphs, and more importantly the struggles, faced in the first year of this study. PMID:23608306

  13. Conducting a Randomized Clinical Trial of an Psychological Intervention for Parents/Caregivers of Children with Cancer Shortly after Diagnosis

    PubMed Central

    Stehl, Meredith Lutz; Alderfer, Melissa A.; Rodriguez, Alyssa; Hwang, Wei-Ting; Pai, Ahna L. H.; Boeving, Alexandra; Reilly, Anne

    2009-01-01

    Objective To report acceptability, feasibility, and outcome data from a randomized clinical trial (RCT) of a brief intervention for caregivers of children newly diagnosed with cancer. Method Eighty-one families were randomly assigned following collection of baseline data to Intervention or Treatment as Usual (TAU). Recruitment and retention rates and progression through the protocol were tracked. Measures of state anxiety and posttraumatic stress symptoms served as outcomes. Results Difficulties enrolling participants included a high percentage of newly diagnosed families failing to meet inclusion criteria (40%) and an unexpectedly low participation rate (23%). However, movement through the protocol was generally completed in a timely manner and those completing the intervention provided positive feedback. Outcome data showed no significant differences between the arms of the RCT. Conclusions There are many challenges inherent in conducting a RCT shortly after cancer diagnosis. Consideration of alternative research designs and optimal timing for interventions are essential next steps. PMID:19091806

  14. Managing clinical trials.

    PubMed

    Farrell, Barbara; Kenyon, Sara; Shakur, Haleema

    2010-01-01

    Managing clinical trials, of whatever size and complexity, requires efficient trial management. Trials fail because tried and tested systems handed down through apprenticeships have not been documented, evaluated or published to guide new trialists starting out in this important field. For the past three decades, trialists have invented and reinvented the trial management wheel. We suggest that to improve the successful, timely delivery of important clinical trials for patient benefit, it is time to produce standard trial management guidelines and develop robust methods of evaluation. PMID:20626885

  15. Conduction in ulnar nerve bundles that innervate the proximal and distal muscles: a clinical trial

    PubMed Central

    2010-01-01

    Background This study aims to investigate and compare the conduction parameters of nerve bundles in the ulnar nerve that innervates the forearm muscles and hand muscles; routine electromyography study merely evaluates the nerve segment of distal (hand) muscles. Methods An electrophysiological evaluation, consisting of velocities, amplitudes, and durations of ulnar nerve bundles to 2 forearm muscles and the hypothenar muscles was performed on the same humeral segment. Results The velocities and durations of the compound muscle action potential (CMAP) of the ulnar nerve bundle to the proximal muscles were greater than to distal muscles, but the amplitudes were smaller. Conclusions Bundles in the ulnar nerve of proximal muscles have larger neuronal bodies and thicker nerve fibers than those in the same nerve in distal muscles, and their conduction velocities are higher. The CMAPs of proximal muscles also have smaller amplitudes and greater durations. These findings can be attributed to the desynchronization that is caused by a wider range of distribution in nerve fiber diameters. Conduction parameters of nerve fibers with different diameters in the same peripheral nerve can be estimated. PMID:20836846

  16. Considerations for the Conduct of Clinical Trials with Antiinflammatory Agents in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report.

    PubMed

    Torphy, Theodore J; Allen, Janet; Cantin, André M; Konstan, Michael W; Accurso, Frank J; Joseloff, Elizabeth; Ratjen, Felix A; Chmiel, James F

    2015-09-01

    Inflammation leads to lung destruction and loss of pulmonary function in patients with cystic fibrosis (CF). Drugs that modulate the cystic fibrosis transmembrane conductance regulator (CFTR) have recently been approved. Although the impact of CFTR modulators on sweat chloride and lung function are exciting, they have not yet demonstrated an effect on inflammation. Therefore, CF antiinflammatory drug development must continue. Unfortunately, the lack of clarity with this process has left investigators and industry sponsors frustrated. The Cystic Fibrosis Foundation established a working group in early 2014 to address this issue. There are many inflammatory processes disrupted in CF, and, therefore, there are many potential targets amenable to antiinflammatory therapy. Regardless of a drug's specific mechanism of action, it must ultimately affect the neutrophil or its products to impact CF. The working group concluded that before bringing new antiinflammatory drugs to clinical trial, preclinical safety studies must be conducted in disease-relevant models to assuage safety concerns. Furthermore, although studies of antiinflammatory therapies must first establish safety in adults, subsequent studies must involve children, as they are most likely to reap the most benefit. The working group also recommended that pharmacokinetic-pharmacodynamic studies and early-phase safety studies be performed before proceeding to larger studies of longer duration. In addition, innovative study designs may improve the likelihood of adequately assessing treatment response and mitigating risk before conducting multiyear studies. Learning from past experiences and incorporating this knowledge into new drug development programs will be instrumental in bringing new antiinflammatory therapies to patients. PMID:26146892

  17. A report of clinical trial conducted on Toto ointment and soap products.

    PubMed Central

    Alebiosu, C. O.; Ogunledun, A.; Ogunleye, D. S.

    2003-01-01

    OBJECTIVE: The efficacy of Toto ointment and soap on common skin disorders was tested. METHODOLOGY: A cohort of Nigerians with common skin conditions such as fungal and bacterial skin infections, scabies, acne vulgaris, and dandruff were selected and followed for a period of 12 weeks. The study is a randomized, comparative, prospective, blinded observational study. Following a placebo run in/wash out period, patients were given either a Toto ointment or soap, or a combination of these, or sulfur ointment alone. Soap use was preferred in patients with Tinea capitis more than patients with any other superficial skin condition for technical reasons--such as ease of application of the soap lather. Expressed preference for either the soap or the cream was at times taken into consideration. Cure rate, adverse drug effects and acceptability of the products were assessed. RESULTS: Out of the 595 patients with common skin diseases selected for the study, 446 (74.9%) had fungal infections, while 64 (10.8%) had scabies infestation. A total of 47 (7.9%) patients had bacterial skin infections, 36 (6.1%) had acne vulgaris, and two (0.3%) had dandruff. At the end of the treatment period, out of the 129 patients with fungal infections treated with Toto ointment alone, 92 (71.3)% were successfully treated; while 41 (87.2%) out of the 47 patients with scabies were successfully treated with Toto ointment alone. Although few patients were seen with bacterial skin infections during the study period, these patients responded well to the ointment, the soap or a combination of the two. Overall, the combination of Toto ointment and soap had a better clinical success rate on all diseases when compared to sulfur ointment alone. The study has shown the efficacy and tolerability of Toto products (skin ointment and soap) in the management of common skin disorders. CONCLUSION: Toto ointment and soap are particularly efficacious in the management of common skin conditions such as fungal and

  18. Design of clinical trials.

    PubMed

    Rollo, David; Machado, Sanjay; Ceschin, Mauro

    2010-09-01

    Clinical trial design for nuclear medicine diagnostic imaging radiopharmaceuticals must include a design for preclinical safety studies. These studies should establish that the investigational product (IP) does not have a toxic effect. As a further requirement, radiopharmaceutical clinical trials include a human study (phase 1) that provides biodistribution, pharmacokinetics, and radiation dosimetry information. These studies demonstrate to the Food and Drug Administration that the IP either meets or exceeds the toxicology and radiation exposure safety limits. Satisfying this requirement can result in the Food and Drug Administration approving the performance of late-phase (phase 2/3) clinical trials that are designed to validate the clinical efficacy of the diagnostic imaging agent in patients who have a confirmed diagnosis for the intended application. Emphasis is placed on the most typical trial design for diagnostic imaging agents that use a comparator to demonstrate that the new IP is similar in efficacy to an established standard comparator. Such trials are called equivalence, or noninferiority, trials that attempt to show that the new IP is not less effective than the comparator by more than a statistically defined amount. Importantly, the trial design must not inappropriately favor one diagnostic imaging agent over the other. Bias is avoided by the use of a core laboratory with expert physicians who are not involved in the trial for interpreting and objectively scoring the image sets obtained at the clinical trial sites. Clinical trial design must also follow Good Clinical Practice (GCP) guidelines. GCP stipulates the clinical trial process, including protocol and Case Report Form design, analyses planning, as well as analyzing and preparing interim and final clinical trial/study reports. PMID:20674592

  19. CLINICAL TRIALS.GOV

    EPA Science Inventory

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

  20. Quality Assurance for Clinical Trials

    PubMed Central

    Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

    2013-01-01

    Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

  1. Evidence and Clinical Trials.

    NASA Astrophysics Data System (ADS)

    Goodman, Steven N.

    1989-11-01

    This dissertation explores the use of a mathematical measure of statistical evidence, the log likelihood ratio, in clinical trials. The methods and thinking behind the use of an evidential measure are contrasted with traditional methods of analyzing data, which depend primarily on a p-value as an estimate of the statistical strength of an observed data pattern. It is contended that neither the behavioral dictates of Neyman-Pearson hypothesis testing methods, nor the coherency dictates of Bayesian methods are realistic models on which to base inference. The use of the likelihood alone is applied to four aspects of trial design or conduct: the calculation of sample size, the monitoring of data, testing for the equivalence of two treatments, and meta-analysis--the combining of results from different trials. Finally, a more general model of statistical inference, using belief functions, is used to see if it is possible to separate the assessment of evidence from our background knowledge. It is shown that traditional and Bayesian methods can be modeled as two ends of a continuum of structured background knowledge, methods which summarize evidence at the point of maximum likelihood assuming no structure, and Bayesian methods assuming complete knowledge. Both schools are seen to be missing a concept of ignorance- -uncommitted belief. This concept provides the key to understanding the problem of sampling to a foregone conclusion and the role of frequency properties in statistical inference. The conclusion is that statistical evidence cannot be defined independently of background knowledge, and that frequency properties of an estimator are an indirect measure of uncommitted belief. Several likelihood summaries need to be used in clinical trials, with the quantitative disparity between summaries being an indirect measure of our ignorance. This conclusion is linked with parallel ideas in the philosophy of science and cognitive psychology.

  2. Clinical trials of homoeopathy.

    PubMed Central

    Kleijnen, J; Knipschild, P; ter Riet, G

    1991-01-01

    OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials. PMID:1825800

  3. AIDS Clinical Trials Group Network

    MedlinePlus

    ... Center Statistical and Data Management Center Glossaries Sites Clinical Trials About the Trial Process Trials Open to Enrollment Recent Study Results Access to Published Data Clinical Trials Resources Committees Executive Scientific Resource Community General Information ...

  4. [A review of international clinical trial registration].

    PubMed

    Yu, He; Liu, Jian-ping

    2007-05-01

    Clinical trials play a critical role in medical research. However, only a few clinical trials conducted at present have been registered at various clinical trial registries. Clinical trial registration can prevent bias in these registered trials effectively and avoid unnecessary waste of resources due to meaningless repeats. Moreover, it will benefit the development of evidence-based medicine, and promote human welfare. Great attention has been paid to the importance and necessity of clinical trial registration. This review briefly introduced the definition, justification, contents, history, current status of clinical trial registration, and introduced the information regarding important international clinical trial registries in detail. Clinical trial registration should be developed toward a transparent, compulsory and comprehensive stage. PMID:17498477

  5. Clinical Trials - Participants

    MedlinePlus

    ... participating in was reviewed by an IRB. Further Reading For more information about research protections, see: Office ... data and decide whether the results have medical importance. Results from clinical trials are often published in ...

  6. Participating in Clinical Trials

    MedlinePlus Videos and Cool Tools

    ... 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 ...

  7. Shuffling Adaptive Clinical Trials.

    PubMed

    Gokhale, Sanjay G; Gokhale, Sankalp

    2016-01-01

    Clinical trials are interventional studies on human beings, designed to test the hypothesis for diagnostic techniques, treatments, and disease preventions. Any novel medical technology should be evaluated for its efficacy and safety by clinical trials. The costs associated with developing drugs have increased dramatically over the past decade, and fewer drugs are obtaining regulatory approval. Because of this, the pharmaceutical industry is continually exploring new ways of improving drug developments, and one area of focus is adaptive clinical trial designs. Adaptive designs, which allow for some types of prospectively planned mid-study changes, can improve the efficiency of a trial and maximize the chance of success without undermining validity and integrity of the trial. However it is felt that in adaptive trials; perhaps by using accrued data the actual patient population after the adaptations could deviate from the originally target patient population and so to overcome this drawback; special methods like Bayesian Statistics, predicted probability are used to deduce data-analysis. Here, in this study, mathematical model of a new adaptive design (shuffling adaptive trial) is suggested which uses real-time data, and because there is no gap between expected and observed data, statistical modifications are not needed. Results are obviously clinically relevant. PMID:23751329

  8. International Clinical Trial Day and clinical trials in Ethiopia and Africa.

    PubMed

    Fekadu, Abebaw; Teferra, Solomon; Hailu, Asrat; Gebre-Mariam, Tsige; Addissie, Adamu; Deressa, Wakgari; Yimer, Getnet; Reja, Ahmed

    2014-01-01

    Low income countries like Ethiopia are underrepresented in clinical research. As a major public commitment to clinical research, Ethiopia celebrated the International Clinical Trial Day (ICTD) for the first time on 20 May 2014 under the auspices of Addis Ababa University. The motto for the day was 'Clinical Trials for Excellence in Patient Care'. The celebration offered an opportunity to inform academic staff, researchers, students and the leadership about clinical trials being conducted and to discuss the future of clinical trials in the country. Although clear challenges to the conduct of trials abound, clinical trials registered from Ethiopia in trial registration databases is increasing. Cross-country collaborations, international funding support, motivation of academic staff to conduct clinical trials and the commitment and engagement of the leadership in research are all improving. The overall impact of clinical trials is also encouraging. For example, some of the trials conducted in Ethiopia have informed treatment guidelines. However, administrative capacity, research infrastructure as well as financial support remain weak. There is a need for enhanced university-industry linkage and translation of research findings into locally relevant evidence. Ethiopia, as well as the whole of Africa, has an unparalleled opportunity to lead the way in clinical trials, given its prospect of development and the need to have locally relevant evidence for its growing population. In this commentary we reflect on the celebration of ICTD, the status and opportunities for conducting clinical trials and the way forward for facilitating clinical trials in Ethiopia and Africa. PMID:25526797

  9. Ethics of clinical trials in Nigeria

    PubMed Central

    Okonta, Patrick I.

    2014-01-01

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

  10. COMPETING COMMITMENTS in CLINICAL TRIALS

    PubMed Central

    Lidz, Charles W.; Appelbaum, Paul S.; Joffe, Steven; Albert, Karen; Rosenbaum, Jill; Simon, Lorna

    2013-01-01

    Most discussion about clinical care in clinical trials has concerned whether subjects’ care may be compromised by research procedures. The possibility that clinical researchers might give priority to helping their “patients” even if that required deviating from the imperatives of the research protocol largely has been ignored. We conducted an on-line survey with clinical researchers, including physicians, research nurses and other research staff, to assess the ways and frequency with which clinical trials may be at risk for being compromised by clinical researchers’ attempting to address the clinical needs of subjects. The survey covered recruitment, clinical management while in the trial, and termination decisions. It produced a 72.0% response rate. Over 20% of respondents agreed that researchers should deviate from the protocol to improve subjects’ care; 28% reported that medications restricted by the protocol were given; 21% reported that subjects who were not eligible had been recruited; and 9% said subjects had been retained in a trial despite meeting termination criteria. Some respondents reported that these deviations from the protocol happened many times. The ramifications of these findings are discussed. PMID:19873835

  11. Safety, Acceptability and Adherence of Dapivirine Vaginal Ring in a Microbicide Clinical Trial Conducted in Multiple Countries in Sub-Saharan Africa

    PubMed Central

    Nel, Annalene; Bekker, Linda-Gail; Bukusi, Elizabeth; Hellstrӧm, Elizabeth; Kotze, Philip; Louw, Cheryl; Martinson, Francis; Masenga, Gileard; Montgomery, Elizabeth; Ndaba, Nelisiwe; van der Straten, Ariane; van Niekerk, Neliëtte; Woodsong, Cynthia

    2016-01-01

    Background This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women. Objectives The trial assessed and compared the safety, acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa. Methods 280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports. Results No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective. Conclusions The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of

  12. Gateways to clinical trials.

    PubMed

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

    2005-11-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (Z)-4-Hydroxytamoxifen, [18F]-FPS; Adalimumab, alefacept, alemtuzumab, alfimeprase, aprepitant, aripiprazole, atomoxetine hydrochloride; Belatacept, bortezomib; C340, caspofungin acetate, clazosentan sodium, Cypher; Darbepoetin alfa, DB-289, decitabine, dronedarone hydrochloride, duloxetine hydrochloride; Eletriptan, entecavir, ertapenem sodium, escitalopram oxalate, eszopiclone, etoricoxib; Gaboxadol, gadofosveset sodium, galiximab, gemifloxacin mesilate, glutamine; Human insulin; I-131 ch-TNT-1/B, indiplon, inhaled insulin, isatoribine; L-Arginine hydrochloride, liposomal doxorubicin, lopinavir/ritonavir, lumiracoxib; Magnesium sulfate; Natalizumab; Olmesartan medoxomil, omapatrilat, OncoVEX (GM-CSF); rDNA insulin, rupatadine fumarate; Sorafenib; Tadalafil, teduglutide, temsirolimus, tenofovir disoproxil fumarate, tiotropium bromide; Valdecoxib, vardenafil hydrochloride hydrate. PMID:16357953

  13. Clinical Trials: CSDRG Overview

    ERIC Educational Resources Information Center

    Logemann, Jeri A.

    2004-01-01

    Recent importance placed upon efficacy research has spawned the development of the Communication Sciences and Disorders Clinical Trials Research Group (CSDRG). This group, funded by the National Institutes of Health (NIH), was organized by the American Speech Language and Hearing Association to address the need for more treatment efficacy research…

  14. Adaptive clinical trial designs in oncology

    PubMed Central

    Zang, Yong; Lee, J. Jack

    2015-01-01

    Adaptive designs have become popular in clinical trial and drug development. Unlike traditional trial designs, adaptive designs use accumulating data to modify the ongoing trial without undermining the integrity and validity of the trial. As a result, adaptive designs provide a flexible and effective way to conduct clinical trials. The designs have potential advantages of improving the study power, reducing sample size and total cost, treating more patients with more effective treatments, identifying efficacious drugs for specific subgroups of patients based on their biomarker profiles, and shortening the time for drug development. In this article, we review adaptive designs commonly used in clinical trials and investigate several aspects of the designs, including the dose-finding scheme, interim analysis, adaptive randomization, biomarker-guided randomization, and seamless designs. For illustration, we provide examples of real trials conducted with adaptive designs. We also discuss practical issues from the perspective of using adaptive designs in oncology trials. PMID:25811018

  15. Gateways to clinical trials.

    PubMed

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

    2005-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in the current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: AAV-NGFbeta, aprepitant, aripiprazole, atomoxetine hydrochloride; beta-Methyl-6-chloromelatonin, BMS-214662, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, CEA-TRICOM, cetuximab, ciclesonide, clofarabine, Cypher; Dalbavancin, darbepoetin alfa, darifenacin hydrobromide, desloratadine, Dexamet, drospirenone, drospirenone/ethinylestradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, ertapenem sodium, escitalopram oxalate, eszopiclone; Fenretinide; Gefitinib, gestodene, ghrelin (human); hMaxi-K, human papillomavirus vaccine; Imatinib mesylate, indiplon, iodine (i131) tositumomab, irofulven, ISS-1018; Lasofoxifene tartrate, levodopa/carbidopa/entacapone, liposomal doxorubicin; Nemifitide ditriflutate, nesiritide; Omalizumab; Pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, phVEGF-A165, pimecrolimus, pramlintide acetate; Rasburicase, rimonabant hydrochloride; Satraplatin, St. John's Wort extract, sunitinib malate; Tadalafil, tanaproget, Taxus, tiotropium bromide, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate; Ximelagatran; Zileuton. PMID:16258596

  16. Gateways to clinical trials.

    PubMed

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

    2005-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. PMID:15834466

  17. Gateways to clinical trials.

    PubMed

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

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  18. Gateways to clinical trials.

    PubMed

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

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  19. Departures from the Protocol During Conduct of a Clinical Trial: A Pattern from the Data Record Consistent with a Learning Curve

    PubMed Central

    Taekman, Jeffrey M.; Stafford-Smith, Mark; Velazquez, Eric J.; Wright, Melanie C.; Phillips-Bute, Barbara G.; Pfeffer, Marc A.; Ann Sellers, Mary; Pieper, Karen S.; Newman, Mark F.; Van de Werf, Frans; Diaz, Rafael; Leimberger, Jeff; Califf, Robert M.

    2011-01-01

    Objective Recognition of learning curves in medical skill acquisition has enhanced patient safety through improved training techniques. Clinical trials research has not been similarly scrutinized. We retrospectively evaluated VALIANT, a large multinational, pragmatic, randomized, double-blind, multicenter trial, for evidence of research conduct consistent with a performance “learning curve.” Design Records provided protocol departure (deviations/violations) and documentation query data. For each site, analysis included patient order (e.g., first, second), recruitment rate, and first enrollment relative to study start date. Setting Computerized data from a trial coordinated by an academic research organization collaborating with 10 academic and two commercial research organizations and an industry sponsor. Interventions 931 sites enrolled 14,703 patients. Departures were restricted to the first year. Exclusions included: patient’s death or loss to follow-up within twelve months and subjects 80th or higher at a site. Departures were assessed for variance with higher patient rank, more frequent recruitment, and later start date. Methods and Results 12,367 patients at 931 sites were analyzed. Departures were more common for patients enrolled earlier at a site (P<0.0001). For example, compared to the 30th patient the first had 47% more departures. Departures were also more common with slower enrollment and site start closer to the trial start date (P<0.0001). Similar patterns existed for queries. Conclusions Research performance improved during VALIANT consistent with a “learning curve.” Although effects were not related to a change in outcome (mortality), learning curves in clinical research may have important safety, ethical, research quality, and economic implications for trial conduct. PMID:20702441

  20. Clinical trials of medicines in neonates: the influence of ethical and practical issues on design and conduct

    PubMed Central

    Turner, Mark A

    2015-01-01

    In the past, there has been a perception that ethical and practical problems limit the opportunities for research in neonates. This perception is no longer appropriate. It is now clear that research about the medicines used in neonates is an ethical requirement. It is possible to conduct high quality research in neonates if the research team adapt to the characteristics of this population. Good practice involves respecting the specific needs of newborn babies and their families by adopting relevant approaches to study design, recruitment, pharmacokinetic studies and safety assessment. Neonatal units have a unique culture that requires careful development in a research setting. Clinical investigators need to recognize the clinical and ethical imperative to conduct rigorous research. Industry needs to engage with neonatal networks early in the process of drug development, preferably before contacting regulatory agencies. Follow-up over 3–5 years is essential for the evaluation of medicines in neonates and explicit funding for this is required for the assessment of the benefit and risk of treatments given to sick newborn babies. The views of parents must be central to the development of studies and the research agenda. Ethical and practical problems are no longer barriers to research in neonates. The current challenges are to disseminate good practice and maximize capacity in order to meet the need for research among newborn babies. PMID:25041601

  1. Gateways to clinical trials.

    PubMed

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

    2002-11-01

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

  2. Gateways to clinical trials.

    PubMed

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

    2002-05-01

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

  3. Gateways to clinical trials.

    PubMed

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

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride. PMID:15672123

  4. Gateways to clinical trials.

    PubMed

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

    2002-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses, which has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, providing information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abacavir sulfate; abciximab; abetimus sodium; adalimumab; aldesleukin; almotriptan; alteplase; amisulpride; amitriptyline hydrochloride; amoxicillin trihydrate; atenolol; atorvastatin calcium; atrasentan; Beclometasone dipropionate; bosentan; Captopril; ceftriaxone sodium; cerivastatin sodium; cetirizine hydrochloride; cisplatin; citalopram hydrobromide; Dalteparin sodium; darusentan; desirudin; digoxin; Efalizumab; enoxaparin sodium; ertapenem sodium; esomeprazole magnesium; estradiol; ezetimibe; Famotidine; farglitazar; fluorouracil; fluticasone propionate; fosamprenavir sodium; Glibenclamide; glucosamine sulfate; Heparin sodium; HSPPC-96; hydrochlorothiazide; Imatinib mesilate; implitapide; Lamivudine; lansoprazole; lisinopril; losartan potassium; l-Propionylcarnitine; Melagatran; metformin hydrochloride; methotrexate; methylsulfinylwarfarin; Nateglinide; norethisterone; Olmesartan medoxomil; omalizumab; omapatrilat; omeprazole; oseltamivir phosphate; oxatomide; Pantoprazole; piperacillin sodium; pravastatin sodium; Quetiapine hydrochloride; Rabeprazole sodium; raloxifene hydrochloride; ramosetron hydrochloride; ranolazine; rasburicase; reboxetine mesilate; recombinant somatropin; repaglinide; reteplase; rosiglitazone; rosiglitazone maleate; rosuvastatin calcium; Sertraline; simvastatin; sumatriptan succinate; Tazobactam sodium; tenecteplase; tibolone; tinidazole; tolterodine tartrate; troglitazone; Uniprost; Warfarin sodium; Ximelagatran. PMID:11980386

  5. Gateways to clinical trials.

    PubMed

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

    2002-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, adalimumab, AERx morphine sulphate, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, almotriptan, amprenavir, aripiprazole, atenolol, atorvastatin calcium; BSYX-A110; Cantuzumab mertansine, capravirine, CDP-571, CDP-870, celecoxib; Delavirdine mesilate, docetaxel, dofetilide, donepezil hydrochloride, duloxetine hydrochloride, dutasteride, dydrogesterone; Efavirenz, emtricitabine, enjuvia, enteryx, epristeride, erlotinib hydrochloride, escitalopram oxalate, etanercept, etonogestrel, etoricoxib; Fesoterodine, finasteride, flt3ligand; Galantamine hydrobromide, gemtuzumab ozogamicin, genistein, gepirone hydrochloride; Indinavir sulfate, infliximab; Lamivudine, lamivudine/zidovudine/abacavir sulfate, leteprinim potassium, levetiracetam, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, losartan potassium; MCC-465, MRA; Nebivolol, nesiritide, nevirapine; Olanzapine, OROS(R)-Methylphenidate hydrochloride; Peginterferon alfa-2a, peginterferon alfa-2b, Pimecrolimus, polyethylene glycol 3350, pramlintide acetate, pregabalin, PRO-2000; Risedronate sodium, risperidone, ritonavir, rituximab, rivastigmine tartrate, rofecoxib, rosuvastatin calcium; Saquinavir mesilate, Stavudine; Tacrolimus, tadalafil, tamsulosin hydrochloride, telmisartan, tomoxetine hydrochloride, treprostinil sodium, trimegestone, trimetrexate; Valdecoxib, venlafaxine hydrochloride; Zoledronic acid monohydrate. PMID:12616965

  6. Gateways to clinical trials.

    PubMed

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

    2003-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adalimumab, alefacept, alemtuzumab, almotriptan, AMGN-0007, anakinra, anti-CTLA-4 Mab, L-arginine hydrochloride, arzoxifene hydrochloride, astemizole, atazanavir sulfate, atlizumab; Belimumab, BG-9928, binodenoson, bosentan, botulinum toxin type B, bovine lactoferrin, BufferGel; Caspofungin acetate, ciclesonide,cilomilast, ciluprevir, clofarabine, CVT-3146; Darbepoetin alfa, desloratadine, diflomotecan, doripenem, dronedarone hydrochloride, drotrecogin alfa (activated), DT388-GM-CSF, duloxetine hydrochloride, E-5564, efalizumab, enfuvirtide, esomeprazole magnesium, estradiol acetate, ETC-642, exenatide, exisulind, ezetimib; Febuxostat; Gallium maltolate, ganirelix acetate, garenoxacin mesilate, gefitinib; H11, HuMax; IL-15, IDD-1, IGIV-C, imatinib mesylate, ISIS-14803, ITF-1697, ivabradine hydrochloride; KRN-5500; L-365260, levetiracetam, levosimendan, licofelone, linezolid, LJP-1082, lopinavir lumiracoxib; MCC-478, melatonin, morphine hydrochloride, morphine-6-glucuronide, moxidectin; N-Acetylcarnosine, natalizumab, NM-702, NNC-05-1869, NSC-703940; Ocinaplon OM-89, omalizumab, omeprazole/ sodium bicarbonate, OPC-28326, ospemifene; PEG-filgrastim peginterferon alfa-2a, pegsunercept, pirfenidone, pralmorelin, pregabalin; Recombinant glucagon-like peptide-1 (7-36) amide, repifermin, RSD-1235; S-8184, selodenoson, sodium dichloroacetate, suberanilohydroxamic acid; TAS-102, terfenadine, teriparatide, tipranavir troxacitabine; Ximelagatran; YM-337. PMID:14735233

  7. Gateways to clinical trials.

    PubMed

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

    2003-04-01

    Gateways to clinical trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5A8; Agomelatine, alefacept, almotriptan, anakinra, APC-8015, atazanavir, atomoxetine hydrochloride, azimilide hydrochloride; Bicifadine; Cannabidiol, caspofungin acetate, CAT-213, CGP-51901, ciclesonide, cipamfylline; Darbepoetin alfa, desloratadine, dibotermin alfa, DX-9065a; Ecogramostim, efalizumab, eletriptan, eniluracil, EPI-KAL2, erlosamide, ertapenem sodium, etilevodopa, etoricoxib, ezetimibe; Fosamprenavir calcium, fosamprenavir sodium, fumagillin; Gadofosveset sodium, gefitinib, gemtuzumab ozogamicin; HSPPC-96, human papillomavirus vaccine; Icatibant Id-KLH, imatinib mesylate, INS-37217, iodine (I131) tositumomab; LAS-34475, levobupivacaine hydrochloride, levocetirizine, linezolid, 131I-lipiodol, lonafarnib, lopinavir, LY-450108; Magnetites, MBI-594AN, melagatran, melatonin, mepolizumab, mycophenolic acid sodium salt; NC-100100; 1-Octanol, omalizumab, omapatrilat, onercept; PEG-filgrastim, (PE)HRG21, peginterferon alfa-2a, peginterferon alfa-2b, pleconaril, pneumococcal 7-valent conjugate vaccine, prasterone; Ranelic acid distrontium salt, rasagiline mesilate, reslizumab, rFGF-2, rhOP-1, rosuvastatin calcium, roxifiban acetate; Sitaxsentan sodium, sodium lauryl sulfate; Tadalafil, telithromycin, tenofovir disoproxil fumarate, tipranavir, TMC-114, tucaresol; Valdecoxib, voriconazole; Ximelagatran; Zofenopril calcium, zosuquidar trihydrochloride. PMID:12743628

  8. Gateways to clinical trials.

    PubMed

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

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  9. Gateways to clinical trials.

    PubMed

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

    2007-12-01

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

  10. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

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

  11. Gateways to clinical trials.

    PubMed

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

    2006-05-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com/. This issue focuses on the following selection of drugs: Adalimumab, adenosine triphosphate, alemtuzumab, alendronate sodium/cholecalciferol, aliskiren fumarate, AMGN-0007, aminolevulinic acid methyl ester, anakinra, anidulafungin, aripiprazole, atomoxetine hydrochloride; Bevacizumab, bosentan; Calcipotriol/beta methasone dipropionate, caldaret hydrate, caspofungin acetate, cetuximab, cinacalcet hydrochloride, clopidogrel, cocaine-BSA conjugate, conivaptan hydrochloride, Cypher; Darbepoetin alfa, delmitide, desloratadine, desmoteplase, desoxyepothilone B, disufenton sodium, DU-176b, duloxetine hydrochloride, dutasteride; EBV-specific CTLs, ecogramostim, edodekin alfa, efalizumab, eletriptan, emtricitabine, entecavir, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, etoricoxib, everolimus, ezetimibe; Fanapanel, fondaparinux sodium; Gefitinib, GTI-2040, GW-501516; Her2 E75-peptide vaccine, human insulin; Ibogaine, icatibant acetate, Id-KLH vaccine, imatinib mesylate, immune globulin subcutaneous [human], indacaterol, inolimomab, ipilimumab, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, lanthanum carbonate, lenalidomide, levocetirizine, levodopa methyl ester hydrochloride/carbidopa, levodopa/carbidopa/entacapone, lidocaine/prilocaine; Maraviroc, mecasermin, melevodopa hydrochloride, mepolizumab, mitumomab; Nesiritide; Omalizumab, oral insulin; Parathyroid hormone (human recombinant), patupilone, pegaptanib sodium, PEG-filgrastim, pemetrexed disodium, photochlor, pimecrolimus, posaconazole, prasterone, prasugrel, pregabalin, prilocaine, PRX-00023; QS-21; Ranibizumab, ranirestat, rhodamine 123, rotigaptide; Sarcosine, sirolimus

  12. Gateways to clinical trials.

    PubMed

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

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABT-510, adalimumab, alefacept, ambrisentan, aminolevulinic acid methyl ester, armodafinil, aselizumab, asenapine maleate, azelnidipine; Bevacizumab, bexarotene, bimosiamose, biphasic insulin aspart, bortezomib, bosentan, BQ-123; C340, cannabidiol, caspofungin acetate, CC-4047, certolizumab pegol, cetuximab, ciclesonide, cilansetron, Cypher; Dabigatran etexilate, darbepoetin alfa, darifenacin hydrobromide, desloratadine, dexosome vaccine (melanoma), dimethyl fumarate, dronabinol/cannabidiol, drospirenone, drospirenone/estradiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Efalizumab, eglumetad hydrate, emoxipin hydrochloride, eplerenone, erlotinib hydrochloride, escitalopram oxalate, etonogestrel/ethinylestradiol; Garenoxacin mesilate, gamma-hydroxybutyrate sodium, gefitinib; H5N1 pandemic influenza vaccine, human growth hormone-(177-191), human insulin; Indacaterol, INKP-100, INKP-102, insulin glargine, i.v. gamma-globulin; KLH; Lapatinib, L-arginine hydrochloride, lasofoxifene tartrate, levocetirizine, licochalcone A, LMI vaccine, lomefloxacin, lubiprostone, lumiracoxib; Miglustat, mycograb; Natalizumab, NCX-4016, nortopixantrone hydrochloride; Olmesartan medoxomil, omalizumab, oral insulin, OrM3; Parathyroid hormone (human recombinant), parecoxib sodium, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, pemetrexed disodium, pexelizumab, photochlor, pimecrolimus, pneumococcal 7-valent conjugate vaccine, polyphenon E; R-126638, R-411, resveratrol, roflumilast, RS-86, ruboxistaurin mesilate hydrate, rupatadine fumarate; Sipuleucel-T, somatropin, St. John's Wort extract; Tadalafil, Taxus

  13. Gateways to clinical trials.

    PubMed

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

    2006-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:(R)-Flurbiprofen, 90Yttrium-DOTA-huJ591; ABT-510, ACP-103, Ad5-FGF4, adalimumab, ademetionine, AG-7352, alemtuzumab, Amb a 1 ISS-DNA, anakinra, apaziquone, aprepitant, aripiprazole, atazanavir sulfate; BAL-8557, bevacizumab, BMS-188797, bortezomib, bosentan, brivudine; Calcipotriol/betamethasone dipropionate, cannabidiol, caspofungin acetate, catumaxomab, CERE-120, cetuximab, ciclesonide, cilomilast, cizolirtine citrate, Cypher, cystemustine; Dalbavancin, darifenacin hydrobromide, dasatinib, deferasirox, denosumab, desmoteplase, dihydrexidine, dimethyl fumarate, dutasteride, DW-166HC; Eculizumab, enfuvirtide, entecavir, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, eszopiclone, etoricoxib, everolimus; Fallypride, febuxostat, fenretinide, fesoterodine, fingolimod hydrochloride; Gabapentin enacarbil, gefitinib; hMaxi-K, human papillomavirus vaccine, HYAL-CT1101; Imatinib mesylate, indiplon, inolimomab, ISAtx-247; J591; Lacosamide, landiolol, lasofoxifene tartrate, lestaurtinib, lidocaine/prilocaine, linezolid, lixivaptan, lonafarnib, lopinavir, lopinavir/ritonavir, lumiracoxib; Natalizumab, nesiritide; OC-108, omalizumab, onercept, OSC; Palifermin, palonosetron hydrochloride, parathyroid hormone (human recombinant), parecoxib sodium, PD-MAGE-3 vaccine, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, pegsunercept, pelitinib, pitavastatin calcium, plerixafor hydrochloride, posaconazole, prasterone sulfate, pregabalin; Ramelteon, ranelic acid distrontium salt, rasburicase, rosuvastatin calcium, rotigotine, RSD-1235, rufinamide, rupatadine fumarate; Sarizotan hydrochloride, SHL-749

  14. Gateways to clinical trials.

    PubMed

    Moral, M A; Tomillero, A

    2008-03-01

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

  15. Gateways to clinical trials.

    PubMed

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

    2006-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000

  16. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

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

  17. Gateways to clinical trials.

    PubMed

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

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide

  18. Gateways to clinical trials.

    PubMed

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

    2004-09-01

    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: 101M, 166Ho-DOTMP, 3-AP; Abatacept, abetimus sodium, ACR-16, adefovir dipivoxil, alefacept, AMD-070, aminolevulinic acid hexyl ester, anatumomab mafenatox, anti-CTLA-4 MAb, antigastrin therapeutic vaccine, AP-12009, AP-23573, APC-8024, aripiprazole, ATL-962, atomoxetine hydrochloride; Bevacizumab, bimatoprost, bortezomib, bosentan, BR-1; Calcipotriol/betamethasone dipropionate, cinacalcet hydrochloride, clofazimine, colchicine, cold-adapted influenza vaccine trivalent, CRM197; Desloratadine, desoxyepothilone B, diethylhomospermine; Edodekin alfa, efalizumab, elcometrine, eletriptan, enfuvirtide, entecavir, EP-2101, eplerenone, erlotinib hydrochloride, etoricoxib, everolimus, exherin, ezetimibe; Febuxostat, fluorescein lisicol, fosamprenavir calcium, frovatriptan; Hemoglobin raffimer, HSPPC-96, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, IRX-2, istradefylline, IV gamma-globulin, ixabepilone; Kahalalide F; L-759274, levodopa/carbidopa/entacapone, licofelone, lonafarnib, lopinavir, lurtotecan, LY-156735; MAb G250, mecasermin, melatonin, midostaurin, muraglitazar; Nesiritide, nitronaproxen; O6-Benzylguanine, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, omapatrilat, oral insulin; Parecoxib sodium, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, peptide YY3-36, PG-CPT, phenoxodiol, pimecrolimus, posaconazole; Rasagiline mesilate, rDNA insulin, RG228, rimonabant hydrochloride, rosuvastatin calcium, rotigotine hydrochloride; S-3304, safinamide mesilate, salcaprozic acid sodium salt, SDZ-SID-791, SGN-30, soblidotin

  19. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-09-01

    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: AAV1/SERCA2a, Abacavir sulfate/lamivudine, Adalimumab, Aliskiren fumarate, Ambrisentan, Aripiprazole, AT-7519, Atazanavir sulfate, Atomoxetine hydrochloride, Azacitidine, Azelnidipine; Besifloxacin hydrochloride, Bevacizumab, Bioabsorbable everolimus-eluting coronary stent, Bortezomib, Bosentan, Budesonide/formoterol fumarate; CAIV-T, Carisbamate, Casopitant mesylate, Certolizumab pegol, Cetuximab, Ciclesonide, Ciprofloxacin/dexamethasone, CTCE-9908; Dalcetrapib, Darunavir, Deferasirox, Desloratadine, Disitertide, Drotrecogin alfa (activated), DTA-H19, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Efalizumab, Emtricitabine, Eribulin mesilate, Escitalopram oxalate, Eszopiclone, EUR-1008, Everolimus-eluting coronary stent, Exenatide; Fampridine, Fluticasone furoate, Formoterol fumarate/fluticasone propionate, Fosamprenavir calcium, Fulvestrant; Gabapentin enacarbil, GS-7904L; HPV-6/11/16/18, Human Secretin, Hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, Imexon, Inalimarev/Falimarev, Indacaterol, Indacaterol maleate, Inhalable human insulin, Insulin detemir, Insulin glargine, Ixabepilone; L-Alanosine, Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Loratadine/montelukast sodium, Lutropin alfa; MeNZB, Mepolizumab, Micafungin sodium, Morphine hydrochloride; Nabiximols, Nikkomycin Z; Olmesartan medoxomil, Omalizumab; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Perifosine, PF-489791, Plitidepsin, Posaconazole, Pregabalin; QAX-576; Raltegravir potassium, Ramelteon, Rasagiline

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X

    2008-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prouse Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M, 3F8; Abatacept, ABT-263, Adalimumab, AG-7352, Agatolimod sodium, Alfimeprase, Aliskiren fumarate, Alvimopan hydrate, Aminolevulinic acid hexyl ester, Ammonium tetrathiomolybdate, Anakinra, Aripiprazole, AS-1404, AT-9283, Atomoxetine hydrochloride, AVE-1642, AVE-9633, Axitinib, AZD-0530; Becocalcidiol, Belotecan hydrochloride, Bevacizumab, BG-9928, BIBF-1120, BMS-275183, Bortezomib, Bosentan; Catumaxomab, Cetuximab, CHR-2797, Ciclesonide, Clevidipine, Cypher, Cytarabine/daunorubicin; Darifenacin hydrobromide, Darunavir, Denosumab, Desvenlafaxine succinate, Disufenton sodium, Duloxetine hydrochloride, Dutasteride; Eculizumab, Efalizumab, Eicosapentaenoic acid/docosahexaenoic acid, Eplerenone, Epratuzumab, Erlotinib hydrochloride, Escitalopram oxalate, Ethynylcytidine, Etravirine, Everolimus, Ezetimibe; Fulvestrant; Garenoxacin mesilate, Gefitinib, Gestodene; HI-164, Hydralazine hydrochloride/isosorbide dinitrate; Icatibant acetate, ICX-RHY, Idraparinux sodium, Indacaterol, Ispronicline, Ivabradine hydrochloride, Ixabepilone; KB-2115, KW-2449; L-791515, Lapatinib ditosylate, LGD-4665, Licofelone, Liposomal doxorubicin, Lisdexamfetamine mesilate, Lumiracoxib; Methoxy polyethylene glycol-epoetin-beta, Miglustat, Mipomersen sodium, Mitumprotimut-T, MK-0822A, MK-0974; Nelarabine; Obatoclax mesylate, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paliperidone, Palonosetron hydrochloride, Panitumumab, Pegfilgrastim, Peginterferon alfa-2a, Pemetrexed disodium, Perospirone hydrochloride, Pertuzumab, Pimecrolimus, Pitrakinra, Pixantrone maleate, Posaconazole, Pregabalin; Quercetin; RALGA, Raltegravir

  1. Gateways to clinical trials.

    PubMed

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

    2004-10-01

    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: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  2. Gateways to clinical trials.

    PubMed

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

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  3. Gateways to clinical trials.

    PubMed

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

    2005-04-01

    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

  4. Relation between the Global Burden of Disease and Randomized Clinical Trials Conducted in Latin America Published in the Five Leading Medical Journals

    PubMed Central

    Perel, Pablo; Miranda, J. Jaime; Ortiz, Zulma; Casas, Juan Pablo

    2008-01-01

    Background Since 1990 non communicable diseases and injuries account for the majority of death and disability-adjusted life years in Latin America. We analyzed the relationship between the global burden of disease and Randomized Clinical Trials (RCTs) conducted in Latin America that were published in the five leading medical journals. Methodology/Principal Findings We included all RCTs in humans, exclusively conducted in Latin American countries, and published in any of the following journals: Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine. We described the trials and reported the number of RCTs according to the main categories of the global burden of disease. Sixty-six RCTs were identified. Communicable diseases accounted for 38 (57%) reports. Maternal, perinatal, and nutritional conditions accounted for 19 (29%) trials. Non-communicable diseases represent 48% of the global burden of disease but only 14% of reported trials. No trial addressed injuries despite its 18% contribution to the burden of disease in 2000. Conclusions/Significance A poor correlation between the burden of disease and RCTs publications was found. Non communicable diseases and injuries account for up to two thirds of the burden of disease in Latin America but these topics are seldom addressed in published RCTs in the selected sample of journals. Funding bodies of health research and editors should be aware of the increasing burden of non communicable diseases and injuries occurring in Latin America to ensure that this growing epidemic is not neglected in the research agenda and not affected by publication bias. PMID:18301772

  5. Enhancing clinical evidence by proactively building quality into clinical trials

    PubMed Central

    Meeker-O’Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

    2016-01-01

    Background: Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. Methods: The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials (“quality-by-design”), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. Conclusion: The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of

  6. Likelihood and clinical trials.

    PubMed

    Hill, G; Forbes, W; Kozak, J; MacNeill, I

    2000-03-01

    The history of the application of statistical theory to the analysis of clinical trials is reviewed. The current orthodoxy is a somewhat illogical hybrid of the original theory of significance tests of Edgeworth, Karl Pearson, and Fisher, and the subsequent decision theory approach of Neyman, Egon Pearson, and Wald. This hegemony is under threat from Bayesian statisticians. A third approach is that of likelihood, stemming from the work of Fisher and Barnard. This approach is illustrated using hypothetical data from the Lancet articles by Bradford Hill, which introduced clinicians to statistical theory. PMID:10760630

  7. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-10-01

    Gateways to clinical trials is a guide to the most recent trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (+)-Dapoxetine hydrochloride, (S)-Tenatoprazole sodium salt monohydrate 19-28z, Acotiamide hydrochloride hydrate, ADV-TK, AE-37, Aflibercept, Albinterferon alfa-2b, Aliskiren fumarate, Asenapine maleate, Axitinib; Bavituximab, Becatecarin, beta-1,3/1,6-Glucan, Bevacizumab, Bremelanotide; Calcipotriol/betamethasone dipropionate, Casopitant mesylate, Catumaxomab, CDX-110, Cediranib, CMD-193, Cositecan; Darinaparsin, Denosumab, DP-b99, Duloxetine hydrochloride; E75, Ecogramostim, Elacytarabine, EMD-273063, EndoTAG-1, Enzastaurin hydrochloride, Eplerenone, Eribulin mesilate, Esomeprazole magnesium, Etravirine, Everolimus, Ezetimibe; Faropenem daloxate, Febuxostat, Fenretinide; Ghrelin (human); I-131 ch-TNT-1/B, I-131-3F8, Iclaprim, Iguratimod, Iloperidone, Imatinib mesylate, Inalimarev/Falimarev, Indacaterol, Ipilimumab, Iratumumab, Ispinesib mesylate, Ixabepilone; Lapatinib ditosylate, Laquinimod sodium, Larotaxel dehydrate, Linezolid, LOR-2040; Mapatumumab, MKC-1, Motesanib diphosphate, Mycophenolic acid sodium salt; NK-012; Olanzapine pamoate, Oncolytic HSV, Ortataxel; Paclitaxel nanoparticles, Paclitaxel poliglumex, Paliperidone palmitate, Panitumumab, Patupilone, PCV-9, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pertuzumab, Picoplatin, Pimavanserin tartrate, Pimecrolimus, Plerixafor hydrochloride, PM-02734, Poly I:CLC, PR1, Prasugrel, Pregabalin, Progesterone caproate, Prucalopride, Pumosetrag hydrochloride; RAV-12, RB-006, RB-007, Recombinant human erythropoietin alfa, Rimonabant, Romidepsin; SAR-109659, Satraplatin, Sodium butyrate; Tadalafil, Talampanel, Tanespimycin, Tarenflurbil, Tariquidar

  8. White Paper: Recommendations on the Conduct of Superiority and Organism-Specific Clinical Trials of Antibacterial Agents for the Treatment of Infections Caused by Drug-Resistant Bacterial Pathogens

    PubMed Central

    2012-01-01

    There is a critical need for new pathways to develop antibacterial agents to treat life-threatening infections caused by highly resistant bacteria. Traditionally, antibacterial agents have been studied in noninferiority clinical trials that focus on one site of infection (eg, pneumonia, intra-abdominal infection). Conduct of superiority trials for infections caused by highly antibiotic-resistant bacteria represents a new, and as yet, untested paradigm for antibacterial drug development. We sought to define feasible trial designs of antibacterial agents that could enable conduct of superiority and organism-specific clinical trials. These recommendations are the results of several years of active dialogue among the white paper's drafters as well as external collaborators and regulatory officials. Our goal is to facilitate conduct of new types of antibacterial clinical trials to enable development and ultimately approval of critically needed new antibacterial agents. PMID:22891041

  9. Gateways to Clinical Trials.

    PubMed

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

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  10. Gateways to clinical trials.

    PubMed

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

    2004-04-01

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

  11. Gateways to clinical trials.

    PubMed

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

    2003-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 81C6; Adefovir dipivoxil, Agalsidase alfa, AGM-1470, albumin interferon alfa, alefacept, alosetron hydrochloride, anakinra, anti-CTLA-4 Mab, aprepitant, aripiprazole, atazanavir; BAY-43-9006, BBR-3438, beta-L-Fd4C, bimatoprost, bortezomib, bosentanBR96-doxorubicin; Caspofungin acetate, ciclesonide, cilengitide, cilomilast, COL-1621, COL-3, CpG-7909, cyclosporine; DCVax-Brain, dexmethylphenidate hydrochloride, dexosome vaccine (melanoma), donepezil hydrochloride, drotrecogin alfa (activated), DTI-015, [99Tc]-DTPA-mannosyldextran, duloxetine hydrochloride; Emivirine, emtricitabine, entecavir, epothilone B, estradiol-MNP, etonogestrel/etonogestrel/ethinylestradiol, etoricoxib; Febuxostat, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GVS-111; Heparinase I, HspE7, human alpha-glucosidase, human insulin; Imatinib mesylate, INGN-241, interferon alfa B/D hybrid, interferon alfa Biphasix, ISIS-14803; Lanicemine hydrochloride, 1311-lipiodol, liposome-encapsulated mitoxantrone, lixivaptan, lumiracoxib, lupus-AHP, LY-466700; Marimastat, MEN-10755, micafungin sodium; Nitronaproxen, NSC-683864 Omalizumab, oral insulin; Palonosetron hydrochloride, peginterferon alfa-2a, pimecrolimus, pralnacasan, pramlintide acetate, pregabalin, pyrazoloacridine; R-165335, ranolazine, risperidone, RPR-109881;, RSD-1235, Satraplatin, seocalcitol, sertindole, SMART anti-interferon gamma antibody, sulfasalazine; T-138067, TAK-013, tegaserod maleate, telithromycin, tenofovir disoproxil fumarate, teriparatide, tiotropium bromide, tipifarnib, TP-38; Valdecoxib, vatalanib succinate, voriconazole; ZD-9331. PMID:12690708

  12. Gateways to clinical trials.

    PubMed

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

    2004-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 101M; Adalimumab, adefovir dipivoxil, adenosine triphosphate, albumin interferon alfa, alefacept, alemtuzumab, aminolevulinic acid hexyl ester, autologous renal tumor vaccine, azimilide hydrochloride; Bortezomib, bosentan, BR-1; C340, cantuzumab mertansine, caspofungin acetate, CGP-36742, CHAMPION everolimus-eluting coronary stent, cypher; Dalbavancin, darbepoetin alfa, desloratadine, duloxetine hydrochloride, dutasteride; Efalizumab, emtricitabine, enfuvirtide, erlosamide, ertapenem sodium, everolimus, ezetimibe; Flesinoxan hydrochloride, fosamprenavir calcium, FR-901228, frovatriptan; Gadofosveset sodium, gadomer-17, galiximab, gamma-hydroxybutyrate sodium, gefitinib; HuOKT3gamma1(Ala234-Ala235); IDN-6556, imatinib mesylate, iodine (I131) tositumomab, iseganan hydrochloride, ixabepilone; Keratinocyte growth factor; LB-80380, levocetirizine, liposomal doxorubicin, LMB-9, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Mecasermin, midostaurin, morphine hydrochloride; Natalizumab, nelfinavir, nesiritide, niacin/lovastatin; Olcegepant, omalizumab, oregovomab; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, perospirone hydrochloride, pexelizumab, pimecrolimus, prinomastat; Resiquimod, rhIGFBP-3, rhIGF-I/rhIGFBP-3, ritanserin, ro-31-7453, rosuvastatin calcium; SCIO-469, SDZ-SID-791, SU-11248, suberanilohydroxamic acid; Tadalafil, taxus, telithromycin, tenofovir disoproxil fumarate, TER-286, tezosentan disodium, TH-9507, tipifarnib, tipranavir, tolvaptan, tramadol hydrochloride/acetaminophen, travoprost, treprostinil sodium, tucaresol

  13. Gateways to clinical trials.

    PubMed

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

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  14. Gateways to clinical trials.

    PubMed

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

    2003-09-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, adefovir dipivoxil, AGI-1067, alefacept, alemtuzumab, ALVAC-p53, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, Anti-CTLA-4 Mab, AOD-9604, apafant, aprinocarsen sodium, arsenic trioxide; Balaglitazone, BIM-23190, bimatoprost, bortezomib, bosentan, BR-1; Canertinib dihydrochloride, CDP-850, cevimeline hydrochloride, cinacalcet hydrochloride, clenoliximab, clevudine, CN-787; D-003, darusentan, deferasirox, desloratadine dexanabinol, duloxetine hydrochloride; E-5564, edaravone, efaproxiral sodium, elvucitabine emfilermin, EN-101, enfuvirtide, entecavir, epithalon, eplerenone, erlotinib hydrochloride, escitalopram oxalate, esomeprazole magnesium, eszopiclone, etilefrine pivalate hydrochloride etoricoxib, everolimus, exenatide; Fidarestat, fondaparinux sodium; Ganstigmine hydrochloride; Homoharringtonine, HuMax-IL-15, hyperimmune IVIG; Imatinib mesylate, IMC-1C11, Inhaled insulin, irofulven, iseganan hydrochloride, ISIS-14803, ISIS-5132, ivabradine hydrochloride; Keratinocyte growth factor; Lafutidine, lanthanum carbonate, LAS-34475, levocetirizine, liraglutide, LY-307161 SR; Magnesium sulfate, maribavir, melatonin, mycobacterium cell wall complex; NN-414, NO-aspirin, nociceptin, nolomirole hydrochloride; Olmesartan medoxomil oral insulin, ospemifene; PDX, perillyl alcohol, pimecrolimus, pitavastatin calcium, pramlintide acetate, prasterone, pregabalin, PRO-542, PV-701, pyrazoloacridine; R-744, ranelic acid distrontium salt, rasburicase, rDNA insulin, resiniferatoxin, reslizumab, ridogrel, riplizumab ropivacaine, rosuvastatin calcium, roxifiban acetate, ruboxistaurin mesilate

  15. Gateways to clinical trials.

    PubMed

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

    2004-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, Ad5-FGF4, adeno-Interferon gamma, AE-941, AERx, alemtuzumab, alicaforsen sodium, almotriptan, alpharadin, anakinra, anatumomab mafenatox, ANG-453, anti-CTLA-4 Mab, AP-12009, aprepitant, aripiprazole, arsenic trioxide, astemizole, atlizumab, atomoxetine hydrochloride; Bevacizumab, BG-9928, BMS-188667, botulinum toxin type B, BufferGel; Caffeine, CDP-870, cetuximab, cilomilast, ciluprevir, clofarabine, continuous erythropoiesis receptor activator, CP-461; Darbepoetin alfa, deferasirox, desloratadine, desoxyepothilone B, diflomotecan, dolasetron, drotrecogin alfa (activated), duloxetine hydrochloride; ED-71, efalizumab, efaproxiral sodium, EKB-569, eletriptan, EMD-72000, enfuvirtide, erlotinib hydrochloride, escitalopram oxalate, etoricoxib; Fampridine, ferumoxytol, fondaparinux sodium; Gadofosveset sodium, gastrazole, gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride glutamine; hLM609, HSPPC-96, human insulin; IDD-1, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; Keratinocyte growth factor; Lapatinib, laquinimod, LDP-02, LE-SN38, levetiracetam, levosimendan, licofelone, liposomal doxorubicin, liposomal NDDP, lopinavir, lumiracoxib, LY-156735; Morphine hydrochloride, morphine-6-glucuronide, motexafin gadolinium, MS-27-275, MVA-5T4, MVA-Muc1-IL-2; Nemifitide ditriflutate, neridronic acid nitronaproxen, NSC-683864, NSC-703940, NVP-LAF-237; Oblimersen sodium, ocinaplon, oncomyc-NG, OPC-28326, ortataxel, ospemifene; Palonosetron hydrochloride, PEG-filgrastim peginterferon alfa-2(a), peginterferon alfa-2b, pegsunercept, pemetrexed disodium, pregabalin, prilocaine, pyridoxamine; RDP

  16. Gateways to clinical trials.

    PubMed

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

    2006-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium

  17. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa

  18. Gateways to clinical trials.

    PubMed

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

    2006-10-01

    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: (-)-Epigallocatechin gallate, (-)-gossypol, 2-deoxyglucose, 3,4-DAP, 7-monohydroxyethylrutoside; Ad5CMV-p53, adalimumab, adefovir dipivoxil, ADH-1, alemtuzumab, aliskiren fumarate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, amrubicin hydrochloride, AN-152, anakinra, anecortave acetate, antiasthma herbal medicine intervention, AP-12009, AP-23573, apaziquone, aprinocarsen sodium, AR-C126532, AR-H065522, aripiprazole, armodafinil, arzoxifene hydrochloride, atazanavir sulfate, atilmotin, atomoxetine hydrochloride, atorvastatin, avanafil, azimilide hydrochloride; Bevacizumab, biphasic insulin aspart, BMS-214662, BN-83495, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, cetuximab, chrysin, ciclesonide, clevudine, clofarabine, clopidogrel, CNF-1010, CNTO-328, CP-751871, CX-717, Cypher; Dapoxetine hydrochloride, darifenacin hydrobromide, dasatinib, deferasirox, dextofisopam, dextromethorphan/quinidine sulfate, diclofenac, dronedarone hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Edaravone, efaproxiral sodium, emtricitabine, entecavir, eplerenone, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, ezetimibe, ezetimibe/simvastatin; Finrozole, fipamezole hydrochloride, fondaparinux sodium, fulvestrant; Gabapentin enacarbil, gaboxadol, gefitinib, gestodene, ghrelin (human); Human insulin, human papillomavirus vaccine; Imatinib mesylate, immunoglobulin intravenous (human), indiplon, insulin detemir, insulin glargine, insulin glulisine, intranasal insulin, istradefylline, i.v. gamma

  19. Gateways to clinical trials.

    PubMed

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

    2005-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T

  20. Gatekeepers for pragmatic clinical trials.

    PubMed

    Whicher, Danielle M; Miller, Jennifer E; Dunham, Kelly M; Joffe, Steven

    2015-10-01

    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

  1. Lessons learned from radiation oncology clinical trials.

    PubMed

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

    2013-11-15

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

  2. Legal and ethical obligations to conduct a clinical drug trial in Australia as an investigator initiated and sponsored study for an overseas pharmaceutical company.

    PubMed

    Beran, Roy G

    2004-01-01

    obligations were addressed in a fashion which allowed the conduct of a trial adopting a proven methodology but novel infrastructure such that it was a totally independent study with regards conduct and reporting of final data, irrespective of the results being either positive or negative. This may represent a more acceptable way to ensure that future clinical trials are devoid of undue influence from the pharmaceutical industry which may still fund the study. PMID:15685926

  3. [Critical reading of clinical trials].

    PubMed

    Aptel, F; Cucherat, M; Blumen-Ohana, E; Denis, P

    2011-12-01

    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. PMID:21992992

  4. Clinical Research and Clinical Trials

    MedlinePlus

    ... you can get involved. Doing your own clinical research project? Then select the Guidance for Clinical Researchers link to learn more about the NICHD's clinical research processes and policies. Last Reviewed: 03/06/2012 ...

  5. Reflections 1 year into the 21-Center National Institutes of Health--funded WRIST study: a primer on conducting a multicenter clinical trial.

    PubMed

    2013-06-01

    The Wrist and Radius Injury Surgery Trial (WRIST) study group is a collaboration of 21 hand surgery centers in the United States, Canada, and Singapore, to showcase the interest and capability of hand surgeons to conduct a multicenter clinical trial. The WRIST study group was formed in response to the seminal systematic review by Margaliot et al and the Cochrane report that indicated marked deficiency in the quality of evidence in the distal radius fracture literature. Since the initial description of this fracture by Colles in 1814, over 2,000 studies have been published on this subject; yet, high-level studies based on the principles of evidence-based medicine are lacking. As we continue to embrace evidence-based medicine to raise the quality of research, the lessons learned during the organization and conduct of WRIST can serve as a template for others contemplating similar efforts. This article traces the course of WRIST by sharing the triumphs and, more important, the struggles faced in the first year of this study. PMID:23608306

  6. Globalization of Alzheimer's disease clinical trials

    PubMed Central

    2011-01-01

    Alzheimer's disease (AD) therapies are increasingly being tested in global clinical trials. A search of ClincalTrials.gov revealed that of 269 currently active trials, 28% are currently being conducted in the United States; the majority of trials and the majority of trial sites are ex-US. The US has the largest number of trial sites of any single country; cumulatively, nearly half of all sites are outside the US. The US conducts more trials in all phases of drug development but has a greater proportion of phase 3 trials. The increasing importance of global participants in clinical trials emphasizes the importance of considering the ethnic and international factors that may influence trial outcome. The International Conference on Harmonization guidelines divide ethnic factors that may affect drug development into intrinsic and extrinsic influences. These include language, cultural factors, educational levels, the general level of health and standard of care, as well as nutrition and diet. Ethnic influences on pharmacokinetics are known for some metabolic pathways. The biology of AD may also differ among the world's populations. The frequency of the apolipoprotein e4 allele, a major risk factor for AD, differs internationally. Genetic variations might also affect inflammatory, excitotoxic, and oxidative components of AD. Diagnostic standards and experience vary from country to country. Levels of practitioner training and experience, diagnostic approaches to AD, and attitudes regarding aging and AD may differ. Experience and sophistication with regard to clinical trial conduct also vary within and between countries. Experience with conducting the necessary examinations, as well as the linguistic and cultural validity of instrument translations, may affect trial outcomes. Operational and regulatory aspects of clinical trials vary and provide important barriers to seamless conduct of multiregional clinical trials. Collection and testing of biological samples, continuous

  7. Gateways to clinical trials.

    PubMed

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

    2005-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate

  8. An Independent Randomized Clinical Trial of Multisystemic Therapy with Non-Court-Referred Adolescents with Serious Conduct Problems

    PubMed Central

    Weiss, Bahr; Han, Susan; Harris, Vicki; Catron, Tom; Ngo, Victoria K.; Caron, Annalise; Gallop, Robert; Guth, Carol

    2013-01-01

    Objective Adolescent conduct problems exact serious social as well as personal costs, and effective treatments are essential. One of the most widely disseminated and effective programs for the treatment of serious conduct problems in adolescents is Multisystemic Therapy (MST). However, most evaluations of MST have involved the developers of MST. The purpose of the present study was to conduct an independent evaluation of MST, with non-court-referred adolescents with conduct problems. Method Participants were 164 adolescents aged 11 to 18 years who were recruited from self-contained behavior intervention classrooms in public schools. Adolescents and their families were randomly assigned to receive MST or services as usual. Outcome measures assessed conduct problems, school functioning, and court records of criminal behavior. Participants were followed for 18 months after baseline using parent, adolescent, and teacher reports; arrest data were collected for 2.5 years post-baseline. Results Two of four primary outcome measures focused on externalizing problems showed significant treatment effects favoring MST. Several secondary and intervention targets pertaining to family functioning and parent psychopathology showed positive effects of MST, and no negative effects were identified. Conclusions Results provide some further support for the effectiveness of MST, although smaller effect sizes than previous studies also suggest the complexity of successful dissemination, particularly to non-court-referred populations. PMID:23937347

  9. The Dynamo Clinical Trial

    NASA Astrophysics Data System (ADS)

    Ayres, Thomas R.

    2016-04-01

    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.)

  10. The Clinical Trials Transformation Initiative (CTTI).

    PubMed

    Grignolo, Alberto

    2011-01-01

    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. PMID:21430332

  11. Social media in clinical trials.

    PubMed

    Thompson, Michael A

    2014-01-01

    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. PMID:24857086

  12. Developing clinical trials for biosimilars.

    PubMed

    Bui, Lynne A; Taylor, Carrie

    2014-02-01

    Biosimilars offer the prospect of providing efficacious and safe treatment options for many diseases, including cancer, while potentially increasing accessibility with greater affordability relative to biologics. Because biologics are large, complex molecules that cannot be exactly duplicated, biosimilars cannot be considered "generic" versions of biologic drugs. This review will examine important considerations for biosimilar clinical trials. Since the aim of biosimilar manufacturing is to produce a molecule highly similar to the reference biologic, a comparability exercise is needed to demonstrate similarity with the reference biologic product based on physicochemical characterization. In vitro analytical studies and in vivo studies as well as pharmacokinetic/pharmacodynamic (PK/PD) assessments also are conducted. Lastly, because it may not be possible to fully characterize a biosimilar in relation to its reference biologic, robust pharmacovigilance strategies are utilized to ensure that any matters in regard to safety can be monitored. Other key topics will be discussed, including regulatory guidance for the evaluation of biosimilars, clinical trial design considerations, and whether data submitted for the approval of a biosimilar for one indication can be extrapolated to other indications for which the reference biologic is approved. European and Canadian experiences in biosimilar development will be reviewed. PMID:24560024

  13. Data fraud in clinical trials

    PubMed Central

    George, Stephen L; Buyse, Marc

    2015-01-01

    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

  14. Hybrid 10 Clinical Trial

    PubMed Central

    Gantz, Bruce J.; Hansen, Marlan R.; Turner, Christopher W.; Oleson, Jacob J.; Reiss, Lina A.; Parkinson, Aaron J.

    2010-01-01

    Acoustic plus electric (electric-acoustic) speech processing has been successful in highlighting the important role of articulation information in consonant recognition in those adults that have profound high-frequency hearing loss at frequencies greater than 1500 Hz and less than 60% discrimination scores. Eighty-seven subjects were enrolled in an adult Hybrid multicenter Food and Drug Administration clinical trial. Immediate hearing preservation was accomplished in 85/87 subjects. Over time (3 months to 5 years), some hearing preservation was maintained in 91% of the group. Combined electric-acoustic processing enabled most of this group of volunteers to gain improved speech understanding, compared to their preoperative hearing, with bilateral hearing aids. Most have preservation of low-frequency acoustic hearing within 15 dB of their preoperative pure tone levels. Those with greater losses (> 30 dB) also benefited from the combination of electric-acoustic speech processing. Postoperatively, in the electric-acoustic processing condition, loss of low-frequency hearing did not correlate with improvements in speech perception scores in quiet. Sixteen subjects were identified as poor performers in that they did not achieve a significant improvement through electric-acoustic processing. A multiple regression analysis determined that 91% of the variance in the poorly performing group can be explained by the preoperative speech recognition score and duration of deafness. Signal-to-noise ratios for speech understanding in noise improved more than 9 dB in some individuals in the electric-acoustic processing condition. The relation between speech understanding in noise thresholds and residual low-frequency acoustic hearing is significant (r = 0.62; p < 0.05). The data suggest that, in general, the advantages gained for speech recognition in noise by preserving residual hearing exist, unless the hearing loss approaches profound levels. Preservation of residual low

  15. Inept media trials of clinical trials

    PubMed Central

    Ramamurthy, N. V.

    2012-01-01

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

  16. How to Plan and Conduct a Mock Trial: Civil Trial.

    ERIC Educational Resources Information Center

    Missouri State Bar Association, Jefferson City.

    This document contains resources and suggested steps to help secondary teachers organize and conduct a mock trial. Although written specifically for use in Missouri, the document can easily be used and adapted by teachers in other states. The authors believe that a mock trial is a valuable learning experience in many ways. It may be used to help…

  17. Clinical Trials and Older People

    MedlinePlus

    ... have a much wider applicability. Researchers need the participation of older people in their clinical trials so ... contact with questions about the study or your participation. Control group —the group of participants who get ...

  18. Birth Control in Clinical Trials

    PubMed Central

    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.

    2015-01-01

    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

  19. Malaria diagnostics in clinical trials.

    PubMed

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

    2013-11-01

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

  20. Malaria Diagnostics in Clinical Trials

    PubMed Central

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

    2013-01-01

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

  1. [Randomized clinical trials and real clinical practice].

    PubMed

    Heerlein, Andrés

    2009-01-01

    One of the emerging problems in modern medicine is that part of its highly efficacious treatments do not show significant effectiveness in real world systems of care. Efficacy studies address the appropriate dosages, short term response and feasibility of treatments in carefully selected populations, but they do not necessarily provide information for decisions in clinical practice. This review aims to present strengths and limitations of different methodological types of trials and to offer an overview of how knowledge from clinical trials can be used for clinical practice. The important effect of funding source on the outcome of randomized controlled trials is discussed. Some key questions in the treatment assessment of depression, schizophrenia and different medical conditions are discussed, with a focus on the possibilities and restrictions of translating clinical trial results into real-world settings. Empirical evidence shows that although randomized controlled trials are the gold standard for proving efficacy of a therapeutic procedure they often suffer from funding source bias and from lack of generalizability. Effectiveness studies evaluate effects of treatments under conditions approximating usual care. Another key area that can be addressed by effectiveness studies is the impact on important health policy measures such as disability days, days of work or medical costs, etc. Conclusions show that the future assessment of treatment regimes for clinical utility requires less biased efficacy studies and more effectiveness studies addressing major issues from all relevant perspectives. PMID:19543562

  2. Elderly patients’ participation in clinical trials

    PubMed Central

    Shenoy, Premnath; Harugeri, Anand

    2015-01-01

    The elderly population is a large and the fastest-growing portion of the population worldwide. The elderly make up the lion's share of patients for certain health conditions including cancer, cardiovascular disease, arthritis, and Parkinson's disease, among others in most parts of the world. Furthermore, elderly make up the majority of patients for many medications treating chronic conditions. Typically, clinical trials conducted in adult population include patients between the ages of 18 and 64 years. However, drugs should be studied in all age groups and trial participants should be representative of the patient population receiving the therapy in daily medical practice. Elderly patients are poorly represented in clinical trials. Hence, there is inadequate evidence and knowledge about responses of geriatric patients to medications. Regulatory authorities in developed countries urge to avoid arbitrary upper age limits and advise researchers and industry not to exclude elderly people from clinical trials without a valid reason. Since last few years Indian regulatory authority has been stipulating upper age limit for studies conducted in India. The Central Drugs Standard Control Organization (CDSCO) will be doing a great contribution to the researchers if it changes its view on stipulating upper age restrictions in clinical studies. This article describes the need for including elderly patients in the clinical trials in order to garner data from geriatric patients who form major medication users in most of the chronic diseases. PMID:26623388

  3. Research misconduct among clinical trial staff.

    PubMed

    Redman, Barbara K; Templin, Thomas N; Merz, Jon F

    2006-07-01

    Between 1993 and 2002, 39 clinical trial staff were investigated for scientific misconduct by the Office of Research Integrity (ORI). Analysis of ORI case records reveals practices regarding workload, training and supervision that enable misconduct. Considering the potential effects on human subjects protection, quality and reliability of data, and the trustworthiness of the clinical research enterprise, regulations or guidance on use of clinical trial staff ought to be available. Current ORI regulations do not hold investigators or institutions responsible for supervision and training of clinical trial staff. Given the important issues at stake, the definition of research misconduct should encompass the intentional or negligent mismanagement of scientific projects. Individual institutions and professional associations not only can but should adopt stricter standards of conduct than those reflected in federal regulations. PMID:16909150

  4. [Quality control in clinical trials].

    PubMed

    Fukushima, M

    1996-01-01

    Quality control (QC) in clinical trials means the procedures which insure protection of human subjects from research risk, reliability of the data, and thereby assures internal consistency. This has been developed since 1970s in the US, by establishing various regulations which are now called GCP. From the viewpoint of total QC, it should be emphasized that rigorous review of protocol by the Institutional Review Board and obtaining Informed Consent are prerequisites for insuring the quality of the given trial at high scientific level. When pursuing a clinical trial, first of all, facilities of the institutions and the ability of investigators must be of high quality. For this reason, at each institution previous data related to trials should be thoroughly reviewed and analyzed prior to developing a protocol. Educational courses in QC in clinical practice are invaluable. QC of diagnosis means, for example, central pathology review and standardization of diagnostic procedures and process. Secondly, at each institution, data managers collect the data and submit them to the central office at the indicated time. In order to evolve clinical trial, continuous education for data managers and expansion of their job are encouraged. Thirdly, at the statistical center independent from the research group office, subject-specific data managers, the biostatistical staff, must check submitted forms for completeness, consistency and accuracy. Finally, at the data analysis, quality evaluation of the research should also be carried out. Throughout the trial, monitoring and audit are particularly important to assure quality. The sponsor has the responsibility of monitoring the trial and make rigorous onsite visits, and the individual study group also have a monitoring program, while the FDA and the NCI audit by themselves. The purpose of audit is not only to assure data reliability but also to check out patient compliance to drug, education as to regulations and rules of clinical

  5. Clinical Trials | Division of Cancer Prevention

    Cancer.gov

    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. |

  6. HIV/AIDS Clinical Trials Fact Sheet

    MedlinePlus

    HIV Prevention HIV/AIDS Clinical Trials (Last updated 9/15/2015; last reviewed 9/15/2015) Key Points HIV/AIDS clinical trials are ... and effective in people. What is an HIV/AIDS clinical trial? HIV/AIDS clinical trials help researchers ...

  7. Cancer nanotherapeutics in clinical trials.

    PubMed

    Lytton-Jean, Abigail K R; Kauffman, Kevin J; Kaczmarek, James C; Langer, Robert

    2015-01-01

    To be legally sold in the United States, all drugs must go through the FDA approval process. This chapter introduces the FDA approval process and describes the clinical trials required for a drug to gain approval. We then look at the different cancer nanotherapeutics and in vivo diagnostics that are currently in clinical trials or have already received approval. These nanotechnologies are catagorized and described based on the delivery vehicle: liposomes, polymer micelles, albumin-bound chemotherapeutics, polymer-bound chemotherapeutics, and inorganic particles. PMID:25895874

  8. Quality of clinical trials: A moving target

    PubMed Central

    Bhatt, Arun

    2011-01-01

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

  9. Complementary and Alternative Medicine Cancer Clinical Trials

    MedlinePlus

    ... patients. Currently, what cancer clinical trials are the NCI and medical community sponsoring involving CAM modalities? Cancer CAM clinical trials are listed in NCI’s PDQ ® (Physician Data Query) computer database of clinical ...

  10. Complementary and Alternative Medicine Cancer Clinical Trials

    MedlinePlus

    ... patients. Currently, what cancer clinical trials are the NCI and medical community sponsoring involving CAM modalities? Cancer CAM clinical trials are listed in NCI's PDQ ® (Physician Data Query) computer database of clinical ...

  11. Clinical Trials in Noninfectious Uveitis

    PubMed Central

    Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

    2015-01-01

    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

  12. The ethics of clinical trials

    PubMed Central

    Nardini, Cecilia

    2014-01-01

    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

  13. Clinical Trials: Key to Medical Progress

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Clinical Trials: Key to Medical Progress Past Issues / Summer 2008 ... this page please turn Javascript on. Photo iStock Clinical trials are research studies that test how well new ...

  14. Clinical Trials in Head Injury

    PubMed Central

    NARAYAN, RAJ K.; MICHEL, MARY ELLEN; Ansell, Beth; Baethmann, Alex; Biegon, Anat; Bracken, Michael B.; Bullock, M. Ross; Choi, Sung C.; Clifton, Guy L.; Contant, Charles F.; Coplin, William M.; Dietrich, W. Dalton; Ghajar, Jamshid; Grady, Sean M.; Grossman, Robert G.; Hall, Edward D.; Heetderks, William; Hovda, David A.; Jallo, Jack; Katz, Russell L.; Knoller, Nachshon; Kochanek, Patrick M.; Maas, Andrew I.; Majde, Jeannine; Marion, Donald W.; Marmarou, Anthony; Marshall, Lawrence F.; McIntosh, Tracy K.; Miller, Emmy; Mohberg, Noel; Muizelaar, J. Paul; Pitts, Lawrence H.; Quinn, Peter; Riesenfeld, Gad; Robertson, Claudia S.; Strauss, Kenneth I.; Teasdale, Graham; Temkin, Nancy; Tuma, Ronald; Wade, Charles; Walker, Michael D.; Weinrich, Michael; Whyte, John; Wilberger, Jack; Young, A. Byron; Yurkewicz, Lorraine

    2006-01-01

    Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research. PMID:12042091

  15. [Internet use in clinical trials].

    PubMed

    Refolo, P; Sacchini, D; Minacori, R; Spagnolo, A G

    2014-01-01

    Recruiting patients is a critical point of today's clinical research and, along the years, several solutions have been proposed, even if their efficacy seems to be doubtful. On the other hand, nowadays, Internet represents a great opportunity for improving clinical trial recruitments. Nevertheless, on-line recruitment services (e-recruitment) could ensure some advantages (such as facilitating interaction between supply and demand of clinical research, time and money savings/optimizations, data entry errors reduction), but also raise some issues (such as those related to sampling, information, consent, real identity of participants and risks for data breaches). The article debates on the difficulties to recruit patients for clinical research, in general, and e-recruitment particularly, discussing some ethical issues raised by internet enrolment. PMID:24589968

  16. Clinical Trials Management | Division of Cancer Prevention

    Cancer.gov

    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.

  17. MindTrial: An Intelligent System for Clinical Trials

    PubMed Central

    Lee, Yugyung; Dinakarpandian, Deendayal; Katakam, Nikhilesh; Owens, Dennis

    2010-01-01

    The recruitment of human subjects for clinical trials research is a critically important step in the discovery of new cures for diseases. However, the current recruitment methodologies are inherently inefficient. Considerable resources are expended in efforts to recruit adequate numbers of patient volunteers who meet the inclusion/exclusion criteria for clinical trials. Recruitment is particularly challenging for trials involving vulnerable, psychiatrically disordered groups. We have developed a prototype system, called MindTrial, that is based on an online model to enhance the efficiency and quality of recruitment of patients with psychiatric disorders for clinical research. The intelligent component of the MindTrial system can facilitate highly specific matches between clinical trial criteria and volunteers for self-enrollment of sufficient numbers of patient volunteers. We believe this system is particularly valuable in optimizing recruitment for clinical trial studies for development of new drugs. PMID:21347017

  18. Key concepts of clinical trials: a narrative review.

    PubMed

    Umscheid, Craig A; Margolis, David J; Grossman, Craig E

    2011-09-01

    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

  19. Target population for clinical trials

    PubMed Central

    Studenski, S

    2016-01-01

    The target population for clinical trials aimed at sarcopenia depends on the goals of treatment and the expected natural history of sarcopenia. Based on a natural history where loss of muscle mass and/or quality leads to loss of strength, and eventually to reduced mobility and functional dependence, treatment goals can be defined for both preventive and therapeutic interventions. For example, a target population with low muscle mass and poor strength could be treated to prevent the onset of mobility disability, or a target population with low muscle mass and poor strength with mobility disability could be treated therapeutically to improve mobility. Eligibility for a trial should also be based on careful consideration of factors that affect 1) the ability to respond to treatment, 2) the safety of treatment, 3) expected prevalence and 4) feasibility. PMID:19657558

  20. [Reporting adverse reactions and events in randomised clinical trials].

    PubMed

    Hemmingsen, Bianca; Støy, Lina; Wetterslev, Jørn; Tarnow, Lise; Friis, Karin Bach; Christensen, Louise Lundby; Sales, Nader; Gluud, Christian

    2010-08-30

    "Good clinical practice" (GCP) is an international guideline on how to conduct clinical trials on medical products involving human participants. Danish statute follows the EU trial directive (2001/20/EF) including the GCP guidelines. This article summarises the practical implementation of reporting adverse events and adverse reactions to the Danish Medicines Agency and the regional ethics committee based on the protocol of the ongoing Copenhagen Insulin and Metformin Therapy (CIMT) trial. PMID:20825743

  1. Pharmacogenomics in cardiovascular clinical trials.

    PubMed

    Shah, R; Darne, B; Atar, D; Abadie, E; Adams, K F; Zannad, F

    2004-12-01

    Genomics - having quickly emerged as the central discipline in basic science and biomedical research - is poised to take the center stage in clinical medicine as well over the next few decades. Although there is no specific regulatory guideline on the application of pharmacogenetics to drug development, some recommendations are already included in several published guidelines on drug development. The patients more likely to provide the most valuable information on the specific contribution of a given gene or its variant are those who fail to respond to a drug ('therapeutic failures') and those who develop toxicity to the drug. However, before drawing definite conclusions on subgroups following pharmacogenomic analyses, one must be aware of disease classification, data collection, and how much is known about the disease process. It seems reasonable to collect genomic DNA from all patients enrolled in clinical drug trials (along with appropriate consent to permit pharmacogenetic studies) for the purpose of post hoc analyses. One exception to post hoc genomic analysis is when patients with a specific genotype are excluded from randomization into a clinical trial. Physicians will need to understand the concept of genetic variability, its interactions with the environment (e.g. drug-drug or drug-disease interactions), and its implication for patient care. PMID:15548243

  2. Ethics: problems of clinical conduct.

    PubMed

    Luglié, P F; Campus, G; Lai, V

    2005-09-01

    The study provides a framework for ethical medical conduct. A number of articles of International Law, the Italian Constitution, the Penal Code and the Medical Code of Conduct have therefore been taken into consideration. Art. 32 of the Italian Constitution, relating to the ''right to health'' is examined, paying particular attention to certain parts, and is related to Art. 35 of the European Union Charter of Fundamental Rights. In considering Art. 43 of the Penal Code, which addresses the psychological element of criminal acts, reference is made to the Medical Code of Conduct and to the Hippocratic Oath. The considerations made point up the importance of a relationship of trust and esteem between doctor and patient in clinical practice, and that this approach must be cultivated starting from the first year of university studies. PMID:16215531

  3. Clinical trials and gender medicine.

    PubMed

    Cassese, Mariarita; Zuber, Veronica

    2011-01-01

    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. PMID:21430348

  4. Enhancing Adherence in Clinical Exercise Trials.

    ERIC Educational Resources Information Center

    O'Neal, Heather A.; Blair, Steven N.

    2001-01-01

    Discusses exercise adherence from the perspective of adhering to an exercise treatment in a controlled trial, focusing on: adherence (to intervention and measurement); the development of randomized clinical trials; exemplary randomized clinical trials in exercise science (exercise training studies and physical activity interventions); and study…

  5. Tuberculosis vaccines in clinical trials

    PubMed Central

    Rowland, Rosalind; McShane, Helen

    2011-01-01

    Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

  6. Contraceptive development and clinical trials.

    PubMed

    Fraser, I S

    1986-02-01

    This article provides an overview of the contraceptive development process, with particular emphasis on the importance of clinical trials. Development of a new contraceptive drug begins with chemical synthesis of a large number of substances that may have antifertility effects. Before human trials are considered, drugs must undergo a complex process of animal toxicology testing. Such studies assess acute, subacute, and chronic toxicity. Once a drug has passed the initial screening process, human testing must follow a logical sequence of clinical trials: phase I, pharmacology testing; phase II, initial assessment of efficacy, safety, acceptability, and ease of use; phase III, acurate assessment of efficacy, side effects, and reasons for discontinuation under controlled conditions; and phase IV, evaluation of effectiveness under field conditions. When these have been satisfactorily completed, a detailed marketing application must be submitted to the drug regulatory agency in each country. The process of assessment of the application often takes as long as 2 years. Once marketing approval has been received, there is still a need for postmarketing surveillance of the performance of the new contraceptive method. In many cases, a careful program of training is required. Among the research and recording strategies for postmarketing surveillance are voluntary recording of possible adverse reactions, longterm prospective cohort studies, retrospective case-control studies, and registered release. As controls on the safety and performance of new contraceptive methods are being tightened, the time scale and costs of development are increasing. The time from the 1st synthesis of a drug to marketing approval often takes 13-14 years and costs US$25-50 million. Since the patent life of a new substance is limited to 17 years in most countries, pharmaceutical companies have little time to recoup development costs, which has caused fewer new methods to be developed. PMID:3708511

  7. 75 FR 4827 - Submission for OMB Review; Comment Request Clinical Trials Reporting Program (CTRP) Database (NCI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... while CTRP is not directly related to the conduct of a clinical trial, the NCI hopes to use the... HUMAN SERVICES National Institutes of Health Submission for OMB Review; Comment Request Clinical Trials... purpose and safety of clinical trials conducted outside of the United States. An e-mail response was...

  8. Genomic sequencing in clinical trials

    PubMed Central

    2011-01-01

    Human genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 human chromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing is rapidly becoming a major part of our translational research efforts to understand and improve human health and disease. This article reviews the current and future directions of clinical research with respect to genomic sequencing, a technology that is just beginning to find its way into clinical trials both nationally and worldwide. We highlight the currently available types of genomic sequencing platforms, outline the advantages and disadvantages of each, and compare first- and next-generation techniques with respect to capabilities, quality, and cost. We describe the current geographical distributions and types of disease conditions in which these technologies are used, and how next-generation sequencing is strategically being incorporated into new and existing studies. Lastly, recent major breakthroughs and the ongoing challenges of using genomic sequencing in clinical research are discussed. PMID:22206293

  9. The challenge of comorbidity in clinical trials for multiple sclerosis

    PubMed Central

    Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A.

    2016-01-01

    Objective: We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). Methods: We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. Results: We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Conclusion: Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to “real world” settings where the MS population commonly has comorbid conditions. PMID:26888986

  10. Good Clinical Practice Guidance and Pragmatic Clinical Trials: Balancing the Best of Both Worlds.

    PubMed

    Mentz, Robert J; Hernandez, Adrian F; Berdan, Lisa G; Rorick, Tyrus; O'Brien, Emily C; Ibarra, Jenny C; Curtis, Lesley H; Peterson, Eric D

    2016-03-01

    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. PMID:26927005

  11. Why are clinical trials necessary in India?

    PubMed Central

    Poongothai, Subramani; Unnikrishnan, Ranjit; Balasubramanian, Jeyakumar; Nair, Mohan Damodaran; Mohan, Viswanathan

    2014-01-01

    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. PMID:24741480

  12. The unintended consequences of clinical trials regulations.

    PubMed

    McMahon, Alex D; Conway, David I; Macdonald, Tom M; McInnes, Gordon T

    2009-11-01

    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. PMID:19918557

  13. Ethical Considerations for Conducting a Randomized Controlled Trial in Transport

    PubMed Central

    Reimer, Andrew P.; Daly, Barbara J.

    2014-01-01

    Although recent studies support the rapid transfer of patients experiencing time-sensitive emergencies, limited data exist to support the use of air transport for non-urgent patient transfers. The nature of medical transport and the heterogeneity of patients who are transferred present unique challenges in designing and conducting clinical research trials that could contribute to the evidence-based decision-making for patient care and transport. The current regulatory framework presents several barriers to conducting such research in the medical transport setting. We present a hypothetical study that randomizes patients to either ground or air transport as an exemplar. We discuss informed consent, risk, and the impracticality of conducting community consultations in a medical transport setting. Finally, recommendations for potential changes to current regulations are presented. These are directed at facilitating the conduct of emergency research through a system of oversight that integrates characteristics of quality improvement and health services research. PMID:25441519

  14. How transparent are migraine clinical trials?

    PubMed Central

    Dufka, Faustine L.; Dworkin, Robert H.

    2014-01-01

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

  15. Prudent precaution in clinical trials of nanomedicines.

    PubMed

    Marchant, Gary E; Lindor, Rachel A

    2012-01-01

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

  16. Immunotherapy for pancreatic ductal adenocarcinoma: an overview of clinical trials

    PubMed Central

    Paniccia, Alessandro; Merkow, Justin; Edil, Barish H.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and current therapeutic strategies are often unsatisfactory. Identification and development of more efficacious therapies is urgently needed. Immunotherapy offered encouraging results in preclinical models during the last decades, and several clinical trials have explored its therapeutic application in PDAC. The aim of this review is to summarize the results of clinical trials conducted to evaluate the future perspective of immunotherapy in the treatment of PDAC. PMID:26361407

  17. The Cooperative Landscape of Multinational Clinical Trials

    PubMed Central

    Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

    2015-01-01

    The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

  18. Challenges in recruitment and retention of clinical trial subjects

    PubMed Central

    Kadam, Rashmi Ashish; Borde, Sanghratna Umakant; Madas, Sapna Amol; Salvi, Sundeep Santosh; Limaye, Sneha Saurabh

    2016-01-01

    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. PMID:27453831

  19. Key Concepts of Clinical Trials: A Narrative Review

    PubMed Central

    Umscheid, Craig A.; Margolis, David J.; Grossman, Craig E.

    2012-01-01

    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

  20. Methodology Series Module 4: Clinical Trials

    PubMed Central

    Setia, Maninder Singh

    2016-01-01

    In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

  1. Methodology Series Module 4: Clinical Trials.

    PubMed

    Setia, Maninder Singh

    2016-01-01

    In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

  2. How individual participant data meta-analyses have influenced trial design, conduct, and analysis

    PubMed Central

    Tierney, Jayne F.; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L.; Burdett, Sarah; Alderson, P.; Askie, L.; Bennett, D.; Burdett, S.; Clarke, M.; Dias, S.; Emberson, J.; Gueyffier, F.; Iorio, A.; Macleod, M.; Mol, B.W.; Moons, C.; Parmar, M.; Perera, R.; Phillips, R.; Pignon, J.P.; Rees, J.; Reitsma, H.; Riley, R.; Rovers, M.; Rydzewska, L.; Schmid, C.; Shepperd, S.; Stenning, S.; Stewart, L.; Tierney, J.; Tudur Smith, C.; Vale, C.; Welge, J.; White, I.; Whiteley, W.

    2015-01-01

    Objectives To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Study Design and Setting Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. Results We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. Conclusions IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. PMID:26186982

  3. Personalized medicine: ethics for clinical trials.

    PubMed

    Sharrer, G Terry

    2012-01-01

    Modern ethical codes in medicine were developed following World War II to provide respect for persons, beneficence, and justice in clinical research. Clinical trial medicine involves greater scrutiny than most research activities. In every instance, clinical trials have institutional review boards to ensure the medical procedure under study complies with regulatory requirements, privacy, informed consent, good practices, safety monitoring, adverse events reporting, and is free of conflicting interests. Mandatory training in medical ethics for all clinical staff is becoming more common, and at some institutions, knowledgeable patient advocates play a watchdog role. In personalized medicine, each patient becomes a clinical trial of one, based on the uniqueness of the person's illness and the relatively tailored treatment. These features imply a shared responsibility between the patient and the researchers because uncertainty exists over the outcome for each individual patient. This chapter introduces ethical considerations using case studies, with historical context, and describes general ethical guidelines for initiating a clinical trial. PMID:22081337

  4. Paperless clinical trials: Myth or reality?

    PubMed

    Gupta, Sandeep K

    2015-01-01

    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

  5. 76 FR 1620 - Trials to Verify and Describe Clinical Benefit of Midodrine Hydrochloride; Establishment of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-11

    ..., we are placing in the docket a brief description of a recommended clinical trial design. We are also... HUMAN SERVICES Food and Drug Administration Trials to Verify and Describe Clinical Benefit of Midodrine... to facilitate communication regarding the conduct of clinical trials needed to verify and...

  6. Microbicide clinical trial adherence: insights for introduction.

    PubMed

    Woodsong, Cynthia; MacQueen, Kathleen; Amico, K Rivet; Friedland, Barbara; Gafos, Mitzy; Mansoor, Leila; Tolley, Elizabether; McCormack, Sheena

    2013-01-01

    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. PMID:23561044

  7. Multiple comparisons in complex clinical trial designs.

    PubMed

    Hung, H M James; Wang, Sue-Jane

    2013-05-01

    Multiple comparisons have drawn a great deal of attention in evaluation of statistical evidence in clinical trials for regulatory applications. As the clinical trial methodology is increasingly more complex to properly take into consideration many practical factors, the multiple testing paradigm widely employed for regulatory applications may not suffice to interpret the results of an individual trial and of multiple trials. In a large outcome trial, an increasing need of studying more than one dose complicates a proper application of multiple comparison procedures. Additional challenges surface when a special endpoint, such as mortality, may need to be tested with multiple clinical trials combined, especially under group sequential designs. Another interesting question is how to study mortality or morbidity endpoints together with symptomatic endpoints in an efficient way, where the former type of endpoints are often studied in only one single trial but the latter type of endpoints are usually studied in at least two independent trials. This article is devoted to discussion of insufficiency of such a widely used paradigm applying only per-trial based multiple comparison procedures and to expand the utility of the procedures to such complex trial designs. A number of viable expanded strategies are stipulated. PMID:23620458

  8. Citation Sentiment Analysis in Clinical Trial Papers

    PubMed Central

    Xu, Jun; Zhang, Yaoyun; Wu, Yonghui; Wang, Jingqi; Dong, Xiao; Xu, Hua

    2015-01-01

    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

  9. DO CANCER CLINICAL TRIAL POPULATIONS TRULY REPRESENT CANCER PATIENTS? A COMPARISON OF OPEN CLINICAL TRIALS TO THE CANCER GENOME ATLAS

    PubMed Central

    Geifman, Nophar; Butte, Atul J.

    2016-01-01

    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. PMID:26776196

  10. Establishing a clinical trials network in nephrology: experience of the Australasian Kidney Trials Network

    PubMed Central

    Morrish, Alicia T; Hawley, Carmel M; Johnson, David W; Badve, Sunil V; Perkovic, Vlado; Reidlinger, Donna M; Cass, Alan

    2014-01-01

    Chronic kidney disease is a major public health problem globally. Despite this, there are fewer high-quality, high-impact clinical trials in nephrology than other internal medicine specialties, which has led to large gaps in evidence. To address this deficiency, the Australasian Kidney Trials Network, a Collaborative Research Group, was formed in 2005. Since then, the Network has provided infrastructure and expertise to conduct patient-focused high-quality, investigator-initiated clinical trials in nephrology. The Network has not only been successful in engaging the nephrology community in Australia and New Zealand but also in forming collaborations with leading researchers from other countries. This article describes the establishment, development, and functions of the Network. The article also discusses the current and future funding strategies to ensure uninterrupted conduct of much needed clinical trials in nephrology to improve the outcomes of patients affected by kidney diseases with cost-effective interventions. PMID:24088955

  11. Project Management of Randomized Clinical Trials: A Narrative Review

    PubMed Central

    Goodarzynejad, Hamidreza; Babamahmoodi, Abdolreza

    2015-01-01

    Context: A well-structured protocol for a clinical trial may be able to answer clinical questions, but it cannot be deemed enough to ensure success in the face of incompetent management of time as well as human and economic resources. To address this problem, in this article, we present our literature review on evidence as to how a good knowledge of proper management among researchers can enhance the likelihood of the success of clinical trial projects. Evidence Acquisition: Using multiple search strategies, we conducted a literature review on published studies in the English language from 2002 to 2012 by searching the Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE. Results: Our review suggests that a successful trial requires a work plan or work scope as well as a timeline. The trial manager should subsequently manage the study in accordance with the plan and the timeline. Many research units have called for a clinical project manager with scientific background and regulatory skills to effect coordination among various aspects of a clinical trial. Conclusions: Project management may benefit both the managerial and scientific aspects of medical projects and reduce fund waste. However, little has been written to date on project management in the context of clinical research. The suggestions represent the views of the individual authors. To provide a high level of evidence in this regard, we recommend that a randomized controlled trial be performed to compare trial projects progressed with and without the use of project management. PMID:26430517

  12. Marketing and clinical trials: a case study

    PubMed Central

    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

    2007-01-01

    Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537

  13. Trials on Trial: The Push for Clinical Data Disclosure

    PubMed Central

    CARROLL, JOHN

    2004-01-01

    Momentum is growing for disclosure of all clinical trial data, not just information that supports a trial sponsor’s product. The importance to patients and P&T committees is clear: Ideally, they would use this information to make informed decisions. The result of this activity, though, could be a cacophony of competing registries with the potential to muddy the very waters they’re designed to clear up. PMID:23390393

  14. Clinical trials and the new good clinical practice guideline in Japan. An economic perspective.

    PubMed

    Ono, S; Kodama, Y

    2000-08-01

    Japanese clinical trials have been drastically changing in response to the implementation of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guideline in 1997. The most important aim of the new guideline is to standardise the quality of clinical trials in the US, European Union and Japan, but it inevitably imposes substantial costs on investigators, sponsors and even patients in Japan. The study environment in Japan differs from that in the US in several ways: (i) historical lack of a formal requirement for informed consent; (ii) patients' attitudes to clinical trials in terms of expectation of positive outcomes; (iii) the implications of universal health insurance for trial participation; (iv) the historical absence of on-site monitoring by the sponsor, with the attendant effects on study quality; and (v) the lack of adequate financial and personnel support for the conduct of trials. Implementation of the new GCP guideline will improve the ethical and scientific quality of trials conducted in Japan. It may also lead to an improved relationship between medical professionals and patients if the requirement for explicit informed consent in clinical trials leads to the provision of a similar level of patient information in routine care and changes the traditional paternalistic attitude of physicians to patients. The initial response of the Japanese 'market' for clinical trials to the implementation of the ICH-GCP guideline has been clinical trial price increases and a decrease in the number of study contracts. These changes can be explained by applying a simple demand-supply scheme. Whether clinical trials undertaken in Japan become more or less attractive to the industry in the long term will depend on other factors such as international regulations on the acceptability of foreign clinical trials and the reform of domestic healthcare policies. PMID:11067647

  15. IPF clinical trial design and endpoints

    PubMed Central

    Nathan, Steven D.; Meyer, Keith C.

    2014-01-01

    Purpose of review There remains a dire need for therapies that impact the clinical course of patients with idiopathic pulmonary fibrosis (IPF). Indeed, there is a surge of interest in IPF therapeutics, with many candidate agents in various stages of development. Optimal design and implementation of the appropriate prospective clinical trials are essential to demonstrate clinical efficacy of promising drugs for the treatment of IPF. A key element in the success of such clinical trials is the choice of the best endpoint(s) to match the design of the study. Recent findings Although the results of many IPF clinical trials have been disappointing, these trials have provided valuable insights into the epidemiology and natural history of the disease and have sparked debate into the best clinical trial designs and endpoints. Summary This review will discuss the various clinical trial endpoints that have been used or proposed with a focus on their potential utility, as well as possible pitfalls that investigators should consider in the design of such studies. Video abstract http://links.lww.com/COPM/A13 PMID:25022315

  16. Using Registries to Recruit Subjects for Clinical Trials

    PubMed Central

    Tan, Meng H; Thomas, Matthew; MacEachern, Mark P

    2015-01-01

    Aim We studied the use of patient/disease registries to recruit potential subjects for prospective clinical trials - describing the number, types and major benefits of using this approach. Methods In December 2013, we conducted a focused database search in PubMed, EMBASE, and Web of Science for studies (English language only) that used registries to recruit subjects for clinical trials published in 2004-2013. Of the 233 unique citations identified, 21 used registries to recruit subjects - 10 papers and 11 abstracts. Pearling and search for subsequent full papers of the abstracts identified 4 more papers. Results Our analysis, based on these 25 citations, showed 14 are related to cancer, 3 to diabetes mellitus, 1 each to stroke, asthma, and celiac disease and 5 are disease neutral. Many types of registries (population-based cancer, quality improvement, disease-specific, web-based disease-neutral registries, local general practice registers, and national health database) are used to recruit subjects for clinical trials and uncover new knowledge. Overall, 16 registries are in the US, 4 in UK, 1 each in Canada, Spain, Australia and I in many countries. Registries can identify very large number of subjects for screening for eligibility for clinical trials, especially in very large trials, rare disease trials, and trials involving minority patients. Conclusions Registries can retrospectively identify very large numbers of potential subjects for screening for eligibility and enrollment in prospective clinical trials. This matching can lead to more timely recruitment and help solve a major problem in conducting clinical trials. PMID:25545027

  17. Statistical properties of randomization in clinical trials.

    PubMed

    Lachin, J M

    1988-12-01

    This is the first of five articles on the properties of different randomization procedures used in clinical trials. This paper presents definitions and discussions of the statistical properties of randomization procedures as they relate to both the design of a clinical trial and the statistical analysis of trial results. The subsequent papers consider, respectively, the properties of simple (complete), permuted-block (i.e., blocked), and urn (adaptive biased-coin) randomization. The properties described herein are the probabilities of treatment imbalances and the potential effects on the power of statistical tests; the permutational basis for statistical tests; and the potential for experimental biases in the assessment of treatment effects due either to the predictability of the random allocations (selection bias) or the susceptibility of the randomization procedure to covariate imbalances (accidental bias). For most randomization procedures, the probabilities of overall treatment imbalances are readily computed, even when a stratified randomization is used. This is important because treatment imbalance may affect statistical power. It is shown, however, that treatment imbalance must be substantial before power is more than trivially affected. The differences between a population versus a permutation model as a basis for a statistical test are reviewed. It is argued that a population model can only be invoked in clinical trials as an untestable assumption, rather than being formally based on sampling at random from a population. On the other hand, a permutational analysis based on the randomization actually employed requires no assumptions regarding the origin of the samples of patients studied. The large sample permutational distribution of the family of linear rank tests is described as a basis for easily conducting a variety of permutation tests. Subgroup (stratified) analyses, analyses when some data are missing, and regression model analyses are also

  18. [Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

    PubMed

    Shimada, Yasuhiro

    2016-04-01

    The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment". PMID:27220797

  19. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    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. PMID:26135330

  20. A guide to clinical trials for cancer

    MedlinePlus

    There are strict federal rules in place to protect your safety during a clinical trial. Safety guidelines (protocols) are agreed to before the study begins. These guidelines are reviewed by health ...

  1. 32 CFR 9.6 - Conduct of the trial.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Conduct of the trial. 9.6 Section 9.6 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE MILITARY COMMISSIONS PROCEDURES FOR TRIALS BY MILITARY COMMISSIONS OF CERTAIN NON-UNITED STATES CITIZENS IN THE WAR AGAINST TERRORISM § 9.6 Conduct of the trial. (a) Pretrial...

  2. Training Residential Staff to Conduct Trial-Based Functional Analyses

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  3. The Myth of Equipoise in Phase 1 Clinical Trials

    PubMed Central

    Shamoo, Adil E.

    2008-01-01

    Phase 1 clinical research trials using healthy volunteers are conducted for the sole purpose of serving the public good (a utilitarian concept). The literature on equipoise analysis does not exclude phase 1 trials with controls or healthy volunteers from the claim of being in “equipoise.” The continued perpetuation of this ethically and scientifically invalid concept undermines the ethics of research with human subjects. PMID:19099004

  4. Review of clinical trials for mitochondrial disorders: 1997-2012.

    PubMed

    Kerr, Douglas S

    2013-04-01

    and the relatively large expense of conducting such trials, advantageous strategies include crossover designs (where possible), multicenter collaboration, and the selection of very few, clinically relevant, primary outcomes. PMID:23361264

  5. Swiss regulations for controlling clinical trials.

    PubMed

    Zanini, G M

    1998-04-01

    Switzerland has recently issued regulations designed to control all trials with drugs in human subjects, namely the 'Regolamento dell'Ufficio Intercantonale per il controllo dei medicamenti in fase di studio clinico' (Intercantonal Regulations Controlling Drugs used in Clinical Trials), which have been operating since 1st January 1995. These new regulations are generally consistent with other international regulations and have introduced the concept of good clinical practice (GCP) into Switzerland. There are other regulations in Switzerland, such as Federal regulations on immunobiological products, special rules governing the administration of radiolabelled drugs to humans, drugs of abuse and medical devices. Any gap in the central regulations must be filled by cantonal regulations, where they exist. This is a comprehensive review of the regulations governing clinical trials in Switzerland, with special attention being devoted to trials with therapeutic compounds and to compatibility between Swiss and international procedures. PMID:9634649

  6. Are clinical trials really the answer?

    PubMed

    Block, G

    1995-12-01

    It has been asserted that clinical trials hold the answer to questions about the role of nutrients in preventing chronic diseases. This is not the case. Clinical trials give us rigorous answers to restricted questions. Rarely can more than one or two substances be tested, usually at a single dose. Subjects usually have to be persons with precancerous conditions or an extremely high risk of the disease in question. Rarely can any diseases other than the most common ones be studied. Most important, clinical trials test the efficacy of an agent that is administered for a limited time, beginning fairly late in life. Few trials will tell us anything about whether dietary amounts of nutrients might contribute to prevention of long-term chronic diseases. They also tell us nothing about whether agents at high doses might reduce disease risk if taken throughout the lifetime. Furthermore, they tell us nothing about other antioxidants, other combinations, or other doses. Clinical trials were developed for therapeutic situations to determine which treatment was better for curing a specific disease. However, the questions about prevention that are of interest may involve persons with no unusual risk of disease, lifetimes of exposure, enormously complex interactions among nutrients, and the effects of these nutrients on hundreds of often uncommon disease conditions. Clinical trials simply cannot answer these questions. Only a solid examination of the laboratory and epidemiologic evidence can approximate the answers to most of the questions of interest. PMID:7495253

  7. A General Framework for the Evaluation of Clinical Trial Quality

    PubMed Central

    Berger, Vance W.; Alperson, Sunny Y.

    2009-01-01

    Flawed evaluation of clinical trial quality allows flawed trials to thrive (get funded, obtain IRB approval, get published, serve as the basis of regulatory approval, and set policy). A reasonable evaluation of clinical trial quality must recognize that any one of a large number of potential biases could by itself completely invalidate the trial results. In addition, clever new ways to distort trial results toward a favored outcome may be devised at any time. Finally, the vested financial and other interests of those conducting the experiments and publishing the reports must cast suspicion on any inadequately reported aspect of clinical trial quality. Putting these ideas together, we see that an adequate evaluation of clinical quality would need to enumerate all known biases, update this list periodically, score the trial with regard to each potential bias on a scale of 0% to 100%, offer partial credit for only that which can be substantiated, and then multiply (not add) the component scores to obtain an overall score between 0% and 100%. We will demonstrate that current evaluations fall well short of these ideals. PMID:19463104

  8. Special article: 2014 Pediatric Clinical Trials Forum.

    PubMed

    Bogue, Clifford; DiMeglio, Linda A; Maldonado, Samuel; Portman, Ronald J; Smith, P Brian; Sullivan, Janice E; Thompson, Charles; Woo, Heide; Flinn, Susan

    2016-04-01

    In November 2014, the American Academy of Pediatrics convened key stakeholders to discuss the feasibility of accelerating children's medical advances by creating an independent global Pediatric Clinical Trials Network. The Forum identified challenges posed by the US and global clinical trial systems regarding testing and disseminating drugs and devices for pediatric patients. Stakeholders mapped a vision to improve the safety and efficacy of pediatric drugs, biological products, and medical devices by creating a global Pediatric Clinical Trials Network. Such a Network would act as a central infrastructure for pediatric subspecialties and enable dedicated staff to provide clinical research sites with scientific, medical, and operational support. A Network would facilitate development and availability of innovative, high-quality therapies to extend and enhance the lives of neonates, infants, children, adolescents, and young adults. Participants expressed strong interest in forming such a Network, since drugs and devices still come to market without adequate pediatric indications-particularly in neonatology and rare diseases. Participants developed a Consensus Statement expressing their shared vision for a Network: Attendees of the Pediatric Clinical Trials Stakeholder Forum resolved to establish a Global Pediatric Clinical Trials Network and are committed to engage in the work to create and sustain it. PMID:26650344

  9. Choosing Alzheimer's disease prevention clinical trial populations.

    PubMed

    Grill, Joshua D; Monsell, Sarah E

    2014-03-01

    To assist investigators in making design choices, we modeled Alzheimer's disease prevention clinical trials. We used longitudinal Clinical Dementia Rating Scale Sum of Boxes data, retention rates, and the proportions of trial-eligible cognitively normal participants age 65 and older in the National Alzheimer's Coordinating Center Uniform Data Set to model trial sample sizes, the numbers needed to enroll to account for drop out, and the numbers needed to screen to successfully complete enrollment. We examined how enrichment strategies affected each component of the model. Relative to trials enrolling 65-year-old individuals, trials enriching for older (minimum 70 or 75) age required reduced sample sizes, numbers needed to enroll, and numbers needed to screen. Enriching for subjective memory complaints reduced sample sizes and numbers needed to enroll more than age enrichment, but increased the number needed to screen. We conclude that Alzheimer's disease prevention trials can enroll elderly participants with minimal effect on trial retention and that enriching for older individuals with memory complaints might afford efficient trial designs. PMID:24119546

  10. Social Media Ups Clinical Trial Enrollment.

    PubMed

    2016-08-01

    In just seven months, the Metastatic Breast Cancer Project has collected clinical and genetic data from more than 2,000 patients who learned about this effort from social media and volunteered to participate. The project could become a model for other cancer types where recruiting sufficient patients for clinical trials through traditional channels is often a challenge. PMID:27329925

  11. Perceptions of Reimbursement for Clinical Trial Participation

    PubMed Central

    Breitkopf, Carmen Radecki; Loza, Melissa; Vincent, Kathleen; Moench, Thomas; Stanberry, Lawrence R.; Rosenthal, Susan L.

    2012-01-01

    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. PMID:21931235

  12. [Clinical trial data validation and user acceptance testing].

    PubMed

    Sun, Hua-long; Dai, Nan

    2015-11-01

    For pharmaceutical industries, clinical data is one of the most valuable deliverables. It is also the basis of analysis, submission, approval, labeling and marketing of a drug product. To ensure the integrity and reliability of clinical data, a scientific standardized quality control (QC) has to be established at each step of a clinical trial. Data validation is conducted to ensure the reasonability and compliance of clinical data by checking data quality before the data is statistically analyzed. This paper focuses on purpose of data validation, creation of data validation plan, rationale of data validation, types of data validation and performance of user acceptance testing on clinical database. PMID:26911047

  13. Catheter ablation of ventricular tachycardia: Lessons learned from past clinical trials and implications for future clinical trials.

    PubMed

    Pokorney, Sean D; Friedman, Daniel J; Calkins, Hugh; Callans, David J; Daoud, Emile G; Della-Bella, Paolo; Jackson, Kevin P; Shivkumar, Kalyanam; Saba, Samir; Sapp, John; Stevenson, William G; Al-Khatib, Sana M

    2016-08-01

    Catheter ablation of ventricular tachycardia (VT) has evolved in recent years, especially in patients with ischemic heart disease. Data from prospective studies show that VT catheter ablation reduces the risk of recurrent VT; however, there is a paucity of data on the effect of VT catheter ablation on mortality and patient-centered outcomes such as quality of life. Performing randomized clinical trials of VT catheter ablation can be fraught with challenges, and, as a result, several prior trials of VT catheter ablation had to be stopped prematurely. The main challenges are inability to blind the patient to therapy to obtain a traditional control group, high crossover rates between the 2 arms of the study, patient refusal to participate in trials in which they have an equal chance of receiving a "pill" vs an invasive procedure, heterogeneity of mapping and ablation techniques as well as catheters and equipment, rapid evolution of technology that may make findings of any long trial less relevant to clinical practice, lack of consensus on what constitutes acute procedural and long-term success, and presentation of patients to electrophysiologists late in the course of their disease. In this article, a panel of experts on VT catheter ablation and/or clinical trials of VT catheter ablation review challenges faced in conducting prior trials of VT catheter ablation and offer potential solutions for those challenges. It is hoped that the proposed solutions will enhance the feasibility of randomized clinical trials of VT catheter ablation. PMID:27050910

  14. Biomarkers and Surrogate Endpoints In Clinical Trials

    PubMed Central

    Fleming, Thomas R.; Powers, John H

    2012-01-01

    One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures and radiological tests, often are considered as replacement endpoints or “surrogates” for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. . PMID:22711298

  15. Clinical trial designs incorporating predictive biomarkers.

    PubMed

    Renfro, Lindsay A; Mallick, Himel; An, Ming-Wen; Sargent, Daniel J; Mandrekar, Sumithra J

    2016-02-01

    Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer "targeted" drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research. PMID:26827695

  16. Current status of quality in Japanese clinical trials.

    PubMed

    Saito, Kazuyuki; Kodama, Yasuo; Ono, Shunsuke; Mutoh, Mizue; Kawashima, Susumu; Fujimura, Akio

    2005-08-01

    The changes in the quality of Japanese clinical trials were evaluated by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year (FY) 1997-1999) with those from April 2001 to March 2002 (FY2001). During both of the periods inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). The audit findings in the former period were based on the audits that covered 331 hospitals and 775 trials conducted under the old GCP guideline. The audits in the latter period targeted 147 hospitals and 238 trials conducted under the old or new GCP guideline. The total number of deficiencies detected by GCP audits in the former three-year period (FY 1997-1999) was 1529, and the corresponding number in the latter single year (FY 2001) was 912. Two remarkable changes in OPSR's findings were observed between FY 1997-1999 and FY 2001 as follows; the proportion of protocol deviations increased from 14.7% (225/1529) to 53.1% (484/912), while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) to 15.4% (140/912). The new GCP guideline sets very high standards for a hospital's qualification: to have sufficient equipment and hospital resources, to have capacity for promptly responding to urgent trial-related problems, to have an IRB, and to have appropriate staff including clinical research coordinators (CRCs) assigned to the clinical trial. Our results suggest that the impact of the regulatory changes of applicable standard is large for a hospital's qualification for conducting clinical trials in Japan. PMID:16054582

  17. How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

    PubMed Central

    Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

    2016-01-01

    Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria.

  18. How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

    PubMed

    Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

    2016-01-01

    Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681

  19. RECENT CLINICAL TRIALS IN LUPUS NEPHRITIS

    PubMed Central

    Ward, Michael M.

    2014-01-01

    SYNOPSIS Recent clinical trials have provided evidence for the efficacy of low-dose intravenous cyclophosphamide and mycophenolate mofetil as induction treatment for patients with proliferative lupus nephritis in comparative trials with standard-dose intravenous cyclophosphamide. Trials of maintenance treatments have had more variable results, but suggest that mycophenolate mofetil may be similar to quarterly standard-dose intravenous cyclophosphamide and somewhat more efficacious than azathioprine. Differential responses to mycophenolate mofetil based on ethnicity suggest that it may be more effective in black and Hispanic patients. Rituximab was not efficacious as an adjunct to induction treatment with mycophenolate mofetil. PMID:25034160

  20. Clinical Trials in Retinal Dystrophies

    PubMed Central

    Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean

    2016-01-01

    Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field – the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. PMID:26957839

  1. Advances in cardiology: clinical trial update.

    PubMed

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

    2011-05-01

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

  2. Disease-mongering through clinical trials.

    PubMed

    González-Moreno, María; Saborido, Cristian; Teira, David

    2015-06-01

    Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple. PMID:25863220

  3. Ethical Issues in Clinical Trials Involving Nanomedicine

    PubMed Central

    Resnik, David B.; Tinkle, Sally S.

    2009-01-01

    Nanomedicine shows tremendous promise for improving medical diagnosis, treatment, and prevention, but it also raises a variety of ethical concerns. Because of the paucity of data on the physicochemical properties of nanoscale materials in biological systems, clinical trials of nanomedicine products present some unique challenges related to risk minimization, management and communication involving human subjects. Although these clinical trials do not raise any truly novel ethical issues, the rapid development of nanotechnology and its potentially profound social and environmental impacts, add a sense of urgency to the problems that arise. PMID:17166777

  4. Seeking harmony: estimands and sensitivity analyses for confirmatory clinical trials.

    PubMed

    Mehrotra, Devan V; Hemmings, Robert J; Russek-Cohen, Estelle

    2016-08-01

    In October 2014, the Steering Committee of the International Conference on Harmonization endorsed the formation of an expert working group to develop an addendum to the International Conference on Harmonization E9 guideline ("Statistical Principles for Clinical Trials"). The addendum will focus on two topics involving randomized confirmatory clinical trials: estimands and sensitivity analyses. Both topics are motivated, in part, by the need to improve the precision with which scientific questions of interest are formulated and addressed by clinical trialists and regulators, specifically in the context of post-randomization events such as use of rescue medication or missing data resulting from dropouts. Given the importance of these topics for the statistical and medical community, we articulate the reasons for the planned addendum. The resulting "ICH E9/R1" guideline will include a framework for improved trial planning, conduct, analysis, and interpretation; a draft is expected to be ready for public comment in the second half of 2016. PMID:26908545

  5. Implications of Look AHEAD for Clinical Trials and Clinical Practice

    PubMed Central

    Wing, Rena R.

    2014-01-01

    Look AHEAD was a randomized clinical trial designed to examine the long-term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow up of 9.6 years was not reduced in the intensive lifestyle group relative to the control group. This finding is discussed, with emphasis on its implications for design of clinical trials and clinical treatment of obese people with type 2 diabetes. PMID:24853636

  6. The Egyptian clinical trials’ registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov)

    PubMed Central

    Zeeneldin, Ahmed A.; Taha, Fatma M.

    2015-01-01

    Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended. PMID:26843968

  7. The Internet and Clinical Trials: Background, Online Resources, Examples and Issues

    PubMed Central

    Seib, Rachael; Prescott, Todd

    2005-01-01

    Both the Internet and clinical trials were significant developments in the latter half of the twentieth century: the Internet revolutionized global communications and the randomized controlled trial provided a means to conduct an unbiased comparison of two or more treatments. Large multicenter trials are often burdened with an extensive development time and considerable expense, as well as significant challenges in obtaining, backing up and analyzing large amounts of data. Alongside the increasing complexities of the modern clinical trial has grown the power of the Internet to improve communications, centralize and secure data as well as to distribute information. As more and more clinical trials are required to coordinate multiple trial processes in real time, centers are turning to the Internet for the tools to manage the components of a clinical trial, either in whole or in part, to produce lower costs and faster results. This paper reviews the historical development of the Internet and the randomized controlled trial, describes the Internet resources available that can be used in a clinical trial, reviews some examples of online trials and describes the advantages and disadvantages of using the Internet to conduct a clinical trial. We also extract the characteristics of the 5 largest clinical trials conducted using the Internet to date, which together enrolled over 26000 patients. PMID:15829477

  8. Ethical challenges in conducting clinical research in lung cancer

    PubMed Central

    Tod, Angela M.

    2016-01-01

    The article examines ethical challenges that arise with clinical lung cancer research focusing on design, recruitment, conduct and dissemination. Design: problems related to equipoise can arise in lung cancer studies. Equipoise is an ethics precondition for RCTs and exists where there is insufficient evidence to decide which of two or more treatments is best. Difficulties arise in deciding what level of uncertainty constitutes equipoise and who should be in equipoise, for example, patients might not be even where clinicians are. Patient and public involvement (PPI) can reduce but not remove the problems. Recruitment: (I) lung cancer studies can be complex, making it difficult to obtain good quality consent. Some techniques can help, such as continuous consent. But researchers should not expect consent to be the sole protection for participants’ welfare. This protection is primarily done elsewhere in the research process, for example, in ethics review; (II) the problem of desperate volunteers: some patients only consent to a trial because it gives them a 50/50 option of the treatment they want and can be disappointed or upset if randomised to the other arm. This is not necessarily unfair, given clinical equipoise. However, it should be avoided where possible, for example, by using alternative trial designs; (III) the so-called problem of therapeutic misconception: this is the idea that patients are mistaken if they enter trials believing this to be in their clinical best interest. We argue the problem is misconceived and relates only to certain health systems. Conduct: lung cancer trials face standard ethical challenges with regard to trial conduct. PPI could be used in decisions about criteria for stopping rules. Dissemination: as in other trial areas, it is important that all results, including negative ones, are reported. We argue also that the role of PPI with regard to dissemination is currently under-developed. PMID:27413698

  9. Biomarkers in T cell therapy clinical trials

    PubMed Central

    2011-01-01

    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. PMID:21851646

  10. Exploring the ethical and regulatory issues in pragmatic clinical trials.

    PubMed

    Califf, Robert M; Sugarman, Jeremy

    2015-10-01

    The need for high-quality evidence to support decision making about health and health care by patients, physicians, care providers, and policy-makers is well documented. However, serious shortcomings in evidence persist. Pragmatic clinical trials that use novel techniques including emerging information and communication technologies to explore important research questions rapidly and at a fraction of the cost incurred by more "traditional" research methods promise to help close this gap. Nevertheless, while pragmatic clinical trials can bridge clinical practice and research, they may also raise difficult ethical and regulatory challenges. In this article, the authors briefly survey the current state of evidence that is available to inform clinical care and other health-related decisions and discuss the potential for pragmatic clinical trials to improve this state of affairs. They then propose a new working definition for pragmatic research that centers upon fitness for informing decisions about health and health care. Finally, they introduce a project, jointly undertaken by the National Institutes of Health Health Care Systems Research Collaboratory and the National Patient-Centered Clinical Research Network (PCORnet), which addresses 11 key aspects of current systems for regulatory and ethical oversight of clinical research that pose challenges to conducting pragmatic clinical trials. In the series of articles commissioned on this topic published in this issue of Clinical Trials, each of these aspects is addressed in a dedicated article, with a special focus on the interplay between ethical and regulatory considerations and pragmatic clinical research aimed at informing "real-world" choices about health and health care. PMID:26374676

  11. [International clinical trials: perspectives of clinical research coordinators].

    PubMed

    Aotani, Eriko

    2007-02-01

    There are several different task roles among the co-medicals who are involved in international clinical trials (ICTs). In this review article, several issues related with ICTs from the view point of clinical research coordinators (CRCs) will be discussed. The discussions include interview results from eight CRCs of four institutions who have been involved in ICTs, current status of education for co-medicals in the field of ICTs, and future perspectives of ICTs from the CRC's view point. The following topics are especially focused in the discussion. 1) It is necessary to establish the infra-structure for free discussion among the ICT team so that opinions of co-medicals as the operation managers of the participating institutions can be openly shared and importantly taken into account. 2) It is also important for co-medicals to conduct research studies to clarify the problems in the current ICT support systems. 3) Lastly, the significance of early involvement of CRCs into the ICT protocol development must be emphasized, because the quality of protocols will be better improved by the practical insight of CRCs, and consequently, the accomplishment of the ICT, such as the speed and the data quality, may be accelerated. PMID:17301551

  12. Clinical trials at AHCs: the perspective of an academic clinical trials office.

    PubMed

    Paller, Mark S; Hostetler, Lisa; Dykhuis, Debra A

    2002-12-01

    Industry-sponsored clinical trials represent a substantial portion of the clinical investigator's portfolio of patient-oriented research. In academia's efforts to reclaim lost ground with respect to the performance of industry-sponsored clinical trials, many academic health centers have established clinical trials offices. An underlying assumption has been that with improved service on the part of universities will come new opportunities for clinical research. The experiences and vantage points of academic research offices have sometimes been ignored and an analysis of what new business might ensue has not been reported. The authors discuss the rationale for creating a centralized clinical trials office and the means of financing such an effort. They then describe the initial experiences (1997-2000) of a central clinical trials office (the Research Services Organization, or RSO) at the University of Minnesota Academic Health Center, analyze the value of such an office to the academic health center, and, based on their experiences with the RSO and elsewhere, consider how industry and academia might further enhance their collaborations. Of 354 clinical research proposals evaluated by the RSO, only 62% were found to be acceptable or highly likely to be acceptable to investigators and the institution. Reasons for not participating in specific clinical trials are discussed. Academic health centers contemplating developing clinical trials offices must be aware of the significant overhead cost associated with evaluating the appropriateness and feasibility of clinical trial proposals that may never be performed. Valuable lessons learned from working with sponsors and from working with investigators are also reviewed. PMID:12480622

  13. Building data quality into clinical trials.

    PubMed

    Crerand, William J; Lamb, Jana; Rulon, Vera; Karal, Bilun; Mardekian, Jack

    2002-01-01

    Meaningful data begin with the collection process. Pharmaceutical companies are using several different strategies in clinical trials to ensure the highest quality of data. This article will examine these approaches, with an emphasis on case report form development through database release. PMID:12432815

  14. Very Low Ventricular Pacing Rates Can Be Achieved Safely in a Heterogeneous Pacemaker Population and Provide Clinical Benefits: The CANadian Multi-Centre Randomised Study-Spontaneous AtrioVEntricular Conduction pReservation (CAN-SAVE R) Trial

    PubMed Central

    Thibault, Bernard; Ducharme, Anique; Baranchuk, Adrian; Dubuc, Marc; Dyrda, Katia; Guerra, Peter G; Macle, Laurent; Mondésert, Blandine; Rivard, Léna; Roy, Denis; Talajic, Mario; Andrade, Jason; Nitzsché, Rémi; Khairy, Paul

    2015-01-01

    Background It is well recognized that right ventricular apical pacing can have deleterious effects on ventricular function. We performed a head-to-head comparison of the SafeR pacing algorithm versus DDD pacing with a long atrioventricular delay in a heterogeneous population of patients with dual-chamber pacemakers. Methods and Results In a multicenter prospective double-blinded randomized trial conducted at 10 centers in Canada, 373 patients, age 71±11 years, with indications for dual chamber DC pacemakers were randomized 1:1 to SafeR or DDD pacing with a long atrioventricular delay (250 ms). The primary objective was twofold: (1) reduction in the proportion of ventricular paced beats at 1 year; and (2) impact on atrial fibrillation burden at 3 years, defined as the ratio between cumulative duration of mode-switches divided by follow-up time. Statistical significance of both co-primary end points was required for the trial to be considered positive. At 1 year of follow-up, the median proportion of ventricular-paced beats was 4.0% with DDD versus 0% with SafeR (P<0.001). At 3 years of follow-up, the atrial fibrillation burden was not significantly reduced with SafeR versus DDD (median 0.00%, interquartile range [0.00% to 0.23%] versus median 0.01%, interquartile range [0.00% to 0.44%], respectively, P=0.178]), despite a persistent reduction in the median proportion of ventricular-paced beats (10% with DDD compared to 0% with SafeR). Conclusions A ventricular-paced rate <1% was safely achieved with SafeR in a population with a wide spectrum of indications for dual-chamber pacing. However, the lower percentage of ventricular pacing did not translate into a significant reduction in atrial fibrillation burden. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ Unique identifier: NCT01219621. PMID:26206737

  15. Risk of discontinuation of Advanced Therapy Medicinal Products clinical trials

    PubMed Central

    Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Objective Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. Methods We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Results Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. Conclusion No failure risk rate per development phase is available for ATMPs. The discontinuation rate may

  16. Multi-regional clinical trials and global drug development.

    PubMed

    Shenoy, Premnath

    2016-01-01

    Drug development has been globalized, and multi-regional clinical trial (MRCT) for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH) has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017. PMID:27141471

  17. Multi-regional clinical trials and global drug development

    PubMed Central

    Shenoy, Premnath

    2016-01-01

    Drug development has been globalized, and multi-regional clinical trial (MRCT) for regulatory submission has widely been conducted by many discovery based global pharmaceutical companies with the objective of reducing the time lag of launch in key markets and improve patient access to new and innovative treatments. Sponsors are facing several challenges while conducting multiregional clinical trials. Challenges under the heads statistics, clinical, regulatory operational, and ethics have been discussed. Regulators in different countries such as USA, EU-Japan, and China have issued guidance documents in respect of MRCT's. Lack of harmonization in the design and planning of MRCT is perceived to create a difficult situation to sponsors adversely affecting progressing MRCT in more and more discoveries. International conference on hormonisation (ICH) has initiated the process for having a harmonized guidance document on MRCT. This document is likely to be issued in early 2017. PMID:27141471

  18. The pharmaceutical industry's responsibility for protecting human subjects of clinical trials in developing nations.

    PubMed

    Kelleher, Finnuala

    2004-01-01

    Pharmaceutical companies increasingly perform clinical trials in developing nations. Governments of host nations see the trials as a way to provide otherwise unaffordable medical care, while trial sponsors are drawn to those countries by lower costs, the prevalence of diseases rare in developed nations, and large numbers of impoverished patients. Local governments, however, fail to police trials, and the FDA does not monitor trials in foreign countries, resulting in the routine violation of international standards for the protection of human subjects. This Note proposes independent accreditation of those institutions involved in clinical trials--the institutional review boards which oversee trial protocol; the organizations, such as pharmaceutical companies, which sponsor the trials; and the research organizations that conduct the trials. Accreditation, similar to that used in the footwear and apparel industries, would increase the transparency of pharmaceutical trials and would enable the United States government and consumers to hold trial sponsors accountable for their actions. PMID:16755695

  19. Aspects of vulnerable patients and informed consent in clinical trials

    PubMed Central

    Kuthning, Maria; Hundt, Ferdinand

    2013-01-01

    Scope: To discuss the rationale behind informed consent in clinical trials focusing on vulnerable patients from a European and German viewpoint. Methods: Scientific literature search via PubMed, Medline, Google. Results: Voluntary informed consent is the cornerstone of policies regulating clinical trials. To enroll a patient into a clinical trial without having obtained written and signed consent is to be considered as a serious issue in the conduct of a clinical trial. Development of ethical guidance for physicians started before Christ Era with the Hippocratic Oath. Main function of consent, as articulated in all guidelines developed for clinical research, is to facilitate an individual’s freedom of choice, respect autonomy, and thus to ensure welfare of the participants in clinical trials. Minors are unable to provide legally binding informed consent, this issue is addressed through a combination of parental permission and minor’s assent. Illiteracy is a critical problem that affects all corners of our earth; it has no boundaries and exists among every race and ethnicity, age group, and economic class. New strategies to improve communication with patients including the use of videotapes or animated cartoon illustrations could be taught. Finally the time with the potential participant seems to be the best way to improve understanding. Conclusion: Discovery of life saving and life enhancing new treatments requires partnership that is based on good communication and trust between patients and researchers, sponsors, ethics committees, authorities, lawyers and politicians so that vulnerable patients can benefit from the results of well controlled clinical trials. PMID:23346043

  20. Generalizability in two clinical trials of Lyme disease

    PubMed Central

    Cameron, Daniel J

    2006-01-01

    Objective To examine the generalizability of two National Institutes of Health (NIH)-funded double-blind randomized placebo-controlled clinical trials in patients with chronic Lyme disease and to determine whether selection factors resulted in the unfavorable outcomes. Design Epidemiologic review of the generalizability of two trials conducted by Klempner et al. This paper considers whether the study group was representative of the general chronic Lyme disease population. Results In their article in The New England Journal of Medicine, Klempner et al. failed to discuss the limitations of their clinical trials. This epidemiologic review argues that their results are not generalizable to the overall Lyme disease population. The treatment failure reported by the authors may be the result of enrolling patients who remained ill after an average of 4.7 years and an average of 3 previous courses of treatment. The poor outcome cited in these trials may be explained by having selected patients who had undergone delayed treatment or multiple treatments unsuccessfully. These selection factors were not addressed by the studies' authors, nor have they been discussed by reviewers. The trials have been over-interpreted by the NIH and widely publicized in a press release. The results have been extrapolated to other groups of Lyme disease patients by commentators, by a case discussant in an influential medical journal, and by health insurance companies to deny antibiotic treatment. Conclusion The Klempner et al. trials are assumed to be internally valid based on a Randomized Control Trial (RCT) design. However, this review argues that the trials have limited generalizability beyond the select group of patients with characteristics like those in the trial. Applying the findings to target populations with characteristics that differ from those included in these trials is inappropriate and may limit options for chronic Lyme disease patients who might benefit from antibiotic treatment

  1. ADULTS: A RANDOMIZED CONTROLLED CLINICAL TRIAL

    PubMed Central

    Shah, Krupa N.; Majeed, Zahraa; Yoruk, Yilmaz B.; Yang, Hongmei; Hilton, Tiffany N.; McMahon, James M.; Hall, William J.; Walck, Donna; Luque, Amneris E.; Ryan, Richard M.

    2016-01-01

    Objective HIV-infected older adults (HOA) are at risk of functional decline. Interventions promoting physical activity that can attenuate functional decline and are easily translated into the HOA community are of high priority. We conducted a randomized, controlled clinical trial to evaluate whether a physical activity counseling intervention based on self-determination theory (SDT) improves physical function, autonomous motivation, depression and the quality of life (QOL) in HOA. Methods A total of 67 community-dwelling HOA with mild-to-moderate functional limitations were randomized to one of two groups: a physical activity counseling group or the usual care control group. We used SDT to guide the development of the experimental intervention. Outcome measures that were collected at baseline and final study visits included a battery of physical function tests, levels of physical activity, autonomous motivation, depression, and QOL. Results The study participants were similar in their demographic and clinical characteristics in both the treatment and control groups. Overall physical performance, gait speed, measures of endurance and strength, and levels of physical activity improved in the treatment group compared to the control group (p<0.05). Measures of autonomous regulation such as identified regulation, and measures of depression and QOL improved significantly in the treatment group compared to the control group (p<0.05). Across the groups, improvement in intrinsic regulation and QOL correlated with an improvement in physical function (p<0.05). Conclusion Our findings suggest that a physical activity counseling program grounded in SDT can improve physical function, autonomous motivation, depression, and QOL in HOA with functional limitations. PMID:26867045

  2. Importance of placebo effect in cough clinical trials.

    PubMed

    Eccles, Ron

    2010-01-01

    Cough is a unique symptom because, unlike sneeze and other symptoms, it can be under voluntary control and this complicates clinical trials on cough medicines. All over-the-counter cough medicines (OTC) are very effective treatments because of their placebo effect. The placebo effect is enhanced by expectancy related to advertising, brand, packaging, and formulation. This placebo effect creates a problem for the conduct of clinical trials on OTC cough medicines that attempt to demonstrate the efficacy of a pharmacological agent above that of any placebo effect. Up to 85% of the efficacy of some cough medicines can be attributed to a placebo effect. The placebo effect apparent in clinical trials consists of several components: natural recovery, regression of cough response toward mean, demulcent effect, effect of sweetness, voluntary control, and effects related to expectancy and meaning of the treatment. The placebo effect has been studied most in the pain model, and placebo analgesia is reported to depend on the activation of endogenous opioid systems in the brain; this model may be applicable to cough. A balanced placebo design may help to control for the placebo effect, but this trial design may not be acceptable due to deception of patients. The placebo effect in clinical trials may be controlled by use of a crossover design, where feasible, and the changes in the magnitude of the placebo effect in this study design are discussed. PMID:19760296

  3. Consent to clinical trials in anaesthesia.

    PubMed

    Montgomery, J E; Sneyd, J R

    1998-03-01

    In order to evaluate satisfaction with, and recollection of, the consent process, we sent a postal questionnaire to 204 patients who had taken part in one of six clinical trials. Three trials were multicentre commercial studies and three were 'in house'. The readability of the different patient information sheets was compared. Seventy-seven per cent of patients responded, of whom 82% remembered having an information sheet. Most (99%) thought this was easy to read and understand. Five patients claimed that they had felt pressurised to take part in the trials. Nearly all patients (97%) realised that participation was voluntary and that other treatment would not be affected; 83% knew they could have changed their minds. There were no differences in the response patterns between the patients taking part in the different trials although the patient information sheets produced by pharmaceutical companies were longer and more complex than the 'in hospital' variety. We conclude that increasing the amount and complexity of information does not alter patient satisfaction. Taken overall, patients were content with the way they were approached when asked for consent for clinical trials. PMID:9613266

  4. Optimizing biologically targeted clinical trials for neurofibromatosis

    PubMed Central

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

    2014-01-01

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

  5. Regulatory aspects of clinical trials in children.

    PubMed

    Mentzer, Dirk

    2009-01-01

    Since introduction of the EU Paediatric Regulation in January 2007 the development and the life cycle of a drug in pre- and post-authorisation period has changed significantly. Pharmacovigilance science has traditionally been a discipline focussed on the post-marketing or post-authorisation period, with due attention directed towards pre-clinical safety data, clinical trials and adverse events. As the biological sciences have evolved, pharmacovigilance has slowly shifted toward earlier, proactive consideration of risks and potential benefits of drugs in the pre- and post-approval stages of drug development, leading to a maturing of drug safety risk management. The development of drugs for the paediatric population has changed the awareness that not only the safety issues need to be thoroughly investigated for a safe treatment of the children. In conjunction with the knowledge about efficacy, pharmacokinetic/pharmacodynamic and the age appropriate formulation for the concerned drug, the impact on the aim to apply safe medicines for children will steadily increase. Therefore, a proposal for a joint effort performing clinical research and appropriate drug development and clinical trials in children needs a strong support from a number of stakeholders like Clinical Trial Network, Paediatric Society, pharmaceutical industry and authorities. PMID:20799462

  6. Recommendations for conducting controlled clinical studies of dental restorative materials.

    PubMed

    Hickel, R; Roulet, J-F; Bayne, S; Heintze, S D; Mjör, I A; Peters, M; Rousson, V; Randall, R; Schmalz, G; Tyas, M; Vanherle, G

    2007-03-01

    About 35 years ago, Ryge provided a practical approach to evaluation of clinical performance of restorative materials. This systematic approach was soon universally accepted. While that methodology has served us well, a large number of scientific methodologies and more detailed questions have arisen that require more rigor. Current restorative materials have vastly improved clinical performance and any changes over time are not easily detected by the limited sensitivity of the Ryge criteria in short term clinical investigations. However, the clinical evaluation of restorations not only involves the restorative material per se but also different operative techniques. For instance, a composite resin may show good longevity data when applied in conventional cavities but not in modified operative approaches. Insensitivity, combined with the continually evolving and non-standard investigator modifications of the categories, scales, and reporting methods, has created a body of literature that is extremely difficult to meaningfully interpret. In many cases, the insensitivity of the original Ryge methods is misinterpreted as good clinical performance. While there are many good features of the original system, it is now time to move to a more contemporary one. The current review approaches this challenge in two ways: (1) a proposal for a modern clinical testing protocol for controlled clinical trials, and (2) an in-depth discussion of relevant clinical evaluation parameters, providing 84 references that are primarily related to issues or problems for clinical research trials. Together, these two parts offer a standard for the clinical testing of restorative materials/procedures and provide significant guidance for research teams in the design and conduct of contemporary clinical trials. Part 1 of the review considers the recruitment of subjects, restorations per subject, clinical events, validity versus bias, legal and regulatory aspects, rationales for clinical trial

  7. Using e-technologies in clinical trials.

    PubMed

    Rosa, Carmen; Campbell, Aimee N C; Miele, Gloria M; Brunner, Meg; Winstanley, Erin L

    2015-11-01

    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. PMID:26176884

  8. Surgeons: A Future Role in Clinical Trials?

    PubMed

    Rusch

    1997-01-01

    Clinical trials, particularly large cooperative group trials, establish the standards that we use to treat many of our cancer patients. The process by which multi-institutional clinical trials are developed, performed and peer-reviewed in the United States is equaled by few other countries around the world. Our clinical cooperative groups should be considered an important national resource. However, they stand at an embattled crossroads. Traditionally, only two to three percent of cancer patients have been entered onto clinical trials. In the past few years, national accrual has declined even further-from approximately 22,000 to 16,000 patients annually. The reasons for this decline are unclear. Although it could simply reflect a hiatus in the activity of some groups (such as the recent reorganization of the National Surgical Adjuvant Breast and Bowel Project [NSABP]), it more likely reflects changes in our health care environment. Few managed care insurance plans permit patient entry into clinical studies on the premise that trials increase patient care costs. Yet, individualized patient care not delivered according to strict peer-reviewed standards may cost more. While this remains undetermined, oncologists in both academic and private practice are being pressured to work harder for fewer rewards. They are being told that investigational treatments are not allowed even if trials evaluating these treatments may ultimately lead to better and more cost-effective patient care. This is a sad state of affairs at a time when, on one hand, treatment for many solid tumors remains desperately inadequate and, on the other hand, new insights into tumor biology promise to alter fundamentally our approach to cancer care. Where do surgeons fit into this picture? The cooperative groups were initiated in the mid-1950s, primarily to evaluate the potential role of chemotherapy in cancer treatment. During the past forty years, surgeons have usually played a supporting role in

  9. [Clinical trial data management and quality metrics system].

    PubMed

    Chen, Zhao-hua; Huang, Qin; Deng, Ya-zhong; Zhang, Yue; Xu, Yu; Yu, Hao; Liu, Zong-fan

    2015-11-01

    Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry. PMID:26911027

  10. Sustainable development of a GCP-compliant clinical trials platform in Africa: the Malaria Clinical Trials Alliance perspective

    PubMed Central

    2010-01-01

    Background The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Case description Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. Conclusion In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The

  11. The legal grounds regarding clinical trial in Turkey.

    PubMed

    Büken, Nüket Ornek; Büken, Erhan

    2011-12-01

    The first mention of clinical trials in a legal document occurred in Turkey many years before the Helsinki Declaration or Belmont report; issued in 1926, the Code of Pharmaceutical Products and Preparations No. 1262 law carries the statement: "Experimental drugs can be used in a patient only by his/her permission". Then the other regulation is the Regulation on Medical Deontology, dated 1960, and still in force. Article 10 and 11 of this Regulation address physicians and dentists who are conducting research. After periods of misconducted and ill-designed studies, the modern era of clinical trials began in 1993 with the introduction of the "Drug Research Bylaw". This document was directly influenced by the initial drafts of ICH-GCP Guidelines, and some parts were very similar. This became the main document that regulates the conduct of clinical trials in Turkey. A good clinical practice (GCP) guidelines document was added in 1995. On the other hand, an amendment made to Article 90 of the New Turkish Penal Code No. 5237 of 26 September 2004, which will come into force on 1st April 2005, envisages that in conflicts between international treaties concerning basic rights and freedoms and national laws, priority will be given to the international treaties. Therefore, in Turkish law, international treaties concerning basic rights and freedoms are given precedence as compared with national laws and other regulations. The Article stipulates the conduct of research on conditions such as not violating human well-being and dignity. PMID:22397183

  12. Unresolved Instrumentation Problems Following Clinical Trials Using Near Infrared Spectroscopy

    NASA Astrophysics Data System (ADS)

    Macnab, Andrew J.; Gagnon, Roy E.; Gagnon, Faith A.

    1998-10-01

    Near infrared spectroscopy (NIRS) clinical trials conducted over a seven year period have identified instrument engineering problems related to fiber optic failure, electromagnetic interference, chromophore algorithms, and computational software. These problems have caused confusion amongst clinicians at the bedside, rejection of large volumes of data, repeated reanalysis of data, and a significant diversion of project resources away from clinical studies and into engineering solutions. This article summarizes previously published studies and presents new data which, together, emphasize the need for improvements in NIRS technology. Instrument designers need to be aware of the need for these improvements if NIRS is to serve clinicians better during research designed to rationally define clinical management protocols.

  13. Creating clinical trial designs that incorporate clinical outcome assessments.

    PubMed

    Gilbert, Mark R; Rubinstein, Lawrence; Lesser, Glenn

    2016-03-01

    Clinical outcome assessments (COAs) are increasingly being used in determining the efficacy of new treatment regimens. This was typified in the recent use of a symptom-based instrument combined with an organ-based measure of response for the approval of ruxolitinib in myelofibrosis. There are challenges in incorporating these COAs into clinical trials, including designating the level of priority, incorporating these measures into a combined or composite endpoint, and dealing with issues related to compliance and interpretation of results accounting for missing data. This article describes the results of a recent panel discussion that attempted to address these issues and provide guidance to the incorporation of COAs into clinical trials, including novel statistical designs, so that the testing of new treatments in patients with cancers of the central nervous system can incorporate these important clinical endpoints. PMID:26989129

  14. Privacy and confidentiality in pragmatic clinical trials.

    PubMed

    McGraw, Deven; Greene, Sarah M; Miner, Caroline S; Staman, Karen L; Welch, Mary Jane; Rubel, Alan

    2015-10-01

    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. PMID:26374682

  15. RANDOMIZED CONTROLLED CLINICAL TRIALS IN ORTHOPEDICS: DIFFICULTIES AND LIMITATIONS

    PubMed Central

    Malavolta, Eduardo Angeli; Demange, Marco Kawamura; Gobbi, Riccardo Gomes; Imamura, Marta; Fregni, Felipe

    2015-01-01

    Randomized controlled clinical trials (RCTs) are considered to be the gold standard for evidence-based medicine nowadays, and are important for directing medical practice through consistent scientific observations. Steps such as patient selection, randomization and blinding are fundamental for conducting a RCT, but some additional difficulties are presented in trials that involve surgical procedures, as is common in orthopedics. The aim of this article was to highlight and discuss some difficulties and possible limitations on RCTs within the field of surgery. PMID:27027037

  16. Anthroposophical medicine: a systematic review of randomised clinical trials.

    PubMed

    Ernst, Edzard

    2004-02-28

    The aim of this systematic review was to summarise and critically evaluate all randomised clinical trials testing the effectiveness of the whole system of anthroposophical medicine either as a sole or as an adjunctive form of treatment. Seven independent literature searches were conducted to locate all such studies. Trials of single remedies within the wider anthroposophical approach were excluded. No language restrictions were applied. Unfortunately not a single study was located which met the inclusion/exclusion criteria. It was therefore concluded that, at present, the question whether the anthroposophical concept of healing generates more good than harm cannot be answered. PMID:15038403

  17. Are You "Tilting at Windmills" or Undertaking a Valid Clinical Trial?

    PubMed Central

    Zariffa, Jose; Kramer, John L.K.

    2011-01-01

    In this review, several aspects surrounding the choice of a therapeutic intervention and the conduct of clinical trials are discussed. Some of the background for why human studies have evolved to their current state is also included. Specifically, the following questions have been addressed: 1) What criteria should be used to determine whether a scientific discovery or invention is worthy of translation to human application? 2) What recent scientific advance warrants a deeper understanding of clinical trials by everyone? 3) What are the different types and phases of a clinical trial? 4) What characteristics of a human disorder should be noted, tracked, or stratified for a clinical trial and what inclusion /exclusion criteria are important to enrolling appropriate trial subjects? 5) What are the different study designs that can be used in a clinical trial program? 6) What confounding factors can alter the accurate interpretation of clinical trial outcomes? 7) What are the success rates of clinical trials and what can we learn from previous clinical trials? 8) What are the essential principles for the conduct of valid clinical trials? PMID:21786433

  18. Rett Syndrome: Reaching for Clinical Trials.

    PubMed

    Pozzo-Miller, Lucas; Pati, Sandipan; Percy, Alan K

    2015-07-01

    Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of-function mutations in MECP2. The methyl CpG binding protein 2 binds methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of target genes, controlling their transcription by recruiting co-repressors and co-activators. Several preclinical studies in mouse models have identified rational molecular targets for drug therapies aimed at correcting the underlying neural dysfunction. These targeted therapies are increasingly translating into human clinical trials. In this review, we present an overview of RTT and describe the current state of preclinical studies in methyl CpG binding protein 2-based mouse models, as well as current clinical trials in individuals with RTT. PMID:25861995

  19. Novel ocular antihypertensive compounds in clinical trials

    PubMed Central

    Chen, June; Runyan, Stephen A; Robinson, Michael R

    2011-01-01

    Introduction: 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 ultimately on demonstrating favorable efficacy and benefit-to-risk ratios relative to currently approved prostaglandin analogs and β-blockers and/or having complementary

  20. How ethical is your clinical trial?

    PubMed Central

    Miller, L; Folayan, M; Allman, D; Nkala, B; Kasirye, L M; Mingote, L R; Calazans, G; Mburu, R; Ntombela, F; Ditmore, M

    2010-01-01

    Is Institutional Review Board (IRB) approval and a rigorous informed consent process enough? It is our view that this is no longer the case. Conventional research ethics emphasise the importance of weighing the risks and benefits for prospective participants as one of the key determinants of deeming a clinical trial ethical. We support the notion that ethical obligations of research should include considerations not only at the individual level, but also at the community level (1,2). PMID:20561091

  1. Health, human rights, and the conduct of clinical research within oppressed populations

    PubMed Central

    Mills, Edward J; Singh, Sonal

    2007-01-01

    Background Clinical trials evaluating interventions for infectious diseases require enrolling participants that are vulnerable to infection. As clinical trials are conducted in increasingly vulnerable populations, issues of protection of these populations become challenging. In settings where populations are forseeably oppressed, the conduct of research requires considerations that go beyond common ethical concerns and into issues of international human rights law. Discussion Using examples of HIV prevention trials in Thailand, hepatitis-E prevention trials in Nepal and malaria therapeutic trials in Burma (Myanmar), we address the inadequacies of current ethical guidelines when conducting research within oppressed populations. We review existing legislature in the United States and United Kingdom that may be used against foreign investigators if trial hardships exist. We conclude by making considerations for research conducted within oppressed populations. PMID:17996056

  2. Gateways to clinical trials. December 2008.

    PubMed

    Tomillero, A; Moral, M A

    2008-12-01

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

  3. Women’s health and clinical trials

    PubMed Central

    Schiebinger, Londa

    2003-01-01

    Women have traditionally been underrepresented in clinical trials. In order to translate recent advances in our understanding of the molecular and physiological bases of sex differences into new therapeutics and health practices, sound sex-specific clinical data are imperative. Since the founding of the Office of Research on Women’s Health within the Office of the Director at the NIH in 1990, inequities in federally funded biomedical research, diagnosis, and treatment of diseases affecting women in the US have been reviewed. Discussed herein is the evolution of gender-related research innovations, primarily within the last decade, and strategies and challenges involved in the success of this recent development. PMID:14523031

  4. What can we do about exploratory analyses in clinical trials?

    PubMed

    Moyé, Lem

    2015-11-01

    The research community has alternatively embraced then repudiated exploratory analyses since the inception of clinical trials in the middle of the twentieth century. After a series of important but ultimately unreproducible findings, these non-prospectively declared evaluations were relegated to hypothesis generating. Since the majority of evaluations conducted in clinical trials with their rich data sets are exploratory, the absence of their persuasive power adds to the inefficiency of clinical trial analyses in an atmosphere of fiscal frugality. However, the principle argument against exploratory analyses is not based in statistical theory, but pragmatism and observation. The absence of any theoretical treatment of exploratory analyses postpones the day when their statistical weaknesses might be repaired. Here, we introduce examination of the characteristics of exploratory analyses from a probabilistic and statistical framework. Setting the obvious logistical concerns aside (i.e., the absence of planning produces poor precision), exploratory analyses do not appear to suffer from estimation theory weaknesses. The problem appears to be a difficulty in what is actually reported as the p-value. The use of Bayes Theorem provides p-values that are more in line with confirmatory analyses. This development may inaugurate a body of work that would lead to the readmission of exploratory analyses to a position of persuasive power in clinical trials. PMID:26390962

  5. Bayesian adaptive clinical trials: a dream for statisticians only?

    PubMed

    Chevret, Sylvie

    2012-05-20

    Adaptive or 'flexible' designs have emerged, mostly within frequentist frameworks, as an effective way to speed up the therapeutic evaluation process. Because of their flexibility, Bayesian methods have also been proposed for Phase I through Phase III adaptive trials; however, it has been reported that they are poorly used in practice. We aim to describe the international scientific production of Bayesian clinical trials by investigating the actual development and use of Bayesian 'adaptive' methods in the setting of clinical trials. A bibliometric study was conducted using the PubMed and Science Citation Index-Expanded databases. Most of the references found were biostatistical papers from various teams around the world. Most of the authors were from the US, and a large proportion was from the MD Anderson Cancer Center (University of Texas, Houston, TX). The spread and use of these articles depended heavily on their topic, with 3.1% of the biostatistical articles accumulating at least 25 citations within 5 years of their publication compared with 15% of the reviews and 32% of the clinical articles. We also examined the reasons for the limited use of Bayesian adaptive design methods in clinical trials and the areas of current and future research to address these challenges. Efforts to promote Bayesian approaches among statisticians and clinicians appear necessary. PMID:21905067

  6. Drug Development and Challenges for Neuromuscular Clinical Trials.

    PubMed

    El Mouelhi, Mohamed

    2016-03-01

    Drug development process faces many challenges, including those encountered in clinical trials for neuromuscular diseases. Drug development is a lengthy and highly costly process. Out of 10 compounds entering first study in man (phase 1), only one compound reaches the market after an average of 14 years with a cost of $2.7 billion. Nevertheless, according to the Centers for Medicare and Medicaid services, prescription drugs constituted only 9 % of each health care dollar spent in USA in 2013. Examples of challenges encountered in neuromuscular clinical trials include lack of validated patient-reported outcome tools, blinding issues, and the use of placebo in addition to lack of health authority guidance for orphan diseases. Patient enrollment challenge is the leading cause of missed clinical trial deadlines observed in about 80 % of clinical trials, resulting in delayed availability of potentially life-saving therapies. Another specific challenge introduced by recent technology is the use of social media and risk of bias. Sharing personal experiences while in the study could easily introduce bias among patients that would interfere with accurate interpretation of collected data. To minimize this risk, recent neuromuscular studies incorporate as an inclusion criterion the patient's agreement not to share any of study experiences through social media with other patients during the study conduct. Consideration of these challenges will allow timely response to the high unmet medical needs for many neuromuscular diseases. PMID:26691331

  7. NCI-supported facility to conduct cancer trials breaks ground in Puerto Rico

    Cancer.gov

    The Puerto Rican government has allocated $196 million dollars to build a 287,000 sq. ft., 96-bed, cancer hospital in San Juan. The new hospital, which will provide cancer treatment and conduct clinical trials, is the first of its kind in the Caribbean.

  8. Operation of a radiopharmacy for a clinical trial.

    PubMed

    Norenberg, Jeffrey P; Petry, Neil A; Schwarz, Sally

    2010-09-01

    in the operation of a radiopharmacy for clinical trials. Sponsors conduct audits as part of the quality assurance of clinical trials. Audits of clinical trial sites by the sponsor, sponsor's clinical research organization, institutional review board, or FDA always include a detailed review of drug accountability records. Audits for radiopharmaceutical drug products typically begin by confirming the clinical site is appropriately licensed and authorized to receive, possess, store, handle, prepare and administer radiopharmaceuticals. All procedures for radiopharmaceutical drug accountability must comply with applicable federal regulations and the specific requirements specified by the study sponsor. PMID:20674594

  9. Progress in defining clinically meaningful changes for clinical trials in nonrenal manifestations of SLE disease activity.

    PubMed

    Choi, Chan-Bum; Liang, Matthew H; Bae, Sang-Cheol

    2016-01-01

    Since the 2002 Dusseldorf meeting, one new agent, Benlysta, has been approved by the US Food and Drug Administration for systemic lupus erythematosus. Experiences from the field in conducting trials of all the agents tested during this period have provided valuable practical insights. There has been incremental progress in defining the minimal clinically important difference (MCID) of key disease manifestations and the view is largely that of the health care providers and not that of the person suffering the disease. This basic methodological work on the MCID should improve the efficiency and the clinical relevance of future trials and their design. PMID:26732314

  10. Pediatric Cardiovascular Clinical Trials: An Analysis of ClinicalTrials.gov and the Food and Drug Administration Pediatric Drug Labeling Database

    PubMed Central

    Hill, Kevin D.; Henderson, Heather T.; Hornik, Christoph P.; Li, Jennifer S.

    2015-01-01

    Recent regulatory initiatives in the United States and Europe have transformed the pediatric clinical trials landscape by significantly increasing capital investment and pediatric trial volume. The purpose of this manuscript is to review the impact of these initiatives on the pediatric cardiovascular trials landscape when compared to other pediatric sub-specialties. We also evaluate factors that may have contributed to the success or failure of recent major pediatric cardiovascular trials so as to inform the optimal design and conduct of future trials in the field. PMID:26377725

  11. Remote ischemic conditioning: a clinical trial's update.

    PubMed

    Candilio, Luciano; Hausenloy, Derek J; Yellon, Derek M

    2011-01-01

    Coronary artery disease (CAD) is the leading cause of death and disability worldwide, and early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome. This process can, however, induce further myocardial damage, namely acute myocardial ischemia-reperfusion injury (IRI) and worsen clinical outcome. Therefore, novel therapeutic strategies are required to protect the myocardium against IRI in patients with CAD. In this regard, the endogenous cardioprotective phenomenon of "ischemic conditioning," in which the heart is put into a protected state by subjecting it to one or more brief nonlethal episodes of ischemia and reperfusion, has the potential to attenuate myocardial injury during acute IRI. Intriguingly, the heart can be protected in this manner by applying the "ischemic conditioning" stimulus to an organ or tissue remote from the heart (termed remote ischemic conditioning or RIC). Furthermore, the discovery that RIC can be noninvasively applied using a blood pressure cuff on the upper arm to induce brief episodes of nonlethal ischemia and reperfusion in the forearm has greatly facilitated the translation of RIC into the clinical arena. Several recently published proof-of-concept clinical studies have reported encouraging results with RIC, and large multicenter randomized clinical trials are now underway to investigate whether this simple noninvasive and virtually cost-free intervention has the potential to improve clinical outcomes in patients with CAD. In this review article, we provide an update of recently published and ongoing clinical trials in the field of RIC. PMID:21821533

  12. Cytomegalovirus vaccine: phase II clinical trial results.

    PubMed

    Rieder, F; Steininger, C

    2014-05-01

    Cytomegalovirus (CMV) is one of the most significant viral pathogens during pregnancy and in immunocompromised patients. Antiviral prophylactic strategies are limited by toxicities, drug-drug interactions and development of antiviral resistance. A safe and protective vaccine against CMV is highly desirable in view of the potential positive impact on CMV-associated morbidity and mortality as well as healthcare costs. Unfortunately, this demand could not be met in the past four decades although development of a CMV vaccine has been ranked at the highest priority by the US Institute of Medicine. Multiple different vaccine candidates have been developed and evaluated in phase I clinical trials and few succeeded to phase II trials. Nevertheless, two different vaccines showed recently promising results in trials that studied healthy adults and immunocompromised solid-organ and bone-marrow transplant recipients, respectively. The gB/MF59 vaccine exhibited a vaccine efficacy of 50% in healthy, postpartum females. In transplant patients, gB/MF59 and the DNA vaccine TransVax both limited the periods of viraemia and consequently the need for antiviral treatment. The success of these trials is encouraging and will probably give new impetus to the development of an effective CMV vaccine. Sterilizing immunity may not be attainable in the near future and may not be necessary for a CMV vaccine to have a significant impact on health care as discussed in the present review. PMID:24283990

  13. Treatment of blepharitis: recent clinical trials.

    PubMed

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

    2014-10-01

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

  14. Conducting Economic Evaluations Alongside Randomised Trials: Current Methodological Issues and Novel Approaches.

    PubMed

    Hughes, Dyfrig; Charles, Joanna; Dawoud, Dalia; Edwards, Rhiannon Tudor; Holmes, Emily; Jones, Carys; Parham, Paul; Plumpton, Catrin; Ridyard, Colin; Lloyd-Williams, Huw; Wood, Eifiona; Yeo, Seow Tien

    2016-05-01

    Trial-based economic evaluations are an important aspect of health technology assessment. The availability of patient-level data coupled with unbiased estimates of clinical outcomes means that randomised controlled trials are effective vehicles for the generation of economic data. However there are methodological challenges to trial-based evaluations, including the collection of reliable data on resource use and cost, choice of health outcome measure, calculating minimally important differences, dealing with missing data, extrapolating outcomes and costs over time and the analysis of multinational trials. This review focuses on the state of the art of selective elements regarding the design, conduct, analysis and reporting of trial-based economic evaluations. The limitations of existing approaches are detailed and novel methods introduced. The review is internationally relevant but with a focus towards practice in the UK. PMID:26753558

  15. The Joys of Clinical Trials: A Case Study of a Multicenter Pharmaceutical Trial.

    ERIC Educational Resources Information Center

    Soronson, Bryan M.; Shaw, Diana V.

    1994-01-01

    A discussion of clinical trials in the pharmaceutical industry describes typical processes and administrative issues, then presents a case in which a foreign pharmaceutical company negotiated with a university for sponsorship of a multicenter clinical trial of a new drug therapy. Problems and important considerations in clinical trials are…

  16. Valerian for insomnia: a systematic review of randomized clinical trials.

    PubMed

    Stevinson; Ernst

    2000-04-01

    Objective: To systematically review the evidence for the effects of the herb valerian (Valeriana officinalis) on insomnia, based on randomized, placebo-controlled, double-blind trials.Background: Valerian has long been advocated and used for promoting sleep but until quite recently evidence was solely anecdotal. However, during the last two decades a number of clinical trials have been conducted.Materials and methods: Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the effect of valerian monopreparations on sleep in human participants. Data were extracted in a standardized manner and methodological quality was assessed by the Jadad score.Results: Nine trials were located meeting the selection criteria. The findings of the studies were contradictory and there was great inconsistency between trials in terms of patients, experimental design and procedures and methodological quality.Conclusion: The evidence for valerian as a treatment for insomnia is inconclusive. There is a need for rigorous trials to determine its efficacy. PMID:10767649

  17. Tyranny of the randomised clinical trial.

    PubMed

    Rosenbek, John C

    2016-06-01

    Researchers and clinicians often disagree about what it means to provide the best possible care. This paper's purpose is to propose ways of resolving the disagreements. The first is to have both groups re-examine the three equal components of evidence-based practice, a re-examination that begins with rejection of the randomised clinical trial's tyranny. The second is for researchers to design rehabilitation research based on a biopsychosocial rather than a biomedical model. The third is for both groups to redefine translational research so that it means both translation from the laboratory to the clinic and from the clinic to the laboratory. The fourth is to advocate for a science of dissemination that is as robust as rehabilitation's present science of discovery. Most examples are drawn from the literature on acquired neurologic speech and language disorders. PMID:27124262

  18. OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in osteoarthritis.

    PubMed

    Hunter, D J; Arden, N; Cicuttini, F; Crema, M D; Dardzinski, B; Duryea, J; Guermazi, A; Haugen, I K; Kloppenburg, M; Maheu, E; Miller, C G; Martel-Pelletier, J; Ochoa-Albíztegui, R E; Pelletier, J-P; Peterfy, C; Roemer, F; Gold, G E

    2015-05-01

    Tremendous advances have occurred in our understanding of the pathogenesis of hand osteoarthritis (OA) and these are beginning to be applied to trials targeted at modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply hand imaging assessments in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations. PMID:25952345

  19. Prostate Cancer Prevention: Concepts and Clinical Trials.

    PubMed

    Hamilton, Zachary; Parsons, J Kellogg

    2016-04-01

    Prevention is an important treatment strategy for diminishing prostate cancer morbidity and mortality and is applicable to both early- and late-stage disease. There are three basic classifications of cancer prevention: primary (prevention of incident disease), secondary (identification and treatment of preclinical disease), and tertiary (prevention of progression or recurrence). Based on level I evidence, 5-alpha reductase inhibitors (5-ARIs) should be considered in selected men to prevent incident prostate cancer. Level I evidence also supports the consideration of dutasteride, a 5-ARI, for tertiary prevention in active surveillance and biochemical recurrence patients. Vitamins and supplements, including selenium or vitamin E, have not been proven in clinical trials to prevent prostate cancer and in the case of Vitamin E has been found to increase the risk of incident prostate cancer. Ongoing and future trials may further elucidate the role of diet and immunotherapy for prevention of prostate cancer. PMID:26957512

  20. An international survey of physicians regarding clinical trials: a comparison between Kyoto University Hospital and Seoul National University Hospital

    PubMed Central

    2013-01-01

    Background International clinical trials are now rapidly expanding into Asia. However, the proportion of global trials is higher in South Korea compared to Japan despite implementation of similar governmental support in both countries. The difference in clinical trial environment might influence the respective physicians’ attitudes and experience towards clinical trials. Therefore, we designed a questionnaire to explore how physicians conceive the issues surrounding clinical trials in both countries. Methods A questionnaire survey was conducted at Kyoto University Hospital (KUHP) and Seoul National University Hospital (SNUH) in 2008. The questionnaire consisted of 15 questions and 2 open-ended questions on broad key issues relating to clinical trials. Results The number of responders was 301 at KUHP and 398 at SNUH. Doctors with trial experience were 196 at KUHP and 150 at SNUH. Among them, 12% (24/196) at KUHP and 41% (61/150) at SUNH had global trial experience. Most respondents at both institutions viewed clinical trials favorably and thought that conducting clinical trials contributed to medical advances, which would ultimately lead to new and better treatments. The main reason raised as a hindrance to conducting clinical trials was the lack of personnel support and time. Doctors at both university hospitals thought that more clinical research coordinators were required to conduct clinical trials more efficiently. KUHP doctors were driven mainly by pure academic interest or for their desire to find new treatments, while obtaining credits for board certification and co-authorship on manuscripts also served as motivation factors for doctors at SNUH. Conclusions Our results revealed that there might be two different approaches to increase clinical trial activity. One is a social level approach to establish clinical trial infrastructure providing sufficient clinical research professionals. The other is an individual level approach that would provide incentives to

  1. Gender Analysis of Moxifloxacin Clinical Trials

    PubMed Central

    Ruiz-Cantero, Ma Teresa; Pardo, Ma Angeles

    2014-01-01

    Abstract Purpose: To determine the inclusion of women and the sex-stratification of results in moxifloxacin Clinical Trials (CTs), and to establish whether these CTs considered issues that specifically affect women, such as pregnancy and use of hormonal therapies. Previous publications about women's inclusion in CTs have not specifically studied therapeutic drugs. Although this type of drug is taken by men and women at a similar rate, adverse effects occur more frequently in the latter. Methods: We reviewed 158 published moxifloxacin trials on humans, retrieved from MedLine and the Cochrane Library (1998–2010), to determine whether they complied with the gender recommendations published by U.S. Food and Drug Administration Guideline. Results: Of a total of 80,417 subjects included in the moxifloxacin CTs, only 33.7% were women in phase I, in contrast to phase II, where women accounted for 45%, phase III, where they represented 38.3% and phase IV, where 51.3% were women. About 40.9% (n=52) of trials were stratified by sex and 15.3% (n=13) and 9% (n=7) provided data by sex on efficacy and adverse effects, respectively. We found little information about the influence of issues that specifically affect women. Only 3 of the 59 journals that published the moxifloxacin CTs stated that authors should stratify their results by sex. Conclusions: Women are under-represented in the published moxifloxacin trials, and this trend is more marked in phase I, as they comprise a higher proportion in the other phases. Data by sex on efficacy and adverse effects are scarce in moxifloxacin trials. These facts, together with the lack of data on women-specific issues, suggest that the therapeutic drug moxifloxacin is only a partially evidence-based medicine. PMID:24180298

  2. Integrated safety in tocilizumab clinical trials

    PubMed Central

    2011-01-01

    Introduction The efficacy and safety of tocilizumab in patients with rheumatoid arthritis have been evaluated in a comprehensive phase 3 program. Patients from these randomized trials could receive tocilizumab treatment in open-label extension trials. Here, the long-term safety profile of tocilizumab, using pooled data from all of these trials, is reported. Methods Cumulative safety data (as of February 6, 2009) from five core phase 3 trials, two ongoing extension trials, and one clinical pharmacology study were analyzed. Two patient populations were evaluated: an all-control population (n = 4,199), which included all patients randomly assigned in the placebo-controlled portions of the five core studies, and an all-exposed population (n = 4,009), which included patients from any of the eight studies who received at least one dose of tocilizumab. Results Total exposure to tocilizumab was 8,580 patient years (PY), and total duration of observation was 9,414 PY. Overall adverse event (AE) and serious AE (SAE) rates were 278.2/100 PY and 14.4/100 PY, respectively. These events included serious infections (4.7/100 PY), opportunistic infections (0.23/100 PY), gastrointestinal perforations (0.28/100 PY), malignancy (1.1/100 PY), myocardial infarction (0.25/100 PY), and stroke (0.19/100 PY). The rates of SAEs and serious infections were stable over time; no increase with prolonged exposure was noted. Conclusions The longer-term safety profile of tocilizumab (mean treatment duration, 2.4 years) is consistent with that observed in the phase 3 studies (duration up to 1 year). PMID:21884601

  3. Five questions to consider before conducting a stepped wedge trial.

    PubMed

    Hargreaves, James R; Copas, Andrew J; Beard, Emma; Osrin, David; Lewis, James J; Davey, Calum; Thompson, Jennifer A; Baio, Gianluca; Fielding, Katherine L; Prost, Audrey

    2015-01-01

    Researchers should consider five questions before starting a stepped wedge trial. Why are you planning one? Researchers sometimes think that stepped wedge trials are useful when there is little doubt about the benefit of the intervention being tested. However, if the primary reason for an intervention is to measure its effect, without equipoise there is no ethical justification for delaying implementation in some clusters. By contrast, if you are undertaking pragmatic research, where the primary reason for rolling out the intervention is for it to exert its benefits, and if phased implementation is inevitable, a stepped wedge trial is a valid option and provides better evidence than most non-randomized evaluations. What design will you use? Two common stepped wedge designs are based on the recruitment of a closed or open cohort. In both, individuals may experience both control and intervention conditions and you should be concerned about carry-over effects. In a third, continuous-recruitment, short-exposure design, individuals are recruited as they become eligible and experience either control or intervention condition, but not both. How will you conduct the primary analysis? In stepped wedge trials, control of confounding factors through secular variation is essential. 'Vertical' approaches preserve randomization and compare outcomes between randomized groups within periods. 'Horizontal' approaches compare outcomes before and after crossover to the intervention condition. Most analysis models used in practice combine both types of comparison. The appropriate analytic strategy should be considered on a case-by-case basis. How large will your trial be? Standard sample size calculations for cluster randomized trials do not accommodate the specific features of stepped wedge trials. Methods exist for many stepped wedge designs, but simulation-based calculations provide the greatest flexibility. In some scenarios, such as when the intracluster correlation coefficient is

  4. Gateways to clinical trials. March 2003.

    PubMed

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

    2003-03-01

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

  5. Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis

    PubMed Central

    Tupasi, Thelma; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

    2016-01-01

    Abstract Problem New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. Approach We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization – Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Local setting Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Relevant changes Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Lessons learnt Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial. PMID:26908964

  6. From Laboratory Research to a Clinical Trial

    PubMed Central

    Keevil, C. William; Salgado, Cassandra D.; Schmidt, Michael G.

    2015-01-01

    Objective: This is a translational science article that discusses copper alloys as antimicrobial environmental surfaces. Bacteria die when they come in contact with copper alloys in laboratory tests. Components made of copper alloys were also found to be efficacious in a clinical trial. Background: There are indications that bacteria found on frequently touched environmental surfaces play a role in infection transmission. Methods: In laboratory testing, copper alloy samples were inoculated with bacteria. In clinical trials, the amount of live bacteria on the surfaces of hospital components made of copper alloys, as well as those made from standard materials, was measured. Finally, infection rates were tracked in the hospital rooms with the copper components and compared to those found in the rooms containing the standard components. Results: Greater than a 99.9% reduction in live bacteria was realized in laboratory tests. In the clinical trials, an 83% reduction in bacteria was seen on the copper alloy components, when compared to the surfaces made from standard materials in the control rooms. Finally, the infection rates were found to be reduced by 58% in patient rooms with components made of copper, when compared to patients' rooms with components made of standard materials. Conclusions: Bacteria die on copper alloy surfaces in both the laboratory and the hospital rooms. Infection rates were lowered in those hospital rooms containing copper components. Thus, based on the presented information, the placement of copper alloy components, in the built environment, may have the potential to reduce not only hospital-acquired infections but also patient treatment costs. PMID:26163568

  7. Clinical Trials in the Era of Personalized Oncology

    PubMed Central

    Maitland, Michael L.; Schilsky, Richard L.

    2011-01-01

    The rapid pace of discoveries in tumor biology, imaging technology, and human genetics hold promise for an era of personalized oncology care. The successful development of a handful of new targeted agents has generated much hope and hype about the delivery of safer and more effective new treatments for cancer. The design and conduct of clinical trials has not yet adjusted to a new era of personalized oncology and so we are more in transition to that era than in it. With the development of treatments for breast cancer as a model, we review the approaches to clinical trials and development of novel therapeutics in the prior era of population oncology, the current transitional era, and the future era of personalized oncology. PMID:22034206

  8. Epothilones: from discovery to clinical trials

    PubMed Central

    Forli, Stefano

    2015-01-01

    Epothilones are natural compounds isolated from a myxobacterium at the beginning of the 1990s, and showed a remarkable anti-neoplastic activity. They act through the same mechanism of action of paclitaxel, by stabilizing microtubules and inducing apoptosis. Although, their chemical structure, simpler than taxanes, makes them more suitable for derivatization. Their interesting pharmacokinetic and bioavailabilty profiles, and the activity against paclitaxel-resistant cell lines make them interesting therapeutic agents. Here a brief historical perspective of epothilones is presented, since their isolation, the identification of their mechanism of action and activity, to the recent clinical trials. PMID:25434353

  9. A survey of clinical trials with fenbufen.

    PubMed

    Mawdsley, P

    1980-01-01

    To date, the efficacy and safety of gamma-oxo(1,1'-biphenyl)-4-butanoic acid (fenbufen) have been evaluated in over 200 clinical trials involving several thousand patients. The program of clinical investigation consisted of open dose ranging studies in patients; short-term, double-blind controlled studies of both cross-over and parallel group design to evaluate efficacy and safety compared to placebo and active reference drugs; long-term, double-blind controlled studies of parallel group design versus an active reference agent; open studies to evaluate the long-term efficacy and safety of fenbufen; and special studies to investigate possible effects on eyes, ears and heart. The overall experience with fenbufen in 60 US and 37 foreign clinical trials is summarized in this report with respect to the following: therapeutic efficacy and safety in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, analgesia and gout. The age range covered in these studies was 13 to 87 years, and included 206 patients over the age of 70. 3457 patients received fenbufen in all phases of these clinical trials, including short-term and long-term studies. The patient total includes: 1462 patients (664 US, 798 foreign) with rheumatoid arthritis, 1225 (420 US, 805 foreign) with osteoarthritis, 55 (19 US, 36 foreign) with ankylosing spondylitis, 39 (foreign) with gout, and 676 patients (103 US, 573 (foreign) who participated in analgesia studies. The worldwide clinical studies have demonstrated very good clinical efficacy of fenbufen in comparison to other non-steroidal antirheumatic (nsa) drugs. The tolerance was much better in many cases compared with tolerance levels of other nsa-drugs. The good results were confirmed by new papers presented during IX International Congress of Rheumatology, Wiesbaden/FR Germany, September 1979. Fenbufen is currently marketed in Brazil, Columbia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Great Britain, Greece, Guatemala, Honduras

  10. Current challenges for clinical trials of cardiovascular medical devices.

    PubMed

    Zannad, Faiez; Stough, Wendy Gattis; Piña, Ileana L; Mehran, Roxana; Abraham, William T; Anker, Stefan D; De Ferrari, Gaetano M; Farb, Andrew; Geller, Nancy L; Kieval, Robert S; Linde, Cecilia; Redberg, Rita F; Stein, Kenneth; Vincent, Alphons; Woehrle, Holger; Pocock, Stuart J

    2014-07-15

    Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches. Anticipation of potential bias should be considered and planned for prospectively in a cardiovascular device trial. Prospective, single-arm studies (often referred to as registry studies) can provide additional data in some cases. They are subject to selection bias even when carefully designed; thus, they are generally not acceptable as the sole basis for pre-market approval of high risk cardiovascular devices. However, they complement the evidence base and fill the gaps unanswered by randomized trials. Registry studies present device safety and effectiveness in day-to-day clinical practice settings and detect rare adverse events in the post-market period. No single research design will be appropriate for every cardiovascular device or target patient population. The type of trial, appropriate control group, and optimal length of follow-up will depend on the specific device, its potential clinical benefits, the target patient population and the existence (or lack) of effective therapies, and its anticipated risks. Continued efforts on the part of investigators, the device industry, and government regulators are needed to reach the optimal approach for evaluating the safety and performance of innovative devices for the treatment of cardiovascular disease. PMID:24861254

  11. Clinical trials for stem cell transplantation: when are they needed?

    PubMed

    Van Pham, Phuc

    2016-01-01

    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. PMID:27121227

  12. Automating risk of bias assessment for clinical trials.

    PubMed

    Marshall, Iain J; Kuiper, Joël; Wallace, Byron C

    2015-07-01

    Systematic reviews, which summarize the entirety of the evidence pertaining to a specific clinical question, have become critical for evidence-based decision making in healthcare. But such reviews have become increasingly onerous to produce due to the exponentially expanding biomedical literature base. This study proposes a step toward mitigating this problem by automating risk of bias assessment in systematic reviews, in which reviewers determine whether study results may be affected by biases (e.g., poor randomization or blinding). Conducting risk of bias assessment is an important but onerous task. We thus describe a machine learning approach to automate this assessment, using the standard Cochrane Risk of Bias Tool which assesses seven common types of bias. Training such a system would typically require a large labeled corpus, which would be prohibitively expensive to collect here. Instead, we use distant supervision, using data from the Cochrane Database of Systematic Reviews (a large repository of systematic reviews), to pseudoannotate a corpus of 2200 clinical trial reports in PDF format. We then develop a joint model which, using the full text of a clinical trial report as input, predicts the risks of bias while simultaneously extracting the text fragments supporting these assessments. This study represents a step toward automating or semiautomating extraction of data necessary for the synthesis of clinical trials. PMID:25966488

  13. Conducting Clinical Research Using Crowdsourced Convenience Samples.

    PubMed

    Chandler, Jesse; Shapiro, Danielle

    2016-03-28

    Crowdsourcing has had a dramatic impact on the speed and scale at which scientific research can be conducted. Clinical scientists have particularly benefited from readily available research study participants and streamlined recruiting and payment systems afforded by Amazon Mechanical Turk (MTurk), a popular labor market for crowdsourcing workers. MTurk has been used in this capacity for more than five years. The popularity and novelty of the platform have spurred numerous methodological investigations, making it the most studied nonprobability sample available to researchers. This article summarizes what is known about MTurk sample composition and data quality with an emphasis on findings relevant to clinical psychological research. It then addresses methodological issues with using MTurk-many of which are common to other nonprobability samples but unfamiliar to clinical science researchers-and suggests concrete steps to avoid these issues or minimize their impact. PMID:26772208

  14. Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination

    PubMed Central

    Williams, Rebecca J.; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A.

    2015-01-01

    Background Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Conclusions Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study

  15. OpenTrials: towards a collaborative open database of all available information on all clinical trials.

    PubMed

    Goldacre, Ben; Gray, Jonathan

    2016-01-01

    OpenTrials is a collaborative and open database for all available structured data and documents on all clinical trials, threaded together by individual trial. With a versatile and expandable data schema, it is initially designed to host and match the following documents and data for each trial: registry entries; links, abstracts, or texts of academic journal papers; portions of regulatory documents describing individual trials; structured data on methods and results extracted by systematic reviewers or other researchers; clinical study reports; and additional documents such as blank consent forms, blank case report forms, and protocols. The intention is to create an open, freely re-usable index of all such information and to increase discoverability, facilitate research, identify inconsistent data, enable audits on the availability and completeness of this information, support advocacy for better data and drive up standards around open data in evidence-based medicine. The project has phase I funding. This will allow us to create a practical data schema and populate the database initially through web-scraping, basic record linkage techniques, crowd-sourced curation around selected drug areas, and import of existing sources of structured and documents. It will also allow us to create user-friendly web interfaces onto the data and conduct user engagement workshops to optimise the database and interface designs. Where other projects have set out to manually and perfectly curate a narrow range of information on a smaller number of trials, we aim to use a broader range of techniques and attempt to match a very large quantity of information on all trials. We are currently seeking feedback and additional sources of structured data. PMID:27056367

  16. 76 FR 51375 - Dialogues in Diversifying Clinical Trials: Successful Strategies for Engaging Women and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... 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....

  17. Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

    MedlinePlus

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

  18. Clinical Trials With Mesenchymal Stem Cells: An Update.

    PubMed

    Squillaro, Tiziana; Peluso, Gianfranco; Galderisi, Umberto

    2016-01-01

    In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs, can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy (ISCT) to issue criteria for identifying unique populations of these cells. Consequently, the isolation of MSCs according to ISCT criteria has produced heterogeneous, nonclonal cultures of stromal cells containing stem cells with different multipotent properties, committed progenitors, and differentiated cells. Though the nature and functions of MSCs remain unclear, nonclonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSC-based clinical trials, either complete or ongoing, appear in the database of the US National Institutes of Health. In the present article, we provide a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes biological properties of MSCs, elucidates recent clinical findings and clinical trial phases of investigation, highlights therapeutic effects of MSCs, and identifies principal criticisms of the use of these cells. In particular, we analyze clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney

  19. Lessons Learned from HIV Vaccine Clinical Efficacy Trials

    PubMed Central

    Day, Tracey A.; Kublin, James G.

    2014-01-01

    The past few years have witnessed many promising advances in HIV prevention strategies involving pre-exposure prophylaxis approaches. Some may now wonder whether an HIV vaccine is still needed, and whether developing one is even possible. The partial efficacy reported in the RV144 trial and the encouraging results of the accompanying immune correlates analysis suggest that an effective HIV vaccine is achievable. These successes have provided a large impetus and guidance for conducting more HIV vaccine trials. A key lesson learned from RV144 is that assessment of HIV acquisition is now a feasible and valuable primary objective for HIV preventive vaccine trials. In this article we review how RV144 and other HIV vaccine efficacy trials have instructed the field and highlight some of the HIV vaccine concepts in clinical development. After a long and significant investment, HIV vaccine clinical research is paying off in the form of valuable lessons that, if applied effectively, will accelerate the path toward a safe and effective vaccine. Together with other HIV prevention approaches, preventive and therapeutic HIV vaccines will be invaluable tools in bringing the epidemic to an end. PMID:24033299

  20. Clinical Research Trials | NIH MedlinePlus the Magazine

    MedlinePlus

    ... version of this page please turn Javascript on. Clinical Research Trials Past Issues / Summer 2012 Table of Contents Let the Opportunities to Join A Clinical Study Find You How does clinical research work? ...

  1. Future Clinical Trials in DIPG: Bringing Epigenetics to the Clinic

    PubMed Central

    Morales La Madrid, Andres; Hashizume, Rintaro; Kieran, Mark W.

    2015-01-01

    In spite of major recent advances in diffuse intrinsic pontine glioma (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 pathogenesis. 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 (histone) 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 will discuss the role of both epigenetic and genetic mutations within DIPG and the development of treatment

  2. Searching ClinicalTrials.gov and the International Clinical Trials Registry Platform to inform systematic reviews: what are the optimal search approaches?*

    PubMed Central

    Glanville, Julie M.; Duffy, Steven; McCool, Rachael; Varley, Danielle

    2014-01-01

    Background: Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. Objectives: The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. Methods: A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. Results: On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. Conclusions: Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. Implications: For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched. PMID:25031558

  3. Acceptance checklist for clinical effectiveness pilot trials: a systematic approach

    PubMed Central

    2013-01-01

    Conducting a pilot trial is important in preparing for, and justifying investment in, the ensuing larger trial. Pilot trials using the same design and methods as the subsequent main trial are ethically and financially advantageous especially when pilot and main trial data can be pooled. For explanatory trials in which internal validity is paramount, there is little room for variation of methods between the pilot and main trial. For pragmatic trials, where generalisability or external validity is key, greater flexibility is written into trial protocols to allow for ‘real life’ variation in procedures. We describe the development of a checklist for use in decision-making on whether pilot data can be carried forward to the main trial dataset without compromising trial integrity. We illustrate the use of the checklist using a pragmatic trial of psychosocial interventions for family carers of people with dementia as a case study. PMID:23758922

  4. Women's involvement in clinical trials: historical perspective and future implications.

    PubMed

    Liu, Katherine A; Mager, Natalie A Dipietro

    2016-01-01

    The importance of considering the differences between the male and female sex in clinical decision-making is crucial. However, it has been acknowledged in recent decades that clinical trials have not always adequately enrolled women or analyzed sex-specific differences in the data. As these deficiencies have hindered the progress of understanding women's response to medications, agencies in the United States have worked towards the inclusion of women in clinical trials and appropriate analysis of sex-specific data from clinical trials. This review outlines the history and progress of women's inclusion in clinical trials for prescription drugs and presents considerations for researchers, clinicians, and academicians on this issue. PMID:27011778

  5. Gateways to Clinical Trials. June 2002.

    PubMed

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

    2002-06-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abacavir sulfate, abarelix, abciximab, alicaforsen sodium, almotriptan, alteplase, amlodipine, amoxicillin trihydrate, amprenavir, argatroban monohydrate, aspirin, atorvastatin calcium, azathioprine; Baclofen, benidipine hydrochloride, benserazide, BMS-214662, bosentan, botulinum toxin type B; Candesartan cilexetil, carbamazepine, carbidopa, carboplatin, ceftriaxone sodium, celecoxib, cetirizine hydrochloride, clarithromycin, clavulanate potassium, clopidogrel hydrogensulfate, clozapine, CPI-1189, cyclophosphamide, cytarabine; Darbepoetin alfa, denileukin diftitox, dexamethasone, dipyridamole, droperidol, DW-166HC; Ebastine, efalizumab, efavirenz, eletriptan, enalapril maleate, enfuvirtide, enoxaparin sodium, enrasentan, entacapone, epoetin, eprosartan mesilate, etanercept, etoricoxib; Fenofibratefexofenadine hydrochloride, filgrastim, fludarabine phosphate, fluoxetine hydrochloride fluvoxamine maleate, frovatriptan, furosemide; Gabapentin, galantamine hydrobromide, gatifloxacin, gefitinib, ghrelin (human), glatiramer acetate; Haloperidol; Ibuprofen, ibuprofen, guaiacol ester, idarubicin hydrochloride, imipramine hydrochloride, imiquimod, interferon beta, interferon beta-1a, interferon beta-1b, interferon omega, irbesartan, itraconazole; Ketorolac, ketorolac tromethamine; Lamifiban, lamotrigine, lanoteplase, lansoprazole, leflunomide, leuprorelin acetate, levetiracetam, levocetirizine, levodopa, lisinopril, loratadine; Manidipine, methylprednisolone, metronidazole, mirtazapine, mizolastine, modafinil, morphine sulfate; Naproxen sodium, naratriptan hydrochloride, nifedipine, NSC-683864; Ofloxacin, olanzapine

  6. Paradigm shifts in clinical trials enabled by information technology.

    PubMed

    Marks, R G; Conlon, M; Ruberg, S J

    The use of the world wide web for clinical trials changes the processes of performing clinical research in several fundamental ways. Greatly improved security, monitoring capability, and accuracy and timeliness of study conduct can be achieved while lowering cost. Data quality is enhanced while co-ordinating centre effort is reduced. The web provides a natural environment for linking the various components of clinical research, leading to new levels of simplicity and efficiency. It also enhances opportunities for recruitment of study investigators and patients. Other information technology tools and databases can be used to assist in this regard as well. Web-based trials change the relationship of the investigator site to the study and the site to the co-ordinating centre. Different roles and responsibilities lead to simplified processes and more and higher quality data. Many standard co-ordinating centre activities, such as randomization, protocol implementation and amending, document tracking, adverse event reporting, site monitoring, report generation and data analysis are all fundamentally changed in a web-based trial. Opportunities are enhanced to identify potential investigators and support their successful study conduct. As the role of investigator sites is changed in web-based research, more primary care medical providers can be attracted to research, providing more typical patients to studies than those sometimes available through more traditional research sites, especially those at academic study sites. Other activities can now be co-ordinated electronically with the advent of the web. The Institutional Review Board (IRB) can use online tools to control investigator participation, resulting in improved study efficiency and patient safety. A web-based research pharmacy provides tremendous efficiencies in managing and distributing study medications. Financial payments to the sites can be performed and recorded electronically, or even administered based on

  7. Design and conduct of a large obstetric or neonatal randomized controlled trial.

    PubMed

    Tarnow-Mordi, William; Cruz, Melinda; Morris, Jonathan

    2015-12-01

    As event rates fall, if mortality and disability are to improve further there is increasing need for large, well-designed trials. These should enroll more patients, more rapidly and at lower cost, with better representation of infants at highest risk and greater integration with routine care. This may require simpler datasets, linkage with routinely collected data, and international collaboration. It may be helpful to draw attention to recent evidence that participation in Phase III randomized controlled trials (RCTs) is at least as safe as receiving established care. Nationally coordinated clinical research networks employing local research staff may be the single most effective strategy to integrate clinical trials into routine practice. Other goals are: international standardization of outcomes; consensus on composite endpoints, biomarkers, surrogates and measures of disability; greater efficiency through randomized factorial designs and cluster or cross-over cluster RCTs; and equipping parents as partners in all aspects of the conduct of RCTs and in implementing their results. PMID:26522427

  8. Removing barriers to participation in clinical trials, a conceptual framework and retrospective chart review study

    PubMed Central

    2012-01-01

    Background Enrollment in interventional therapeutic clinical trials is a small fraction of all patients who might participate given reasonable access. Methods A hierarchical approach is utilized in measuring staged participation from trial availability to patient enrollment. Our framework suggests that concern for justice comes in the design and eligibility criteria for clinical trials; attention to beneficence is given in the eligibility and physician triage stages. The remaining four stages rely on respect for persons. An example is given where reasons for nonparticipation or barriers to participation in prostate cancer clinical trials are examined within the framework. In addition, medical oncology patients with an initial six month consultation are tracked from one stage to the next by race using the framework to assess participation comparability. Results We illustrated seven transitions from being a patient to enrollment in a clinical trial in a small study of prostate cancer cases who consulted SKCCC Medical Oncology Department in early 2010. Pilot data suggest transition probabilities as follows: 65% availability, 84% eligibility, 92% patient triage, 89% trials discussed, 45% patient interested, 63% patient consented, and 92% patient enrolled. The average transition probability was 77.7%. The average transition probability, patient-trial-fit was 50%; opportunity was 51%, and acceptance was 66.7%. Trial availability, patient interest and patient consented were three transitions that were below the average; none were statistically significant. Conclusions The framework may serve to streamline comprehensive reporting of clinical trial participation to the benefit of patients and the ethical conduct of clinical trials. PMID:23227880

  9. Novel Methods and Technologies for 21st-Century Clinical Trials

    PubMed Central

    Dorsey, E. Ray; Venuto, Charles; Venkataraman, Vinayak; Harris, Denzil A.; Kieburtz, Karl

    2015-01-01

    IMPORTANCE New technologies are rapidly reshaping health care. However, their effect on drug development to date generally has been limited. OBJECTIVES To evaluate disease modeling and simulation, alternative study design, novel objective measures, virtual research visits, and enhanced participant engagement and to examine their potential effects as methods and tools on clinical trials. EVIDENCE REVIEW We conducted a systematic search of relevant terms on PubMed (disease modeling and clinical trials; adaptive design, clinical trials, and neurology; Internet, clinical trials, and neurology; and telemedicine, clinical trials, and neurology), references of previous publications, and our files. The search encompassed articles published from January 1, 2000, through November 30, 2014, and produced 7976 articles, of which 22 were determined to be relevant and are included in this review. FINDINGS Few of these new methods and technologies have been applied to neurology clinical trials. Clinical outcomes, including cognitive and stroke outcomes, increasingly are captured remotely. Other therapeutic areas have successfully implemented many of these tools and technologies, including web-enabled clinical trials. CONCLUSIONS AND RELEVANCE Increased use of new tools and approaches in future clinical trials can enhance the design, improve the assessment, and engage participants in the evaluation of novel therapies for neurologic disorders. PMID:25730665

  10. A TRIAL OF PROFICIENCY OF NERVE CONDUCTION: GREATER STANDARDIZATION STILL NEEDED

    PubMed Central

    Dyck, Peter J.; Albers, James W.; Wolfe, James; Bolton, Charles F.; Walsh, Nancy; Klein, Christopher J.; Zafft, Andrew J.; Russell, James W.; Thomas, Karen; Davies, Jenny L.; Carter, Rickey E.; Melton, L. Joseph; Litchy, William J.

    2014-01-01

    Introduction The aim of this study was to test the proficiency (accuracy among evaluators) of measured attributes of nerve conduction (NC). Methods Expert clinical neurophysiologists, without instruction or consensus development, from 4 different medical centers, independently assessed 8 attributes of NC in 24 patients with diabetes mellitus (DM) on consecutive days. Results No significant intraobserver differences between days 1 and 2 were found, but significant interobserver differences were seen. Use of standard reference values did not correct for these observed differences. Conclusions Interobserver variability was attributed to differences in performance of NC. It was of sufficient magnitude that it is of concern for the conduct of therapeutic trials. To deal with interrater variability in therapeutic trials, the same electromyographers should perform all NC assessments of individual patients or, preferably, NC procedures should be more standardized. A further trial is needed to test whether such standardization would eliminate interobserver variability. PMID:23861198

  11. Reference Intervals in Healthy Adult Ugandan Blood Donors and Their Impact on Conducting International Vaccine Trials

    PubMed Central

    Eller, Leigh Anne; Eller, Michael A.; Ouma, Benson; Kataaha, Peter; Kyabaggu, Denis; Tumusiime, Richard; Wandege, Joseph; Sanya, Ronald; Sateren, Warren B.; Wabwire-Mangen, Fred; Kibuuka, Hannah; Robb, Merlin L.; Michael, Nelson L.; de Souza, Mark S.

    2008-01-01

    Background Clinical trials are increasingly being conducted internationally. In order to ensure enrollment of healthy participants and proper safety evaluation of vaccine candidates, established reference intervals for clinical tests are required in the target population. Methodology/Principal Findings We report a reference range study conducted in Ugandan adult blood bank donors establishing reference intervals for hematology and clinical chemistry parameters. Several differences were observed when compared to previously established values from the United States, most notably in neutrophils and eosinophils. Conclusions/Significance In a recently conducted vaccine trial in Uganda, 31 percent (n = 69) of volunteers screened (n = 223) were excluded due to hematologic abnormalities. If local reference ranges had been employed, 83% of those screened out due to these abnormalities could have been included in the study, drastically reducing workload and cost associated with the screening process. In addition, toxicity tables used in vaccine and drug trial safety evaluations may need adjustment as some clinical reference ranges determined in this study overlap with grade 1 and grade 2 adverse events. PMID:19079547

  12. Health Providers’ Perceptions of Clinical Trials: Lessons from Ghana, Kenya and Burkina Faso

    PubMed Central

    Angwenyi, Vibian; Asante, Kwaku-Poku; Traoré, Abdoulaye; Febir, Lawrence Gyabaa; Tawiah, Charlotte; Kwarteng, Anthony; Ouédraogo, Alphonse; Sirima, Sodiomon Bienvenue; Owusu-Agyei, Seth; Imoukhuede, Egeruan Babatunde; Webster, Jayne; Chandramohan, Daniel; Molyneux, Sassy; Jones, Caroline

    2015-01-01

    Background Clinical trials conducted in Africa often require substantial investments to support trial centres and public health facilities. Trial resources could potentially generate benefits for routine health service delivery but may have unintended consequences. Strengthening ethical practice requires understanding the potential effects of trial inputs on the perceptions and practices of routine health care providers. This study explores the influence of malaria vaccine trials on health service delivery in Ghana, Kenya and Burkina Faso. Methods We conducted: audits of trial inputs in 10 trial facilities and among 144 health workers; individual interviews with frontline providers (n=99) and health managers (n=14); and group discussions with fieldworkers (n=9 discussions). Descriptive summaries were generated from audit data. Qualitative data were analysed using a framework approach. Results Facilities involved in trials benefited from infrastructure and equipment upgrades, support with essential drugs, access to trial vehicles, and placement of additional qualified trial staff. Qualified trial staff in facilities were often seen as role models by their colleagues; assisting with supportive supervision and reducing facility workload. Some facility staff in place before the trial also received formal training and salary top-ups from the trials. However, differential access to support caused dissatisfaction, and some interviewees expressed concerns about what would happen at the end of the trial once financial and supervisory support was removed. Conclusion Clinical trials function as short-term complex health service delivery interventions in the facilities in which they are based. They have the potential to both benefit facilities, staff and communities through providing the supportive environment required for improvements in routine care, but they can also generate dissatisfaction, relationship challenges and demoralisation among staff. Minimising trial related

  13. A data grid for imaging-based clinical trials

    NASA Astrophysics Data System (ADS)

    Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

    2007-03-01

    Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

  14. Analyzing acute procedural pain in clinical trials.

    PubMed

    Lang, Elvira V; Tan, Gabriel; Amihai, Ido; Jensen, Mark P

    2014-07-01

    Because acute procedural pain tends to increase with procedure time, assessments of pain management strategies must take that time relationship into account. Statistical time-course analyses are, however, complex and require large patient numbers to detect differences. The current study evaluated the abilities of various single and simple composite measures such as averaged pain or individual patient pain slopes to detect treatment effects. Secondary analyses were performed with the data from 3 prospective randomized clinical trials that assessed the effect of a self-hypnotic relaxation intervention on procedural pain, measured every 10-15 minutes during vascular/renal interventions, breast biopsies, and tumor embolizations. Single point-in-time and maximal pain comparisons were poor in detecting treatment effects. Linear data sets of individual patient slopes yielded the same qualitative results as the more complex repeated measures analyses, allowing the use of standard statistical approaches (eg, Kruskal-Wallis), and promising analyses of smaller subgroups, which otherwise would be underpowered. With nonlinear data, a simple averaged score was highly sensitive in detecting differences. Use of these 2 workable and relatively simple approaches may be a first step towards facilitating the development of data sets that could enable meta-analyses of data from acute pain trials. PMID:24731852

  15. Clinical trials in India: Where do we stand globally?

    PubMed Central

    Selvarajan, Sandhiya; George, Melvin; Kumar, Suresh S; Dkhar, Steven Aibor

    2013-01-01

    Aims: To evaluate the trend of clinical trials in India over the last 4 years compared to the well-established countries using clinical trial registries since the advent of clinical trial registry of India (CTRI). Materials and Methods: The data of clinical trials registered in India, United States (US), and European Union (EU) were obtained from websites of CTRI, clinicaltrial.gov and EU clinical trial registry, respectively from July 20, 2007 to August 29, 2011 for a period of 4 years. Trials registered in Australia, Canada, China, and Japan were obtained from WHO's international clinical trial registry platform for the same period. We used search words for the common diseases such as diabetes, hypertension, etc., Results: The total number of clinical trials registered during the study period was 67,448 across seven study nations. Clinical trials from India constituted only 2.7% of the total number of trials carried out, compared to US constituting 47% of the total number of trials registered, followed by 18% from EU and 11% from Japan. However, India, China, and Japan have been found to show an increase of 3.7%, 5.1%, and 13.1% increase in the number of trials registered in 2011 compared to 2007. In contrast, US and EU showed a decline of 11.3% and 11.95% respectively in the total number of trials registered in 2011 compared to 2007. Conclusions: Although India shows gradual increase in trials registered since the advent of CTRI, still it continues to lag behind established countries in clinical research. PMID:24010056

  16. Newer Antibacterials in Therapy and Clinical Trials

    PubMed Central

    Paknikar, Simi S; Narayana, Sarala

    2012-01-01

    In order to deal with the rising problem of antibiotic resistance, newer antibacterials are being discovered and added to existing pool. Since the year 2000, however, only four new classes of antibacterials have been discovered. These include the oxazolidinones, glycolipopeptides, glycolipodepepsipeptide and pleuromutilins. Newer drugs were added to existing classes of antibiotics, such as streptogramins, quinolones, beta-lactam antibiotics, and macrolide-, tetracycline- and trimethoprim-related drugs. Most of the antibacterials are directed against resistant S. aureus infections, with very few against resistant gram-negative infections. The following article reviews the antibacterials approved by the FDA after the year 2000 as well as some of those in clinical trials. Data was obtained through a literature search via Pubmed and google as well as a detailed search of our library database. PMID:23181224

  17. Methodology of Clinical Trials Aimed at Assessing Interventions for Cutaneous Leishmaniasis

    PubMed Central

    Olliaro, Piero; Vaillant, Michel; Arana, Byron; Grogl, Max; Modabber, Farrokh; Magill, Alan; Lapujade, Olivier; Buffet, Pierre; Alvar, Jorge

    2013-01-01

    The current evidence-base for recommendations on the treatment of cutaneous leishmaniasis (CL) is generally weak. Systematic reviews have pointed to a general lack of standardization of methods for the conduct and analysis of clinical trials of CL, compounded with poor overall quality of several trials. For CL, there is a specific need for methodologies which can be applied generally, while allowing the flexibility needed to cover the diverse forms of the disease. This paper intends to provide clinical investigators with guidance for the design, conduct, analysis and report of clinical trials of treatments for CL, including the definition of measurable, reproducible and clinically-meaningful outcomes. Having unified criteria will help strengthen evidence, optimize investments, and enhance the capacity for high-quality trials. The limited resources available for CL have to be concentrated in clinical studies of excellence that meet international quality standards. PMID:23556016

  18. Using Clinical Trial Simulators to Analyse the Sources of Variance in Clinical Trials of Novel Therapies for Acute Viral Infections

    PubMed Central

    Weverling, Gerrit-Jan; de Wolf, Frank; Anderson, Roy M.

    2016-01-01

    Background About 90% of drugs fail in clinical development. The question is whether trials fail because of insufficient efficacy of the new treatment, or rather because of poor trial design that is unable to detect the true efficacy. The variance of the measured endpoints is a major, largely underestimated source of uncertainty in clinical trial design, particularly in acute viral infections. We use a clinical trial simulator to demonstrate how a thorough consideration of the variability inherent in clinical trials of novel therapies for acute viral infections can improve trial design. Methods and Findings We developed a clinical trial simulator to analyse the impact of three different types of variation on the outcome of a challenge study of influenza treatments for infected patients, including individual patient variability in the response to the drug, the variance of the measurement procedure, and the variance of the lower limit of quantification of endpoint measurements. In addition, we investigated the impact of protocol variation on clinical trial outcome. We found that the greatest source of variance was inter-individual variability in the natural course of infection. Running a larger phase II study can save up to $38 million, if an unlikely to succeed phase III trial is avoided. In addition, low-sensitivity viral load assays can lead to falsely negative trial outcomes. Conclusions Due to high inter-individual variability in natural infection, the most important variable in clinical trial design for challenge studies of potential novel influenza treatments is the number of participants. 100 participants are preferable over 50. Using more sensitive viral load assays increases the probability of a positive trial outcome, but may in some circumstances lead to false positive outcomes. Clinical trial simulations are powerful tools to identify the most important sources of variance in clinical trials and thereby help improve trial design. PMID:27332704

  19. The Use of Electronic Data Capture Tools in Clinical Trials: Web-Survey of 259 Canadian Trials

    PubMed Central

    Jonker, Elizabeth; Sampson, Margaret; Krleža-Jerić, Karmela; Neisa, Angelica

    2009-01-01

    Background Electronic data capture (EDC) tools provide automated support for data collection, reporting, query resolution, randomization, and validation, among other features, for clinical trials. There is a trend toward greater adoption of EDC tools in clinical trials, but there is also uncertainty about how many trials are actually using this technology in practice. A systematic review of EDC adoption surveys conducted up to 2007 concluded that only 20% of trials are using EDC systems, but previous surveys had weaknesses. Objectives Our primary objective was to estimate the proportion of phase II/III/IV Canadian clinical trials that used an EDC system in 2006 and 2007. The secondary objectives were to investigate the factors that can have an impact on adoption and to develop a scale to assess the extent of sophistication of EDC systems. Methods We conducted a Web survey to estimate the proportion of trials that were using an EDC system. The survey was sent to the Canadian site coordinators for 331 trials. We also developed and validated a scale using Guttman scaling to assess the extent of sophistication of EDC systems. Trials using EDC were compared by the level of sophistication of their systems. Results We had a 78.2% response rate (259/331) for the survey. It is estimated that 41% (95% CI 37.5%-44%) of clinical trials were using an EDC system. Trials funded by academic institutions, government, and foundations were less likely to use an EDC system compared to those sponsored by industry. Also, larger trials tended to be more likely to adopt EDC. The EDC sophistication scale had six levels and a coefficient of reproducibility of 0.901 (P< .001) and a coefficient of scalability of 0.79. There was no difference in sophistication based on the funding source, but pediatric trials were likely to use a more sophisticated EDC system. Conclusion The adoption of EDC systems in clinical trials in Canada is higher than the literature indicated: a large proportion of

  20. Institutional mistrust in the organization of pharmaceutical clinical trials

    PubMed Central

    2010-01-01

    In this paper I explore the politics of trust in the clinical testing of pharmaceuticals in the US. Specifically, I analyze trust in terms of its institutional manifestations in the pharmaceutical clinical trials industry. In the process of testing new drugs, pharmaceutical companies must (1) protect their proprietary information from the clinicians who conduct their studies, and (2) find a way to ensure human subjects' compliance to study protocols. Concern with these two critical issues leads drug companies to approach clinicians and research subjects with an attitude of mistrust and the desire to exert control over their activities. This orientation results in an institutionalization of mistrust that structures the relationships and activities required for the clinical development of new pharmaceutical products. PMID:18633728

  1. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy.

    PubMed

    Tunis, Sean R; Stryer, Daniel B; Clancy, Carolyn M

    2003-09-24

    Decision makers in health care are increasingly interested in using high-quality scientific evidence to support clinical and health policy choices; however, the quality of available scientific evidence is often found to be inadequate. Reliable evidence is essential to improve health care quality and to support efficient use of limited resources. The widespread gaps in evidence-based knowledge suggest that systematic flaws exist in the production of scientific evidence, in part because there is no consistent effort to conduct clinical trials designed to meet the needs of decision makers. Clinical trials for which the hypothesis and study design are developed specifically to answer the questions faced by decision makers are called pragmatic or practical clinical trials (PCTs). The characteristic features of PCTs are that they (1) select clinically relevant alternative interventions to compare, (2) include a diverse population of study participants, (3) recruit participants from heterogeneous practice settings, and (4) collect data on a broad range of health outcomes. The supply of PCTs is limited primarily because the major funders of clinical research, the National Institutes of Health and the medical products industry, do not focus on supporting such trials. Increasing the supply of PCTs will depend on the development of a mechanism to establish priorities for these studies, significant expansion of an infrastructure to conduct clinical research within the health care delivery system, more reliance on high-quality evidence by health care decision makers, and a substantial increase in public and private funding for these studies. For these changes to occur, clinical and health policy decision makers will need to become more involved in all aspects of clinical research, including priority setting, infrastructure development, and funding. PMID:14506122

  2. Recruitment and Retention of Patients into Emergency Medicine Clinical Trials

    PubMed Central

    Cofield, Stacey; Conwit, Robin; Barsan, William; Quinn, James

    2010-01-01

    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

  3. Ethical responsibilities toward indirect and collateral participants in pragmatic clinical trials.

    PubMed

    Smalley, Jaye Bea; Merritt, Maria W; Al-Khatib, Sana M; McCall, Debbe; Staman, Karen L; Stepnowsky, Carl

    2015-10-01

    Pragmatic clinical trials are designed to inform decision makers about the benefits, burdens, and risks of health interventions in real-world settings. Pragmatic clinical trials often use for research purposes data collected in the course of clinical practice. The distinctive features of pragmatic clinical trials demand fresh thinking about what is required to act properly toward people affected by their conduct, in ways that go beyond ensuring the protection of rights and welfare for "human research subjects" under conventional research ethics regulations. To stimulate such work, we propose to distinguish among categories of research participants in pragmatic clinical trials as follows: Direct participants: (1) individuals being directly intervened upon and/or (2) individuals from whom personal identifiable data are being collected for the purposes of the pragmatic clinical trial. Indirect participants: individuals who are (1) not identified as direct participants and (2) whose rights and welfare may be affected by the intervention through their routine exposure to the environment in which the intervention is being deployed. Collateral participants: patient groups and other stakeholder communities who may be otherwise affected by the occurrence and findings of the pragmatic clinical trial. We illustrate these distinctions with case examples and discuss the distinctive responsibilities of researchers and pragmatic clinical trial leadership toward each type of participant. We suggest that pragmatic clinical trial investigators, institutional review boards, health systems leaders, and others engaged in the research enterprise work together to identify these participants. For indirect participants, risks and benefits to which they are exposed should be weighed to ensure that their rights and welfare are protected accordingly, and communication strategies should be considered to help them make well-informed decisions. Collateral participants could provide input on the

  4. [Global views on clinical trials and data quality].

    PubMed

    Liu, Daniel; Han, Xiu-lan; Sun, Hua-long; Dai, Nan

    2015-11-01

    The quality and integrity of clinical trials and associated data are not only derived from accuracy of trial data analyses, but also closely embodied to the authenticity and integrity of those data and data documents as well as the compliant procedures obtaining those data and relevant files in the life cycle of clinical trials. The compliances of good clinical practices and standards suggest the reliability, complete and accuracy of data and data documents, which is constructing the convincible foundation of drug efficacy and safety validated via clinical trials. Therefore, the monitoring and auditing on clinical trials and associated data quality keep eyes on not only verifications of reliability and correctness on the data analytic outcomes, but also validation of science and compliance of the trial management procedure and documentations in the process of data collections. PMID:26911039

  5. Issues in Designing and Implementing a Spanish-Language Multi-Site Clinical Trial

    PubMed Central

    Suarez-Morales, Lourdes; Matthews, Julie; Martino, Steve; Ball, Samuel A.; Rosa, Carmen; Farentinos, Christine; Szapocznik, José; Carroll, Kathleen M.

    2013-01-01

    To address at least in part health disparities in Hispanic populations, the NIDA Clinical Trials Network implemented the first multi-site randomized clinical trial of substance abuse treatment conducted entirely in Spanish. This trial was intended to evaluate the effectiveness of Motivational Enhancement Therapy in a diverse population of Hispanics. In the conduct of this trial, several barriers to the successful implementation of a Spanish-language multi-site trial had to be addressed, including the appropriate translation of assessment instruments, shortage of appropriately trained Spanish-speaking clinical staff, and barriers to recruitment and retention of this population. To encourage similar research, strategies are described that were developed by the study team to meet these challenges. PMID:17612825

  6. Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

    PubMed

    Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

    2016-02-01

    This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings. PMID:26683233

  7. 77 FR 49449 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... announcing a public workshop. The public workshop on FDA's clinical trial requirements is designed to aid the... FDA and clinical trial staff, investigators, and institutional review boards (IRBs). Individual...

  8. Trial design innovations: Clinical trials for treatment of neuropsychiatric symptoms in Alzheimer's Disease.

    PubMed

    Cummings, J; Zhong, K

    2015-11-01

    Neuropsychiatric symptoms are common in Alzheimer's disease (AD) and other neurodegenerative disorders. Recent progress has been made with clinical trials, advancing new therapies for psychosis in Parkinson's disease (PD), agitation in AD, and apathy in AD. Definitions have emerged for agitation and apathy in patients with cognitive impairment, facilitating recruitment of clinical trial populations. Progress in clinical trial design and the agents being assessed promise to advance therapies for disabling symptoms and improve quality of life for patients and caregivers. PMID:26206713

  9. Privacy and confidentiality in pragmatic clinical trials

    PubMed Central

    McGraw, Deven; Greene, Sarah M.; Miner, Caroline S.; Staman, Karen L.; Welch, Mary Jane; Rubel, Alan

    2015-01-01

    With pragmatic clinical trials (PCTs) 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 PCTs. In this paper we explore both the ethical foundation and regulatory framework intended to protect privacy in PCTs. We then review examples of novel approaches to respecting persons in research that may have the added benefit of honoring patient privacy considerations. PMID:26374682

  10. Design of clinical trials in sepsis: problems and pitfalls.

    PubMed

    Finch, R G

    1998-01-01

    The pathophysiology of sepsis has been studied intensively in recent years and a variety of opportunities for therapeutic intervention have been identified. A number of biological products including endotoxin antibodies, cytokine inhibitors and receptor antagonists have been evaluated after the failure of pharmacological doses of steroids to influence survival in septic shock. Despite a number of large, international multi-centre studies, the therapeutic promise of these various interventions remains unfulfilled. These trials have largely been conducted in intensive care units in a heterogeneous population of patients with various entry criteria and end-points of response. While the clinical trial must remain the standard for assessing safety and efficacy of new interventions there are opportunities to improve on the design, execution and analysis of these studies. Factors such as the appropriateness of antibiotic therapy, the adequacy of medical and surgical management, and the issue of withdrawal or withholding of life support are discussed in relation to these studies. Furthermore the role of an independent scientific extramural review committee is stressed, particularly in relation to the impact of confounding events of an unforeseen nature. The potential for improving the quality of the analyses of clinical trials of sepsis is illustrated by a recently completed study of the efficacy of a murine monoclonal antibody to human tumour necrosis factor-alpha. PMID:9511091

  11. Issues and Challenges With Integrating Patient-Reported Outcomes in Clinical Trials Supported by the National Cancer Institute–Sponsored Clinical Trials Networks

    PubMed Central

    Bruner, Deborah Watkins; Bryan, Charlene J.; Aaronson, Neil; Blackmore, C. Craig; Brundage, Michael; Cella, David; Ganz, Patricia A.; Gotay, Carolyn; Hinds, Pamela S.; Kornblith, Alice B.; Movsas, Benjamin; Sloan, Jeff; Wenzel, Lari; Whalen, Giles

    2016-01-01

    Purpose The objective of this report is to provide a historical overview of and the issues and challenges inherent in the incorporation of patient-reported outcomes (PROs) into multinational cancer clinical trials in the cancer cooperative groups. Methods An online survey of 12 cancer cooperative groups from the United States, Canada, and Europe was conducted between June and August of 2006. Each of the cooperative groups designated one respondent, who was a member of one of the PRO committees within the cooperative group. Results There was a 100% response rate, and all of the cancer clinical trial cooperative groups reported conducting PRO research. PRO research has been conducted in the cancer cooperative groups for an average of 15 years (range, 6 to 30 years), and all groups had multidisciplinary committees focused on the design of PRO end points and the choice of appropriate PRO measures for cancer clinical trials. The cooperative groups reported that 5% to 50% of cancer treatment trials and an estimated 50% to 75% of cancer control trials contained PRO primary and secondary end points. There was considerable heterogeneity among the cooperative groups with respect to the formal and informal policies and procedures or cooperative group culture towards PROs, investigator training/mentorship, and resource availability for the measurement and conduct of PRO research within the individual cooperatives. Conclusion The challenges faced by the cooperative groups to the incorporation of PROs into cancer clinical trials are varied. Some common opportunities for improvement include the adoption of standardized training/mentorship mechanisms for investigators for the conduct of PRO assessments and data collection and the development of minimal criteria for PRO measure acceptability. A positive cultural shift has occurred in most of the cooperative groups related to the incorporation of PROs in clinical trials; however, financial and other resource barriers remain and need

  12. Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

    PubMed Central

    Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

    2013-01-01

    Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0

  13. Clinical trials face heightened scrutiny as science and commerce appear to merge.

    PubMed

    Lorman, Alvin J

    2001-01-01

    Clinical trials involving human subjects face increased scrutiny and regulation by the federal government that may lead to costly changes to the process. Prompted by a highly publicized death in a gene therapy trial, federal regulators are examining almost all aspects of clinical trial conduct, from how patients are recruited and how they give informed consent, to the relationship between the researchers and the company sponsoring the research. In addition to the heightened regulation, the government has announced that it will seek the power to impose civil money penalties on researchers who do not observe applicable patient protection regulations. In an effort to include more senior citizens in clinical trials, the government for the first time will cover certain costs of Medicare beneficiaries who participate in clinical trials. The risk of increased government involvement includes criminal prosecution of physicians for failing to follow the rules, as an innovative case in California demonstrates. PMID:12751494

  14. Acceptability of a Mobile Health Unit for Rural HIV Clinical Trial Enrollment and Participation

    PubMed Central

    Miles, Margaret Shandor; Banks, Bahby; Corbie-Smith, Giselle

    2013-01-01

    Few rural minorities participate in HIV clinical trials. Mobile health units (MHUs) may be one strategy to increase participation. We explored community perceptions of MHU acceptability to increase clinical trial participation for rural minorities living with HIV/AIDS. We conducted 11 focus groups (service providers and community leaders) and 35 interviews (people living with HIV/AIDS). Responses were analyzed using constant comparative and content analysis techniques. Acceptable MHU use included maintaining accessibility and confidentiality while establishing credibility, community ownership and control. Under these conditions, MHUs can service rural locations and overcome geographic barriers to reaching major medical centers for clinical trials. PMID:22350829

  15. A mixture gatekeeping procedure based on the Hommel test for clinical trial applications.

    PubMed

    Brechenmacher, Thomas; Xu, Jane; Dmitrienko, Alex; Tamhane, Ajit C

    2011-07-01

    When conducting clinical trials with hierarchically ordered objectives, it is essential to use multiplicity adjustment methods that control the familywise error rate in the strong sense while taking into account the logical relations among the null hypotheses. This paper proposes a gatekeeping procedure based on the Hommel (1988) test, which offers power advantages compared to other p value-based tests proposed in the literature. A general description of the procedure is given and details are presented on how it can be applied to complex clinical trial designs. Two clinical trial examples are given to illustrate the methodology developed in the paper. PMID:21516567

  16. Estimation of drug cost avoidance and pathology cost avoidance through participation in NCIC Clinical Trials Group phase III clinical trials in Canada

    PubMed Central

    Tang, P.A.; Hay, A.E.; O’Callaghan, C.J.; Mittmann, N.; Chambers, C.R.; Pater, J.L.; Leighl, N.B.

    2016-01-01

    Background Cost avoidance occurs when, because of provision of a drug therapy [drug cost avoidance (dca)] or a pathology test [pathology cost avoidance (pca)] during trial participation, health care payers need not pay for standard treatments or testing. The aim of our study was to estimate the total dca and pca for Canadian patients enrolled in relevant phase iii trials conducted by the ncic Clinical Trials Group. Methods Phase iii trials that had completed accrual and resulted in dca or pca were identified. The pca was calculated based on the number of patients screened and the test cost. The dca was estimated based on patients randomized, the protocol dosing regimen, drug cost, median dose intensity, and median duration of therapy. Costs are presented in Canadian dollars. No adjustment was made for inflation. Results From 1999 to 2011, 4 trials (1479 patients) resulted in pca and 17 trials (3195 patients) resulted in dca. The total pca was estimated at $4,194,849, which included testing for KRAS ($141,058), microsatellite instability ($18,600), and 21-gene recurrence score ($4,035,191). The total dca was estimated at $27,952,512, of which targeted therapy constituted 43% (five trials). The combined pca and dca was $32,147,361. Conclusions Over the study period, trials conducted by the ncic Clinical Trials Group resulted in total cost avoidance (pca and dca) of approximately $7,518 per patient. Although not all trials lead to cost avoidance, such savings should be taken account when the financial impact of conducting clinical research is being considered. PMID:26985151

  17. Rufinamide from clinical trials to clinical practice in the United States and Europe.

    PubMed

    Resnick, Trevor; Arzimanoglou, Alexis; Brown, Lawrence W; Flamini, Robert; Kerr, Michael; Kluger, Gerhard; Kothare, Sanjeev; Philip, Sunny; Harrison, Miranda; Narurkar, Milind

    2011-05-01

    Rufinamide is a triazole derivative structurally unrelated to other antiepileptic drugs that is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥4 years. Originally granted orphan drug status, marketing authorisation was obtained on the basis of a randomised, double-blind, placebo-controlled trial conducted in 138 LGS patients. An open-label extension study subsequently demonstrated that rufinamide's efficacy and tolerability were maintained over the longer term (median duration of treatment, 432 days). Recently published reports from Europe and the United States have described the use of adjunctive rufinamide to treat LGS in clinical practice. These data complement the clinical trial results, by providing information on the efficacy and tolerability of rufinamide when used on an individualised basis in real-world practice, under less tightly restricted conditions in terms of patient population and dosing strategies. A comparison of the data reveals that a "lower and slower" dosing strategy tends to be adopted in clinical practice, in comparison with the clinical trial, which does not appear to compromise efficacy, but may provide improvements in tolerability. Individual case reports provide additional valuable information on how rufinamide is being used to treat different seizure types associated with LGS. Since clinical experience with rufinamide is currently at an early stage, there are still unanswered questions relating to its use, and it is likely that its place in the adjunctive treatment of LGS will evolve as further data emerge. PMID:21669560

  18. End points in dermatologic clinical trials: A review for clinicians.

    PubMed

    Wei, Erin X; Kirsner, Robert S; Eaglstein, William H

    2016-07-01

    Clinical trials are critical for the development of new therapies in dermatology, and their results help determine US Food and Drug Administration (FDA) approval and guide care. Of special relevance is the clinical trial efficacy end point, the metric from which statistically significant outcome is derived. Clinicians' understanding of a clinical trial's end point is necessary for critical analysis of the trial results and for applying those results to daily practice. This review provides practical knowledge and critical evaluation of end points used in treatment approvals by the FDA. The end points for actinic keratosis, acne vulgaris, atopic dermatitis, onychomycosis, and cutaneous ulcer serve as examples. PMID:26936300

  19. Implementation of the NCI’s National Clinical Trials Network

    Cancer.gov

    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

  20. Future vision for the quality assurance of oncology clinical trials.

    PubMed

    Fitzgerald, Thomas J; Bishop-Jodoin, Maryann; Bosch, Walter R; Curran, Walter J; Followill, David S; Galvin, James M; Hanusik, Richard; King, Steven R; Knopp, Michael V; Laurie, Fran; O'Meara, Elizabeth; Michalski, Jeff M; Saltz, Joel H; Schnall, Mitchell D; Schwartz, Lawrence; Ulin, Kenneth; Xiao, Ying; Urie, Marcia

    2013-01-01

    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. PMID:23508883

  1. Activities of Tannins--From In Vitro Studies to Clinical Trials.

    PubMed

    Sieniawska, Elwira

    2015-11-01

    Tannins are considered as valuable plant secondary metabolites providing many benefits for human health. In this review information was gathered about bioactivity in vitro and in vivo, as well as about conducted clinical trials. The literature research was based on ScienceDirect, Scopus, and Cochrane databases and presents a wide range of tested activities of tannins. The described clinical trials verify laboratory tests and show the effective health benefits taken from supplementation with tannins. PMID:26749816

  2. Clinical trials in "emerging markets": regulatory considerations and other factors.

    PubMed

    Singh, Romi; Wang, Ouhong

    2013-11-01

    Clinical studies are being placed in emerging markets as part of global drug development programs to access large pool of eligible patients and to benefit from a cost effective structure. However, over the last few years, the definition of "emerging markets" is being revisited, especially from a regulatory perspective. For purposes of this article, countries outside US, EU and the traditional "western countries" are discussed. Multiple factors are considered for placement of clinical studies such as adherence to Good Clinical Practice (GCP), medical infrastructure & standard of care, number of eligible patients, etc. This article also discusses other quantitative factors such as country's GDP, patent applications, healthcare expenditure, healthcare infrastructure, corruption, innovation, etc. These different factors and indexes are correlated to the number of clinical studies ongoing in the "emerging markets". R&D, healthcare expenditure, technology infrastructure, transparency, and level of innovation, show a significant correlation with the number of clinical trials being conducted in these countries. This is the first analysis of its kind to evaluate and correlate the various other factors to the number of clinical studies in a country. PMID:24070788

  3. Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

    MedlinePlus

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

  4. Application of critical path analysis in clinical trials

    PubMed Central

    Kumar, Amal; Chakraborty, Bhaswat S.

    2016-01-01

    Clinical research operates in a strictly regulated environment under various management models, but a distinct management model of clinical trial (CT) still needs exploration and research. Critical path analysis (CPA) is a management approach can be used for monitoring, analysis, and prediction of success of its time-bound operational activities. A model CT was compiled with 78 activities, which were further merged into 35 major activities. After performing dependence analysis, the list was finalized with 25 activities which were taken in activity predecessor to create a network diagram and perform CPA considering patients, conduct, and outcome. Activities were inclusive, described the trial entirely with accuracy, and were in chronological and logical sequences. This approach does not replace an understanding of or adherence to the requirements contained in all applicable regulations, guidelines or standard operating procedures governing clinical studies but ensures the proper use of operational and decisional approaches including optimal resource management. As the need to meet deadlines becomes more important and the need to produce good, stable project plans, CPA is very useful for determining activities that can lead to project delay. With this approach, project may be effectively monitored, and realistic schedules can be maintained. PMID:26955606

  5. Application of critical path analysis in clinical trials.

    PubMed

    Kumar, Amal; Chakraborty, Bhaswat S

    2016-01-01

    Clinical research operates in a strictly regulated environment under various management models, but a distinct management model of clinical trial (CT) still needs exploration and research. Critical path analysis (CPA) is a management approach can be used for monitoring, analysis, and prediction of success of its time-bound operational activities. A model CT was compiled with 78 activities, which were further merged into 35 major activities. After performing dependence analysis, the list was finalized with 25 activities which were taken in activity predecessor to create a network diagram and perform CPA considering patients, conduct, and outcome. Activities were inclusive, described the trial entirely with accuracy, and were in chronological and logical sequences. This approach does not replace an understanding of or adherence to the requirements contained in all applicable regulations, guidelines or standard operating procedures governing clinical studies but ensures the proper use of operational and decisional approaches including optimal resource management. As the need to meet deadlines becomes more important and the need to produce good, stable project plans, CPA is very useful for determining activities that can lead to project delay. With this approach, project may be effectively monitored, and realistic schedules can be maintained. PMID:26955606

  6. Placebos used in clinical trials for Chinese herbal medicine.

    PubMed

    Qi, Guan D; We, Ding A; Chung, Leung P; Fai, Cheng K

    2008-06-01

    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. PMID:19076001

  7. Representation of older patients in clinical trials for drug approval in Japan.

    PubMed

    Asahina, Y; Sugano, H; Sugiyama, E; Uyama, Y

    2014-05-01

    To examine how target patients seen in clinical practice are represented in clinical trials for approved drugs in Japan, we compared the age distribution of older patients enrolled in confirmatory clinical trials for regulatory approval with that of the estimated actual patient population. Drugs for 6 chronic conditions common among older patients (diabetes mellitus, hypertension, rheumatoid arthritis, non-small cell lung cancer, depression and Alzheimer's disease) launched by 2012 in Japan were selected. The disparity in age distribution between patients in trials and patients seen in clinical practice varied depending on the disease, but older patients, especially those aged 75 or older, were generally underrepresented in clinical trials for regulatory approval in Japan. Under-representation of older patients in hypertension trials was particularly marked compared to other conditions, despite the similarity in age distribution of patients seen in clinical practice. One factor causing this disparity may be an upper age limit in clinical trial protocols. More effort is needed to properly characterize the benefits and risks of drugs for older patients. This should include the active enrollment of older patients in clinical trials, the establishment of better assessment tools such as pharmacometric approaches, and the appropriate planning and conducting of post-marketing surveys and studies. PMID:24886739

  8. [Clinical trials registers. Introduction to the topic and backgrounds].

    PubMed

    Antes, G; Dreier, G; Hasselblatt, H; Blümle, A; Schumacher, M

    2009-04-01

    It is a moral responsibility of those performing clinical studies towards patients, funding organizations, the scientific community and towards the general public to publish the results of clinical trials. Under-reporting of clinical trials with null or even negative results as well as over-reporting of trials with positive results can lead to a biased assessment of (new) treatments, which leads to overestimation of potential benefits and underestimation of potential risks. Comprehensive, publicly accessible clinical trial registries are now widely accepted as an essential tool to fill the information gap. Here, the background for implementing a clinical trials register in Germany is described, whereby publication bias, in particular, is addressed. PMID:19343283

  9. The duty to disclose adverse clinical trial results.

    PubMed

    Liao, S Matthew; Sheehan, Mark; Clarke, Steve

    2009-08-01

    Participants in some clinical trials are at risk of being harmed and sometimes are seriously harmed as a result of not being provided with available, relevant risk information. We argue that this situation is unacceptable and that there is a moral duty to disclose all adverse clinical trial results to participants in clinical trials. This duty is grounded in the human right not to be placed at risk of harm without informed consent. We consider objections to disclosure grounded in considerations of commercial interest, and we argue that these concerns are insufficient to override the moral duty to disclose adverse clinical trial results. However, we also develop a proposal that enables commercial interests to be protected, while promoting the duty to disclose adverse clinical trial results. PMID:19998154

  10. Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial

    PubMed Central

    Rodon, J.; Soria, J. C.; Berger, R.; Batist, G.; Tsimberidou, A.; Bresson, C.; Lee, J. J.; Rubin, E.; Onn, A.; Schilsky, R. L.; Miller, W. H.; Eggermont, A. M.; Mendelsohn, J.; Lazar, V.; Kurzrock, R.

    2015-01-01

    Advances in ‘omics’ technology and targeted therapeutic molecules are together driving the incorporation of molecular-based diagnostics into the care of patients with cancer. There is an urgent need to assess the efficacy of therapy determined by molecular matching of patients with particular targeted therapies. WINTHER is a clinical trial that uses cutting edge genomic and transcriptomic assays to guide treatment decisions. Through the lens of this ambitious multinational trial (five countries, six sites) coordinated by the Worldwide Innovative Networking Consortium for personalized cancer therapy, we discovered key challenges in initiation and conduct of a prospective, omically driven study. To date, the time from study concept to activation has varied between 19 months at Gustave Roussy Cancer Campus in France to 30 months at the Segal Cancer Center, McGill University (Canada). It took 3+ years to be able to activate US sites due to national regulatory hurdles. Access to medications proposed by the molecular analysis remains a major challenge, since their availability through active clinical trials is highly variable over time within sites and across the network. Rules regarding the off-label use of drugs, or drugs not yet approved at all in some countries, pose a further challenge, and many biopharmaceutical companies lack a simple internal mechanism to supply the drugs even if they wish to do so. These various obstacles should be addressed to test and then implement precision medicine in cancer. PMID:25908602

  11. Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial.

    PubMed

    Rodon, J; Soria, J C; Berger, R; Batist, G; Tsimberidou, A; Bresson, C; Lee, J J; Rubin, E; Onn, A; Schilsky, R L; Miller, W H; Eggermont, A M; Mendelsohn, J; Lazar, V; Kurzrock, R

    2015-08-01

    Advances in 'omics' technology and targeted therapeutic molecules are together driving the incorporation of molecular-based diagnostics into the care of patients with cancer. There is an urgent need to assess the efficacy of therapy determined by molecular matching of patients with particular targeted therapies. WINTHER is a clinical trial that uses cutting edge genomic and transcriptomic assays to guide treatment decisions. Through the lens of this ambitious multinational trial (five countries, six sites) coordinated by the Worldwide Innovative Networking Consortium for personalized cancer therapy, we discovered key challenges in initiation and conduct of a prospective, omically driven study. To date, the time from study concept to activation has varied between 19 months at Gustave Roussy Cancer Campus in France to 30 months at the Segal Cancer Center, McGill University (Canada). It took 3+ years to be able to activate US sites due to national regulatory hurdles. Access to medications proposed by the molecular analysis remains a major challenge, since their availability through active clinical trials is highly variable over time within sites and across the network. Rules regarding the off-label use of drugs, or drugs not yet approved at all in some countries, pose a further challenge, and many biopharmaceutical companies lack a simple internal mechanism to supply the drugs even if they wish to do so. These various obstacles should be addressed to test and then implement precision medicine in cancer. PMID:25908602

  12. Integrating pain metrics into oncology clinical trials.

    PubMed

    Cleeland, Charles S; O'Mara, Ann; Zagari, Martin; Baas, Carole

    2011-11-01

    Cancer-related pain is highly prevalent and often severe, and as a result is often one of the defining experiences for patients with malignancy. Patients and patients' families almost always live with the ever-present reality that cancer treatment and progression may be accompanied by pain. For patients nearing the end of life, most fear that their final days will be spent living with the terrible effects of the disease, the most important of which is pain. Despite this, there is far less systematic research on the mechanisms of cancer-related pain or on the development of new agents to reduce or eliminate pain in cancer patients compared with research to combat the disease itself. Further, even when the focus of research is treatment of the tumor, the effects of anticancer treatments on pain are often underreported in publications and other forums. To illustrate the relative drought in the cancer pain control area, there have been no new drugs approved for cancer-related pain in recent years. A number of methodologic and logistical challenges that hinder the ability to assess pain response in clinical trials are discussed in this article. Possible ways to address these challenges are also discussed. PMID:22046026

  13. Improving Alzheimer's disease phase II clinical trials.

    PubMed

    Greenberg, Barry D; Carrillo, Maria C; Ryan, J Michael; Gold, Michael; Gallagher, Kim; Grundman, Michael; Berman, Robert M; Ashwood, Timothy; Siemers, Eric R

    2013-01-01

    Over the past 30 years, many drugs have been studied as possible treatments for Alzheimer's disease, but only four have demonstrated sufficient efficacy to be approved as treatments, of which three are in the same class. This lack of success has raised questions both in the pharmaceutical industry and academia about the future of Alzheimer's disease therapy. The high cost and low success rate of drug development across many disease areas can be attributed, in large part, to late-stage clinical failures (Schachter and Ramoni, Nat Rev Drug Discov 2007;6:107-8). Thus, identifying in phase II, or preferably phase I, drugs that are likely to fail would have a dramatic impact on the costs associated with developing new drugs. With this in mind, the Alzheimer's Association convened a Research Roundtable on June 23 and 24, 2011, in Washington, DC, bringing together scientists from academia, industry, and government regulatory agencies to discuss strategies for improving the probability of phase II trial results predicting success when considering the go/no-go decision-making process leading to the initiation of phase III. PMID:23164548

  14. A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials

    PubMed Central

    Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T.; Wang, Chen; Heflin, Jeff; Chute, Christopher G.

    2015-01-01

    Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials. PMID:26306257

  15. A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials.

    PubMed

    Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G

    2015-01-01

    Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials. PMID:26306257

  16. The Clinical Trials Involvement of Latino and White Physicians

    PubMed Central

    Ramirez, Amelie G.; Wildes, Kimberly; Talavera, Greg; Nápoles-Springer, Anna; Gallion, Kipling; Pérez-Stable, Eliseo J.

    2008-01-01

    Background Ethnic differences in physicians’ attitudes and behaviors related to clinical trials might partially account for disparities in clinical trial participation among Latino patients. Literature regarding Latino physicians’ involvement in clinical trials, in comparison to White physicians, could not be found. Methods Cross-sectional data from randomly selected physicians (N=695), stratified by ethnicity, were analyzed to test associations of ethnicity with physicians’ participation in and attitudes toward referral of patients to clinical trials. Results Chi-square analyses showed significant (p<0.05) associations of physician race/ethnicity and clinical trials involvement, type of trial for which the physician is likely to recommend a patient, belief in scientific value, and factors that would influence recommendation for a patient to participate. Multivariate analyses resulted in several significant (p<0.05) predictors of clinical trials outcomes, including physician race/ethnicity. Conclusions Latino physicians were significantly less involved in clinical trials than White physicians and found less scientific value in them, highlighting areas for future education and intervention. PMID:18155966

  17. How transparent are migraine clinical trials? Repository of Registered Migraine Trials (RReMiT).

    PubMed

    Dufka, Faustine L; Dworkin, Robert H; Rowbotham, Michael C

    2014-10-01

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

  18. 77 FR 49448 - Food and Drug Administration Clinical Trial Requirements, Compliance, and Good Clinical Practice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... HUMAN SERVICES Food and Drug Administration Food and Drug Administration Clinical Trial Requirements... public workshop on FDA's clinical trial requirements is designed to aid the clinical research... interaction with FDA representatives. The program will focus on the relationships among FDA and clinical...

  19. Statistical challenges for central monitoring in clinical trials: a review.

    PubMed

    Oba, Koji

    2016-02-01

    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. PMID:26499195

  20. Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

    PubMed Central

    Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

    2015-01-01

    Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis

  1. New generation of breast cancer clinical trials implementing molecular profiling

    PubMed Central

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2016-01-01

    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. PMID:27458530

  2. Reliability of Japanese clinical trials estimated from GCP audit findings.

    PubMed

    Saito, K; Kodama, Y; Ono, S; Maida, C; Fujimura, A; Miyamoto, E

    2008-08-01

    To describe the reliability of Japanese clinical trials, we compared the results of a Good Clinical Practice (GCP) audit conducted between April 1997 and March 2000 (fiscal year (FY) 1997 - 1999) with those from April 2004 - March 2005 (FY2004). The number and proportion of various types of deficiencies described in GCP audit reports were compared between the 2 periods. The audit findings in the former period were based on official audits that covered 331 hospitals and 775 trials. The audits in the latter period targeted 114 hospitals and 189 trials. The inspection of former period was undertaken by the Organization for Pharmaceuticals Safety and Research (OPSR). On the other hand, the latter period was undertaken by the Pharmaceuticals and Medical Devices Agency (PMDA). The total number of deficiencies detected in GCP audits was 1,529 in the former 3-year period (FY1997 - 1999) and 819 in the latter period (FY2004). The total number of deficiencies detected and reported was more than 1.5-fold on an annual basis in the latter period. By category of deficiencies, the proportion of protocol deviations increased from 14.7 (225/1,529) to 45.7% (374/819), while the proportion of errors in case report forms (CRFs) decreased from 43.6 (666/ 1,529) to 27.1% (222/819). There were two remarkable changes in audit findings between FY1997 - 1999 and FY2004; the increase in the proportion of protocol deviations and the decrease in the proportion of CRF-related deficiencies. We think that in Japan the improvement of research environments is needed to provide reliable clinical data responsible for the regulatory standard of GCP. PMID:18793583

  3. Assessment of treatment response in chronic constipation clinical trials

    PubMed Central

    Ervin, Claire M; Fehnel, Sheri E; Baird, Mollie J; Carson, Robyn T; Johnston, Jeffrey M; Shiff, Steven J; Kurtz, Caroline B; Mangel, Allen W

    2014-01-01

    Background While chronic constipation (CC) clinical trials have focused primarily on bowel symptoms (symptoms directly related to bowel movements), abdominal symptoms are also prevalent among patients. The United States Food and Drug Administration’s (FDA’s) guidance on the use of patient-reported outcome measures to support product approvals or labeling claims recommends that endpoints be developed with direct patient input and include all symptoms important to patients. Aim To identify a comprehensive set of CC symptoms that are important to patients for measurement in clinical trials. Methods Following a targeted literature review to identify CC symptoms previously reported by patients, 28 patient interviews were conducted consistent with the FDA’s guidance on patient-reported outcomes. Subsequent to open-ended questions eliciting descriptions of all symptoms, rating and ranking methods were used to identify those of greatest importance to patients. Results All 67 studies reviewed included bowel symptoms; more than half also addressed at least one abdominal symptom. Interview participants reported 62 potentially distinct concepts: 12 bowel symptoms; 21 abdominal symptoms; and 29 additional symptoms/impacts. Patients’ descriptions revealed that many symptom terms were highly related and/or could be considered secondary to CC. The rating and ranking task results suggest that both bowel (for example, stool frequency and consistency) and abdominal symptoms (for example, bloating, abdominal pain) comprise patients’ most important symptoms. Further, improvements in both bowel and abdominal symptoms would constitute an improvement in patients’ CC overall. Conclusion Abdominal symptoms in CC patients are equal in relevance to bowel symptoms and should also be addressed in clinical trials to fully evaluate treatment benefit. PMID:24940076

  4. AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT): Rationale, Design, and Baseline Characteristics

    PubMed Central

    Smurzynski, Marlene; Collier, Ann C.; Koletar, Susan L.; Bosch, Ronald J.; Wu, Kunling; Bastow, Barbara; Benson, Constance A.

    2009-01-01

    Purpose ALLRT is a longitudinal cohort study of HIV-infected subjects prospectively randomized into selected clinical trials for antiretroviral (ARV) treatment-naïve and ARV treatment-experienced individuals conducted by the AIDS Clinical Trials Group (ACTG). We describe the rationale, design, and baseline characteristics of the ALLRT cohort and its potential to address important research questions related to ARV therapy. Method Standardized visits occur every 16 weeks to evaluate long-term clinical, virologic, and immunologic outcomes associated with ARV treatment. Results A total of 4,371 subjects enrolled in ALLRT from January 2000 through June 2007. Of these, 3,146 (72%) were ARV naïve at parent study entry (18% female, 44% white, 32% black, 21% Hispanic; median age 37 years, CD4 count 218 cells/μL, follow-up 3.6 years; 343 [11%] followed ≥8 years) and 1,225 (28%) were treatment experienced (13% female, 59% white, 20% black, 17% Hispanic; median age 42 years, CD4 count 325 cells/μL, follow-up 5.7 years). Conclusions ALLRT provides the opportunity to understand long-term ramifications of therapeutic ARV choices and determine whether these vary by treatment regimen, timing of treatment initiation, or treatment changes over long-term follow-up. Investigations based on uniform data and specimen collection in the context of randomized ARV treatments will be critical to developing more successful long-term therapeutic strategies for HIV treatment. PMID:18753121

  5. An Analysis of Sponsors/Collaborators of 69,160 Drug Trials Registered with ClinicalTrials.gov

    PubMed Central

    Keezhupalat, Shruthi Muralidharan; Naik, Ankeet; Gupta, Saurabh; Srivatsan, Raghunathan; Saberwal, Gayatri

    2016-01-01

    Background Clinical trials have been criticized on various counts. Any attempt to improve how trials are conducted or reported requires—amongst other things—an understanding of the number, the nature and the location of those that sponsor them or collaborate on them. Here we sought to identify the nature and location of each sponsor/collaborator. Methods and Findings We examined the 'sponsor/collaborator' field for the 69,160 drug trials that were registered with ClinicalTrials.gov over a 9-year period (2005–2014). Of the 12,823 unique sponsors, 56% had sponsored only one and 27% had sponsored 2–5 trials each. Just 18% were involved with six or more trials each, and we have (arbitrarily) labeled these organizations as 'more experienced' in sponsoring/collaborating on trials. These 18% (2,266 sponsors/collaborators) were analyzed further: (a) 951 were corporate organizations and (b) 1,145 were non-corporates (including 31 individuals) with (c) 170 unclassified. Further, we identified the location of each organization in (a) and (b). Conclusions Clinical trials are an important part of a nation's research endeavors, and ultimately contribute to the health of its people. Thus, understanding the clinical trial landscape—including the number and nature of sponsors, and how active they are—is important for every country. We believe that policy makers in particular should be interested in this study to understand the current situation, and to use the numbers as a baseline for the evolving landscape, to assess the impact of their strategies in future. PMID:26886868

  6. Foetal Injury in Clinical Trials and Accountability to the Child Once Born.

    PubMed

    Sheppard, Maria K

    2016-04-01

    Sponsors of clinical trials have excluded pregnant women from trial participation mainly because of the fear of legal liability for foetal injury. Yet, to prevent untested treatments exposing foetuses generally to unwarranted risks, it is necessary that pregnant women are included in clinical trials. Despite sponsors' fears there are, however, major stumbling blocks for the child once born claiming compensation under English law. Neither the new EU Regulation 536/2014 on clinical trials nor tort law or statutory regulations have achieved a clear and fair avenue for the compensation of children injured in utero. There are also inadequacies with the voluntary pharmaceutical industry guidelines regarding such compensation. Greater clarity and fairness regarding tort and civil liability might encourage sponsors to conduct more trials in pregnant women and more pregnant women to volunteer taking part in research in the knowledge that their children will be compensated if they sustain injuries in utero. PMID:27228682

  7. Selection of patients for clinical trials: an interactive web-based system.

    PubMed

    Fink, Eugene; Kokku, Princeton K; Nikiforou, Savvas; Hall, Lawrence O; Goldgof, Dmitry B; Krischer, Jeffrey P

    2004-07-01

    The purpose of a clinical trial is to evaluate a new treatment procedure. When medical researchers conduct a trial, they recruit participants with appropriate health problems and medical histories. To select participants, they analyze medical records of the available patients, which has traditionally been a manual procedure. We describe an expert system that helps to select patients for clinical trials. If the available data are insufficient for choosing patients, the system suggests additional medical tests and finds an ordering of the tests that reduces their total cost. Experiments show that the system can increase the number of selected patients. We also present an interface that enables a medical researcher to add clinical trials and selection criteria without the help of a programmer. The addition of a new trial takes 10-20 min, and novice users learn the functionality of the interface in about an hour. PMID:15302090

  8. Money and morals: ending clinical trials for financial reasons.

    PubMed

    Eaton, Margaret L; Kwon, Brian K; Scott, Christopher Thomas

    2015-01-01

    Too often, biopharmaceutical companies stop their clinical trials solely for financial reasons. In this chapter, we discuss this phenomenon against the backdrop of a 2011 decision by Geron Corporation to abandon its stem cell clinical trial for spinal cord injury (SCI), the preliminary results of which were released in May 2014. We argue that the resultant harms are widespread and are different in nature from the consequences of stopping trials for scientific or medical reasons. We examine the ethical and social effects that arise from such decisions and discuss them in light of ethical frameworks, including duties of individual stakeholders and corporate sponsors. We offer ways that sponsors and clinical sites can ensure that trials are responsibly started, and once started adequately protect the interests of participants. We conclude with recommendations that industry sponsors of clinical trials should adopt in order to advance a collective and patient-centered research ethic. PMID:25062706

  9. Mitigating the Effects of Nonadherence in Clinical Trials.

    PubMed

    Shiovitz, Thomas M; Bain, Earle E; McCann, David J; Skolnick, Phil; Laughren, Thomas; Hanina, Adam; Burch, Daniel

    2016-09-01

    Accounting for subject nonadherence and eliminating inappropriate subjects in clinical trials are critical elements of a successful study. Nonadherence can increase variance, lower study power, and reduce the magnitude of treatment effects. Inappropriate subjects (including those who do not have the illness under study, fail to report exclusionary conditions, falsely report medication adherence, or participate in concurrent trials) confound safety and efficacy signals. This paper, a product of the International Society for CNS Clinical Trial Methodology (ISCTM) Working Group on Nonadherence in Clinical Trials, explores and models nonadherence in clinical trials and puts forth specific recommendations to identify and mitigate its negative effects. These include statistical analyses of nonadherence data, novel protocol design, and the use of biomarkers, subject registries, and/or medication adherence technologies. PMID:26634893

  10. DICOM Structured Reporting and Cancer Clinical Trials Results

    PubMed Central

    Clunie, David A

    2007-01-01

    The use of biomarkers derived from radiological images as surrogate end-points in therapeutic cancer clinical trials is well established. DICOM is the ubiquitous standard for the interchange of images for both clinical use as well as research. It also has capabilities for the exchange of image-related information, including categorical and quantitative information derived from images. The use of DICOM Structured Reporting for the encoding and interchange of clinical trial results in a standard manner is reviewed. PMID:19390663

  11. Learning from hackers: open-source clinical trials.

    PubMed

    Dunn, Adam G; Day, Richard O; Mandl, Kenneth D; Coiera, Enrico

    2012-05-01

    Open sharing of clinical trial data has been proposed as a way to address the gap between the production of clinical evidence and the decision-making of physicians. A similar gap was addressed in the software industry by their open-source software movement. Here, we examine how the social and technical principles of the movement can guide the growth of an open-source clinical trial community. PMID:22553248

  12. Clinical Trial Design Issues in Mild to Moderate Alzheimer Disease

    PubMed Central

    Knopman, David S.

    2009-01-01

    The field of clinical trials and therapeutics in Alzheimer Disease (AD) is little more than 20 years old. Considerable progress has been made in crafting appropriate designs for clinical trials of promising therapeutic agents for AD. This article reviews basic issues in diagnostic criteria, choice of outcome measures, duration of trials and analytic strategies. Through trial and error, a general set of strategies has evolved for the assessment of putative therapies for mild to moderate AD. The experience of the past two decades has set the stage for discovering the next generation of anti-AD drugs and introducing those therapies at milder stages of the disease. PMID:19057167

  13. Randomization in clinical trials: conclusions and recommendations.

    PubMed

    Lachin, J M; Matts, J P; Wei, L J

    1988-12-01

    The statistical properties of simple (complete) randomization, permuted-block (or simply blocked) randomization, and the urn adaptive biased-coin randomization are summarized. These procedures are contrasted to covariate adaptive procedures such as minimization and to response adaptive procedures such as the play-the-winner rule. General recommendations are offered regarding the use of complete, permuted-block, or urn randomization. In a large double-masked trial, any of these procedures may be acceptable. For a given trial, the relative merits of each procedure should be carefully weighed in relation to the characteristics of the trial. Important considerations are the size of the trial, overall as well as within the smallest subgroup to be employed in a subgroup-specific analysis, whether or not the trial is to be masked, and the resources needed to perform the proper randomization-based permutational analysis. PMID:3203526

  14. Impact assessment of the European Clinical Trials Directive: a longitudinal, prospective, observational study analyzing patterns and trends in clinical drug trial applications submitted since 2001 to regulatory agencies in six EU countries

    PubMed Central

    2012-01-01

    Background Shifts in clinical trial application rates over time indicate if the attractiveness of a country or region for the conduct of clinical trials is growing or decreasing. The purpose of this observational study was to track changes in drug trial application patterns across several EU countries in order to analyze the medium-term impact of the EU Clinical Trials Directive 2001/20/EC on the conduct of drug trials. Methods Rates of Clinical Trial Applications (CTA) for studies with medicinal products in those six countries in the EU, which authorize on average more than 500 trials per year, were analyzed. Publicly available figures on the number of annually submitted CTA, the distribution of trials per phase and the type of sponsorship were tracked; missing data were provided by national drug agencies. Results Since 2001, the number of CTA in Italy and Spain increased significantly (5.0 and 2.5% average annual growth). For Italy, the gain was driven by a strong increase of applications from academic trial sponsors; Spain's growth was due to a rise in trials run by commercial sponsors. The Netherlands, Germany, France and the UK saw a decline (1.9, 2.3, 3.0 and 5.3% average annual diminution; significant (P < 0.05) except for Germany) in clinical drug trials. The decrease in the UK was caused by a sharp fall in academic trial activities. Across the six analyzed countries, no EU-wide trial-phase-specific patterns or trends were observed. Conclusions The EU Clinical Trials Directive 2001/20/EC did not achieve the harmonization of clinical trial requirements across Europe. Rather, it resulted in the leveling of clinical trial activities caused by a continuing decrease in CTA rates in the Netherlands, Germany, France and the UK. Southern European countries, Italy and Spain, benefited to some extent from policy changes introduced by the Directive. In Italy's case, national funding measures helped to considerably promote the conduct of non-commercial trials. On the

  15. Is Religiosity Related to Attitudes Towards Clinical Trials Participation?

    PubMed Central

    Daverio-Zanetti, Svetlana; Schultz, Kathryn; del Campo, Miguel A. Martin; Malcarne, Vanessa; Riley, Natasha; Sadler, Georgia Robins

    2014-01-01

    Research indicates that a low percentage of cancer patients enroll in cancer clinical trials. This is especially true among minority groups such as Hispanic Americans. Considering the importance of religion in the Hispanic American community, it is important to understand its relationship to perceptions of clinical trials. Five hundred and three Latina women completed the Barriers to Clinical Trials Participation Scale and the Duke University Religion Index. For the total sample, higher organizational and intrinsic religiosity were significantly associated with perceived lack of community support for clinical trials participation. In subgroup analysis, the relationship between organizational religiosity and lack of support was stronger among Latinas who were Spanish language-preference, and Latinas who were Catholic. Intrinsic religiosity was associated with mistrust among Spanish language-preference Latinas, and both organizational and intrinsic religiosity were associated with lack of familiarity with clinical trials among Christian (non-Catholic) Latinas. These results indicate religious institutions that serve Latinas may be an effective venue for disseminating clinical trial education programs to improve attitudes toward clinical trials participation. PMID:24953236

  16. Is religiosity related to attitudes toward clinical trials participation?

    PubMed

    Daverio-Zanetti, Svetlana; Schultz, Kathryn; del Campo, Miguel A Martin; Malcarne, Vanessa; Riley, Natasha; Sadler, Georgia Robins

    2015-06-01

    Research indicates that a low percentage of cancer patients enroll in cancer clinical trials. This is especially true among minority groups such as Hispanic Americans. Considering the importance of religion in the Hispanic American community, it is important to understand its relationship to perceptions of clinical trials. Five hundred and three Latina women completed the Barriers to Clinical Trials Participation Scale and the Duke University Religion Index. For the total sample, higher organizational and intrinsic religiosity was significantly associated with a perceived lack of community support for clinical trials participation. In subgroup analysis, the relationship between organizational religiosity and lack of support was stronger among Latinas who were Spanish language preferred and Latinas who were Catholic. Intrinsic religiosity was associated with mistrust among Spanish language-preferred Latinas, and both organizational and intrinsic religiosities were associated with a lack of familiarity with clinical trials among Christian (non-Catholic) Latinas. These results indicate that religious institutions that serve Latinas may be an effective venue for disseminating clinical trial education programs to improve attitudes toward clinical trials participation. PMID:24953236

  17. Health literacy and usability of clinical trial search engines.

    PubMed

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

    2014-01-01

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

  18. Gene therapy clinical trials worldwide 1989-2004-an overview.

    PubMed

    Edelstein, Michael L; Abedi, Mohammad R; Wixon, Jo; Edelstein, Richard M

    2004-06-01

    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

  19. Phytochemistry, pharmacology, and clinical trials of Morus alba.

    PubMed

    Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin

    2016-01-01

    The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. PMID:26850343

  20. PPARs: Interference with Warburg' Effect and Clinical Anticancer Trials

    PubMed Central

    Vamecq, Joseph; Colet, Jean-Marie; Vanden Eynde, Jean Jacques; Briand, Gilbert; Porchet, Nicole; Rocchi, Stéphane

    2012-01-01

    The metabolic/cell signaling basis of Warburg's effect (“aerobic glycolysis”) and the general metabolic phenotype adopted by cancer cells are first reviewed. Several bypasses are adopted to provide a panoramic integrated view of tumoral metabolism, by attributing a central signaling role to hypoxia-induced factor (HIF-1) in the expression of aerobic glycolysis. The cancer metabolic phenotype also results from alterations of other routes involving ras, myc, p53, and Akt signaling and the propensity of cancer cells to develop signaling aberrances (notably aberrant surface receptor expression) which, when present, offer unique opportunities for therapeutic interventions. The rationale for various emerging strategies for cancer treatment is presented along with mechanisms by which PPAR ligands might interfere directly with tumoral metabolism and promote anticancer activity. Clinical trials using PPAR ligands are reviewed and followed by concluding remarks and perspectives for future studies. A therapeutic need to associate PPAR ligands with other anticancer agents is perhaps an important lesson to be learned from the results of the clinical trials conducted to date. PMID:22654896

  1. Practical Clinical Trials in Psychopharmacology: a Systematic Review

    PubMed Central

    Vitiello, Benedetto

    2015-01-01

    Practical clinical trials (PCT) are randomized experiments under typical practice conditions with the aim of testing the “real life” benefits and risks of therapeutic interventions. Influential PCTs have been conducted in cardiology, oncology, and internal medicine. Psychotropic medications are widely and increasingly used in medical practice. This review examines recent progress in conducting PCTs in psychopharmacology. The January 2000 – October 2014 MEDLINE, Scopus, and ClinicalTrials.gov databases were searched for peer-reviewed publications of PCTs with at least 100 subjects per treatment arm. Most PCTs in psychiatry evaluated mental health services or psychosocial interventions rather than specific pharmacotherapies. Of 157 PCTs in psychiatry, 30 (19%) were in psychopharmacology, with a median of 2 publications per year and no increase over the period of observation. Sample size ranged from 200 to 18,154; only 11 studies randomized 500 patients or more. Psychopharmacology PCTs were equally likely to be funded by industry as by public agencies. There were 10 PCTs of antidepressants, for a total of 4,206 patients (in comparison with at least 46 PCT of antihypertensive medications, for a total of 208,014 patients). Some psychopharmacology PCTs used suicidal behavior, treatment discontinuation, or mortality as primary outcome, and produced effectiveness and safety data that have influenced both practice guidelines and regulatory decisions. PCTs can constitute an important source of information for clinicians, patients, regulators, and policy makers, but have been relatively underutilized in psychopharmacology. Electronic medical records and integrated practice research networks offer promising platforms for a more efficient conduct of PCTs. PMID:25679131

  2. Differential Globalization of Industry- and Non-Industry–Sponsored Clinical Trials

    PubMed Central

    Atal, Ignacio; Trinquart, Ludovic; Porcher, Raphaël; Ravaud, Philippe

    2015-01-01

    Background Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry–sponsored clinical trials and its evolution over time. Methods We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry–sponsored international trials. Results 119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry–sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry–sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry–sponsored trials (from 42.4% to 37.2%). Conclusions Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry–sponsored clinical research. Only 3% of

  3. Clinical Trials For Cytoprotection In Stroke

    PubMed Central

    Labiche, Lise A.; Grotta, James C.

    2004-01-01

    Summary: To date, many cytoprotective drugs have reached the stage of pivotal phase 3 efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the neuroprotective literature, the phrase “failure to demonstrate efficacy” prevails as a common thread among the many neutral or negative trials, despite the largely encouraging results encountered in preclinical studies. The reasons for this discrepancy are multiple, and have been discussed by Dr. Zivin in his review. Many of the recent trials have addressed deficiencies of the previous ones with more rigorous trial design, including more specific patient selection criteria (ensure homogeneity of stroke location and severity), stratified randomization algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic monitoring. Current trials have also incorporated biologic surrogate markers of toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal therapies and coupled cytoprotection/reperfusion strategies are being investigated to optimize tissue salvage. This review will focus on individual therapeutic strategies and we will emphasize what we have learned from these trials both in terms of trial design and the biologic effect (or lack thereof) of these agents. PMID:15717007

  4. 'Cloud computing' and clinical trials: report from an ECRIN workshop.

    PubMed

    Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques

    2015-01-01

    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. PMID:26220186

  5. Statistical Controversies in Reporting of Clinical Trials: Part 2 of a 4-Part Series on Statistics for Clinical Trials.

    PubMed

    Pocock, Stuart J; McMurray, John J V; Collier, Tim J

    2015-12-15

    This paper tackles several statistical controversies that are commonly faced when reporting a major clinical trial. Topics covered include: multiplicity of data, interpreting secondary endpoints and composite endpoints, the value of covariate adjustment, the traumas of subgroup analysis, assessing individual benefits and risks, alternatives to analysis by intention to treat, interpreting surprise findings (good and bad), and the overall quality of clinical trial reports. All is put in the context of topical cardiology trial examples and is geared to help trialists steer a wise course in their statistical reporting, thereby giving readers a balanced account of trial findings. PMID:26670066

  6. Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action

    PubMed Central

    Tillie, Nicole A.; Parker, Jayson L.; Feld, Jordan J.

    2016-01-01

    Background and Aims. This study analyzed the risk of clinical trial failure of new drugs for hepatitis C between January 1998 and January 2015. Methods. Hepatitis C drug development trials that were in phases I–III of clinical trial testing were obtained from the publicly accessible clinical trial repository and other publicly available databases. Drug compounds were excluded from the study if they began their phase I testing before 1998, if they were not industry sponsored, or if they treated secondary complications of hepatitis C. Clinical trial success rates were analyzed in comparison to industry expectations. Further analysis was conducted on the molecule classifications, the mechanisms of action, and the trial endpoints. Results. One hundred and twenty-three unique drug compounds were found to fulfill the inclusion criteria, eight of which had FDA approval. The overall cumulative pass rate for hepatitis C drugs was 20%, which is double the industry expectation rate. Viral inhibitor small molecule drugs significantly reduced the risk of drug failure during clinical trials compared to other mechanisms of action. Conclusion. On average, one in every five drugs that began clinical testing will be approved for market. Viral inhibitor small molecule drugs are the most promising and hold the least risk.

  7. Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action.

    PubMed

    Tillie, Nicole A; Parker, Jayson L; Feld, Jordan J

    2016-01-01

    Background and Aims. This study analyzed the risk of clinical trial failure of new drugs for hepatitis C between January 1998 and January 2015. Methods. Hepatitis C drug development trials that were in phases I-III of clinical trial testing were obtained from the publicly accessible clinical trial repository and other publicly available databases. Drug compounds were excluded from the study if they began their phase I testing before 1998, if they were not industry sponsored, or if they treated secondary complications of hepatitis C. Clinical trial success rates were analyzed in comparison to industry expectations. Further analysis was conducted on the molecule classifications, the mechanisms of action, and the trial endpoints. Results. One hundred and twenty-three unique drug compounds were found to fulfill the inclusion criteria, eight of which had FDA approval. The overall cumulative pass rate for hepatitis C drugs was 20%, which is double the industry expectation rate. Viral inhibitor small molecule drugs significantly reduced the risk of drug failure during clinical trials compared to other mechanisms of action. Conclusion. On average, one in every five drugs that began clinical testing will be approved for market. Viral inhibitor small molecule drugs are the most promising and hold the least risk. PMID:27446855

  8. Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

    PubMed

    Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

    2016-04-01

    Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML. PMID:26515793

  9. 78 FR 63479 - Meta-Analyses of Randomized Controlled Clinical Trials (RCTs) for the Evaluation of Risk To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... HUMAN SERVICES Food and Drug Administration Meta-Analyses of Randomized Controlled Clinical Trials (RCTs... scientific approaches for the conduct and assessment of meta-analyses of randomized controlled clinical... others from the general public, about the use of meta-analyses of randomized trials as a tool for...

  10. Clinical trials in developing countries: Discussions at the '9th International Symposium on Long Term Clinical Trials', London, UK, 19-20 June 2000

    PubMed Central

    Johnatty, Rachel N

    2000-01-01

    This symposium provided a useful forum for the discussion of issues relating to the design and conduct of clinical trials. There is a need for greater awareness of the complexity of modern day trials, in which a host of statistical, logistical, regulatory and ethical issues are involved. Issues discussed ranged from the effect of sample size on the outcome, and subgroup analysis, to defining and maintaining discrete endpoints. Some useful debate centred on the use of meta-analysis and the current limitations of combining information from different data sets. This brought up the subjects of trial registries and raw data repositories for all clinical trials. Progress and relevance of the Cochrane collaboration were reviewed. The economics of clinical trials was another important topic. Regulatory issues such as the role of data and safety monitoring boards (DSMB) and the guidelines in place for effective data monitoring and progress analysis were discussed. Representatives of government organisations and industry gave both European and American perspectives. This report however focuses specifically on the section devoted to the subject of clinical trials in developing countries. PMID:11714410

  11. Sample sizes in dosage investigational clinical trials: a systematic evaluation.

    PubMed

    Huang, Ji-Han; Su, Qian-Min; Yang, Juan; Lv, Ying-Hua; He, Ying-Chun; Chen, Jun-Chao; Xu, Ling; Wang, Kun; Zheng, Qing-Shan

    2015-01-01

    The main purpose of investigational phase II clinical trials is to explore indications and effective doses. However, as yet, there is no clear rule and no related published literature about the precise suitable sample sizes to be used in phase II clinical trials. To explore this, we searched for clinical trials in the ClinicalTrials.gov registry using the keywords "dose-finding" or "dose-response" and "Phase II". The time span of the search was September 20, 1999, to December 31, 2013. A total of 2103 clinical trials were finally included in our review. Regarding sample sizes, 1,156 clinical trials had <40 participants in each group, accounting for 55.0% of the studies reviewed, and only 17.2% of the studies reviewed had >100 patient cases in a single group. Sample sizes used in parallel study designs tended to be larger than those of crossover designs (median sample size 151 and 37, respectively). In conclusion, in the earlier phases of drug research and development, there are a variety of designs for dosage investigational studies. The sample size of each trial should be comprehensively considered and selected according to the study design and purpose. PMID:25609916

  12. Methods for enhancing the efficiency of dental/oral health clinical trials: current status, future possibilities.

    PubMed

    Barnett, M L; Pihlstrom, B L

    2004-10-01

    In recent years, there has been an increasing demand for clinical trials to study oral, dental, and craniofacial diseases and conditions. This has resulted from such factors as the increasing pace of discoveries requiring translational research to develop them for clinical use, FDA requirements for product approval, a need for additional data to support evidence-based dental practice, and the expansion of the NIDCR's clinical research programs. The complexity, size, and duration of clinical trials often make them quite costly to conduct, and may impede the development of novel diagnostic, preventive, and therapeutic methods that could have a significant impact on clinical practice and inform public health policy. Recent advances in such areas as genomics and proteomics, coupled with the development of new technologies, have expanded our knowledge of the etiology and pathogenesis of disease and, from this, have provided new insights into the design and conduct of clinical trials. The workshop, "Methods for Enhancing the Efficiency of Dental/Oral Health Clinical Trials: Current Status, Future Possibilities", held on May 6-7, 2004, considered a variety of ways in which these insights are being, or have the potential to be, applied to clinical trials so as to enhance their efficiency and, hence, their cost-effectiveness, without diminishing the quality of information produced. The focus of this workshop was to assess the state of the science and identify research needs for the use of biomarkers, surrogate endpoints, and new technologies in oral disease clinical trials. Examples of ways in which clinical trials of other diseases have benefited from the use of new methods and technologies and FDA considerations were also discussed. PMID:15381712

  13. Influences on visit retention in clinical trials: Insights from qualitative research during the VOICE trial in Johannesburg, South Africa

    PubMed Central

    2014-01-01

    Background Although significant progress has been made in clinical trials of women-controlled methods of HIV prevention such as microbicides and Pre-exposure Prophylaxis (PrEP), low adherence to experimental study products remains a major obstacle to being able to establish their efficacy in preventing HIV infection. One factor that influences adherence is the ability of trial participants to attend regular clinic visits at which trial products are dispensed, adherence counseling is administered, and participant safety is monitored. We conducted a qualitative study of the social contextual factors that influenced adherence in the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study participation in general, and study visits in particular. Methods The research used qualitative methodologies, including in-depth interviews (IDI), serial ethnographic interviews (EI), and focus group discussions (FGD) among a random sub-sample of 102 female trial participants, 18 to 40 years of age. A socio-ecological framework that explored those factors that shaped trial participation and adherence to study products, guided the analysis. Key codes were developed to standardize subsequent coding and a node search was used to identify texts relating to obstacles to visit adherence. Our analysis includes coded transcripts from seven FGD (N = 40), 41 IDI, and 64 serial EI (N = 21 women). Results Women’s kinship, social, and economic roles shaped their ability to participate in the clinical trial. Although participants expressed strong commitments to attend study visits, clinic visit schedules and lengthy waiting times interfered with their multiple obligations as care givers, wage earners, housekeepers, and students. Conclusions The research findings highlight the importance of the social context in shaping participation in HIV prevention trials, beyond focusing solely on individual characteristics. This points to the need to focus interventions to improve

  14. Black raspberries in cancer clinical trials: Past, present and future

    PubMed Central

    Kresty, Laura A.; Mallery, Susan R.; Stoner, Gary D.

    2016-01-01

    BACKGROUND Black raspberries (BRB) inhibit a broad range of cancers in preclinical models, including in vivo models of oral, esophageal, colon, breast and skin cancer. Promising preclinical results have led to clinical evaluations in cancer patients or patients at increased risk for cancer development. OBJECTIVE To summarize clinical investigations targeting cancer or precancerous lesions with BRB and discuss future directions. METHODS A thorough literature search was conducted through December 1, 2015 to identify all published studies evaluating BRB in cancer focused clinical trials. RESULTS Research investigating BRB in clinical settings report positive effects on preneoplastic lesions or cancers of the oral cavity, esophagus and colon. BRB treatment resulted in: histologic regression of oral intraepithelial neoplasia associated with improved histologic grade and significantly reduced loss of heterozygosity at tumor suppressor gene loci, modulated genes linked to RNA processing and growth factor recycling; in the colon, BRB inhibited FAP-associated polyp progression, demethylated tumor suppressor genes and improved plasma cytokine profiles; in Barrett’s patients, BRB consumption increased tissue levels of GST-pi and decreased 8-isoprostane, a marker of lipid peroxidation/oxidative stress. CONCLUSIONS The precise dose, duration and optimum mode of BRB delivery for cancer inhibition remains to be fully elucidated. Common themes across studies support that BRB are anti-proliferative, anti- inflammatory, reduce oxidative stress and restore tumor suppressive activity. Future directions are included in the conclusions section.

  15. Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

    PubMed Central

    Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

    2013-01-01

    Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

  16. Lessons learned in the conduct of a global, large simple trial of treatments indicated for schizophrenia.

    PubMed

    Kolitsopoulos, Francesca M; Strom, Brian L; Faich, Gerald; Eng, Sybil M; Kane, John M; Reynolds, Robert F

    2013-03-01

    Large, "practical" or streamlined trials (LSTs) are used to study the effectiveness and/or safety of medicines in real world settings with minimal study imposed interventions. While LSTs have benefits over traditional randomized clinical trials and observational studies, there are inherent challenges to their conduct. Enrollment and follow-up of a large study sample of patients with mental illness pose a particular difficulty. To assist in overcoming operational barriers in future LSTs in psychiatry, this paper describes the recruitment and observational follow-up strategies used for the ZODIAC study, an international, open-label LST, which followed 18,239 persons randomly assigned to one of two treatments indicated for schizophrenia for 1 year. ZODIAC enrolled patients in 18 countries in North America, South America, Europe, and Asia using broad study entry criteria and required minimal clinical care intervention. Recruitment of adequate numbers and continued engagement of both study centers and subjects were significant challenges. Strategies implemented to mitigate these in ZODIAC include global study expansion, study branding, field coordinator and site relations programs, monthly site newsletters, collection of alternate contact information, conduct of national death index (NDI) searches, and frequent sponsor, contract research organization (CRO) and site interaction to share best practices and address recruitment challenges quickly. We conclude that conduct of large LSTs in psychiatric patient populations is feasible, but importantly, realistic site recruitment goals and maintaining site engagement are key factors that need to be considered in early study planning and conduct. PMID:23246610

  17. Advances in designs for Alzheimer’s disease clinical trials

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development. PMID:23383393

  18. African American women's perceptions of cancer clinical trials.

    PubMed

    Haynes-Maslow, Lindsey; Godley, Paul; Dimartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William

    2014-10-01

    Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical trials and identified leverage points that future interventions may use to improve enrollment rates. Study findings highlight variation in community knowledge regarding cancer clinical trials, and the importance of community education regarding clinical trials and overcoming historical stigma associated with clinical research specifically and the health care system more generally. Study participants commented on the centrality of churches in their communities, and thus the promise of the church as loci of such education. Findings also suggested the value of informed community leaders as community information sources, including community members who have a previous diagnosis of cancer and clinical trial experience. The sample size and location of the focus groups may limit the generalizability of the results. Since the women in the focus groups were either cancer survivors or caregivers, they may have different experiences than nonparticipants who lack the close connection with cancer. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials. PMID:24905181

  19. African American women's perceptions of cancer clinical trials

    PubMed Central

    Haynes-Maslow, Lindsey; Godley, Paul; Dimartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William

    2014-01-01

    Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical trials and identified leverage points that future interventions may use to improve enrollment rates. Study findings highlight variation in community knowledge regarding cancer clinical trials, and the importance of community education regarding clinical trials and overcoming historical stigma associated with clinical research specifically and the health care system more generally. Study participants commented on the centrality of churches in their communities, and thus the promise of the church as loci of such education. Findings also suggested the value of informed community leaders as community information sources, including community members who have a previous diagnosis of cancer and clinical trial experience. The sample size and location of the focus groups may limit the generalizability of the results. Since the women in the focus groups were either cancer survivors or caregivers, they may have different experiences than nonparticipants who lack the close connection with cancer. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials. PMID:24905181

  20. [Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

    PubMed

    Benninger-Döring, G; Boos, J

    2006-07-01

    Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed. PMID:16763801

  1. Clinical Trials: A Crucial Key to Human Health Research

    MedlinePlus

    ... other federal agencies, pharmaceutical companies, universities and nonprofit organizations. Here's how it works. After you enter the ClinicalTrials.gov Web site, you can search for a trial by the name of the disease, the location of the study, the type of treatment or the sponsoring institution. ...

  2. Reforms speed initiation of NCI-sponsored clinical trials

    Cancer.gov

    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

  3. Evaluating the first-in-human clinical trial of a human embryonic stem cell-based therapy.

    PubMed

    Chapman, Audrey R; Scala, Courtney C

    2012-09-01

    Phase I clinical trials generally raise greater ethical and human protection challenges than later stage clinical trials, suggesting a need to proceed cautiously. This is particularly the case for Phase I trials with a novel therapy being tested in humans for the first time, usually termed first-in-human (FIH) trials. In January 2009, the Food and Drug Administration approved the Investigational New Drug application of Geron Corporation, a small California-based biopharmaceutical company, to initiate a clinical trial to assess GRNOPC1, a human embryonic stem cell-derived candidate therapy for severe spinal cord injuries. This article evaluates the ethical and human subject protection issues raised by the Geron FIH trial. It identifies problems with the approval process and with the conduct of the trial, and then recommends ways to improve review of future proposed trials with novel and high-risk therapies. PMID:23285793

  4. Detecting data fabrication in clinical trials from cluster analysis perspective.

    PubMed

    Wu, Xiaoru; Carlsson, Martin

    2011-01-01

    Detecting data fabrication is of great importance in clinical trials. As the role of statisticians in detecting abnormal data patterns has grown, a large number of statistical procedures have been developed, most of which are based on descriptive statistics. Based upon the fact that substantial data fabrication cases have certain clustering structures, this paper discusses the potential for the use of statistical clustering method in fraud detection. Three clustering patterns, angular, neighborhood and repeated measurements clustering, are identified and explored. Correspondingly, simple and efficient test statistics are proposed and randomization tests are carried out. The proposed methods are applied to a 12-week multi-center study for illustration. Extensive simulations are conducted to validate the effectiveness of the procedures. PMID:20936626

  5. The Place of Adoption in the NIDA Clinical Trials Network

    PubMed Central

    Jessup, Martha A.; Guydish, Joseph; Manser, Sarah Turcotte; Tajima, Barbara

    2009-01-01

    The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) was established in 1999 to determine effectiveness of drug abuse treatment interventions among diverse client populations and settings. To address dissemination of research findings, the CTN also has as its mission the transfer of research findings to treatment providers. In a qualitative study of adoption of evidence based practice in the context of two CTN clinical trials, we interviewed 29 participants from seven organizational levels of the multisite study organization about post-trial adoption, their role in the clinical trial, and interactions between the research initiative and clinic staff and setting. Analysis of interview data revealed a range of opinion among participants on the place of adoption within the CTN. Innovation within the CTN to support adoption and further observational research on dynamics of adoption within the CTN can increase dissemination of evidence-based drug abuse treatment interventions in the future. PMID:20126428

  6. Textual inference for eligibility criteria resolution in clinical trials.

    PubMed

    Shivade, Chaitanya; Hebert, Courtney; Lopetegui, Marcelo; de Marneffe, Marie-Catherine; Fosler-Lussier, Eric; Lai, Albert M

    2015-12-01

    Clinical trials are essential for determining whether new interventions are effective. In order to determine the eligibility of patients to enroll into these trials, clinical trial coordinators often perform a manual review of clinical notes in the electronic health record of patients. This is a very time-consuming and exhausting task. Efforts in this process can be expedited if these coordinators are directed toward specific parts of the text that are relevant for eligibility determination. In this study, we describe the creation of a dataset that can be used to evaluate automated methods capable of identifying sentences in a note that are relevant for screening a patient's eligibility in clinical trials. Using this dataset, we also present results for four simple methods in natural language processing that can be used to automate this task. We found that this is a challenging task (maximum F-score=26.25), but it is a promising direction for further research. PMID:26376462

  7. Temporal knowledge representation for scheduling tasks in clinical trial protocols.

    PubMed Central

    Weng, Chunhua; Kahn, Michael; Gennari, John

    2002-01-01

    Clinical trial protocols include detailed temporal constraints on treatment and associated tasks. Unlike health-care guidelines, protocols are highly prescriptive. Therefore, informatics applications that enforce such temporal constraints are more directly useful with protocols than with guidelines. Although there are some temporal knowledge representation efforts for health-care guidelines, we find these to be insufficiently expressive for clinical trial protocols. In this paper, we focus on temporal knowledge representation for clinical trial protocols and the task of patient-specific scheduling in protocols. We define a temporal ontology, use it to encode clinical trial protocols, and describe a prototype tool to carry out patient-specific scheduling for the tasks in protocols. We predict that an expressive temporal knowledge representation can support a number of scheduling and management tasks for protocol-based care. PMID:12463951

  8. Clinical Research Trials and You: Questions and Answers

    MedlinePlus

    ... volunteers and to preserve the integrity of the science. Ethical guidelines in place today were primarily a response to past research abuses. Informed Consent Informed consent is the process of learning the key facts about a clinical trial before ...

  9. What Are the Possible Benefits and Risks of Clinical Trials?

    MedlinePlus

    ... of questions to ask your doctor and the research staff, go to "How Do Clinical Trials Protect Participants?" Featured Video ... children and their own motivations for pursuing research in this field. Learn more at http://www. ...

  10. CliniProteus: A flexible clinical trials information management system

    PubMed Central

    Mathura, Venkatarajan S; Rangareddy, Mahendiranath; Gupta, Pankaj; Mullan, Michael

    2007-01-01

    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

  11. ClinicalTrials.gov | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of Contents “...a powerful tool for the healthcare consumer” Clinical trials are research studies that use volunteers to help medical professionals test new treatments for a wide array of diseases and ...

  12. Processes for quality improvements in radiation oncology clinical trials.

    PubMed

    FitzGerald, T J; Urie, Marcia; Ulin, Kenneth; Laurie, Fran; Yorty, Jeffrey; Hanusik, Richard; Kessel, Sandy; Jodoin, Maryann Bishop; Osagie, Gani; Cicchetti, M Giulia; Pieters, Richard; McCarten, Kathleen; Rosen, Nancy

    2008-01-01

    Quality assurance in radiotherapy (RT) has been an integral aspect of cooperative group clinical trials since 1970. In early clinical trials, data acquisition was nonuniform and inconsistent and computational models for radiation dose calculation varied significantly. Process improvements developed for data acquisition, credentialing, and data management have provided the necessary infrastructure for uniform data. With continued improvement in the technology and delivery of RT, evaluation processes for target definition, RT planning, and execution undergo constant review. As we move to multimodality image-based definitions of target volumes for protocols, future clinical trials will require near real-time image analysis and feedback to field investigators. The ability of quality assurance centers to meet these real-time challenges with robust electronic interaction platforms for imaging acquisition, review, archiving, and quantitative review of volumetric RT plans will be the primary challenge for future successful clinical trials. PMID:18406943

  13. NIH-Supported Clinical Trial Finds Antidepressant Reduces Alzheimer's Agitation

    MedlinePlus

    ... Plan National Alzheimer's Project Act (NAPA) About ADEAR NIH-supported clinical trial finds antidepressant reduces Alzheimer’s agitation February 25, 2014 NIH-funded researchers are testing interventions to alleviate psychiatric ...

  14. Strategies for dealing with fraud in clinical trials.

    PubMed

    Herson, Jay

    2016-02-01

    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. PMID:26194810

  15. Unconventional Anticancer Agents: A Systematic Review of Clinical Trials

    PubMed Central

    Vickers, Andrew J.; Kuo, Joyce; Cassileth, Barrie R.

    2006-01-01

    Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials. PMID:16382123

  16. Clinical Trial Application in Europe: What Will Change with the New Regulation?

    PubMed

    Giannuzzi, Viviana; Altavilla, Annagrazia; Ruggieri, Lucia; Ceci, Adriana

    2016-04-01

    The European framework surrounding clinical trials on medicinal products for human use is going to change as demonstrated by the large debate at European institutional level. One of the major challenges is to overcome the lack of harmonisation of clinical trial procedures among countries. This aspect is gaining more and more importance, considering the increasing number of multicentre and multinational studies. In this work, the actual European rules governing the Clinical Trial Application have been analysed throughout the different steps including the registration of the trial in the European database; the preparation of documents to be submitted and their contents; the preparation of documents related to the information and consent process; the submission to competent bodies. Specific issues related to paediatric research and trials involving non EU/EEA countries have been addressed as well. Results reveal that the European legislation offers a well defined set of European rules covering different aspects of a Clinical Trial Application. However, these are not suitable to meet the challenges from multicentre and multinational clinical studies. A stronger set of rules, such as is available in a composite European Regulation has been adopted and is expected to harmonise practices and enable sponsors to carry out well conducted trials. But will the new regulation overcome the existing criticisms of Directive 2001/20/EC? PMID:26037896

  17. Attitudes Toward Participation in Breast Cancer Randomized Clinical Trials in the African American Community

    PubMed Central

    Linden, Hannah M.; Reisch, Lisa M.; Hart, Alton; Harrington, Margaret A.; Nakano, Connie; Jackson, J. Carey; Elmore, Joann G.

    2013-01-01

    Participation of African Americans in research trials is low. Understanding the perspectives of African American patients toward participation in clinical trials is essential to understanding the disparities in participation rates compared with whites. A qualitative study was conducted to discover attitudes of the African American community regarding willingness to participate in breast cancer screening and randomized clinical trials. Six focus groups consisting of 8 to 11 African American women (N = 58), aged 30 to 65, were recruited from local churches. Focus group sessions involved a 2-hour audiotaped discussion facilitated by 2 moderators. A breast cancer randomized clinical trial involving an experimental breast cancer treatment was discussed to identify the issues related to willingness to participate in such research studies. Six themes surrounding willingness to participate in randomized clinical trials were identified: (1) Significance of the research topic to the individual and/or community; (2) level of trust in the system; (3) understanding of the elements of the trial; (4) preference for “natural treatments” or “religious intervention” over medical care; (5) cost-benefit analysis of incentives and barriers; and (6) openness to risk versus a preference for proven treatments. The majority (80%) expressed willingness or open-mindedness to the idea of participating in the hypothetical trial. Lessons learned from this study support the selection of a culturally diverse research staff and can guide the development of research protocols, recruitment efforts, and clinical procedures that are culturally sensitive and relevant. PMID:17666974

  18. 78 FR 7437 - Proposed Collection; Comment Request (60-Day FRN); The Clinical Trials Reporting Program (CTRP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-01

    ... Clinical Trials Reporting Program (CTRP) Database (NCI) SUMMARY: In compliance with the requirement of... publication. Proposed Collection: The Clinical Trials Reporting Program (CTRP) Database, 0925-0600,...

  19. Meta-analysis of five photodisinfection clinical trials for periodontitis

    NASA Astrophysics Data System (ADS)

    Andersen, Roger C.; Loebel, Nicolas G.; Andersen, Dane M.

    2009-06-01

    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.

  20. Phase 0/I/II Cancer Prevention Clinical Trials Program (Consortia) | Division of Cancer Prevention

    Cancer.gov

    Five cancer research centers lead multiple collaborative networks to assess potential cancer preventive agents and to conduct early clinical development of promising preventive agents. Also called the Consortia for Early Phase Prevention Trials, the studies require extensive biomarker analysis, investigation of the biologic effects of the cancer preventive agents on their intended molecular targets and on multiple endpoints associated with carcinogenesis, and correlation with clinically relevant endpoints.  | Systematic early clinical development of promising preventive agents through five major medical research centers.

  1. Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). The Fiber Study, a randomized controlled trial on symptom management for FI, successfully enrolled 189 community-living adu...

  2. Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network

    Cancer.gov

    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

  3. A centralized informatics infrastructure for the National Institute on Drug Abuse Clinical Trials Network

    PubMed Central

    Pan, Jeng-Jong; Nahm, Meredith; Wakim, Paul; Cushing, Carol; Poole, Lori; Tai, Betty; Pieper, Carl F.

    2009-01-01

    Background Clinical trial networks were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research. Purpose In 2005, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) transitioned from a distributed data management model to a centralized informatics infrastructure to support the network’s trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor. Methods During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization. Results We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%–1.0% before centralization to 0.01%–0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial. Limitations A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings. Conclusions The identified informatics components provide the information and infrastructure needed for our clinical trial

  4. Bach flower remedies: a systematic review of randomised clinical trials.

    PubMed

    Ernst, Edzard

    2010-01-01

    Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos. PMID:20734279

  5. Clinical Trials: past, current and future for atypical parkinsonian syndromes

    PubMed Central

    Tsai, Richard M.; Boxer, Adam L.

    2016-01-01

    There are currently no effective, Food and Drug Administration (FDA) approved treatments for atypical parkinsonian disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), dementia with lewy bodies (DLB) or multiple system atrophy (MSA). Previous treatment trials for these disorders were focused on symptomatic support and did not affect disease progression. Recent breakthroughs in neuropathology and pathophysiology have allowed a new eunderstanding of these disorders and investigation into potentially disease modifying therapies. Randomized, placebo-controlled clinical trials of these disorders will be reviewed here. Suggestions for future therapeutic targets, clinical trial design, with a focus on PSP will also be provided. PMID:24963682

  6. Behavioral risk assessment in HIV Vaccine Trials Network (HVTN) clinical trials: A qualitative study exploring HVTN staff perspectives

    PubMed Central

    Andrasik, Michele Peake; Karuna, Shelly T.; Nebergall, Michelle; Koblin, Beryl A.; Kublin, Jim G.

    2013-01-01

    In HIV vaccine trials, the collection and analysis of participant behavior data associated with risk of acquiring HIV-infection is important for a number of reasons. Although the rationale for behavioral risk assessment in HIV vaccine clinical trials is clear, consistent collection of behavioral data over time and across protocols has been challenging for the HIV Vaccine Trials Network (HVTN). Integrating biomedical and behavioral research within the same preventive vaccine clinical trial has proven difficult. The HVTN conducted an internal landscape analysis to: (1) evaluate the challenges of behavioral risk assessment in HIV vaccine trials and observational studies; (2) explore the impact of the Step Study on behavioral risk assessment measures; and (3) identify strategies to overcome existing challenges and improve the quality of data resulting from behavioral risk analysis. These analyses of behavioral risk within the HVTN revealed several challenges and recommendations for improved behavioral risk data collection in future protocols. The recommendations for improvement include: (1) establishment of protocol-specific behavioral risk working groups that include social and behavioral experts; (2) provision of behavioral rationale and objectives to the development team; (3) creation of a template for geographic- and population-specific assessment of low and high risk behaviors; and (4) pilot testing of behavioral risk assessments. Results also underscored the need for routinely conducted analyses of behavioral data. PMID:23859840

  7. Unfulfilled translation opportunities in industry sponsored clinical trials.

    PubMed

    Smed, Marie; Getz, Kenneth A

    2013-05-01

    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. PMID:23454567

  8. [Legal regulation of clinical drug trials for the use in military-medical organisations].

    PubMed

    Ivchenko, E V; Ivanov, V S; Shustov, S B

    2015-06-01

    The authors identified problematic issues of legal regulation of clinical drug trials for medical use, and proposed possible solutions. It has been established that the conduction of clinical trials, of medicinal products is based on the norms of various branches of law embodied in the Constitution of the Russian Federation, the norms of international law, the Civil Code of the Russian Federation and federal laws and subordinate legislations regulating health and pharmaceutical activity. According to the authors, the norms of bioethics can be attributed to the sources of legal doctrine. It is proposed to oblige executives of clinical trials to make a report about effectiveness and safety of drugs and pass the results to the customer, in his/her turn the customer is obliged to accept the results of these trials and pay for them. PMID:26442317

  9. [Activity and Future Perspective of Local Independent Clinical Trial Group (OGSG)].

    PubMed

    Tsujinaka, Toshimasa

    2016-04-01

    Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) was established in 2000 and has been conducting investigator initiated multi-institutional collaboration trials regarding the treatment of gastrointestinal cancer, especially using chemotherapeutic agents. Although organization of OGSG has been renovated to perform post-marketing clinical trials with high quality, OGSG is now facing severe financial crisis because of shortage of donation from pharmaceutical companies. Here, present problems and future perspectives are discussed. PMID:27220796

  10. Being PRO-ACTive: What can a Clinical Trial Database Reveal About ALS?

    PubMed

    Zach, Neta; Ennist, David L; Taylor, Albert A; Alon, Hagit; Sherman, Alexander; Kueffner, Robert; Walker, Jason; Sinani, Ervin; Katsovskiy, Igor; Cudkowicz, Merit; Leitner, Melanie L

    2015-04-01

    Advancing research and clinical care, and conducting successful and cost-effective clinical trials requires characterizing a given patient population. To gather a sufficiently large cohort of patients in rare diseases such as amyotrophic lateral sclerosis (ALS), we developed the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) platform. The PRO-ACT database currently consists of >8600 ALS patient records from 17 completed clinical trials, and more trials are being incorporated. The database was launched in an open-access mode in December 2012; since then, >400 researchers from >40 countries have requested the data. This review gives an overview on the research enabled by this resource, through several examples of research already carried out with the goal of improving patient care and understanding the disease. These examples include predicting ALS progression, the simulation of future ALS clinical trials, the verification of previously proposed predictive features, the discovery of novel predictors of ALS progression and survival, the newly identified stratification of patients based on their disease progression profiles, and the development of tools for better clinical trial recruitment and monitoring. Results from these approaches clearly demonstrate the value of large datasets for developing a better understanding of ALS natural history, prognostic factors, patient stratification, and more. The increasing use by the community suggests that further analyses of the PRO-ACT database will continue to reveal more information about this disease that has for so long defied our understanding. PMID:25613183

  11. Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives

    PubMed Central

    Katz, Michael G.; Fargnoli, Anthony S.; Kendle, Andrew P.; Hajjar, Roger J.; Bridges, Charles R.

    2016-01-01

    The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID:26801060

  12. Building clinical trial priorities at the University of Rwanda.

    PubMed

    Condo, Jeanine; Kateera, Brenda; Mutimura, Eugene; Birungi, Francine; Ndagijimana, Albert; Jansen, Stefan; Kamwesiga, Julius; Forrest, Jamie I; Mills, Edward J; Binagwaho, Agnes

    2014-01-01

    After the genocide in Rwanda, the country's healthcare system collapsed. Remarkable gains have since been made by the state to provide greater clinical service capacity and expand health policies that are grounded on locally relevant evidence. This commentary explores the challenges faced by Rwanda in building an infrastructure for clinical trials. Through local examples, we discuss how a clinical trial infrastructure can be constructed by (1) building educational capacity; (2) encouraging the testing of relevant interventions using appropriate and cost-effective designs; and, (3) promoting ethical and regulatory standards. The future is bright for clinical research in Rwanda and with a renewed appetite for locally generated evidence it is necessary that we discuss the challenges and opportunities in drawing up a clinical trials agenda. PMID:25429819

  13. Gene Therapy in Cardiac Surgery: Clinical Trials, Challenges, and Perspectives.

    PubMed

    Katz, Michael G; Fargnoli, Anthony S; Kendle, Andrew P; Hajjar, Roger J; Bridges, Charles R

    2016-06-01

    The concept of gene therapy was introduced in the 1970s after the development of recombinant DNA technology. Despite the initial great expectations, this field experienced early setbacks. Recent years have seen a revival of clinical programs of gene therapy in different fields of medicine. There are many promising targets for genetic therapy as an adjunct to cardiac surgery. The first positive long-term results were published for adenoviral administration of vascular endothelial growth factor with coronary artery bypass grafting. In this review we analyze the past, present, and future of gene therapy in cardiac surgery. The articles discussed were collected through PubMed and from author experience. The clinical trials referenced were found through the Wiley clinical trial database (http://www.wiley.com/legacy/wileychi/genmed/clinical/) as well as the National Institutes of Health clinical trial database (Clinicaltrials.gov). PMID:26801060

  14. Considerations in Applying the Results of Randomized Controlled Clinical Trials to the Care of Older Adults With Kidney Disease in the Clinical Setting: The SHARP Trial.

    PubMed

    Butler, Catherine R; O'Hare, Ann M

    2016-01-01

    The Study of Heart and Renal Protection (SHARP) found that treatment with ezetemibe and low-dose simvastatin reduced the incidence of major atherosclerotic events in patients with kidney disease. Due to the paucity of evidence-based interventions that lower cardiovascular morbidity in this high-risk population, the SHARP trial will likely have a large impact on clinical practice. However, applying the results of clinical trials conducted in select populations to the care of individual patients in real-world settings can be fraught with difficulty. This is especially true when caring for older adults with complex comorbidity and limited life expectancy. These patients are often excluded from clinical trials, frequently have competing health priorities, and may be less likely to benefit and more likely to be harmed by medications. We discuss key considerations in applying the results of the SHARP trial to the care of older adults with CKD in real-world clinical settings using guiding principles set forth by the American Geriatrics Society's Expert Panel on the Care of Older Adults with Multimorbidity. Using this schema, we emphasize the importance of evaluating trial results in the unique context of each patient's goals, values, priorities, and circumstances. PMID:26709060

  15. Wrongful termination: lessons from the Geron clinical trial.

    PubMed

    Scott, Christopher Thomas; Magnus, David

    2014-12-01

    Geron Corporation is a publically traded company that launched a phase I clinical trial of a human embryonic stem cell-based therapy for spinal cord injury. The company enrolled the first patient in October 2010 and stopped the trial 1 year later. The fifth patient had been enrolled but not transplanted when the company announced the trial's end. After discussions with clinical staff and family, an agreement was reached to add her to the cohort and proceed with the transplant. Two and half years later, the research is still waiting to restart. With this background in mind, we discuss the major ethical and social questions raised by the Geron case. We offer recommendations for institutional review boards and clinical sites as they deliberate approvals of early-phase trials in frontier medicine. PMID:25298371

  16. Pediatric obesity pharmacotherapy: current state of the field, review of the literature and clinical trial considerations.

    PubMed

    Kelly, A S; Fox, C K; Rudser, K D; Gross, A C; Ryder, J R

    2016-07-01

    Despite the increasing number of medications recently approved to treat obesity among adults, few agents have been formally evaluated in children or adolescents for this indication. Moreover, there is a paucity of guidance in the literature addressing best practices with regard to pediatric obesity pharmacotherapy clinical trial design, and only general recommendations have been offered by regulatory agencies on this topic. The purposes of this article are to (1) offer a background of the current state of the field of pediatric obesity medicine, (2) provide a brief review of the literature summarizing pediatric obesity pharmacotherapy clinical trials, and (3) highlight and discuss some of the unique aspects that should be considered when designing and conducting high-quality clinical trials evaluating the safety and efficacy of obesity medications in children and adolescents. Suggestions are offered in the areas of target population and eligibility criteria, clinical trial end-point selection, trial duration, implementation of lifestyle modification therapy and recruitment and retention of participants. Efforts should be made to design and conduct trials appropriately to ensure that high-quality evidence is generated on the safety and efficacy of various medications used to treat pediatric obesity. PMID:27113643

  17. Towards clinical trials of lie detection with fMRI.

    PubMed

    Hakun, J G; Ruparel, K; Seelig, D; Busch, E; Loughead, J W; Gur, R C; Langleben, D D

    2009-01-01

    Recent reports of successful fMRI-based discrimination between lie and truth in single subjects raised the interest of prospective users and a public concern about the potential scope of this technology. The increased scrutiny highlighted the lack of controlled "real life", i.e. prospective clinical trials of this technology that conform to the common standards of medical device development. The ethics of conducting such trials given the paucity of data on fMRI-based lie detection has also been questioned. To probe the potential issues of translating the laboratory research into practice, we conducted a case study in which we adapted the standard Guilty Knowledge Test (GKT), a well-established model of producing deception, to the common scenario of lying on a resume. The task consisted of questions about pertinent items on the subject's resume, three of which could be independently verified as truth (KNOWN) and three that could not be verified and were thus termed UNKNOWN. The subject had an incentive to lie on all UNKNOWN items, and on debriefing confirmed that he had done so. Data was preprocessed, masked with a priori regions of interest, thresholded, and qualitatively evaluated for consistency with the previously reported prefronto-parietal Lie > Truth pattern. Deceptive responses to two out of the three UNKNOWN items were associated with the predicted prefronto-parietal fMRI pattern. In the third UNKNOWN this pattern was absent, and instead, increased limbic (amygdala and hippocampus) response was observed. Based on published prefronto-parietal Lie response pattern, only the first two items could be categorized as Lie. If confirmed, this demonstration of amygdala and hippocampus activation in a Lie > Truth contrast illustrates the need to integrate the limbic system and its emotional and cognitive correlates into the existing model of deception. Our experiment suggests an approach to a naturalistic scenario and the research questions that need to be answered

  18. Management of Patient-Reported Outcome (PRO) Alerts in Clinical Trials: A Cross Sectional Survey.

    PubMed Central

    Kyte, Derek; Ives, Jonathan; Draper, Heather; Calvert, Melanie

    2016-01-01

    Background Assessment of patient-reported outcomes (PROs) provides valuable information to inform patient-centered care, but may also reveal ‘PRO alerts’: psychological distress or physical symptoms that may require an immediate response. Ad-hoc management of PRO alerts in clinical trials may result in suboptimal patient care or potentially bias trial results. To gain greater understanding of current practice in PRO alert management we conducted a national survey of personnel involved in clinical trials with a PRO endpoint. Methods and Findings We conducted a national cross-sectional survey of 767 UK-based research nurses, data managers/coordinators, trial managers and chief/principal investigators involved in clinical trials using PROs. Respondents were self-selected volunteers from a non-randomised sample of eligible individuals recruited via 55 UK Clinical Research Collaboration Registered Clinical Trials Units and 19 Comprehensive Local Research Networks. Questions centred on the proportion of trial personnel encountering alerts, how staff responded to PRO alerts and whether current guidance was deemed sufficient to support research personnel. We undertook descriptive analyses of the quantitative data and directed thematic analysis of free-text comments. 20% of research nurses did not view completed PRO questionnaires and were not in a position to discover alerts, 39–50% of the remaining respondent group participants reported encountering PRO alerts. Of these, 83% of research nurses and 54% of data managers/trial coordinators reported taking action to assist the trial participant, but less than half were able to record the intervention in the trial documentation. Research personnel reported current PRO alert guidance/training was insufficient. Conclusions Research personnel are intermittently exposed to PRO alerts. Some intervene to help trial participants, but are not able to record this intervention in the trial documentation, risking co

  19. Establishing a Canadian national clinical trials network for kidney disease: proceedings of a planning workshop.

    PubMed

    Rigatto, Claudio; Walsh, Michael; Zalunardo, Nadia; Clase, Catherine M; Manns, Braden J; Madore, François; Samuel, Susan M; Morgan, Catherine J; Wolfs, Wim; Suri, Rita S

    2015-01-01

    Knowledge generation through randomized controlled trials (RCTs) is critical to advance the medical evidence base, inform decision-making, and improve care and outcomes. Unfortunately, nephrology has typically lagged behind other medical specialties in this regard. The establishment of formal clinical trial networks can facilitate the successful conduct of RCTs and has significantly increased the number of RCTs performed worldwide in other medical specialties. No such formal network of nephrology trialists exists in Canada. On April 24, 2014, the Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) Clinical Trials Committee held a stakeholder engagement meeting to address this gap and improve the nephrology clinical trial landscape in Canada. The meeting was held in Vancouver in association with the 2014 Canadian Society of Nephrology Annual General Meeting and was co-sponsored by the Kidney Foundation of Canada and CANN-NET. Attendees included nephrologists from university- and non-university-affiliated nephrology practices, administrators, and representatives from the Kidney Foundation of Canada. Through structured presentations and facilitated group discussions, the group explored the extent to which nephrology trials are currently happening in Canada, barriers to leading or participating in larger investigator-initiated trials, and strategies to improve clinical trial output in nephrology in Canada. The themes and action items arising from this meeting are discussed. PMID:26583070

  20. 77 FR 74670 - Draft Guidance for Industry on Enrichment Strategies for Clinical Trials to Support Approval of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... potential clinical trial designs, and discusses potential regulatory considerations when using enrichment... discusses general clinical trial design considerations, provides examples of potential clinical trial..., will represent the Agency's current thinking on clinical trial designs employing enrichment...

  1. Case-based reasoning using electronic health records efficiently identifies eligible patients for clinical trials

    PubMed Central

    Miotto, Riccardo

    2015-01-01

    Objective To develop a cost-effective, case-based reasoning framework for clinical research eligibility screening by only reusing the electronic health records (EHRs) of minimal enrolled participants to represent the target patient for each trial under consideration. Materials and Methods The EHR data—specifically diagnosis, medications, laboratory results, and clinical notes—of known clinical trial participants were aggregated to profile the “target patient” for a trial, which was used to discover new eligible patients for that trial. The EHR data of unseen patients were matched to this “target patient” to determine their relevance to the trial; the higher the relevance, the more likely the patient was eligible. Relevance scores were a weighted linear combination of cosine similarities computed over individual EHR data types. For evaluation, we identified 262 participants of 13 diversified clinical trials conducted at Columbia University as our gold standard. We ran a 2-fold cross validation with half of the participants used for training and the other half used for testing along with other 30 000 patients selected at random from our clinical database. We performed binary classification and ranking experiments. Results The overall area under the ROC curve for classification was 0.95, enabling the highlight of eligible patients with good precision. Ranking showed satisfactory results especially at the top of the recommended list, with each trial having at least one eligible patient in the top five positions. Conclusions This relevance-based method can potentially be used to identify eligible patients for clinical trials by processing patient EHR data alone without parsing free-text eligibility criteria, and shows promise of efficient “case-based reasoning” modeled only on minimal trial participants. PMID:25769682

  2. A Model of Placebo Response in Antidepressant Clinical Trials

    PubMed Central

    Rutherford, Bret R; Roose, Steven P.

    2012-01-01

    Placebo response in clinical trials of antidepressant medications is substantial and increasing. High placebo response rates hamper efforts to detect signals of efficacy for new antidepressant medications, contributing to more failed trials and delaying the delivery of new treatments to market. Media reports seize upon increasing placebo response and modest advantages for active drugs as reasons to question the value of antidepressant medication, which may further stigmatize treatments for depression and dissuade patients from accessing mental health care. Conversely, enhancing the factors responsible for placebo response may represent a strategy for improving available treatments for Major Depressive Disorder. A conceptual framework describing the causes of placebo response is needed in order to develop strategies for minimizing placebo response in clinical trials, maximizing placebo response in clinical practice, and talking with depressed patients about the risks and benefits of antidepressant medications. This review examines contributors to placebo response in antidepressant clinical trials and proposes an explanatory model. Research aimed at reducing placebo response should focus on limiting patient expectancy and the intensity of therapeutic contact in antidepressant clinical trials, while the optimal strategy in clinical practice may be to combine active medication with a presentation and level of therapeutic contact that enhances treatment response. PMID:23318413

  3. Imaging and Data Acquisition in Clinical Trials for Radiation Therapy.

    PubMed

    FitzGerald, Thomas J; Bishop-Jodoin, Maryann; Followill, David S; Galvin, James; Knopp, Michael V; Michalski, Jeff M; Rosen, Mark A; Bradley, Jeffrey D; Shankar, Lalitha K; Laurie, Fran; Cicchetti, M Giulia; Moni, Janaki; Coleman, C Norman; Deye, James A; Capala, Jacek; Vikram, Bhadrasain

    2016-02-01

    Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials. PMID:26853346

  4. The Impacts of Inclusion in Clinical Trials on Outcomes among Patients with Metastatic Breast Cancer (MBC)

    PubMed Central

    Lee, Ji Yun; Lim, Sung Hee; Lee, Min-Young; Kim, Hae Su; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    Background Metastatic breast cancer (MBC) remains a devastating and incurable disease. Over the past decade, the implementation of clinical trials both with and without molecular targeted therapeutics has impacted the daily clinical treatment of patients with MBC. In this study, we determine whether including MBC patients in clinical trials affects clinical outcomes. Methods We retrospectively reviewed data for a total of 863 patients diagnosed with initial or recurrent (after receiving adjuvant systemic treatments following surgery) metastatic disease between January 2000 and December 2013. Data were obtained from the breast cancer database of Samsung Medical Center. Results Among the 806 patients selected for inclusion, 188 (23%) had participated in clinical trials. A total of 185 clinical trials were conducted from 2000 to 2014. When compared with earlier periods (n = 10 for 2000–2004), clinical trial enrollment significantly increased over time (n = 103 for 2005–2009, P = 0.024; n = 110 for 2010–2014, P = 0.046). Multivariate analyses revealed that biologic subtype, distant recurrence free interval (DRFI), and clinical trial enrollment were independent predictors of overall survival. Patients who participated in clinical trials showed improved survival, with a hazard ratio of 0.75 (95% CI, 0.59–0.95), which was associated with a 25% reduction in the risk of death. However, subgroup analysis showed that this improved survival benefit was not maintained in patients with triple negative breast cancer (TNBC). Conclusions Although not conclusive, we could speculate that there were differences in the use of newer agents or regimens over time, and these differences appear to be associated with improved survival. PMID:26901062

  5. Design of clinical trials for therapeutic cancer vaccines development.

    PubMed

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate. PMID:19835869

  6. Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial

    PubMed Central

    Jacobsen, Paul B.; Wells, Kristen J.; Meade, Cathy D.; Quinn, Gwendolyn P.; Lee, Ji-Hyun; Fulp, William J.; Gray, Jhanelle E.; Baz, Rachid C.; Springett, Gregory M.; Levine, Richard M.; Markham, Merry-Jennifer; Schreiber, Fred J.; Cartwright, Thomas H.; Burke, James M.; Siegel, Robert D.; Malafa, Mokenge P.; Sullivan, Daniel

    2012-01-01

    Purpose The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. Patients and Methods A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. Results Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. Conclusion A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials. PMID:22614993

  7. An Ongoing Randomized Clinical Trial in Dysphagia

    ERIC Educational Resources Information Center

    Robbins, JoAnne; Hind, Jackie; Logemann, Jerilyn

    2004-01-01

    Most of us who have clinical practices firmly contend that the treatments we provide cause beneficial changes in the lives of our patients. Indeed, our clinical experience engenders strong convictions to the point of believing that withholding treatment creates ethical violations. Intellectually, however, we must recognize that the value of…

  8. What Leads Indians to Participate in Clinical Trials? A Meta-Analysis of Qualitative Studies

    PubMed Central

    Shah, Jatin Y.; Phadtare, Amruta; Rajgor, Dimple; Vaghasia, Meenakshi; Pradhan, Shreyasee; Zelko, Hilary; Pietrobon, Ricardo

    2010-01-01

    Background With the globalization of clinical trials, large developing nations have substantially increased their participation in multi-site studies. This participation has raised ethical concerns, among them the fear that local customs, habits and culture are not respected while asking potential participants to take part in study. This knowledge gap is particularly noticeable among Indian subjects, since despite the large number of participants, little is known regarding what factors affect their willingness to participate in clinical trials. Methods We conducted a meta-analysis of all studies evaluating the factors and barriers, from the perspective of potential Indian participants, contributing to their participation in clinical trials. We searched both international as well as Indian-specific bibliographic databases, including Pubmed, Cochrane, Openjgate, MedInd, Scirus and Medknow, also performing hand searches and communicating with authors to obtain additional references. We enrolled studies dealing exclusively with the participation of Indians in clinical trials. Data extraction was conducted by three researchers, with disagreement being resolved by consensus. Results Six qualitative studies and one survey were found evaluating the main themes affecting the participation of Indian subjects. Themes included Personal health benefits, Altruism, Trust in physicians, Source of extra income, Detailed knowledge, Methods for motivating participants as factors favoring, while Mistrust on trial organizations, Concerns about efficacy and safety of trials, Psychological reasons, Trial burden, Loss of confidentiality, Dependency issues, Language as the barriers. Conclusion We identified factors that facilitated and barriers that have negative implications on trial participation decisions in Indian subjects. Due consideration and weightage should be assigned to these factors while planning future trials in India. PMID:20505754

  9. The automation of clinical trial serious adverse event reporting workflow

    PubMed Central

    London, Jack W; Smalley, Karl J; Conner, Kyle; Smith, J Bruce

    2011-01-01

    Background The reporting of serious adverse events (SAEs) is a requirement when conducting a clinical trial involving human subjects, necessary for the protection of the participants. The reporting process is a multi-step procedure, involving a number of individuals from initiation to final review, and must be completed in a timely fashion. Purpose The purpose of this project was to automate the adverse event reporting process, replacing paper-based processes with computer-based processes, so that personnel effort and time required for serious adverse event reporting was reduced, and the monitoring of reporting performance and adverse event characteristics was facilitated. Methods Use case analysis was employed to understand the reporting workflow and generate software requirements. The automation of the workflow was then implemented, employing computer databases, web-based forms, electronic signatures, and email communication. Results In the initial year (2007) of full deployment, 588 SAE reports were processed by the automated system, eSAEy™. The median time from initiation to Principal Investigator electronic signature was less than 2 days (mean 7 ± 0.7 days). This was a significant reduction from the prior paper-based system, which had a median time for signature of 24 days (mean of 45 ± 5.7 days). With eSAEy™, reports on adverse event characteristics (type, grade, etc.) were easily obtained and had consistent values based on standard terminologies. Limitation The automated system described was designed specifically for the work flow at Thomas Jefferson University. While the methodology for system design, and the system requirements derived from common clinical trials adverse reporting procedures are applicable in general, specific work flow details may not relevant at other institutions. Conclusion The system facilitated analysis of individual investigator reporting performance, as well as the aggregation and analysis of the nature of reported adverse

  10. Implementation of the Exception from Informed Consent Regulations in a Large Multicenter Emergency Clinical Trials Network; the RAMPART Experience

    PubMed Central

    Silbergleit, Robert; Biros, Michelle H.; Harney, Deneil; Dickert, Neal; Baren, Jill

    2012-01-01

    Clinical trials investigating therapies for acutely and critically ill and injured patients in the earliest phases of treatment often can only be performed under regulations allowing for exception from informed consent (EFIC) for emergency research. Implementation of these regulations in multicenter clinical trials involves special challenges and opportunities. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), the first EFIC trial conducted by the Neurological Emergencies Treatment Trials (NETT) network, combined centralized resources and coordination with retention of local control and flexibility to facilitate compliance with the EFIC regulations. Specific methods used by the NETT included common tools for community consultation and public disclosure, sharing of experiences and knowledge, and reporting of aggregate results. Tracking of community consultation and public disclosure activities and feedback facilitates empirical research on EFIC methods in the network and supports quality improvements for future NETT trials. The NETT model used in RAMPART demonstrates how EFIC may be effectively performed in established clinical trial networks. PMID:22506949

  11. Clinical Trial Design Issues in Systemic Sclerosis: an Update.

    PubMed

    Gordon, Jessica K; Domsic, Robyn T

    2016-06-01

    Systemic sclerosis (scleroderma, SSc) is a multisystem disease characterized by vasculopathy, autoimmunity, and fibrosis. SSc has the highest disease-related mortality rate among the rheumatologic illnesses. In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations. It can be difficult to discern disease activity from damage. SSc is highly heterogeneous, with multiple different phenotypes, and predicting who will have progressive disease is not currently well understood. Biomarkers are in early stages of development and do not represent surrogate outcomes at this time. Given that SSc is uncommon, studies of similar disease aspects or populations can lead to competition for patients. This review will focus on current issues in SSc clinical trial design. PMID:27146381

  12. Reporting, access, and transparency: better infrastructure of clinical trials.

    PubMed

    Antonelli, Massimo; Mercurio, Giovanna

    2009-01-01

    Open access to information in medical science and adequate reporting of clinical trials may allow investigators and editors to recognize bias in study designs and avoid unnecessary duplication of efforts. Unfortunately, most of clinical trials are very expensive and are often supported by industries that may have financial reasons to hide or partially disclose results. However, investigators and editors have a greater interest in publishing results that can immediately change clinical practice rather than negative results, thus contributing to facilitate publication biases. Several years ago, legislation in several countries mandated the registration of clinical trials as an effective means of promoting information access and full transparency in medical research. However, comprehensive registers have not been adequately supported by law, particularly in Europe, where legislation has ironically contributed to fragmented research, and dampened its competitiveness and productivity. In this context, appropriate strategies help to protect the independence of academic research and ensure full transparency in medical science. PMID:19104221

  13. Clinical trials transparency and the Trial and Experimental Studies Transparency (TEST) act.

    PubMed

    Logvinov, Ilana

    2014-03-01

    Clinical trial research is the cornerstone for successful advancement of medicine that provides hope for millions of people in the future. Full transparency in clinical trials may allow independent investigators to evaluate study designs, perform additional analysis of data, and potentially eliminate duplicate studies. Current regulatory system and publishers rely on investigators and pharmaceutical industries for complete and accurate reporting of results from completed clinical trials. Legislation seems to be the only way to enforce mandatory disclosure of results. The Trial and Experimental Studies Transparency (TEST) Act of 2012 was introduced to the legislators in the United States to promote greater transparency in research industry. Public safety and advancement of science are the driving forces for the proposed policy change. The TEST Act may benefit the society and researchers; however, there are major concerns with participants' privacy and intellectual property protection. PMID:24440100

  14. In Silico Simulation of a Clinical Trial Concerning Tumour Response to Radiotherapy

    SciTech Connect

    Dionysiou, Dimitra D.; Stamatakos, Georgios S.; Athanaileas, Theodoras E.; Merrychtas, Andreas; Kaklamani, Dimitra; Varvarigou, Theodora; Uzunoglu, Nikolaos

    2008-11-06

    The aim of this paper is to demonstrate how multilevel tumour growth and response to therapeutic treatment models can be used in order to simulate clinical trials, with the long-term intention of both better designing clinical studies and understanding their outcome based on basic biological science. For this purpose, an already developed computer simulation model of glioblastoma multiforme response to radiotherapy has been used and a clinical study concerning glioblastoma multiforme response to radiotherapy has been simulated. In order to facilitate the simulation of such virtual trials, a toolkit enabling the user-friendly execution of the simulations on grid infrastructures has been designed and developed. The results of the conducted virtual trial are in agreement with the outcome of the real clinical study.

  15. Clinical Trials of Adult Stem Cell Therapy in Patients with Ischemic Stroke

    PubMed Central

    2016-01-01

    Stem cell therapy is considered a potential regenerative strategy for patients with neurologic deficits. Studies involving animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. With current advances in the understanding regarding the effects of introducing stem cells and their mechanisms of action, several clinical trials of stem cell therapy have been conducted in patients with stroke since 2005, including studies using mesenchymal stem cells, bone marrow mononuclear cells, and neural stem/progenitor cells. In addition, several clinical trials of the use of adult stem cells to treat ischemic stroke are ongoing. This review presents the status of our understanding of adult stem cells and results from clinical trials, and introduces ongoing clinical studies of adult stem cell therapy in the field of stroke. PMID:26610894

  16. Developments in clinical trials: a Pharma Matters report.

    PubMed

    Arjona, A; Nuskey, B; Rabasseda, X; Arias, E

    2014-08-01

    As the pharmaceutical industry strives to meet the ever-increasing complexity of drug development, new technology in clinical trials has become a beacon of hope. With big data comes the promise of accelerated patient recruitment, real-time monitoring of clinical trials, bioinformatics empowerment of quicker phase progression, and the overwhelming benefits of precision medicine for select trials. Risk-based monitoring stands to benefit as well. With a strengthening focus on centralized data by the FDA and industry's transformative initiative, TransCelerate, a new era in trial risk mitigation has begun. The traditional method of intensive on-site monitoring is becoming a thing of the past as statistical, real-time analysis of site and trial-wide data provides the means to monitor with greater efficiency and effectiveness from afar. However, when it comes to big data, there are challenges that lie ahead. Patient privacy, commercial investment protection, technology woes and data variability are all limitations to be met with considerable thought. At the Annual Meeting of the American Academy of Dermatology this year, clinical trials on psoriasis, atopic dermatitis and other skin diseases were discussed in detail. This review of clinical research reports on novel therapies for psoriasis and atopic dermatitis reveals the impact of these diseases and the drug candidates that have been successful in phase II and III studies. Data-focused highlights of novel dermatological trials, as well as real-life big data approaches and an insight on the new methodology of risk-based monitoring, are all discussed in this edition of Developments in Clinical Trials. PMID:25187907

  17. Teacher-Conducted Trial-Based Functional Analyses as the Basis for Intervention

    ERIC Educational Resources Information Center

    Bloom, Sarah E.; Lambert, Joseph M.; Dayton, Elizabeth; Samaha, Andrew L.

    2013-01-01

    Previous studies have focused on whether a trial-based functional analysis (FA) yields the same outcomes as more traditional FAs, and whether interventions based on trial-based FAs can reduce socially maintained problem behavior. We included a full range of behavior functions and taught 3 teachers to conduct a trial-based FA with 3 boys with…

  18. Drug-Resistant Tuberculosis Clinical Trials: Proposed Core Research Definitions in Adults

    PubMed Central

    Furin, J.; Alirol, E.; Allen, E.; Fielding, K.; Merle, C.; Abubakar, I.; Andersen, J.; Davies, G.; Dheda, K.; Diacon, A.; Dooley, K.E.; Dravnice, G.; Eisenach, K.; Everitt, D.; Ferstenberg, D.; Goolam-Mahomed, A.; Grobusch, M.P.; Gupta, R.; Harausz, E.; Harrington, M.; Horsburgh, R.; Lienhardt, C.; McNeeley, D.; Mitnick, C.D.; Nachman, S.; Nahid, P.; Nunn, A.J.; Phillips, P.; Rodriguez, C.; Shah, S.; Wells, C.; Thomas-Nyang’wa, B; du Cros, P.

    2016-01-01

    Structured Summary Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades there are new drugs for treatment of this disease. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximize policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. In order to elaborate these definitions, a search of clinical trials registries, published manuscripts, and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in MDR-TB clinical trials. PMID:27046707

  19. Drug-resistant tuberculosis clinical trials: proposed core research definitions in adults.

    PubMed

    Furin, J; Alirol, E; Allen, E; Fielding, K; Merle, C; Abubakar, I; Andersen, J; Davies, G; Dheda, K; Diacon, A; Dooley, K E; Dravnice, G; Eisenach, K; Everitt, D; Ferstenberg, D; Goolam-Mahomed, A; Grobusch, M P; Gupta, R; Harausz, E; Harrington, M; Horsburgh, C R; Lienhardt, C; McNeeley, D; Mitnick, C D; Nachman, S; Nahid, P; Nunn, A J; Phillips, P; Rodriguez, C; Shah, S; Wells, C; Thomas-Nyang'wa, B; du Cros, P

    2016-03-01

    Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades, new drugs for the treatment of this disease have been developed. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximise policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. To elaborate these definitions, a search of clinical trials registries, published manuscripts and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in clinical trials on multidrug-resistant TB. PMID:27046707

  20. Recommendations for Obesity Clinical Trials in Cancer Survivors: American Society of Clinical Oncology Statement.

    PubMed

    Ligibel, Jennifer A; Alfano, Catherine M; Hershman, Dawn; Ballard, Rachel M; Bruinooge, Suanna S; Courneya, Kerry S; Daniels, Elvan C; Demark-Wahnefried, Wendy; Frank, Elizabeth S; Goodwin, Pamela J; Irwin, Melinda L; Levit, Laura A; McCaskill-Stevens, Worta; Minasian, Lori M; O'Rourke, Mark A; Pierce, John P; Stein, Kevin D; Thomson, Cynthia A; Hudis, Clifford A

    2015-11-20

    Observational evidence has established a relationship between obesity and cancer risk and outcomes. Interventional studies have demonstrated the feasibility and benefits of lifestyle change after cancer diagnosis, and guidelines recommend weight management and regular physical activity in cancer survivors; however, lifestyle interventions are not a routine part of cancer care. The ASCO Research Summit on Advancing Obesity Clinical Trials in Cancer Survivors sought to identify the knowledge gaps that clinical trials addressing energy balance factors in cancer survivors have not answered and to develop a roadmap for the design and implementation of studies with the potential to generate data that could lead to the evidence-based incorporation of weight management and physical activity programs into standard oncology practice. Recommendations highlight the need for large-scale trials evaluating the impact of energy balance interventions on cancer outcomes, as well as the concurrent conduct of studies focused on dissemination and implementation of interventions in diverse populations of cancer survivors, including answering critical questions about the degree of benefit in key subgroups of survivors. Other considerations include the importance of incorporating economic metrics into energy balance intervention trials, the need to establish intermediate biomarkers, and the importance of integrating traditional and nontraditional funding sources. Establishing lifestyle change after cancer diagnosis as a routine part of cancer care will require a multipronged effort to overcome barriers related to study development, funding, and stakeholder engagement. Given the prevalence of obesity and inactivity in cancer survivors in the United States and elsewhere, energy balance interventions hold the potential to reduce cancer morbidity and mortality in millions of patients, and it is essential that we move forward in determining their role in cancer care with the same care and

  1. Volunteering for Clinical Trials Can Help Improve Health Care for Everyone

    MedlinePlus

    ... Trials Volunteering for Clinical Trials Can Help Improve Health Care for Everyone Past Issues / Fall 2010 Table of ... Research / Volunteering for Clinical Trials Can Help Improve Health Care for Everyone Fall 2010 Issue: Volume 5 Number ...

  2. Designing clinical trials in trauma surgery

    PubMed Central

    Perry, D. C.; Griffin, X. L.; Parsons, N.; Costa, M. L.

    2014-01-01

    The surgical community is plagued with a reputation for both failing to engage and to deliver on clinical research. This is in part due to the absence of a strong research culture, however it is also due to a multitude of barriers encountered in clinical research; particularly those involving surgical interventions. ‘Trauma’ amplifies these barriers, owing to the unplanned nature of care, unpredictable work patterns, the emergent nature of treatment and complexities in the consent process. This review discusses the barriers to clinical research in surgery, with a particular emphasis on trauma. It considers how barriers may be overcome, with the aim to facilitate future successful clinical research. Cite this article: Bone Joint Res 2014;3:123–9. PMID:24764547

  3. Recommendations for Soluble Biomarker Assessments in Osteoarthritis Clinical Trials

    PubMed Central

    Kraus, Virginia Byers; Blanco, Francisco J; Englund, Martin; Henrotin, Yves; Lohmander, L Stefan; Losina, Elena; Önnerfjord, Patrik; Persiani, Stefano

    2015-01-01

    Objective To describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. Methods The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from 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. Results This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at 5 stages, including preclinical development and phase I to phase IV trials. Conclusions Biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety 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 treatment at a time more amenable to disease modification. PMID:25952342

  4. The protection of patients' rights in clinical trials.

    PubMed

    Czarkowski, Marek

    2006-01-01

    The Helsinki Declaration is a very important document regarding the protection of patients' rights in clinical trials and one of the fundamental sources of operational principles for every ethics committee. Although they have been updated, the international guidelines for ethics committees continually fail to address certain issues pertaining to the protection of patients' rights in clinical trials. These issues include, most significantly, the method of electing ethics committees (a free, secret ballot should be preferred to direct appointment), the avoidance of conflict of interest during the election of ethics committee members, and the necessary insurance coverage for the participants of clinical trials. Polish law should, on the other hand, be developed in such way as to not limit the effectiveness of ethics committees in protecting patients' rights in clinical trials. The ideal solution would be to draft a uniform law concerning not only clinical trials, but all medical experiments. The opinions of experts who have been reviewing medical research projects for several years may prove to be especially valuable in this setting. PMID:16501654

  5. Patient and physician attitudes regarding clinical trials in neurofibromatosis 1.

    PubMed

    McQueen, Mary; MacCollin, Mia; Gusella, James; Plotkin, Scott R

    2008-12-01

    Neurofibromatosis 1 (NF1) is a multisystem genetic disorder that primarily affects the skin (freckling and café-au-lait macules), nervous system (neurofibromas, optic gliomas, and learning disabilities), and skeletal system (pseudoarthroses). The interest in pharmacological intervention for patients with NF1 has grown in recent years. However, little is known about the attitudes and priorities of patients, families, and physicians regarding participation in clinical trials. We surveyed 74 adult patients or parents of patients with NF1 and 69 care providers participating in a neurofibromatosis clinic to assess their willingness to participate in clinical trials and their opinions about which conditions they thought were most important to treat. Both patients and care providers are willing to participate in clinical trials for NF1 and both groups rate malignant peripheral nerve sheath tumors as the most urgent for new treatments. There are concordant views among patients and physicians concerning clinical trials for NF1, and patients do not dismiss participation in placebo-controlled trials. Neuroscience nurses are poised to facilitate the research process from conception through implementation as they take the viewpoints of our study populations into consideration. PMID:19170300

  6. Multicenter clinical trial using next-generation Internet technology

    NASA Astrophysics Data System (ADS)

    Ingeholm, Mary-Lou; Levine, Betty A.; Eichler, Florian; Tu, Huacheng; Jimenez-Sanchez, Gerardo; Moser, Hugo

    2001-08-01

    The capacity to evaluate therapies in a multi-center clinical trial for a rare disease like X-linked adrenoleukodystrophy (ALD) can be improved by establishing a network for transmitting magnetic resonance imaging (MRI) data using current Internet and Next Generation Internet (NGI) technologies. A Digital Imaging and Communications in Medicine (DICOM) 3.0 application has been installed; it functions as a storage service class provider (SCP), query/retrieve SCP and central database. Sites with query/retrieve (Q/R) service class user (SCU) applications have access to the images. Using the DICOM Q/R SCU application, timing studies of image retrieval for a standard Internet connection and an NGI connection have been conducted. Standard Internet results indicate that performance is affected by bandwidth limitation and is constrained by network traffic, inhibiting the standard Internet as a useful tool for real-time therapy evaluation. NGI results indicate a higher and more consistent data throughput. The increased transmission speed along with the promise of improved quality of service offered by the NGI connection allows for physicians to discuss the images, correlate them with other disease findings, measure disease severity, and request additional MRI studies in real-time permitting a more efficient clinical evaluation strategy. The elimination of variability of transmission speed is no less significant, allowing the physicians to reserve the time needed for such consultations.

  7. South Asian participation in clinical trials: the views of lay people and health professionals.

    PubMed

    Hussain-Gambles, Mah; Atkin, Karl; Leese, Brenda

    2006-07-01

    There is little UK-based empirical research on South Asian participation in clinical trials. The predominantly US literature rarely engages with mainstream debates about ethnicity, diversity and difference. This study was prompted by a lack of knowledge about how South Asian people perceive trial involvement and the risks and benefits involved. Face to face interviews were conducted with 25 health professionals (consultants, GPs, nursing staff, academics, non-medically trained trial co-ordinators, LREC and MREC members) and 60 South Asian lay people (20 Indians, 20 Pakistanis and 20 Bangladeshis) who had not taken part in a trial. The study took place in the Leeds and Bradford areas of England. It was found that lay South Asian attitudes towards clinical trial participation focused on similarities rather than differences with the general UK population, suggesting that the relevance of ethnicity should be kept in perspective. There was no evidence of antipathy amongst South Asians to the concept of clinical trials, and awareness was a correlate of social class, education and younger age. Lay factors that might affect South Asian participation in clinical trials included: age; language, social class; feeling of not belonging/mistrust; culture and religion. Approachable patients (of the same gender, social class and fluent in English) tended to be 'cherry picked' to clinical trials. This practice was justified because of a lack of time, resources and inadequate support. South Asian patients might be systematically excluded from trials due to the increased cost and time associated with their inclusion, particularly in relation to the language barrier. Under-representation might also be due to passive exclusion associated with cultural stereotypes. The paper concludes by applying the theoretical framework of institutional racism as a means of making sense of policy and practice. At the same time, caution is advocated against using ethnicity as the only form of

  8. Clinical trials in palliative care: an ethical evaluation.

    PubMed

    Janssens, R; Gordijn, B

    2000-08-01

    On first sight, clinical trials do not seem to fit well within the concept of palliative care. In palliative care, the needs and wishes of the patient set the norm while participation in experimental trials is potentially harmful for the patient. The dilemma seems hard to solve as optimal care for the dying and improvement of treatment for future patients are both imperative. Yet, the one seems to exclude the other. However, on closer examination it becomes less evident that clinical trials in palliative care confront us with an unsolvable dilemma. Some patients' lives may gain meaning through participation in trials out of solidarity with future patients. In order to clarify this, the notions of authenticity and hope can be illuminative. PMID:10900367

  9. The FDA and designing clinical trials for chronic cutaneous ulcers.

    PubMed

    Maderal, Andrea D; Vivas, Alejandra C; Eaglstein, William H; Kirsner, Robert S

    2012-12-01

    Treatment of chronic wounds can present a challenge, with many patients remaining refractory to available advanced therapies. As such, there is a strong need for the development of new products. Unfortunately, despite this demand, few new wound-related drugs have been approved over the past decade. This is in part due to unsuccessful clinical trials and subsequent lack of Food and Drug Administration (FDA) approval. In this article, we discuss the FDA approval process, how it relates to chronic wound trials, common issues that arise, and how best to manage them. Additionally, problems encountered specific to diabetic foot ulcers (DFU) and venous leg ulcers (VLU) are addressed. Careful construction of a clinical trial is necessary in order to achieve the best possible efficacy outcomes and thereby, gain FDA approval. How to design an optimal trial is outlined. PMID:23063664

  10. A Randomized Clinical Trial of Alternative Stress Management Interventions in Persons with HIV Infection

    ERIC Educational Resources Information Center

    McCain, Nancy L.; Gray, D. Patricia; Elswick, R. K., Jr.; Robins, Jolynne W.; Tuck, Inez; Walter, Jeanne M.; Rausch, Sarah M.; Ketchum, Jessica McKinney

    2008-01-01

    Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of…

  11. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

  12. When Ethics Constrains Clinical Research: Trial Design of Control Arms in “Greater Than Minimal Risk” Pediatric Trials

    PubMed Central

    de Melo-Martín, Inmaculada; Sondhi, Dolan

    2011-01-01

    Abstract For more than three decades clinical research in the United States has been explicitly guided by the idea that ethical considerations must be central to research design and practice. In spite of the centrality of this idea, attempting to balance the sometimes conflicting values of advancing scientific knowledge and protecting human subjects continues to pose challenges. Possible conflicts between the standards of scientific research and those of ethics are particularly salient in relation to trial design. Specifically, the choice of a control arm is an aspect of trial design in which ethical and scientific issues are deeply entwined. Although ethical quandaries related to the choice of control arms may arise when conducting any type of clinical trials, they are conspicuous in early phase gene transfer trials that involve highly novel approaches and surgical procedures and have children as the research subjects. Because of children's and their parents' vulnerabilities, in trials that investigate therapies for fatal, rare diseases affecting minors, the scientific and ethical concerns related to choosing appropriate controls are particularly significant. In this paper we use direct gene transfer to the central nervous system to treat late infantile neuronal ceroid lipofuscinosis to illustrate some of these ethical issues and explore possible solutions to real and apparent conflicts between scientific and ethical considerations. PMID:21446781

  13. Practicing Research Ethics: Private-Sector Physicians & Pharmaceutical Clinical Trials

    PubMed Central

    2008-01-01

    This paper focuses on constructions of research ethics by primary care physicians in the USA as they engage in contract research for the pharmaceutical industry. Drawing first upon historical studies of physicians as investigators and then upon 12 months of qualitative fieldwork in the South Western US, this paper analyzes the shifting, contextualized ethics that shape physicians’ relationships with patients/subjects and pharmaceutical companies. Just as physicians followed professional codes of ethics prior to the codification of acceptable research conduct in the 1980s, physicians today continue to develop tacit systems of research ethics. This paper argues that private-sector physicians primarily conceptualize their ethical conduct in relation to the pharmaceutical companies hiring them, not to human subjects they enroll in clinical trials. This is not to say that these physicians do not follow the formal U.S. regulation to protect human subjects, but rather that their financial relationships with the pharmaceutical industry have a greater influence on their identities as researchers and on their constructions of their ethical responsibilities. PMID:18353515

  14. Clinical Trials for Rare Lung Diseases: Lessons from Lymphangioleiomyomatosis

    PubMed Central

    McCormack, Francis X.

    2010-01-01

    Abstract Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive neoplasm that causes gradual but often life-threatening cystic destruction of the lung. Advances in our understanding of the molecular and cellular pathogenesis have LAM have identified a number of promising targets for testing in therapeutic trials. However, the design, prioritization, organization, and implementation of clinical trials in rare lung diseases poses unique challenges, including geographically disperse populations, sluggish enrollment, off- label drug use, burdensome regulations, and paucity of validated surrogate endpoints. PMID:20235889

  15. Progesterone neuroprotection: The background of clinical trial failure.

    PubMed

    Schumacher, Michael; Denier, Christian; Oudinet, Jean-Paul; Adams, David; Guennoun, Rachida

    2016-06-01

    Since the first pioneering studies in the 1990s, a large number of experimental animal studies have demonstrated the neuroprotective efficacy of progesterone for brain disorders, including traumatic brain injury (TBI). In addition, this steroid has major assets: it easily crosses the blood-brain-barrier, rapidly diffuses throughout the brain and exerts multiple beneficial effects by acting on many molecular and cellular targets. Moreover, progesterone therapies are well tolerated. Notably, increased brain levels of progesterone are part of endogenous neuroprotective responses to injury. The hormone thus emerged as a particularly promising protective candidate for TBI and stroke patients. The positive outcomes of small Phase 2 trials aimed at testing the safety and potential protective efficacy of progesterone in TBI patients then provided support and guidance for two large, multicenter, randomized and placebo-controlled Phase 3 trials, with more than 2000 TBI patients enrolled. The negative outcomes of both trials, named ProTECT III and SyNAPSE, came as a big disappointment. If these trials were successful, progesterone would have become the first efficient neuroprotective drug for brain-injured patients. Thus, progesterone has joined the numerous neuroprotective candidates that have failed in clinical trials. The aim of this review is a reappraisal of the preclinical animal studies, which provided the proof of concept for the clinical trials, and we critically examine the design of the clinical studies. We made efforts to present a balanced view of the strengths and limitations of the translational studies and of some serious issues with the clinical trials. We place particular emphasis on the translational value of animal studies and the relevance of TBI biomarkers. The probability of failure of ProTECT III and SyNAPSE was very high, and we present them within the broader context of other unsuccessful trials. PMID:26598278

  16. Immunological monitoring of anticancer vaccines in clinical trials

    PubMed Central

    Ogi, Chizuru; Aruga, Atsushi

    2013-01-01

    Therapeutic anticancer vaccines operate by eliciting or enhancing an immune response that specifically targets tumor-associated antigens. Although intense efforts have been made for developing clinically useful anticancer vaccines, only a few Phase III clinical trials testing this immunotherapeutic strategy have achieved their primary endpoint. Here, we report the results of a retrospective research aimed at clarifying the design of previously completed Phase II/III clinical trials testing therapeutic anticancer vaccines and at assessing the value of immunological monitoring in this setting. We identified 17 anticancer vaccines that have been investigated in the context of a completed Phase II/III clinical trial. The immune response of patients receiving anticancer vaccination was assessed for only 8 of these products (in 15 distinct studies) in the attempt to identify a correlation with clinical outcome. Of these studies, 13 were supported by a statistical correlation study (Log-rank test), and no less than 12 identified a positive correlation between vaccine-elicited immune responses and disease outcome. Six trials also performed a Cox proportional hazards analysis, invariably demonstrating that vaccine-elicited immune responses have a positive prognostic value. However, despite these positive results in the course of early clinical development, most therapeutic vaccines tested so far failed to provide any clinical benefit to cancer patients in Phase II/III studies. Our research indicates that evaluating the immunological profile of patients at enrollment might constitute a key approach often neglected in these studies. Such an immunological monitoring should be based not only on peripheral blood samples but also on bioptic specimens, whenever possible. The evaluation of the immunological profile of cancer patients enrolled in early clinical trials will allow for the identification of individuals who have the highest chances to benefit from anticancer vaccination

  17. Multi-modality neuro-monitoring: conventional clinical trial design.

    PubMed

    Georgiadis, Alexandros L; Palesch, Yuko Y; Zygun, David; Hemphill, J Claude; Robertson, Claudia S; Leroux, Peter D; Suarez, Jose I

    2015-06-01

    Multi-modal monitoring has become an integral part of neurointensive care. However, our approach is at this time neither standardized nor backed by data from randomized controlled trials. The goal of the second Neurocritical Care Research Conference was to discuss research prior