Evolution of Clinical Trials throughout History (original) (raw)
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The natural history of conducting and reporting clinical trials: interviews with trialists
Trials, 2015
Background: To investigate the nature of the research process as a whole, factors that might influence the way in which research is carried out, and how researchers ultimately report their findings. Methods: Semi-structured qualitative telephone interviews with authors of trials, identified from two sources: trials published since 2002 included in Cochrane systematic reviews selected for the ORBIT project; and trial reports randomly sampled from 14,758 indexed on PubMed over the 12-month period from August 2007 to July 2008. Results: A total of 268 trials were identified for inclusion, 183 published since 2002 and included in the Cochrane systematic reviews selected for the ORBIT project and 85 randomly selected published trials indexed on PubMed. The response rate from researchers in the former group was 21% (38/183) and in the latter group was 25% (21/85). Overall, 59 trialists were interviewed from the two different sources. A number of major but related themes emerged regarding the conduct and reporting of trials: establishment of the research question; identification of outcome variables; use of and adherence to the study protocol; conduct of the research; reporting and publishing of findings. Our results reveal that, although a substantial proportion of trialists identify outcome variables based on their clinical experience and knowing experts in the field, there can be insufficient reference to previous research in the planning of a new trial. We have revealed problems with trial recruitment: not reaching the target sample size, over-estimation of recruitment potential and recruiting clinicians not being in equipoise. We found a wide variation in the completeness of protocols, in terms of detailing study rationale, outlining the proposed methods, trial organisation and ethical considerations. Conclusion: Our results confirm that the conduct and reporting of some trials can be inadequate. Interviews with researchers identified aspects of clinical research that can be especially challenging: establishing appropriate and relevant outcome variables to measure, use of and adherence to the study protocol, recruiting of study participants and reporting and publishing the study findings. Our trialists considered the prestige and impact factors of academic journals to be the most important criteria for selecting those to which they would submit manuscripts.
Clinical trials, the State and society: where does science end and profit-making begin?
Ugalde and Homedes (1) present a timely discussion of clinical trials sponsored by large multinational pharmaceutical companies in Latin America. With a forceful tone and a rare, ethically justified partiality, the authors discuss scientific frauds and manipulations of study results, financial interests disguised as science and the instrumental use of people in conditions of social vulnerability.
Clinical Trials of New Drug Products: What Gets Compared to Whom
American Journal of Clinical and Experimental Medicine, 2015
Two of the most controversial aspects of phase III clinical trial design are the choice of the control group(s) and the choice of the outcome variable(s). Each of these choices has overlapping scientific and ethical ramifications, and the tension between maximizing scientific validity on the one hand, and protecting the rights and welfare of the human participants in the trial on the other, is the main source of the controversy. The intensity of the debate is increased whenever these choices are motivated not by scientific or ethical principles, but are driven by conflicts of interest. And so it comes to pass that in testing the safety and efficacy of new drug products, when study design choices are made more to achieve rapid market approval than to accurately assess safety and efficacy, thereby putting the welfare of both the trial participants and future patients at risk, the public and its advocates will recoil. In this paper, we study two issues of this kind: the use of placebo controls when an established intervention for the condition under consideration exists, and the use of surrogate outcome measures. There is a rich and growing literature on both of these topics and we will have little to contribute to a greater theoretical understanding of either of them. Our aim is to point to the ethical ramifications of these choices in the context of clinical trials of new drug products, and to suggest how these choices may be better made to serve public health interests. What is to come is portended by the observation that, "In the United States, the long tradition of leaving to the pharmaceutical industry the task of evaluating the efficacy and safety of its products has permitted manufacturers to make study design choices that largely determine the shape of the answers eventually provided by the trials" (Psaty and Weiss, 2007, p. 330).
The Economics of Investment In Clinical Trials!
2005
Scandals of selective reporting of clinical trial results by pharmaceutical …rms have underlined the need for more transparency in clinical trials. We provide a theoretical framework which reproduces incentives for selective reporting and yields three key implications concerning regulation. First, a compulsory clinical trial registry complemented through a voluntary clinical trial results database can implement full transparency (the existence of all trials as well as their results is known). Second, full transparency comes at a price. It has a deterrence e¤ect on the incentives to conduct clinical trials, as it reduces the …rms' gains from trials. Third, in principle, a voluntary clinical trial results database without a compulsory registry is a superior regulatory tool; but we provide some quali…ed support for additional compulsory registries when medical decision-makers cannot anticipate correctly the drug companies' decisions whether to conduct trials.
Unveiling the Dark Side of Clinical Trials
PARIPEX INDIAN JOURNAL OF RESEARCH
There is an old saying-“public health is public wealth”.The evolution of drug discovery traverses a long and fascinating journey.The security of drugs is pivotal because no drug is absolutely safe for all people,in all places,at all times.In the last few decades,biomedical research has grown tremendously and the use of animals has also increased as a research model for clinical trials.Clinical trials are crucial for identifying novel disease treatments as well as innovative methods of disease detection,diagnosis, and risk reduction.Researchers can learn things about what works and doesn't work in humans through clinical trials that cannot be discovered through laboratory or animal testing.Biomedical research also assists medical professionals in determining whether a novel treatment's adverse effects are tolerable in comparison to its potential benefits.There should be strong reasons based on laboratory,animal,and human trials if greater doses are to be examined. But there w...
Redundant, Secretive, and Isolated: When are clinical trials scientifically valid?
Clinical research has at least three problematic features: it tends to be redundant, secretive, and isolated. Research with these features not only wastes resources and causes harm, it also fails to meet a basic ethical requirement of research: scientific validity. According to a recent editorial in the BMJ, bioethicists and members of research ethics committees have been “notable by their absence” among those exposing persistent problems with clinical research and proposing solutions (Chalmers, Glasziou, and Godlee, BMJ 346, 2013, f105). In this paper I offer a theoretical diagnosis for the complicity of bioethicists and research ethics committees in these ongoing problems, as well as a partial solution in the form of a modified ethical requirement of scientific integrity.
Publication of Noninferiority Clinical Trials: Changes Over a 20-Year Interval
Pharmacotherapy, 2011
Study Objectives. The primary objective was to evaluate the change in publication rate of noninferiority trials over a 20-year interval . Secondary objectives were to analyze the frequency of noninferiority trials by therapeutic category, the frequency of noninferiority trial publication by journal, the impact factors of the publishing journals, any potential special advantages of the study drug over the control, the funding sources of the trials, pharmaceutical industry affiliation of the authors, and the use of ghostwriters in the creation of manuscripts. Design. Retrospective literature review of 583 articles. Data Sources. PubMed (January 1989-December 2009) and EMBASE (first quarter 1989-fourth quarter 2009) databases. Measurements and Main Results. A total of 583 articles of the results of randomized controlled clinical trials with a noninferiority study design that evaluated drug therapies, published in English, between 1989 and 2009, were included in the analysis. A consistent increase was noted in their yearly publication rates, with no trials published in 1989 versus 133 in 2009. One hundred twenty-six articles (21.6%) were in the therapeutic category of infectious diseases, followed by 78 (13.4%) in cardiology. Among the journals identified, The New England Journal of Medicine had the highest publication rate of trials with a noninferiority design, with 29 (5.0%) of the identified trials published in this journal. The median impact factor of the journals publishing noninferiority trials was 4.807 (interquartile range 3.064-7.5). The most common advantage of the study drug over the control was reduced duration of treatment or reduced pill burden (80 studies [22.9%]). A total of 425 trials (72.9%) listed the pharmaceutical industry as the only funding source. Among 369 trials with authors employed by the pharmaceutical industry, 101 (17.3%) disclosed an acknowledgment to an individual, other than those listed as authors, who contributed to writing the manuscript and who was affiliated with a medical information company and/or a pharmaceutical company (i.e., potential ghostwriters). Conclusion. The publication of noninferiority trials increased during the 20 years from 1989 until 2009, particularly in the therapeutic areas of infectious diseases and cardiology. Because of this growth, clinicians and researchers need to be familiar with the caveats of the noninferiority study design to appropriately interpret and design these clinical studies.
Managing Conflicts of Interest in the Conduct of Clinical Trials
JAMA, 2002
NEW TRENDS IN CLINICAL RESEARCH The interaction between medical research and for-profit corporations is not new, but it has expanded considerably in recent years. Some of the recent trends may accelerate the research process, particularly when large clinical trials are required, but caution is essential. Investment in research and development by the top 20 pharmaceutical companies has more than doubled in the past 7 years. 1 In contrast, revenues are expected to grow only by 7% per annum for the coming years. Therefore, companies will need to generate more than $25 billion in sales to maintain current levels of profitability, which will require industry leaders to launch between 24 and 34 new drugs per year. 1 Furthermore, new drugs will have to cost less to develop or else be sold at higher prices to maintain current profit levels. To achieve this, the pharmaceutical industry will need to pursue more costefficient means of developing products. One way this can be achieved is by turning away from academic health centers , which often are slowed by lengthy review processes and have large overhead expenses. Instead, industry increasingly relies on for-profit intermediary companies to seek less costly venues for the conduct of trials. 2 These organizations-contract research organizations and site management organizations-enable physicians in the private sector to be involved in trials outside academic settings. 3,4 Parallel to the proliferation of these organizations, the overall number of physicians involved in clinical research has increased 600% in 10 years, reaching more than 30000 by 1998. 5 Investigators based in academic medical centers now represent only 46% of those conducting research, a decrease from 80% 10 years ago. 5 Also, only 40% of industry research funding is allocated to clinical trials performed in aca