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Background If trials of therapeutic interventions are to serve society9s interests, they must be of high methodological quality and must satisfy moral commitments to human subjects. The authors set out to develop a clinical-trials compendium in which standards for the ethical treatment of human subjects are integrated with standards for research methods. Methods The authors rank-ordered the world9s nations and chose the 31 with >700 active trials as of 24 July 2008. Governmental and other authoritative entities of the 31 countries were searched, and 1004 English-language documents containing ethical and/or methodological standards for clinical trials were identified. The authors extracted standards from 144 of those: 50 designated as ‘core’, 39 addressing trials of invasive procedures and a 5% sample (N=55) of the remainder. As the integrating framework for the standards we developed a coherent taxonomy encompassing all elements of a trial9s stages. Findings Review of the 144 documents yielded nearly 15 000 discrete standards. After duplicates were removed, 5903 substantive standards remained, distributed in the taxonomy as follows: initiation, 1401 standards, 8 divisions; design, 1869 standards, 16 divisions; conduct, 1473 standards, 8 divisions; analysing and reporting results, 997 standards, four divisions; and post-trial standards, 168 standards, 5 divisions. Conclusions The overwhelming number of source documents and standards uncovered in this study was not anticipated beforehand and confirms the extraordinary complexity of the clinical trials enterprise. This taxonomy of multinational ethical and methodological standards may help trialists and overseers improve the quality of clinical trials, particularly given the globalisation of clinical research.

Unlike medications, the dissemination of surgical procedures into practice is not regulated. Before marketing, pharmaceutical products are required to be shown safe and efficacious in comparative clinical trials which utilize bias-reducing strategies designed to reduce the distortion of estimates of treatment effect by predispositions towards the investigational intervention or control. Unless an investigational device is involved, the corresponding process for surgical innovations is usually unregulated and therefore may not be based upon adequate evidence. Given these differences, we sought to evaluate the state of clinical research on invasive procedures. We conducted a systematic review of publications from 1999–2008 that reported the results of studies evaluating the effects of invasive therapeutic procedures, focusing on trials which appeared to influence practice. Our objective was to determine what proportion of studies evaluating surgical procedures use a comparative clinical trial design and methods to control bias. This paper reports our results and raises concerns about the methodological, and therefore the ethical, quality of clinical research used to justify the implementation of surgical procedures into practice.

There has been a growing concern over establishing norms that ensure the ethically acceptable and scientifically sound conduct of clinical trials. Among the leading norms internationally are the World Medical Association's Declaration of Helsinki, guidelines by the Council for International Organizations of Medical Sciences (CIOMS), the International Conference on Harmonization's standards for industry (ICH), and the CONSORT group's reporting norms (Consolidated Standards of Reporting Trials), in addition to the influential U.S. Federal Common Rule, Food and Drug Administration's (FDA) body of regulations, and information sheets by the Department of Health and Human Services. There are also many norms published at more local levels by official agencies and professional groups.Any account of international standards should cover both scientific and ethical norms at once – the two are conceptually intertwined. Recent sources recognize that “[s]cientifically unsound research on human subjects is unethical in that it exposes research subjects to risks without possible benefit.”

This paper focuses on invasive therapeutic procedures, defined as procedures requiring the introduction of hands, instruments, or devices into the body via incisions or punctures of the skin or mucous membranes performed with the intent of changing the natural history of a human disease or condition for the better. Ethical and methodological concerns have been expressed about studies designed to evaluate the effects of invasive therapeutic procedures. Can such studies meet the same standards demanded of those, for example, evaluating pharmaceutical agents? This paper describes a research project aimed at examining the interplay and sometimes apparent conflict between ethical standards for human research and standards for methodological rigor in trials of invasive procedures. The paper discusses how the authors plan to develop a set of consensus standards that, if met, would result in substantial and much-needed improvements in the methodological and ethical quality of such trials.

Background Regulatory and professional bodies issue an ever-increasing number of guidance documents on the ethics and methods of clinical trials, but the quality of clinical trials of invasive therapeutic procedures continues to be a concern. We interviewed aspiring and accomplished surgical trialists to understand how they use guidance documents and other resources in their work. Methods We performed a qualitative research study involving semistructured interviews of a diverse sample of 15 surgical trialists. Results Professional development as a surgical trialist was haphazard, inefficient, and marked by avoidable mistakes. Four types of resources played constructive roles: formal education; written materials on clinical trials; experience with actual trials; and interpersonal interactions with peers, experts, collaborators, and mentors. Recommendations for improvement centered on education, mentoring, networking, participating in trials, and facilitation by department chairs. Conclusions The haphazard and unstructured nature of the current system is adding unnecessarily to the numerous challenges faced by surgical trialists.