Background: The approval of a research ethics committee and obtaining informed consent from patients could be considered the main issues in the ethics of research with human beings. The aim of this study was to assess both methodological quality and ethical quality, and also to assess the relationship between these two qualities in randomised phase III cancer trials.Method: Methodological quality and ethical quality were assessed for all randomised controlled trials published in 10 international journals between 1999 and 2001 .Results: The (...) mean Jadad score was 9.86 ± 1.117. The methodological quality was poor in 75 RCTs . The mean Berdeu score was 0.42 ± 0.133. The mean ethical quality score for poor methodological quality RCTs was 0.39 ± 0.133; it was 0.43 ± 0.133 for good methodological quality RCTs . There was improvement in ethical quality according to the year of commencement of the trials . There was no correlation between methodological quality and the number of participating patients , between ethical quality and the number of participating patients , or between ethical quality and methodological quality . ICP and REC approval were not obtained for 21 and 77 trials respectively.Conclusion: The association between methodological quality and the reporting of ethical requirements probably reflects the respect shown for patients during the whole research process. These results suggest that closer attention to the conduct of clinical research, as well as the reporting of its ethical aspects, is needed. (shrink)

Research ethics is an integral part of research, especially that involving human subjects. However, concerns have been expressed that research ethics has come to be seen as a procedural concern focused on a few well-established ethical issues that researchers need to address to obtain ethical approval to begin their research. While such prospective review of research is important, we argue that it is not sufficient to address all aspects of research ethics. We propose retrospective review as an important complement to (...) prospective review. We offer two arguments to support our claim that prospective review is insufficient. First, as currently practiced, research ethics has become for some a ‘tick box’ exercise to get over the ‘hurdle’ of ethics approval. This fails to capture much of what is important in ethics and does not promote careful reflection on the ethical issues involved. Second, the current approach tends to be rules-based and we argue that research ethics should go beyond this to develop people’s capacity to be sensitive to the relevant moral features of their research, their ethical decision-making skills and their integrity. Retrospective review of a project’s ethical issues, and how they were addressed, could help to achieve those aims better. We believe that a broad range of stakeholders should be involved in such retrospective review, including representatives of ethics committees, participating communities and those involved in the research. All stakeholders could then learn from others’ perspectives and experiences. An open and transparent assessment of research could help to promote trust and understanding between stakeholders, as well as identifying areas of agreement and disagreement and how these can be built upon or addressed. Retrospective review also has the potential to promote critical reflection on ethics and help to develop ethical sensitivity and integrity within the research team. Demonstrating this would take empirical evidence and we suggest that any such initiatives should be accompanied by research into their effectiveness. Our article concludes with a discussion of some possible objections to our proposal, and an invitation to further debate and discussion. (shrink)

Institutional Review Boards can play vital roles in observing, monitoring, and responding to research integrity issues among researchers, yet many questions remain concerning whether, when, and in what ways these boards in fact adopt these roles. Increasingly, RI is being challenged due to many factors, yet the extent of violations, and institutional responses to these, remain unknown. As the amount and complexity of experiments on human participants, often funded by for-profit industry, mushrooms, scandals have occurred, posing dilemmas concerning how to (...) best oversee research to protect these participants from harm.For over 15 years, many institutions have been developing research compliance programs that monitor misconduct and conflict of interest, and may interact with IRBs. In 2002, the Institute of Medicine report, “Responsible Research: A Systems Approach to Protecting Research Participants,” called for increased assessment of the overall human research protections system, and oversight of research. (shrink)

Institutional Review Boards (IRBs) can play vital roles in observing, monitoring, and responding to research integrity (RI) issues among researchers, yet many questions remain concerning whether, when, and in what ways these boards adopt these roles. I contacted 60 IRBs (every fourth one in the list of the top 240 institutions by NIH funding), and interviewed leaders from 34 (response rate=55%), and an additional 12 members and administrators. IRBs become involved in a variety of RI problems, broadly defined, and face (...) challenges in deciding how and when to do so. IRBs vary in how they define, discover, and respond to RI problems, and interact with other institutional offices concerning these issues; and what types of RI violations they encountered. While many institutions establish separate Compliance Offices, the boundaries and relationships between these entities and IRBs vary; and many IRBs discover and monitor RI violations, and struggle with how to respond. Larger questions arise of how IRBs decide whether to trust vs. closely monitor individual PIs. IRBs' roles are often indirect, and not fully systematic, raising questions of whether these functions should be enhanced, and if so, to what degree, and how. These areas require heightened investigation and discussion. (shrink)

The voluntary and informed consent of subjects has been the central focus of concern in research reviews, overshadowing the importance of all other considerations. The Nuremberg Code, with its rights-based protection of the subject's autonomy above all else, made it difficult to justify research with no intended benefit when subjects are incompetent to make a valid informed choice to participate. Subsequent codes providing for research with incompetent subjects followed the lead of Nuremberg, substituting the informed authorization of a proxy for (...) the informed consent of the subject. (shrink)

Data Safety and Monitoring Boards were introduced in the 1960s to monitor data in clinical trials to ensure subject safety. It was thought important that DSMB members be experts in the field of interest, but not otherwise involved in the study in order to maximize objectivity. Since then, the use of DSMBs has increased dramatically, and their scope has expanded to include scientific issues — in particular, to avoid bias that can result when trials are stopped early because of evidence (...) that one treatment has greater efficacy or causes greater harm than another; or that no treatment is likely to do better than any other. (shrink)

Data Safety and Monitoring Boards have been referred to as a “growth industry,” and this trend continues to be fueled by recent FDA guidance and the NIH's requirement that DSMBs be employed in virtually all phase III clinical trials. The widening role of DSMBs has been sporadically questioned on ethical grounds, but growth has continued, despite the fact that many of the questions endure, unanswered, save for repeated references to safeguarding the scientific integrity of trials. This may be about to (...) change. The recently appointed director of the Office for Human Research Protections , Jerry Menikoff, is on record as regarding current practices — where consent forms often promise what the DSMB has been assembled to specifically not provide — as constituting fraudulent behavior. That is, a subject may inherently rely on, to their detriment, information that has been misrepresented in the consent document. In this paper, we assemble some of the enduring questions and top them off with Menikoff's tour de force to present what we hope will be a compelling argument to require that consent forms fairly represent what the DSMB will do — and not do — with trial data as they accumulate. We argue that DSMBs should be used only in rare circumstances, and question the practice of precluding principal investigators from DSMB membership, but our main thrust is to ensure that DSMBs, when used at all, are properly described in trial consent forms. (shrink)