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Part III

Chapter 15


Methodology of the RPRP

Findings of the RPRP

Independent Review of Proposals


Chapter 15: Discussion

We turn now to a consideration of the implications of the results of the RPRP, as bolstered by Katz's review, for our understanding of the current status of human subjects protections. It should be reemphasized that these results were based solely on an evaluation of the documents available to the Committee. It is therefore possible that some of the research projects that raised concerns for us based on the documents we reviewed would, with the provision of additional information, be deemed unproblematic from a human subjects perspective. It is also possible that some of the research projects whose documents raised no concerns may nevertheless have inadequacies affecting the rights and interests of human subjects that we could not detect.

There is no evidence in this review that research in which human subjects are exposed to radiation is any more ethically problematic than other kinds of research involving human subjects; in fact, our results suggest that human subject protections may be more effective in radiation research then elsewhere, perhaps because some radiation research is reviewed by a radiation safety committee as well as an IRB. Because we failed to find any systematic differences between radiation research and nonradiation research in our review, our observations based on the RPRP results are directed at human subjects research generally, not solely at radiation research.

About 40 percent of the research whose documents we reviewed appeared to pose no greater than minimal risk to participants. Most of these studies raised no concerns about ethics, or only minor ones. Many studies that involved greater than minimal risks to subjects were similarly ethically unproblematic. Specifically, more than half of the greater-than-minimal-risk studies reviewed raised no or only minor concerns about ethics. There are important lessons to be learned from these studies. It is possible to conduct complex research that puts subjects at greater than minimal risk of harm in an ethically acceptable fashion. It is possible to develop good consent forms for this kind of research. Not only is it possible, but it appears that this happens frequently.

At the same time, our review suggests that there are significant deficiencies in some aspects of the current system for the protection of human subjects. We have evidence that the documents provided to IRBs often do not contain enough information about topics that are central to the ethics of research involving human subjects such as voluntariness of participation, fairness in the selection of subjects, and scientific merit. Although we have already noted that IRBs do not necessarily rely solely on documents in making their evaluations, clear, complete written documents are important. These documents form the core of the information upon which IRBs rely in protecting the rights and interests of human subjects; in some cases, they are the only source of information available. These documents also provide a written record of the research subject protection process for both administrative and historical purposes.

In some cases, the Committee found that it was difficult to assess the scientific merit of a protocol based on the documentation provided. This is particularly problematic for proposals in which the IRB provides the only opportunity for peer review, as is sometimes the case for research that is not funded by the federal government.

The Committee also found evidence suggesting that in some studies women are being excluded from participation in research, explicitly or presumably because of the possibility that they might become pregnant during the course of the study. This finding is disturbing in light of the fact that much of this research was undertaken after a national policy had been instituted, advocating the inclusion of women in research, and a general rejection of the mere possibility of pregnancy as a justifiable reason for not permitting women to become research subjects.[31] The conditions under which pregnant women ought to be included as research subjects remain controversial. That pregnant women are frequently excluded from research was clearly evidenced in the RPRP; this occurred in more than half the studies in our review.

Some of the Committee's most serious concerns focus on informed consent. The results of the RPRP, as well as of Katz's review, suggest that some consent forms currently in use are flawed in morally significant respects, not merely because they are difficult to read but because they are uninformative or even misleading. These are consent forms that have been approved by an IRB, and still they are problematic, to the point where Committee reviewers viewed them as raising serious ethical issues. Most of these concerns centered on research involving patient-subjects with poor prognoses, people who are particularly vulnerable to confusion about the relationship of research to treatment. The consent forms to be used with such patient-subjects sometimes appeared to suggest a greater prospect of benefit than the research as described in the documents we reviewed warranted. In a few Phase I studies, any intimation that subjects would benefit appeared questionable. At the same time, the disadvantages of participation, particularly as they would affect quality of life, were sometimes inadequately described or not presented at all. The Committee recognizes that the consent form is only a document and is never to be confused with the entire process of soliciting informed consent, which includes far more than the form itself. It is possible that in some of these cases potential patient-subjects were provided more balanced and straightforward information in discussions with investigators or their own physicians. At the same time, however, the consent form as approved by the IRB is a powerful symbol of what the system considers an adequate disclosure. Moreover, this may convey to investigators that meeting ethical obligations to potential subjects requires the investigators to say nothing different and nothing more than what is approved on the consent form.

Our review also raises serious concerns about some research involving children and adults with questionable decision-making capacity. Although we looked at documents from only 125 proposals, we found examples of three controversial, unresolved issues in the ethics of research: research with patients in the midst of a potential medical emergency; research involving children that may offer them no prospect of direct benefit but that may put them at greater than minimal risk, depending on how minimal risk is understood; and research on adults with questionable decision-making capacity that offers them no benefit but that involves unpleasant procedures and exposes them to greater than minimal risk of harm.

All told, the documents of almost half the studies reviewed by the Committee that involved greater than minimal risk raised serious or moderate concerns. Katz, who focused exclusively on the informed consent process, had serious concerns about 50 percent of the greater-than-minimal-risk proposals he evaluated. These are findings that cannot be ignored. At the same time, our review provides evidence that research involving human subjects, even complex research, can and often is being conducted in an ethically responsible manner. The challenge is to identify what needs to be changed to ensure that all research involving human subjects is conducted in accord with the highest ethical standards.

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