Part IV

In parts I and II of this report, the Advisory Committee attempted to come to terms with the past. We told the history of standards for conducting human subject research in part I, and the history of human radiation experiments through representative case studies in part II. Here in part III of our final report, we attempt to assess whether the current protections for human subjects are better than the prevailing standards and practices during the 1944 to 1974 period to help recommend what changes, if any, ought to be instituted in current policies governing human subject research.

The Advisory Committee's study of contemporary research ethics is three-pronged. It comprises a review of agency policies and oversight practices, a review of documents from recently funded research proposals (the Research Proposal Review Project, or RPRP) to examine the extent to which the rights and interests of the subjects of federally sponsored research appear to be protected, and the Subject Interview Study (SIS) in which the attitudes and beliefs of patients about medical research and their decisions and experiences regarding participation in research are examined. These projects together form the basis of the Advisory Committee's picture of the protections now afforded the subjects of biomedical research and, along with findings regarding radiation experiments during the 1944-1974 period, inform the forward-looking recommendations of the Advisory Committee, found in part IV.

Chapter 14 reviews the current regulatory structure for human subjects research conducted or supported by federal departments and agencies, a structure that has been in place since 1991. This "Common Rule" has its roots in the human subject protection regulations promulgated by the then-Department of Health, Education, and Welfare (DHEW) in 1974. The historical developments behind these regulations are described in chapter 3. Following a summary of the essential features of the Common Rule, chapter 14 discusses several subjects of particular relevance to the Advisory Committee's work, such as special review processes for ionizing radiation research, protection for human subjects in classified research, and audit procedures of institutions performing human subject research.

Chapter 15 describes the Research Proposal Review Project (RPRP), the Advisory Committee's examination of documents from research projects conducted at institutions throughout the country, including both radiation and nonradiation proposals. Documents utilized in the RPRP were those available to the local institutional review boards (IRBs) at the institutions where the research was conducted. The goals of the RPRP were to gain an understanding of the ethics of radiation research as compared with nonradiation research; how well research proposals address central ethical considerations such as risk, voluntariness, and subject selection; and whether informed consent procedures seem to be appropriate.

The RPRP reviewed documents prepared by investigators and institutions and submitted in IRB applications. This study was complemented by a nationwide effort to learn about research from the perspective of patients themselves, including those who were and were not research subjects. The Subject Interview Study (SIS), described in chapter 16, was conducted through interviews with nearly 1,900 patients throughout the country. The SIS aimed to learn the perspectives of former, current, and prospective research subjects by asking about their attitudes and beliefs regarding the endeavor of human subject research generally and their participation specifically.

The RPRP tried to understand the experience of human subjects research from the standpoint of the local oversight process, while the SIS tried to understand it from the standpoint of the participant. Although the two studies related to different research projects and different groups of patients and subjects, some common tensions in the human research experience emerge in both projects, and they are described in the "Discussion" section of part III. For example, it has long been recognized that the physician who engages in research with patient-subjects assumes two roles that could conflict: that of the caregiver and that of the researcher. The goals inherent in each role are different: direct benefit of the individual patient in the first case and the acquisition of general medical knowledge in the second case. The interviews with SIS participants suggest that at least some patient-subjects are not aware of this distinction or of the potential for conflict. In our review of documents in the RPRP we found that the written information provided to potential patient-subjects sometimes obscured, rather than highlighted, the differences between research and medical care and thus likely contributed to the potential for patients to confuse the two.

To help complete the picture of current human subject research and its regulation and oversight, the Committee also gathered limited information in two areas: (1) the federal system of human subject protection as viewed by those charged with implementing it at the local level, the chairs of IRBs; and (2) the particular review process applied to human subject research involving radiation as viewed by those charged with implementing it at the local level, the chairs of radiation safety committees.[*]

* The Committee also contacted a sample of institutions at which therapeutic human radiation research involving higher doses of radiation, and therefore imposing substantial risk, had recently been conducted according to reports in the medical literature. The Committee was interested in learning whether the research projects reported in these journal articles had been reviewed by an IRB, and if IRB review had depended upon whether the research was supported by federal funds. Information was received from only nine of the sixteen institutions requested. Although the projects about which we were inquiring were sometimes described as clinical investigations in the journal reports, these institutions did not always view them as satisfying the definition of human subject research and thus did not appear to require IRB review for these projects.

A letter was written to forty-one chairs of IRBs and forty chairs of radiation safety committees at institutions throughout the country, attempting to gain their perspectives on the current regulatory systems their committees seek to apply. Many of these letters are reproduced in a supplemental volume to this report. Most of the replies from IRB chairs indicated a general approval of the current system, but many also had useful observations and suggestions for improvement. For example, several expressed concern about what they believed to be a disparity in the procedures of IRBs from one institution to another. The chairs of radiation safety committees, on the other hand, reported a nearly universal confidence in, and approval of, the review process for human subject research involving the use of radiation. The Committee's recommendations, in part IV of this report, address some of the concerns outlined in response to our queries.

As the Committee's work in part III shows, in the discussion section, contemporary human subject research does not suffer from the same shortcomings witnessed in the 1940s and 1950s, but poses different issues that need to be addressed. With a system of human subjects protections comes issues related to implementation and interpretation of rules and regulations. And with a change in the culture of medicine comes a change in the relationship between researchers and subjects. In the historical period of the Committee's review, we found that subjects needed protections to ensure their basic rights to consent to or to refuse participation in research. While this need to protect the right of consent continues, in the current period we found that subjects also need protections to ensure their interests are served in understanding the distinctions between research and therapy and the limits of the benefits research may offer. These findings and conclusions suggest the need for changes in an oversight system designed to address the concerns of an earlier time, and the Committee makes recommendations for such change in part IV of this report.