2-International One

s we stand poised on the frontiers of biomedical science, populations worldwide face a broad range of health concerns as well as many different issues related to the conduct of clinical trials in international health research. The multiple contexts within which biomedical research proceeds call for an array of research designs in order to forge scientific developments and advance clinical knowledge and treatment approaches. Any of a number of research designs may be appropriate for a clinical trial, depending on the context and circumstances of the research; however, every clinical trial must be scientifically sound and must incorporate important ethical principles regarding the treatment of research participants. With respect to the ethical treatment of research participants, current U.S. regulations require that Institutional Review Boards (IRBs) determine that a research design is such that “risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result” (45 CFR 46.111(a)(2)). However, although the federal regulations do not require IRBs to review the scientific merit of a research design, research with a scientifically flawed methodology will not generate valid or reliable data or produce generalizable and beneficial knowledge. In such cases, it is the participants in the research who will incur the risks, inconveniences, or discomforts that might be involved. Because it would be wrong to put people at risk or even to inconvenience or discomfort them through participation in a poorly designed study, the scientific merit of research becomes an ethical issue (OPRR 1993). Therefore, the National Bioethics Advisory Commission (NBAC) believes that IRBs should assure themselves of both the ethical and scientific merits of the protocols they review. The Commission is not proposing that IRBs become responsible for conducting scientific peer review (as they may lack specific expertise, and in most instances the proposed studies of research sponsors must undergo independent scientific review)—but only that IRBs have confidence that a study has scientific merit. Even when a clinical trial uses a scientifically sound research design and addresses important questions, conducting the proposed research might be unethical if it would result in the violation of certain ethical principles. However, because determining the appropriate design for a clinical trial depends on various contextual considerations, what might be an ethically acceptable design in one situation could be problematic in another. For example, it might be unethical to conduct a clinical trial for a health condition in a country where that condition is unlikely to be found, but the same trial might be appropriately conducted where the results could be important to the local population. A more challenging question is whether a research design that could not be ethically implemented in the sponsoring country could be ethically justified in a host country when the health problem that the research is addressing is common to both countries. It may be useful to classify international collaborative research projects in developed and developing countries on a continuum. At one end of the continuum is research that has no practical relevance to the health needs of the host country, but is important to the foreign sponsor or researcher. At the other end of the spectrum is research that is directly relevant to the health concerns of the host country, but not to sponsors or researchers. These two