Beyond the question of placebo controls: ethical issues in psychopharmacological drug studies.

Rationale: There is a broad range of complex ethical issues in the conduct of psychopharmacological drug studies that go beyond the question of the ethics of placebo controls. However, our empirical knowledge with respect to these issues is very limited. This review, although not exhaustive, highlights an array of ethical issues that arose from discussions within the NIMH Human Subjects Research Council Workgroup.

Objectives: To delineate issues in psychopharmacological drug studies that require debate and would benefit from research leading to the development of empirically-supported guidelines.

Methods: Information included in this report was drawn from the first author's participation as chair of the NIMH Human Subjects Research Council Workgroup, guidelines for the ethical conduct of research proposed by professional organizations to which the first and third author belong, and relevant research literature.

Results: We have focused on general issues relating to informed consent, research with special populations, and long-term treatment studies. Additionally, we raise issues relevant to large research-oriented institutions.

Conclusions: The essential ethical challenge in psychopharmacological trials is to balance risks and benefits in the context of the needs and capacities of individual research subjects. The IRB system must become evidence-based and not rely on unproven assumptions. Specific research studies should be undertaken to address many of the issues of informed consent and research ethics postulated in this paper.