April 16, 1999

Steven Hyman, M.D., director of the National Institute of Mental Health, last month established an explicit, formal process to review "high-risk" study designs in clinical research on mental illness.

"The best possible science and human protections must be the shared foundation of clinical research," he said. "NIMH is committed to clinical research because mental disorders are terrible illnesses that destroy lives and families. Despite our successes we must do better."

Hyman was responding to concerns about the protection of human subjects in clinical research on mental illness, raised in part by the report of the National Bioethics Advisory Commission released in January. That report, followed by lay press accounts critical of some study protocols, called for additional federal protections of people with mental illness participating in clinical studies.

A special 10-member Human Subject Research Workgroup of the National Advisory Mental Health Council (NAMHC) will help the full council address research designs in which symptom challenges or medication "washout" protocols-whereby medications are withdrawn to assess effect on symptoms-risk potential harm to patients. The work group will consist of approximately four council members, four bioethicists, and four advocates/consumers who have personal experience with mental illness, along with serveral outside experts.

This is the process by which study protocols will be reviewed: Applications requiring review will be identified by NIMH staff, the NAMHC, or peer review, with a focus on studies that increase symptoms or distress as part of the design. Work group members will then review summary statements and patient consent documents, and any other pertinent information they require. Where the scientific question is considered sufficiently important to justify the risk, investigators will be asked to address work group concerns.

Hyman said the process should begin immediately after review of a protocol by an Institutional Review Board. He also said that delays in funding grants should be minimal.

"The NAMHC is an independent, officially chartered, federal committee. . . charged by law with providing a second tier of review prior to the funding of an application, and it is the place where judgments about science and about human-subject protections come together," Hyman said. "In addition to making recommendations for funding, the council has the authority to request additional information about protocols, including study design and human subject protection. The current NAMHC has been scrutinizing high-risk designs effectively and independently, but an explicit, formal process is clearly warranted."