Structuring the review of human genetics protocols: gene localization and identification studies.

Knowledge about the relationship between the structure of genes and biological function has increased rapidly over the past twenty years, clarifying the importance of genetics in human health and disease. Advances in molecular genetics and DNA technology and their uses in medicine have created new challenges for both the conduct and review of human subjects research. Continuously developing technologies are presenting unfamiliar issues concerning risk, consent, and disclosure. Institutional review board members have begun to ask whether or how genetics protocols fit into the ordinary review structure. Do they raise novel medical, ethical, or legal questions? And if so. how can we accommodate them in the context of protocol review? In the ordinary course Of its review, an IRB evaluates such issues as the validity and value of the research, subject eligibility criteria and recruitment strategies, trial design, quantification or prediction of risks and benefits. disclosure to subjects, privacy and confidentiality, subject follow-up requirements, and monitoring.1,2 The challenge in their review of genetics research is to recognize when a particular protocol raises new issues, and if so, whether they are addressed appropriately by the investigators. IRBs must be prepared to address these issues before recommending approval, amendment or disapproval of protocols. We have designed this article to assist investigators and IRB members in their review of gene localization and identification protocols, sometimes referred to as “gene hunting” research. We provide a general description of “gene hunting” studies, set out a checklist/critical path identifying issues for IRB review (table 1), and discuss in greater detail several points of controversy raised by this kind of research. A glossary of terms that have not been defined in the body of the text is also provided (table 2). Throughout the article, we cite materials for readers seeking further information.