Chapter 8 - Unanticipated risk in clinical research

Abstract

The process of clinical research is serious and charged with risk, both for the subject and the investigator. Some adverse outcomes in clinical studies are predictable, based on what is known of the underlying medical condition of the research subjects and the nature of the experimental intervention, whereas others may not be. These latter, unanticipated risks are particularly challenging in that they erode public trust in research and lead to progressive changes in research regulation, oversight, and conduct. Unanticipated risks emerging in early human gene therapy trials for severe combined immunodeficiency have led to patient deaths and reassessment of the hazards of viral vectors for human gene replacement, but far fewer investigations and regulatory adjustments. Certain risks cannot be readily foreseen, but become evident only during the course of the research. By prohibiting all studies of novel clinical interventions, one can reliably prevent all unforeseeable risks to research subjects. This chapter discusses the mechanics of clinical research: how one designs a protocol, how the sample size should be calculated, optimal ways of managing data, which interventions are ethical, and which interventions are proscribed. Clinical research is a complex undertaking—so complex that, as in all things in medicine today, one acquires expertise only through prolonged practice.