Minimizing Risk in Clinical Research

The randomized clinical trial, the gold standard of modern clinical investigation, is a remarkable social construction. Its overall goal is the scientific demonstration that a new drug or device produces a health benefit that justifies its risk. Ultimately, the therapeutic fruits of all biomedical advance have to be submitted to this scrutiny before they can enter clinical use.

Normal volunteers and patients are by far the most important participants in the process. Since many of these are in the group receiving the placebo, and since many trials fail, many sick and well participants have little likelihood of benefiting in the trial. The protection of these individuals from harm is therefore a compelling moral responsibility.

Three pillars undergird this morality. One is the evolution of ethical statements about human research that began with the Nuremberg trials and have undergone several major reconstructions since that time (1). The most familiar of these is the Belmont Report (2), which emphasized the autonomy of the participants (in deciding whether to consent); the respect for persons (in the investigator's design of the trial); and beneficence (in minimizing the risk facing volunteers). The second pillar of protection is the institutional review board (IRB), a group of necessarily fallible humans charged with reviewing a research proposal for its importance, scientific merit, …