When clinical context does not provide a sufficient number of research subjects for an adequately powered and controlled trial—for example, because treatments are unavailable for a rare disorder or a unique patient populations such as astronauts, or because studies require the participation of patients with terminal or severely debilitating or incapacitating disorders— researchers are often faced with insufficient design and analysis tools that would allow them to move forward.

In response to the need for such tools, an Institute of Medicine committee was asked to assess the current methodologies and appropriate situations for conducting clinical trials with small sample sizes. The committee’s report, Small Clinical Trials: Issues and Challenges, contains recommendations that describe approaches that can be taken in the design and analysis of trials involving a small sample of individuals to obtain reliable and valid results.