FDA issues draft guidance on trial enrichment

FDA issued draft guidance outlining enrichment strategies to improve the efficiency of clinical trials, including strategies to reduce heterogeneity, or non-drug variability. The agency, which has been working on the guidance since 2006, defines enrichment as the prospective use of patient characteristics to select a study population in which detection of a drug effect, if one is present, is more likely than it would be in an unselected population. FDA suggested using placebo lead-in periods to eliminate patients who improve spontaneously or who have large placebo responses as a way of reducing heterogeneity, as well as excluding patients who are likely to drop out for non-medical reasons (see BioCentury, July 31, 2006).

FDA also recommended a number of prognostic strategies to identify patients who are at high-risk in order to increase the chance of detecting a treatment effect in a smaller sample size than in an unselected population. The agency's strategies include choosing patients with a greater likelihood of having a "disease-related endpoint event" or a substantial worsening in condition. FDA also recommended predictive strategies to identify probable responders, including screening patients more likely to respond based on genomic or proteomic factors, pathophysiology, past history of response or disease characteristics. ...