The Food and Drug Administration (FDA) recently issued a guidance document related to the conduct of clinical trials to support approval of human drugs and biological products “Draft Guidance for Industry: Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products” (“Guidance Document”). The document is intended to provide guidance for enrichment strategies that can be used in clinical trials intended to support effectiveness and safety claims in new drug applications (NDAs) and biologics licensed applications (BLAs).

As used in the Guidance Document, the term “enrichment” is defined as the prospective use of any patient characteristic 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. The Guidance Document notes that the FDA is interested in targeting treatments to the people who can benefit from the therapy (i.e., personalized medicine) but that the decision to use an enrichment design is largely left to the study sponsor. The Document notes that there are many reasons to use such study designs, including an enhanced benefit-risk relationship if a population with an increased likelihood of response can be identified, and efficiency in drug development, as smaller studies can often be used to demonstrate effectiveness. In addition, enrichment studies can be used to identify patients to whom the drug should be given and to obtain information as to whether the drug or biologic can be used in a broader population than was studied.

Genomic and proteomic markers, typically used in companion diagnostics and personalized medicine, are two of the several suggested patient characteristics for selecting an enriched study population. When proteomic or genetic markers are used in an enrichment strategy, adequate characterization of the test for the marker is noted to be critical. If the marker is to be used after approval of the drug, the quality of the marker continues to be relevant to the drug, even after approval. In some cases, the Guidance Document notes, the performance characteristic of the marker is not well documented, but the enriched trial itself may constitute an important source of information about the sensitivity and specificity of the marker.

In addition, several designs are suggested for predictive enrichments studies: (1) a study randomizing only marker-positive patients; (2) a study containing both marker positive and negative patients; (3) a study in alternative therapy non-responders to support claim of effectiveness in non-responders; and (4) a study in patients intolerant of a prior treatment.

Comments and suggestions regarding the Guidance Document should be submitted by February 15, 2013 to the Division of Dockets Management (HFA-305), Food and Drug Administration,5630 Fishers Lane, Room 1061,Rockville,MD20852. For questions regarding the Draft Guidance, individuals are encouraged to contact (CDER) Robert Temple, 301-796-2270 (CBER) Office of Communication, Outreach and Development, 301-827-1800, or (CDRH) Robert L. Becker, Jr. 301-796-6211.

This Guidance Document joins a number of FDA guidances regarding clinical trial designs (including enrichment studies) and demonstrating effectiveness. Agency guidances are available at