Author: Steve Kates, Ph.D.
A draft guidance has recently been issued (Dec 2012) entitled “Enrichment Strategies for Clinical Trials to Support Approval of Human Drugs and Biological Products.” The document required more than 6 years to prepare and provides guidance to industry on enrichment strategies that can be used in clinical trials intended to support effectiveness and safety claims.
This guidance outlines three enrichment strategies.
1. Strategies to decrease heterogeneity
o Selecting patients with baseline measurement in a narrow range (decreased inter-patient variability) and excluding patients whose disease or symptoms improve spontaneously or whose measurements are highly variable (decreased intra-patient variability). The decreased variability provided should increase study power.
2. Prognostic enrichment strategies
o Choosing patients with a greater likelihood of having a disease-related endpoint event (for event-driven studies) or substantial worsening in condition (for continuous measurement endpoints). These strategies should increase the absolute effect difference between groups but will not alter relative effect.
3. Predictive enrichment strategies which include
o Choosing patients more likely to respond to the drug treatment than other patients with the condition being treated. This should result in large effect size and use of a smaller study population. Selection of patients could be based on a specific aspect of a patient’s physiology or a disease characteristic that is related in some manner to the study drug’s mechanism.
The use of enrichment designs will often have implications for labeling (Indications and Usage, Dosage and Administration). As the FDA comments regarding the use of enrichment design, it is important to consider whether the strategy can be used in practice to identify the patients to whom the drug should be given and whether the drug might be useful in a broader population than will be studied as well as the accuracy of the measurements used to identify the enrichment population and the sensitivity and specificity of the enrichment criterion in distinguishing responders and non-responders.
Although the decision to incorporate an enrichment strategy is solely the responsibility of the Sponsor, FDA is very interested in targeting treatments to the people who can benefit from them.