In research that could potentially help increase the efficiency of drug development and support precision medicine, Ming Zhu, PhD, identified ways to further enhance FDA-proposed enrichment strategies. Ming presented his findings in early July at the International Chinese Statistical Association (ICSA) conference in China.
The FDA defines enrichment as the “prospective use of any patient characteristic to select a study population in which detection of a drug effect (if one is in fact present) is more likely than it would be in an unselected population.” Examples of patient characteristics include demographic, pathophysiologic, historical, genetic or proteomic, clinical and psychological.
As a part of his analysis to inform on potential areas for strengthening these guidelines, Ming compared the enrichment strategies employed in several clinical trials, while closely reviewing and factoring in the respective study design, the statistical analysis used, along with lessons learned from the trial’s success or failure.
Among Ming’s recommendations are determining the suitability for the disease area in question, adapting quickly from previous studies and enhanced communication with regulatory agencies, when considering an enrichment strategy.
With regard to adapting quickly, Ming discussed a successful phase 3 trial that had benefited from information just released from another trial, pointing to the importance of staying abreast of and acting quickly on related, emerging evidence. In this example, the newly reported data informed on the enrollment of a more enriched study population for the current trial.
Ming emphasized that having early and open communications with regulatory agencies are critical for sponsors in order to secure endorsement of the planned enrichment strategies and statistical methods before undertaking the pivotal trials. As a case in point, Ming cited successful clinical programs that progressed all the way to regulatory submission, only to be rejected when the agency found the enrichment strategies applied to be unacceptable.
He hopes that his research will provide helpful insight into enrichment design and guidance for clinical investigators to develop appropriate strategies toward improved probability of success of clinical trials.