Critical Path Wants Adaptive Clinical Trial Designs, Temple Says
The FDA is encouraging the use of adaptive trials, saying the practice will modernize the development process and shorten the time needed to show a drug is effective. The agencyâ€™s associate director for medical policy, Robert Temple, said the Critical Path Initiative encourages the use of this kind of trial when researchers use accumulating data to modify the ongoing trial. Temple, speaking at the Critical Path Executive Briefing sponsored by FDAnews and the Center for Medicine in the Public Interest, said the FDA is working on an adaptive design guidance it promised to release in 2008.
Some of the more familiar adaptations include changing sample sizes based on variance and starting and dropping extra trial groups. When researchers determine a drug effect is present in a population subset, they can adapt the trial by modifying the trialâ€™s entry criteria or increasing the number of patients assigned to receive the effective treatment.
While almost every clinical trial uses enrichment in some way to improve the trialâ€™s patient population, there are more steps that can be taken to increase the chances a drug effect is detected, Temple said. Some enrichment efforts can decrease variants while others can choose high-risk patients or patients more likely to respond to treatment because of some genetic characteristic.
â€œEveryone agrees about finding the people who are most likely to respond â€¦ it enormously enhances the power of the study,â€ Temple said. Enrichment will help researchers by decreasing heterogeneity and identifying a population that responds to the treatment.
For example, researchers can screen patients with the treatment first and then enroll them in the study if they respond to the drug. In addition, researchers can study a large group of patients and only randomize those with a good response.
Scientists are beginning to be able to search for genetic characteristics or other factors that will predict a patientâ€™s response to a drug, Temple said. Part of the Critical Path Initiative is to identify biomarkers and determine why some patients and not others experience adverse events with the same drug.
Researchers can select trial subjects based on either understanding of a disease or a drug mechanism, but they also can run a trial in patients to link a genetic baseline finding with a drug response, Temple added.