FDA Initiative for Innovative Clinical Trial Designs to Expedite Product Approval 
[Posted on: Thursday, August 30, 2018]

This week FDA announced a new initiative to encourage disruptive clinical trial designs aiming to expedite market approval of promising drugs and biologics. Several of these trial designs have been proposed in the recent years, mostly for products intended to treat cancers. The new initiative, called Complex Innovative Trial Design (CID) expands innovative trial designs to drugs for all indications with emphasis on products that fill unmet medical needs. Clinical trial programs have come a long way in the last decade from the traditional Phase 1 to Phase 3 clinical trials to development programs where trial Phases are merged, sub-phases are created, and conventional stages of development eliminated for faster approval. Many programs start with Phase 2a proof-of-concept trials, followed by adaptive trial designs merging Phases such as Phase 2/3 and, in many cases, elimination of traditional large Phase 3 trials. Drugs intended to treat diseases with no or few treatment options, rare diseases, using new mechanisms of action, and those that offer significant improvement on available therapies usually have their clinical development programs curtailed to bare minimum. To further encourage the out-of-the-box thinking, FDA encourages smart clinical trial designs that reduce the time to identify and evaluate promising drug candidates such as master protocols, seamless design and adaptive trials. The CID program is designed to further encourage sponsors to use these innovative designs by creating a holistic platform where all options for innovative clinical trial design are discussed. Under the CID program sponsors can request up to 4 meetings each quarter with FDA to discuss all applicable innovative designs such as seamless trial designs, modeling and simulations to assess trial operating characteristics, the use of biomarker enriched populations, complex adaptive designs, Bayesian models and other benefit-risk determinations, and other novel designs. To be eligible for the program, the sponsor must have completed early clinical trials under an active IND and be ready to conduct trials intended to support market approval. In addition, the sponsors must agree that FDA can publicly disclose any innovative trial designs that results from this discussion. Public disclosure would allow other companies with similar products to learn and adjust their development programs as well. To be selected for the program, applicants must demonstrate that they need innovative features in their trials, and that their products are intended for unmet medical needs. The application process is similar to that for requesting other meetings with the Agency. The description of the program and its selection criteria indicates this program may be available mostly to products that are also eligible to other FDA expedited programs such as Breakthrough Therapy, Fast Track, Priority Review, Orphan Indication, and Regenerative Advanced Medicine Therapy. Those expedited programs already allow sponsors to have frequent meetings with FDA to discuss their clinical trial designs. So, it is not clear what advantages would be imparted by the new program if it overlaps extensively with other existing programs. The key take home from the announcements is FDA emphasis on novel clinical approaches in drug development programs where these trial constructs can expedite approval.