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Tips on Using to Align Your Product Clinical Trial Designs with FDA expectations

February 23, 2021  •  Blog  •  Mark Thornton, MD, MPH, PhD; Senior Clinical Consultant
Posted In Compliance News & Insights – Biologics Consulting  •  Tagged FDA, clinical trials, FDA Compliance, pivotal trials

One of the Clinical areas in which we at Biologics Consulting are asked to consult involves assisting a company that is planning clinical trials for their product and wishes to do so with minimal risk of failure.

In the oncology clinical development space especially, the pace of change can result in confusion about what FDA expects for design of  clinical trials required to obtain regulatory approval. For example, due to the rapidly evolving science of outcomes that best predict clinical benefit, a company could hear conflicting advice from key opinion leaders or other authoritative voices (e.g., consensus literature publications and/or National Comprehensive Cancer Network Guidelines) on an important feature such as the optimal primary efficacy endpoint, resulting in uncertainty on what the FDA will require for regulatory purposes.

The obvious way to determine what FDA will expect for regulatory approval of such a clinical trial is to meet with FDA and ask. But FDA typically limits sponsors to certain meetings at certain times during drug development, the scheduling of which may not fit with a company’s timeline. One solution is to tap into the sometimes underappreciated level of clinical and regulatory strategic insight that can be gleaned on the NIH website

Originally mandated by Congress as a public information platform for patients, its modest start was to merely inform patients of the availability and location of clinical trials of products for diseases of interest that were underway or nearing their start in the United States. However, over time the site expanded its variety of information to include ex-U.S. studies, the product’s phase of development, and whether it was being funded by industry or other sources (e.g., NIH). For several years now, the sponsor of the study has additionally been required to present detailed clinical trial design elements such as primary and secondary endpoints, inclusion and exclusion criteria, statistical features such as sample size calculations, and the like. In so doing, it morphed from a patient-centric information site to a treasure trove of information for product development, not only related to strategies being implemented by industry competitors, but also on relevant data and analyses FDA was requiring of IND sponsors.

What we do with information gleaned from is to integrate (1) the website’s vast information with (2) our insights obtained during years of interaction with FDA and clinical/regulatory experience to try to read the mind of the FDA and have a crystal ball view of its latest regulatory framework for product approval in specific clinical settings.

The key to detective work on is the use of appropriate search terms and combinations of terms that offers. As an example, suppose a start-up biotech company, possessing great scientific assets but perhaps new to the regulatory arena, wants to know what will be expected by FDA as it enters development in Phase 1 clinical trials. At the same time, perhaps for investor funding purposes, the client would also like a prediction of how much time and money it might cost to get the product to market (and therefore needs to understand the landscape of Phase 2 and Phase 3 clinical/regulatory expectations). For Phase 1, the search terms are generally similar across most oncology studies, although sometimes companies attempt (and FDA has allowed) novel accelerated titration designs. An experienced consultant can analyze the specific situation (product class, oncology setting, etc.) in which FDA has shown flexibility and determine if this more rapid Phase 1 design might be appropriate and applicable to the client’s program. Moving to Phase 3, say for a program for an immunotherapy for sarcoma, searching the US (and at times ex-US) spectrum of pivotal trials of other products in Phase 3 development, one can ascertain a model of, for example, (1) optimal safety and efficacy endpoints, (2) any specific product class safety issues that could be applicable to the product, and/or (3) common statistical analysis metrics being applied. Again, since no clinical trial can proceed in the U.S. without FDA approval, by definition the design features found on would have been signed off on or required by FDA.

If your company is in need of insights such as these for your clinical development program, we at Biologics Consulting stand ready to assist you in optimizing clinical trial designs geared towards minimal regulatory risk and maximal gain for your product development strategy.