More Efficient, Informative Clinical Trials Is the Goal of FDA Leaders

Jill Wechsler

In his two years as FDA commissioner, Scott Gottlieb promoted policies and programs to streamline clinical research to facilitate the development of new medical products at reduced costs. Gottlieb repeated this theme in his farewell talk to agency staffers on April 4, where he included on his list of accomplishments that FDA took “new steps to modernize the development process for novel medical technologies” such as gene therapies, targeted drugs, and regenerative medicine.

At the same time, Richard Pazdur, director of FDA’s Oncology Center of Excellence (OCE), urged developers of cutting-edge cancer therapies to collaborate more in developing biomarkers and establishing platform trials to gain efficiencies in testing cancer treatments. With a limited number of patients suitable and willing to enter clinical trials to test new PD-1 and PD-L1 inhibitors, Pazdur advised companies to work together more to avoid waste in developing remedies that are very similar to one another. Too often sponsors conduct multiple Phase III trials using similar agents and a common comparator, Pazdur complained at the recent annual meeting of the American Association for Cancer Research (AACR).

Because inefficient testing can lead to very costly therapies, Pazdur further encouraged researchers in China and other regions to seek U.S. approval of their similar therapies to inject competition into the U.S. oncology market. Pazdur suggested that FDA could approve a foreign drug based on clinical data from China that meets quality standards, and that a streamlined development strategy may be supported by earlier FDA experience in reviewing and approving related applications.

Next stage: Knowledge management

Support from FDA leaders for adoption and confirmation of biomarkers and surrogate endpoints echo long-time admonitions from Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), who regularly urges research sponsors to adopt more streamlined research practices. Moving forward, a new “knowledge management” approach to new drug testing and regulation promises further gains in streamlining drug development. Under this CDER initiative, sponsors will submit applications that present data in a structured format so that the information on a new therapy can be transmitted to teams of agency experts for timely and efficient assessment.

The aim, explained Woodcock at the April Biostatistics Industry & Regulator Forum sponsored by the Drug Information Association (DIA) and FDA, is to shift sponsors away from long, narrative documents filed in PDF format that are repetitive and often bury the important issues. Instead, CDER assessment teams composed of medical reviewers, pharmacologists, statisticians, pharmacists, and other specialists will examine data to answer specific questions relevant to the product under review.

Woodcock is finalizing this new assessment process to handle a surge in submissions arising from important advances in biopharmaceutical science, as well as the digital revolution that has expanded exponentially the data and information supporting biomedical research. Our understanding of clinical pharmacology, and the vast amount of data from gene sequencing, she commented, along with greater scrutiny of the value of new medical products, require “a new approach” in providing an assessment-not a review-of new drug applications (NDAs) and biologics license applications (BLAs).

To be able to assess efficiently a rising number of applications for increasingly complex therapies, review teams will identify key issues during the investigational new drug (IND) stage to be able to focus on those items in the application more efficiently and with appropriate expertise. The resulting assessment document will present a benefit/risk evaluation, the drug development program, key issues, and recommendations. Ideally, CDER teams will finish this initial assessment midway through the review period to leave ample time for FDA and the sponsor to discuss post-market research commitments and the need for a REMS (Risk Evaluation and Mitigation Strategy) well before approval deadlines. This will lead to “high quality, more uniform work products,” Woodcock said, “with fewer surprises and last-minute changes.” And the process should be more transparent and provide advisory committees with clear issues to address.

Implementation of this new assessment process coincides with a significant reorganization of CDER’s Office of New Drugs (OND). It will expand from six to eight offices to better provide patients and researchers with identifiable experts in leading disease areas: neuroscience (including pain and addiction); inflammation/immunology (rheumatic conditions, transplant therapies); internal medicine (diabetes, hematology); oncology; human reproduction (urology, OB-GYN, pediatrics, maternal health); over-the-counter (OTC) drugs; and other treatments (ophthalmology, medical imaging, compounding).

OND also will have a centralized project management group to ensure that all divisions and teams follow consistent processes and to help external stakeholders and other FDA operations identify appropriate contacts. OND is trying out this team approach on a few applications and hopes to have it in place by the end of this year.

Jill Wechsler is the Washington Correspondent for Applied Clinical Trials