Gottlieb Seeks Modern Clinical R&D to Promote Innovation, Public Health

The new FDA commissioner, Scott Gottlieb, took the helm of the agency last month as its staff began the considerable task of implementing important initiatives authorized by the 21st Century Cures legislation. The day Gottlieb was confirmed, the FDA Science Board approved a detailed work plan for allotting the $500 million (over nine years) provided by Cures to develop multiple programs intended to advance new therapies and ensure patient access to treatment. The legislation imposes numerous tight deadlines for FDA

Jill Wechsler

to issue new guidances, reports and regulations and to hold public meetings with stakeholders to devise and revise these and other policies.

Gottlieb also is busy setting priorities and redefining FDA’s role related to numerous health and medical issues. The opioid epidemic is top priority, as FDA seeks to balance the critical need for effective treatment of patients living with pain, with efforts to limit unauthorized access to medicines subject to abuse and misuse. Main initiatives are to encourage development of abuse-resistant formulations, new non-opioid pain therapies, and better treatments for patients who overdose. 

FDA also is at the forefront of efforts to develop new vaccines and therapies to combat deadly infectious diseases, a role that requires greater research capacity and regulatory flexibility. During the confirmation process, Gottlieb earned points by discounting claims of a link between vaccines and autism. And in the name of greater FDA transparency, he has proposed public release of “complete response” letters on nonapproval of  drug applications, despite strong objections from sponsors. The commissioner also faces pressure for FDA to do more to reduce high drug costs, which focuses on efforts to bring more complex generic drugs and biosimilars to market more quickly. And he is expected to advocate for looser restrictions on sponsor communication of off-label information.

Internally, FDA is implementing a major overhaul of its field force as part of the Program Alignment initiative in the works for several years. Agency officials also are embroiled in contentious debate over regulation of tobacco and laboratory-developed tests. For now, Gottlieb benefits from a notable budget increase for FDA through September and indications that Congress will move to pass legislation before summer that reauthorizes critical new FDA user fee programs for drugs, medical devices, generic drugs and biosimilars. But future agency funding is uncertain, and the agency still faces hurdles in recruiting the scientists and experts it needs to efficiently evaluate ever-more-complex medical products. Administration deregulatory policies, moreover, raise uncertainty about which FDA standards and rules will remain in effect. 

Innovation and research

Some of the Cures initiatives are familiar, such as qualifying more biomarkers and other drug development tools, modernizing clinical trial design, using more real-world evidence (RWE) to approve new indications and postmarketing studies, expanding the role of patients in assessing new drug risks, and promoting more coordination among FDA Centers, particularly for combination products. New to the agency is a framework for approving regenerative therapies, which gained a new designation and submission process under Cures.

Gottlieb supports such approaches in Cures and the next drug user fee program as part of the broader goal of modernizing research for innovative medical products. He has said that clinical trials may not always require randomization, and that faster studies don’t necessarily compromise on safety or undermine the FDA gold standard for assuring medical product efficacy, despite critics who predict dire consequences from such approaches. 

The new commissioner may find support for modernizing clinical research from Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER). At the DIA/FDA annual Statistics Forum in April, she highlighted development of more sensitive measures of clinical outcomes and improvements in patient-reported outcomes to better measure product performance. And she noted the value of strategies for incorporating more RWE into modern clinical trials, possibly by using health system data and methods for randomizing patients that remain in a healthcare system. 

In the future, sequential, randomized trials won’t be able to answer the multiple questions involving rare subgroups with rare diseases, Woodcock noted, pointing to the need for platform trials with master protocols to more efficiently evaluate disease outcomes for multiple experimental treatments.