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Applied Clinical Trials
FDA's new commissioner advocates for a "learning healthcare system" and less-complex clinical trial models that tap efficiencies in study design and enrollment.
Among the multiple items on the “to-do” list of new FDA Commissioner Robert Califf is to make clinical research more efficient and reliable to accelerate the development of safe and effective treatments for patients. Califf has long advocated for a “learning healthcare system” that taps electronic health records to facilitate clinical trial design and enrollment, and to provide ongoing information on the effects and side effects of therapies in real-world use. Now Califf has a ready platform to promote such strategies to further precision medicine and expedited approval of innovative medical products.
In a March appearance before a Senate Appropriations subcommittee to discuss FDA’s requested budget for fiscal year 2017, Califf noted the agency’s success in approving more innovative drugs for market, many facilitated by expedited review programs and patient engagement in product development. His testimony cited efforts to refine clinical trial design and statistical methods of analysis, and to utilize advances in genomics and information technology to gain “more rapid, less expensive and more reliable answers about medical products.”
Most of the hearing, though, focused on the many other FDA activities important to the legislators, from effective monitoring of the nation’s food supply to halting the lethal abuse of opioids. Other top priorities for FDA involve tobacco regulation, combating antibiotic resistance, reducing high-risk drug compounding, and developing medical countermeasures to Ebola and Zika. Califf promised to soon issue guidances and regulations to further biosimilar development and to better manage FDA’s IT infrastructure. He also will have to seek Congressional backing for multiple new user fee proposals now being finalized by FDA and industry task forces.
During his confirmation process, Califf pledged that he would not lower FDA’s standards in evaluating the safety and efficacy of drugs and medical devices in response to challenges from legislators who feared that his ties to pharma would bias him towards industry. And while he avoids discussing drug prices, he recognizes that FDA can promote drug access by bringing more generic drugs to market, and that good information about medical product risks and benefits can support those who make coverage decisions.
Califf’s expertise in biomedical research should help him tackle these and other difficult regulatory and policy issues, as seen in his activity as FDA deputy commissioner for the past year. At a December 2015 FDA workshop on enhancing the collection and assessment of clinical data on diverse patient subgroups, he described the challenges in managing trials to generate such data. He recently opened a meeting of FDA’s Science Board that was called to advise the agency on the development and regulation of medical treatments for pain, where new product research is important for lowering opioid abuse.
A blog posted on FDA’s website in February cites progress in clarifying terms and definitions related to the development of biomarkers and other tools needed to advance biomedical research and inform clinical trials. And last October, the commissioner endorsed an FDA report on coordinating the review of combination products, a hot topic in the biomedical research community. Cancer advocates have been pressing for a new entity to coordinate the development and oversight of cancer therapies and diagnostics, and Califf has said he will establish such a center under the White House Cancer MoonShot initiative.
At a March Institute of Medicine (IOM) workshop on “Neuroscience Trials of the Future,” Califf described some of the difficulties and opportunities facing FDA and sponsors in achieving more effective clinical studies on treatments for nervous system disorders. In the “ideal world” of a learning healthcare system, Califf commented, sponsors and investigators would conduct concept studies that lead to informed clinical trials, and those results then would be used to write practice guidelines and to guide more “real-world” studies that, in turn, would provide more evidence and refine practice.
Complexity and costs
Unfortunately, Califf sees the research community opting for larger, more complex clinical trials, with the result that costs are “going off the scale.” Investigators enroll fewer patients per site because “we’re making things more and more complex,” something that he hopes FDA can address. He suggested that trials stop running multiple blood tests and collecting rare, non-serious adverse events from all patients, which “costs a ton of money.”
It’s not necessarily FDA that seeks more data from larger studies, Califf observed, but sponsors that shy away from simplified studies-often to avoid greater uncertainty. The challenge for FDA, he said, is to develop study models that all parties “feel good about.” FDA can’t promise it will approve a new product if the researchers do things in a certain way, as there are “always surprises with medical products,” he commented. But the agency can assure, Califf said, that it won’t come back later and say it didn’t like that approach.