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Better clinical data are needed, as well as strategies for tackling opioid abuse, tobacco use, and food safety.
Amidst a host of serious challenges for maintaining FDA operations and programs, FDA Commissioner Robert Califf is most determined to combat erroneous reports about medical treatments and clinical practice. “Misinformation is the leading cause of death in the United States today,” Califf stated at a online briefing sponsored by the Alliance for Health Policy on July 28, 2022. He noted that a poor understanding of the effects of medical treatments “leads people to make decisions that are harmful to health.”
Unfortunately, Califf fears that FDA is “actually losing the battle on misinformation” related to COVID, as seen in the large number of Americans who have not been vaccinated, he observed in a conversation with the editor of Health Affairs on August 3, 2022. Millions of people are refusing vaccines and therapies despite evidence that such treatments can reduce the risk of dying from the disease by 90%. “Vaccines are basically working,” Califf stated, yet he sees many people who won’t take a treatment that’s free and highly effective.
Califf hopes to address this conundrum with a strategy for dealing with the “avalanche of differing opinions” that is confusing and difficult for Americans to navigate. This cardiologist recalls such problems throughout his career, as experts failed to reach agreement on treatment strategies for critical conditions. And today, when FDA makes a regulatory decision, it draws comments from all corners of the world, he notes, which ends up providing the public with a “sea of information” that’s difficult to navigate.
Califf’s response is to establish a “better evidence generation system” in the United States, with expert networks devoted to developing reliable information and to checking facts to overcome misleading statements. He recognizes that there is a highly effective clinical trial system in the US, where pre-approval studies produce needed data on product safety and effectiveness. But problems arise in postapproval confirmatory studies, where answers can take years, even decades, to emerge. To gain needed evidence, Califf would like to see clinical trials embedded in care and utilizing information systems that can tap larger samples of patients to answer questions very quickly.
Clinical research has experienced some success is becoming more diverse in several ways, Califf believes, as seen in “tremendous progress” in including children in research, a group that he saw completely left out of clinical trials in the past. He would like to see similar gains in bringing research to rural America, where inadequate health care has reduced life expectancy notably. Califf would like clinical research to address disparities between urban and rural areas, as well as differing treatment responses of ethnic and racial populations.
A continuing challenge for FDA is the use of expedited clinical research approaches to accelerate the development and approval of treatments for lethal and rare diseases. The agency’s accelerated approval pathway has raised questions about abbreviated testing methods and chronic delays in follow-on trials. Califf indicated that while abbreviated, single-arm trials may be appropriate for testing new therapies for untreated cancers and rare diseases, randomized trials with proper controls may be more acceptable in providing evidence for treating conditions with approved therapies.
In addition to addressing the harmful effects of medical misinformation, Califf faces a host of regulatory and policy crises across the board. Not the least is the looming loss of funding due to delays in Congress reauthorizing user fees and a new budget for 2023.
In addition, a broad overhaul of the agency’s oversight of tobacco and related products is a top priority. With 30 million Americans still using tobacco, plus a rise in vaping products, Califf sees FDA entering a new era in tobacco product oversight, with key decisions looming on menthol cigarettes and reduced-nicotine products. Califf anticipates “major disagreements” no matter what FDA does but hopes that transparent communications will build support.
Opioid addiction remains a critical challenge. Califf seeks new strategies for providing education and oversight of prescribing and access to regulated opioids, while also dealing with a huge increase in illegal high-dose fentanyl pills sent through the mail. FDA is preparing a plan for more collaborative approaches to address these issues, but Califf recognizes there is “no magic bullet” for dealing with this ongoing national crisis.
Califf also has launched a broad review of food oversight and regulation by the agency, spurred in part by the recent infant formula crisis. FDA seeks better funding and improved hiring authority for its food programs, as well as a broader assessment of the impact of changes in how food is grown and distributed in the US. And the sudden drop in infant formula supplies has highlighted the need to diversify sources and increase US production of such critical products.
Califf observed during these briefings that when he decided to return to FDA for another stint as commissioner, he anticipated there would be very serious challenges, but not as many as have erupted. But he re-upped for the job because he also recognized that heading FDA would “take someone with not much at stake.” His long experience overseeing clinical trials has made clear to him the importance of good evidence and strong collaboration in organizing programs and making sound decisions, and he continues to work to apply such approaches to the complexities and diversity of FDA.
Jill Wechsler is Washington editor for Pharmaceutical Technology.