Recently it was reported that the President Biden appears ready to nominate former FDA Commissioner Robert Califf to boomerang back and head the agency for a second time. If so, he returns to very different circumstances than when he left FDA in January 2017 after an 11-month stay. While FDA is accustomed to controversy while making difficult decisions, lately, it is much more than that. A number of factors have been at play that together have begun to tear at the very reputational fabric of the agency, tarnishing the “gold standard” that has been maintained for so long.
In fact, on the one hand, FDA is doing pretty well. It has been maintaining operations throughout the COVID-19 pandemic. Like everyone else, the agency has had to convert operations to a virtual existence which is no small task when responsible for regulating one-fifth of the U.S. economy. For everything from inspections of manufacturing facilities to managing a large staff to conducting the regulatory review of new drug applications, including conducting advisory committee meetings virtually and transparently. In addition, the agency has maintained a solid pace. Last year in spite of the pandemic, there were 53 new molecular entities approved – nearly a record. And so far this year, there have been 41, which puts us on pace to nearly meet or exceed last year.
But on the other hand, a number of circumstances – all of which are inter-related, have come to play that have cast a shadow over the bright reputation of FDA and present some very specific challenges for the future.
- Science is Under Attack – This is nothing new. In the middle ages the roundness of the Earth was rebuffed (and apparently still is). There were those who challenged the fact that our planet did indeed circle the sun and not the other way around. And anti-vaxxers have been a reality since vaccines came into being. And of course, the science behind climate change has been repeatedly attacked in the last few decades. But the COVID-19 pandemic has a potent chorus of science skeptics who, thanks to amplification provided by social media, have a louder voice than they otherwise would have. The bottom line is that for an agency where the very foundation is one of scientific rigor, an attack on science is an attack on the very bedrock of FDA.
- The Perceived Politicization of FDA – Against a backdrop of political polarization that is in hyperdrive, many have felt that the agency has become unusually politicized. During both the Trump and Biden Administrations statements about the use of COVID-related products were made ahead of the regulatory process that would consider their approval, making it seem for some that the outcome were pre-determined. In sum, even if not intended, the optics were not good. The fact that the process has not been politicized is separate from the perceptions that some may have.
- The COVID-19 Pandemic – From the origins of the virus to the degree to which it makes people ill, the pandemic has been a focus of controversy and extreme opinions. Suddenly everyone is an epidemiologist and virologist. Apart from the controversies, FDA entered some unprecedented waters utilizing the Emergency Use Authorization for prevention, treatment, vaccines and diagnostics – a regulatory mechanism with which most people were unfamiliar. The speed with which vaccines were developed and cleared, combined with a new vaccine platform added fuel for detractors and skeptics.
- FDA’s Accelerated Approval Program is Under Scrutiny – The Accelerated Approval pathway for expedited access for medicines where there is a high unmet medical need for serious health conditions has been a focus in recent months. Accelerated Approval allows for the early approval of drugs based on early indications and looking at outcomes that appear to offer promise, pending later confirmatory clinical trials by the drug manufacturers. This year FDA has been reviewing drugs approved under the program to assess approvals in light of the changing treatment landscape and the status of the confirmatory trials. This has led to a close-up critical examination of the pathway by critics and a defense by FDA officials.
- Controversial Approvals – And speaking of accelerated approvals – there are always going to be difficult calls on clearing the way for some treatments, particularly where patient populations are facing dire consequences and treatment choices are few or non-existent. But no approval has caused as much of an uproar among so many stakeholders as the approval this year of a new treatment for Alzheimer’s following an overwhelmingly negative vote against a recommendation for approval by an FDA Advisory Committee. Several members of the committee resigned in protest, following publications from both FDA and those in opposition to the approval. FDA approved the label and then reversed course to narrow the treatment for a subset of patients. Paragraphs could (and have) been written about it, but in the end, there was an investigation announced by both Health and Human Services and by Congress into the process for approval. Confidence in the agency and the approval process was left shaken.
The combined result has left FDA with a trust issue – not something one wants at any time, much less in the middle of a pandemic. The Robert Wood Johnson Foundation and the Harvard T.H.Chan School of Public Health conducted a poll “The Public’s Perspective on the United States Health System” earlier this year. FDA did not show up so well with a lower degree of trust than other sources like the CDC and the Surgeon General and a higher percentage of people stating that they did not have much trust. So if Dr. Califf returns, it is a very different set of circumstances by far than in 2017.
And as with any reputational crisis, there are no simple answers and a solution involves a process, not an event. (1) It begins with communication and lots of it. Dr. Califf’s successor Dr. Gottlieb was extremely engaged in communications and the number, range and types of communications increased dramatically while he was Commissioner. It may be time to take a page from that notebook. (2) There needs to be be not only a good volume of communications, but they need to be consistent. (3) The messaging – which needs to pass a smell test – on a wide range of topics needs to be pegged down and the leaders of the agency need to embrace and use that messaging. (4) In addition, there needs to be an effort to get the backing of third parties who are credible to the stakeholders. The RWJF/Harvard survey indicated people trust local sources more than national ones. A grassroots strategy may be advisable. (5) The agency needs to embark on an historical education effort and enunciate a vision rather than respond to each and every issue. (6) There are a lot of loose ends to clean up, particularly with the Accelerated Approval program and the agency has to ensure both transparency and consistency in dealing with them.
FDA has always been driven by science. But most of FDA’s stakeholders are not scientists and they need to have things explained very clearly, consistently with coordinated messaging that is repeated often and is well-planned. With care and effort, this crisis will resolve. Science has always been under attack, but the arc of progress in medicine thankfully always bends to the gravity of science and not the distractions that sometimes stand in the way.