Health Policy$ense

During COVID-19, FDA’s Vaccine Advisory Committee Has Worked To Boost Public Trust – It Can Still Do More

[Original post: Ravi Gupta, Jason L. Schwartz, Joseph S. Ross, Genevieve Kanter, During COVID-19, FDA’s Vaccine Advisory Committee Has Worked To Boost Public Trust – It Can Still Do More, Health Affairs Blog, February 26, 2021. https://www.healthaffairs.org/do/10.1377/hblog20210225.712221/full/. Copyright ©2021 Health Affairs by Project HOPE – The People-to-People Health Foundation, Inc.]

This morning, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet to discuss Johnson & Johnson's/Janssen’s EUA request for what would be the third COVID-19 vaccine to be authorized by the U.S. Food and Drug Administration (FDA). Long an obscure but influential part of the FDA approval process for new treatments and vaccines, VRBPAC has received unparalleled attention during the COVID-19 pandemic. It already met an unprecedented three times in a two-month period late 2020, first to discuss COVID-19 vaccine licensure and the emergency use authorization (EUA) process, and then to consider EUA requests for specific COVID-19 vaccine products from Pfizer/BioNTech and Moderna. Composed of a group of nongovernmental scientists, clinicians, and other experts, VRBPAC helps the FDA obtain independent, expert advice on scientific and regulatory matters, including evaluating vaccine safety and efficacy, and critically, makes these deliberations public and transparent.

Amidst the challenges of promoting and sustaining public confidence in the FDA and COVID-19 vaccines  – and vaccines, generally – VRBPAC has come to play a pivotal additional role: engendering trust. Dr. Peter Marks, director of the FDA Center for Biologics Evaluation and Research, has repeatedly emphasized the value of public VRBPAC deliberations in building public trust in COVID-19 vaccines. In contrast to prior VRBPAC meetings for emerging infections like Ebola and H1N1, those for COVID-19 have set a new, encouraging precedent in terms of their frequency, their timely discussions of individual vaccine products, and their direct and repeated acknowledgment of the importance of vaccine confidence and public trust.

Why has public trust – or a lack thereof – become such a challenge? We believe it can be explained, in part, by the confluence of a global pandemic, extraordinarily rapid development timelines, and the relatively novel use of an EUA for vaccine candidates rather than traditional approval. But it is also of a piece with a broader cultural phenomenon in which trust has become precarious in general. This was compounded last year by early worries of political interference in the review and approval process. The success of COVID-19 vaccines fundamentally rests on delivery of a trusted vaccine.

We believe policy makers should consider additional actions through which VRBPAC can meet its fundamental charge of evaluating scientific evidence, while also buttressing trust in vaccines and the FDA. This is particularly salient as additional, potentially less efficacious COVID-19 vaccines are considered for emergency authorization and previously authorized ones move towards traditional approval, and is also important for maintaining trust during the post-pandemic period.

Past Epidemic VRBPAC Meetings

VRBPAC meetings during pandemics and epidemics have reflected the specific historical period within which they were convened, though in the past they largely addressed scientific and licensure questions. In July 2009, VRBPAC met within two months of the H1N1 pandemic’s onset. Aside from a brief discussion of the anticipated low vaccine yield and the ensuing distribution challenges, the committee discussion focused on the use of existing seasonal influenza licenses to expeditiously approve an H1N1 pandemic vaccine as a supplement. A November 2009 VRBPAC meeting mentioned post-marketing surveillance after multiple H1N1 vaccines had been approved, but no other meetings discussed H1N1 pandemic vaccines.

In 2015, during the largest Ebola outbreak to date, a VRBPAC meeting focused on the use of immunologic markers and animal studies to demonstrate pre-licensure effectiveness of Ebola vaccines. This discussion helped inform the specific regulatory pathway for a vaccine’s potential approval. Notably, the committee did not meet again to discuss Ebola vaccine candidates, despite another outbreak from 2018 to 2020, during which time the first and only Ebola vaccine was approved by the FDA. Furthermore, no VRBPAC meetings were held to discuss Zika, SARS, or MERS.

VRBPAC And COVID-19

While much of the format and content of the October 2020 meeting on COVID-19 vaccines was familiar, the tenor was markedly different from prior meetings held during pandemics or epidemics. Prior to the meeting, referring to VRBPAC, Dr. Marks noted that “approval should be something that we can make transparent.” The meeting was clearly intended to showcase the deliberative process of evaluating scientific evidence to build public trust and confidence in COVID-19 vaccines. The meeting was promoted as being open to the public and live-streamed, and the recording was immediately made available online. The agenda included numerous presentations focused on mitigating vaccine distrust. Nearly all of the comments from invited public speakers raised concerns about diminishing trust in vaccines and the FDA. Many speakers brought up the vital importance of ensuring diversity in clinical trials. The significance of a transparent process to promote trust in vaccines was again emphasized during the product-specific December meetings, where committee members were repeatedly asked to consider the role of vaccine trust and hesitancy.

Convening multiple VRBPAC meetings during such a short time span, particularly to discuss individual vaccine candidates, was also unprecedented and of enormous significance given COVID-19’s consequences and the urgent need for an effective vaccine. Moreover, the committee grappled with novel questions of EUA standards for the safety and efficacy of COVID-19 vaccine products, such as the appropriate clinical endpoint (for example, infection or serious illness) and sufficient follow-up time. The FDA faces a perennial challenge of balancing speed and certitude, a task made all the more difficult amidst a historic health crisis. The agency must present a transparent, thorough VRBPAC process while avoiding the perception that the committee meetings are simply a gesture in which the authorization of a vaccine is a foregone conclusion.

Strengthening VRBPAC: COVID-19 And Beyond

As we work to end the current pandemic and also anticipate future epidemics, what more can be done to further strengthen the FDA’s processes and the perceived integrity of vaccines, as well as VRBPAC?

One step would be to schedule earlier meetings to inform vaccine development efforts, such as to contribute directly to FDA guidance documents on licensure and EUAs. As more evidence was generated and made public as part of the VRBPAC meeting process, vaccine confidence appeared to increase. Additional structural changes to VRBPAC – such as permitting real-time review of data from ongoing clinical trials and earlier, more frequent meetings to discuss crucial questions as they arise – would make the committee even more nimble.

In addition, VRBPAC members and speakers should be broadly representative—including both scientists and members of the public, and reflect a diversity of perspectives —and financial conflicts of interest among VRBPAC members should be minimized to further strengthen trust in the committee's deliberative process. Currently, the committee consists of scientists and physicians with expertise in infectious diseases, immunology, biostatistics, and epidemiology, among others; a consumer representative; and a non-voting industry representative, with a group of invited public speakers. It is critically important to ensure that the views of marginalized communities are well represented. Committee members with substantial financial interests are required to recuse themselves, but others are given waivers to participate despite their conflicts because the benefits of their expertise outweigh potential harms. Although the frequency of meeting waivers among FDA advisory committees has diminished since the mid-2000s, VRBPAC meeting waivers are still issued with some regularity. Waivers for two members were issued over the three COVID-19 meetings and several other members who had previously disclosed a conflict of interest, including the committee chair, did not attend the meetings. Minimizing financial conflicts is critical for the FDA's trust-building process.

Moving forward, meetings to discuss COVID-19 vaccine post-authorization adverse events will be essential, particularly given the novel vaccine technological and surveillance platforms and the speed of vaccine development. VRBPAC will also need to discuss standards for traditional approval of vaccines that were initially granted EUAs, an issue compounded by challenges of maintaining placebo arms in clinical trials. Beyond the current pandemic, annual VRBPAC meetings to discuss emerging infections may be necessary for anticipating difficult regulatory and scientific questions.

Transparent VRBPAC deliberations alone will not curb vaccine hesitancy. A commitment to clear public communication and thoughtful community engagement rooted in evidence-based behavioral science is also critical. But VRBPAC will play an increasing and essential role in lifting public trust in vaccines and in the FDA beyond the current pandemic, particularly as more vaccines are developed using newly validated technological platforms. The end of this pandemic may be near, but much work remains.