As part of its routine review process, the U.S. Food and Drug Administration (FDA), the agency responsible for evaluating and deciding if the handful of COVID-19 vaccines currently being studied are safe and effective enough to use by people around the world, convened a committee on Oct. 22 to allow experts and the public to learn about and comment on the review process.
The FDA’s Vaccines and Related Biological Products Advisory Committee is responsible for reviewing any applications by manufacturers hoping to get vaccines to market. The 18-member committee includes scientists and doctors with infectious disease, virology, and epidemiology expertise from academia, industry and government. Over a period of four and a half hours, the committee, which met virtually, heard from invited speakers from the government agencies responsible for developing testing and distributing COVID-19 vaccines about the latest plans for evaluating how safe and effective the vaccines are. Experts provided updates from the National Institutes of Health (which provided basic research that led to many of the vaccine candidates), the Centers for Disease Control and Prevention (which is responsible for working with state and local health departments to lay out plans for distributing the vaccines if and when they are authorized), the FDA (which provides criteria for what makes a vaccine safe and effective), BARDA (a Department of Health and Human Services office overseeing research and development of treatments against public health threats) and the inter-agency Operation Warp Speed (which is coordinating development, testing and distribution efforts).
Marion Gruber, director of the office of vaccines research and review at the FDA’s Center for Biologics Evaluation and Research (CBER), opened the meeting by saying “I want to take a minute to assure the American public that facilitating the development of safe, effective COVID-19 vaccines is the highest priority of my office, CBER and the agency. Today’s discussion provides transparency about the data we will request and evaluate in support of the safety and effectiveness of vaccines.”
The FDA confirmed it will consider a COVID-19 vaccine effective if it achieves 50% effectiveness in protecting against the illness. The members and speakers debated about what this protection means, and raised the possibility that it could indicate that immunized people would still get infected, but then not progress on to serious disease.
Another key question centered around what type of green light the FDA would give vaccines developed and tested on an accelerated timeline. The traditional approval process can take years from development to market, but the leading COVID-19 vaccine candidates sped from development to human testing in a matter of months. Emergency use authorization, or EUA, would further shorten the review process, as it requires shorter follow-up of people in the studies for effectiveness of the vaccines and their potential side effects (EUAs are allowed during public health crises, such as the pandemic, when the urgency of the need for treatments justifies the shorter research and development time). The FDA guidelines for COVID-19 vaccines currently require at least two months of follow up, although some experts questioned whether that was long enough to truly get a sense of a vaccine’s efficacy. That’s especially true since the coronavirus is so new to the world that the vaccine makers aren’t yet sure what immune reactions are needed to constitute a “strong” or
“appropriate” response that would provide protection against infection. FDA scientists reiterated that their guidelines for EUA are generally as stringent as those for full approval, except for the shorter time frame.
Another unresolved issue centers around what will happen to ongoing placebo controlled studies if one or more of the vaccines are given EUA ahead of others. Given that the virus is still spreading in parts of the U.S., participants in ongoing trials may want to drop out of their studies and get vaccinated with an authorized shot, once available. But because the trials are all blinded, neither they, nor their doctors, will know if they received the experimental vaccine or a placebo. Those studies would have be unblinded if volunteers will be allowed to drop out, but that would mean researchers will not get the same high quality data on vaccines still being studied if those trials are stopped.
“Once a decision is made to unblind it can’t be walked back,” said Doran Fink, deputy director in division of vaccines and related products applications at FDA. “That control [group] is lost forever.”
Many speakers also stressed the need to continue to follow trial participants in order to collect more data on the vaccines’ effectiveness and side effects. The FDA noted that all of the participants will be followed for two years even after the trials end. During the public comment period, patient advocates and other infectious disease experts argued that the FDA should consider at least a six month follow-up period before allowing any manufacturer to request authorization or approval. That’s in stark contrast to the Trump Administration’s view; the White House initially opposed even the two month window.
Members and speakers also raised the importance of addressing vaccine hesitancy, and the need to understand and address the many reasons why people have expressed reluctance to get vaccinated if and when COVID-19 shots become available. These range from general vaccine skepticism, to mistrust of the government and science, and more specific concerns about COVID-19 immunizations that have been developed in record time and seem to be rushing through the testing process. Some people may also intentionally wait to get vaccinated because they are skeptical of the first shots to come off the assembly line, which could keep infections percolating for longer.
“People may be waiting to see what the first candidates are, and even waiting for a more ‘favorable’ candidate,” said Dr. Janell Rough, medical officer and program lead in the division of viral diseases at the CDC. “That’s not a message we want to convey.”
Shifting those views may be one of the bigger challenges facing a massive COVID-19 immunization effort. Federal and state pubic health officials are taking this into consideration as they formulate plans for distributing the vaccines when they become available. All 64 state and local health groups in the country have submitted their plans for ordering and distributing vaccines. The CDC is now reviewing those plans and will work with local officials to refine them and provide resources necessary to educate the public about the vaccines themselves as well as the need for getting vaccinated more broadly.
An FDA advisory committee got a primer on criteria they should consider when evaluating COVID-19 vaccine candidates on safety and effectiveness