The Oval Office, biopharmaceutical executives, and federal agencies have signaled that COVID-19 vaccines could be ready to go this fall; however, leading experts believe that proof of a safe and effective vaccine before Election Day is unlikely. President Trump has said that “we can probably have [a COVID-19 vaccine] sometime in October.” Pfizer and BioNTech executives think they could know whether their joint COVID-19 vaccine candidate works by the end of October, and that the Food and Drug Administration (FDA) will grant it an Emergency Use Authorization (EUA). The Centers for Disease Control and Prevention (CDC) wants states ready to distribute a COVID-19 vaccine as soon as late October, with distribution sites operational by November 1st. While it is certainly important to be primed to distribute life-saving vaccines, a more realistic scenario is that thorough analyses determining the safety and efficacy of COVID-19 vaccine candidates should be possible at the very end of this year, or beginning of next year.
Nevertheless, extremely optimistic COVID-19 vaccine approval timelines that converge with Election Day are being broadcast to the American public, and during Wednesday’s Senate Health, Education, Labor, and Pensions (HELP) Committee hearing, lawmakers demanded assurances that scientific data, not political agendas, will drive the COVID-19 vaccine approval process.
The path forward for phase III COVID-19 vaccine candidates
Three COVID-19 vaccine candidates that could be made available to Americans are currently in phase III clinical trials, and their paths forward rely on the actions that are taken by the vaccine-makers, FDA, the Department of Health and Human Services (HHS, FDA’s parent agency), and the President.
Whereas vaccine candidate clinical trials have historically been designed and executed by biopharmaceutical companies alone, COVID-19 vaccine candidate trials have been overseen by the US Government. To gauge if any of the vaccine candidates prevent or decrease the severity of disease with at least 50 percent efficacy – the bar FDA set at the end of June – tens of thousands of people are being enrolled in each COVID-19 vaccine candidate phase III clinical trial. In fact, on Saturday, Pfizer proposed to FDA that it enroll up to 44,000 participants, almost 50 percent more than the initial target of 30,000. Half are dosed with the vaccine candidate, the other half are dosed with placebo, and, to prevent bias, only a select group of experimentalists – not the trial participants, not the professionals administering the doses – know who gets what. During Wednesday’s hearing, Dr. Francis Collins, the director of the National Institutes of Health, asserted (2:26:10 mark in video) that once 150 people in the entire trial have developed symptomatic disease, it should be possible to determine whether a vaccine candidate is 50 percent effective. However, some experts say that even the point at which the trial reaches 150 cases of disease is unlikely to provide enough time to prove vaccine candidate safety.
Each individual COVID-19 vaccine candidate trial is tracked by a unique Data Safety and Monitoring Board (DSMB). DSMBs are multidisciplinary groups, independent of both the vaccine-maker and the federal government, composed of clinical trials specialists, biostatisticians, bioethicists, immunologists, vaccinologists, and virologists. As trials progress, DSMBs regularly review the data as they accumulate, and make recommendations to the company and to FDA about whether a vaccine has met safety and efficacy standards. Ultimately, DSMBs are only advisory groups, and it is up to the company as to whether it submits a Biologics License Application (BLA) to FDA for their COVID-19 vaccine candidate.
FDA will review the clinical trial data in the BLA for safety and efficacy. Following FDA’s review, the company and the FDA have the option of presenting their findings to FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), another expert body independent of both the federal government and the vaccine-maker. If consulted, VRBPAC would provide advice to FDA regarding the safety and efficacy of the vaccine. Regardless, FDA could then approve or deny the vaccine candidate for use.
Alternatively, a vaccine-maker could request an EUA from FDA, which opens up the possibility of a vaccine being approved for use before the conclusion of the clinical trial, which could complicate the trial’s full evaluation of safety and efficacy. Another tool FDA could possibly use is Accelerated Approval, a process that could base vaccine approval only on antibody levels or another surrogate biochemical marker produced in trial participants, rather than measuring actual protection from disease. Notably, HHS, or possibly President Trump, could even overrule an FDA rejection of a request for an EUA.
Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, believes there would be a moral obligation to end a trial early and make a vaccine accessible if the data from the trial were to be overwhelming that the vaccine candidate is safe and effective.
Federal officials testify that COVID-19 vaccine decisions will be based only on science
During the hearing, Senator Bernie Sanders (D, VT) pressed (1:14:27 mark in video) the witnesses to affirm that the COVID-19 vaccine approval process will only be driven by science. Dr. Collins pledged that he and all US Government scientists will be basing COVID-19 vaccine candidate evaluations and assessments only on science, or else he would have no part in the process. He also expressed cautious optimism that the US will produce a safe and effective vaccine by the end of the year, adding “certainly to try to predict whether it happens on a particular week before or after a particular date in early November is well beyond anything that any scientist right now could tell you and be confident that they know what they’re saying.”
Vice Admiral Jerome Adams, the US Surgeon General, concurred with this sentiment, stating that a COVID-19 vaccine will not be moved along unless it is proven to be safe and effective, that shortcuts will not be taken, and that once approved or authorized by FDA, he and his family would not hesitate to receive the vaccine.
Will words translate into action as Election Day approaches?
Dr. Collins and Vice Admiral Adams are not the only ones giving assurances that science, not political influence, will drive COVID-19 vaccine approval. Career civil servants at FDA reiterated their resolve to working “with agency leadership to maintain FDA’s steadfast commitment to ensuring our decisions will continue to be guided by the best science.” The head of Operation Warp Speed (the US effort to accelerate COVID-19 vaccine development), Dr. Moncef Slaoui, says he will “immediately resign if there is undue interference in this process.” And nine COVID-19 vaccine-making companies have pledged to “uphold the integrity of the scientific process as they work towards potential global regulatory filings and approvals of the first COVID-19 vaccines.”
We will be tracking this issue closely as Election Day nears, and will be sure to alert the community to new developments. To review the entirety of this week’s hearing, click here.