{"id":50415,"date":"2021-06-08T15:41:22","date_gmt":"2021-06-08T14:41:22","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=50415"},"modified":"2021-07-30T07:59:46","modified_gmt":"2021-07-30T06:59:46","slug":"why-we-petitioned-the-fda-to-refrain-from-fully-approving-any-covid-19-vaccine-this-year","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2021\/06\/08\/why-we-petitioned-the-fda-to-refrain-from-fully-approving-any-covid-19-vaccine-this-year\/","title":{"rendered":"Why we petitioned the FDA to refrain from fully approving any covid-19 vaccine this year"},"content":{"rendered":"

We are part of a group of clinicians, scientists, and patient advocates who have lodged a <\/span>formal \u201cCitizen Petition\u201d<\/span><\/a> with the United States Food and Drug Administration (FDA), asking the agency to delay any consideration of a \u201cfull approval\u201d of a covid-19 vaccine. The message of our petition is \u201cslow down and get the science right\u2014there is no legitimate reason to hurry to grant a license to a coronavirus vaccine.\u201d We believe the existing evidence base\u2014both pre- and post-authorization\u2014is simply not mature enough at this point to adequately judge whether clinical benefits outweigh the risks in all populations.<\/span><\/p>\n

The covid-19 vaccines in widespread use <\/span>have emergency authorizations (EUA), not actual approvals<\/span><\/a>, a crucial regulatory distinction that reflects major differences in the level of regulatory scrutiny and certainty about the risk-benefit balance.<\/span><\/p>\n

Our petition doesn\u2019t argue that risks outweigh benefits\u2014or that benefits outweigh risks. Rather, we focus on methods and processes, outlining the many remaining unknowns about safety and effectiveness\u2014and suggest the kinds of studies needed to address the open questions.<\/span><\/p>\n

If the FDA listens to us, they won\u2019t give serious consideration to approving a covid-19 vaccine until 2022. Our first request is that the FDA require manufacturers to submit data from completed Phase III trials\u2014not interim results. Trials by vaccine manufacturers were designed to follow participants for two years, and should be completed before they are evaluated for full approval, even if they are <\/span>now unblinded and lack placebo group<\/span><\/a>s. These Phase III trials are not simply efficacy studies; they also are necessary and important safety studies (as <\/span>the<\/span><\/a> study<\/span><\/a> titles<\/span><\/a> say), and all collected data remain invaluable.<\/span><\/p>\n

We also call on FDA to require a more thorough assessment of spike proteins produced <\/span>in-situ<\/span><\/i> by the body following vaccination\u2014including studies on their full biodistribution, pharmacokinetics, and tissue-specific toxicities. We ask the FDA to demand manufacturers complete proper biodistribution studies that would be expected of any new drug and request additional studies to better understand the implications of mRNA translation in distant tissues. We call on data demonstrating a thorough investigation of <\/span>all<\/b> serious adverse events reported to pharmacovigilance systems, carried out by independent, impartial individuals, and for safety data from individuals receiving more than two vaccine doses, in consideration of plans for future booster shots. We ask the FDA to request necessary studies in specific populations, including those previously infected with SARS-CoV-2, pediatric subjects, and those with immunological or other underlying medical complexities. Given the nature of the novel vaccine platforms, our petition asks for experts in gene therapy to be included among the external committee advising the FDA.<\/span><\/p>\n

These are several of our major requests. The petition has been signed by a group of 27 clinicians, researchers, and consumer advocates with diverse experiences and thoughts about the pandemic. We all agree that there remain many open, unanswered questions surrounding the efficacy and safety of covid-19 vaccines that must be answered before the FDA gives serious consideration to granting full approval.<\/span><\/p>\n

These are the reasons why we lodged our petition. There is no need to rush approval to help stop the pandemic because the vaccines already have Emergency Use Authorization. Yet a rushed process is the very possibility that now confronts us. In the past month, Pfizer and Moderna submitted formal applications for \u201cfull approval.\u201d<\/span><\/p>\n

Covid-19 vaccines are already fully accessible to all Americans who want one. EUAs have enabled their widespread use, and can remain in place even after the expiry of the SARS-CoV-2 public health emergency declaration, as is the case for various Zika products. Even without full approval, covid-19 vaccines will remain available for all who want them under EUA.<\/span><\/p>\n

Some surveys suggest that vaccine hesitancy in the United States is due, in part, to lack of full FDA approval. While approval might lead to increased public confidence in covid-19 vaccines, as well as provide legal support for employer-instituted vaccine mandates, to approve a medical product for these reasons is outside FDA\u2019s regulatory purview. Approval decisions must be driven by the safety and efficacy data. The potential unintended consequences of a rushed approval may contribute to growing mistrust of the US public health and regulatory institutions.<\/span><\/p>\n

Finally, regarding the elephant in the room: publicly raising any element of hesitation about covid-19 vaccines will be seen by some as irresponsible, stoking unfounded fears in the public\u2019s mind and contributing to the \u201cvaccine hesitancy\u201d problem trumpeted every day. But the alternatives\u2014privately raising concerns or simply remaining silent\u2014are arguably more detrimental to public trust in the long run. Staying silent is not the responsible option.\u00a0 And the implications of only privately raising concerns to regulatory bodies are murky\u2014most would probably not be acted upon, and if they were, it would promulgate the baggage of insufficient accountability and transparency in decision making.<\/span><\/p>\n

To us, the Citizen Petition seemed the most responsible approach: voice our concerns in our own words, in a professional and transparent manner, through a formal mechanism that can promote accountability in regulatory decision making.<\/span><\/p>\n

Approving a covid-19 vaccine now risks setting a precedent of lowered standards for future vaccine approvals. The \u201cFDA approved\u201d seal must represent a high bar\u2014and premature licensure of a covid-19 vaccine could seriously damage public confidence in regulatory authorities, particularly if long-term safety issues were to emerge following licensure. Keeping covid-19 vaccines under EUA regulations would also encourage vaccine manufacturers to continue investing resources in completing the necessary safety and efficacy studies for a potential FDA consideration of full licensure in the future.<\/span><\/p>\n

For each covid-19 vaccine, the benefits may ultimately outweigh the harms. Or not. Or we may end up in a more nuanced position, finding that benefits outweigh harms for some populations, but not others.\u00a0 Only time\u2014and better evidence\u2014will tell.\u00a0 And so it is vital we allow the scientific process the time required to gather and assess the evidence to be confident in the decisions we ultimately have to make.<\/span><\/p>\n

Our <\/span><\/i>citizen petition<\/span><\/i><\/a> <\/i>is filed under Docket ID <\/span><\/i>FDA-2021-P-0786 <\/span><\/i><\/a>on regulations.gov. Anybody <\/span><\/i>can comment<\/span><\/i><\/a> on the petition, or <\/span><\/i>read others\u2019 comments<\/span><\/i><\/a>, including the FDA\u2019s official reply once it arrives.<\/span><\/i><\/p>\n

See also:<\/p>\n