With promising phase III clinical trial results and subsequent Emergency Use Authorization (EUA) submissions for vaccine candidates developed by BioNTech/Pfizer and Moderna, it is anticipated the first effective medicines against the SARS-CoV-2 virus, the virus that causes COVID-19, may reach the public before year’s end. Notably, the pace of vaccine development has been unprecedented, as vaccine development normally spans a decade. This has naturally caused many to have concerns about the safety of these soon to arrive vaccines. The availability of an effective and safe vaccine trusted by the public is imperative, as in most countries infections are rapidly spreading at rates faster than this past spring. Therefore, it is vital that key agencies, such as the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), as well as influential infectious disease experts, inform the public on how safety is being monitored amongst vaccine candidates to provide reassurance and prompt vaccine participation.
COVID-19 vaccine EUA submission guidelines
Officials from the committees Center of Biologics Evaluation and Research and Vaccines and Related Biological Products, within the FDA, previously met with experts from the CDC, National Institute of Health (NIH), and Biomedical Advanced Research and Development Authority (BARDA). This meeting, held on October 22, 2020, created guidelines for companies requesting EUAs for COVID-19 vaccines (1). With regard to the safety and efficacy data requirements, there are two important general criteria that need to be met. First, there must be scientific evidence collected from sufficiently powered and controlled clinical trials that suggests the vaccine candidate will be effective to prevent infection from SARS-CoV-2. Second – and likely the most important for those with safety concerns – the data must showcase that both the known and potential benefits of their vaccine will outweigh any known and potential risks.
Potential risks that concern the public
The major safety concern centers around mistrust due to the speed and lack of transparency of the developed vaccines. The current vaccine candidates are using an RNA-based technology against the “spike” protein of SARS-CoV-2 to elicit an immune response. Like the concept of all vaccines, this will allow our immune systems to make antibodies against this protein so that upon subsequent exposure, our immune cells can recognize the virus and mount a swift and effective immune response. However, an RNA platform has never been the basis of any current FDA approved vaccines to date (2), leaving reasonable concerns that there could be unforeseen adverse events, and the expedited timeline for vaccine development is not sufficient to delineate let alone detect any potential side effects. Furthermore, there is concern whether the timeline allows for enough time to evaluate vaccine effectiveness, which is essential for the favorable benefit-risk determination required.
Addressing the publics’ fears
To curb these concerns, the publicly available requirements for EUA read as follows. All vaccine developers must have clinical data collected from an endpoint of a well-designed placebo-controlled phase 3 clinical trial that shows at least 50% efficacy against preventing COVID-19 infection. A median of at least two months of safety follow-up is required, which is a more stringent criterion than usual. In addition, companies must obtain the efficacy and safety data requirements, as stated above, through sufficiently powered (i.e. adequate number of subjects) trials. Lastly, sponsors are expected to continue their trials until full approval, which includes the standard six-month active safety follow-up analysis.
Infectious disease experts and public health officials have also tried to dampen the fear surrounding COVID-19 vaccine development. Dr. Saad Omer, director of the Yale Institute for Global Health and key member for a group within the World Health Organization evaluating the safety of COVID-19 vaccines, suggested that the compressed timeline of vaccine development is due to higher efficiency of the process rather than cutting corners (3). For example, most developers ran combined phase 1 and 2 clinical trials and have already begun preparations for high-scale manufacturing. He also commented that since current trials are event-driven trials and are defining efficacy as whether those exposed can become infected by SARS-CoV-2, the current rates of infection and chances of exposure in the United States are speeding up the trial. In essence, trials are reaching the minimum number of participants and results much quicker. With regard to unknown adverse events, by using a RNA-based vaccine platform, thus far, side effect symptoms have been injection site pain and low grade fever, which are common to vaccines in general. The more stringent two-month safety requirement, as well as the expanded plans being set in place by the CDC and FDA to monitor vaccine safety, is likely sufficient to dampen concerns, especially since serious adverse events surrounding any vaccine usually cluster within the first months after administration.
With once again rising cases of COVID-19, it is more important than ever that a safe and effective vaccine become available. Therefore, it is crucial that the FDA, in addition to other public health offices and key infectious disease experts continue to publicize factual, unbiased data that is easily digestible to the general public. This will ensure the public has the confidence in making an informed decision about a COVID-19 vaccine, with the overall hopeful outcome to defeat COVID-19.
About the author:
Lindsay Gurska Lindsay Gurska is a Cell Biology PhD trainee at Albert Einstein College of Medicine. She is interested in pursuing a career in science communication. Her current interest is in writing and creating promotional content for the therapeutic landscape.