The Effect of Approved COVID-19 Vaccines on Ongoing Clinical Trials

February 8, 2021

While new vaccines typically take years to develop, the unprecedented urgency of the COVID-19 pandemic has led to several new vaccines being developed and distributed within a year. In the U.S., there are currently two vaccines that have been granted Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) based on recommendations from the Center for Disease Control’s (CDC) Advisory Committee on Immunization Practices (ACIP) [1]. One of these is Comirnaty (BNT-162b2), commonly known as the BioNTech-Pfizer vaccine, and the other is mRNA-1273, better known as the Moderna vaccine. The decision to grant an EUA to these two COVID-19 vaccines has generated debate over the ethical and practical implications of ongoing clinical trials, not only for BNT-162b2 and mRNA-1273, but for dozens of vaccine candidates that remain in development.  

The FDA has suggested certain considerations be made regarding the continuation of ongoing trials once one or more COVID-19 vaccines have been approved. One consideration is whether researchers have the obligation to “unblind” their trials by vaccinating placebo recipients once the vaccine is considered safe and effective [2]. The urgency of this consideration has been accelerated by the efforts of trial participants, some of whom have begun lobbying the companies who developed the two original vaccines to inform them of whether or not they received the real vaccine, and to administer it to them if they received the placebo. Participants in the Moderna trial have begun to be immunized, while those who participated in the BioNTech-Pfizer trial have been notified that they could receive the first of the vaccine’s two doses as early as March 1 [3]. Proponents of unblinding trials argue that researchers have a moral obligation to their participants, whose health and well-being they have been entrusted to maintain. However, unblinding a vaccine trial can make it more difficult for researchers to collect long-term data regarding the safety and efficacy of the vaccine.  

The EUA is only relevant so long as there is an ongoing public health crisis. Currently, no vaccine has received the regular FDA approval which would ensure it could continue being marketed and distributed after the pandemic ends. The current EUA depends on the judgement of regulators that the benefits of the two vaccines outweigh any risks. If Pfizer and Moderna wanted to continue administering their COVID-19 vaccines beyond the near future, they would have to provide evidence that the benefits continue to outweigh the risks, which would come from continued trials to determine long-term safety and efficacy [4, 5]. Opponents of unblinding the trials note that researchers are obligated only to meet the ethical conditions of an Independent Review Board (IRB) in the U.S. based on available evidence, not to administer a vaccine to placebo recipients once it has been judged effective [4].  

In studies documenting the trials for the Pfizer vaccine, researchers emphasized that regulators should authorize vaccines as quickly as possible [6][7]. While the efficacy threshold of an authorized vaccine is important in predicting the impact it will have on infection and hospitalization rates in the population, the speed and efficiency of production and distribution are also factors in the success of a vaccination effort [8]. Although Moderna and Pfizer have received an EUA, distribution limitations impair the ability of these vaccines to curb the effects of the pandemic, especially in places with insufficient healthcare infrastructure. Limited availability and transportation issues have complicated the rollout of the Pfizer and Moderna vaccines. The distribution of Pfizer’s vaccine poses particular problems as it must be stored at very low temperatures. The two vaccines were first authorized in December 2020, meaning implementation strategies could still improve in the coming months. However, if the current vaccination campaign continues to falter, it could incentivize the continued development and authorization of more vaccines to meet demand [5]. 


[1] James Kingsland | Medical News Today | Jan 4, 2021. “Is it Ethical to Continue COVID-19 Vaccine Trials?” Medical News Today, 4 Jan. 2021, is-it-ethical-to-continue-covid-19-vaccine-trials.  

[2] Wendler, David, et al. “COVID-19 Vaccine Trial Ethics Once We Have Efficacious Vaccines.” Science, vol. 370, no. 6522, 2020, doi: 10.1126/science.abf5084.  

[3] Judy Peres | Chicago Tribune | Jan 14, 2021. “Vaccine Trial Participants Who Received Placebo Now Hop the Line for the Real Thing from Pfizer, Moderna.” Chicago Tribune, 14 Jan. 2021.  

[4] Karen Kaplan | Science and Medicine Editor | Los Angeles Times | Dec 12, 2020. “The FDA Didn’t ‘Approve’ Pfizer’s COVID-19 Vaccine. Here’s Why.” Los Angeles Times, 12 Dec. 2020,  

[5] Cohen, Jon. “Vaccine Wagers on Coronavirus Surface Protein Pay Off.” Science, vol. 370, no. 6519, 2020, doi: 10.1126/science.370.6519.894.   

[6] Polack, Fernando P., et al. “Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine.” New England Journal of Medicine, vol. 383, no. 27, 2020, pp. 2603–2615., doi:10.1056/nejmoa2034577. 

[7] Walsh, Edward E., et al. “Safety and Immunogenicity of Two RNA-Based COVID-19 Vaccine Candidates.” New England Journal of Medicine, vol. 383, pp. 2439-2450., doi: 10.1056/nejmoa2027906.    

[8] Paltiel, A. David, et al. “Clinical Outcomes of a COVID-19 Vaccine: Implementation Over Efficacy.” Health Affairs, vol. 40, no. 1, 2020, doi: 10.1377/hlthaff.2020.02054.