New England Journal of Medicine
November 5, 2020 Vol. 383 No. 19
Emergency Use Authorization of Covid Vaccines — Safety and Efficacy Follow-up Considerations P.R. Krause and M.F. Gruber
… Use of an investigational vaccine under an EUA would not be subject to the usual informed consent requirements for clinical investigations; nevertheless, vaccine recipients will be provided a fact sheet that describes the investigational nature of the product, the known and potential benefits and risks, available alternatives, and the option to refuse vaccination. To minimize the risk that use of a vaccine under an EUA will interfere with long-term assessment of safety and efficacy in ongoing trials, it will be essential to continue to gather data about the vaccine even after it is made available under the EUA. Continued follow-up of clinical trial participants to further refine efficacy estimates, further evaluate the potential for enhanced disease and waning of immunity, and obtain additional active safety follow-up will be essential in order to ensure public confidence in a broadly administered vaccine. The quality of the data available to inform ongoing assessment of a vaccine’s benefits and risks will depend on the ability to continue evaluating the vaccine against a placebo comparator in clinical trials for as long as feasible. Moreover, evaluation of other potentially superior vaccines will depend on the ability to continue to maintain placebo controls in ongoing trials. Thus, issuance of an EUA should not, in and of itself, require unblinding of a Covid-19 vaccine trial and immediate vaccination of placebo recipients, since doing so may jeopardize approval of these products.
In setting criteria for EUAs, regulators determine the amount of data that could support a positive benefit–risk assessment, providing people who wish to receive an investigational vaccine the opportunity to realize that benefit while also providing confidence that a vaccine is unlikely to cause net harm when used in this manner.
From a safety perspective, a 2-month median follow-up (meaning that at least half of vaccine recipients in clinical trials have at least 2 months of follow-up) after completion of the full vaccination regimen will allow identification of potential adverse events that were not apparent in the immediate postvaccination period and will also provide greater confidence in their absence, if none are observed…