To understand the usual approval process followed by the FDA, researchers of the Yale University School of Medicine have systematically evaluated all novel vaccines approved by the FDA over the last decade, characterizing the premarket development and regulatory review times, the clinical evidence
on which approval was based, and the size and follow-up duration of the prelicensure safety database.
Between January 2010 and June 2020, the FDA approved 21 vaccines, most commonly for influenza (5 [23.8%]) and meningococcus (5 [23.8%]). Of these, 4 (19.0%) received Accelerated Approval. The median premarket clinical development period (investigational new drug submission to FDA
approval) was 8.1 (interquartile range [IQR], 6.1-10.5) years, including a median FDA review period (BLA submission to FDA approval) of 12.0 (10.8-21.0) months.
Each vaccine approval was supported by a median total of 7 (IQR, 5-13) clinical trials, including 2 (IQR, 1-3) pivotal efficacy trials and 1 (IQR, 1-1) trial considered essential to establishing lot-to-lot consistency.
The median number of patients in the prelicensure safety database was 6710 (IQR, 4576- 15 997), and the median follow-up for serious adverse events was 6 months (IQR, 6-12).
The median aggregated number of patients enrolled among all pivotal efficacy trials supporting a given vaccine approval was 4961 (IQR, 3537-7775).
All 21 vaccines were approved based on at least 1 randomized pivotal efficacy trial and 14 (66.7%) based on at least 2 pivotal efficacy trials. Among the 21 vaccines, 17 (81.0%) had at least 1 pivotal efficacy trial that used masking, 20 (95.2%) that used an active or placebo comparator group, and 8 (38.1%) approved based on a clinical primary end point; of these, themedian vaccine efficacy was 91.9% (IQR, 79.6%-98.0%).
Among the 5 vaccines for diseases for which no FDA-approved vaccine existed at time of approval, 4 (80%) used a clinical primary end point.
Given the urgency of developing a COVID-19 vaccine, trials will need
to be larger than those supporting prior vaccine approvals and include sufficient follow-up time for emergence of adverse effects.
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