The evidence base for emergency use authorizations for COVID‐19 treatments: A rapid review

Abstract

Background and Aims During the COVID‐19 pandemic, US Food and Drug Administration (FDA) permitted emergency use authorizations (EUAs) for vaccines/treatments with promising data. Eight treatments were issued EUAs by May 31, 2021; one of these was approved (Remdesivir for certain populations) and two were revoked (chloroquine phosphate/hydroxychloroquine and bamlanivimab) by September 30, 2021. The aim of this study is to find out what evidence the EUAs were based on and how many studies were published while they remained active (up to September 30, 2021). Methods A review of published clinical studies for the 6 months before each EUA was issued, and the time after (until September 30, 2021, or until revoked). PubMed and the identified systematic reviews were the sources for identifying published literature. Results The number of clinical studies published pre‐EUA varied from a single case study (for chloroquine phosphate/hydroxychloroquine) to numerous studies of multiple types (for convalescent plasma). Four treatments had a single randomized controlled trial (RCT) as evidence (bamlanivimab monotherapy, REGN‐COV, bamlanivimab + etesevimab, sotrovimab) and two also had other study types (remdesivir and baricitinib). The number of clinical studies published post‐EUA (for those active on September 30, 2021) was widely varied. Eighteen RCTs were published for Convalescent plasma, while Remdesivir had eight. Baricitinib, REGN‐COV, and bamlanivimab + etesevimab all had one, but none were published for sotrovimab. Conclusion The number of trials for treatments with EUAs was limited in all cases before the EUA was issued, and in most cases for those with EUAs ongoing at the end of September 2021. The presence of EUAs may discourage participation in relevant clinical trials, which delays the widespread implementation of evidenced‐based therapies. Large, robust RCTs should be completed, such as the RECOVERY trial in the United Kingdom, to quickly find the answers desperately required during a pandemic.

The emergency use authorization for COVID‐19 convalescent plasma reduced mortality

“…In their review of the evidence base for emergency use authorizations (EUAs) by the US Food and Drug Administration (FDA), 1 the authors assert that "The presence of EUAs may discourage participation in relevant clinical trials." But the data in the paper suggest otherwise.…”

“…In their review of the evidence base for emergency use authorizations (EUAs) by the US Food and Drug Administration (FDA), 1 the authors assert that “ The presence of EUAs may discourage participation in relevant clinical trials .” But the data in the paper suggest otherwise. Tables 2 and 3 show that for the eight agents examined, more than four times as many randomized controlled trials (RCTs) were conducted between the time the EUAs were issued and September 2021 than before the EUAs.…”