The clinical evaluation of three COVID-19 vaccine candidates in 2020 and 2021 during a global pandemic that killed or fell ill with millions of people was unprecedented in both urgency and scope. Responsibility for the safety, integrity and scientific validity of the studies in the USA rests with 12 experts from the federally appointed COVID-19 Vaccine Data and Safety Monitoring Board (DSMB), who in turn report to a supervisory group.
This COVID-19 DSMB team, which included author Richard Whitley, MD, Distinguished Professor of Pediatrics at the University of Alabama at the Birmingham School of Medicine, has taken the unusual step of including details of his review process in. to publish The Journal of Infectious Diseases.
The aim of the authors is to ensure the public’s independence of the panel and the interference of external actors while it was operating under exceptional conditions. Some of the challenges the board faced included:
- The remarkable size and speed of the experiments.
- The frequency of safety events in a combined enrollment of more than 100,000 people, many of whom were elderly adults or those with comorbidities who put them at independent risk for major health events.
- The need to monitor a portfolio of related studies rather than a single study and the need to harmonize those studies.
- The politicized environment in which the trials took place, including a US presidential election.
Despite these challenges, members say the COVID-19 vaccine DSMB can also “serve as a model for future situations where there is an urgent need for coordinated development of multiple therapeutic or preventive measures to address rapidly evolving public health threats” .
The story began in May 2020 when the federal government launched Operation Warp Speed to expedite COVID-19 vaccine development. The operation included funding several large, randomized trials to evaluate the safety and efficacy of vaccine candidates and agreements to purchase hundreds of millions of doses to ensure that sufficient quantities of vaccine were produced in a timely manner.
To ensure rigorous, independent, and unbiased scientific and ethical oversight of vaccine field trials, the National Institute of Allergy and Infectious Diseases (NIAID) has introduced the COVID-19 vaccine, DSMB. The board consists of 11 members from the United States, Brazil, South Africa and the United Kingdom, including experts in infectious diseases, vaccinology, immunology, biostatistics, pharmacoepidemiology, public health and bioethics, and a biostatistician who is a full-time NIAID employee and acts as Executive Secretary
The DSMB’s article describes its trial review process for three formal preliminary efficacy studies of trials for vaccine makers Moderna, Janssen, and AstraZeneca. The Board is currently overseeing the studies carried out by Moderna, Janssen, AstraZeneca and Novavax. The Pfizer / BioNTech vaccine study, which was not federally funded, has a separate DSMB.
The safety of the participants was a central task of the Board of Directors, who paid close attention to the review of the preliminary safety metrics at each meeting. In view of the large number of study participants, the Executive Board also received regular reports between the meetings on individual undesirable security incidents and determined which further information or measures might be required in response.
The highly politicized atmosphere included a tweet from then President Donald Trump in August 2020 that the US Food and Drug Administration (FDA) “deep state” is delaying COVID-19 vaccines and his September proposal that a vaccine against COVID-19 could be ready by election day. Another political challenge arose when then-FDA director Stephen Hahn said he was ready to approve a vaccine before Phase III trials were completed.
“Conducting clinical trials in these circumstances requires careful attention to participant safety and data integrity so that the public and medical community ultimately have confidence in the vaccines and the process of their development,” reports the Board of Directors. “Although (the Board of Directors) due to its access to non-blinded intermediate data, its role in recommending changes to ongoing studies based on that data, and its ability to examine emerging data across multiple parallel studies, the COVID-19 ( the board) working in the background Vaccine DSMB is uniquely positioned to ensure that these goals are achieved. “
Edited by Gary Cramer