University of Alabama at Birmingham

Data and Safety Review Board Reports How it Monitored the COVID-19 Vaccine Trials

Responsibility for the safety, integrity and scientific validity of the trials fell to 12 experts of the COVID-19 Vaccine Data and Safety Monitoring Board, who now have taken the unusual step of publishing details of their review process.

Newswise — BIRMINGHAM, Ala. – Clinical evaluation of three COVID-19 vaccine candidates in 2020-21 during a worldwide pandemic that killed or sickened millions was unprecedented in terms of urgency and scope. Responsibility for the safety, integrity and scientific validity of the trials in the United States fell to 12 experts of the federally appointed COVID-19 Vaccine Data and Safety Monitoring Board, or COVID-19 DSMB, who in turn report to an oversight group.

This COVID-19 DSMB team — which included co-contributing author Richard Whitley, M.D., distinguished professor of pediatrics in the University of Alabama at Birmingham School of Medicine — has now taken the unusual step of publishing details of their review process in The Journal of Infectious Diseases.

Their goal, they say, is to assure the public of the board’s independence and lack of interference from external actors, while they operated under exceptional conditions. Challenges the board faced included:

  • The remarkable scale and pace of the trials.
  • The frequency of safety events among a combined enrollment of more than 100,000 people, many of whom were older adults or persons with comorbidities that put them at independent risk of serious health events.
  • The need to monitor a portfolio of related trials rather than a single trial, and the need to harmonize these studies.
  • The politicized setting in which the trials have taken place, including a United States presidential election.

Despite these challenges, they say that the COVID-19 Vaccine DSMB also “can serve as a model for future situations in which there is an urgent need for coordinated development of multiple therapeutic or preventive interventions to address rapidly evolving public health threats.”

The story began in May 2020, as the federal government launched Operation Warp Speed to accelerate COVID-19 vaccine development. The operation included funding for multiple large randomized trials to assess the safety and efficacy of candidate vaccines and agreements to purchase hundreds of millions of doses to assure timely manufacture of ample quantities of vaccine.

To ensure rigorous, independent and unbiased scientific and ethical oversight of the vaccine field trials, the National Institute of Allergy and Infectious Diseases, or NIAID, empaneled the COVID-19 Vaccine DSMB. The board has 11 members from the United States, Brazil, South Africa and the United Kingdom, including experts in infectious disease, vaccinology, immunology, biostatistics, pharmacoepidemiology, public health and bioethics, as well as a biostatistician, who is a full-time NIAID employee and serves as executive secretary.

The DSMB’s Journal of Infectious Diseases article details their study review process as they reviewed three formal interim efficacy analyses of trials for vaccine makers Moderna, Janssen and AstraZeneca. The board currently is monitoring the Moderna, Janssen, AstraZeneca and Novavax trials. The trial of the Pfizer/BioNTech vaccine, which was not federally funded, has a separate DSMB.

The DSMB reports that it has met by videoconference more than 25 times, generally for two to three hours at a time. As needed, the board holds ad hoc meetings to address emerging safety concerns. If accrual or event milestones were met between scheduled meetings, the board met to review interim analyses.

The board focused on trial conduct, safety and vaccine efficacy. This included a close look at accrual of trial participants, including the numbers and proportions of people in relevant subgroups like age, sex, race, ethnicity and people with risk factors that predispose them to severe COVID-19.

“The DSMB’s role in overseeing a portfolio of multiple trials,” the board writes, “has facilitated its ability to perform safety monitoring across all trials. For example, when concerns first surfaced about thromboembolic events associated with AstraZeneca’s vaccine in Europe, the DSMB was able to review relevant categories of adverse events across its portfolio of trials to look for broader patterns associated with SARS-CoV-2 vaccines as a class.”

Participant safety was a central responsibility for the board, which devoted much attention at each meeting to review interim safety metrics. Given the large number of participants in the trials, the board also received regular reports of individual adverse safety events between meetings and determined what further information or actions in response might be needed.

Among the political challenges the board faced was what Science magazine called its “extraordinary rebuke” last March, when the board said the company had used potentially misleading and outdated data in its initial analysis.

The highly politicized atmosphere also included an August 2020 tweet by then-President Donald Trump that the United States Food and Drug Administration “deep state” was delaying COVID-19 vaccines, and his September suggestion that a vaccine for COVID-19 could be ready by Election Day. Another political challenge came when then-FDA Director Stephen Hahn said he was prepared to authorize a vaccine before Phase 3 trials were complete.

Yet politics did not affect the board’s work. In its report, the COVID-19 Vaccine DSMB concluded that “Operation Warp Speed is an unprecedented effort to develop safe and effective vaccines that will help end the COVID-19 pandemic.

“Conducting clinical trials under these circumstances requires the utmost attention to participant safety and to data integrity, so that the public and the medical community will ultimately have trust in the vaccines and the process used to develop them. Although (the board) operates behind the scenes, by virtue of its access to unblinded interim data, its charge to recommend changes to ongoing studies based on these data, and its ability to examine emerging data across multiple parallel trials, the COVID-19 Vaccine DSMB is uniquely positioned to ensure that these goals are met.”

Co-authors with corresponding author Steven Joffe, M.D., University of Pennsylvania, and Whitley, of the report “Data and safety monitoring of COVID-19 vaccine clinical trials” are the other board members and the executive secretary. They are Abdel Babiker, University College London, United Kingdom; Susan S. Ellenberg, University of Pennsylvania; Alan Fix, Center for Vaccine Innovation and Access, PATH, Washington, D.C.; Marie R. Griffin, Vanderbilt School of Medicine, Nashville, Tennessee; Sally Hunsberger, NIAID, Rockville, Maryland; Jorge Kalil, Universidade de São Paulo, São Paulo, Brazil; Myron M. Levine, University of Maryland School of Medicine, Baltimore, Maryland; Malegapuru W. Makgoba, Office of Health Standards and Compliance, Pretoria, Republic of South Africa; Reneé H. Moore, Emory University, Atlanta, Georgia; and Anastasios A. Tsiatis, North Carolina State University, Raleigh, North Carolina.

Support for operations of the COVID-19 Vaccine DSMB came from NIAID.


Filters close

Showing results

110 of 6110
Released: 2-Aug-2021 6:05 PM EDT
Rethinking Remdesivir
University of California San Diego Health

UC San Diego researchers modify remdesivir, creating oral version that can be taken earlier in COVID-19 diagnoses. In cell and animal studies, revised drug proved effective and safe.

Newswise: Researchers from Hackensack Meridian University Medical Center and Colleagues Develop New Model to Help Clinicians Predict Risk of Death in Patients Hospitalized with COVID-19
Released: 2-Aug-2021 4:25 PM EDT
Researchers from Hackensack Meridian University Medical Center and Colleagues Develop New Model to Help Clinicians Predict Risk of Death in Patients Hospitalized with COVID-19
Hackensack Meridian Health

New COVID-19 40-day mortality risk model, published in The Public Library of Science ONE, has potential for use in patient treatment planning, comparisons of therapeutic strategies, and public-health preparations.

Released: 2-Aug-2021 4:05 PM EDT
Town Hall on Effectiveness of COVID-19 Vaccination in Immunosuppressed Patients Hosted by the American College of Rheumatology
American College of Rheumatology (ACR)

How effective COVID-19 vaccines have been in immunosuppressed and rheumatic disease patients remains an incompletely answered question. The American College of Rheumatology (ACR) has organized an expert panel to share what we are learning from real-world data and answer questions.

Released: 2-Aug-2021 2:00 PM EDT
CDC withdrawing its request for emergency use authorization for its COVID-19 PCR diagnostic test does not mean the test failed

Social media is now rife with claims about why the CDC is withdrawing its request for emergency use authorization for its COVID-19 PCR diagnostic test after December 2021.

Newswise: Existing Drug Is Shown to Inhibit Virus That Causes COVID-19
Released: 2-Aug-2021 1:30 PM EDT
Existing Drug Is Shown to Inhibit Virus That Causes COVID-19
Argonne National Laboratory

Scientists using the Advanced Photon Source have discovered that a drug used to fight tumors in animals might be effective against many types of coronaviruses, including SARS-CoV-2.

Released: 2-Aug-2021 11:25 AM EDT
Award-Winning Journalist and CDC Principal Investigator to Serve as ACR Convergence 2021 Keynote Speaker
American College of Rheumatology (ACR)

Convergence 2021, the annual meeting of the American College of Rheumatology (ACR), returns to a virtual meeting platform Nov. 1 - 10. This year’s meeting will include presentations from over 320 clinicians, researchers and health experts, including this year’s keynote speaker, Dr. Seema Yasmin.

Newswise: COVID-19: Small Sign of Hope as Vaccinations Rise
Released: 2-Aug-2021 10:45 AM EDT
COVID-19: Small Sign of Hope as Vaccinations Rise

As COVID-19 cases spike in Los Angeles and throughout the Golden State, driven by the spread of the delta variant among unvaccinated residents, there may be a small sign of hope: More people are finally getting their shot.

Newswise: New Evidence Shows the COVID-19 Delta Variant Rapidly Rising
Released: 31-Jul-2021 10:05 AM EDT
New Evidence Shows the COVID-19 Delta Variant Rapidly Rising
University of Miami Health System, Miller School of Medicine

The University’s coronavirus sequencing effort uncovered that there are several variants present in its patient population, but Delta is chief among them and easily transmitted. And its presence is likely triggering a local surge in the infectious disease. University of Miami researchers and physicians are seeing firsthand how rapidly the Delta variant of COVID-19 is spreading through the local population.

Released: 30-Jul-2021 2:05 PM EDT
Thinking Impaired in 60% of COVID-19 Survivors, Study Finds
University of Texas Health Science Center at San Antonio

In a sample of over 400 older adults in Argentina who had recovered from COVID-19, more than 60% displayed some degree of cognitive impairment, a researcher from The University of Texas Health Science Center at San Antonio reported July 29 at the Alzheimer’s Association International Conference.

Showing results

110 of 6110