Data and Safety Review Board reports how it monitored COVID-19 vaccine trials – News
The clinical evaluation of three COVID-19 vaccine candidates in 2020-2021 during a global pandemic that has killed or sickened millions of people was unprecedented in terms of urgency and scope. Responsibility for the safety, integrity, and scientific validity of trials in the United States rests with 12 experts from the Federal Council for Data Surveillance and Vaccine Safety COVID-19, or COVID-19 DSMB, who report to in turn a monitoring group.
This COVID-19 DSMB team – which included co-contributing author Richard Whitley, MD, distinguished professor of pediatrics at the University of Alabama at Birmingham School of Medicine – has now taken the unusual step of releasing details of their review process in The Journal of Infectious Diseases.
Their aim, they say, is to ensure the independence of the board of directors and the absence of interference from external actors, while they were operating under exceptional conditions. The challenges the board faced included:
- The remarkable scale and pace of the events.
- The frequency of safety events among a combined recruitment of over 100,000 people, many of whom were elderly or people with co-morbidities that put them at independent risk for 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 took place, including a presidential election in the United States.
Despite these challenges, they say the COVID-19 DSMB vaccine “may also serve as a model for future situations where there is an urgent need for the coordinated development of multiple therapeutic or preventive interventions to address rapidly evolving public health threats. “.
The story began in May 2020, when the federal government launched Operation Warp Speed to accelerate the development of the COVID-19 vaccine. The transaction included funding for several large randomized trials to assess the safety and efficacy of candidate vaccines and agreements to purchase hundreds of millions of doses to ensure the timely manufacture of large quantities of vaccines.
To ensure rigorous, independent and impartial scientific and ethical oversight of the vaccine’s field trials, the National Institute of Allergy and Infectious Diseases, or NIAID, has established the COVID-19 DSMB vaccine. The board has 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, as well as a biostatistician, who is an Employee of NIAID and serves as the executive secretary.
The DSMB Journal of Infectious Diseases article details their study review process as they reviewed three formal interim efficacy reviews of trials for vaccine manufacturers Moderna, Janssen and AstraZeneca. The board of directors is currently monitoring the Moderna, Janssen, AstraZeneca and Novavax trials. The Pfizer / BioNTech vaccine trial, which was not federally funded, has a separate DSMB.
The DSMB reports that it has met by videoconference more than 25 times, typically for two to three hours at a time. As needed, the board holds ad hoc meetings to discuss emerging security issues. If any accumulation or event milestones were reached between scheduled meetings, the board would meet to review interim analyzes.
The council focused on the conduct of trials, safety and efficacy of vaccines. This included careful consideration of the number of trial participants, including the number and proportions of people in relevant subgroups such as age, sex, race, ethnicity, and people with disabilities. risk factors that predispose them to severe COVID-19.
“The role of the DSMB in overseeing a portfolio of multiple trials,” the board wrote, “facilitated its ability to perform safety oversight in all trials. For example, when concerns first surfaced regarding thromboembolic events associated with AstraZeneca vaccine in Europe, the DSMB was able to examine relevant categories of adverse events in its trial portfolio to look for broader patterns. associated with SARS-CoV-2 vaccines as a class. “
The safety of the participants was a central responsibility of the board, which devoted a great deal of attention at each meeting to reviewing the interim safety measures. Given the large number of trial participants, the board also received regular reports on individual adverse safety events between meetings and determined what additional information or actions might be needed.
Among the political challenges the board faced was what Science magazine called its “extraordinary reprimand” last March when the board said the company had used potentially misleading data and obsolete in its initial analysis.
The highly politicized atmosphere also included an August 2020 tweet from then-President Donald Trump that the US Food and Drug Administration’s “deep state” was delaying COVID-19 vaccines, and his September suggestion that a COVID-19 vaccine could be ready by Election Day. Another political challenge arose when then FDA director Stephen Hahn said he was ready to clear a vaccine before Phase 3 trials were completed.
Yet the politics did not affect the work of the council. 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 data integrity, so that the public and the medical community ultimately have confidence in the vaccines and the process used to develop them. Although (the council) operates behind the scenes, due to its unblinded access to provisional data, its responsibility to recommend changes to ongoing studies based on that data, and its ability to examine emerging data in Several parallel trials, the COVID-19 DSMB vaccine is uniquely positioned to ensure that these goals are met.
The co-authors with corresponding author Steven Joffe, MD, University of Pennsylvania and Whitley, of the report “Data Monitoring and Safety of COVID-19 Vaccine Clinical Trials” are the other members of the Board of Directors and the executive secretary. They are Abdel Babiker, University College London, United Kingdom; Susan S. Ellenberg, University of Pennsylvania; Alan Fix, Center for Innovation and Access to Vaccines, PATH, Washington, DC; 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 the COVID-19 DSMB vaccine operations came from NIAID.