The clinical evaluation of three candidates against the COVID-19 vaccine in 2020-21 during a global pandemic that killed or sickened millions was unprecedented in terms of urgency and scope. Responsibility for the safety, integrity, and scientific validity of trials in the United States rested with 12 experts from the COVID-19 Vaccine Data and Safety Monitoring Board, or COVID-19 DSMB, who in turn report to a monitoring group.
This team from COVID-19 DSMB, which included co-collaborating author Richard Whitley, MD, a distinguished professor of pediatrics at the University of Alabama at Birmingham School of Medicine, has now taken the unusual step of publishing details of the your review process a The Journal of Infectious Diseases.
They say their goal is to assure the public of board independence and the lack of interference from outside actors, while operating in exceptional conditions. Challenges faced by the board included:
- The remarkable scale and rhythm of the essays.
- The frequency of safety events between a combined enrollment of more than 100,000 people, many of whom were older adults or people with comorbidities that put them at independent risk of serious health events.
- The need to control a portfolio of related trials rather than a single trial and the need to harmonize these studies.
- The politicized environment in which the trials have taken place, including the U.S. presidential election.
Despite these challenges, they state that the COVID-19 DSMB vaccine can also “serve as a model for future situations where there is an urgent need for coordinated development of multiple therapeutic or preventive interventions to address threats to public health that they evolve rapidly “.
The story began in May 2020, when the federal government launched Operation Warp Speed to accelerate the development of the COVID-19 vaccine. The operation included funding for multiple large randomized trials to evaluate 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 vaccine.
To ensure rigorous, independent, and impartial scientific and ethical oversight of vaccine field trials, the National Institute of Allergy and Infectious Diseases (NIAID) promoted 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 works at full time. NIAID employee and executive secretary.
The DSMB Journal of Infectious Diseases The article details the study review process while reviewing three provisional formal analyzes of trial efficacy for vaccine manufacturers Moderna, Janssen, and AstraZeneca. The board currently oversees the trials of Moderna, Janssen, AstraZeneca and Novavax. The Pfizer / BioNTech vaccine trial, which did not receive federal funding, has an independent DSMB.
The DSMB reports that it has met by video conference more than 25 times, usually for two or three hours at a time. As needed, the board holds ad hoc meetings to address emerging security issues. If accumulation or event milestones were met between scheduled meetings, the board met to review the interim reviews.
The board focused on conducting testing, safety and efficacy of vaccines. This included a detailed look at the accumulation of participants in the trials, including the number and proportions of people in relevant subgroups such as age, sex, race, ethnicity, and people with risk factors that predispose them. and severe COVID-19.
“The role of the DSMB in overseeing a multi-trial portfolio,” the board writes, “has facilitated its ability to perform safety checks on all trials. For example, when concerns about associated thromboembolic events arose. to the AstraZeneca vaccine in Europe, able to review relevant categories of adverse events in its test portfolio to look for broader patterns associated with SARS-CoV-2 vaccines as a class. “
The safety of participants was a central responsibility of the board, which devoted much attention at each meeting to reviewing interim safety metrics. Given the large number of participants in the trials, the board also received periodic reports of 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 the magazine called its “extraordinary reprimand” 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 from then-President Donald Trump, according to which the U.S. Food and Drug Administration “deepened” would delay COVID-19 vaccines and its suggestion of September that a vaccine against COVID-19 could be prepared for Election Day. Another political challenge came when then-FDA Director Stephen Hahn said he was willing to authorize a vaccine before completing the phase 3 trials.
However, the policy did not affect the work of the council. In its report, the COVID-19 DSMB vaccine 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 in these circumstances requires the utmost care for participants security and the integrity of the data, so that the public and the medical community have confidence in the vaccines and the process used to develop them. Although (the dashboard) operates behind the scenes, by virtue of its access to provisional blind data, its role is to recommend changes to ongoing studies based on this data and its ability to examine emerging data in multiple parallel trials. The COVID-19 DSMB vaccine has a unique position to ensure that these objectives are met. ”
Steven Joffe et al, Data monitoring and safety of COVID-19 vaccine clinical trials, The Journal of Infectious Diseases (2021). DOI: 10.1093 / infdis / jiab263
University of Alabama at Birmingham
Citation: The Data and Safety Review Panel reports on how it controlled the COVID-19 vaccine trials (2021, June 15) retrieved June 16, 2021 at https://medicalxpress.com/news/2021-06- safety-board-covid-vaccine-trials .html
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