Open letter to the CEOs of Pfizer and Moderna
As co-authors of a recent study on the safety of mRNA covid-19 vaccines that called for the full transparency of covid-19 vaccine clinical trial data, we wish to share this open letter to the CEOs of Pfizer and Moderna.
Dear Albert Bourla and Stéphane Bancel,
In the summer of 2020, before results from the trials were announced, vaccine manufacturers were criticized for keeping the trial protocols secret. In response, the protocols were released.[2,3] Yet the same did not happen for the trial data.
To the best of our knowledge, regulators such as the European Medicines Agency, UK MHRA, and Health Canada lack electronic individual participant data (IPD) datasets. As discussed below, these data can answer lingering questions regarding what the trials indicated regarding the balance of benefit to harm in December 2020, questions which are difficult to answer with what has been made public. The effort to prepare these datasets is minimal, and no potentially identifying data is needed. We therefore add our names to the call on Pfizer and Moderna to release the data.
Today (Aug 31), our study of serious adverse events in the Pfizer and Moderna phase 3 covid-19 vaccine trials was published in the peer-reviewed journal Vaccine. The results showed the Pfizer and Moderna both exhibited an absolute risk increase of serious adverse events of special interest (combined, 1 per 800 vaccinated), raising concerns that mRNA vaccines are associated with more harm than initially estimated at the time of emergency authorization.
We acknowledge that our estimates are only approximations because the original data remain sequestered. For example, we could not stratify by age, which would help clarify the populations in which benefits outweigh harms.
A more definitive determination of the actual harms and benefits requires individual participant data (IPD) that remain unavailable to research investigators. Unlike its European counterpart, the US regulator FDA does hold electronic IPD datasets, and in a meeting to discuss our study last March, we requested they repeat our analysis using IPD, but to our knowledge, this has not occurred. With the publication of our study, we have written the FDA again to reiterate our request.
Specifically, to allow assessment of the items of concern, for each and every hospitalization and SAE (including covid-19 and covid-19 sequelae), we need: a unique participant ID number, demographic details (participant’s age, sex, etc.), the type of SAE, some dates (enrollment, dose 1 and 2 administration, date of SAE or hospitalization), and whether or not the participant was included in the “FDA safety” subgroup (participants with median ≥ 2 months followup post dose 2). The above data should be extracted from the dataset at the timepoint that supported emergency use authorization (data cutoff 14 Nov 2020 for Pfizer, 25 Nov 2020 for Moderna). To support a more thorough analysis, manufacturers should also provide datasets with the above information at the timepoint that supported the vaccines’ subsequent approval (BLA).
Covid-19 vaccines are now among the most widely disseminated medicines in the history of the world. Yet, results from the pivotal clinical trials cannot be verified by independent analysts. The public has a legitimate right to an impartial analysis of these data. COVID vaccinations have cost taxpayers tens of billions of dollars, perhaps even rivaling the annual NIH budget for all aspects of biomedical and behavioral research.
Transparency, reproducibility, and replication are cornerstones of high-quality science. The time is overdue for Pfizer and Moderna to allow independent scientists and physicians to see the original data and to replicate the analyses. These small datasets can help answer very important questions and lay to rest widespread concerns over lack of transparency.
Joseph Fraiman, MD
Thibodaux Regional Health System, Thibodaux, LA, U.S.A.
Juan Erviti, PharmD, PhD
Unit of Innovation and Organization, Navarre Health Service, Spain
Mark Jones, PhD
Institute of Evidence-Based Healthcare, Bond University, Gold Coast, QLD, Australia
Sander Greenland, MA, MS, DrPH
Fielding School of Public Health and College of Letters and Science, University of California, Los Angeles, CA, U.S.A.
Patrick Whelan, MD PhD
Geffen School of Medicine, University of California, Los Angeles, CA, U.S.A.
Robert M. Kaplan, PhD
Clinical Excellence Research Center, School of Medicine, Stanford University, CA, U.S.A.
Peter Doshi, PhD
University of Maryland School of Pharmacy, Baltimore, MD, U.S.A.
1. Thomas K. Vaccine Makers Keep Safety Details Quiet, Alarming Scientists. The New York Times [Internet]. 2020 Sep 13 [cited 2020 Oct 5]; Available from: https://www.nytimes.com/2020/09/13/science/coronavirus-vaccine-trials.html
2. Grady D, Thomas K. Moderna and Pfizer Reveal Secret Blueprints for Coronavirus Vaccine Trials. The New York Times [Internet]. 2020 Sep 17 [cited 2022 Aug 21]; Available from: https://www.nytimes.com/2020/09/17/health/covid-moderna-vaccine.html
3. Grady D, Wu KJ, LaFraniere S. AstraZeneca, Under Fire for Vaccine Safety, Releases Trial Blueprints. The New York Times [Internet]. 2020 Sep 19 [cited 2022 Aug 21]; Available from: https://www.nytimes.com/2020/09/19/health/astrazeneca-vaccine-safety-blu...
4. Demasi M. From FDA to MHRA: are drug regulators for hire? BMJ [Internet]. 2022 Jun 29;377:o1538. Available from: http://dx.doi.org/10.1136/bmj.o1538
5. Doshi P, Godlee F, Abbasi K. Covid-19 vaccines and treatments: we must have raw data, now. BMJ [Internet]. 2022 Jan 19;376:o102. Available from: http://dx.doi.org/10.1136/bmj.o102
6. Fraiman J, Erviti J, Jones M, Greenland S, Whelan P, Kaplan RM, Doshi P. Serious Adverse Events of Special Interest Following mRNA COVID-19 Vaccination in Randomized Trials in Adults. Vaccine. 2022 August 31. https://doi.org/10.1016/j.vaccine.2022.08.036
Competing interests: JF, JE, MJ, SG, PW, RK: none to declare. PD has received travel funds from the European Respiratory Society (2012) and Uppsala Monitoring Center (2018); grants from the FDA (through University of Maryland M-CERSI; 2020), Laura and John Arnold Foundation (2017-22), American Association of Colleges of Pharmacy (2015), Patient-Centered Outcomes Research Institute (2014-16), Cochrane Methods Innovations Fund (2016-18), and UK National Institute for Health Research (2011-14); was an unpaid IMEDS steering committee member at the Reagan-Udall Foundation for the FDA (2016-2020) and is senior editor, investigations, The BMJ. The views expressed here are those of the authors and do not necessarily reflect those of their employers.