Key Pfizer covid-19 vaccine trial dataset still not released
Dear Editor,
The U.S. FDA granted a license (in the recent vernacular, “full approval”) to Pfizer’s mRNA covid-19 vaccine, Comirnaty, on August 23, 2021.
The US Code of Federal regulations (21 CFR 601.51(e)) states that “After a license has been issued, the following data and information in the biological product file are immediately available for public disclosure unless extraordinary circumstances are shown…” [1]
On this basis, a group known as Public Health and Medical Professionals for Transparency (PHMPT, a very large group of which we are co-signatories) submitted a Freedom of Information Act (FOIA) request to FDA requesting these data (i.e. the data Pfizer submitted to FDA to obtain licensure). After the FDA denied PHMPT’s request for expedited processing, PHMPT sued the FDA; in January 2022, a US federal judge ordered the FDA to produce at least 55,000 pages a month (the FDA initially estimated that it held 329,000 pages and argued it should not be required to produce more than 500 pages a month due to limited resources).[2]
Hundreds of thousands of pages have now been released, including 37 patient level datasets for Pfizer’s phase III trial (C4591001), all of which are posted for public download from the PHMPT website.[3]
While release is still not complete, we reviewed the datasets to understand what analyses might be possible with what has been released thus far. To our disappointment, despite some datasets being gigabytes in size, a key analysis dataset known as ADSL (Subject-Level Analysis Data) remains unreleased. Pfizer’s Analysis Data Reviewer Guide states that “This [ADSL] dataset supported the creation of all other analysis datasets” (p.23) and that “ADSL.sas (adsl-sas.txt) must be run first before any other ADaM datasets; all other programs are dependent on ADSL output.” (p.37) [4]
This means that replicating even the most basic safety and efficacy analyses that Pfizer presented in its reports (see pp.42-65 in ref [4]) is still not directly possible. (We say “directly” because such analyses may still be “reverse engineered” using the available data.) More than one year after licensure, and nearly two years since widespread use under an Emergency Use Authorization commenced, the inability to directly replicate these analyses is unacceptable.
Competing interests:
PD and LW helped organize the Coalition Advocating for Adequately Licensed Medicines (CAALM), which formally petitioned the FDA to refrain from fully approving any covid-19 vaccine last year (docket FDA-2021-P-0786). They are also members of Public Health and Medical Professionals for Transparency, discussed in this letter. In addition, 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 and opinions do not necessarily reflect the official policy or position of the University of Maryland.
Rapid Response:
Key Pfizer covid-19 vaccine trial dataset still not released
Dear Editor,
The U.S. FDA granted a license (in the recent vernacular, “full approval”) to Pfizer’s mRNA covid-19 vaccine, Comirnaty, on August 23, 2021.
The US Code of Federal regulations (21 CFR 601.51(e)) states that “After a license has been issued, the following data and information in the biological product file are immediately available for public disclosure unless extraordinary circumstances are shown…” [1]
On this basis, a group known as Public Health and Medical Professionals for Transparency (PHMPT, a very large group of which we are co-signatories) submitted a Freedom of Information Act (FOIA) request to FDA requesting these data (i.e. the data Pfizer submitted to FDA to obtain licensure). After the FDA denied PHMPT’s request for expedited processing, PHMPT sued the FDA; in January 2022, a US federal judge ordered the FDA to produce at least 55,000 pages a month (the FDA initially estimated that it held 329,000 pages and argued it should not be required to produce more than 500 pages a month due to limited resources).[2]
Hundreds of thousands of pages have now been released, including 37 patient level datasets for Pfizer’s phase III trial (C4591001), all of which are posted for public download from the PHMPT website.[3]
While release is still not complete, we reviewed the datasets to understand what analyses might be possible with what has been released thus far. To our disappointment, despite some datasets being gigabytes in size, a key analysis dataset known as ADSL (Subject-Level Analysis Data) remains unreleased. Pfizer’s Analysis Data Reviewer Guide states that “This [ADSL] dataset supported the creation of all other analysis datasets” (p.23) and that “ADSL.sas (adsl-sas.txt) must be run first before any other ADaM datasets; all other programs are dependent on ADSL output.” (p.37) [4]
This means that replicating even the most basic safety and efficacy analyses that Pfizer presented in its reports (see pp.42-65 in ref [4]) is still not directly possible. (We say “directly” because such analyses may still be “reverse engineered” using the available data.) More than one year after licensure, and nearly two years since widespread use under an Emergency Use Authorization commenced, the inability to directly replicate these analyses is unacceptable.
Peter Doshi
Linda Wastila
References
[1] 21 CFR § 601.51 - Confidentiality of data and information in applications for biologics licenses. https://www.law.cornell.edu/cfr/text/21/601.51
[2] https://news.bloomberglaw.com/health-law-and-business/why-a-judge-ordere...
[3] https://phmpt.org/pfizers-documents/
[4] Analysis Data Reviewer Guide. BLA Analysis for Participants ≥16 Years of Age BioNTech SE and PFIZER INC. Study C4591001 https://phmpt.org/wp-content/uploads/2022/03/125742_S1_M5_c4591001-A-adr...
Competing interests: PD and LW helped organize the Coalition Advocating for Adequately Licensed Medicines (CAALM), which formally petitioned the FDA to refrain from fully approving any covid-19 vaccine last year (docket FDA-2021-P-0786). They are also members of Public Health and Medical Professionals for Transparency, discussed in this letter. In addition, 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 and opinions do not necessarily reflect the official policy or position of the University of Maryland.