Why did FDA sit on Pfizer vaccine safety signals?

The US Food and Drug Administration (FDA) has found a statistically significant signal of blood clots in the lungs in elderly people who received the Pfizer mRNA vaccine – but has yet to warn the public.

Early last month, in a little noticed preprint, the agency published its analysis.

As I previously reported in an October investigation for The BMJ, the FDA first disclosed findings in July 2021, noting the detection of four types of potential serious adverse events following receipt of Pfizer’s vaccine in the elderly (65s & over);

1. acute myocardial infarction,

2. disseminated intravascular coagulation,

3. immune thrombocytopenia, and

4. pulmonary embolism.

But these findings were only posted on the agency’s website, with no corresponding press release, preprint, or journal publication.  The webpage stated that the FDA “will further investigate these findings” and “share further updates and information with the public as they become available.”

But over one year later, there were no updates.  Experts that spoke with The BMJ called on the FDA to publish its research.

In the new preprint, now also published in the journal, Vaccine, the FDA says that “after further evaluation,” of the four serious adverse events only pulmonary embolism – blood clots in the lungs – continued to meet the agency’s statistical threshold for a signal.

The FDA also reported that no statistical signals were identified following vaccination with either the Moderna or Johnson and Johnson (Janssen) vaccines.

But why has it taken so long to see these results? And why hasn’t the FDA issued a press release, or notified doctors or changed the product label or consent forms?

Peter Doshi, associate professor at the University of Maryland School of Pharmacy and senior editor at The BMJ, said “In July 2021, the FDA promised to update the public, and it has clearly failed to do this.”

The FDA says it is “currently not taking any regulatory actions based on these signal detection activities because these signals are still under investigation and require more robust study.”

“How long does a ‘robust study’ take?” asked Doshi. “Back in April 2021, just weeks after the rollout of Johnson and Johnson vaccine began, the CDC and FDA issued a major advisory about that vaccine following six post-marketing reports of a serious blood clotting disorder. Why is pulmonary embolism in Pfizer vaccine being handled differently?”

Data was obtained from the Centers for Medicare & Medicaid Services (CMS) and, using a “near real time surveillance” system called Rapid Cycle Analysis (RCA), the FDA monitored a list of 14 adverse events of special interest. 

The RCA is supposed to be an “early warning safety system” allowing the FDA to “rapidly identify potential new and important safety concerns.” But the new study reveals that the FDA knew about a signal for pulmonary embolism since 27 February 2021.

Over four  months went by before the FDA quietly posted the detection of the safety signals to its website – there was no accompanying press release or other public announcement so the data went virtually unnoticed.

“I cannot think of any legitimate reason why the FDA would not alert healthcare providers and the public months earlier when the signal was first detected,” said Doshi. “The FDA calls it a ‘near real-time safety monitoring’ system for ‘rapidly detecting’ safety concerns. Taking over four months to post findings on a website is not ‘rapid’,” added Doshi.

The FDA did not answer why it took over four months to post the findings.

The FDA even kept the information from its own advisory committee.

On 26 Oct 2021, the FDA met with its Vaccines and Related Biological Products Advisory Committee (VRBPAC) to discuss the covid-19 vaccines, and did not disclose the early safety signals it had found.

The FDA justified keeping the data under wraps.

“The more robust, epidemiological study had not been completed by that time. Furthermore, the VRBPAC meeting on October 26 was to discuss Pfizer-BioNTech’s EUA request for administration of their COVID-19 mRNA vaccine to children 5 to 11 years of age. Data on people 65 years of age and older was not relevant to the question,” said the FDA.

But as Doshi pointed out, “Preliminary and emerging evidence is frequently presented at these meetings. What makes this case any different?”

Another concern about the FDA’s analysis was that the cut-off for data collection was on 15 Jan 2022 (four months before the study was submitted to Vaccine), which has raised serious concerns that the FDA’s analysis is already out of date.

Doshi said, “the January 2022 cut-off date is a concern because today in late 2022, this means there is now about a year’s worth of additional data that has not been reported on by the FDA.”

The FDA also claims its analysis shows the system is working to support the public and clinical decision-making, but Doshi disagrees.

“How can the FDA seriously assert it’s supporting decision-making when, in the 20 months that they have been aware of the signal, there has not been a single press release or Dear Health Care Provider letter about the FDA's studies on safety signals, and the label has yet to be updated?” said Doshi.

A source within the FDA that spoke on background said the agency has continued to do further ‘more robust’ analyses on the data and did not find an association between the Pfizer vaccine and pulmonary embolism. Release of the study findings is expected in early 2023.

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