@bubu12
 

Fever and pain medications, unblinding, and primary event adjudication committees

Last month I expressed concern about the potential confounding role of pain and fever medications to treat symptoms. I posited that such drugs could mask symptoms, leading to underdetection of covid-19 cases, possibly in greater numbers in people who received the vaccine in an effort to prevent or treat adverse events. However, it seems their potential to confound results was fairly limited : although the results indicate that these medicines were taken around 3–4 times more often in vaccine versus placebo recipients (at least for Pfizer’s vaccine—Moderna did not report as clearly), their use was presumably concentrated in the first week after vaccine use, taken to relieve post-injection local and systemic adverse events. But the cumulative incidence curves suggest a fairly constant rate of confirmed covid-19 cases over time, with symptom onset dates extending well beyond a week after dosing.

That said, the higher rate of medication use in the vaccine arm provides further reason to worry about unofficial unblinding. Given the vaccines’ reactogenicity, it’s hard to imagine participants and investigators could not make educated guesses about which group they were in. The primary endpoint in the trials is relatively subjective making unblinding an important concern. Yet neither FDA nor the companies seem to have formally probed the reliability of the blinding procedure, and its effects on the reported outcomes.

Nor do we know enough about the processes of the primary event adjudication committees that counted covid-19 cases. Were they blinded to antibody data and information on patients’ symptoms in the first week after vaccination ? What criteria did they employ, and why, with a primary event consisting of a patient-reported outcome (covid-19 symptoms) and PCR test result, was such a committee even necessary ? It’s also important to understand who was on these committees. While Moderna has named its four-member adjudication committee—all university-affiliated physicians—Pfizer’s protocol says three Pfizer employees did the work. Yes, Pfizer staff members.