FDA RotaTeq Data Placebo Deaths Inexplicably 35% Higher Than Trials; Vaccinated Data Consistent
A Detailed Breakdown with Calculations and References
An analysis of the FDA Package Insert for RotaTeq reveals a significant, unexplained discrepancy in reported placebo group deaths compared to the data found in its cited clinical trials.
The FDA Package Insert states:
“Across the clinical studies, 52 deaths were reported. There were 25 deaths in the RotaTeq recipients compared to 27 deaths in the placebo recipients.”
However, the sum of the referenced trials shows 25 deaths in the RotaTeq recipients, and 20 deaths in the placebo recipients.
The FDA Package Insert combines data from four primary Merck Phase III clinical trials: Study 006, 007, 009, and 029. The insert notes:
“Overall, 73,086 infants were randomized in 4 placebo-controlled, phase 3 studies conducted in 12 countries on 4 continents. The data demonstrating the efficacy of RotaTeq in preventing rotavirus gastroenteritis come from 7,744 of these infants from the US (including Navajo and White Mountain 10 Apache Nations), Finland, and Japan who were enrolled in 3 of these studies: Study 006, Study 007, and Study 029. A fourth trial, Study 009, provided clinical evidence supporting the consistency of manufacture and contributed data to the overall safety evaluation.”
The “ADVERSE REACTIONS” section, where deaths are listed, states as its source:
“71,725 infants were evaluated in 3 placebo-controlled clinical trials including 36,165 infants in the group that received RotaTeq and 35,560 infants in the group that received placebo.”
So only 3 of the trials are used for the death total, although it doesn’t state which.
The Individual Studies and Their Reported Deaths:
Study 006 (REST): Results posted on ClinicalTrials.gov April 2011 without complete mortality data.
Rotavirus Efficacy and Safety Trial (REST)(V260-006)
Published in The New England Journal of Medicine January 2006.
Safety and Efficacy of a Pentavalent Human–Bovine (WC3) Reassortant Rotavirus Vaccine
“Overall, 44 deaths occurred during the study, 24 among vaccine recipients (<0.1 percent) and 20 among placebo recipients (<0.1 percent).”
Vaccinated: 34,035 children → 24 deaths
Placebo: 34,004 children → 20 deaths
Study 007: Results posted on ClinicalTrials.gov July 2009.
Dose Confirmation Efficacy Study (V260-007)
Published in Pediatrics January 2007 (paywalled).
“One death occurred in a Hispanic male who received PRV.”
Vaccinated: 650 children → 1 death
Placebo: 660 children → 0 deaths
Study 009: Results posted on ClinicalTrials.gov March 2011 without mortality data.
Consistency Lots Vaccine Study (V260-009)
Mortality data for Study 009 was published by The Cochrane Database of Systematic Reviews October 2019.
Vaccines for preventing rotavirus diarrhoea: vaccines in use (Appendix 9)
Vaccinated: 680 children → 0 deaths
Placebo: 113 children → 0 deaths
Study 029: Results posted on ClinicalTrials.gov June 2010 without mortality data.
Phase III Placebo-controlled Study of V260 (RotaTeq™) in Japanese Healthy Infants (V260-029)
Published in Human Vaccines & Immunotherapeutics May 2013.
Efficacy and safety of pentavalent rotavirus vaccine in Japan
“1 subject in the RV5 group died on day 36 post dose 2 owing to respiratory syncytial virus bronchiolitis”
Vaccinated: 381 children → 1 death
Placebo: 381 children → 0 deaths
The Math Discrepancy
Study 006:
Vaccinated: 34,035 children → 24 deaths
Placebo: 34,004 children → 20 deathsStudy 007:
Vaccinated: 650 children → 1 death
Placebo: 660 children → 0 deathsStudy 009:
Vaccinated: 680 children → 0 deaths
Placebo: 113 children → 0 deathsStudy 029:
Vaccinated: 381 children → 1 death
Placebo: 381 children → 0 deaths
Total
Vaccinated: 26 deaths
Placebo: 20 deaths
For those 4 studies we have a total of 26 vaccinated deaths and 20 placebo deaths. However, the FDA Package Insert, which says its data is from 3 of these clinical trials pooled together, only shows 25 deaths in the vaccinated group and somehow shows 27 in the placebo group.
It makes sense that the vaccinated total could have fewer deaths by removing a study. Calculations on the trial sizes (omitted for brevity) indicate Study 029 was not included, which accounts for the 1 missing vaccinated death. This does not help make sense that there are unexplained additional deaths. It makes even less sense that all additional deaths are in the placebo group.
I have done quite a bit of research trying to find a reasonable explanation for this. Across the papers I have found that reference these studies, there are many inconsistent numbers, but nothing that explains the difference in placebo deaths.