I’m not one prone to hyperbole but MHRA’s latest response to one of my freedom of information (FOI) requests seems to me to be a straightforward admission that it missed Covid vaccine safety signals up to mid 2022 (not to mention safety signals with other vaccines).
Last year, whilst trawling through minutes of meetings of the Commission on Human Medicines (here and specifically here), I discovered that MHRA had been concerned about the large numbers of Covid vaccine Yellow Card reports swamping the database and distorting the statistical analysis it relies on to detect safety signals. MHRA was concerned enough to conduct an investigation, write a report and consult the Commission on Human Medicines about it in June 2022. So I submitted an FOI last December asking for a copy of MHRA’s report. This was all mentioned in the Perseus Report of which I was a co-author.
Nearly four months after my FOI, and after two complaints to the ICO (here and here) including the threat of legal action, MHRA eventually sent me its report. It’s quite technical but it makes very interesting reading.
First, though, a bit of background. I expect this will come as a shock, but MHRA’s safety monitoring of medicines doesn’t rely on investigating individual Yellow Card reports and assessing causality (more on that at the end). Instead, it relies on statistical analysis called ‘disproportionality analysis’. This involves mining the database of Yellow Card reports looking for statistically significant differences in the frequencies of different types of side-effect between the drug of interest and other drugs. All medicine regulators use disproportionality analysis but there are differences in the algorithms (ROR, PRR, EBGM etc.) and the signal detection thresholds they use.
As its report says, MHRA was concerned about the effect on its own disproportionality analysis due to the very large proportion of COVID-19 vaccine reports in its Yellow Card database (by June 2022 it was over 80% of all vaccine-related Yellow Cards). Specifically, they were concerned that:
- “With the majority of the vaccine dataset now comprised of reports for COVID-19 vaccines, these have the potential to unduly influence the disproportionality statistics for other vaccines.”
- “If the safety/reporting profile for the COVID-19 vaccines differs significantly from other vaccines then this will impact disproportionality statistics and either mask potential signals or result in more false positive signals.”
- “Additionally, there are potential issues with the large volume of COVID-19 vaccine reports impacting the disproportionality analyses for the COVID-19 vaccines themselves.”