MHRA response to BMJ Editor’s Choice – ‘A tale of two vaccines’
We fully agree with Fiona Godlee (“Editor's Choice - A tale of two vaccines”) [1], that public trust in vaccination programmes is easily undermined by misinformation, and that the “spectre of Andrew Wakefield should not deter us from proper scrutiny and openness about vaccine safety”. However, diligence and objectivity are also paramount when investigating and communicating vaccine safety issues. We believe that the safety of both Pandemrix and Arepanrix vaccines have been scrutinised entirely appropriately, and the extensive materials published by the European Medicines Agency (EMA) and national authorities are evidence of such openness.
Fiona Godlee asks the question “When do public health officials have a duty to warn the public over possible harms detected through pharmacovigilance? How much detail should the public be provided with, and who should provide it?”. These are important and valid questions. Public health authorities and regulators should act, and alert health professionals and the public, as soon as scientific evaluation of the available evidence suggests that a risk is reasonably possible. The detail should be sufficient to allow informed choices to be made and risks to be minimised. Health professionals also have an important role in communicating and minimising such risks.
The theme of Peter Doshi’s article [2], and his response to MHRA [3], is that public health authorities and regulators were not transparent about what he perceives as ‘early warning signs’ about the safety of Pandemrix during late 2009/early 2010. He also questions whether “proper investigations were ever done”. We consider it important to highlight here the evidence that proper investigations of the suspected adverse reactions (ADRs) were in fact done.
In addition to its weekly publication of suspected ADR reports for Pandemrix over this time, the EMA issued a public report that described its licensing evaluation of Arepanrix [4]. This public report detailed not only the evaluation of suspected ADR reports during the time period in question, but also a comparison of adverse events from a head-to-head clinical trial of Pandemrix and Arepanrix (H1N1-017). The conclusion was “Overall the safety profiles appear to be comparable”. The EU product licence for Arepanrix also referred to this comparative safety review from the trial [5]. The evidence, reviewed thoroughly at the time, did not indicate a “higher rate of serious adverse events” for Pandemrix, as claimed in Fiona Godlee’s article [1].
In response to our entirely plausible explanation that the higher post-marketing reporting rate of suspected ADRs for Pandemrix compared to Arepanrix was most probably an artefact of different passive reporting systems [6], Peter Doshi also asks [3] “where are the data that should lead us to believe that these explanations are anything more than hypotheses”. The above information, which has long been available on the EMA’s website [7], answers this question.
For the reasons already outlined [6], it is clear that there was no suggestion of a safety concern with Pandemrix at the time and no justification for communicating to the public what was actually a very low spontaneous reporting rate of suspected ADRs for Arepanrix, a vaccine that was not being used in Europe.
Dr Philip Bryan; Head of Vaccine Safety, Vigilance and Risk Management of Medicines (VRMM), Medicines and Healthcare products Regulatory Agency (MHRA)
Dr June Raine; Director, VRMM-MHRA
Dr Ian Hudson; Chief Executive, MHRA
Rapid Response:
MHRA response to BMJ Editor’s Choice – ‘A tale of two vaccines’
We fully agree with Fiona Godlee (“Editor's Choice - A tale of two vaccines”) [1], that public trust in vaccination programmes is easily undermined by misinformation, and that the “spectre of Andrew Wakefield should not deter us from proper scrutiny and openness about vaccine safety”. However, diligence and objectivity are also paramount when investigating and communicating vaccine safety issues. We believe that the safety of both Pandemrix and Arepanrix vaccines have been scrutinised entirely appropriately, and the extensive materials published by the European Medicines Agency (EMA) and national authorities are evidence of such openness.
Fiona Godlee asks the question “When do public health officials have a duty to warn the public over possible harms detected through pharmacovigilance? How much detail should the public be provided with, and who should provide it?”. These are important and valid questions. Public health authorities and regulators should act, and alert health professionals and the public, as soon as scientific evaluation of the available evidence suggests that a risk is reasonably possible. The detail should be sufficient to allow informed choices to be made and risks to be minimised. Health professionals also have an important role in communicating and minimising such risks.
The theme of Peter Doshi’s article [2], and his response to MHRA [3], is that public health authorities and regulators were not transparent about what he perceives as ‘early warning signs’ about the safety of Pandemrix during late 2009/early 2010. He also questions whether “proper investigations were ever done”. We consider it important to highlight here the evidence that proper investigations of the suspected adverse reactions (ADRs) were in fact done.
In addition to its weekly publication of suspected ADR reports for Pandemrix over this time, the EMA issued a public report that described its licensing evaluation of Arepanrix [4]. This public report detailed not only the evaluation of suspected ADR reports during the time period in question, but also a comparison of adverse events from a head-to-head clinical trial of Pandemrix and Arepanrix (H1N1-017). The conclusion was “Overall the safety profiles appear to be comparable”. The EU product licence for Arepanrix also referred to this comparative safety review from the trial [5]. The evidence, reviewed thoroughly at the time, did not indicate a “higher rate of serious adverse events” for Pandemrix, as claimed in Fiona Godlee’s article [1].
In response to our entirely plausible explanation that the higher post-marketing reporting rate of suspected ADRs for Pandemrix compared to Arepanrix was most probably an artefact of different passive reporting systems [6], Peter Doshi also asks [3] “where are the data that should lead us to believe that these explanations are anything more than hypotheses”. The above information, which has long been available on the EMA’s website [7], answers this question.
For the reasons already outlined [6], it is clear that there was no suggestion of a safety concern with Pandemrix at the time and no justification for communicating to the public what was actually a very low spontaneous reporting rate of suspected ADRs for Arepanrix, a vaccine that was not being used in Europe.
Dr Philip Bryan; Head of Vaccine Safety, Vigilance and Risk Management of Medicines (VRMM), Medicines and Healthcare products Regulatory Agency (MHRA)
Dr June Raine; Director, VRMM-MHRA
Dr Ian Hudson; Chief Executive, MHRA
Competing interests: None
1. https://doi.org/10.1136/bmj.k4152
2. https://www.bmj.com/lookup/doi/10.1136/bmj.k3948
3. https://www.bmj.com/content/362/bmj.k3948/rr-13
4. https://www.ema.europa.eu/documents/assessment-report/arepanrix-epar-pub...
5. https://www.ema.europa.eu/documents/product-information/arepanrix-epar-p...)/
6. https://www.bmj.com/content/362/bmj.k3948/rr-2
7. https://www.ema.europa.eu/en/human-regulatory/overview/public-health-thr...
Competing interests: No competing interests