Pandemrix vaccine: why was the public not told of early warning signs?

On 20 September 2018, the BMJ published a feature article entitled “Pandemrix vaccine: why was the public not told of early warning signs?”. This was written by the BMJ’s associate editor, Peter Doshi, based on court documents obtained by Tom Jefferson. It contains serious inaccuracies as detailed below.

Pandemrix was a ‘flu vaccine manufactured by GlaxoSmithKline and used in Europe during the swine ‘flu pandemic in 2009/10. The background to this piece is that Pandemrix vaccine was eventually associated with a very small increased risk of narcolepsy. This association is now well-documented [1,2]. The nature of an influenza pandemic requires vaccines to be used in large populations over a relatively short time period. Because it takes several months for a condition like narcolepsy to develop and be diagnosed, this association did not emerge until after the pandemic vaccination period. This safety issue was entirely unpredictable and, because it was extremely rare (studies subsequently indicated the risk was in the order of 6 per 100,000 vaccinees [2]), could not have been detected in any clinical trial. This is why post-marketing safety surveillance is so important. As alluded to in the article, this issue was rapidly acted upon when it emerged and any use of the vaccine was restricted by EU regulators [3].

The proposition of this article is that, before this issue emerged, there was already evidence of serious harm from the vaccine which European health authorities failed to communicate to the public or act upon. The suggestion is that the public was therefore placed at avoidable risk.

These are serious allegations. But they are unfounded and the author misrepresents the data on which his assertions are based. In understanding why, we first need to appreciate the nature of these data.

The data underpinning Doshi’s conclusions are reports of suspected adverse reactions (ADRs). Most countries have a system of passive surveillance. In the UK, the system is the ‘Yellow Card Scheme’ operated by the MHRA, through which anyone can report a suspected ADR. Suspected ADRs are not necessarily proven side effects but these are continually evaluated to detect possible new risks. The pharmaceutical industry is also required to collect such reports. The European Medicines Agency collates reports at an EU level, from pharmaceutical companies and Member States. The level of reporting of such reports is highly variable, both within countries (between different pharmaceutical products) and between countries. Many factors can influence this variability. Important factors in relation to the allegations in this article are awareness and publicity about the reporting system. In the UK, during the swine ‘flu pandemic use of the reporting system was specifically publicised. There was also likely to be a heightened level of awareness of the need to report in other EU countries.

The main plank of the article is that the reporting rate of suspected ADRs for Pandemrix was much higher than comparable vaccines, notably Arepanrix. Arepanrix was a similar vaccine to Pandemrix, used mainly in Canada and South America during the pandemic. Doshi argues that ‘alarm bells’ should have rang earlier over this higher rate, and that health authorities should have acted upon this (and communicated it to the public). As stated in the article, the overall rate was 254 suspected ADRs per million doses, or 0.25 per 1,000 doses. The reporting rate of serious suspected ADRs was 76 per million doses, or 0.076 per 1,000 doses. The reality is that this is a very low reporting rate, much lower than the actual frequency of most common expected side effects (which occur at a rate between 1 in 10 to 1 in 100).

In fact, based on UK Yellow Card reporting, it’s a similar reporting rate to other types of routine vaccine, and lower than other new vaccines (which tend to have a reporting rate up to 1 per 1,000 doses). Doshi bases these calculations on around 3,800 suspected ADR reports. Again, not a huge number given the millions of people vaccinated across the EU during the pandemic. He doesn’t discuss the type of suspected ADRs included amongst these, but they were, in fact, mostly what we expected to see with this vaccine. This included the likes of fever, injection reactions, aches and pains, nausea, vomiting and malaise. However, the article selects several serious suspected ADRs such as death, facial palsy, Guillain Barre Syndrome, demyelinating disorders and convulsions as being reported. These were also closely evaluated by EU health authorities at the time of reporting. The reporting rates were low and consistent with the background incidence, and so ‘alarm bells’ should not have rang. Subsequent epidemiological studies did not support a causal association for such events [4,5,6].

So, the number and nature of suspected ADRs associated with Pandemrix during the pandemic did not raise concerns. Arepanrix was not used in Europe, but Doshi uses its lower reporting rate to suggest a serious problem with Pandemrix at that time. There is no logic to this assertion. What Doshi has failed to observe or discuss is that the Arepanrix reporting rate was actually much lower than what we should expect to see for a new vaccine. This is probably due to the differing nature of reporting systems outside the EU. The fact is that suspected ADR reporting raised no real safety concerns and gave absolutely no early indication of the subsequent association with narcolepsy. There was therefore no failure whatsoever of pharmacovigilance.

The other main plank of the article focuses on a lack of transparency amongst health authorities in communicating these data. Transparency is important and health authorities should commit to it. The reality is that the MHRA did in fact publish a weekly summary of Yellow Card reports for pandemic vaccines [7]. The article alludes to the fact that the EMA also did the same [8], but ignores this clear commitment to transparency in its conclusions and allegations.

Dr Philip Bryan
Head of Vaccine Safety
Vigilance and Risk Management of Medicines (VRMM)
Medicines and Healthcare products Regulatory Agency

1. Weibel et al. Vaccine. 2018 Oct 1;36(41):6202-6211.
2. Sarkanen et al. Curr Neurol Neurosci Rep. 2018 Jun 1;18(7):43
3. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_R... - accessed 21 September 2018
4. Ghaderi S et al. Eur J Epidemiol. 2016 Jan;31(1):67-72
5. Andrews et al. Vaccine. 2011 Oct 19;29(45):7878-82.
6. Bardage et al. BMJ. 2011 Oct 12;343:d5956.
7. http://webarchive.nationalarchives.gov.uk/20100408181132/http://www.mhra... – accessed 21 September 2018
8. http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general... – accessed 21 September 2018