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Rapid response to:

Editor's Choice

A tale of two vaccines

BMJ 2018; 363 doi: (Published 04 October 2018) Cite this as: BMJ 2018;363:k4152

Rapid Response:

Re: A tale of two vaccines - MHRA Had 178 Pandemrix Altered Consciousness Adverse Event Reports in 67 Days

Dear Editor,

It seems the position regarding the MHRA's practices is considerably worse than I reported in prior Rapid Responses [1], [2]. What is troubling is how is it a lawyer notices but the MHRA - whose job it is to do so and with all the medical and scientific expertise and resources at its disposal - did not and still does not?

In addition to the six reports of hypersomnia I noted previously [1], the MHRA had [and still has] another 172 reports of Pandemrix Adverse Events which relate in some form to what I will call here "abnormalities in the regulation of consciousness". And this total of 178 Pandemrix Adverse Event reports were received by the MHRA within the 67 day period to 21st December 2009.

What is related here is in addition to my identifying that the MHRA splits up Yellow Card reported symptoms in its analyses of Adverse Events. [2] This somewhat odd practice for a supposed drug safety regulator has the effect of preventing the identification of a condition or syndrome characterised by a group of symptoms presenting in each individual the subject of a Yellow Card report.

So what of this total of 178 reports relating to abnormalities in the regulation of consciousness? Should a competent medical professional have considered these reports together as potentially in some way linked?

Professor David Healy has expressed the view in a recent blog “Khashoggi and Pandemrix” that most if not all should have been and that view is expressed with little or no doubt. In addition, it appears the MHRA's practices determine its approach to reports of Adverse Events for all pharmaceuticals.

These are the examples of the MHRA's 31 December 2009 published Pandemrix Adverse Events [3] grouped together and cited by Professor Healy relating to abnormalities in the regulation of consciousness:

- under the heading of Narcolepsy and Hypersomnia:
6 reports of hypersomnia.

- under Disturbances in Initiating and Maintaining Sleep:
30 reports of Insomnia,

- under Parasomnias
3 reports of Abnormal Dreams (a classic feature of narcolepsy),
7 reports of Nightmares (ditto),
1 report of Sleep Terror (ditto).

- under Sleep disorders Not Elsewhere Classified:
9 reports

- under Disturbances in Consciousness Not Elsewhere Classified:
73 reports of lethargy,
5 reports of loss of consciousness,
1 of sedation,
27 of Somnolence
22 of syncope.

Professor Healy comments on these signals received by the MHRA well "before any reports of narcolepsy from Finland":

"Ordinarily, when patients present with what is later diagnosed as narcolepsy, on average there is a wait of 15 years before the diagnosis is made. This is well known. Initially doctors diagnose fatigue syndromes or somnolence disorders and all sorts of other things. The average doctor will have seen very few cases of narcolepsy if any.

"Given how few events are ever reported to MHRA or FDA or any regulator ... there was as good a case that Pandemrix Caused narcolepsy ...."

The MHRA appears to avoid identifying a condition from symptoms and signals from Yellow Cards and did not identify narcolepsy in particular because "no British doctors used the word narcolepsy".

Professor Healy goes on to identify the problem is more widespread stating "This not just a narcolepsy issue. There is a vanishingly small number of doctors who will send a report of PSSD (post SSRI sexual dysfunction), or PRSD (post retinoid sexual dysfunction) or PFS (post finasteride syndrome) to the regulator in their country. They’ve never heard of these conditions. They will send reports of sexual dysfunction of one sort or the other on antidepressants and other drugs."

"They don’t send reports of any old sexual dysfunction because everyone knows that happens on antidepressants and regulators don’t want reports of things already in the label. If doctors report at all it will be because there is something striking about what their patients are saying to them. So how many reports do the regulators have of significant sexual dysfunction on antidepressants? Over a thousand in the UK alone. There are reports of permanent sexual dysfunction going back to 1987 – before Prozac."

So in addition to Sweden and Finland identifying narcolepsy as a Pandemrix Adverse Drug Reaction when the MHRA did not, the decades long deficiencies in the MHRA's approach to monitoring drug safety are and remain manifold and uncorrected.

Other Pandemrix Adverse Events relating to abnormalities in the regulation of consciousness [mainly epilepsy, seizures and convulsions] as published by the MHRA on 31 December 2009 [3] include:

Generalised tonic-clonic seizures
Grand mal convulsion 3
Convulsion in childhood 1
Partial simple seizures NEC
Simple partial seizures 1
Seizures and seizure disorders NEC
Convulsion 9
Epilepsy 3 [1 fatal]
Febrile convulsion 2
Tonic convulsion 1

[1] Re: A tale of two vaccines - MHRA - 6 Reports of "rare" suspected ADR in 60 days ignored Clifford G Miller 18th October 2018

[2] Re: A tale of two vaccines - MHRA Published Incomplete ADR Data Clifford G Miller 14th October 2018

[3] MHRA'S UK Suspected Adverse Reaction Analysis Swine Flu (H1N1) Vaccines – Celvapan and Pandemrix 31 December 2009

Competing interests: No competing interests

23 October 2018
Clifford G Miller
Lawyer with science background London England