The MHRA - taking patient reporting seriously - Part IV

Well, I feel properly satisfied with the outcome of this. Thank goodness my experience isn't a trivial matter for those who have an interest in the drugs I take:


Dear (redacted),

Many thanks for this. I believe it answers my questions satisfactorily, and I consider the complaint dealt with.

The issue, then, lies elsewhere: the manufacturers are not responsible, because the risk of suicidal ideation was noted on the PIL; my GP was not responsible, even though he was responsible for my care, because he brought the side effect to my attention, when he prescribed the drug (and then, when I experienced the side effect, told me that it wasn't the drug); the MHRA is not responsible, because it is not required to be responsible.

May I ask who is responsible - and this is not a rhetorical question, I would like an answer? Could you seek guidance from the Secretary of State on this one, please, because I am keen to understand whether it is believed that I should be responsible for my reaction to chemicals that, with the greatest of respect to the MHRA, are not controlled particularly effectively, judging by the less than scientific approach that is taken to licensing (both by manufacturers and regulators)?

I have to be honest, rarely have I experienced such a sorry catalogue of failure and incompetence as this. There are so many gaps in this system that it is a wonder to me that anybody survives it. More to the point, when a flaw is identified, the MHRA (and others) appear determined to argue that everything is just hunky dory, and that a complainant is somehow deranged to even suggest that anything is wrong. In short, full defensive mode is initiated. And yet, the MHRA is characterized as a world leader?

Best regards

(redacted)




********************************
From: "Pharmacovigilance,"
To: (redacted)
Subject: Yellow Card Complaint
Date: Mon, 10 Sep 2007 10:36:39 +0100


Dear (redacted)

You raised a formal complaint that your Yellow Card report was not subject to follow-up. This complaint has been investigated by the Signal Management Group and I will address your concerns below.

Further to your Freedom of Information (FOI) request FOI 07-246 on the 15th August 2007 concerning the Yellow Card Scheme, a response was sent to you on 30 August 2007 explaining what a ‘follow-up’ is and detailing the process by which it is determined whether it is necessary for a Yellow Card report to be followed-up. Please refer to this communication for further explanations of the process of ‘follow-up’. In summary I will reiterate that the term follow-up refers to the communication with the reporter to request further information regarding their Yellow Card report.

The following up of a report is at the discretion of our pharmacovigilance scientists and assessors at the MHRA and is in no way a compulsory part of the Yellow Card Scheme. As stated in the FOI 07-246 response the request for further information or ‘following up’ of a report does not necessarily signify these reports are of greater importance or interest.

With regards to your Yellow Card report, I can confirm it was determined a request for further information from yourself was not necessary at that time for two main reasons:

Firstly the report you completed was adequately filled in to provide enough information to be entered onto our database for rapid analysis and assessment by our physicians, pharmacists and scientists.

Secondly the suspected adverse reaction reported by yourself was suicidal ideation. As you are well aware, Suicidal ideation is listed as a potential side effect in the Patient Information Leaflet (PIL) for fluoxetine. Whilst we are not in any way dismissing the seriousness of this reaction, this in itself does not necessarily warrant a Yellow Card report being followed up.

The risk of suicidal ideation and suicide with SSRIs are continually monitored by the MHRA. In May 2003, in response to continuing public concerns about the safety of SSRIs, an Expert Working Group of the Committee on Safety of Medicines (CSM) was convened to investigate ongoing safety concerns with these medicines, in particular around suicidal behaviour and withdrawal reactions/dependence. I believe you are already aware of this ‘Report of the CSM Expert Working Group on the Safety of SSRI’s’ and your questions regarding its contents and conclusions have already been satisfactorily addressed.

With regards to provision of the manufacturer’s details of the generic fluoxetine you were prescribed, I am unable to provide you with this information. Currently there are approximately 32 marketing authorisation holders for generic brands of fluoxetine in the UK and therefore I am not able to inform you which of these MAHs provided the fluoxetine you were prescribed by your practitioner. However the MAHs name would clearly have been stated on the packaging and also on the Patient Information Leaflet provided with the pack as a legal requirement.

I hope you feel this letter addresses your complaint in all respects. If you remain dissatisfied, you can make representations to the Central Complaints Officer:

(redacted)
MHRA
16-107 Market Towers
1 Nine Elms Lane
Vauxhall
SW8 5NQ

The MHRA: taking patient reporting seriously

Dear All,

I've just spent a short break down in the West Country. And very nice it was, too. Now, fully rejuvenated, I felt inclined to escalate my complaints up the MHRA foodchain. To which end, I've just had this little exchange with our esteemed drugs regulator. I've emboldened the MHRA's reply, for convenience:

Dear Sean,

It's remarkable how one's memory can play tricks on one, is it not? Perhaps it was the DoH that I had that conversation with. Or the ABPI. Or my doctor. Or the NHS. Or the Samaritans. Or my colleagues. Or my blog. In any event, my primary concern is not that the MHRA overlooked an issue that I believe I raised with it, but rather that it appears to have failed to do what it purports to do; that which it appears to exist to perform; and, moroever, that which it asserted to be valuable. Perhaps we should focus on that?

In any case, thank you for your kind attention. Given the background to this particular request, perhaps I can rely on the MHRA not to brand it vexatious, on this occasion?

Best regards

Matthew Holford

From: [redacted]
To: Matthew Holford, "MHRA Information Centre" info@mhra.gsi.gov.uk
CC: [Alan Johnson], [Shailesh Vara], [Alasdair Breckenridge], [Kent Woods]
Subject: RE: Yellow Card scheme
Date: Wed, 15 Aug 2007 10:38:31 +0100

Dear Mr Holford,

I refer to your email below.

Having read through your earlier FOI requests which form the subject of my review, I have not encountered any questions which relate to the Yellow Card Scheme. You are, therefore, correct in stating that this is not under consideration in my review.

As there does not appear to be a record of you having asked a question on the Yellow Card Scheme before, I have requested the Information Centre to treat this as a new FOI request. They will acknowledge your request and refer your questions to the appropriate unit who will respond to you directly.

Kind regards,

[redacted]

From: Matthew Holford [mailto:m.holford@hotmail.co.uk]
Sent: 15 August 2007 02:46
To: MHRA Information Centre
Cc: Alan Johnson; [Shailesh Vara]; [redacted]; [Alasdair Breckenridge]; [Kent Woods]
Subject: Yellow Card scheme

Dear Sean,

It occurred to me recently that I have asked about the Yellow Card scheme, during the course of my enquiries. However, this does not appear to be under consideration, in your review.

I was keen to understand how the scheme operated, or didn't operate, as the case may be. At the time of its roll-out, back in October, 2005, Dr Patricia Wilkie, Chairman of the CSM’s Working Group on Patient Reporting, declared that direct patient reporting was essential for medicines safety monitoring. Moreover, it would be an important source of information for patients about their medicines. Meanwhile, the MHRA's CEO, Kent Woods, declared that it would provide new insight - he was right about that, at least - and that it would permit patient involvement in regulation. I would be interested to understand how those objectives are achieved? In detail, please.

Also, you may be aware that just less than half of Yellow Card reports are followed up (according to your esteemed Chairman, Professor Sir Alasdair (that's D-A-I-R) Breckenrdige). Perhaps the MHRA could explain to me how it is that this fact contributes to either Dr Wilkie's or Mr Wood's objectives?

Finally, having submitted a Yellow Card myself, following suicidal ideations experienced whilst taking fluoxetine, I regret to report that I have been one of the unlucky 51% who has received a perfunctory hard copy, but no follow up. Having no experience of the process, I would be grateful if the MHRA could explain what "follow up" means? Does it have any familial relationship with NICE's "careful and frequent monitoring," by any chance?

I find it difficult to believe that my experience is untypical. However, I don't imagine that I'm your typical dissatisfied customer, either. The MHRA's response has been slipshod at best. At worst I daren't think what it is. Either way, I'm going to find out.

Best regards


Matthew Holford

PS to Mr Johnson: is it true that the Police and Criminal Justice Act 2001 had several key provisions introduced at the behest of the Worshipful Company of Apothecaries (ie, Big Pharma)? If so, could I request just one inclusion, the next time an amendment is made to the CJA - not to be treated like a twat by government bodies? I know that this is a personal request, but I'm sure others could benefit. Thanks everso.

Forty-three Years of Yellow Cards, or Ethon's Retribution

The Yellow Card Scheme is a British initiative run by the Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission on Human Medicines (CHM) to gather information on Adverse Drug Reactions (ADRs) to medicines. This includes all licensed medicines from medicines and vaccines issued on prescription to medicines bought over the counter from a pharmacist or supermarket. The Scheme also includes all herbal preparations and unlicensed medicines found in cosmetic treatments. ADRs can be reported by anyone; generally healthcare professionals including doctors, pharmacists and nurses, as well as patients and carers.

The sort of ADRs that should be reported are:

• ADR's that have caused death or a serious illness
• Any ADR, however minor, if associated with a new medicine or one that is under continued monitoring (highlighted in the British National Formulary (BNF) with a ▼ black triangle)
• Any ADR, however minor, if associated with a child (under 18 years of age)

Yellow Cards are available from pharmacies and a few are presented near the back of the BNF as tear-off pages.

Reports from the Yellow Card scheme are available from the MHRA website.

Source: Wikipedia

Well, that's clear enough, isn't it? Incidentally, to all intents and purposes, the above is the information provided on the MHRA website, where it accompanies links to online Yellow Card forms. So, if our doctor doesn't complete a Yellow Card on our behalf, when we complain to him/her of something subsequent to taking a drug, we can always go online and complete a form, which the MHRA will address. Incidentally, I should mention that the Yellow Card scheme was set up in 1964, following the Thalidomide tragedy (this is the language used by the NHS Wales website, by the way).

Mind you, this business of patients reporting their own experiences is a relatively new thing, seemingly prompted by a recommendation made by the Health Select Committee, following its report into the influence of the pharmaceutical industry, in 2005 - the only recommendation it made that was taken up, to my knowledge - which suggested that a country-wide system of patient reporting be put in place "as soon as possible". The NHS Wales website carries a nice little piece, complete with jolly quotes-you-like from your favourite healthcare bureaucrats, which is dated October, 2005, at the time of the UK pilot roll-out. I didn't realize it was as recent as that. Importantly, for Kent Woods, CEO of the MHRA, patient reporting would provide new insight and permit the public to become involved in medicines regulation. My own experience with the MHRA suggests that public involvement goes no further than filling out Yellow Cards.

Meanwhile, Dr Patricia Wilkie, Chairman of the CSM’s Working Group on Patient Reporting, was even more effusive about the role of direct patient reporting, declaring that it was essential for medicines safety monitoring. Moreover, it would be an important source of information for patients about their medicines. However, as ever, there is a counterproposition to this optimistic propoganda.

Back in August, 2003, Charles Medawar reported that he had conducted an analysis of anonymized Yellow Cards pursuant to a series of investigations undertaken by the BBC's Panorama, concerning the risks associated with Seroxat. He and his co-authors discovered significant failings in the way the system was being operated. "Chaotic and misconceived" was the upshot, if I remember correctly. The MHRA had seemingly systematically failed to follow up on reports of patient suicidality. Yellow cards submitted by drug companies used euphemistic language to conceal the true nature of the side effect experienced. Similarly, several different terminologies would be used to describe essentially the same complaint, thus making a side effect look less significant in terms of its occurrence than was the true case. And so on.

However, you will be pleased to know that the MHRA's excellent Chairman, Prof Sir Alasdair (that's D-A-I-R) Breckenridge, regarded the Yellow Card scheme as "an important way that the MHRA monitors drug safety." Back in January, 2005, when Prof Breckenridge gave this thunderous endorsement of the reporting scheme, the Health Minister, Lord Warner, was announcing the publication of anonymized data, taken from Yellow Cards, on the MHRA's website, thus permitting public scrutiny, and access to data for the purposes of further research.

But I think it's worth taking another look at the view of Prof Alasdair (that's D-A-I-R) Breckenridge. We've already established that the Yellow Card scheme is important in providing fresh data on side effects, post-licensing. The MHRA, which has as its primary goal the protection of the public from shite medical products, lest we forget, has told us that this is true, in the person of its Chairman. I just thought I'd reiterate that.

In fact, the MHRA regarded the Seroxat Yellow Cards as so important that Prof Breckenridge claimed that

"...in the appropriate... in the appropriate cases, this is... these patients are followed up. The follow up rate for Yellow Card reports is some 48% - 49%."

That quotation is taken from the transcript of the Panorama programme Taken on Trust, a precursor to Secrets of the Drugs Trials. And, yes, he really did struggle as much as those ellipses suggest (no, they don't indicate that I have edited his words!). I should say that I'm not quite clear as to whether Breckenridge is referring to Yellow Cards in general, or Seroxat suicide reports, when he advises Shelley Jofre that 49% are followed up.

So, we have euphemisms. We have semantics. We have poor follow up - certainly in the case of Seroxat suicidality reports, and, I suspect, more generally. Indeed, I filed a Yellow Card myself, consequent to suicidal ideations experienced when I took fluoxetine. I received a hard copy of the report, and I've heard nothing since. This patient regards that as unforgiveable.

The MHRA is four years old.

Matt