The MHRA - taking patient reporting seriously - Part III

The MHRA excelled itself with the speed of its reply (emboldened). My response is at the bottom:

****************************
From: (redacted)
To: (redacted)
Subject: RE: FOI 07 246
Date: Fri, 31 Aug 2007 12:52:17 +0100


(redacted)

Thank you for your further email of 30 August 2007.

As I said in my last reply, the purpose of the Yellow Card Scheme is to provide the MHRA and CHM with information on adverse drug reactions (ADRs) so that they can take necessary action to protect public health, and update product information where appropriate. Information on all ADR reports that we receive is available to patients and the public on our website and under the Freedom of Information Act.

The MHRA sends regular communications to health professionals about changes to the safety profile of medicines including "Dear Doctor letters", and in August 2007 we launched a new bulletin "Drug Safety Update," sent to all health professionals and available on the MHRA website.

I have nothing further to add to my previous reply dated 30 August 2007 and consider this correspondence closed. As I said in my last reply, issues relating to the Yellow Card you submitted will be handled in your complaint.

Yours sincerely

(redacted)
****************************
Dear (redacted),

Your previous mail was certainly full of information and tightly worded, and I can see that you would not wish to add to it. I imagine that (redacted) felt the same way, when he branded my repeated requests for clarification on certain points "vexatious". I am not on a fishing trip, (redacted), the MHRA's answers are just unclear to me, that's all.

However, while the excellence of the Yellow Card scheme (indeed, the MHRA regulatory practises, in general), is not in doubt from the perspective of providing information to the MHRA and CHM, I am still a little confused about the mechanics of getting that information to the patient, other than via the GP. Given my experience of the MHRA's willingness to provide basic details of its regulatory activities to me, you will, perhaps, forgive me if I am skeptical on the question of transparency.

As it happens, my own issue is not with respect to the information that I received, although nothing quite prepares one for that sensation of "not wanting to go on," when it hits. Much less is one prepared for what happens next.

The position, then, is this: we have a drug that has acknowledged side effects, which are severe by anybody's estimation. This drug has question marks over its efficacy that the MHRA is seemingly unable, or unwilling, to dispel (although it is keen to dismiss them). We have a system of assessment, which by Prof Breckenridge's own admission (please see the HSC's Report), seemingly amounts to rubber stamping the submitting company's application portfolio (I think he used the word "trust" somewhere, in this respect - you will find that there is a distinct absence of that commodity outside the relationship between the Worshipful Company and the MHRA). We have a system for reporting side effects that is seemingly, by accident or design, only capable of moving information in one direction, at any speed.

I regret to advise you that the vast majority of that summary is derived from the MHRA's answers to my questions, over the past six months, or so. And then, when a patient experiences the (acknowledged) side effects, (s)he may well find that (s)he is advised that this had nothing to do with the drug, based on nothing whatsoever, in my case, seeing as I have no history of mental illness, prior to my experience 2/3 years ago.

Your system, (redacted), is working perfectly, as far as I can establish. Everybody is doing their job to their utmost capabilities, and I congratulate them for that. I do. From the bottom of my heart. However, things are going wrong, and it is patients who are bearing the fall out - it is the patients' fault, in short.

I wish to know what the benefit of Seroxat is, and then, I suspect, we can dispense with the discussion about side effects, and reporting, because it will be irrelevant. I am already satisifed that the MHRA is incompetent, based on its ability to discuss side effects at length, but to be unable to discuss efficacy for more than a few paras. How does the MHRA know that Seroxat is efficacious? Because Smithkline Beecham told the MCA so? It rather looks that way, from the outside, which is all that counts.

Best regards

(redacted)

The MHRA - Taking patient reporting seriously - Part II

I think I may withdraw my complaint about the MHRA's failure to follow-up on my Yellow Card report. It seems that the last thing the scheme is about is providing feedback and "follow-up" really doesn't mean to me what it means to the MHRA. My most recent reply is below the MHRA's:


Mr Matthew Holford
Email: m.holford@hotmail.co.uk

FOI 07-246 Yellow Card Scheme

Dear Mr Holford,

Thank you for your Freedom of Information (FOI) Act request of 15 August about the Yellow Card Scheme. As this is for my division it has been passed to me for reply.

The Yellow Card Scheme is the UK system for collecting and monitoring information on suspected Adverse Drug Reactions (ADRs). The Scheme is run by the Medicines and Healthcare products Regulatory Agency (MHRA) on behalf of the Commission on Human Medicines (CHM), and relies on the voluntary reporting of suspected ADRs by health professionals and patients. Adverse Drug Reaction reports are also received from pharmaceutical companies who have a legal obligation to send the MHRA reports of serious suspected ADRs they receive which are associated with their products. The purpose of the Scheme is to continually monitor the safety of medicines and to provide an early warning that the safety of a product may require further investigation.

Please note, the National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health. It is a separate body from the MHRA and as such is not involved in the Yellow Card Scheme.

There are a number of possible actions when a new safety issue is confirmed, in order to prevent or minimise the level of risk to patients. Very rarely, if the risks of a medicine are found to outweigh the benefits, it may be necessary to remove the medicine from the market. More usually, the risk of a side effect may be avoided or reduced in the following ways: by including warnings in the product information (Summary of Product Characteristics and Patient Information Leaflet) or on the package label; and by restricting the indications for use of a medicine.

All Yellow Card reports received are entered onto our database for rapid analysis, allowing us to identify potential new safety concerns. For this reason each report we receive (whether from a healthcare professional or a patient) is valuable as it may represent a previously unrecognised side effect. All spontaneous Adverse Drug Reaction (ADR) reports that we receive at the MHRA are treated identically regardless of whether the reporter is a patient or a health professional.

When a report is entered onto our database, it is analysed by our physicians, pharmacists, and scientists who use Yellow Card reports (including both those from patients and healthcare professionals) to assess the relationship between the suspected medicine and reported side-effect. We also evaluate information on medicines safety from other data sources from the United Kingdom and from around the world including data from international medicines regulators, clinical trial data, and medical literature.

If during the assessment of the report it is felt further information is required for a full evaluation, additional information may be requested. The term ‘follow up’ refers to this communication with the reporter of the Yellow Card, to ask for further information. For example, reports with a fatal outcome are routinely followed up to request a copy of the post mortem report. Other reports that may be subjected to follow-up requests include reports that concern previously unrecognised potential side effects and new drugs that are on the intensive monitoring list (These are known as ‘Black Triangle’ products and are new drugs and vaccines which are being intensively monitored in order to confirm the risk/benefit profile of the product).

However the request for further information or ‘following up’ of a report does not necessarily signify these reports are of greater importance or interest. It may simply be due to the fact that only basic information had been provided or that the information provided was unclear and therefore unassessable at present. Furthermore all reporters are encouraged to report additional information should this become available at a later date and details of how to do so are provided in the reporter’s acknowledgement letter.

Health professionals and patients do not receive direct feedback on their particular Yellow Cards from the MHRA. A key role of the MHRA is to provide doctors with advice on the safe use of medicines, although the final responsibility for the clinical care of their patient remains with the doctor. Given their specific knowledge of the patient and clinical expertise, it is for the doctor to decide on the treatment and/or tests which the patient may receive.

As you are aware Yellow Card reporting has been extended to include patients as well as health professionals. Since the launch of the pilot scheme for patients in January 2005, the MHRA has received over 5000 Yellow Card reports from patients. Each individual report is acknowledged in order to provide a unique reference number so individual reports can easily be located on our pharmacovigilance system for any future correspondence and also to direct patients to the relevant sources if they are concerned.

Patient reporting offers a variety of advantages including greater insight into patient experience, as well as permitting patient involvement in regulation and greater availability of information to patients concerning their medication. The objectives for patient reporting are achieved through the promotion of the Yellow Card Scheme and working together with patients as much as possible. To develop the patient reporting scheme, a Working Group of the Committee on Human of Medicines was set up in 2004, which included patient and consumer groups, pharmacist and medical representatives to work alongside the MHRA to provide helpful insight into patient’s opinions and help in gauging effectiveness of systems to enable patients to send reports of the suspected ADR experiences. This patient working group was involved in the production of the patient Yellow Card in order to ensure the form is user friendly and effective. Furthermore a new patient acknowledgement letter is currently being developed with the Yellow Card Strategy Group and Patient Working Group to manage patient’s expectations from filling out a Yellow Card and to provide greater insight into the processes behind the Yellow Card Scheme.

You may also be interested to note that independent research is planned in order to formally evaluate the patient reporting component of the Yellow Card Scheme. This project is due to commence on the 1st September 2007 for a duration of 2 years.

You also asked about how your own Yellow Card report was handled. On 27 August you raised a separate, formal complaint about this you will receive a response to this in due course.

I hope this information is of use to you.

Yours sincerely

[redacted]

Information for Public Health Group, VRMM Division
Medicines and Healthcare products Regulatory Agency (MHRA)
Market Towers 14-110 1, Nine Elms Lane, London SW8 5NQ


Dear [redacted],

Many thanks for this. I have a couple of questions/comments, below.

If I understand your words aright, then, the Yellow Card scheme is not specifically designed to provide feedback to patients on side effects? If that is correct, may I ask how Dr Wilkie imagined that the Yellow Card scheme would provide information about drugs to patients? Incidentally, (and I generalize, for my own case), if the scheme does not provide feedback to patients routinely, then I imagine that you will find that "patient involvement in regulation" (TM Kent Woods), is such a one-sided thing that patients will tend not to bother. Indeed, I understand that healthcare professionals tend only to report the most serious side effects, as it is. That is to say, at its best "involvement" is a reciprocal arrangement, I would argue.

In fact, if I understand correctly, the Yellow Card scheme currently operates for the sole purpose of providing information to the regulator - it permits greater understanding for the regulator, and others, but there is no prompt reciprocation? The regulator collects, collates and disseminates the information as it sees fit - the patient is there as a provider of information, and any "feedback" will be limited to any modifications that the regulator may choose to make to the PIL, at some disconnected point in the future, by which time the patient may have lost interest. Or, not wishing to be melodramatic, died.

The upshot is, then, that the GP is responsible for the patient, and if the GP's knowledge is deficient, or information concerning an emerging pattern of serious side effects is not available, then the GP's care may not be to the standard that it might? At what point are GPs notified of an apparent emerging risk? It seems to me that there are several large gaps, there, for patients to fall through. As I did, of course.

Best regards

Matthew Holford

That MHRA Complaints Procedure in full

Please note that this procedure is followed in the event that the MHRA receives a complaint about its administrative activities. There is a separate review procedure, with respect to FOIA requests (which I don't have copy of).

Matt

MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
AGENCY PROCEDURES Ref : GEN020/04
Title : Handling Complaints
Effective date
29/03/07
Review date
28/03/09

1. SCOPE

1.1. To define the MHRA procedures for the handling of complaints about administration or levels of service. It does not cover formal appeals against licensing, regulatory decisions on devices or enforcement decisions. It includes details of the "Independent Complaints Adviser" system, and referral to the Ombudsman.

2. INTRODUCTION

2.1. All organisations receive complaints from time to time and the MHRA is no exception. Information from complainants can be used positively, as a way of improving our services. The following procedure is intended to ensure that all complaints are handled consistently and effectively throughout the Agency, with the aim of treating all complainants fairly and, as far as possible, to their satisfaction.

2.2. The procedures described in this SOP apply to all MHRA staff.

3. GENERAL

3.1 What is a complaint?

3.1.1 There can be no hard and fast rules about what constitutes a complaint, and this part of the SOP is intended as guidance only. Broadly speaking, a complaint is an expression of dissatisfaction about the MHRA's service provision. These can be made both orally and in writing. If an oral complaint is made the complainant should be asked to submit the complaint in writing.

3.1.2 In short, for the purposes of these procedures, a complaint is a representation from someone who is:

- disagreeing with an administrative decision, concerning them, taken by the MHRA; or

- unhappy with the way an administrative matter has been handled by the MHRA.

3.1.3 In addition, the MHRA may receive complaints concerning Parliamentary Questions (PQs), Private Office cases (POs), Ministerial statements or articles published by MHRA staff. These should be dealt with in the following ways:

- Parliamentary Questions or Private Office cases or other Ministerial statements.

Complaints regarding Parliamentary Questions or Private Office cases or other Ministerial statements should not be addressed by MHRA staff and should be referred to Private Office. If the complaint covers PQs etc., together with other issues concerning the Agency, staff will be advised by the Agency’s Central Complaints Officer (CCO) as to which areas of the complaint they should address.

- Published Articles.
If the complaint relates to published articles where MHRA staff are authors or part authors the complaint should be referred to the CCO for advice.

4. SPECIFIC

4.1 What to do if you receive a complaint

4.1.1 When a complaint is received it should be acknowledged within 5 working days. The complaint should be logged, investigated and a response sent directly to the complainant from the relevant unit/division. For the majority of complaints, they will be resolved at a local level with the initial response, without the need for further action.

A full record of all correspondence in relation to the complaint should be kept.

If a complaint is received, in the first instance, by the Central Complaints Officer (CCO), the CCO will forward it to the relevant unit/division for resolution at a local level. A copy of the complaint should be held on file by the CCO. Again, the unit/division should acknowledge receipt of the complaint within 5 working days and proceed with its investigation and response.

4.1.2 The guiding principles at all stages of dealing with a complaint should be:

- speedy handling;

- answering all points of concern;

- being factually correct;

- fair investigation;

- effective response;

- confidentiality.

4.1.3 Replies should also:

- provide an apology (if appropriate);

- correct any misunderstandings;

- be signed by the officer dealing with the complaint;

- provide contact details (including fax and e-mail).

4.2 Specific action to be followed

Resolve the complaint locally

4.2.1 Attempts should be made to resolve the complaint as quickly as possible at a local level i.e. group/unit/divisional head level whichever is the most appropriate. The response should advise the complainant that “if they remain dissatisfied, they may make representations to the Central Complaints Officer”.

Complaint to the Central Complaints Officer (CCO)

4.2.2 As soon as a complaint to the CCO is received in writing, it should be sent to Central Complaints Co-ordinator (CCC) (see details below). Written complaints sent directly to the Chief Executive or Board Member should also be referred to the CCC immediately.

4.2.3 The CCC will send an acknowledgement letter to the complainant within 5 working days, register the complaint, inform the CCO and raise a file with an identifying number. The file will contain the letter of complaint and all subsequent correspondence.

4.2.4 The registered file will then be sent, by the CCC, to the relevant part of the Agency for a report. Relevant staff should maintain a simple record on the file of the action taken (by whom and when) as it may be necessary to refer to this later if the complaint cannot be resolved quickly or becomes more involved.

4.2.5 The report should be sent (by email) to the CCO within 6 working days of the date of receipt. The report should be placed on file. If this is not possible to provide a report within the stipulated time-frame, the CCO should be notified and given an indication of when the report will be provided.

4.2.6 All complaints will be considered thoroughly by the CCO. The circumstances leading up to the complaint should be fully and objectively reviewed before a reply is drafted. If it is necessary to consult with others for information or opinions, a record should be made and copies of any exchange of correspondence should be kept on the file.

4.2.7 The CCO will communicate the outcome of the review to both the
complainant and the relevant unit/division.

If the outcome of the review is in the complainant's favour, remedial action/an apology (or both) may be necessary.

- If the outcome is not in the complainant's favour, a full explanation must be included in the reply, even if one has been given previously.

- If the outcome raises questions of policy or is likely to have an impact elsewhere in the Agency, the necessary information should be passed by the CCO to the relevant person(s).

4.3 Referral to the Chief Executive

4.3.1 If, following an investigation and reply by the CCO, the complainant writes to say he/she is still dissatisfied with the outcome or the way the complaint has been handled, the CCO may decide, if appropriate (e.g. if referring the matter to the Chief Executive will add value to the complaints process), to refer the matter to the Chief Executive's Office.

4.3.2 Further action, including a further substantive reply, will be directed by the Chief Executive in discussion with the relevant part of the Agency. The Chief Executive’s office will respond within 20 working days. At this stage, the Chief Executive will advise the complainant of his/her right to contact the Independent Complaints Adviser, who has the power to investigate complaints fully and make representations to us on behalf of the complainant.

4.4 The Independent Complaints Adviser (ICA)

4.4.1 A matter may be referred to the ICA either after the CCO has unsuccessfully tried to resolve it, or one stage later after the Chief Executive has also unsuccessfully tried to resolve it.

4.4.2 The role of the Independent Complaints Adviser is: "To investigate complaints against the Medicines and Healthcare products Regulatory Agency leading to a dispute between it and the complainant, on matters relating to administrative actions. To make recommendations concerning resolution of the specific complaint, and, where appropriate, advise on a suitable form of redress. Also, where MHRA operating procedures appear at fault, to make recommendations for improvement."

4.4.3 The ICA will acknowledge the complaint within 5 working days.

4.4.4 Initially, the ICA may try to resolve the matter informally by discussion with the Board Member or line manager concerned. If a more formal course of action proves necessary, the ICA will investigate the circumstances fully and provide a report of any findings and any recommendations simultaneously to the complainant, the MHRA's Chief Executive and the relevant Board Member.

4.4.5 If the report cannot be sent within 20 working days, the ICA will write to the complainant explaining that the matter is being dealt with and giving reasons for any delay.

4.4.6 Following the submission of the ICA's report to the complainant, the Chief Executive and Board member, the report will be submitted to the next MHRA Board meeting for discussion and agreement on any policy or procedural changes recommended by the ICA.

4.5 The Ombudsman

4.5.1 If, following the ICA's report and the MHRA Board's consideration of any policy or procedure changes recommended by him, the complainant is still dissatisfied, he/she may refer the complaint to the Ombudsman through an MP. The letter from the ICA accompanying his report to the complainant should include a statement to this effect.

4.6 Monitoring

4.6.1 The Central Complaints Officer will be responsible for ensuring a record is maintained of complaints received and dealt with by him/her, of subsequent action and for supplying statistics to the MHRA Board.

A summary of the full process is at Appendix A.

For further information and advice on Risk Management contact the Central Complaints Officer, Deputy Central Complaints Officer or Central Complaints Co-ordinator whose details can be obtained on Policy’s site on Insite.

5. APPENDICES

Appendix A – Summary of the complaints process

6. CROSS-REFERENCES
GEN 037: Corrective Action
GEN 038: Preventive Action

7. REVISION HISTORY

Issue Effective Date Reason for revision Prepared by

01 01/01/2000 M Gosling
02 01/03/2005 Updating L O’Brien
03 19/06/2006 Reformatting and S Jones/

Updating S Fletcher
04 29/03/2007 Updating S Jones/S Fletcher

8. KEY WORDS
Complaint; parliamentary question; private office case; central complaints officer;
central complaints co-ordinator; independent complaints adviser; ombudsman

APPENDIX A


SUMMARY OF COMPLAINTS PROCEDURE


C O M P L A I N T
MHRA UNIT / DIVISION LOG AND ACKNOWLEDGE COMPLAINT WITHIN 5 WORKING DAYS
INVESTIGATE COMPLAINT AT GROUP / UNIT / DIVISIONAL
HEAD LEVEL
RESPONSE TO COMPLAINT
IF COMPLAINANT REMAINS DISSATISFIED WITH THE AGENCY’S REPLY, THEY MAY MAKE REPRESENTATIONS TO THE C.C.O.
CENTRAL COMPLAINTS OFFICER (C.C.O.) LOG AND ACKNOWLEDGE COMPLAINT WITHIN 5 WORKING DAYS
REPORT FROM RELEVANT DIVISION TO C.C.O. WITHIN 6 WORKING DAYS OF RECEIPT OF FILE
OUTCOME IN COMPLAINANT’S FAVOUR
REMEDIAL ACTION / APOLOGY
ACKNOWLEDGE COMPLAINT WITHIN 5 WORKING DAYS REPORT / UPDATE MATTER AND REASON FOR DELAY
WITHIN 20 WORKING DAYS
INDEPENDENT COMPLAINTS ADVISER
CHIEF EXECUTIVE: RESPONSE SENT WITHIN 20 WORKING DAYS
OUTCOME NOT IN COMPLAINANT’S FAVOUR
COMPLAINANT NOTIFIED OF OUTCOME.
IF COMPLAINANT REMAINS DISSATISFIED:

That Hare definition of psychopathy in full...

Is this somebody you know?

"...the most devastating features of psychopathy are a callous disregard for the rights of others and a propensity for predatory and violent behaviors. Without remorse, psychopaths charm and exploit others for their own gain. They lack empathy and a sense of responsibility, and they manipulate, lie and con others with no regard for anyone's feelings."

Read on: http://www.crimelibrary.com/criminal_mind/psychology/robert_hare/3.html

Just in case you were wondering about Dr Hare's credentials, he co-wrote DSM-IV.

Matt

Abuse of Trust V - Yellow card report - complaint

I have a keen desire to understand why it is that shite is so often characterized as excellence, so I sent this to the MHRA, copied to Breckenridge, Woods, Vara, Johnson and a whole bunch of daily newspapers:

Dear Sir or Madam,

I would like to complain formally about the fact that my Yellow Card report has not been followed up.

I experienced suicidal ideations coincidental to fluoxetine use, which I take to be about as serious as it can possibly be, short of incapacity or death, and yet I have heard nothing following the receipt of a hard copy of my submission. I would like an explanation for the MHRA's failure to follow up. I wish to be advised of the manufacturer's details (it being a generic drug that I was prescribed). I wish to understand why the system that I was subjected to was so monumentally incompetent, and I imagine the MHRA's contribution will be definitive, in this regard.

I would like the explanation to be full, and detailed, with all considerations properly (as assessed by me) discussed. And I would like an apology, please, even though it's a bit late for that.

Best regards

Matthew Holford

Abuse of Trust IV - Russia charges 3 doctors over Glaxo vaccine tests

""Many of the children sent for trials had been diagnosed with diseases. They (GSK) had no right to put children with health problems through these clinical tests. It can lead to a deterioration in the child's condition, which has happened in the case of some of these children.”

...A company spokeswoman said its own internal audit showed informed consent had been given by all parents and doctors involved in the trial."

Read on: http://glaxosmithklinenews.blogspot.com/2007/03/uninformed-consent.html

This is a relatively old story (5 or 6 months, or so, and there doesn't appear to be anything new on it, judging by my Google search). This was the case that I contacted the DoH (and the MHRA) about, and it is the case that the One of the Four contacted me about ("Delighted to engage GSK shareholders" (below)). I was told that the MHRA knew no more about it than what was avaialable in the press.

What a bunch of jobsworths!

Matt

Abuse of Trust III - New York's HIV Experiment

"In fact it was the drugs that were making the children ill and the children had been enrolled on the secret trials without their relatives' or guardians' knowledge."

Read on: http://news.bbc.co.uk/1/hi/programmes/this_world/4038375.stm

Yes, there's a common theme here, all right. The question is "why?" Because people think that they can get away with it? I suppose that if one wishes to find out what people are capable of, one has to put them in a position where they believe that there will be no repercussions from their conduct, irrespective of how low the motivation was for that conduct.

Matt

Abuse of Trust II - Stolen Generation

"The policy typically involved the removal of children into internment camps, orphanages and other institutions"

Read on: http://en.wikipedia.org/wiki/Stolen_Generation

I was struck by a series of little connections between the previous post and this one. And if we are able to treat the utterly defenceless in this way, what does it say about us, what we have learnt about what is appropriate, and what we are ultimately capable of, as we seek to defend our interests?

We don't actually like children very much, do we?

Matt

Abuse of Trust I - U of Iowa Pays $1 Million to Settle "Monster Experiment"

"Whatever the culpability borne by the academic researchers involved in this 1939 experiment, their colleagues in academia put their head in the sand, failed to recognize the immoral nature of the experiment, and thought only of career ramifications: "the other professors at the time told [Johnson] that it would ruin his reputation to publish the data."..."

Read on: http://ahrp.blogspot.com/2007/08/u-of-iowa-pays-1-million-to-settle.html

Something about this piece on the Alliance for Human Research Protection attracted my attention. So much so, that I 'mailed it to Alan Johnson. It's obviously a grotesque abuse of power, but something tells me that it's indicative of a certain mindset, rather than an isolated incident, limited to one rogue "scientist". Naturally, evil machines (I've had this accusation levelled at me, so I have no compunction in forwarding it), such as Dr Johnson, who appears to have been pursuing his research for his own, private purposes, perhaps even with a view to repairing himself, are few and far between. I don't doubt that the vast majority are geared towards the serving of the Greater Good, whatever that might be.

Matt

Re: FOIA 07/040

I just thought I'd put the previous two posts into context:

Sent: 01 February 2007 01:53
To: MHRA Information Centre
Subject: Panorama: Secrets of the Drugs Trials

Dear Sir or Madam,

I note from the BBC's reportage that the MHRA initiated criminal proceedings against GSK, presumably with respect to its (GSK's) claims and misrepresentations about its anti-depression drug, Seroxat (Paxil, in the US):

http://news.bbc.co.uk/1/hi/health/6308871.stm

I note that this case is some three years old, and wondered what, if any, progress had been made? For what it's worth, the allegations have caused consternation, anger and resentment amongst the "depressed community", if commentary on the internet forums that I post on are anything to go by. If you were able to disclose the status of the investigation, I imagine it would be a benefit to a lot of people to know that this matter is being taken very seriously indeed by those in a position to regulate the drugs industry, and to punish those who take advantage of the desperation of people, who have little choice but to take drugs owing to the paucity of alternatives offered, generally-speaking.

Please note, for your information, that I have discussed this matter (in the context of corporate manslaughter/gross negligence manslaughter) with my local police force, and it is currently logged as an incident.


MHRA Reply

Sent: 21 February 2007 15:19
To: @hotmail.co.uk
Cc: MHRA Information Centre
Subject: RE: FOI 07/040 - FW: Panorama: Secrets of the Drugs Trials

Dear

Thank you for your e-mail of 1st February concerning reports of an MHRA investigation into GSK with respect to claims and misrepresentations concerning its anti-depression drug, Seroxat.

MHRA has considered your request under the provisions of the Freedom of Information Act 2005 and I am pleased to be able to provide the following response. The MHRA has a duty to protect public health and takes seriously any report of a suspected breaches of medicines regulations.

The MHRA investigation into GlaxoSmithKline and its alleged failure to supply pharmacovigilance information to the MHRA relating to the paediatric use of Seroxat (paroxetine) commenced on 1st October 2003. The investigation is still in progress and will continue until the relevant lines of enquiries have been concluded. No decision has yet been made on whether or not to prosecute GSK.

I hope this clarifies the position.

Re: FOI 07/118

I had an afterthought, this morning, which I've just communicated to the Clinical Trials Unit:

Dear [redacted],

As an afterthought: if it is not a criminal offence to withhold trials data, nor, as I understand it from your letter, is it a criminal offence to fail to provide a summary of results/statistical analysis, may I ask how it is possible for the MHRA to investigate GSK for withholding trials data (an investigation that has gone on for over three years, now, I understand)?

Put another way, is there an offence on the statute book that amounts to "Withholding clinical trials data/statistical analysis/summary of results"?

Best regards

Matthew Holford

Re: FOI 07/118

I received a response from the MHRA to a query I put to it back in April, but which it overlooked, at the time. Much as it galls me, I've had to type it up, because I can't work out how to drop in the original Acrobat document, which was attached! My original 'mail is immediately below and my reply is beneath the MHRA's missive, which I've emboldened, for convenience. Make of it what you will, although I would like to draw your attention to the MHRA's "catchphrase," which is "Safeguarding Public Health."

Matt

From: Matthew Holford
Sent: 12 April 2007 15:51
To: MHRA Information Centre
Cc: [redacted]@gsk.com; [one of the Four]@parliament.uk; [one of the Four]@parliament.uk; [one of the Four]@cix.co.uk; [one of the Four]@parliament.uk; [my MP]@parliament.uk
Subject: FOI 07/118 - Medicines regulation and the pharmaceutical industry


Dear Sir or Madam,

I was interested to read the article, by your esteemed Chairman and CEO, respectively, Prof Breckenridge and Kent Woods:

http://www.bmj.com/cgi/content/full/331/7520/834

I must confess myself surprised and delighted to discover that the MHRA charges companies, for the purpose of licensing trials. As such, it is presumably aware of any trial, for which it has granted a licence, and for which it does not receive trials results, including details of elements of that trial conducted in other countries? Does the MHRA keep records of any such failure to notifiy, or is its interest limited to collection of the trial fee? If it does, may I ask from what date it began keeping this information? Also, may I ask what percentage of authorized trials do not have the results notified to the MHRA? May I ask what action it takes, in the event that a failure to notify has taken place? Indeed, may I ask what period of grace, after the end of the trial, does the MHRA permit companies, before commencing legal action, under the relevant legislation (The Medicines for Human Use (Clincial Trials) Regulations 2004 (http://www.opsi.gov.uk/si/si2004/20041031.htm#28))?

Finally, I note that the offences, identified under ss49-50, shall be subject to a fine or a maximum period of imprisonment not exceeding two years (ie, they are considered not to be a serious arrestable offences), upon conviction on indictment. The maximum fine, which is defined by statute, is currently £5,000, I believe. To what extent does the MHRA understand these penalties to be an adequate deterrant to non-compliance with the Law?

Best regards


Matthew Holford

***********************

22 August, 2007

Dear Mr Holford

It has been brought to my attention that you have not been provided with a response to your request for information under the Freedom of Information Act (FOIA) made on 12 April 2007. I apologise for this oversight and I provide a response below:

The Clinical Trials Directive 2001/20/EC and the UK implementing legislation (SI 2004/1031) refer to the sponsors' liability to notify the competent authorities of concerned Member States of the end of a trial within 90 days of its completion. There is no reference however to notification of trial results.

The implementing European Commission guidance ENTR/F2/BL/D 2003 Revision 2:

Detailed guidance for the request for authorisation of a clinical trial on a medicinal product for human use to the competent authorities, notification of substantial amendments and declaration of the end of the trial. [MHRA's emphasis]

refers in section 4.3.2.4: Clinical Trial Report: "The sponsor should provide a summary of the clinical trial report within one year of the end of the trial to the competent authorities of the concerned member states..."

The above legislation and guidance came into effect on 01 May, 2004. In the UK prior to that date the clinical trial legislation placed no obligation on trial sponsors to notify the competent authority of the results from clinical trials, at the end of the trial.

The MHRA has therefore to date, not kept records of where trials results have not been notified to it, following completion of clinical trials in the UK.

I hope this is helpful and once again I apologise for the delay in replying.

Yours sincerely

[redacted]
Clinical Trials Unit

*************************

Dear [redacted]

As you may appreciate, I'm not fully conversant with the way in which the various pieces of legislation "mesh". If I understand correctly, then, a clinical trial must be licensed in order to proceed. Upon completion (or presumably early termination) this must be communicated to the MHRA (in the UK), within a certain specified period of time, with failure to do so being a criminal offence. It is also my understanding that the Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended) provide that information must not be provided that is false or misleading. Regulation 50 provides, if I remember aright.

From your comments, it is apparent that a sponsor may, if it so wishes, not provide the results of trials that have been completed and such completion presumably properly reported. If received wisdom is to be believed, this will be because a trial has "failed". In any event, results data is regarded as proprietary within the industry, and a company may not be compelled to give it up. Indeed, if I understand correctly, trials data is not generally given up, even where a trial is deemed "successful" and used in the marketing authorization application portfolio to demonstrate the "efficacy" of a drug, even where, as is apparently the case with Seroxat, the level of efficacy has not been demonstrated. Instead, a statistical analysis is usually provided. None of this sounds terribly scientific to me, but then I'm a compliance professional, not a drugs regulator.

I would be interested to understand how the MHRA views this withholding of data? We know that certain Seroxat trials "failed", and the results were not made public. Others were held to demonstrate efficacy, and a statistical report based on the successful trials was presumably made available to the MCA/MHRA with the licensing portfolio. This presumably purported to demonstrate efficacy (although not very precisely, as I understand it), safety and quality, or else the product would not have been licensed.

If something similar were to happen today, would this withholding of data be deemed to amount to an offence under Regulation 50 by the MHRA? That is, if a company provides less than all the information about a drug, and the information withheld is negative, then the information that is provided is presumably false, or misleading. Also, does the MHRA endeavour to ensure that it has, at least, a statistical report from all trials conducted on a particular drug, in the event that a marketing authorization is sought for that drug?

I would be interested to read of your views.

Best regards

Matthew Holford

"I am called a bringer of help throughout the world"

It seems that there is a very close link between somebody who grinds up ingredients with a pestle and mortar, and the person who prescribes it. The text below is taken from the Worshipful Society's "History," which, while I suspect it is not entirely complete, is quite interesting. On further reading, I was delighted to discover that the Worshipful Society formulates courses and examines postgraduate qualifications in medical ethics, amongst other things. I nearly pissed myself!

The word 'apothecary' is derived from apotheca, meaning a place where wine, spices and herbs were stored. During the thirteenth century it came into use in this country to describe a person who kept a stock of these commodities, which he sold from his shop or street stall.

London apothecaries were originally members of another livery company, the Grocers', and together these tradesmen can be traced back to the Guild of Pepperers, an association formed in the City in 1180. By 1316, the Pepperers had been joined by the Spicers.

The Pepperers subsequently became wholesale merchant traders dealing en gros (hence the word 'grocer') and in 1428 were incorporated as the Worshipful Company of Grocers. The trade in spicery and the development of pharmacy, on the other hand, became interdependent and led to the emergence of spicer-apothecaries. These members of the Grocers' Company had their shops in Bucklersbury where they stored and sold spices, confectionery, perfumes, spiced wines, herbs and drugs which they compounded and dispensed to the public.

By the mid-sixteenth century apothecaries had become the equivalent of today's community pharmacists, dealing mainly with the preparation and sale of substances for medicinal purposes. Authority over medical practice, however, lay with the College of Physicians.

The London apothecaries with their specialist pharmacy skills petitioned for several years to secede from the Grocers' Company. Gideon de Laune, a wealthy and influential Huguenot, led the separatists. He was Apothecary to Anne of Denmark, wife of James I, which may have helped them gain the king's approval. The Worshipful Society of Apothecaries of London was incorporated by royal charter on 6 December 1617.

King James justified his decision in the House of Commons in 1624: "I myself did devise that corporation and do allow it. The grocers, who complain of it, are but merchants; the mystery of these apothecaries were belonging to apothecaries, wherein the grocers are unskilful; and therefore I think it is fitting they should be a corporation of themselves."

The Society's Hall in Blackfriars, formerly the guesthouse of the Dominican Priory of the Black Friars, was acquired in 1632. Destroyed in the Great Fire of London, it was re-built by 1672 on the same site, where it still stands.

From 1672 until 1922, the Society of Apothecaries manufactured and sold medicinal and pharmaceutical products at the Hall, and in 1673 it founded the Chelsea Physic Garden, only relinquishing managerial control in 1899.

In 1704 the Society won a key legal suit (known as the Rose Case) against the Royal College of Physicians in the House of Lords, which ruled that apothecaries could both prescribe and dispense medicines. This led directly to the evolution of the apothecary into today's general practitioner of medicine.

Just over a century later, as a result of the Apothecaries' Act of 1815, the Society was given the statutory right to conduct examinations and to grant licences to practise Medicine throughout England and Wales, as well as the duty of regulating such practice. It continues to license doctors today as a member of the United Examining Board, the only non-university medical licensing body in the United Kingdom.

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.