More opaque than an opaque thing, with a very good reason for being opaque

I'm just engaged in a couple of discussions with the MHRA. I'm not quite sure what they're about, but I'm sure I'll find out eventually. The MHRA's mails are emboldened, as usual:


Dear (redacted),

Many thanks for your prompt reply.

I am (reasonably) familiar with the relevant legislation. However, I wonder if you could confirm that I have understood your previous mail correctly, which I think I've paraphrased (more or less) in the second para of my response, below?

I am surprised that the MHRA is unable to provide a statement of its position, relative to the questions asked in the last para of my mail. I understand that the MHRA has an Intelligence and Enforcement Unit, which would presumably be able to provide the definitive position on what it regards to be a transgression of Regulation 50, given that it is the MHRA that makes decisions as to whether any investigation is initiated? In short, what I am asking for is expert guidance, such that I am able to understand something which, while it looked straight forward enough when I was reading the Regulations, has suddenly become opaque. If I may not ask the MHRA for such a thing, could you direct me to the appropriate body?

As to the question concerning statistical reports: surely that is a matter of fact, not opinion?

Best regards

(redacted)

****************************
From: (redacted)
To: (redacted)
CC: (redacted)
Subject: RE: FOI 07/118 - Medicines regulation and the pharmaceutical industry
Date: Thu, 6 Sep 2007 13:06:26 +0100


Dear (redacted)

Please find a response attached.

Yours sincerely
(redacted)
Medicines and Healthcare products Regulatory Agency
Room 12-204, Market Towers
1 Nine Elms Lane
London SW8 5NQ

Tel: 020 7084 2487
Fax: 020 7084 2443

Attachment:
Dear (redacted)

Re: FOI 07/118 (FU)

I am responding to your emails of 23rd and 24th August in which you have presented additional questions to my Freedom of Information response to you of 22nd August.

My original response to you indicated what was required under the EU and UK clinical trials legislation and guidance in relation to your initial questions. For further information I would refer you to the UK Statutory Instrument 2004/1031 which can be accessed on the web at the following link: http://www.opsi.gov.uk/si/si2004/20041031.htm and Volume 10 of the European Commission Pharmaceutical Documentation at: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/homev10.htm

Beyond this your emails appear to be asking me for views and opinions on certain issues which I believe to be beyond the scope of the FOIA.

Yours sincerely

(redacted)
****************************
From: (redacted)
Sent: 23 August 2007 22:31
To: (redacted)
Cc: (redacted)
Subject: RE: FOI 07/118 - Medicines regulation and the pharmaceutical industry

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

(redacted)

****************************
From: (redacted)
To: (redacted)
CC: (redacted)
Subject: RE: FOI 07/118 - Medicines regulation and the pharmaceutical industry
Date: Wed, 22 Aug 2007 17:23:41 +0100


Dear (redacted)

Please find attached a response to your request for information below.

Regards
(redacted)
Medicines and Healthcare products Regulatory Agency
Room 12-204, Market Towers
1 Nine Elms Lane
London SW8 5NQ

Tel: 020 7084 2487
Fax: 020 7084 2443
--------------------------------------------------------------------------------
From: (redacted)
Sent: 12 April 2007 15:51
To: MHRA Information Centre
Cc: (redacted)
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


(redacted)