Thursday, 23 August 2007

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."


From: Matthew Holford
Sent: 12 April 2007 15:51
To: MHRA Information Centre
Cc: [redacted]; [one of the Four]; [one of the Four]; [one of the Four]; [one of the Four]; [my MP]
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:

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 (

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 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

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

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