{"id":16881,"date":"2012-05-08T14:45:29","date_gmt":"2012-05-08T13:45:29","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmj\/?p=16881"},"modified":"2012-05-08T14:45:29","modified_gmt":"2012-05-08T13:45:29","slug":"andrew-burd-ethics-and-clinical-trial-registration","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmj\/2012\/05\/08\/andrew-burd-ethics-and-clinical-trial-registration\/","title":{"rendered":"Andrew Burd: Ethics and clinical trial registration"},"content":{"rendered":"

\"Andrew These days I do not so often have a gauntlet dispatched in my direction, but when one lands at my feet I have an irresistible urge to pick it up.\u00a0 By way of explanation, one of my passing pleasures is to engage in debate and discussion in the WAME<\/a> list serve, a discussion forum for members of the World Association of Medical Editors (WAME).<\/p>\n

Questions are posed and discussion ensues, sometimes ending in a consensus position, sometimes not.\u00a0 It is, for me, an opportunity to ponder topics outwith my daily routine, and occasionally I find myself challenging the unchallenged assumptions of a somewhat privileged elite.\u00a0<\/p>\n

And so a question was posed regarding clinical trial registration. In essence an editor had received a report of a randomised controlled trial; the study was approved by the local ethical committee; it had been well conducted and the paper was of good quality; but there was no clinical trial registration number.\u00a0 When the authors were asked about this they responded with a registration number with a date indicating this had been assigned retrospectively.\u00a0 The editor of the journal was wondering what to do.<\/p>\n

It is not a matter of virtue but a fact of the celestial universe that, living in the Far East we start our day before those in the West.\u00a0 As such I am invariably the first to comment on new questions for debate posted in the WAME forum.\u00a0 The matter under discussion appeared to me quite straightforward and my pragmatic response was – accept.\u00a0<\/p>\n

My subtext was “What is the big deal?”\u00a0 The answer to that question came from some subsequent postings, where the implications of clinical trial registration began to emerge.\u00a0 It became apparent to me that we were, as is so often the case, entering the arena of confrontation between common sense and vested interests.\u00a0 I suggested that not all clinical trials are equal and questioned the ethical and indeed moral basis for mandatory registering of all clinical trials, unaware that such a position is like wafting a red flag in front of an elderly bull.\u00a0<\/p>\n

The “bull” in this case was not Richard Smith or indeed Richard Horton, although both waxed lyrical on this topic as long ago as 1999.\u00a0 (BMJ 1999;319:865-6<\/a>).\u00a0 In a joint editorial they began with the statement “The case for registering all clinical trials \u2013 first advanced a decade ago \u2013 is now unanswerable.”\u00a0 I am not writing to offend or upset such luminaries in the field of medical publication.\u00a0 What I want to do is to look at a complex situation and ask for more precision in definition, debate and understanding.\u00a0<\/p>\n

It has been put to me, and I quote, “Inviting patients to participate in clinical trials implies a duty to ensure that the results of their participation should be made public.”\u00a0 My perspective is that there are those who take a very blinkered and absolutist attitude towards semantics; and, to crudely paraphrase, Gertrude Stein would say, “A clinical trial, is a clinical trial, is a clinical trial.”\u00a0<\/p>\n

I disagree.\u00a0 Indeed I see that there are clinical trials that are well designed, randomised, controlled, relevant but very, very different in context and consequence.\u00a0 Unless and until this is appreciated, editorials such as that written by the \u2018Richards\u2019 and crusades relentlessly pursued by the blinkered elite will continue.\u00a0 And they will fail to generate the response that they deserve because the authors, the crusaders, have failed to just step back and consider what clinical trials really are.<\/p>\n

\u00a0The spectrum is vast but I see three very distinct types of trial.\u00a0 I see a trial created by an individual doctor who is trying to determine which of two options is better for his patients.\u00a0 The patients are aware of the dilemma; they participate and on the basis of the collaborative efforts of an informed group of patients and their doctor, an \u2018evidence based\u2019 consensus can be achieved.\u00a0 Another form of clinical trial does not result in an outcome that can be qualified as good or bad.\u00a0 These are the trials that look for a mechanistic effect that may lead to better patient selection, or prognosis.\u00a0 Again, this is a trial that is predicated on the ethical doctor trying to do the best for his or her patients in terms of favouring management choices or information analysis.<\/p>\n

I think the critical element in these two scenarios is the ethical duty of care of the investigator to his\/her study population\/patients.\u00a0 Of course they need to know the results but what is the logical imperative that mandates that the investigator has to register the trial and report the results.\u00a0 The supposition is that doctors who conduct clinical trials out of their ethical duty of care to their patients (we call this beneficence, by the way) are of dubious integrity and may suppress results they do not like.\u00a0 What nonsense, and isn\u2019t such a view rather insulting to the majority of honest and ethical doctors?!<\/p>\n

No.\u00a0 The clinical trials that Horton and Smith were referring to are a different matter altogether.\u00a0 These are trials where money is a stake.\u00a0 They may even be trials where there is no intrinsic doctor patient relationship<\/a>.<\/p>\n

That is to say that they are usually industry sponsored where the doctor acts as an agent, usually for a fee, to recruit and treat patients.\u00a0 I absolutely agree that these trials should all be pre-registered and the results should be made public.\u00a0 Question?\u00a0 Does that mean NOT publishing them in restricted access journals?\u00a0 How will that affect impact factors?\u00a0 But back on point, can arbitrary guidelines be drawn up to define which clinical trials mandate pre-registration and public reporting?<\/p>\n

Might I suggest<\/p>\n

1)\u00a0Any industry or institutionally funded trial
\n2)\u00a0Any trial with more than 50 subjects<\/p>\n

That should do for a start.\u00a0 I hope my position is clearer.<\/p>\n

Let us not call for blanket registration or even reporting of all clinical trials.\u00a0 Let us specify which trials must be registered and subsequently reported.\u00a0 Is that so difficult?<\/p>\n

Competing interest<\/strong><\/p>\n

I have just received ethical committee approval of a trial where I shall be looking at the micro RNA response to two low dose formulations of standard medications.\u00a0 It is a randomised prospective, clinical trial and I have been asked to register the study.\u00a0 This involves filling in many details on a multi-page form, details that would be appropriate if these were new drugs, but in the context of this trial details which are completely irrelevant.\u00a0<\/p>\n

To add insult to injury I see that a recent paper in JAMA is now acknowledging that even if trials are registered much of the information suggests they are of dubious quality (JAMA 2012;307:1838-1847<\/a>) and the whole clinical trial registration \u201cideal\u201d is being questioned.<\/p>\n","protected":false},"excerpt":{"rendered":"

These days I do not so often have a gauntlet dispatched in my direction, but when one lands at my feet I have an irresistible urge to pick it up.\u00a0 By way of explanation, one of my passing pleasures is to engage in debate and discussion in the WAME list serve, a discussion forum for […]<\/p>\n

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