Monday, 14 January 2013

Publication of all results from clinical trials

Publish all Clinical Trial Results

Hazel Thornton drew our attention to the correction to the NEWS item published in the issue of the BMJ: Patients are urged to boycott trials that do not guarantee publication.
The correction reads:

"This News story states that the Cochrane Collaboration backs the initiative, but the organisation has yet to officially sponsor the campaign (BMJ2013;346:f106, doi:10.1136/bmj.f106). It also says that the Centre for Evidence-Based Medicine is at Bond University, when it is in fact at the University of Oxford."

BMJ Editor's Choice

Timely publication of all trial results may mean less overtreatment

Fiona Godleeeditor, BMJ
Two BMJ campaigns coincide this week: for publication of all results from clinical trials, and against overdiagnosis and overtreatment.

Sentinel node biopsy (removal of the sentinel lymph node) is widely used to stage disease in patients with breast cancer and malignant melanoma. It carries a risk of lymphoedema and other complications, which increases if patients with positive sentinel nodes go on to have further lymph nodes removed in an effort to improve their survival. Evidence from several large trials has saved women with breast cancer from having axillary lymph node dissection if they have no clinical signs of axillary involvement: the trials found no significant difference in overall or disease free survival when axillary dissection was added to sentinel node biopsy.

But as Ingrid Torjesen reports, patients in the United Kingdom, the United States, and elsewhere who have malignant melanoma are routinely undergoing sentinel node biopsy, followed by regional lymphadenectomy if the biopsy is positive (doi:10.1136/bmj.e8645). This is despite guidance from the UK’s National Institute for Health and Clinical Excellence that there is, as yet, no published evidence from randomised controlled trials that sentinel node biopsy improves survival.

What trial evidence there is comes from the Multicenter Selective Lymphadenectomy trial (MSLT-1). Five year follow-up data published in the New England Journal of Medicine in 2006 found no overall survival advantage in patients who had sentinel node biopsy compared with those who didn’t. But controversy has arisen over the authors’ claims of improved disease free survival. These claims are based on a lower rate of nodal recurrence in the biopsy group, but critics say this finding is unsurprising, since the patients in the intervention group who are most at risk—those with a positive sentinel node—have had their regional nodes removed.

The researchers promised further analyses after 10 years of follow-up and at an interim point, and had these been published as expected in 2008 and 2011, the controversy might have been resolved by now. But these data have not yet been published. The authors say they are working on their analysis. Meanwhile, sentinel node biopsy has become the standard of care in many countries. NICE says the procedure is justified only in the context of clinical trials, but Torjesen has learnt that it is carried out in at least 19 trusts in England, only two of which are involved in ongoing trials. Is this another example of harmful overtreatment? Only the trial data will tell.

This is not the only case in which clinical trial data have been published late or not at all. In addition to the well documented suppression of data by drug companies, there are clear examples of delayed or non-publication in non-industry sponsored trials. Last week we reported on the long delay in publication of a trial of deworming and vitamin A that was completed in 2005 (BMJ 2013;346:e8558). This week in an editorial we reference a large trial of adenoidectomy that has only just reported after nearly a decade (doi:10.1136/bmj.f105). The editorial calls for ethics committees, funders, and institutions to take responsibility for ensuring that the trials they approve, support, and host are published in full and in good time. Working with others, we are taking the campaign to patients and the public. If you agree that all clinical trials should be published, sign the petition at
Cite this as: BMJ 2013;346:f159

Call for release of all drug trial results
The Times – 10.01.2013

The failure of academics and pharmaceutical companies to release the full results of clinical trials is stifling medical discovery and putting lives at risk, doctors say. The British Medical Journal is calling on the public to sign a petition at demanding the results of all trials be published.

Dr Ben Goldacre said that the petition was a response to “years of foot dragging” around what he described as the “biggest systemic flaw in evidence-based medicine”.

“For 20 years now, people have claimed this is being fixed,” he said. “People have acted as if this is an embarrassing secret, that should only be discussed behind closed doors. But that approach has demonstrably failed, so now we are making it public.”

At present, doctors and researchers do not have access to the full results of clinical studies. With approximately half of all trials conducted on patients never published, this means that doctors prescribe drugs without the full available evidence, or worse, with misleading evidence.

“The best available evidence shows that studies with positive results are twice as likely to get published,” said Dr Goldacre. “Those with negative results are more likely to go missing in action, so doctors see biased evidence. When we are misled about effects of treatments, we cannot make the best decisions for patients.”

Supporters of the petition argue that this means information about the efficacy of drugs — and the relative importance of side effects — is lost, but also that trials are needlessly repeated, by researchers who are unaware they are replicating prior work. They are also asking for the release of all the relevant previous results on all drugs still currently being prescribed.

“Most of all, the current situation is a betrayal of the trust that patients, and trial participants, place in us,” said Dr Goldacre. “Patients participate in trials, sometimes enduring extra discomfort or inconvenience, because they believe the results will inform practice and help others in the future. When the results are buried, those patients have been misled. We need people to participate in trials, but we can’t ethically pretend that this problem doesn’t exist. We should either make sure all the results are published or be honest and say, ‘If the researcher or sponsor company doesn’t like the results we won’t publish’.”

One of the most-cited cases of results being withheld is with Tamiflu, an antiviral drug produced by Roche. Dr Carl Heneghan, Director of the University of Oxford’s Centre of Evidence-Based Medicine, works on the drug, on which the UK government has spent half a billion pounds. He believes that because of a failure by Roche to release full clinical trial reports, despite promising to do so, we still don’t know if that was money well spent.

“We’re still awaiting data from Roche which they have refused to give us for years,” he told The Times. “Eight of the initial ten studies into the drug were never published. When we asked Roche for them they refused to make the full study results available. We’ve spent £500m on Tamiflu and we still don’t know if works.”
“When data is withheld it can look initially that a drug is promising. However when full data is available, we might realise that there are more harms than benefits. Any treatment we use is about the relationship between how much it benefits a patient and how much it harms them. That ratio is incredibly important. The withholding of data skews this. We will look back in 20 or 30 years and think what we do now is ridiculous.”
· Sense About Science’s petition can be signed at

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