Editorial
The publication of the Cochrane review into the use of neuraminidase inhibitors on April 10 underlined the concerns raised in the Jan 3 UK House of Commons Committee of Public Accounts report on the stockpiling of oseltamivir by the UK Government. The committee’s concerns centred on their discovery that clinical trial data for treatments prescribed in the UK are routinely withheld from doctors and researchers. They also acknowledged that this problem is not new and has been recognised in academic circles for many years. The committee concluded that the government should take action to ensure data for all trials are made available and that there should be an audit of unpublished trial data. The story of the Cochrane review dates back to the 2009 influenza pandemic when billions of dollars were spent stockpiling oseltamivir worldwide. The potential reliance on oseltamivir prompted the Australian and UK governments to ask the Cochrane Collaboration to update their 2008 review of the drug. The earlier review suggested that oseltamivir reduced the rates of complications. However, Keiji Hayashi, a Japanese paediatrician, had noted in the review’s online comments that the conclusion hinged on a single paper, which was a summary of ten previous trials, of which only two had been published. The authors of the Cochrane review acknowledged this concern and set about acquiring all the data so they could more robustly address the question of oseltamivir’s efficacy. This could have been the end of the story; however, it ultimately took the manufacturer, Roche, 4 years to release these data. Adding these newly released data into the review overturned the earlier findings. The authors concluded that oseltamivir did not prevent influenza-related complications and only reduced symptomatic disease by about half a day. Unsurprisingly, Roche has disputed the findings of the Cochrane review and the UK Department of Health has stood by its decision to stockpile the drug. However, this is not perhaps the key issue. More farreaching is the matter of withholding scientific findings and the implications that such an incomplete picture has on biomedical research. The problem of withheld trial data is restricted neither to oseltamivir nor Roche. The need for greater www.thelancet.com/infection Vol 14 June 2014
transparency of trial results was acknowledged in the Public Accounts Committee report and, in the past year, argued for by the AllTrials campaign, calling for all past and present clinical trials to be registered and their results reported. Although the need for full reporting of trial data has been recognised for decades, little tangible progress seems to have been made. For this reason a broad movement like AllTrials is necessary to drive a shift in, essentially cultural, attitudes about the reporting of trial findings. One such cultural change, highlighted by Iain Chalmers, now the coordinator of the James Lind Initiative, as long ago as 1985, is the use of the term “negative trial”. Such language falsely gives the impression that this work is of lesser value; however, as Chalmers stated 29 years ago “all trials that have been well conceived and well conducted—whatever their results—represent positive contributions to knowledge”. It is often this negative perception that leads to some trials going unpublished. But this is not the sole reason trials go unpublished. There is at least the perception that many trials are hidden from view for commercial reasons. The biased under-reporting of work has two primary disadvantages: it can lead to harm when it skews the application of treatment, and it can lead to the waste of resources in health care and health research. The Lancet recently addressed the issue of wasted resources in its Series Research: increasing value, reducing waste. The Series showed that, even when published, best practice is still woefully lacking in a substantial proportion of biomedical research. Adding under-reporting to these shortcomings raises serious questions about what guidance can be drawn from much of the body of biomedical literature. The fourth paper in the Series, about addressing inaccessible research, puts the scale of the problem succinctly, “when full information about studies is inaccessible, billions of dollars in investment is wasted, bias is introduced, and research and care of patients are detrimentally affected”. Researchers should operate by a simple credo: if a study is worth doing it is worth reporting. When the consequences are weighed up, this is as much a moral as a professional obligation. ■ The Lancet Infectious Diseases
GIphotostock/Science Photo Library
Research transparency: a moral obligation
For the Cochrane review on neuraminidase inhibitors see http://onlinelibrary.wiley.com/ doi/10.1002/14651858. CD008965.pub4/abstract For the Committee of Public Accounts report see http:// www.publications.parliament. uk/pa/cm201314/cmselect/ cmpubacc/295/29502.htm For more on the AllTrials campaign see http://www. alltrials.net/ For more on the James Lind Initiative see http://www. lindalliance.org/ For more on the Lancet Series Research: increasing value, reducing waste see http://www. thelancet.com/series/research
441
The publication of the Cochrane review into the use of neuraminidase inhibitors on April 10 underlined the concerns raised in the Jan 3 UK House of Commons Committee of Public Accounts report on the stockpiling of oseltamivir by the UK Government. The committee’s concerns centred on their discovery that clinical trial data for treatments prescribed in the UK are routinely withheld from doctors and researchers. They also acknowledged that this problem is not new and has been recognised in academic circles for many years. The committee concluded that the government should take action to ensure data for all trials are made available and that there should be an audit of unpublished trial data. The story of the Cochrane review dates back to the 2009 influenza pandemic when billions of dollars were spent stockpiling oseltamivir worldwide. The potential reliance on oseltamivir prompted the Australian and UK governments to ask the Cochrane Collaboration to update their 2008 review of the drug. The earlier review suggested that oseltamivir reduced the rates of complications. However, Keiji Hayashi, a Japanese paediatrician, had noted in the review’s online comments that the conclusion hinged on a single paper, which was a summary of ten previous trials, of which only two had been published. The authors of the Cochrane review acknowledged this concern and set about acquiring all the data so they could more robustly address the question of oseltamivir’s efficacy. This could have been the end of the story; however, it ultimately took the manufacturer, Roche, 4 years to release these data. Adding these newly released data into the review overturned the earlier findings. The authors concluded that oseltamivir did not prevent influenza-related complications and only reduced symptomatic disease by about half a day. Unsurprisingly, Roche has disputed the findings of the Cochrane review and the UK Department of Health has stood by its decision to stockpile the drug. However, this is not perhaps the key issue. More farreaching is the matter of withholding scientific findings and the implications that such an incomplete picture has on biomedical research. The problem of withheld trial data is restricted neither to oseltamivir nor Roche. The need for greater www.thelancet.com/infection Vol 14 June 2014
transparency of trial results was acknowledged in the Public Accounts Committee report and, in the past year, argued for by the AllTrials campaign, calling for all past and present clinical trials to be registered and their results reported. Although the need for full reporting of trial data has been recognised for decades, little tangible progress seems to have been made. For this reason a broad movement like AllTrials is necessary to drive a shift in, essentially cultural, attitudes about the reporting of trial findings. One such cultural change, highlighted by Iain Chalmers, now the coordinator of the James Lind Initiative, as long ago as 1985, is the use of the term “negative trial”. Such language falsely gives the impression that this work is of lesser value; however, as Chalmers stated 29 years ago “all trials that have been well conceived and well conducted—whatever their results—represent positive contributions to knowledge”. It is often this negative perception that leads to some trials going unpublished. But this is not the sole reason trials go unpublished. There is at least the perception that many trials are hidden from view for commercial reasons. The biased under-reporting of work has two primary disadvantages: it can lead to harm when it skews the application of treatment, and it can lead to the waste of resources in health care and health research. The Lancet recently addressed the issue of wasted resources in its Series Research: increasing value, reducing waste. The Series showed that, even when published, best practice is still woefully lacking in a substantial proportion of biomedical research. Adding under-reporting to these shortcomings raises serious questions about what guidance can be drawn from much of the body of biomedical literature. The fourth paper in the Series, about addressing inaccessible research, puts the scale of the problem succinctly, “when full information about studies is inaccessible, billions of dollars in investment is wasted, bias is introduced, and research and care of patients are detrimentally affected”. Researchers should operate by a simple credo: if a study is worth doing it is worth reporting. When the consequences are weighed up, this is as much a moral as a professional obligation. ■ The Lancet Infectious Diseases
GIphotostock/Science Photo Library
Research transparency: a moral obligation
For the Cochrane review on neuraminidase inhibitors see http://onlinelibrary.wiley.com/ doi/10.1002/14651858. CD008965.pub4/abstract For the Committee of Public Accounts report see http:// www.publications.parliament. uk/pa/cm201314/cmselect/ cmpubacc/295/29502.htm For more on the AllTrials campaign see http://www. alltrials.net/ For more on the James Lind Initiative see http://www. lindalliance.org/ For more on the Lancet Series Research: increasing value, reducing waste see http://www. thelancet.com/series/research
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