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EDITOR'S CHOICE: Kamran Abbasi Trial results: the next battle BMJ 2005; 330: 0-g [Full text]

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we should welcome the initiative

Madhu Chittarvu   (14 January 2005)

It's not enough, long way to go.

Vineet Gupta   (14 January 2005)

Disclosure of trial results

David G Wilkinson   (16 January 2005)

Published Conclusions Must Accurately Reflect Research Results

Stefan P. Kruszewski   (19 January 2005)

Trial Results: the next battle

John R Kirwan   (21 January 2005)

we should welcome the initiative 14 January 2005
Madhu Chittarvu, consultant physician Hyderabad India 500013 Send response to journal: Re: we should welcome the initiative	Dear Editor Instead of being cynical I feel we should welcome the move of drug companies to disclose their trial results voluntarily or by other means. It is still better than not revealing any thing until it would be too late. The fiasco of Rofebax and other cox 2 inhibitors leaves one saddened and disillusioned. In our country we prescribed these drugs tremendously and indiscriminately. I still remember the vigorous propaganda and exuberant launchimg of these drugs in my city. Only now we are biting our lips in anger and near repentance. We comment on other systems of medicine as unscientific, but how ethical are we? At least the publication of trial results will leave the prescribing doctor to decide for himself and decide to prescribe a drug. Of course legislation and proper analysis of results by competent statisticians will certainly help. Leading journals like BMJ must take the lead to suggest ways to the proper implementation of a monitoring system. Competing interests: None declared
It's not enough, long way to go. 14 January 2005
Vineet Gupta, Junior Resident,Emergency Medicine AIIMS, NEW DELHI 110029 Send response to journal: Re: It's not enough, long way to go.	Cursory glance over the decision by the pharma companies incite a sense of responsibility among the profit-earning firms. But an indepth analysis, force us to accord with the editor in terms of “cautious welcome”. Obviously ,the recent debacle of Rofecoxib and few other drugs compounded with the financial implications have compelled the Pharma firms for hurrying on with such a decision. Infact they could have sensed the legislation in near future. Without doubt the role of leading medical journals including BMJ cannot be ignored ,as they have declared publication of only the registered trials(this certainly would have had an impact- though small) . As cited by the editor there are still few lacunae in the decision and several measures need to be taken to make it effective: 1) The disclosure and registration of trials be made mandatory instead of voluntary nature 2) An international regulatory authority be constituted , with it’s website to provide the platform for registration and display of any trial – new or old. This will in turn check the possible chaos of searching innumerable databases . 3) Moreover, uniform guidelines should be released for declaration of the results and not left to the companies to define the registration . 4) More importantly the inclusion of companies of developing countries ,which hardly have stringent laws back home to regulate the use of drugs (either on trial or unapproved) should be made compulsory. Clearly there appears to be a lack of resolve among the Pharma companies ,but implementation of above suggestions by means of stringent laws can surely help doctors in dispensing safe drugs(and avoid repentance later on ) instead of unconsciously carrying on unregistered covert trials on poor patients. Competing interests: None declared
Disclosure of trial results 16 January 2005
David G Wilkinson, Consultant in Old Age Psychiatry Moorgreen Hospital Southampton Send response to journal: Re: Disclosure of trial results	I wonder what Kamran Abassi's experience is in clinical trials or indeed medicine. This piece was badly written, petulant and ingenuous. During my involvement with pharma sponsored trials, I have, at every opportunity, demanded full publication of all trial results. Apart from the issue of non publication of results it behoves us as the clinicians involved not to support the publication of papers which include just the results, or worse the overanalysed results, cherry picked by the marketing departments. I am therefore in favour of the general thesis of this editorial but the argument was disarmed by the juvenile style, which does not do the bmj credit. Competing interests: None declared
Published Conclusions Must Accurately Reflect Research Results 19 January 2005
Stefan P. Kruszewski, Psychiatrist Harrisburg, Pennsylvania USA Send response to journal: Re: Published Conclusions Must Accurately Reflect Research Results	Dr. Vineet Gupta details several important ideas in his rapid response to Kamran Abbasi’s “Editor’s Choice” article from 15 January 2005. (1) I am responding specifically to Dr. Gupta’s remarks suggesting that, “uniform guidelines should be released for declaration of the results and not left to the companies to define the registration.” (2) My understanding of the above comment is this: It is essential that the declaration of any results---those summaries that are provided in clinical research papers that form the basis of the abstract and conclusions---be guided by certain accepted, mandated and rigorously applied publication standards. They must accurately represent the findings of the clinical research. The reason is straightforward. Neither voluntary nor mandated registration of clinical trials at their inception or the publication of all clinical trial results requires that the conclusions of those research findings accurately reflect the content of the research. Here is a case-in-point from a paper that I recently reviewed from previously published neuropsychiatric research. The results of the research were published in The Journal of the American Medical Association in an article entitled, “Gabapentin for the Treatment of Postherpetic Neuralgia.” Two of the authors of the study, Leslie Magnus-Miller, M.D. and Ms Paula Bernstein, MS, were paid employees of Parke- Davis. The pharmaceutical company, subsequently acquired by Pfizer, also paid the compensation for study expenses related to this research effort. The conclusion of the article summarizes the author’s findings as follows: “Gabapentin is effective in the treatment of pain and sleep interference associated with postherpetic neuralgia. Mood and quality of life also improve with gabapentin therapy.” There is a problem with those robust summary statements, however. They do not accurately reflect the data found within the body of the results section of the same research paper. Certain findings within the body of the published ‘results’ and ‘safety’ sections do not corroborate the authors’ stated conclusions about mood and quality of life. Specifically, the clinical research results demonstrated that the persons receiving gabapentin suffered emotionally and were ‘less well’ when compared to those receiving placebo. That finding, numerically depicted in the ‘Role-emotional’ section of the Quality of Life Domains as judged by the authors’ use of Short Form-36 Quality of Life Questionnaire, was omitted from mention in the abstract’s Results and/or Conclusion sections. Likewise, in the same Short-Form 36, under item ‘General Health,’ individuals receiving placebo improved more and were judged healthier than the comparison gabapentin group. That research finding was also ignored in the Results and/or Conclusion sections of the abstract. Finally, the gabapentin ‘treatment’ group had a higher drop-out rate and suffered significantly more adverse events than the dissimilar placebo group to which it was compared---findings that did not make it into the conclusions. The significance of these omissions: Inaccurate conclusions from pharmaceutically-sponsored research are published in a prestigious peer- reviewed journal. The authors specifically misrepresent their own findings in their otherwise robustly positive summary statements by failing to include data that contradicts their published conclusions. And, the problem with that? Pharmaceutical firms base much of their marketing efforts, including physician detailing, on the summary statements and the conclusions of work that they choose to support and publish. If those conclusions misrepresent their findings, then the subsequent advertising and the marketing of their pharmaceuticals based upon that misrepresentation is, at best, inaccurate and, at worst, purposefully and deceptively misleading. 1. Abbasi, K. Trial results: The next battle. BMJ: 2005; 330 (15 January), doi:10.1136/bmj.330.7483.0-g 2. Gupta, V. Rapid Response to No. 1(above) 3. Rowbotham, M et al. Gabapentin for the Treatment of Postherpetic Neuralgia. JAMA. 1998; 280(21): 1837-42. Competing interests: None declared
Trial Results: the next battle 21 January 2005
John R Kirwan, Consultant Rheumatologist and Professor of Rheumatic Diseases University of Bristol Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol, BS2 8HW Send response to journal: Re: Trial Results: the next battle	Dear Editor, Trial Results: the next battle In Editor’s Choice you describe the next battleground with the pharmaceutical industry as ‘full disclosure of trial results’ and wonder how this battle might be won (BMJ 15 January 2005). It is arguable that there is an ethical imperative to make full data from clinical studies widely available (1) and the important benefits to be gained from secondary analysis of data derived from prospective clinical studies have been discussed (2). I undertook an enquiry to consider the possibility of making original data from published clinical studies available for alternative analyses and to sought the opinion of those in pharmaceutical companies working in the field of rheumatology. (3). Appropriate personnel in 25 pharmaceutical companies were sent a letter identifying the issue and asking: 1. Is it a good idea to require that authors of a published clinical study deposit the data relating to that publication in a data bank accessible to their colleagues? 2. Do you foresee any particular difficulties in implementing such a scheme in relation to confidentiality of commercially sensitive information? Twenty one (84 percent) replies were received. Fifteen respondents added additional comments. One quarter were in favour of making original data available, and 38 percent did not foresee any commercial difficulty in doing so. Common objections related to departure from study protocol analysis and misinterpretation of the data. However, arguments against these and other objections are straightforward and a closer review of the additional comments received suggests that there may be greater acceptance of this proposal when it is more deeply considered (3). However, two important problems remain. The first is that publishing original data may make it possible to identify individual patient participants in a study and hence break the rule of confidentiality under which research is conducted. Authors who recognised this problem (which would probably be very rare) could justifiably present their data in aggregate or summary form alone. There may also be computer generated re- coding methodologies which could be employed(8). The second remaining problem is that an alternative analysis of the data may itself be commercially important. If this were recognised by the company concerned, the analysis should be conducted as part of the study itself, prior to publication. If it is not recognised by those publishing the original paper then all the more reason for ensuring that others in the field are in a position to identify the need for and conduct the analysis. The respondents in favour of making data available recognised that once a decision to publish has been made, this implies that every facet of the study will be published, subject only to the limits of space and convention. Thus a proportion of senior members of pharmaceutical companies already recognise the advantages of making published trial summary data available in its original form. It may be relatively straightforward to overcome the reservations expressed by others. Journal editors should continue to press for this method of improving the usefulness of published clinical studies. John Kirwan Consultant Rheumatologist and Professor of Rheumatic Diseases 1. Munro AJ. Publishing the findings of clinical research. British Medical Journal 1993; 307: 1340-1341. 2. Davey Smith G. Increasing the accessibility of data. British Medical Journal 1994; 308: 1519-20. 3. Kirwan JR. Making original data from clinical studies available for alternative analysis. The Journal of Rheumatology 1997; 24: 822-825. Competing interests: None declared