Giuseppe
Emeritus
Why don't we have all the evidence on oseltamivir? -- Godlee and Clarke 339: b5351 (BMJ, extract, edited)
[Source Full Free Document: LINK. EDITED.]
Published 8 December 2009, doi:10.1136/bmj.b5351
Cite this as: BMJ 2009;339:b5351
Editorials
Why don?t we have all the evidence on oseltamivir?
The full data from drug trials must be available for scrutiny by the scientific community
This week the BMJ publishes an updated Cochrane review on neuraminidase inhibitors in adults with influenza.1 The review and a linked investigation undertaken jointly by the BMJ and Channel 4 News2 cast doubt not only on the effectiveness and safety of oseltamivir (Tamiflu) but on the system by which drugs are evaluated, regulated, and promoted.
In the process of updating their review, Jefferson et al found several important inconsistencies. Prompted by a reader of their previous update,3 they attempted to reconstruct the evidence from a much cited analysis on which they had based their previous conclusions. The analysis, by Kaiser et al,4 looked specifically at the effects of oseltamivir on the risk of hospital admission and complications (pneumonia and other lower respiratory tract infections) in people with influenza. Jefferson et al noted that the Kaiser analysis was funded by the drug?s manufacturer Roche and was based entirely on 10 trials funded by Roche, only two of which had been published as articles in peer reviewed journals. All 10 included trials were authored by Roche employees and paid academic consultants. The Cochrane reviewers could find no independently funded trials of oseltamivir in healthy adults.
Other questions also arose, as outlined by one of the Cochrane reviewers Peter Doshi5 and by Deborah Cohen in our feature.2 Which authors of the trials had seen the raw data? Why were key authors of the published papers and abstracts not named in company documents submitted for drug approval, while people named in these documents were not included in the published papers? Were ghost writers involved in some of the manuscripts, as alleged by former employees of the medical communication company hired by Roche? Why were the rates of influenza infection in the trials so high? And why were serious adverse events under-reported?
Jefferson et al asked for clarification from the authors, who directed them to Roche. After initially declining to provide the necessary data, staff at Roche sent the Cochrane reviewers a selection of files, which answered some questions but still left the reviewers unable to reconstruct the Kaiser dataset. Of particular concern, the eight unpublished trials, involving 2691 patients, included one of the biggest trials of oseltamivir. More worrying still, the academic author named on the trial?s abstract in the Kaiser analysis and in company documents has told the BMJ he was not involved in the trial.
Noting that the number of complications in the trial populations was small, Roche also provided some observational studies of oseltamivir as evidence of its "real world" effects on hospital admissions. The BMJ has since commissioned Nick Freemantle and Mel Calvert to review these and additional observational studies. They concluded that the studies provided only weak evidence and that any absolute benefit was small.6
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<cite cite="http://www.bmj.com/cgi/content/full/339/dec08_3/b5351">Why don't we have all the evidence on oseltamivir? -- Godlee and Clarke 339: b5351 -- BMJ</cite>Published 8 December 2009, doi:10.1136/bmj.b5351
Cite this as: BMJ 2009;339:b5351
Editorials
Why don?t we have all the evidence on oseltamivir?
The full data from drug trials must be available for scrutiny by the scientific community
This week the BMJ publishes an updated Cochrane review on neuraminidase inhibitors in adults with influenza.1 The review and a linked investigation undertaken jointly by the BMJ and Channel 4 News2 cast doubt not only on the effectiveness and safety of oseltamivir (Tamiflu) but on the system by which drugs are evaluated, regulated, and promoted.
In the process of updating their review, Jefferson et al found several important inconsistencies. Prompted by a reader of their previous update,3 they attempted to reconstruct the evidence from a much cited analysis on which they had based their previous conclusions. The analysis, by Kaiser et al,4 looked specifically at the effects of oseltamivir on the risk of hospital admission and complications (pneumonia and other lower respiratory tract infections) in people with influenza. Jefferson et al noted that the Kaiser analysis was funded by the drug?s manufacturer Roche and was based entirely on 10 trials funded by Roche, only two of which had been published as articles in peer reviewed journals. All 10 included trials were authored by Roche employees and paid academic consultants. The Cochrane reviewers could find no independently funded trials of oseltamivir in healthy adults.
Other questions also arose, as outlined by one of the Cochrane reviewers Peter Doshi5 and by Deborah Cohen in our feature.2 Which authors of the trials had seen the raw data? Why were key authors of the published papers and abstracts not named in company documents submitted for drug approval, while people named in these documents were not included in the published papers? Were ghost writers involved in some of the manuscripts, as alleged by former employees of the medical communication company hired by Roche? Why were the rates of influenza infection in the trials so high? And why were serious adverse events under-reported?
Jefferson et al asked for clarification from the authors, who directed them to Roche. After initially declining to provide the necessary data, staff at Roche sent the Cochrane reviewers a selection of files, which answered some questions but still left the reviewers unable to reconstruct the Kaiser dataset. Of particular concern, the eight unpublished trials, involving 2691 patients, included one of the biggest trials of oseltamivir. More worrying still, the academic author named on the trial?s abstract in the Kaiser analysis and in company documents has told the BMJ he was not involved in the trial.
Noting that the number of complications in the trial populations was small, Roche also provided some observational studies of oseltamivir as evidence of its "real world" effects on hospital admissions. The BMJ has since commissioned Nick Freemantle and Mel Calvert to review these and additional observational studies. They concluded that the studies provided only weak evidence and that any absolute benefit was small.6
(...)
-