BMJ Editor Bitch Slaps* Roche
In the midst of the 2009 pandemic influenza epidemic, BMJ editor Fiona Godlee takes Roche to task for not supplying the necessary data to confirm or refute the benefits of oseltamivir (Tamiflu) in otherwise healthy people with influenza. In one of 2 BMJ editorials, Godlee chides Roche for not supplying unconditional access to raw data from a pooled analysis of 10 company-sponsored trials (Kaiser et al; PubMed link here) to Cochrane reviewers Jefferson et al. Consequently the reviewers were "obliged to disregard" the bulk of these data (8 of the 10 trials) and were unable to verify that oseltamivir prevents lower-respiratory-tract complications (eg, pneumonia) due to influenza.
In their previous 2006 Cochrane review, Jefferson et al had concluded that oseltamivir 150 mg daily prevents such complications on the basis of the Kaiser article. However, the authors were criticized through a public feedback mechanism for using the 10-trial analysis without having access to the raw data. Prompted by this criticism, Jefferson et al then conducted another review, published this week in the BMJ, in which they affirmed their critic's perspective:
Data on the effectiveness of oseltamivir against complications of influenza principally came from one study...This was a meta-analysis of 10 trials containing a mixture of published and unpublished data, two of which are reported in this update and the remainder inaccessible to proper scrutiny, so that we are now obliged to disregard them. The remaining data showed no benefit for oseltamivir against complications.
In her editorial, Godlee asks, "Where does this leave oseltamivir, on which governments around the world have spent billions of pounds?" She, moreover, emphasizes that the Cochrane review data apply only to healthy adults with influenza, but they "say nothing about [oseltamivir's] use in patients judged to be at high risk of complications—pregnant women, children under 5, and those with underlying medical conditions." Even the drug's ability to reduce influenza-related symptoms (which Jefferson et al reconfirmed) are doubted, because there are no head-to-head studies with oseltamivir and NSAIDs, for instance.
In another BMJ editorial (with Cochrane director Mike Clarke), Godlee concludes that the latest Cochrane review and a "linked investigation undertaken jointly by the BMJ and Channel 4 News 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 their investigation, Cochrane reviewers became concerned about the actual involvement of listed authors on the Kaiser analysis, the possibility of ghostwriting, the high rates of influenza in the trials, and the low rates of serious adverse events.
Initial responses from Roche employees, who first declined to provide the data and then offered selected files, were less than satisfactory to the reviewers. The latest response from the company: it is "committed to making the 'full study reports' available on a password protected site soon."
On the basis of this experience, Godlee and Clarke conclude that the current system for reporting drug research "isn't working" and offer a number of potential remedies—including government-mandated access to raw data that are used to license and market a drug (eg, something in the spirit of the FDA Amendments Act of 2007).
News sources are all over this story (eg, Bloomberg), and the BMJ offers full-text access to the following relevant articles, including a response from a Roche employee—who chastises Jefferson et al for enlisting the investigative help of a TV news station.**
- Godlee F. We want raw data, now.
- Godlee F, Clarke M. Why don't we have all the evidence on oseltamivir?
- Smith J, on behalf of Roche. Roche replies to the authors of the Cochrane Review on oseltamivir.
- Cohen D. Complications: tracking down the data on oseltamivir.
- Doshi P. Neuraminidase inhibitors--the story behind the Cochrane review.
- Freemantle N, Calvert M. What can we learn from observational studies of oseltamivir to treat influenza in healthy adults?
- Jefferson T, Jones M, Doshi P, Del Mar C. Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis.
- Web extra (including the criticism that got the ball rolling).
* And I mean that in the nicest possible way.
** Roche's Smith writes, "It is unclear to us why Dr Jefferson would adopt this approach, particularly given that he was a paid ad hoc consultant to Roche working on flu and oseltamivir between 1997 and 1999. During that period he worked closely with Roche experts, many of whom are still in the company, and he would therefore not have had difficulty in contacting them directly to discuss his requirements."
Photo from Vermin Inc at Flickr.
