Wednesday 12 November 2014

The bias of systematic reviews and the neuraminidase inhibitors

6.9 billion dollars were spent around the world in 2009 stockpiling oseltamivir to combat pandemic influeza. So this drug must have magical powers. There’s little doubt it was magic for Roche. But does it actually benefit patients? Maybe we should look for the answer in systematic reviews of the neuraminidase inhibitors. These reviews and meta-analysis are meant to be about the highest form of evidence we have. But could they be subject to substantial bias? Could authors have financial conflict of interest that might sway their conclusions? Unfortunately the answer is an emphatic yes.

The author from the University of NSW Sydney found 26 systematic reviews about the neuraminidase inhibitors. Of these 13 examined prophylaxis and 24 examined treatment accounting for 37 distinct assessments. Two blinded reviewers looked at each of these to determine if the review was positive or negative. They then looked to see if there was a financial conflict of interest.

I think we can all predict the results but I was genuinely surprised at the extent of the results. Of the 8 reviews determined to have a conflict of interest, 7 (88%) were determined to be favourable. Of those without conflict of interest only 5 out of 29 (17%) were in favour. In addition, those without conflicts were much more likely to mention problems with publication bias, the quality of the studies and missing data.

So there is little doubt that systematic reviews can have substantial bias. Many assumptions go in to the selection of included studies, the grading of the evidence and all of this can be easily corrupted. Perhaps it is time we ditch the notion of systematic reviews being high quality evidence- especially if there are any conflicts of interest. Maybe we should bury them under the pile of 6.9 billion dollars worth of oseltamivir rotting in the ground.

Dunn AG, Arachi D, Hudgins J, et al. Financial Conflicts of Interest and Conclusions About Neuraminidase Inhibitors for Influenza. Ann Intern Med. 2014;161:513-518.

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