Ensuring safe and effective drugs: who can do what it takes?

In the midst of the H1N1 flu “pandemic,” the Australian and UK governments commissioned an update of our longstanding Cochrane review on neuraminidase inhibitors for influenza in (otherwise) healthy adults. The review had first been published in 1999 with updates in 2006 and 2008. While preparing the 2009 update, we received a comment from a Japanese paediatrician. He questioned our conclusion that oseltamivir (Tamiflu) reduces the risk of complications (such as pneumonia) and pointed out that the evidence underlying this conclusion in our 2006 review was based on a single paper—a manufacturer funded meta-analysis1 of 10 manufacturer trials, of which only two had been published in the peer reviewed literature.2 3 To verify the quality and reliability of our previous conclusions, we wrote to the lead author of the meta-analysis, Laurent Kaiser, to obtain original data. We also wrote to Nicholson and Treanor, authors of the two published trials in the Kaiser meta-analysis. Months later, and despite additional correspondence with Roche, oseltamivir’s manufacturer, we remained unable to access any data. In our updated 2009 review we did not include the unpublished trial data from the Kaiser paper, and concluded that the ability of oseltamivir to reduce complications was unknown.

Although our review was praised by some for highlighting important questions about the evidence base of a global public health drug,4 we were left feeling that conclusions drawn from only a proportion of all existing trials (that is, just the published ones) are wholly inadequate. The extent to which unpublished data are included in evidence syntheses is low; a recent survey found that less than 10% of Cochrane reviews did.5 …