The Tamiflu trials

This week sees the publication of the updated Cochrane systematic review on the neuraminidase inhibitors oseltamivir and zanamivir.1 The review, which is also reported in two papers published in The BMJ,2 3 provides the most complete analysis so far of what is known from randomised trials about the effectiveness and safety of these antiviral drugs. It is also the culmination of a four and a half year battle for access to the raw data from industry funded trials of oseltamivir, a drug on which the world has spent billions of dollars.4

Through their exhaustive scrutiny of the data contained in clinical study reports (the lengthy documents held by the drug’s manufacturer Roche and previously seen only in part by drug regulators), the Cochrane authors have set exacting new standards for systematic reviewers and decision makers. Their fight for the data has also shown us, in more detail than ever, that the entire ecosystem of drug evaluation and regulation is deeply flawed.

The Cochrane review and BMJ papers represent a huge amount of work. The authors—Tom Jefferson, Carl Heneghan, and colleagues—are among just a handful of systematic reviewers who have made use of clinical study reports (CSRs) to reach their conclusions. CSRs are intended to provide regulatory authorities with a structured detailed report of a clinical trial.5 In contrast to the abbreviated information about a trial contained in a journal article, one CSR can extend to hundreds of pages. The “compression factor”—the length (in pages) of the CSR of a trial compared with the length of the corresponding journal article—has been found to range from one to an astonishing 8805.6 7

It is a formidable task to sift through this amount of information, which is …