25 Apr, 14 | by BMJ Group
The two updated Cochrane reviews on the benefits and harms in influenza of the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) attracted lots of attention after The BMJ published them earlier this month. This is my third blog about the feedback. The first blog focussed on rapid responses to the two research articles, and the second looked at how they were covered in the blogosphere. This final one examines the media coverage.
Debora Mckenzie, New Scientist’s correspondent on infectious diseases, agrees that RCTs are the gold standard method for drug assessment.
But, she argues that, while people with “relatively mild winter flu… can be randomly given the drug or a placebo without raising ethical dilemmas… pandemic stockpiles are intended mainly for people with severe flu.”
Moreover, she argues that the Cochrane reviewers should not have discarded the trials’ data on “reported pneumonia”, and quotes researchers Jonathan Van-Tam (the lead author of the recent systematic review of observational studies and Alison McGeer of the University of Toronto, who say the pneumonia would have been diagnosed by doctors [and hence was valid].
She also cites Marc Lipsitch of the Harvard School of Public Health in Boston, who has reviewed Roche’s Tamiflu data, and agrees that, although observational studies are never as good as RCTs for testing interventions, “It would be unethical to give severely ill people placebo because there is too much evidence Tamiflu saves lives.” Given all this, and the forthcoming meta-analysis of individual patient data from Roche’s trials by the Multiparty Group for Advice on Science (MUGAS, which is part funded by Roche) [link], stockpiling of neuraminidase inhibitors is still justified, Mckenzie concludes.
Richard Van Noorden’s news piece for Nature reports the press briefing at the Science Media Centre by The BMJ and the Cochrane Collaboration, and adds comments from sceptics. He quotes van Tam and Lipsitch again, along with Peter Openshaw, director of the Centre for Respiratory Infection at Imperial College London, who says: “We should demand better-designed clinical trials and greater transparency, but we should not put lives at risk by ignoring the overwhelming body of evidence accumulated over the past five years that supports the use of antivirals.”
Declan Butler’s follow up story for Nature quotes Peter Openshaw again, along with another flu researcher. It goes on “Jody Lanard and Peter Sandman, independent risk-communication experts in New York, say that the press release on the review omits findings that in their opinion are key. For example, it rounds down Tamiflu’s reported 17-hour reduction in symptom duration in adults to “just half a day”, and describes the reduction as “small”. It also does not report the 29-hour reduction in children. Lanard and Sandman claim that there has been “cherry-picking of the results to make them look worse for antivirals”.” Butler sent The BMJ and the Cochrane reviewers a long list of questions about this, but – ironically – he picked only a couple of our answers to report in his article. Anyway, here’s The BMJ’s press release.
The European Medicines Agency (EMA), reports Van Noorden, stands by its risk–benefit assessments and considers that the updated Cochrane reviews add nothing new.
Over in The Pharmaceutical Journal a news article reports Stephen Whitehead, the Association of the British Pharmaceutical Industry’s (ABPI) chief executive, as saying that “there was no reason for the “game of cat and mouse” that went on between Roche and the Cochrane reviewers.” Mr Whitehead told PJ Online that ABPI guidance instructs its members to comply with any “reasonable request” [and] “the Cochrane request was reasonable.” Roche left the ABPI in 2009, but the association says it is still bound by the industry’s code of practice. In contrast, GlaxoSmithKline, an ABPI member, gave the Cochrane reviewers the data on Relenza (zanamivir) without a fight.
Mr Whitehead questioned why Roche could not have behaved similarly and told PJ Online “It doesn’t help the image of the industry.” Speaking at the ABPI’s annual conference on 10 April, Mr Whitehead also said “there could now be a question mark over whether Tamiflu remains on the World Health Organization’s list of essential medicines.”
Competing interests: I chaired the research manuscript committee meeting where we accepted the updated Cochrane reviews on oseltamivir and zanamivir. Last year I observed and blogged about a key meeting of the Multiparty Group for Advice on Science (MUGAS). On behalf of The BMJ I am an active participant in the AllTrials campaign and the Ottawa Group’s IMPACT study, have contributed to several working groups that led to revision of the EU Clinical Trials Directive, and regularly act as an advocate for and give talks on data sharing and particularly on increasing transparency in the reporting of clinical trials.
Trish Groves is deputy editor and head of research, The BMJ