Re: Study claiming Tamiflu saved lives was based on “flawed” analysis
On Wednesday 19th March 2014, researchers from the PRIDE Consortium(1) published the first outputs from a project investigating the effectiveness of neuraminidase inhibitors against outcomes of public health importance during the 2009 pandemic, in The Lancet Respiratory Medicine(2). The headline results suggested that neuraminidase were associated with statistically significant reductions in mortality: overall adjusted odds ratio (OR)=0.81 (95% CI 0.70–0.93; p=0.0024) vs. no treatment; and OR=0.50 (95% CI 0.37–0.67; p<0.0001) if treatment was started within two days of symptom onset.
Within 48 hours, the BMJ issued an article written by a staff journalist, which claimed that the new study “was based on flawed analysis”(3). Zosia Kmietowicz had contacted Dr Mark Jones, University of Queensland, who is also working with the Cochrane Collaboration on another project related to neuraminidase inhibitors. In turn, Jones had provided a detailed statistical critique of the PRIDE study, which formed the centerpiece of Kmietowicz’s article. The PRIDE Consortium were not forewarned about the article and, rather more importantly, not offered any a priori right of reply, as would normally be the case during post-publication correspondence. Faced with such a one-sided critique of its work, the PRIDE Consortium had no option but to post its initial rebuttal in the BMJ(4). There has since been a further critique from Jones and a further statistical rebuttal from the PRIDE Consortium(4).
Thus, the correspondence and debate relating to a major publication in a Lancet Group paper has been played out in the pages of the BMJ, fronted by an entirely one-sided article from a BMJ staff journalist. The major question here, seems to be the propriety of the BMJ and Dr Jones in going beyond the reasonable response to a press release, by asking potential opponents for a detailed statistical critique, without offering the authors of the study any right to reply alongside. A more conventional and considerably more ethical approach would have been to submit correspondence post-publication to The Lancet Respiratory Medicine, which could then have considered the response in the normal way, including offering the PRIDE Consortium a realistic period of time to consider the critique and write a rejoinder.
Jonathan S. Nguyen-Van-Tam
Senior Author, PRIDE Consortium
University of Nottingham, UK
2. Muthuri SG, Venkatesan S, Myles PR, et al. (2014) Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med; published online March 19. http://dx.doi.org/10.1016/S2213-2600(14)70041-4
3. Kmietowicz Z. Study claiming Tamiflu saved lives was based on “flawed” analysis. BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g2228 (Published 19 March 2014)
Rapid Response:
Re: Study claiming Tamiflu saved lives was based on “flawed” analysis
On Wednesday 19th March 2014, researchers from the PRIDE Consortium(1) published the first outputs from a project investigating the effectiveness of neuraminidase inhibitors against outcomes of public health importance during the 2009 pandemic, in The Lancet Respiratory Medicine(2). The headline results suggested that neuraminidase were associated with statistically significant reductions in mortality: overall adjusted odds ratio (OR)=0.81 (95% CI 0.70–0.93; p=0.0024) vs. no treatment; and OR=0.50 (95% CI 0.37–0.67; p<0.0001) if treatment was started within two days of symptom onset.
Within 48 hours, the BMJ issued an article written by a staff journalist, which claimed that the new study “was based on flawed analysis”(3). Zosia Kmietowicz had contacted Dr Mark Jones, University of Queensland, who is also working with the Cochrane Collaboration on another project related to neuraminidase inhibitors. In turn, Jones had provided a detailed statistical critique of the PRIDE study, which formed the centerpiece of Kmietowicz’s article. The PRIDE Consortium were not forewarned about the article and, rather more importantly, not offered any a priori right of reply, as would normally be the case during post-publication correspondence. Faced with such a one-sided critique of its work, the PRIDE Consortium had no option but to post its initial rebuttal in the BMJ(4). There has since been a further critique from Jones and a further statistical rebuttal from the PRIDE Consortium(4).
Thus, the correspondence and debate relating to a major publication in a Lancet Group paper has been played out in the pages of the BMJ, fronted by an entirely one-sided article from a BMJ staff journalist. The major question here, seems to be the propriety of the BMJ and Dr Jones in going beyond the reasonable response to a press release, by asking potential opponents for a detailed statistical critique, without offering the authors of the study any right to reply alongside. A more conventional and considerably more ethical approach would have been to submit correspondence post-publication to The Lancet Respiratory Medicine, which could then have considered the response in the normal way, including offering the PRIDE Consortium a realistic period of time to consider the critique and write a rejoinder.
Jonathan S. Nguyen-Van-Tam
Senior Author, PRIDE Consortium
University of Nottingham, UK
1. http://www.nottingham.ac.uk/research/groups/healthprotection/projects/pr... (last accessed 01 April 1, 2014)
2. Muthuri SG, Venkatesan S, Myles PR, et al. (2014) Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med; published online March 19. http://dx.doi.org/10.1016/S2213-2600(14)70041-4
3. Kmietowicz Z. Study claiming Tamiflu saved lives was based on “flawed” analysis. BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g2228 (Published 19 March 2014)
4. http://www.bmj.com/content/348/bmj.g2228?tab=responses
Competing interests: Senior author of the paper Muthuri et al. (2014) that is being critiqued