Tamiflu Re-analysis


Paul Roblin, GP & CEO BBOLMC

On 30.1.15 the Lancet published a re-analysis of Oseltamavir effects in symptomatic influenza like illness “Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials”.  This trial was authored by Joanna Dobson, Richard J Whitley, Stuart Pocock, Arnold S Monto.

The lancet supplemented this re-analysis with an article by Heath Kelly and Benjamin Cowling entitled “Influenza: the rational use of oseltamivir

The Kelly and Cowling article claims that the re-analysis was done by an independent research group. I am concerned that not all relevant links of the authors of the Dobson Lancet paper have been sufficiently declared.  The competing interests are very vaguely presented, omitting key facts

The Dobson paper contains the following: 

Page 9 of the paper has the text below
JD did the statistical analyses and prepared data tables and figures. All authors contributed to writing of the manuscript and made substantial contributions to conception and design of the study, and analysis and interpretation of data.
Declaration of interests
ASM reports fees from Biocryst and Roche outside of the submitted work. RJW reports fees as a board member of Gilead Sciences, funding for travel from Roche to attend an Influenza Resistance Committee meeting, and fees as Associate Editor of the Journal of Infectious Diseases. JD and SP declare no competing interests.
This study was funded by the Multiparty Group for Advice on Science (MUGAS) Foundation through an unrestricted grant from Roche Pharmaceuticals. Neither party had a role in analysis, interpretation, reporting or the decision to submit for publication. We thank Roche for providing the data and answering data specific queries.

Page 4 of the paper has the text below
Role of the funding source
The meta-analysis was funded by the Multiparty Group for Advice on Science (MUGAS) who assembled a multidisciplinary team to examine the overall data from trials of oseltamivir in adults. The team agreed an individual patient data analysis was the most robust approach, and to cover the costs the MUGAS Board applied for an unrestricted grant from Roche. This unrestricted grant stipulates that Roche would not be involved in the actual review process in any way other than providing the requested data dictionaries and datasets. The results were not shared with Roche until the analysis was completed. The London School of Hygiene & Tropical Medicine received a grant from MUGAS to partly fund Joanna Dobson’s salary while she worked on this project. No other monies were received by any of the authors.

I have looked into the biographies of the authors and found the following

  1. Prof Richard J Whitley is a paediatrician interested in viruses and works with/for CDC
    His declaration given above seems inadequate.
    The relevance of the reference to Gilead is that Gilead Science holds the patent for Tamiflu and this should be explicitly stated
    Should something like this not be declared in the Lancet paper?
    Gilead directors are listed HERE
    Whitley joined Gilead’s Board of Directors in 2008.
  2. Prof Arnold Monto
    He reports fees from Biocryst and Roche outside of the submitted work but also received about 41,000 US $ he got from GSK in 2009-13.
    See list HERE
    GSK produces Relenza the other antiviral product advocated for flu
  3. Ms Joanna Dobson
    There are 10 publications since 2010 but not a single one on influenza, not a single first authored and not a single systematic review
    This raises the question of what qualifies Dr Dobson to be the lead author on such a paper
  4. Prof Stuart Pocock
    He has expertise in statistical methods and clinical trials and describes his clinical area as being CV disease.
    Statisticians can only deal with the information given to them by others

There are further issues about the trial being funded by MUGAS
Comment about MUGAS  (see block of text below)

In 2013, Roche announced that in the interests of transparency it would supply any data requested by what it described as a “third party group”, the Multiparty Group for Advice in Science (MUGAS).
In fact, while the name might lead you to imagine an independent body bringing together representatives of a number of organisations to consider a range of issues (rather like All-Party Groups in the UK Parliament), MUGAS is funded by Roche and is led by four scientists, three of whom are advisers to Roche. It appears to have been set up specifically as part of the attempt to counter the Cochrane’s criticisms.
Another organisation involved is European Scientists Working on Influenza (ESWI).  On their websites, MUGAS and ESWI give as their point of contact the same mobile telephone number in Belgium [13, 14]. The name MUGAS is a registered trademark of Semiotics, a company that describes its mission as “translating science to the world,” but whose actual activity seems mostly to be concerned with influenza and in particular oseltamivir [15].

Details of Semiotics
Both MUGAS and ESWI are brands of Semiotics
See also  Semiotics Mind Map

We need to know a lot more about how Semiotics, MUGAS and ESWI are funded and who influences what they say and do.

2 comments on “Tamiflu Re-analysis

  1. You should start, of course, by dismissing everything I say. I am clearly in the pay of the pharma industry and hence everything I ever say is misleading. If you want to know how wicked I am, here is my general declaration http://www.senns.demon.co.uk/Declaration_Interest.htm . However, it does include one thing I find singularly lacking from most declarations I see from the EBM movement. ‘my career is furthered by publishing. Controversial topics often attract greater publicity and this should always be borne in mind’. It seems to me that the whole Tamiflu story has been milked for what it is worth by many. In epidemiology, careers are made by sensational (often bad) news and the temptation is clearly there.

    However, if you are going to argue ad hominem about The Lancet authors, then you are on a very sticky wicket. I think most true medical statisticians would have a far higher opinion of Stuart Pocock (a leading medical statistician I have known for 25 years) than of any of the authors of the BMJ paper.

    As for attacking Ms Dobson, this is as pointles as it is discourteous to a junior researcher. My first published article of any note (aged 24) was pointing out a mathematical error in a paper in The British Journal of Social and Preventive Medicine (as it then was). The reputation of the author of the paper I was criticising was, deservedly, much higher than mine. The editor did not say ‘I’m sorry but you are going to have to find someone more senior to be the lead author’. In any case, once it’s down in black and white, that’s what we discuss.

    I find it baffling to what extent people who support the call for open data & publishing everything nevertheless talk in the language of the last century as to who has the right to appear as first author on a paper. How awful that a junior researcher with only ten papers to her name should be allowed to be first author in The Lancet just because she has done most of the hard work. More credit to her co-authors, I say. Many a senior lab-head could learn from them.

    Can’t we get away from this sort of discussion? We have now had several meta-analyses of the Tamiflu data. No doubt some are better than others but it might be that even the worst of them have useful things in them that further the debate as a whole. I am sure that the BMJ authors think they have produced the best possible analysis of the data. Maybe The Lancet authors think oherwise. How dare they! What we need is a careful comparison of them all, not mudslinging at authors.

    My general declaration is here

    In addition, I once gave paid advice on analysis of Tamiflu trials in the late 1990s. This note represents my own views and should be ascribed to no other party: not my employers, not Roche, not MUGAS, not Dobson et al.

  2. I agree its not a completely arm’s length assessment, but there are problems with the Cochrane review as well.

    Conflicts of interest can involve a wide range of non-financial as well as financial interests. In the present case, the Cochrane analysis was written by authors who had made Tamiflu their poster child for the ALLTRIALs campaign. They could hardly have waged this very public PR campaign with Roche for 2 years and then written an analysis that concluded that “We have confirmed what Roche was telling us all along” without undercutting that effort.

    The Cochrane Review was published in the BMJ, whose editors had previously produced and published several “investigative journalism” articles suggesting that Tamiflu was a scam. Given the very public and hostile position taken by the BMJ editorial staff on Tamiflu, how can the Cochrane paper be thought to have received anything resembling genuine peer review by reviewers selected by unbiased editors?

    There are a lot of problems with both publications. I suspect we will all have to wait a while for a credible review.

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