Ensuring safe and effective drugs: who can do what it takes?BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.c7258 (Published 11 January 2011) Cite this as: BMJ 2011;342:c7258
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Dear Dr Godlee,
This article, which focuses mainly on the Tamiflu story, provides excellent background information on the issues raised when selected clinical trials of drug interventions remain unpublished.
It was written before the BMJ started its Open Data Campaign.
Can the article be made Open Access so that it can be widely shared?
For one thing,it contains an important sentence which would be very difficult to dispute:
“We believe we need to change the way information is identified, appraised, and synthesised and regard any industry sponsored trial published in journals as marketing, unless proved otherwise”.
Competing interests: I am a member of Healthy Skepticism
In our recent Analysis, we mentioned the existence of a large
oseltamivir (Tamiflu) trial carried out by Roche Shanghai (ML16369) about
which Roche Basel--the company's headquarters, with whom we are in
correspondence--seemed unaware, as it was missing in the list of 101 Roche
-supported and Roche-sponsored trials that Roche Basel provided us.
Since publication of our article, we have become aware of two
additional trials that Roche Basel failed to disclose to us. They were
noticed in the course of our ongoing review of regulatory documents.
Details about these trials remain scant. They are designated as open
-label Phase III pediatric clinical trials testing the bioavailability and
bioequivalence of Tamiflu. We do not know how large these trials were, or
precisely when they took place. We do know, however, where they took
* Protocol WP15979: Clinical Pharmacology Unit, Produits Roche S.A.,
1, Place de l'Hopital B.P. 20, F-67064 Strasbourg Cedex, France
* Protocol WP16137: Charterhouse Clinical Research Unit Ltd. The
Stamford Hospital (formerly the Royal Masonic), Ravenscourt Park, London,
W6 0TN, United Kingdom
Discovery of three manufacturer-funded trials which the manufacturer
failed to disclose to us confirms how important it is that independent
investigators take a role in constructing a complete list of trials as a
first step in any rigorous systematic review. It is not sufficient to
rely on trust. Nor is it sufficient to rely on automated database
searches: while ML16369 was published, WP15979 and WP16137 appear to
have remained unpublished. Only a handsearch and careful reading of
regulatory documents brought their existence to light.
The discovery of these additional trials also highlights the
unacceptable state of research ethics: some trialists apparently feel it
is acceptable to conduct experiments on minors, but not to disseminate the
results of this research.
Tom Jefferson, Peter Doshi, Matthew Thompson, Carl Heneghan
1. Jefferson T, Doshi P, Thompson M, Heneghan C. Ensuring safe and
effective drugs: who can do what it takes? BMJ. 2011;342:c7258.
2. Li L, Cai B, Wang M, Zhu Y. A double-blind, randomized, placebo-
controlled multicenter study of oseltamivir phosphate for treatment of
influenza infection in China. Chin. Med. J. 2003 Jan;116(1):44-48.
Competing interests: We are authors of the Analysis piece, and the same competing interests statement applies: All authors have completed the unified competing interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organisation for the submitted work. In 1998-9, TJ was an ad hoc consultant for Hoffman-La Roche; all authors are co-applicants for a NIHR grant to carry out the Cochrane review.