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Search for evidence goes on

BMJ 2012; 344 doi: (Published 17 January 2012) Cite this as: BMJ 2012;344:e458

Rapid Response:

Re: Search for evidence goes on

26 January 2012

Dr. Fiona Godlee
Editor-in-Chief, BMJ

Dear Dr. Godlee:

My colleagues and I are writing to correct two inaccurate statements regarding our published oseltamivir studies in Deborah Cohen’s recent commentary [1]. First, the pivotal adult treatment trial published in JAMA in 2000 was not ghost-written, as implied in her editorial. As indicated in a previous BMJ commentary in 2009 [2], John Treanor, the lead author, wrote the first draft of the manuscript. In addition to helping to generate the primary data, I and the other co-authors provided extensive input and editing of the subsequent revisions and approved the final version. In 2009 [2] Dr. Cohen acknowledged that Dr. Treanor met accepted criteria for authorship, namely that he “made substantial contributions to the study, was involved in drafting or reviewing the manuscript, and approved the submission.” This was true for all of the authors of this study.

Second, the pooled analysis of complications published in Archives of Internal Medicine in 2003 [3] was not funded by Roche. Neither Laurent Kaiser, nor I, nor the University of Virginia received financial compensation for this work. The study was based on our earlier pooled analysis of antibiotic use during the randomized, controlled trials of inhaled zanamivir [4]. In both instances, we conceived the studies and were responsible for choosing the analysis plans, reviewing the data, and writing the publications. The involved companies provided the database and valuable support in terms of its management, help with the statistics, and review of the manuscripts. Our conclusion that oseltamivir treatment in ambulatory adults reduced physician-diagnosed lower respiratory tract complications leading to antibiotic use, primarily bronchitis, has been independently confirmed in a recent meta-analysis [5].

Perhaps of greater medical importance is the substantial body of observational studies that have found evidence that oseltamivir treatment, compared to no or very delayed antiviral therapy, reduces the risk of more serious complications and hospitalizations, including one study showing reduced radiographically documented pneumonia episodes in adults with pandemic 2009 A(H1N1) illness published in BMJ [6]. Other studies have shown reduced mortality if hospitalized patients are treated, including one study of adults hospitalized with seasonal influenza published in Thorax [7]. A systematic review of these studies has been commissioned by WHO and will be important in informing future antiviral policy recommendations [ clinical_ management_2012/en/index.html].

We fully support Dr. Cohen’s call to provide access to the data from the published and unpublished studies of oseltamivir and zanamivir to legitimate investigators for further analyses but would ask that the misleading statements related to our work in her commentary be corrected.


Frederick G. Hayden, M.D.
Richardson Professor of Clinical Virology
Professor of Medicine
University of Virginia School of Medicine
Charlottesville, Virginia, USA

John Treanor, M.D.
Professor of Medicine, Microbiology and Immunology
Chief, Division of Infectious Diseases
Department of Medicine, University of Rochester Medical Center
Rochester, New York, USA

Laurent Kaiser, M.D.
Director, Laboratory of Virology
University Hospitals of Geneva
Division of Infectious Diseases
Division of Laboratory Medicine
Geneva, Switzerland

Cc: Howard Bauchner, MD, Editor-in-Chief, JAMA
Rita F. Redberg, MD, MSc, Editor, Archives of Internal Medicine

Reference List

1. Cohen D. Search for evidence goes on. BMJ 2012;344:e458.
2. Cohen D. Complications: tracking down the data on oseltamivir. BMJ 2009;339:b5387.
3. Kaiser L, Wat C, Mills T, Mahoney P, Ward P, Hayden F. Impact of oseltamivir treatment on influenza-related lower respiratory tract complications and hospitalizations. Arch Intern Med 2003 July 28;163(14):1667-72.
4. Kaiser L, Keene ON, Hammond JM, Elliott M, Hayden FG. Impact of zanamivir on antibiotic use for respiratory events following acute influenza in adolescents and adults. Arch Intern Med 2000 November 27;160(21):3234-40.
5. Hernan MA, Lipsitch M. Oseltamivir and risk of lower respiratory tract complications in patients with flu symptoms: a meta-analysis of eleven randomized clinical trials. Clin Infect Dis 2011 August 1;53(3):277-9.
6. Yu H, Liao Q, Yuan Y, Zhou L, Xiang N, Huai Y, Guo X, Zheng Y, van Doorn HR, Farrar J, Gao Z, Feng Z, Wang Y, Yang W. Effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A H1N1: opportunistic retrospective study of medical charts in China. BMJ 2010;341:c4779.
7. Lee N, Choi KW, Chan PK, Hui DS, Lui GC, Wong BC, Wong RY, Sin WY, Hui WM, Ngai KL, Cockram CS, Lai RW, Sung JJ. Outcomes of adults hospitalised with severe influenza. Thorax 2010 June;65(6):510-5.

Competing interests: Dr. Hayden received lecture and/or consulting honoraria from GSK until 2002 and from Roche until 2004. Roche provided grant support to the University of Virginia in 2002 and 2005 for oseltamivir studies on which he was PI. Dr. Hayden served as medical officer in the Global Influenza Programme from 2006-2008 with funding provided to the University of Virginia through the National Institute of Allergy and Infectious Diseases (NIAID). Since 2008 to present the University of Virginia has received funding from the Wellcome Trust for his part-time work as influenza research coordinator at the Trust and through NIAID for his work as consultant the Southeast Asia Infectious Diseases Clinical Research Network. From 2008-11 the University also received honoraria for his participation in the Neuraminidase Inhibitor Susceptibility Network which received funding from Roche and GSK. Since 2008 to present, Dr. Hayden has been an unpaid consultant to multiple companies engaged in the development or marketing of influenza antivirals including Roche and GSK. Dr. John Treanor reports receiving compensation as a member of the scientific advisory boards of Novartis and Immune Targeting Systems, and has performed consulting work for Pfizer. Within the last 3 years, his group has been funded to perform laboratory assays or conduct clinical trials for Sanofi, GlaxoSmithKline, Protein Sciences Corp, Wyeth, PaxVax, Ligocyte, and Vaxinnate. Dr. Kaiser reports on financial disclosures.

30 January 2012
Infectious Diseases Physician
John Treanor, University of Rochester; Laurent Kaiser, University of Geneva
University of Virginia
PO Box 800473, University of Virginia Health Sciences Center, Charlottesville, VA 22908