Timeline of events since the publication of Cochrane Review on Neuraminidase Inhibitors

Compiled by Tom Jefferson, Peter Doshi, Mark Jones, Rokuro Hama and Carl Heneghan

This time line charts significant events since the publication of the Cochrane review on neuraminidase inhibitors. The main actors of the timeline are the same as those in the original story: Cochrane, academics funded by industry, industry itself, the media and public health bodies.

The idea of the timeline came in the preparation to Tom Jefferson’s talk “diary of a tamiflu research parasite” which he held during Evidence Live 2016.


WHO downgrades status of oseltamivir

July 12, 2017
WHO downgrades status of oseltamivir

Mark Ebell: WHO downgrades status of oseltamivir BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3266 (Published 12 July 2017)   Cite this as:…

Read more

WHO’s new list focuses on antibiotic resistance, adds expensive drugs, and downgrades Tamiflu

July 7, 2017
WHO’s new list focuses on antibiotic resistance, adds expensive drugs, and downgrades Tamiflu

Michael McCarthy: What makes an essential medicine? WHO’s new list focuses on antibiotic resistance, adds expensive drugs, and downgrades Tamiflu….

Read more

Early administration of neuraminidase inhibitors in adult patients hospitalized for influenza does not benefit survival: a retrospective cohort study.

April 18, 2017
Early administration of neuraminidase inhibitors in adult patients hospitalized for influenza does not benefit survival: a retrospective cohort study.

Early administration of neuraminidase inhibitors in adult patients hospitalized for influenza does not benefit survival: a retrospective cohort study. Choi…

Read more

WHO committee recommend transfer of Tamiflu from the Core to the Complementary Essential Medicines List

March 31, 2017
WHO committee recommend transfer of Tamiflu from the Core to the Complementary Essential   Medicines List

WHO committee recommend transfer of Tamiflu from the Core to the Complementary Essential   Medicines List “and its use be restricted…

Read more

Unmasking survival biases in observational treatment studies of influenza patients – Wolkewitz, Schumacher

February 7, 2017
Unmasking survival biases in observational treatment studies of influenza patients – Wolkewitz, Schumacher

Abstract Background Several observational studies reported that Oseltamivir (Tamiflu) reduced mortality in infected and hospitalized patients. Due to the restriction…

Read more

Dunn AG, Zhou X, Hudgins J, Arachi D, Mandl KD, Coiera E, et al. Journal of Clinical Epidemiology, December 2016.

January 13, 2017
Dunn AG, Zhou X, Hudgins J, Arachi D, Mandl KD, Coiera E, et al. Journal of Clinical Epidemiology, December 2016.

Dunn AG, Zhou X, Hudgins J, Arachi D, Mandl KD, Coiera E, et al. Financial competing interests were associated with…

Read more

Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data

September 23, 2016
Neuraminidase Inhibitors and Hospital Mortality in British Patients with H1N1 Influenza A: A Re-Analysis of Observational Data

Statisticians Wolkewitz and Schumaker using methods to avoid survival biases on observational data from 1391 patients hospitalised in UK during…

Read more

Jones M, Fowler R. Immortal time bias in observational studies of time-to-event outcomes.

August 17, 2016
Jones M, Fowler R. Immortal time bias in observational studies of time-to-event outcomes.

Cochrane reviewer Mark Jones and intensive care specialist Robert Fowler using simulation and an example demonstrate the impact of immortal…

Read more

Rokuro Hama reviews the evidence of harms on neuraminidase inhibitors (2016)

June 27, 2016

Cochrane author Rokuro Hama reviews the evidence of harms on neuraminidase inhibitors with a special focus on the two earliest…

Read more

Tom Jefferson: The neuraminidase inhibitors evidence of harms – in context (2016)

June 27, 2016

A linked commentary by Tom Jefferson explains the significance of Rokuro Hama’s paper.  

Read more

No effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza

June 14, 2016
No effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza

No effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza? HTA review What did we do? As part of…

Read more

HTA systematic review of regulatory and mortality data published

May 31, 2016
HTA systematic review of regulatory and mortality data published

HTA review reports Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza and Oseltamivir and zanamivir cause…

Read more

Independent drug Bulletin “Med Check The Informed Prescriber” (Japanese)

May 9, 2016

Introduces the Cochrane team’s critical comments on the ECDC experts’ draft advice on neuraminidase inhibitor use. Med Check TIP in…

Read more

Peter Doshi and colleagues challenge the CDC

March 31, 2016
Peter Doshi and colleagues challenge the CDC

They challenge the evidence base used by the CDC to make recommendation on the use of Oseltamivir and their lack…

Read more

JAMA editors publish an editorial on data sharing

March 22, 2016

“For instance, previous reports involving rofecoxib and oseltamivir illustrate the problem of incomplete or misleading reporting of clinical trial data”….

Read more

Cochrane reviewers respond to ECDC consultation

March 14, 2016

Hama R, Jefferson T, Heneghan C . Cochrane reviewers’ comments on the ECDC draft preliminary Scientific Advice paper “Expert Opinion…

Read more

UK Cochrane Centre publishes timeline of media coverage

March 1, 2016

The Tamiflu Timeline. A timeline of key links and articles, in response to the drugs company Roche  to publishing all…

Read more

Independent drug bulletin Prescrire summarises story

February 1, 2016

“Over a 15-year period, Roche, the company that markets Tamiflu, has hampered independent analysis of the assessment data on oseltamivir…

Read more

ECDC launches consultation

February 1, 2016
ECDC launches consultation

ECDC PRELIMINARY SCIENTIFIC ADVICE Expert Opinion on Neuraminidase Inhibitors for prevention and treatment of influenza. pdf draft scientific advice A…

Read more

JAMA viewpoint on using observational studies

October 19, 2015

The authors judge the randomized controlled trial (RCT) evidence as inadequate as RCTs have not been carried out in “high…

Read more

Academy of Medical Sciences and Wellcome Trust publish report

October 8, 2015
Academy of Medical Sciences and Wellcome Trust publish report

In October 2015, the Academy and Wellcome Trust published a report exploring the scientific evidence around the treatment of influenza,…

Read more

The Conversation publishes on the Tamiflu story

September 29, 2015
The Conversation publishes on the Tamiflu story

The piece draws several comments. Cochrane reviewer Jefferson points out McVernon’s attempts at blurring the Dobson authors’ conflicts of interest…

Read more

Letter responses to Dobson et al published in Lancet

September 1, 2015
Letter responses to Dobson et al published in Lancet

Series of responses to Dobson et al  meta-analyses of individual patient published in the Lancet including concerns over the methods….

Read more

Imbalance of baseline renal function between oseltamivir and placebo group reported

March 19, 2015
Imbalance of baseline renal function between oseltamivir and placebo group reported

Participants in five prophylaxis randomized controlled trials with high baseline creatinine level (154μmol/L or more) were significantly less reported in…

Read more

CDC continues recommending use of antivirals

March 3, 2015
CDC continues recommending use of antivirals

“Since 1999 a large and growing body of observational data, including in hospitalized patients, shows there are benefits to using…

Read more

Australian Broadcasting Corporation (ABC) Catalyst documentary on Tamiflu

March 3, 2015
Australian Broadcasting Corporation (ABC) Catalyst documentary on Tamiflu

“Imagine a Hollywood doomsday scenario: a flu pandemic sweeps the world, hundreds of millions of people are infected. How prepared…

Read more

Cochrane reviewers summarise results of review

March 1, 2015

The authors subsequently published the underlying documents simultaneously with the Cochrane review, endorsing the concept of open science” Roche and…

Read more

Lenzer documents citation bias in CDC statements on the use of antivirals and Roche funding of CDC’s “Take 3” campaign.

February 5, 2015
Lenzer documents citation bias in CDC statements on the use of antivirals and Roche funding of CDC’s “Take 3” campaign.

The second article of the series reports a statement by CDC Director Thomas Frieden declining to comment on the CDC’s…

Read more

Family doctor, Paul Roblin, challenges the independence of the Dobson et al meta-analysis

February 5, 2015

Paul Roblin on Dobson et al’s Lancet Tamiflu reanalysis: an independent review group. Really? Repsosted from www.cebm.net and blogs.bmj.com On…

Read more

Tools for Practice evaluates the evidence on clinically relevant primary care topics

February 3, 2015
Tools for Practice evaluates the evidence on clinically relevant primary care topics

The Alberta College of Family Physicians (ACFP)’s Tools for Practice summarises the evidence (www.acfp.ca) so far: Biased, poor quality, mostly…

Read more

JAMA republishes an article from The Medical Letter on Drugs and Therapeutics

January 1, 2015

Concludes “Chemoprophylaxis with antiviral drugs is not recommended for healthy persons exposed to influenza. A neuraminidase inhibitor, either oseltamivir (Tamiflu)…

Read more

Roche funded IPD meta-analysis (Dobson et al) published in Lancet – covering editorial refers to as “independent”.

January 1, 2015
Roche funded IPD meta-analysis (Dobson et al) published in Lancet – covering editorial refers to as “independent”.

“The re-analysis was funded by an unrestricted grant from Roche but was done by an independent research group, thus seeking…

Read more

Review on the harm of oseltamivir and its mechanism of toxicities (Japanese)

December 1, 2014

Published in the Japanese Independent Drug bulletin “The Informed Prescriber”. Hama R. Harm of oseltamivir and the mechanisms of toxicities…

Read more

BMJ Editor in Chief and Cochrane review group responses to CMO’s evidence

November 24, 2014
BMJ Editor in Chief and Cochrane review group responses to CMO’s evidence

Public Accounts Committee on Tamiflu. Statement from Dr Fiona Godlee, Editor in Chief, The BMJ, November 24 2014. CMO defends…

Read more

Public Health England publishes guidance on use of antivirals in influenza

November 1, 2014

The recommendations are based on observational data and conclude that “it is essential that physicians treating severely unwell patients in any…

Read more

UK CMO UK rejects review findings for non-applicability of evidence

October 20, 2014

Public Accounts Committee Oral evidence: Tamiflu Recall, HC 677. Monday 20 October 2014 Public Accounts Committee Oral evidence : Tamiflu…

Read more

Roche detailed 69 page response to Cochrane review

October 16, 2014
Roche detailed 69 page response to Cochrane review

The response states: “the Cochrane authors have made basic errors in their assessment of oseltamivir efficacy data, overinterpreted the limited…

Read more

Cochrane reviewers respond to Van Tam et al’s Lancet editorial

October 4, 2014
Cochrane reviewers respond to Van Tam et al’s Lancet editorial

“Observational data are useful to answer many questions, such as whether treatments are harmful or not. However, the fact that…

Read more

Van Tam et al’s reply to Cochrane reviewers is published

October 4, 2014
Van Tam et al’s reply to Cochrane reviewers is published

“We do not dismiss the findings in the Cochrane review.2 The finding that no signal exists suggesting that neuraminidase inhibitors…

Read more

NICE states that the Cochrane review provides no new evidence

October 1, 2014

Final recommendation post consultation: The technology appraisal programme recommends that, as proposed to consultees, TA158 should remain on the ‘static…

Read more

Reviewers with financial conflicts of interest more likely to present evidence about NIs in a favorable manner

October 1, 2014
Reviewers with financial conflicts of interest more likely to present evidence about NIs in a favorable manner

Review concludes that “Reviewers with financial conflicts of interest may be more likely to present evidence about neuraminidase inhibitors in…

Read more

Risk of bias in industry-funded oseltamivir trials published

September 30, 2014
Risk of bias in industry-funded oseltamivir trials published

“As information increased in the document, this increased our assessment of bias. This may mean that risk of bias has…

Read more

New Zealand’s Medsafe Medicines Committee rejects Cochrane review findings

September 1, 2014

New Zealand Medicines and Medical Devices Safety Authority Medicines Adverse Reaction Committee. Oseltamivir (Tamiflu) for Influenza. 11 September 2014. Released…

Read more

Zhou X. et al. Journal of Clinical Epidemiology, October 2014.

September 1, 2014
Zhou X. et al. Journal of Clinical Epidemiology, October 2014.

Zhou X et al. Citations alone were enough to predict favorable conclusions in reviews of neuraminidase inhibitors. Journal of Clinical…

Read more

Responses to Muthuri et al published

June 16, 2014
Responses to Muthuri et al published

“However, Muthuri and colleagues’ analysis of time-dependent exposure seems to be wrong.” Jones et al.   Muthuri et al is…

Read more

Lancet editorial

May 15, 2014
Lancet editorial

The editorial suggests that Cochrane review results and observational data are broadly consistent and decisions on influenza complications management should…

Read more

Cochrane review included in the James Lind Library

May 1, 2014

The first Cochrane review to be based exclusively on regulatory data.    

Read more

Mark Jones criticises methods used by Muthuri et al.

April 15, 2014
Mark Jones criticises methods used by Muthuri et al.

Specifically failing to account of immortal time bias. The criticism reported in a BMJ news item draws fierce replies and…

Read more

Roche press release on Cochrane review findings

April 10, 2014
Roche press release on Cochrane review findings

Roche Products Limited press release. Cochrane Acute Respiratory Infections Group’s analysis is flawed in assessment of Tamiflu® (oseltamivir) Roche fundamentally…

Read more

Network blogger: Tamiflu and the Ethics of the British Medical Journal.

April 10, 2014

Blogger Rober Dingwall challenges the BMJ and the Cochrane Collaboration to engage in some soulsearching about their evident desire for…

Read more

News by the Independent drug Bulletin “Web Med Check”

April 10, 2014

“Insufficient efficacy and harm of Tamiflu are proven by the latest systematic review of Cochrane team” Independent Drug bulletin “Web…

Read more

Ben Goldacre: What the Tamiflu saga tells us about drug trials and big pharma

April 10, 2014

We now know the government’s Tamiflu stockpile wouldn’t have done us much good in the event of a flu epidemic….

Read more

Cochrane review published in BMJ

April 9, 2014
Cochrane review published in BMJ

BMJ publications, with linked analysis and editorials published. Heneghan CJ, Onakpoya I, Thompson M, Spencer EA, Jones M, Jefferson T….

Read more

Complete set of 107 full clinical study reports are made available

April 9, 2014
Complete set of 107 full clinical study reports are made available

Data from: Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children http://dx.doi.org/10.5061/dryad.77471 Tamiflu, Relenza, and influenza: what…

Read more

Complete set of peer reviewers’ comments from 2009 are made available

April 9, 2014
Complete set of peer reviewers’ comments from 2009 are made available

174 pages of peer review comments to the BMJ review articles made available at bmj.com   http://www.bmj.com/content/suppl/2014/04/09/bmj.g2545.DC1/jeft017746.ww8_default.pdf

Read more

CDC responds in record time

April 9, 2014
CDC responds in record time

“CDC continues to recommend the use of the neuraminidase inhibitor antiviral drugs (oral oseltamivir and inhaled zanamivir) as an important…

Read more

Cochrane review A159 published

April 9, 2014
Cochrane review A159 published

Jefferson T, Jones MA, Doshi P, Del Mar CB, Hama R, Thompson MJ, et al. Neuraminidase inhibitors for preventing and…

Read more