Analysis

Multisystem failure: the story of anti-influenza drugs

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g2263 (Published 10 April 2014) Cite this as: BMJ 2014;348:g2263

An open letter to all US Presidential candidates

Medical experiments on humans (clinical trials) are carried out in the hope of improving health and furthering science. By their very nature they entail uncertainty about potential harms and benefits of a treatment or a procedure. This is why following WWII, prior ethics review by an independent committee has gradually been introduced as a key condition.

No benefit can be derived from trials which are either invisible or reported partially or selectively.

To avoid this risk, a growing number of organisations have made efforts to allow access to clinical trial results in a detail hitherto unknown.

Despite the growing international effort and a notable legislative effort in the EU, the US lags behind.

Study results posted on clinicaltrials.gov are, by definition, incomplete and unverified. Even so, eight years after the introduction of federal law FDAAA 2007 a very small number of results of registered trials have been made available and updated.

No detailed regulatory documents are available from the FDA. Physicians and patients require access to clinical study reports and anonymized individual patient data from trials of approved drugs and biologics.

US law and regulations globally affect organizational and professional behaviors with huge impact on health worldwide. The international composition of this letter's signatories reflect this reality.

We call for a statement by all US presidential candidates on whether they support access to clinical trial data held by federal agencies, irrespective of topic, sponsor, country in which the trial was run or results.

We ask that they state what measures they would put forward, if elected, to address the scandal of invisible and distorted clinical trials.

John Abramson MD MSc
Lecturer Dept. of Health Care Policy
Harvard Medical School
Boston, MA, USA
John_Abramson@hms.harvard.edu

Marcia Angell MD
Senior Lecturer
Department of Global Health and Social Medicine
Harvard Medical School
Boston, MA, USA
marcia_angell@hms.harvard.edu

Shannon Brownlee, MSc
Senior Vice President
Lown Institute
Boston USA
sbrownlee@lowninstitute.org

Vikas Saini, M.D.
President, Lown Institute
Boston USA
vsaini@lowninstitute.org

Hazel Thornton Hon. DSc (Leicester)
Independent Citizen Advocate for Quality in Research and Healthcare
UK
hazelcagct@keme.co.uk

Thomas Faunce PhD
Professor, jointly in ANU College of Law and College of Medicine, Biology and the Environment
Australian National University
Canberra. ACT 0200 Australia
thomas.faunce@anu.edu.au

Trisha Greenhalgh MD
Professor of Primary Care Health Sciences
University of Oxford
Oxford, OX2 6GG
trish.greenhalgh@phc.ox.ac.uk

Susan Bewley MD
Professor of Complex Obstetrics
Kings College London
London UK
susan.bewley@kcl.ac.uk

Meryl Nass MD
Board Member,
Alliance for Human Research Protection
Maine, USA.
merylnass@gmail.com

John H Noble Jr, PhD
Emeritus Professor,
State University of New York at Buffalo
USA
jhnoblejr@icloud.com

David Misselbrook FRCGP
Senior Lecturer in Family Medicine
RCSI Bahrain
Adliya,
Kingdom of Bahrain
DMisselbrook@rcsi-mub.com

Miran Epstein MD PhD
Reader in Medical Ethics
Barts and The London School of Medicine and Dentistry
Queen Mary University of London
London, United Kingdom
m.epstein@qmul.ac.uk

Trudo Lemmens DCL
Faculties of Law and Public health
University of Toronto
Toronto, Canada
trudo.lemmens@utoronto.ca

Carl Elliott MD PhD
Center for Bioethics, University of Minnesota USA
ellio023@gmail.com

Lynette Reid, PhD
Associate Professor
Department of Bioethics
Faculty of Medicine, Dalhousie University
Halifax NS B3H 4R2 Canada
Lynette.Reid@dal.ca

James Brophy MD PhD
Professor of Medicine
McGill University
Canada
james.brophy@mcgill.ca

Udo Schuklenk, PhD
Ontario Research Chair in Bioethics
Joint Editor in Chief of Bioethics
Queen's University, Kingston,
Canada
udo.schuklenk@gmail.com

Matthew Herder, JSM
Associate Professor, Faculties of Medicine and Law
Dalhousie University, NS, Canada
Matthew.Herder@dal.ca

John M. Nardo MD
Emory University Psychoanalytic Institute
Georgia, USA
nardo.mickey@gmail.com

Jeanne Lenzer
Associate editor
The BMJ, USA
jlenzer@bmj.com

Julian Savulescu PhD
Oxford Uehiro Centre for Practical Ethics
Oxford, UK
jsavulescu@gmail.com

Peter C. Gøtzsche MD
Nordic Cochrane Centre
Copenhagen, Denmark
pcg@cochrane.dk

Joel Lexchin MD
School of Health Policy and Management
York University
Toronto ON
Canada M3J 1P3
jlexchin@yorku.ca

Sergio Sismondo PhD
Department of Philosophy
Queen's University
Kingston, Canada K7L 3N6
sismondo@queensu.ca

Jon F. Merz
Department of Medical Ethics & Health Policy
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA USA
merz@upenn.edu

Françoise Baylis, PhD, FRSC, FCAHS
Professor and Canada Research Chair in Bioethics and Philosophy
Faculty of Medicine, Dalhousie University, Canada
Francoise.baylis@dal.ca

Barbara Mintzes, PhD
Faculty of Pharmacy, University of Sydney
Sydney, Australia
barbara.mintzes@sydney.edu.au

Janice E. Graham, PhD
Faculty of Medicine
Dalhousie University, CANADA B3H 4R2
Janice.Graham@dal.ca

Adriane Fugh-Berman MD
Department of Pharmacology and Physiology
Georgetown University Medical Center
Washington DC USA
ajf29@georgetown.edu

Wendy Rogers PhD
Macquarie University, Sydney, Australia
wendy.rogers@mq.edu.au

Amar Jesani, MBBS
Editor
Indian Journal of Medical Ethics
Mumbai
India
amar.jesani@gmail.com

Peter R Mansfield OAM BMBS
Healthy Skepticism Inc
Hallett Cove, Australia
peter.mansfield@adelaide.edu.au

Alain Braillon M.D., Ph.D.
Alcohol Treatment Unit
University Hospital
80054 Amiens CEDEX 1. France
braillon.alain@gmail.com

Richard Ashcroft PhD
School of Law
Queen Mary University of London
r.ashcroft@qmul.ac.uk

David H Newman, MD, FACEP
Professor of Emergency Medicine
The Icahn School of Medicine, Mt Sinai
New York, NY 10029-6574 USA
david.newman@mountsinai.org

Vera Sharav
President
Alliance for Human Research Protection USA
verahsharav@gmail.com

Arthur Schafer
Centre for Professional and Applied Ethics
University of Manitoba
Canada
Arthur.Schafer@umanitoba.ca

Lex M. Bouter, PhD
Professor of Methodology and Integrity
VU University Medical Center Amsterdam
Department of Epidemiology & Biostatistics
lm.bouter@vumc.nl

Lisa Cosgrove, PhD
Professor, Department of Counseling Psychology
University of Massachusetts-Boston USA
lisa.cosgrove@umb.edu

Nancy F. Olivieri, MD
Professor, Pediatrics, Medicine and Public Health Sciences,
University of Toronto, Canada
nancy@hemoglobal.org

Dale E. Hammerschmidt, MD
Professor of Medicine (emeritus)
University of Minnesota USA
hamme001@umn.edu

Edwin Gale MD,
Emeritus Professor of Diabetic Medicine
University of Bristol, UK
Edwin.Gale@bristol.ac.uk

Fiona Godlee FRCP
The BMJ
London WC1H 9JR
fgodlee@bmj.com

John Hoey MD, FRCP, FACP
Physician Internist
Former Editor, Canadian Medical Association Journal.
Ontario, Canada
johnhoeymd@gmail.com

Alastair V. Campbell, ThD, CorrFRSE
Professor in Medical Ethics and Director, Centre for Biomedical Ethics
National University of Singapore
medavc@nus.edu.sg

Marc A. Rodwin JD PhD
Professor of Law
Suffolk University Law School
Boston, MA 02108 USA
mrodwin@suffolk.edu

Jay Siwek, MD
Professor of Family Medicine
Georgetown University Medical Center
Washington, DC 20007 USA
siwekj@georgetown.edu

Michael McDonald
Professor Emeritus of Applied Ethics
W. Maurice Young Centre for Applied Ethics
School of Population and Public Health
University of British Columbia
mcdonald@ethics.ubc.ca

Virginia Barbour MD
Brisbane, Australia
v.barbour@griffith.edu.au

Marc-André Gagnon, PhD
School of Public Policy and Administration
Carleton University
Canada
ma.gagnon@carleton.ca

Peter Doshi PhD
Department of Pharmaceutical Health Services Research
University of Maryland School of Pharmacy
Baltimore, MD 21201, USA
pdoshi@rx.umaryland.edu

Giovanni A. Fava
Editor, Psychotherapy and Psychosomatics
University at Buffalo USA
giovanniandrea.fava@unibo.it

Mark Jones PhD
School of Public Health
University of Queensland
Brisbane, Queensland 4006
Australia
m.jones@sph.uq.edu.au

Luca DeFiore
Associazione Alessandro Liberati
Il Pensiero Scientifico Editore
Roma, Italy
luca.defiore@pensiero.it

David Tovey, FRCGP
Cochrane Editorial Unit, London, UK
dtovey@cochrane.org

Juan Erviti Lopez
Unit of Drug Assessment, Advice and Research
Navarre Regional Health Service
31002 Pamplona, Spain
jervitil@navarra.es

Florence Bourgeois MD, MPH
Pediatric Emergency Medicine
Boston Children's Hospital
Harvard Medical School
Boston, MA, USA
Florence.Bourgeois@childrens.harvard.edu

Tom Jefferson MD
Centre for Evidence Based Medicine
Oxford, UK
jefferson.tom@gmail.com

Corresponding authors:
Dr John Abramson (john_abramson@hms.harvard.edu)
Dr Tom Jefferson (jefferson.tom@gmailcom)

Competing interests: John Abramson is an expert in litigation involving the pharmaceutical and device industries. Tom Jefferson receives royalties from his books published by Blackwells and Il Pensiero Scientifico Editore, Rome. TJ is occasionally interviewed by market research companies for anonymous interviews about Phase 1 or 2 pharmaceutical products. In 2011-2013, TJ acted as an expert witness in a litigation case related to oseltamivir phosphate; Tamiflu [Roche] and in a labour case on influenza vaccines in healthcare workers in Canada. In 1997-99 TJ acted as a consultant for Roche, in 2001-2 for GSK, and in 2003 for Sanofi-Synthelabo for pleconaril (an anti-rhinoviral, which did not get approval from the Food and Drug Administration). TJ was a consultant for IMS Health in 2013, and in 2014 was retained as a scientific adviser to a legal team acting on the drug Tamiflu (oseltamivir, Roche). In 2014-15 TJ was a member of two advisory boards for Boerhinger and is in receipt of a Cochrane Methods Innovations Fund grant to develop guidance on the use of regulatory data in Cochrane reviews. TJ has a potential financial conflict of interest in the investigation of the drug oseltamivir. TJ is acting as an expert witness in a legal case involving the drug oseltamivir (Roche). TJ is a member of an Independent Data Monitoring Committee for a Sanofi Pasteur clinical trial. Peter Doshi (PD) and Tom Jefferson (TJ) were co-recipients of a UK National Institute for Health Research grant (HTA – 10/80/01 Update and amalgamation of two Cochrane Reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children—http://www.nets.nihr.ac.uk/projects/hta/108001). They are also co-recipients of a Cochrane Methods Innovations Fund grant to develop guidance on the use of regulatory data in Cochrane reviews. In addition: PD received €1500 from the European Respiratory Society in support of his travel to the society’s September 2012 annual congress in Vienna, where he gave an invited talk on oseltamivir. PD gratefully acknowledges the American Association of Colleges of Pharmacy for its funding support ($10,000) for a study to analyze written medical information regarding the possible harms of statins. PD is also an associate editor at The BMJ. Matthew Herder is a member of the Health Policy Translation research group of the Canadian Center for Vaccinology (CCfV), which has carried out a number of clinical trials sponsored by vaccine manufacturers. MH has not been involved, in any way, with the conduct of these trials, nor received any funds from CCfV to carry out research. He has no other personal, organization, or relational conflicts of interest to disclose. Jon F Merz has received payment in the last 36 months for: 1) consultation with Novartis on issues of clinical trial design; 2) continuing membership on a pharmacogenomics ethics advisory board for Merck; and 3) being an expert witness in two personal injury lawsuits arising from research participation. Alain Braillon is a member of Healthy Skepticism, a non-profit organisation aiming to improve health by reducing harm from misleading health information (www.healthyskepticism.org/ ), and of HealthWatch-UK, a charity (#1003392) that has been promoting evidence-based science and integrity in healthcare since 1991 (www.healthwatch-uk.org/). Barbara Mintzes has acted as an expert witness in two Canadian class action suits, on post-menopausal hormone therapy and breast cancer risks, and testosterone and cardiac risks. Edwin Gale has been an expert witness in litigation involving the pharmaceutical industry. Sergio Sismondo receives royalties on sales of his books published by Wiley Blackwell. Lisa Cosgrove is the principle investigator for an RO3 grant funded by AHRQ (Grant No. R03HS022940-01A1). She has no financial conflicts of interest to report. Luca De Fiore is the president of the Associazione Alessandro Liberati - Network Italiano Cochrane, a non profit group of researchers, clinicians, and patients involved in independent clinical research and research synthesis. LDF is also the Chief Executive Officer of Il Pensiero Scientifico Editore, an independent Italian publishing company. Virginia Barbour has no competing iterests to declare. She is Chair of COPE and is employed by the Australasian Open Access Support Group, but she is not signing on behalf of either of these groups but in a personal capacity. Fiona Godlee is editor in chief of The BMJ; The BMJ is a founder member of Alltrials and is also running its own campaign for access to clinical trial data (bmj.com/open-data). Meryl Nass receives no money from government or from pharmaceutical companies and does no clinical trial work. In 2015 she practised as medicien part-time for pay and practised as a volunteer in a free clinic. Marc A Rodwin is an expert witness in qui tam litigation providing opinion on duty to disclose information and on off label drug use. None declared: Arthur Schafer, John H Noble Jr, David H Newman, John Hoey, Françoise Baylis, John M Nardo, Michael McDonald, James Brophy, Joel Lexchin, Lex M Bouter, Shannon Brownlee, Wendy Rogers, Alastair V Campbell, Juan Erviti Lopez, Mark Jones, David Misselbrook, Peter C Gøtzsche, Hazel Thornton, Amar Jesani, Peter R Mansfield, Giovanni A Fava, Janice E Graham, Jay Siwek, Miran Epstein, Vera Sharav, Trudo Lemmens, Florence Bourgeois, Lynette Reid, Susan Bewley, Carl Elliott, Jeanne Lenzer, Marcia Angell, Richard Ashcroft, Dale E Hammerschmidt, Julian Savulescu, Udo Schuklenk, Vikas Saini

09 November 2015
Tom Jefferson
Honorary Research Fellow
John Abramson MD and 58 others
Centre for Evidence Based Medicine
Oxford, UK
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