Virology blog post, by Vincent Racaniello, 29 August 2016: Once Again, Lancet Stumbles on PACE
Last February, Virology Blog posted an open letter to The Lancet and its editor, Dr. Richard Horton, describing the indefensible flaws of the PACE trial of treatments for ME/CFS, the disease otherwise known as chronic fatigue syndrome (link to letter). Forty-two well-regarded scientists, academics and clinicians put their names to the letter, which declared flatly that the flaws in PACE “have no place in published research.” The letter called for a completely independent re-analysis of the PACE trial data, since the authors have refused to publish the results they outlined in their original protocol. The letter was also sent directly to Dr. Horton.
The open letter was based on the extensive investigative report written by David Tuller, the academic coordinator of UC Berkeley’s joint program in journalism and public health, which Virology Blog posted last October (link to report). This report outlines such egregious failings as outcome thresholds that overlapped with entry criteria, mid-trial promotion of the therapies under investigation, failure to provide the original results as outlined in the protocol, failure to adhere to a specific promise in the protocol to inform participants about the investigators’ conflicts of interest, and other serious lapses.
Virology Blog first posted the open letter in November, with six signatories (link to letter). At that time, Dr. Horton’s office responded that he would reply after returning from “traveling.” Three months later, we still had not heard back from Dr. Horton–perhaps he was still “traveling”–so we decided to republish it with many more people signed on.
The day the second open letter was posted, Dr Horton e-mailed me and solicited a letter from the group. (He did not explain where he had been “traveling” for the previous three months.) Here’s what he wrote: “Many thanks for your email. In the interests of transparency, I would like to invite you to submit a letter for publication–please keep your letter to around 500 words. We will then invite the authors of the study to reply to your very serious allegations.”
Dr. Horton’s e-mail clearly indicated that the letter would be published, with the PACE authors’ response to the charges raised; there was no equivocation or possibility of misinterpretation. In good faith, we submitted a letter for publication the following month, with 43 signatories this time, through The Lancet’s online editorial system (see the end of this article for a list of those who signed the letter). After several months with no response, we learned only recently by checking the online editorial system that The Lancet had flatly rejected the letter, with no explanation. No one contacted me to explain the decision or why we were asked to spend time creating a letter that The Lancet clearly had no intention of publishing.
I wrote back to Dr. Horton, pointing out that his behavior was highly unprofessional and requesting an explanation for the rejection. I also asked him if he was in the habit of soliciting letters from busy scientists and researchers that his journal had no actual interest in publishing. I further asked if the journal planned to reconsider this rejection, in light of the recent First-Tier Tribunal decision, which demolished the PACE authors’ bogus reasons for refusing to provide data for independent analysis.
Dr. Horton did not himself apologize or even deign to respond. Instead, Audrey Ceschia, the Lancet’s correspondence editor, replied, explaining that the Lancet editorial staff decided, after discussing the matter with the PACE authors, that the letter did not add anything substantially new to the discussion. She assured us that if we submitted another letter focused on the First-Tier Tribunal decision, it would be “seriously” considered. I’m not sure why she or Dr. Horton think that any such assurance from The Lancet is credible at this point.
The reasons given for the rejection are clearly specious. The letter for publication reflected the matters addressed in the open letter that prompted Dr. Horton’s invitation in the first place, and closely adhered to his directive to outline our “serious allegations”. If outlining these allegations was not considered publication-worthy by The Lancet, it is incomprehensible to us why Dr. Horton solicited the letter in the first place. Perhaps it was just an effort to hold off further criticism for a period of months while we awaited publication of the letter, unaware of the journal’s intention to reject it. It is certainly surprising that The Lancet appears to have given the PACE authors some power to determine what letters appear in the journal itself.
Dr. Tuller’s investigation, based on the groundbreaking analyses conducted by many savvy patients and advocates since The Lancet published the first PACE results in 2011, has effectively demolished the credibility of the findings. So has a follow-up analysis by Dr. Rebecca Goldin, a math professor at George Mason University and director of Stats.org, a think tank co-sponsored by the American Statistical Association. In short, the PACE study is a sham, with meaningless results. In this case, the emperor truly has no clothes. Dr. Horton and his editorial team at The Lancet are stark naked.
Yet the PACE study remains in the literature. Its recommendation of treatments that are potentially harmful to patients–specifically, graded exercise therapy and cognitive behavior therapy, both designed specifically to increase patients’ activity levels–remains highly influential.
Of particular concern, the PACE findings have laid the groundwork for the MAGENTA study, a so-called “PACE for kids” that will be testing graded exercise therapy in children and adolescents. A feasibility study, sponsored by Royal United Hospitals Bath NHS Foundation Trust, is currently recruiting participants. It is, of course, completely unacceptable that any study should justify itself based on the uninterpretable findings of the PACE trial. The MAGENTA trial should be halted until the PACE authors have done what the First-Tier Tribunal ordered them to do–release their raw data and allow others to analyze it according to the outcomes specified in the PACE trial protocol.
Today, because of the urgency of the issue, we are posting on PubMed Commons the letter that The Lancet rejected. That way readers can judge for themselves whether it adds anything to the current debate.
Please note that the opinions in this blog post are mine only, not those of any of the other signers of the Lancet letter
Vincent R. Racaniello, PhD
Professor of Microbiology and Immunology
Columbia University
New York, New York
Ronald W. Davis, PhD
Professor of Biochemistry and Genetics
Stanford University
Stanford, California
Jonathan C.W. Edwards, MD
Emeritus Professor of Medicine
University College London
London, England, United Kingdom
Leonard A. Jason, PhD
Professor of Psychology
DePaul University
Chicago, Illinois
Bruce Levin, PhD
Professor of Biostatistics
Columbia University
New York, New York
Arthur L. Reingold, MD
Professor of Epidemiology
University of California, Berkeley
Berkeley, California
******
Dharam V. Ablashi, DVM, MS, Dip Bact
Scientific Director – HHV-6 Foundation
Former Senior Investigator
National Cancer Institute, NIH
Bethesda, Maryland
James N. Baraniuk, MD
Professor, Department of Medicine
Georgetown University
Washington, D.C.
Lisa F. Barcellos, PhD, MPH
Professor of Epidemiology
School of Public Health
California Institute for Quantitative Biosciences
University of California
Berkeley, California
Lucinda Bateman MD PC
MECFS and Fibromyalgia clinician
Salt Lake City, Utah
Alison C. Bested MD FRCPC
Clinical Associate Professor of Hematology
University of British Columbia
Vancouver, British Columbia, Canada
John Chia, MD
Clinician/Researcher
EV Med Research
Lomita, California
Lily Chu, MD, MSHS
Independent Researcher
San Francisco, California
Derek Enlander, MD, MRCS, LRCP
Attending Physician
Mount Sinai Medical Center, New York
ME CFS Center, Mount Sinai School of Medicine
New York, New York
Mary Ann Fletcher, PhD
Schemel Professor of Neuroimmune Medicine
College of Osteopathic Medicine
Nova Southeastern University
Professor Emeritus, University of Miami School of Medicine
Fort Lauderdale, Florida
Kenneth Friedman, PhD
Associate Professor of Pharmacology and Physiology (retired)
New Jersey Medical School
University of Medicine and Dentistry of NJ
Newark, New Jersey
Robert F. Garry, PhD
Professor of Microbiology and Immunology
Tulane University School of Medicine
New Orleans, Louisiana
Rebecca Goldin, PhD
Professor of Mathematics
George Mason University
Fairfax, Virginia
David L. Kaufman, MD,
Medical Director
Open Medicine Institute
Mountain View, California
Susan Levine, MD
Clinician, Private Practice
Visiting Fellow, Cornell University
New York, New York
Alan R. Light, PhD
Professor, Department of Anesthesiology
Department of Neurobiology and Anatomy
University of Utah
Salt Lake City, Utah
Patrick E. McKnight, PhD
Professor of Psychology
George Mason University
Fairfax, Virginia
Zaher Nahle, PhD, MPA
Vice President for Research and Scientific Programs
Solve ME/CFS Initiative
Los Angeles, California
James M. Oleske, MD, MPH
Francois-Xavier Bagnoud Professor of Pediatrics
Senator of RBHS Research Centers, Bureaus, and Institutes
Director, Division of Pediatrics Allergy, Immunology & Infectious Diseases
Department of Pediatrics
Rutgers – New Jersey Medical School
Newark, New Jersey
Richard N. Podell, M.D., MPH
Clinical Professor
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey
William Satariano, PhD
Professor of Epidemiology and Community Health
University of California, Berkeley
Berkeley, California
Paul T Seed MSc CStat CSci
Senior Lecturer in Medical Statistics
King’s College London, Division of Women’s Health
St Thomas’ Hospital
London, England, United Kingdom
Charles Shepherd, MB BS
Honorary Medical Adviser to the ME Association
London, England, United Kingdom
Christopher R. Snell, PhD
Scientific Director
WorkWell Foundation
Ripon, California
Nigel Speight, MA, MC, BChir, FRCP, FRCPCH, DCH
Pediatrician
Durham, England, United Kingdom
Philip B. Stark, PhD
Professor of Statistics
University of California, Berkeley
Berkeley, California
Eleanor Stein, MD FRCP(C)
Assistant Clinical Professor
University of Calgary
Calgary, Alberta, Canada
John Swartzberg, MD
Clinical Professor Emeritus
School of Public Health
University of California, Berkeley
Berkeley, California
Ronald G. Tompkins, MD, ScD
Summer M Redstone Professor of Surgery
Harvard University
Boston, Massachusetts
Rosemary Underhill, MB BS.
Physician, Independent Researcher
Palm Coast, Florida
Dr Rosamund Vallings MNZM, MB BS
General Practitioner
Auckland, New Zealand
Michael VanElzakker, PhD
Research Fellow, Psychiatric Neuroscience Division
Harvard Medical School and Massachusetts General Hospital
Boston, Massachusetts
Mark Vink, MD
Family Physician
Soerabaja Research Center
Amsterdam, The Netherlands
Prof Dr FC Visser
Cardiologist
Stichting CardioZorg
Hoofddorp, The Netherlands
William Weir, FRCP
Infectious Disease Consultant
London, England, United Kingdom
John Whiting, MD
Specialist Physician
Private Practice
Brisbane, Australia
Marcie Zinn, PhD
Research Consultant in Experimental Neuropsychology, qEEG/LORETA, Medical/Psychological Statistics
NeuroCognitive Research Institute, Chicago
Center for Community Research
DePaul University
Chicago, Illinois
Mark Zinn, MM
Research consultant in experimental electrophysiology
Center for Community Research
DePaul University
Chicago, Illinoi
