By David Tuller, DrPH
*October is crowdfunding month at UC Berkeley. If you like my work, consider making a tax-deductible donation to Berkeley’s School of Public Health to support the Trial By Error: project: https://crowdfund.berkeley.edu/project/33528
This month marks the seventh anniversary of Virology Blog’s publication of my 15,000-word investigation of the egregiously flawed and fraudulent (i.e. misleading, deceptive) piece of crap known as the PACE trial. (Incidentally, it is also the one-year anniversary of the new and much-improved guidelines for ME/CFS from the National Institute for Health and Care Excellence.) To write that piece, I spent more than a year reading and interviewing people about the trial, traveled to England to meet with PACE participant and others, and consulted extensively with academic colleagues in epidemiology, biostatistics, and infectious diseases. And as I have always acknowledged, I relied extensively on the knowledge and wisdom of the amazing ME/CFS patient community.
(The PACE authors and the editor of The Lancet, which published the first results, refused to talk with me.)
My initial series, published in three installments from October 21st to 23rd, 2015, was covered in major media outlets—Science, The Guardian, Slate, STAT, and so on. I expected it to be a one-off; after all, what trial could survive the revelation that it included the kinds of flagrant methodological and ethical flaws that marred PACE? Unfortunately, the Lancet editor, Richard Horton, one-time champion of Andrew Wakefield’s discredited study of the purported link between vaccines and autism, proved himself to be as deluded about the trial’s quality as the PACE authors themselves. So nothing happened. That’s one reason I’ve kept at it.
What is it about this trial that captured my ongoing interest? I was truly fascinated that the entire academic-medical-industrial complex appeared to be gripped by some form of societal hysteria or “emperor-has-no-clothes-ism” regarding the purported merits of the trial. The unaccountable acclaim for PACE was prevalent not only in the UK but among health care professionals and public health experts around the world, including in the US.
How could anyone praise a trial in which patients could get worse on the two primary outcome measures—self-reported physical function and fatigue—and still be found to have improved or even recovered on those measures? This bizarre anomaly was evident in both the 2011 Lancet paper on “improvement” and the laughable “recovery” paper published two years later in Psychological Medicine. Given this and other unacceptable irregularities, the widespread acceptance of the trial mystified me; the claims made for its greatness routinely smacked of Trumpian-style logic and deception.
To cite the most eye-opening example: Patients could enter the trial with a score of 65 or below out of 100 on the physical function questionnaire—a score that indicates serious disability. While the trial protocol indicated that a score of 75 at the end would designate “improvement” and a score of 85 would indicate “recovery” on that specific physical function scale, those outcome thresholds were dramatically weakened by the time results were published. In both the Lancet and Psychological Medicine papers, the outcome threshold for physical function had dropped to 60—below the required entry score of 65.
Needless to say, this made no sense then and it still makes no sense. It is, in fact, a form of insanity to argue that patients can be simultaneously disabled and recovered on the same measure. No one can be both positive and negative on an HIV test. No one can be pregnant and not pregnant at the same time. As it turned out, 13% of participants in the trial were already “recovered” for physical function at baseline, per the revised outcome threshold, even as they were being defined as seriously disabled. Huh?
How did studies with this frank impossibility manage to pass peer review? How could The Lancet and Psychological Medicine not retract studies featuring this anomaly, once it was pointed out? I pressed the PACE authors and Dr Horton to provide me with another example of a trial in which entry and outcome thresholds criss-crossed. They never did. If any such studies exist, I haven’t seen them. And if they do exist, it is because the peer-review system failed, as it did in the case of the PACE trial. For journals to reject these criticisms and reaffirm support for PACE indicates an astonishing level of corruption and ethical bankruptcy at the highest levels of UK science.
To omit key information and misrepresent data in ways that convey a distorted impression of findings falls well within standard definitions of research misconduct. I have no hesitation stating that, in my professional opinion, PACE is a prime example of this—that’s one reason why it has been used in Berkeley epidemiology seminars as a case study of how not to conduct a clinical trial. Is it fraudulent? According to this definition, “fraudulent” can mean “unjustifiably claiming or being credited with particular accomplishments or qualities.” A study which fails to disclose the highly salient fact that 13% of participants are “recovered” on an outcome threshold at baseline certainly meets that definition, in my opinion.
Does that mean it is an example of actual “fraud”? That’s a more complicated question. “Fraud” has legal meanings related to criminal activities and is characterized in different ways in different jurisdictions and countries. I’m not a lawyer and have no idea if the PACE trial would be found to be an example of fraud under UK statutes. Whether it can and should be investigated as possible fraud is not my call. In any event, the researchers should be held to account for wasting £5,000,000 of taxpayer funds on this nonsense—not least in the form of permanent damage to their reputations and academic standing.
This project has not always been easy. Listening to repeated accounts of the abuse and neglect experienced by patients has been heartbreaking. I have often cried in the course of this work–most prominently during an interview on Australian TV. Among other challenges, I’ve been harassed in various ways by high-profile investigators (Professor Esther Crawley); had my employment threatened by a major English academic institution (University of Bristol); been portrayed as a money-grubbing grifter by a leading news organization (Reuters); and had my work misrepresented by a top medical journal (BMJ Open).
But I’m not complaining–that’s the price of doing business and challenging authorities who hold themselves in high esteem despite abundant evidence that this self-regard is seriously misplaced. Pursuing this project, exposing fallacious scientific reasoning, and puncturing the egos of these pompous pooh-bahs has been one of the highlights of my career to date—an incredibly rich and rewarding experience. I have no regrets.