2016 brought exciting news for ME/CFS patients. The researchers behind the PACE trials were finally forced to release their raw data, which revealed that their initial conclusions – that graded exercise therapy and cognitive behavioural therapy were the only effective interventions for ME/CFS – were unsubstantiated.
Usually the retraction of positive results would not be cause for celebration. But the PACE trial was not only unethically conducted, it contained numerous methodological errors, drew conclusions which were not supported by the evidence, and promoted therapies which are greatly harmful to ME/CFS patients. It was only due to those same patients’ dogged research and tenacity in the face of abuse that the truth was revealed. Here’s how it happened.
In 2011, The Lancet published a study nicknamed the PACE trial, which assessed interventions for ME/CFS. It compared specialist medical care (SEM) alone to SEM with adaptive pacing therapy (APT), graded exercise therapy (GET) or cognitive behavioural therapy (CBT). Its conclusion seemed, at the time, groundbreaking: that “when added to SMC, CBT and GET had greater success in reducing fatigue and improving physical function than did APT or SMC alone.” (Researchers strengthened their position in a follow-up study to claim that 22% of patients recovered with CBT and GET, which was upgraded to 30% in a comment in The Lancet.)
The impact of these results cannot be understated. ME/CFS had, up until that point, been regarded as an untreatable mystery ailment, which baffled doctors and patients both. Media organisations reprinted PACE recommendations uncritically, with headlines blaring: “Got ME? Fatigued patients who go out and exercise have best hope of recovery.” Medical bodies fell over themselves in a rush to implement GET and CBT as treatment for ME/CFS.
Consider the underlying assumption behind these findings. CBT and GET as treatments were based on the theory that ME/CFS is not a disease, but a pattern of dysfunctional behaviour. Patients are held back not by any real, physical limitations, but by “fear avoidance” and deconditioning. That is, patients erroneously believe that their condition is tangible and lasting, and unnecessarily avoid exertion as a result. This causes them to weaken and become so afraid of activity that they engage in classic anxiety-avoidance behaviours.
CBT and GET are administered, not to learn coping skills for living with chronic illness or to gently regain some strength to the body, but to teach the patient that their “unhelpful cognitions” (ie, that they are unwell) are untrue, and to push their body into aerobic exercise (which is generally contraindicated for ME/CFS patients) as if they were recovering from bedrest with no underlying conditions.
Already, we see the researchers had a certain perspective of ME/CFS which influenced their research. They implicitly rejected APT as a therapy, not because of what it involved, but for what it implied: that ME/CFS was an organic disease which needed to be adapted to, not dismissed as a fiction.
Whether it was these already-formed views, utter disdain for ME/CFS patients, a vested interest in having ME/CFS classified as a psychiatric disorder, or plain incompetence that dictated how this study was conducted, we can’t know. What we do know is that it was shockingly bad science, which was so uncritically received by medical institutions and the media that it directed medical treatment for years, harming countless patients in the process.
Problems with the initial research included:
- An overly-inclusive criteria for participation: participants merely had to show signs of fatigue for 6 months with poor self-assessed physical function, which could include any person with a chronic illness or even depression, who would most certainly improve with CBT and exercise! (In fact, depression was accepted as a co-morbid condition, and one-third of participants listed it as such.)
- Participants had to be well enough to travel to hospital for treatment, thus excluding a significant proportion of ME/CFS patients*
- Participants were given promotional material during the study, with glowing testimonials from patients espousing the benefits of CBT and GET,** and recommendations from government bodies that they were proven treatments for ME/CFS (not disclosing that one of the researchers had worked on said recommendations)
“To let participants know that interventions have been selected by a government committee ‘based on the best available evidence’ strikes me as the height of clinical trial amateurism.”
– Dr. Bruce Levin, Columbia University
- Scales for measuring disability were so poorly defined, that you could be considered sick enough to qualify for the study, and well enough to be considered recovered at the same time (these measures were adjusted during the study to support the researchers’ hypothesis, so that you could actually deteriorate in condition and still be considered “recovered”)***
- “Recovery” was based only on subjective criteria (patient’s self-assessments of fatigue and physical function). Objective criteria, such as walking tests and work capacity, were measured but rejected by the researchers as “irrelevant” when it did not support their hypothesis
- Researchers had undisclosed links to the disability insurance industry, and had for years worked in advising insurance companies that the treatments promoted in PACE could be used to remove ME/CFS patients from disability and force them back to work
“This is a classic bad study. I would like to use it as a teaching tool, to have medical students read it and ask them, ‘How many things can you find wrong with this study?’”
– Ron Davis, director of the Stanford Genome Technology Center and director of the Science Advisory Board of the End ME/CFS Project.
Clearly there were issues with PACE – but not enough to prevent the CDC and countless medical bodies from adopting GET and CBT as standard treatment for ME/CFS patients. Meanwhile, alarm bells started ringing for patients. We know from experience that forced exercise is harmful – 74% of respondents to a survey said GET worsened their condition. And the idea that ME/CFS is merely a collection of “illness beliefs” is no more than a rehashing of the tired hysteria/somatic symptom disorder/conversion disorder/”you’re just crazy” argument used against us by so many.
It was thanks to the tireless work of a group of dedicated ME/CFS patients that the flaws of the PACE trial were exposed. Still, it took years to gain traction, and the PACE researchers would not go quietly. They performed a vigorous and, to me, disturbing campaign against ME/CFS patients who only wished for the release of their raw data for independent analysis.
ME/CFS patients were characterised as “borderline sociopathic or psychopathic” in their requests, and PACE researchers made absurd claims, such as being stalked by knife-bearing ME/CFS patients, or receiving death threats. (These claims were later assessed in court, and found to be false.)
“One sees a fairly small, but highly organised, very vocal and very damaging group of individuals who have, I would say, actually hijacked this agenda and distorted the debate so that it actually harms the overwhelming majority of patients.”
– Richard Horton, Lancet editor
PACE researchers also seemingly believed themselves exempt from freedom of information laws. The Queen Mary University of London spent over £200,000 fighting an order to release this data. Finally, in August 2016, the QMUL was forced by court to reveal certain raw data from the PACE trials. The tribunal condemned both the researchers’ refusal to comply with FOI requests, and their attacks on the ME/CFS community.
The raw data, of course, revealed what already suspected – the PACE trial was a sham. Once you peeled back the researchers’ layers of deception, the differences in recovery outcomes between groups were not statistically significant.**** Six years of research direction, treatment, and unmeasurable pain for ME/CFS patients were based on a lie.
We shouldn’t take solace in the comforting notion that science is self-correcting. Many people, including many very sick people, had to invest immense effort and withstand vitriol to use science to correct these mistakes.
So where does that leave ME/CFS patients? In some ways, I have more hope for the future of ME/CFS research. The NYTimes, The Guardian, and The Conversation, as well as other media organisations, have reported on the bad science of the PACE trial and the harm done to ME/CFS patients. There is strong evidence building as to the biological nature of this disease.
Yet, the uncritical reporting of the initial research and the way it was so readily accepted by the medical community is concerning to me. Just why were the PACE trial’s recommendations so universally implemented, when the science they were based upon was barely science at all? The answer is, unfortunately, one I find myself too often repeating.
The reason people believed that ME/CFS was not a real illness, and that patients had deluded “unhelpful cognitions”, was because they wanted to believe. It is too easy to believe that ME/CFS patients are malingers, and that when they sought the truth they were “vexatious” patients. The PACE researchers had an agenda, yes – but so did the many who adopted CBT and GET as the cornerstone of ME/CFS treatment, and the media which egged them on.
The PACE trial and its subsequent adoption is nothing more than another entry in a sustained history of abuse against ME/CFS patients. I doubt the day will come when we will see an apology for the harm done us by inappropriate interventions or the lies fabricated by PACE researchers regarding patient harassment towards them.
This is personal for me – a prescribed course of GET caused me immense harm, sending me to bed and making me so weak I could not sit up, eat, or shower. Perhaps I should not have placed so much trust in medical professionals, and never will again. But I also know I will never look those medical professionals in the eye, and have them apologise to me for making me bedbound, for nearly killing me, for creating 3/4 of the debilitating symptoms I now live with today.
The PACE trial is dead, but there is work yet to be done. The attitudes which spawned it are very much alive – at this moment, a trial of GET is being conducted on children with ME/CFS, and many medical bodies still recommend CBT and GET as treatment. ME/CFS patients will never be able to rest easy until the medical establishment chooses science over bias, and begins to right the wrongs done to a much-maligned patient body.
If this episode has taught me anything, it is that ME/CFS patients will never be broken. It is in our limitless tenacity, our knowledge, our tireless research, and our voice that I place my trust.
OK – this wasn’t as “brief” as I’d hoped! But it’s certainly shorter than the best published work on the PACE trial, to which I am entirely indebted. This post is essentially a summary of the remarkable investigative journalism done by David Tuller, Julie Reymeher and others. You can read their pieces below, if you’d like to know more (or are a stats lover!). Thanks for sticking around!
*Interestingly, a “sister study” to PACE was conducted some years before. The FINE trial studied the same interventions on homebound people, and was buried when the results showed no difference in outcome in any groups – even though the study had some of the same methodological errors as the PACE trial, designed to promote a positive result from CBT and GET.
**Treatments were not named, but strongly implied in the wording.
***In fact, patients in the GET arm that the study considered a success still displayed exercise capability well below the level of elderly women, people with pacemakers, people with heart failure, and cystic fibrosis patients. That is, they were still seriously disabled.
****Alem Matthees, an ME patient from Perth, analysed certain PACE trial data obtained in the FOI case with the aid of two academic statisticians. They found that when the original criteria for recovery was adhered to, there was no statistical significance between the groups (ie, patients did not “recover” with CBT and GET). The full data from the trial is still unavailable, but QMUS released a re-analysis a day before (forcedly) complying with the FOI request, assumedly to mitigate its impact. They concluded that only 10% of patients in the GET and CBT arms showed “improvement” compared to the other treatment groups – a significant drop from their original figure of 60%. Without independent analysis, these findings cannot be confirmed, and the numerous methodological problems with this study deem them questionable, at best.
TRIAL BY ERROR: The Troubling Case of the PACE Chronic Fatigue Syndrome Study – David Tuller, DrPH, academic coordinator of the concurrent masters degree program in public health and journalism at the University of California, Berkeley . He actually wrote a series of articles about the PACE trials – all his writings on ME/CFS can be viewed here.
Bad science misled millions with chronic fatigue syndrome. Here’s how we fought back – Julie Rehmeyer, mathematician, scientist, former professor, journalist, ME patient.
Getting It Wrong on Chronic Fatigue Syndrome (published in the NY Times) – David Tuller and Julie Rehmeyer
Hope for Chronic Fatigue Syndrome – Julie Rehmeyer
PACE: The research that sparked a patient rebellion and challenged medicine – Rebecca Goldin, Professor of Mathematical Sciences at George Mason University, Director of STATS.org
Uninterpretable: Fatal flaws in PACE Chronic Fatigue Syndrome follow-up study – James C. Coyne, PhD, Professor of Health Psychology at University Medical Center, Groningen
How Alem Matthees’ letter helped solve Chronic Fatigue Syndrome mystery – about the FOI request from an Aussie ME/CFS patient which led to the publication of PACE data.
Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial – original research published in The Lancet, if you want to see how truly shitty it is for yourself.