An excellent podcast was released recently regarding the egregious flaws of the PACE Trial, an $8 million study published in The Lancet in 2011 that purported to compare the effectiveness of adaptive pacing therapy, graded exercise therapy (GET), cognitive behavioral therapy (CBT), and ‘standardized specialist medical care’ in treating ME/CFS. The tale is long and twisted, and this podcast presents the controversy in an easy-to-digest narrative.
The PACE study was run by a group of psychiatrists in the UK who believe ME/CFS is the result of maladaptive thought processes regarding exercise that cause patients to avoid activity after an illness and thereby become deconditioned. There are lots of studies to refute this biopsychosocial model, but that’s a blog post for another day.
Both CBT and GET strategies emphasized to patients that they do not have a biological illness and encouraged them to increase activity levels even in the face of worsening symptoms. A primary component of ME/CFS is something called post-exertional malaise in which exertion can trigger a significant physical decline.
In practice, encouraging increases in activity can cause devastating setbacks for patients. A survey of over 1,400 patients conducted by the ME Association found 74% of respondents reported worsening symptoms after a course of GET. In contrast, the PACE authors reported that CBT and GET can each lead to recovery in 22% of ME/CFS patients.
Upon close examination, the PACE Trial reads like a cautionary tale of how NOT to science. Just a few highlights include failure to obtain fully informed consent, conflicts of interest, setting ‘recovery’ criteria worse than the criteria required for a patient to be included in the study such that 13% of the patients were considered ‘recovered’ before they even entered the study, throwing out all objective outcome measures mid-way through the non-blinded trial, weakening all 4 recovery criteria midway through the non-blinded trial, and using a flawed diagnostic criteria that likely lead to the inclusion of individuals with other fatiguing illnesses such as primary depression. In addition, the study’s cutoffs for ‘recovery’ were ludicrous, with patients scoring similar in physical functioning to individuals with congestive heart failure qualifying as ‘recovered’ based on study criteria.
This particular podcast features David Tuller, a health journalist and lecturer at Berkeley who has devoted countless hours of unpaid time and effort to lead the charge outside of the patient community against the paper’s unsupported claims. It is hosted by Vincent Racaniello, a microbiology and immunology professor at Columbia University’s College of Physicians and Surgeons who runs a virology blog and does several weekly science podcasts in addition to his scientific research. It’s worth the listen even if you have kept up with Tuller’s writings.
Alarmingly, there is so much wrong with this study that it can’t all be covered in an hour and a half long podcast. If this were any other disease, this journal article would not be allowed to stand. Had this been a study on MS, I have no doubt the article would have been retracted within a month of publication.
My primary goal in writing this post is not to perform my own analysis. I only wish to add one more arrow pointing towards the work that has already been contributed by others, and to share this important issue with my own small corner of the science world.
Included in the ranks of ME/CFS patients are qualified statisticians, mathematicians, and medical researchers. Many sharp critiques have been published by skilled patients, journalists, and other prominent scientists regarding PACE and its follow-up publications.
This battle has been waging for the last five years, and there is more than ample justification to call for the retraction of the paper. Despite this, the authors continue to evade questions and Freedom of Information Act requests for them to release the anonymized data so it can be reanalyzed based on their original recovery criteria. At this point, Queen Mary University of London, one of the study’s parent institutions, has spent over $300,000 in taxpayer money to keep publicly funded data from the public. *facepalm*
“It’s not a benign academic dispute, it’s a dispute that has incredible impact on people’s lives.”
In David Tuller’s words, “What they’ve done has been established in the UK and other countries as the standard of care…They’ve applied a standard of care [of GET and CBT] on families with really sick kids and it’s very harmful…It’s not a benign academic dispute, it’s a dispute that has incredible real impact on people’s lives.”
Prominent sources of medical information such as the CDC and Mayo Clinic still recommend GET and CBT in their clinical treatment guidelines. Chances are if you go to the doctor as a ME/CFS patient, the only ‘help’ they will offer you is to strongly advise you to exercise or “go to the gym”. Following this advice risks triggering worsening of symptoms and potentially months- or years-long relapses. And if you don’t follow the recommendation, you are labeled a malingerer who is unwilling to fix their own health. We have the PACE Trial to thank for this.
As a scientist, I’m disgusted. As a patient, I feel wronged. May we keep fighting until this article is retracted.
You can find the podcast here.
Many of David Tuller’s pieces on ME/CFS are housed at Virology Blog. They can be found here.