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04.04.17- Treating CFS with CBT and GET: How the PACE Trial Got It Wrong

Treating Chronic Fatigue Syndrome with Cognitive Behavioral Therapy and Graded Exercise Therapy: How the PACE Trial Got It Wrong

The PACE trial found that cognitive behavioral therapy and graded exercise therapy were effective treatments for chronic fatigue syndrome and could produce recovery in 22% of patients. It seems they got it wrong.

The PACE trial said graded exercise is an effective treatment for CFS. CFS patients disagree.

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), and the recently-suggested IOM term systemic exertion intolerance disease (SEID), is characterized by long-term fatigue and a host of other symptoms that impair the patient’s ability to function. It sometimes develops after a flu-like illness, but can also come on gradually with no apparent antecedent. The cause is unknown. There is controversy about the diagnostic criteria, and treatment has not been very successful. Between 8-63% of patients improve during follow-up, but fewer than 10% of adult patients return to pre-illness levels of functioning.

A 2001 review in the Journal of the American Medical Association (JAMA) found that cognitive behavioral therapy (CBT) and graded exercise therapy (GET) were the most promising treatments, but the evidence was mixed and the supporting studies had methodological inadequacies. They warned that positive results on subjective measures in these studies did not mean the participants had actually improved their physical capacities. The PACE trial was designed to look for better evidence.


Together, the two PACE reports concluded that CBT and GET, when added to SMC, were safe and effective treatments for CFS, with a moderate effect size; and with those treatments, a substantial number of patients could achieve recovery from CFS.

Criticism of the PACE study by patients

There was an extensive reaction from patient and advocacy communities. CFS patients were offended by the suggestion that their symptoms were psychological: they knew there was a large body of research indicating that CFS was a biological condition. CFS patients could not accept the results of the study, because in their experience, even mild exertion could increase all the other symptoms of the disease, and they knew that their exercise tolerance varied from day to day. They knew that starting low and building slowly simply wouldn’t work for them. They had learned to rest as soon as they felt tired.


Criticism of the PACE study by scientists

Dr. David Tuller, writing on the Virology blog, identified several major flaws.


Tuller quoted several top researchers who agreed that the study was fraught with indefensible methodological problems. Comments included statements like “I’m shocked that The Lancet published it” and “It’s a mass of uninterpretability.”

The struggle to access the trial data

Critics pushed for an independent review of the trial data. They submitted dozens of freedom-of-information (FOI) requests for PACE-related documents and data. The National Institutes of Health (NIH) and the Institute of Medicine (IOM) chimed in, and experts said the deconditioning hypothesis was flawed and untenable.


When the trial data were finally made available (only after long persistence, many FOI requests, and a court order), an independent group did a preliminary analysis of “recovery” from CFS using individual participant data. 


The authors of the re-analysis said:

The PACE trial provides a good example of the problems that can occur when investigators are allowed to substantially deviate from the trial protocol without adequate justification or scrutiny. We therefore propose that a thorough, transparent, and independent re-analysis be conducted to provide greater clarity about the PACE trial results. Pending a comprehensive review or audit of trial data, it seems prudent that the published trial results should be treated as potentially unsound, as well as the medical texts, review articles, and public policies based on those results.


Conclusion: A flawed study with lessons to be learned

Studies like the PACE trial can have a strong impact on patient care, and flawed studies can result in harm to patients. Conventional peer review is obviously not enough: the effective peer review in this case came after publication. Numerous flaws were found that should have been addressed before publication. Critics called for the study to be retracted; so far, it hasn’t been. This unfortunate episode can serve as a wake-up call and it points out the value of freely sharing raw data with other researchers. Good scientists want to know if they are wrong. They want to have their work scrutinized and should be willing to share their data without the requesters having to resort to a court order.

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