From the Journal of Neurology and Neurobiology, 10 January 2017.
Assessment of Individual PACE Trial Data: in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, Cognitive Behavioral and Graded Exercise Therapy are Ineffective, Do Not Lead to Actual Recovery and Negative Outcomes may be Higher than Reported
Family Physician, Soerabaja Research Center, Amsterdam, The Netherlands
*Corresponding author: Mark Vink, Family Physician, Soerabaja Research Center, Amsterdam, the Netherlands, E-mail: firstname.lastname@example.org
The PACE trial concluded that Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) are moderately effective in managing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and yielded a 22% recovery rate. Nonetheless, the recently released individual participant data shows that 13.3% of patients had already recovered, on one or both primary outcomes, upon entering the trial. Moreover, no one classified as recovered achieved the physical functioning, together with the fatigue scores, of the healthy sedentary controls from another trial by the PACE trial‘s lead principal investigator or achieved Kennedy‘s definition of recovery, whereby symptoms are eliminated and patients return to premorbid levels of functioning, due to CBT or GET (alone). Therefore, CBT and GET do not lead to actual recovery.
After CBT and GET therapy, 59% and 61% of participants, respectively were labeled as improvers in the original paper, which was lowered by the PACE trial authors to 20% and 21% in the newly released papers in which they used the original protocol; nevertheless, only 3.7% and 6.3% were objective improvers in the objective 6-minute walk test as defined by the same improvement of 50% or more, as used by the trial itself, to classify someone as an improver.
If the effect of Specialist Medical Care had been removed from the analysis, then 0% and 1.3% of patients improved objectively with CBT and GET, respectively. Highlighting the fact that unblinded trials like the PACE trial, should not rely on subjective primary outcomes, but use either objective primary outcomes alone, or combined with subjective primary outcomes, as a methodological safeguard against the erroneous inference of efficacy in its absence.
The objective individual participant data shows that in up to 82.2% and 79.8% of ME patients their health might have been negatively affected by CBT and GET, respectively.
The independent PACE trial review had shown that this proportion was between 46% and 96%, and found to be between 63% and 74% by surveys involving more than 3000 patients by the Norwegian, British, and the Dutch ME Associations. These data confirm the conclusions of a number of studies that patient health was negatively affected by CBT and GET, including one that found that in 82% of patients with severe ME their symptoms were made worse by GET.
Analysis of the individual participant PACE trial data has shown that CBT and GET are ineffective and (potentially) harmful, which invalidates the assumption and opinion-based biopsychosocial model. Consequently, we should stop using CBT and GET as (compulsory) treatments for ME/ CFS to prevent further unnecessary suffering inflicted on patients by physicians, which is the worst of all harms, yet totally preventable.