By David Tuller, DrPH
It is refreshing to read a study about a rehabilitative intervention for ME/CFS or Long Covid or so-called “medically unexplained symptoms” that acknowledges the lack of meaningful benefits. This is a rare event. In multiple cases, the trialed interventions produce marginally positive results in subjective measures, which are then touted as evidence in favor of the approach. Given that the studies are generally highly prone to bias, these meager findings in fact support the opposite interpretation—that the interventions are largely ineffective.
That’s what happened with a recently published trial of cognitive behavior therapy (CBT) for treating ME/CFS. The trial found extremely modest benefits for the intervention at three months, right after therapy ended. However, these benefits had disappeared by the six-month follow-up. However, the investigators presented the intervention as promising and called for larger clinical trials. (I commented on the trial here.)
The new, more honest paper is called “Evaluation of an Integrated Multidisciplinary Care Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Open-label, Non-randomized Controlled Intervention Study.” It was posted as a pre-print and has not yet been peer-reviewed.
Here is the straightforward conclusion of the abstract:
“The integrated multidisciplinary care model was feasible and associated with high retention but did not improve physical functioning or key secondary outcomes at 12 months. Current rehabilitative and management strategies may be insufficient to alter disease trajectory, underscoring the need for more effective, disease-modifying therapeutic interventions.”
Unlike most of these efforts, this study was conducted by experts who take ME/CFS seriously as a biomedical disorder. The venue was the Fatigue Center at Charite, a major teaching hospital in Berlin, and Carmen Scheibenbogen, one of the many co-authors, is a leading ME/CFS and Long Covid investigator. According to the study, “growing evidence suggests that ME/CFS is underpinned by immune dysregulation, including autoantibody-mediated mechanisms and low-level inflammation, as well as autonomic and endothelial dysfunction.”
The intervention was not based—or at least does not appear to have been based—on the biopsychosocial assertion that the symptoms are perpetuated by the combination of “unhelpful beliefs” about having a biomedical disease and deconditioning caused by sedentary behavior. As far as I could tell, it did not promote graded activity. (Details about the intervention were said to be in an appendix, but the appendix did not seem to be included as part of the pre-print.)
Per the paper: “We conducted and evaluated an integrated, multidisciplinary care approach for patients with ME/CFS, combining specialist diagnostic assessment and symptomatic therapy including patient education, physiotherapy, relaxation-based interventions, pharmacological treatment…delivered within a specialized ME/CFS outpatient clinic and an inpatient rehabilitation center.”
The intervention, noted the investigators, “was specifically tailored to the needs of ME/CFS patients, an approach that is not typically implemented in standard rehabilitation programs.” One predicate for the research was that German insurance companies frequently require people with ME/CFS who seek disability benefits to undergo some form of rehabilitation program.
The primary outcome was self-reported physical function at 12 months, assessed with a standard questionnaire called the SF-36. Secondary outcomes included fatigue, disability, health-related quality of life, autonomic symptoms, daytime sleepiness, handgrip strength, physical activity, sick leave, and health-care costs.
This was not a clinical trial—the participants were not randomized. They were offered the intervention if their form of insurance covered it. The others received a single outpatient consultation and a medical report for their primary physician. In the end, 97 participants were assigned to the intervention, and 100 were not. However, only 89 and 93 participants, respectively, provided data for the primary outcome at the 12-month time point.
The study was unblinded—obviously everyone knew whether or not they were receiving the intervention—and relied on subjective measures. This study design is a recipe for an unknown amount of bias. That’s why it wouldn’t have been surprising if the investigators had reported marginally positive results for the intervention, as has occurred in many other studies. But that didn’t happen here.
At 12 months, the intervention group actually fared a bit worse than the comparison arm on the SF-36, although the difference was not statistically or clinically significant. The overall results for the secondary measures were equally dismal. On a measure called the Bell Disability Scale, commonly used to assess people with ME/CFS, 42 of the 94 patients who went through the intervention, or 45%, got worse. Only 13, or 14%, improved on the scale. On the other hand, despite these negative results, participants reported that the intervention helped them “cope better with the disease in daily life,” noted the study.
Rather than trying to sugar-coat these results and calling for more research in the same vein, the investigators pointed out that their findings were “consistent with expert recommendations, emphasizing symptomatic therapy and disease stabilization rather than recovery as a realistic goal.” And they pushed back against the entire rehabilitation approach:
“Our findings question the clinical value of current rehabilitation in ME/CFS, even when specifically adapted to the disease…These findings have important implications for clinical practice and health policy, especially in settings where participation in rehabilitation is linked to social or disability benefits. Our data suggest that such requirements should be carefully reconsidered to avoid potential harm and unnecessary burden for patients. Overall, these results underscore the urgent need for mechanism-based therapeutic approaches and well-controlled clinical trials aimed at developing disease-modifying treatments for ME/CFS.”