The Draft Report by the Institute for Quality and Efficiency in Healthcare Does Not Provide Any Evidence That Graded Exercise Therapy and Cognitive Behavioral Therapy Are Safe and Effective Treatments for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

The German Institute for Quality and Efficiency in Healthcare (IQWiG) recently published its draft report to the government about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The IQWiG concluded that graded exercise therapy (GET) and cognitive behavioral therapy (CBT) should be recommended in the treatment for mild and moderate ME/CFS based on two CBT and two GET studies. In this article, we reviewed the evidence used by IQWiG to support their claims, because their conclusion is diametrically opposed to the conclusion by the British National Institute for Health and Care Excellence (NICE) in its recently updated ME/CFS guidelines. Our analysis shows that the trials IQWiG used in support suffered from serious flaws, which included badly designed control groups; relying on subjective primary outcomes in non-blinded studies; alliance and response shift bias, including patients in their trials who did not have the disease under investigation, selective reporting, making extensive endpoint changes and low to very low adherence of treatments. Our analysis also shows that the report itself used one CBT and one GET study that both examined a different treatment. The report also used a definition of CBT that does not reflect the way it is being used in ME/CFS or was tested in the studies. The report noted that one study used a wrong definition of post-exertional malaise (PEM), the main characteristic of the disease, according to the report. Yet, it ignored the consequence of this, that less than the required minimum percentage of patients had the disease under investigation in that study. It also ignored the absence of improvement on most of the subjective outcomes, as well as the fact that the IQWiG methods handbook states that one should use objective outcomes and not rely on subjective outcomes in non-blinded studies. The report concluded that both treatments did not lead to objective improvement in the six-minute walk test but then ignored that. The report did not analyze the other objective outcomes of the studies (step test and occupational and benefits status), which showed a null effect. Finally, the report states that the studies do not report on safety yet assumes that the treatments are safe based on a tendency towards small subjective improvements in fatigue and physical functioning, even though the adherence to the treatments was (very) low and the studies included many patients who did not have the disease under investigation and, consequently, did not suffer from exertion intolerance contrary to ME/CFS patients. At the same time, it ignored and downplayed all the evidence that both treatments are not safe, even when the evidence was produced by a British university. In conclusion, the studies used by the report do not provide any evidence that CBT and GET are safe and effective. Consequently, the report and the studies do not provide any support for the recommendation to use CBT and GET for ME/CFS or long COVID, which, in many cases, is the same or resembles ME/CFS, after an infection with SARS-CoV-2.

An understanding of the immune dysfunction in susceptible people who develop the post-viral fatigue syndromes Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID

“…Initially there was much controversy about the aetiology of ME/CFS and a large focus developed on treating ME/CFS as a psychological disorder by using cognitive behavioural therapy (CBT) and graded exercise therapy (GET) 135 . We now know that these are not efficacious and can be harmful [136][137][138] . Some patients have claimed daily CBT according to a prescribed programme can incrementally alleviate symptoms over time and therefore the potential use of these treatments should not be discounted fully 50 .…”

The Role of Psychotherapy in the Care of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…This fundamental comprehension that ME/CFS is a physical disease is crucial because it delimits both patients' and therapists' expectations regarding treatment, and thus establishes a framework within which psychotherapeutic work can be possible as a standard that is appropriate for tackling emotional needs and the support of pacing. By now, there is an vast body of empirical findings from many areas of somatic medicine that demonstrate the physiologic nature of ME/CFS [1][2][3][4][11][12][13][14][15]. Nonetheless, there is still no clear single diagnostic biomarker for the disease and no scientific consensus on the underlying mechanisms of pathology.…”

“…In Germany, the responsible Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, i.e., IQWiG) inferred a weak effect for both GET and CBT in a first draft based on very few studies [12]. However, careful examination of these studies and the arguments put forward by IQWiG suggest that this assessment and the recommendations (already very cautiously worded by the IQWIG itself) are very problematic because they ignore IQWiG's own methodological handbook, as well as the absence of evidence for objective post-GET/CBT improvement in the examined studies [13,14].…”