By David Tuller, DrPH
As I have recently written, four major clinical trials of CBT for so-called MUS have documented the opposite of what the investigators hoped to prove. In fact, the evidence from this research suggests that CBT is not an effective treatment for these conditions. That hasn’t stopped these investigators from claiming otherwise, of course. As my earlier post indicated, they have deployed a range of methodological, statistical and rhetorical strategies to obfuscate or downplay their poor results. Three of these studies were based at King’s College London, and one, the now-discredited PACE trial, at Queen Mary University of London.
A 2007 article in the journal Clinical Psychology Review, €œThe cognitive behavioural model of medically unexplained symptoms: A theoretical and empirical review€–sheds some light on the background and possible genesis of these various trials. (One of the co-authors of the review was a lead investigator in all four of the MUS clinical trials.) This review outlined the rationale behind the CBT treatment approach to MUS, including specifically chronic fatigue syndrome (CFS) and irritable bowel syndrome (IBS), and suggested that these conditions are essentially self-sustaining. The review also helped clarify–for me, why I get a sense of dÃ©jÃ vu whenever I read another article from this group of investigators. Each one basically says the same thing, except with a change in the targeted condition.
Sure enough, the authors of the 2007 paper included a reference to a favorite meme among those who share their theoretical orientation: the €œvicious circle€ that purportedly leads to a downward spiral of increasing misery. Here’s how the authors presented this bedrock element of their construct: €œThe sine qua non of any CBT model [for MUS] is a vicious circle, the hypothesis that a self perpetuating interaction between different domains maintains symptoms, distress and disability. Irrespective of the symptom type€¦the CBT models of MUS, IBS and CFS propose a model of perpetuation that is, to borrow a term from systems theory and cell biology, autopoietic.€
These CBT models, noted the authors, provided guidance for studies of specialized interventions that could disrupt the €œvicious circle€ and, in doing so, lend support to the theory: €œTreatment is aimed at elaborating the unique inter-play of factors in any given patient and dismantling the autopoietic mechanism by making changes in target areas. In as far as treatment studies are a test of this hypothesis, it has good but at present only indirect support. More direct research support, based on testing this theoretical model of MUS is needed.€
The review focused on various elements that have been hypothesized as part of the process of perpetuation, such as a heightened focus on symptoms and attributing illness to somatic causes. Illness related beliefs, the authors noted, have emerged as €œpotentially important factors€ in the persistence of symptoms. The hypothesis, they explained, €œis that the beliefs inform behaviour, in this case activity avoidance, which in turn affects physiology and symptoms, providing the rudiments of a vicious circle of symptom maintenance.€
This hypothesis about the generation of the €œvicious circle€ assumes that the beliefs lead to the symptoms, with behavior as the mediator. It is just as reasonable that causal relationships run in the other direction. Perhaps those with a serious illness–especially one characterized by the symptom of post-exertional malaise–accurately believe that activity is potentially harmful, and it should not be surprising that they would have poor outcomes.
In any event, as the 2007 paper suggested, the proof is in the pudding, that is, in the findings of trials designed to test interventions based on the CBT hypothesis. The authors’ appeal for more research appears to have been successful, given the quartet of big trials that have investigated this MUS model. For each study, the investigators published a protocol that cited supposedly promising preliminary data and presented the proposed research as necessary for obtaining authoritative evidence for clinical decision-making and public health policy.
And yet, when faced with null or minimal results, the investigators have not questioned their own attachment to their theoretical framework. Instead, they have found ways to minimize or ignore or argue away the reality of their findings, that CBT does not work as intended.
This is not how science is supposed to go. €œSelf-correcting€ is supposed to mean what it says. But the onus isn’t really on €œscience.€ It is on scientists. And if scientists refuse to self-correct no matter how poor their results, then what’s the point?
CBT Trial for Q-Fever Fatigue Syndrome Also Generates Inflated Claims
Looking beyond the UK, a 2017 study from a team of Dutch investigators–a large trial of CBT for prolonged fatigue after an acute bout of Q fever, a bacterial infection–could fit in with this MUS quartet. This phenomenon, known as Q-fever Fatigue Syndrome (QFS), afflicts a significant minority of patients after an acute bout of Q-fever. The Netherlands experienced a Q-fever epidemic in the late 2000s, providing an opportunity to conduct a large clinical trial of CBT for QFS. The investigators published a trial protocol in 2013. In 2019, they published both a long-term follow-up and a mediation analysis. The trial also tested a regimen of antibiotics.
(A robust critique of the trial, by Dr Mark Vink and Alexandra Vink-Niese, outlined serious methodological concerns that undermined the claims of CBT’s effectiveness. Lou Corsius also deconstructed the study effectively in two posts on his blog It’s About ME, here and here.)
The 2017 trial report in Clinical Infectious Diseases noted that the CBT approach to QSF was based on its purported success for CFS: €œCognitive-behavioral therapy (CBT), aimed at fatigue-related cognitions and behavior thought to perpetuate symptoms, can reduce symptoms and improve functioning in CFS. A considerable overlap in fatigue-perpetuating factors between QFS and CFS implies that CBT might also reduce fatigue severity in QFS.€
And here is how the intervention was described: €œFirst, the model of fatigue perpetuating beliefs and behaviors is explained to patients. At the start of the therapy patients formulate their goals in behavioral terms. These goals usually include the resumption of work, hobbies, and other activities that imply that the patient is no longer severely fatigued and disabled, which is the goal of CBT for QFS€¦During the sessions, the therapist elicits and challenges patients’ non-accepting and catastrophising beliefs with respect to fatigue. Additionally, patients are taught how to distract their attention from their fatigue.€
The primary outcome was fatigue at 26 weeks, the end of the treatment period. (The study used a different fatigue scale than the one used in the PACE trial, the Chalder Fatigue Scale.) The difference between the mean scores of the CBT group and the placebo group on the fatigue scale was modest–less than what was deemed a €œclinically meaningful improvement€ on the measure for an individual. Even these small reported benefits wore off by the one-year follow-up study, as reported fatigue increased again after treatment among those who had received CBT.
The study also measured activity levels objectively by having participants wear actometers for a period of time at the beginning and end of treatment. For some reason, this measure was not officially a primary or secondary outcome but was included as a potential mediating variable. In any event, the intervention did not lead to benefits in physical activity levels, despite the subjective reports of improvement in fatigue. The investigators did not report those disappointing data until the mediation analysis paper published two years after they had already claimed success.
Even after the subsequent null results for the primary outcome in the one year follow-up study, the investigators continued to argue that CBT should be recommended. Doubling down on their approach, they called for research into ways to maximize the supposed early benefits, perhaps with €œbooster sessions€ of CBT. Given the anemic results of this major trial, others might reach a different conclusion.