Quartet of Trials Reveals Limitations of CBT for “Medically Unexplained Symptoms”

By David Tuller, DrPH

A year ago, I wrote a post about how the biopsychosocial ideological brigades had completed a trifecta of major studies that investigated cognitive behavior therapy for a variety of so-called “medically unexplained symptoms” (MUS). As a group, the studies demonstrated the overall ineffectiveness of CBT as a treatment for this category of disorders—despite herculean efforts to spin the results the other way. MUS is usually defined to include chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, functional neurological disorders, and other conditions for which pathophysiological mechanisms have not been identified.

These three trials were: the PACE trial for chronic fatigue syndrome, which also tested graded exercise therapy; the ACTIB trial for irritable bowel syndrome; and the CODES trial for psychogenic non-epileptic seizures, a form of functional neurological disorder also called dissociative seizures. Now a fourth major trial can be added to the group. PRINCE Secondary is a recently published study of CBT to treat so-called “persistent physical symptoms” (PPS), another term for MUS. I blogged last month about how the investigators tried to present the trial as a success despite null results for the primary outcome.

These trials were the biggest in their domains to date. In each case, the investigators published trial protocols, which cited evidence from earlier research supporting their approach and generally presented the proposed study as the essential next step in obtaining authoritative information for guiding clinical care and/or public health policy. All four were centered at leading UK universities—PACE at Queen Mary University of London and the other three at King’s College London. And they were all based on the same unproven biopsychosocial hypothesis—that symptoms were perpetuated by unhelpful cognitions, excessive focusing on somatic sensations, and related psychological factors. The CBT interventions were said to be designed specifically to target the faulty perceptions presumed to be perpetuating the symptoms in each condition.

What is remarkable about this quartet of trials is that the evidence is pretty clear: CBT did not work as intended in any of them. But you wouldn’t necessarily know that from the papers, which all claimed success to one degree or another. In none of the studies did the poor findings lead the investigators to raise serious questions about the appropriateness of the interventions or the robustness of the theoretical assumptions behind them. Instead, all four studies engaged in methodological and/or statistical gymnastics to avoid having to conclude or at least consider the possibility that CBT might not be an effective intervention after all.

There is significant overlap among the investigators in these four studies, as there is among the strategies deployed to downplay and/or obscure the exceedingly modest or null results. The studies also share an overall design problem—they are unblinded to participants and rely on subjective outcomes for their claims of success. Therapeutic interventions are understandably difficult if not impossible to blind, which makes it all the more imperative for investigators to make sure to include some kind of objective measurements, not to mention adequate control groups. No less an authority than the Journal of Psychosomatic Research has noted in a recent commentary that subjective outcomes in studies in which blinding is not rigorous are at increased risk of bias. Any such findings must therefore be interpreted with that limitation in mind.

(For more on the MUS mess overall, read Goodelf’s series of posts on the Opposing MEGA blog, starting with this one. Also, Dr Keith Geraghty has taken a hard look at the CBT model of chronic fatigue syndrome and found it wanting; I was a co-author on this paper.)


Turning Bad Results into Positive News

Here is a brief summary of how investigators in these studies managed to turn unappealing results into positive news:

*In PACE, the investigators weakened their assessment methods with rampant outcome-switching, enabling them to report modestly attractive results in favor of their interventions. They ignored or dismissed the null or minimal results of their own objective measures. Subsequent re-analyses based on data that were released under court order revealed that the results per the methods outlined in the protocol were either null or easily within what would be expected by bias inherent in the study design. At long-term follow-up, the authors prioritized “within-group” comparisons over the “between-group” comparisons that are of interest in a clinical trial—another form of outcome-switching. A commentary accompanying the publication of the initial results, written by colleagues of the investigators,  amplified the questionable claims of success.

*The ACTIB trial tested both telephone CBT and web-based CBT. For the latter, results for both of the study’s two co-primary outcomes—a symptom severity scale and a work and social adjustment scale–were below the identified thresholds for clinical significance. The investigators did not highlight this information. (The telephone CBT fared a bit better across the board.) King’s College London, which touted the findings in a press release, has licensed the web-based CBT program to a private company. The company has received approval to market the program in the US and UK. It will presumably be promoted as “evidence-based.” At least two of the investigators have declared a financial interest in the program. At long-term follow-up, the results for web-based CBT were even worse on both measures.

*The CODES trial tested CBT for psychogenic non-epileptic seizures, also called dissociative seizures. At 12 months, the trial reported null results for its primary outcome—in fact, it found a non-statistically significant trend toward greater seizure reduction in the non-intervention group. The investigators touted instead several of their secondary outcomes, most of them vague and non-specific to the condition.* [Correction: In this sentence, I wrote initially that they touted “a minority of” their secondary outcomes. In fact, nine out of 16 secondary outcomes had statistically significant findings, although only five were statistically significant after correcting for multiple comparisons.] After years of promoting seizure reduction as the appropriate primary outcome, they argued unconvincingly in CODES that other outcomes besides seizure reduction were likely more important to patients. In an accompanying commentary, a friendly colleague defended CBT based on his own clinical experiences and reinforced the trial’s effort to downplay the null results from the primary outcome. King’s College London issued a press release that hailed the study’s findings but did not mention that the primary outcome had null results.

*The Prince Secondary trial found no benefits at 12 months for its CBT intervention on the primary outcome measure—the same work and social adjustment scale used in the ACTIB trial. In fact, the entire confidence interval for the results on this scale fell under the threshold for clinical significance for that measure. The conclusion of the abstract did not mention the null results of the primary outcome but focused on very modest improvements in a minority of the secondary outcomes. The investigators suggested that these reported benefits, which would have disappeared if subjected to the standard conservative method of correcting for multiple comparisons, indicated “preliminary evidence” that CBT might be “helpful.” This conclusion ignored the fact that the trial was designed to provide definitive and actionable evidence related to efficacy, not more “preliminary” data requiring further research.

A review of this collection of trials indicates that all of them have benefited from one or more of the following strategies:

*claiming success based on secondary outcomes
*ignoring/dismissing objective findings
*prioritizing results that are not corrected for multiple comparisons
*misinterpreting minimal or null results at long-term follow-up
*being accompanied by a friendly commentary that amplifies the claims of success
*being promoted in a positive light by university public relations departments

Looking beyond the UK, a 2017 study from a team of Dutch investigators could fit in with this group—a large trial of CBT for prolonged fatigue after an acute bout of Q fever, a bacterial infection. (The trial also investigated a regimen of antibiotics.) This fatigue would indisputably fall into the MUS category; the investigators cited CBT’s purported success in treating CFS as the rationale for the trial. Modest reported benefits for CBT at the end of the treatment wore off by the one-year follow-up. A robust critique of the trial, which was published last year, outlined serious methodological issues and undermined any claims of CBT’s effectiveness. (More on this interesting trial later.)





9 responses to “Quartet of Trials Reveals Limitations of CBT for “Medically Unexplained Symptoms””

  1. Barbara McMullen Avatar
    Barbara McMullen

    With their top drawer ability to spin bad results, they deserve an honourary degree in Public Relations.

  2. tugrus Avatar

    Their efforts remind me of the Sir Humphrey Appleby character. Experts in spin & deception while smiling & sounding plausible to the non-experts.

  3. Rigmor Avatar

    Could it be that there is (partly) a gender aspect to the theories these people are promoting? I ask because this reminds me of earlier times’ focus on womens tendency to hysteria…

  4. CT Avatar

    Many thanks for highlighting and clearly summarizing this important issue.

    I think it’s important to say that the vast majority of ME patients, advocates and campaigners wouldn’t be against ME or MUS patients trying CBT if those patients felt it could help them in any way. But CBT doesn’t replace chemotherapy and radiotherapy for cancer patients and it shouldn’t replace biomedical treatments and approaches for ME or MUS. It should definitely not be employed to persuade patients that their symptoms are “perpetuated by unhelpful cognitions, excessive focusing on somatic sensations, and related psychological factors.” OK, so the BPS crew would say that there aren’t any biomedical treatments for ME yet so their CBT (plus GET) is all that’s currently available, but that’s because research funding has been wasted on way too much psychological research that has set biomedical advancement back by decades. This urgently needs to change.

    Also, if traditional CBT is supposed to work so well then why the recent shift towards ACT (Acceptance and Commitment Therapy)? If it’s not broken, why fix it? Why not stick to what (supposedly) works? [eg ACT is raised in this report about the CODES trial -https://www.journalslibrary.nihr.ac.uk/hta/hta25430#/s6 under “Recommendations for future research”.] They seem to just keep on trying to make their square peg therapies fit round hole problems.

    Rigmor writes above:

    “Could it be that there is (partly) a gender aspect to the theories these people are promoting? I ask because this reminds me of earlier times’ focus on womens tendency to hysteria… ”

    I’m not sure if it’s the theories per se or the mindset, (considering point 4 in the ‘Despicable MUS: …’ post by Goodelf -https://opposingmega.wordpress.com/2020/10/19/despicable-mus-document-leads-uk-healthcare-commissioners-up-a-perilous-garden-path/ ).

  5. Peter Trewhitt Avatar
    Peter Trewhitt

    The effective use of CBT depends on achievable objectives being agreed between the practitioner and the client. In a sense CBT is a neutral tool, dependent on content relevant to the situation.

    However, with PACE type CBT for ME or MUS, the content its supporters advocate is at odds with both mist clients’ subjective reality and current scientific understanding. The goal of using talking to cure ME or the various conditions lumped together under the unhelpful MUS umbrella is based on unevidenced beliefs and simply does not work. Using CBT to effectively try to convince the clients they are deluded, when what evidence we have contradicts this characterisation, is pure gaslighting.

    As David’s blog indicates, the very research held up to support this approach if objectively analysed is rather evidence that it does not work.

    It may be that CBT with more appropriate content or objectives has a role in helping people live with their currently untreatable life limiting conditions, for example I personally undertook a course of CBT aimed at helping me accept the limitations on what activity I could do, to overcome my unhelpful resistance to pacing myself, however so far we have no research relevant to how CBT might help people manage their activities within their current capabilities or to adjust psychologically to the limits placed on them by their condition.

    CBT aimed at treating an underlying condition such as ME simply does not work, and so far we have no evidence relating to its use as a tool for psychological support or adjustment to a life limiting condition such as ME. It could be argued that evidence for its benefit in other situations might justify its speculative trialing in this context, though, even if that evidence is stronger than the papers discussed in the above blog, it should be remembered that such is speculative. Its use currently should not be automatic rather restricted to those who understand these limitations but still feel it might be helpful in their specific circumstances.

  6. CT Avatar

    Put so well, thanks Peter.

  7. SusanC Avatar

    A couple of thoughts after reading some of the PNES literature:

    – patients can lose consciousness or have involuntary motor movements for a variety of different reasons, of which epilepsy is only one
    – doctors seem to have difficulty with differential diagnosis. Complicating factors include
    – epilepsy, as confirmed by EEG, can present in a variety of different ways. So without an EEG, it’s hard to say for sure that some unusual symptom isn’t epilepsy
    – doctor often has to rely on the patients self report of the seizure, as doctor was not present to witness it
    – patients might not be all that good at describing episodes of unconsciousness. It might, by its very nature, be hard to describe

    I don’t have epilepsy or PNES. Nearest I’ve come recently to that kind of experience is my reaction to the Astra Zeneca vaccine. That the reaction occurred after a vaccine shot, and not at any other time (well, except another time when I went down with cellulitis, which seemed to cause a similar reaction) might be considered very strong circumstantial evidence against it being due to epilepsy (vasovagal syncope or PNES triggered by situational stress vs some kind of physical reaction might be a closer call to diagnose). Now, if someone were to ask me to describe it for diagnostic purposes… well, no idea. Next thing I know I’m regaining consciousness, I’m on the floor, I can’t stand back up on my feet due to pain in my knee joints, I have a temperature measured as being 100F, no respiratory difficulty, no skin rash. What did it feel like before that .. no idea.
    (p.s. I was fine a couple of days later, and the experience wasn’t all that bad.)
    (P.p.s mods, feel free to delete this post if you think it’s something I shouldn’t say)

    Which is long winded way of saying: getting patients to describe the experience of other forms of consciousness loss for diagnostic purposes might be equally hopeless.

  8. SB Avatar

    David, worth reminding ourselves this is primarily about extra money for psychiatry and psychology. In the UK most doctors do not believe ME/CFS even exists and is simply a psychiatric disorder and they send patients on CBT so they can say they did something whether it works is irrelevant. CBT in medical terms is quite cheap so no one is interested in the trials issues they are simply adverts. Its quite clever really.

  9. Jules Lewis Avatar
    Jules Lewis

    I find it very concerning that IAPT in England (I’m unclear about the other UK countries) is now being used to treat both MUS and Long Term Conditions…