Trial By Error: Tack and I Write to Psych Medicine; Struthers Writes to Medical Research Council

By David Tuller, DrPH

A recent study of cognitive behavior therapy (CBT) for patients with “persistent physical symptoms” (PPS), a category alsocalled “medically unexplained symptoms,” reported null results for its primary outcome. These null results were not mentioned in the conclusion of the abstract, which instead focused on minimal reported benefits for a minority of secondary outcomes. This is not cool! The study was published in Psychological Medicine, a journal with close ties to the PACE investigators and other members of the CBT ideological brigades.

I have written a letter to the journal with Michiel Tack, an ME/CFS patient who comments incisively about research on his blog, ME/CFS Skeptic. In addition being submitted as correspondence, the letter has also been posted on a pre-print server. Most pre-print servers have functioned as venues for research, not for correspondence, but posting the letter seemed like a good idea.

In the past, I haven’t bothered much with submitting formal correspondence to journals. I’m not that interested in waiting for however long for editors to decide to publish it, or not. Also, journals seem to prefer to publish letters pointing out serious flaws in papers rather than actually correcting the serious flaws themselves. So instead I’ve mostly sent letters directly to editors about my concerns. Then I have posted the letters on Virology Blog or Facebook. Sometimes these interventions have generated an appropriate response; sometimes not. In contrast, the big advantage of formal correspondence is that, unlike blog posts–it becomes incorporated into the official scientific record, is indexed in databases, and can be cited.

The availability of the pre-print option essentially breaks some of the journals’ stranglehold over public debate. In the coronavirus era, pre-prints have become essential elements of the science communications eco-system. Submission to a journal no longer precludes simultaneously posting a paper, or a letter, to a pre-print server.

Here is part of our letter:

PRINCE Secondary was a randomized trial to test the efficacy and cost-effectiveness of therapist-delivered, transdiagnostic cognitive behavioural therapy (TDT-CBT) for patients with persistent physical symptoms (PPS). (Chalder et al., 2021) 324 PPS patients were randomized to receive either TDT-CBT plus standard medical care (SMC) or SMC alone. The trial’s primary outcome was the mean score on the Work and Social Adjustment Scale (WSAS) at follow-up assessment 52 weeks post-randomization. The trial also included several secondary outcomes.

In the conclusion of the abstract, the authors state that the trial provides “preliminary evidence that TDT-CBT + SMC may be helpful for people with a range of PPS.” This statement is misleading since it ignores the null findings of the trial’s primary outcome. Although the intervention group reported a modest benefit on the WSAS over the SMC group, it was not statistically or clinically significant. For the WSAS, the authors designated a reduction of -3.6. as a minimum clinically important difference (MCID). At 12 months, the mean for the intervention group was -1.48 points less than for the SMC group, with a 95 per cent confidence interval of -3.44 to 0.48. The confidence interval thus excluded what the authors had predefined as the MCID. This indicates that the trial was adequately powered to provide strong and actionable evidence of efficacy but that it failed to do so.

You can read the rest here.


A Letter to the UK’s Medical Research Council

Three summers ago, I organized an open letter about the PACE trial to The Lancet that garnered some attention. The letter condemned the trial’s “unacceptable methodological flaws” and requested a fully independent review of the data. More than 100 scientists, clinicians, academics and other experts from around the world signed the letter, along with ten members of Parliament and more than 70 patient and advocacy organizations.

The Times (UK) wrote an article about it. BMJ followed up with a short report on its own news site. The negative attention flushed out the UK’s Medical Research Council, the main funder of the PACE trial. Professor Fiona Watt, the MRC’s executive chair, issued a tepid defense of PACE that relied in part on the methodologically deficient Cochrane reviews of CBT and graded exercise therapy for ME/CFS. (In Cochrane’s framing, these are interventions for CFS.)

Caroline Struthers–a self-described “citizen scientist and patient-directed research enthusiast” who comments on twitter as @healthy_control–has been relentless in pushing Cochrane to be more transparent about the acknowledged problems with these reviews. Thanks to her persistence, Cochrane recently revamped its pages to make its own advisories about the reviews more visible to readers. Now she has taken the logical step of pointing out these and other recent developments to Professor Watt, in light of her 2018 defense of PACE.

Here are a couple of key paragraphs from Struthers’ recent letter:

The review Cognitive behaviour therapy for chronic fatigue syndrome in adults now has an editorial note on it saying it is out of date, will not be updated, and should not be used for clinical decision-making. Hardly gold-standard evidence.

The review Exercise therapy for chronic fatigue syndrome was amended in 2019 and has an editorial note linking to a news article acknowledging a whole new approach is needed.  Cochrane’s Editor in Chief says in the news article that the “… amended review is still based on a research question and a set of methods from 2002 and reflects evidence from studies that applied definitions of ME/CFS from the 1990s”.  Hardly gold standard either.

You can read the rest here.

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