The continuing trials and tribulations of PACE

I honestly hadn't intended talking about the PACE trial - "pacing, graded activity, and cognitive behaviour therapy: a randomised evaluation" in relation to chronic fatigue syndrome (CFS) - quite so much on this blog. Others have done it so much better than I ever could.

My interest however keeps being piqued in relation to the results originally produced suggesting that: "CBT [cognitive behaviour therapy] and GET [graded exercise therapy] can safely be added to SMC to moderately improve outcomes for chronic fatigue syndrome" and the subsequent myriad of voices quite unanimously suggesting that one perhaps needs to be a little careful with such sweeping generalisations (see here).

OK, for anyone new to this topic, below are a few of the previous occasions that it has been discussed on this blog in chronological order:

• Chronic Fatigue Syndrome and various factors (2014) (see here)
• Chronic fatigue syndrome and the detrimental application of the 'biopsychosocial model' (2016) (see here)
• PACE-gate! (2016) (see here)
• PACE trial recovery data and chronic fatigue syndrome (2017) (see here)
• PACE trial recovery data and chronic fatigue syndrome - a reply (2017) (see here)

I want to add a few more 'science references' to this issue because some important things are being discussed in the peer-reviewed domain, in the context that CBT and GET at the moment, are considered 'best practice' here in the UK and beyond when it comes to CFS. That may change in future times (see here) as it has in other parts of the world (see here) but that's where we are at the time of writing. I might add that the addition of new references to this post is a rather more descriptive thing minus too much additional commentary from me, and that the views represented are those of the authors. I wrote this post on 9 April 2017 so it is accurate up to that point.

OK, starting with the editorial from Keith Geraghty [1] mentioned in that PACE-gate! post, we have an authors reply to some of the points raised [2]. The main crux of the reply is to correct "misunderstandings and misrepresentations of the PACE trial." Next up was a paper by Leonard Jason [3] (someone with quite an impressive research track record when it comes to CFS) and some comments on the pacing intervention (adaptive pacing therapy, APT) used and "patient selection ambiguity." This is a particularly interesting paper because APT - "based on the envelope theory of chronic fatigue syndrome" where the symptoms of CFS are "not reversible by changes in behaviour" - did not hit the 'research spot' according to the original PACE trial results.

I want to next include the paper by Luis Nacul and colleagues [4] into proceedings, and a role for "selection bias and disease misclassification" when it comes to studies on CFS (and myalgic encephalomyelitis, ME). To quote from them: "When studies using the broad Oxford criteria... were excluded, a virtual disappearance of effect for graded exercise therapy (GET), cognitive behaviour therapy (CBT) and other psychological therapies recommended by the NICE guidelines (National Institute for Health and Care Excellence.. was revealed." Guess which criteria (among the many available) were used in the original trial?

Onward. The paper by Steven Lubet [5] titled: 'Investigator bias and the PACE trial' sets out quite an 'accusation' in that: "the PACE investigators “impartiality might reasonably be questioned”." This is a theme that crops up again shortly. The paper by Tom Kindlon [6] asked whether graded exercise in particular, could be thought of as 'safe and risk-free'? I set this question within the context that the original PACE trial did find that: "Non-serious adverse events were common" and GET did seem to produce the largest number of 'serious adverse effects' in number if not in participants.

Nearly there. Next up is the paper from Carolyn Wishire [7] who, when talking about "lively discussion", reports on various potential forms of bias in behavioural intervention studies using the PACE study as a kind of template. This author was the lead on the recent peer-reviewed commentary (open-access) re-analysing the 'recovery' data subsequently published in relation to the PACE trial. Then, we have the paper by Jonathan Edwards [8] who notes that the PACE trial represents a lesson in how research design needs to develop further when it comes to science in general. To quote: "The failure of the academic community to recognise the weakness of trials of this type suggests that a major overhaul of quality control is needed." And finally Charles Shepherd [9] provides further commentary on the PACE trial and a call for independent review.

And rest.

There is quite a lot to take in from those various publications and I don't doubt that this is not the last we are going to hear about the PACE trial. Allied to articles such as this one describing how: "Physicians used to dismiss the disease as psychosomatic" (past tense) it certainly would not out of place to suggest that there are still questions that need to be answered about the design and results obtained from the PACE trial and their applicability to the (very) wide CFS/ME population. To quote again from the paper by Edwards [8]: "If they are still ill [those diagnosed with CFS/ME], presumably these approaches have failed and the priority is to find something more effective." Wise words indeed.

To close, it's here... the first glimpse of The Last Jedi.

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[1] Geraghty KJ. ‘PACE-Gate’: When clinical trial evidence meets open data access. J Health Psychology. 2016. Nov 1.

[2] White PD. et al. Response to the editorial by Dr Geraghty. J Health Psychology. 2017. Jan 24.

[3] Jason LA. The PACE trial missteps on pacing and patient selection. J Health Psychology. 2017. Feb 1.

[4] Nacul L. et al. How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies? J Health Psychology. 2017. March 1.

[5] Lubet S. Investigator bias and the PACE trial. J Health Psychology. 2017. March 7.

[6] Kindlon T. Do graded activity therapies cause harm in chronic fatigue syndrome? J Health Psychology. 2017. March 20.

[7] Wilshire C. The problem of bias in behavioural intervention studies: Lessons from the PACE trial 2017. J Health Psychology. March 23.

[8] Edwards J. PACE team response shows a disregard for the principles of science. 2017. J Health Psychology. March 28.

[9] Shepherd CB. PACE trial claims for recovery in myalgic encephalomyelitis/chronic fatigue syndrome – true or false? It’s time for an independent review of the methodology and results. J Health Psychology. April 9.

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Edwards, J. (2017). PACE team response shows a disregard for the principles of science Journal of Health Psychology DOI: 10.1177/1359105317700886





White, P., Chalder, T., Sharpe, M., Angus, B., Baber, H., Bavinton, J., Burgess, M., Clark, L., Cox, D., DeCesare, J., Goldsmith, K., Johnson, A., McCrone, P., Murphy, G., Murphy, M., O’Dowd, H., Potts, L., Walwyn, R., & Wilks, D. (2017). Response to the editorial by Dr Geraghty Journal of Health Psychology DOI: 10.1177/1359105316688953