Letter to Medical Research Council’s Fiona Watt about 2018 defence of the PACE Trial (July 2021)

Yesterday I wrote to Professor Fiona Watt, Executive Chair of the UK’s Medical Research Council

It was to follow up on her statement in response to an open letter to The Lancet, signed by more than 100 experts, ten members of Parliament, and 70 patient and advocacy organizations.

19 July 2021

Dear Professor Watt

I am writing in a personal capacity, not as a representative of my employer.

I am following up on your statement of August 2018 and letter to the Times about criticism of the PACE Trial.  You rejected the view that the scientific evidence provided by the trial for using cognitive behavioural theory and exercise therapy in the treatment of ME/CFS was unsound.

Cochrane reviews as “gold standard”

You said in your statement that while “…most of the criticism focuses on the PACE trial, there is a large amount of evidence from other studies that also shows CBT and graded exercise therapy (GET) can be helpful to some CFS/ME patients…This evidence is summarised in three Cochrane reviews…. internationally recognised as the gold standard in evidence-based healthcare.”

One of the three reviews, Traditional Chinese medicinal herbs for the treatment of idiopathic chronic fatigue and chronic fatigue syndrome, was withdrawn in October 2018 and did not summarise the evidence for CBT and Graded Exercise Therapy.

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review Cognitive behaviour therapy for chronic fatigue syndrome in adults now has an editorial note on it saying it is out of date, will not be updated, and should not be used for clinical decision-making.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

The most recent independent evidence review is from NICE which published its draft updated guideline on the diagnosis and management of myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome (ME/CFS) in November 2020.  In the evidence review of non-pharmacological treatments the reviewers reported they could not use the Cochrane reviews of CBT and Exercise because they did not include all critical outcomes specified in the NICE protocol, and included study populations where not all participants had ME/CFS.  They also judged the trial evidence for CBT and GET (including that from the PACE trial) as low or very low quality.  In other words unsound.

NICE has therefore updated its 2007 recommendations on the use of psycho-behavioural treatments for ME/CFS, concluding that Graded Exercise Therapy (GET) should no longer be offered to patients and that Cognitive Behavioural Therapy (CBT) is not a treatment or cure for ME/CFS.

Supporting PACE triallists with their data sharing obligations

Later in the statement you say that the “….MRC has recently started (with other research funders) a pilot of a new facility for academic researchers to share data via the Clinical Study Data Request (CSDR) web portal. We hope to include the PACE trial on the CSDR portal within the next 6-12 months. This will allow researchers to apply to the CSDR Independent Review Panel to gain access to the dataset for their own analyses.

We are currently supporting the PACE trial investigators to anonymise the study data from over 600 participants so that it can be made available to other researchers in a way that protects the privacy of those patients who took part.”

It is nearly three years since you said you were supporting the PACE triallists to anonymise the study data in order to share it.  However, I would have hoped that such eminent and experienced investigators would not need your support to anonymise data, which is standard practice in clinical trials, in order fulfil their ethical data sharing obligations.  Please can you let me know why, despite your support, the anonymised data from the PACE trial has not been included in the CSDR portal within 6-12 months as you had intended?  Any correspondence between you and the investigators which could explain this disappointing outcome would be welcome.

With best wishes

Caroline

Caroline Struthers
Senior EQUATOR Research Fellow
UK EQUATOR Centre
Centre for Statistics in Medicine
NDORMS – University of Oxford
Botnar Research Centre
Old Road, OX3 7LD
Oxford, United Kingdom