What’s wrong with the PACE trial anyway?

Empty shoes lined up on the groun, with a red Millions Missing poster alongside it
Photo from a Millions Missing protest, which takes place around the world every May to draw attention to the plight of ME/CFS patients

What is ME/CFS?

ME/CFS is a chronic illness that affects the immune, endocrine, and nervous systems, and for which there is currently no cure. It commonly begins after a virus, and of the 15–30 million sufferers worldwide, 25% are housebound or bedbound, and 75% are unable to work.

What is the PACE trial?

The PACE Trial was a trial of behavioural and psychiatric treatments for ME/CFS, which examined 641 patients. The researchers compared standardised specialist medical care (SMC) alone, to SMC plus either Adaptive Pacing Therapy, Cognitive Behavioural Therapy, or Graded Exercise Therapy.

Funding, Timeline, and Design

The PACE trial cost £5 million, and to date it is the most expensive and influential piece of research into ME/CFS ever conducted.

Initial Impact in Medicine and the Media

When the first PACE trial paper was published in 2011, researchers Professor Michael Sharpe and Professor Trudie Chalder held a press conference, in which Professor Chalder claimed:

Campaign and Tribunal

Despite its lauding by the trial authors and in the press, the results of the PACE trial directly contradicted many decades of patient experience, in which exertion was found to cause profound and sometimes permanent worsening of symptoms.

Criticisms of the Study Data

Once the data was finally released, criticisms of the way the PACE trial was conducted came from all quarters. The full PACE data led to over 40 scientists writing to The Lancet to raise serious concerns about the study, and asking for a new independent analysis of the results to be carried out.

“The authors have not been meticulous in trying to avoid bias that might arise. On the contrary, they appear to have acted in ways more or less guaranteed to maximise bias.”

Among the many critiques, the most damning fall into the following categories:

1. That the authors used the Oxford Criteria to select trial patients

The Oxford Criteria is an out-of-date set of diagnostic criteria for the diagnosis of Chronic Fatigue Syndrome, which was established by a group made up of mostly psychiatrists (including PACE trial author Professor Michael Sharpe) in 1991.

2. The authors changed their criteria for effectiveness half-way through

Partway through the trial the authors introduced post-hoc “normal ranges” for fatigue and physical function. These ranges have been heavily criticised for having thresholds so low, that patients could theoretically worsen during the trial, and yet still be within these “normal” ranges of fatigue, and therefore marked as recovered.

3. Use of subjective main outcome measures

The PACE trial is further criticised for having subjective primary analyses in an unblinded trial. Subjective measures are known to be susceptible to bias, which can arise from patient expectations and social pressure, either knowingly or unknowingly exerted by the researchers.

During the trial, the CBT and GET groups, but not the others, were told that there was nothing to stop them from recovering if they gradually increased their activity.

Critics have argued that these different expectations could have inflated patient’s self-assessments at the end of the trial, compared to the groups that weren’t told that they were going to recover, and therefore perceived less expectation of recovery from the researchers as a result.

4. Conflicts of interest and lack of informed consent

The 42 scientists and clinicians who initially wrote the open letter to The Lancet, criticised the authors’ failure to disclose a potential conflict of interest to trial participants.

“The main investigators have had financial and consulting relationships with disability insurance companies, advising them that rehabilitative therapies like those tested in PACE could help ME/CFS claimants get off benefits and back to work.

“They disclosed these insurance industry links in The Lancet but did not inform trial participants, contrary to their protocol commitment. This serious ethical breach raises concerns about whether the consent obtained from the 641 trial participants is legitimate.”

Impact on Patients

Far from being a set of harmless behavioural interventions which are at best curative, and at worst useless, an initial survey conducted in 2012 by the ME Association showed that 74% of patients had their symptoms worsen after a course of GET.

Current Guidelines

Following the PACE trial controversy, in 2019, MP Carol Monaghan brought the plight of ME/CFS patients to Parliament.

Why does this matter for Long Covid?

While many Long Covid patients have testable damage to their internal organs following severe infection and hospital admittance, an ever-growing subset of sufferers experienced milder acute symptoms, but nevertheless developed troubling chronic problems afterwards. This follows the same pattern repeated in ME/CFS patients over many decades, who initially experienced glandular fever/mono, the flu, swine flu, an enterovirus or a respiratory virus, and subsequently became chronically unwell.

Disabled freelance journalist and copywriter. Words on feminism, disability, books, and healthcare — probably. Twitter @TinyWriterLaura

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