Lancet Psychiatry have published three letters criticising a paper published in the journal on the long-term follow-up results of the PACE trial. A response from the study authors was also published.
The paper, published in October, showed little difference in self-rated fatigue and physical function between the four treatment arms and thus no benefit of adding cognitive behavioural therapy (CBT) or graded exercise therapy (GET) to standard medical care. Despite the null result, the study authors claimed that the findings showed CBT and GET to be beneficial for chronic fatigue syndrome.
The first letter, by Professors James Coyne of the University of Groningen, Netherlands, and Keith Laws of the University of Hertfordshire, England, described the study as now “uninterpretable” due to patients having been encouraged by the study authors to cross to other treatments in a non-randomised way during the follow-up period. Coyne and Laws pointed out that, even regardless of this issue making between-group comparison impossible, the average physical function scores for all groups at long-term follow-up were poor, and similar to those of patients with lupus and Class II congestive heart failure.
The second letter, by Dr Charles Shepherd, Medical Advisor of the UK’s ME Association, pointed out the “anger and despair” expressed by patients in relation to the paper and its media coverage. He emphasised the mismatch between the the results claimed for the trial and an ME Association survey of over 1,400 patients in which 74% reported being made worse by GET. Without better evidence from PACE, he said, “the ME patient community will continue to regard the PACE trial as a tremendous waste of money”.
The third letter, from Frank Twisk, of the Dutch ME-de-patiënten Foundation, pointed out that the only evidence in PACE suggesting that the CBT and GET groups did better than the other groups was in better subjective measures at 52 weeks. But objective measures at 52 weeks contradicted these findings, he said, as did the lack of difference in even subjective measures at long-term follow-up.
In their response, led by Professor Michael Sharpe of Oxford University, the PACE authors defended their use of subjective measures, saying that “chronic fatigue syndrome is diagnosed by self-report” and that these self-ratings were thus “the best way to measure improvement”. The authors stated that an increase of 20 points out of 100 in self-rated physical function was of value to patients, even if the final scores were similar to those of patients with other serious diseases. They pointed out that their follow-up study was not “a continuation of the trial” but “a naturalistic follow-up after trial completion”.
Professor Sharpe and his co-authors said that there was “marked antipathy of some toward this study, apparent in the correspondence and elsewhere”. Professors Coyne and Laws, in their letter, said, “the PACE investigators have previously complained… of ‘the apparent campaign to bring the robust findings of the trial into question’. We think the further scrutiny that the follow-up study has brought casts further doubt on whether there ever were ‘robust findings’. The investigators should get more accustomed to rigorous post-publication peer review, which is not a campaign, but a reality of the 21st century.”
On Twitter, Professor Coyne described the authors’ reply as “non-responsive” and said, “PACE investigators went from calling critics ‘vexatious’ to claiming ‘marked antipathy.’ Nothing personal, critics just dislike junk science.”