It is difficult to know where to start when it comes to the PACE trial given what we now know.
Do we start with the conflicts of interests of the authors?
‘I can confirm that I was aware of the potential for competing interests that you have stated. The roles that Professor White, Professor Sharpe and Professor Chalder have undertaken for the agencies and companies that you stipulate (i.e. the DWP and the medical and permanent health insurance industry) were in the public domain prior to the publication of the NHS Plus guideline.’ Dr Ira Madan, Director of Clinical Standards, NHS Plus (who, with Wessely and Chalder, was based at King’s College)
- or the methodological failings?
Subjective outcomes for an unblinded trial leads to bias. Moreover sending a newsletter midway through the trial to patient participants saying how well graded exercise therapy and cognitive behavioural therapy work increases that bias, it is also unethical and goes against all tenets of what is regarded as acceptable in scientific research.
‘..so profoundly flawed that it cannot be trusted.’ Mike Godwin
‘..multiple flaws that are inexcusable…the PACE Study is a sham, with meaningless results. In this case, the emperor truly has no clothes.’ Professor Vincent Racaniello (professor of Microbiology and Immunology at Columbia University).
- or the outcome switching with no justification mid-trial?
- or breaching the Declaration of Helsinki with which they stated they would comply in the PACE protocol, meaning trial participants were unable to give informed consent?
- or their strange ‘normal range’ for physical function that enabled patients to enter a trial and get worse but still be deemed ‘recovered’, with said recovery demonstrating physical function at a level usually associated with an octogenarian or someone with heart failure?
‘I have never seen a trial design where eligibility requirements for a disease alone would qualify some patients for having had successful treatment’ Dr Bruce Levin (professor of Biostatistics at Columbia University Mailman School of Public Health).
- or that they recruited patients based on the flawed Oxford criteria?
These problems have been extensively examined by Dr David Tuller (Senior Fellow in Public Health Journalism) on virology blog after patients notified him of the flaws and are available here. Tuller arranged for a signed open letter to be delivered to The Lancet journal calling for an independent review of PACE. The Journal of Health Psychology has also published a special PACE edition collating papers detailing the issues outlined above. The PACE trial is now used as an example of how not to conduct a trial in universities and text books.
Queen Mary University of London have spent approximately £250,000 trying to keep data from the PACE trial hidden, however a Freedom of Information request by ME patient Alem Mathees resulted in a tribunal that ruled in patients’ favour and the data was released following a decision by the information commissioner’s office. This enabled a reanalysis of PACE to be conducted that concluded:
‘These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.’ Wiltshire et al.
Recently, Cochrane announced that one of its reviews into ME/CFS would be withdrawn because of similar issues to PACE, however this caused a surge in media activity by the BPS lobby, including Professor Sir Simon Wessely’s wife, Dr Clare Gerada (ex president of the Royal College of GPs). This included a Reuters article and a Guardian podcast from Prof Sharpe, an author of the PACE trial, in which BPS proponents were able to promote their views virtually unchallenged (as is often the case in the British media). This campaign by BPS supporters resulted in Cochrane issuing a note that the authors have until November to respond to concerns. We are yet to see a withdrawal.
Nevertheless, there is little support left for the BPS paradigm that CBT and GET is useful in treating ME patients, save from those with financial and reputational interests in seeing it continued. Unfortunately, in the UK at least, such vested interests still enjoy considerable influence, clearly demonstrated by the composition of the NICE committee reviewing the efficacy of GET and CBT as therapies for ME.
‘That the Pace Trial continues to be so doggedly defended, despite a litany of damaging critiques, shows us how psychologists can retain an unswerving allegiance to their own ideas’ Professor Brian Hughes.