In “PACE Trial Results Misleading: Part I – Background,” I discussed the media coverage of the study's results and the disturbing history behind the UK's PACE trial. Now we'll take a look at some of the specific problems with the study itself.
In all the years I've been reading research reports, I don't think I have ever seen a more poorly constructed or biased study. It is so bad that a year before the study results were published, Dr. Malcom Hooper, Emeritus Professor of Medicinal Chemistry at the University of Sunderland, wrote a 442-page paper outlining in great detail the flaws in the study's premises and design. His concerns were based on the manuals to be used in the trial, minutes of meetings between Investigators planning the trial and other trial-related documents – all obtained under the Freedom of Information Act. He titled his paper “Magical Medicine: How to make a disease disappear.”
A False Premise
Ignoring all of the scientific evidence to the contrary, the study was designed around the premise that ME/CFS (or CFS/ME according to the study) is a behavioral disorder and that patients have the potential for full recovery using CBT and GET. Since the alleged purpose of the study was to compare the effectiveness and safety of four different treatments, presupposing that two of the treatments are highly effective goes against all accepted scientific principles.
Evidence that the PACE trial was designed to get a predetermined set of results was demonstrated in the recruitment of patients for the trial. There were multiple recruitment tactics that did not follow sound scientific principles:
- The Oxford criteria were used, which excludes people with neurological disorders. Since ME is classified as a neurological disorder, there is an obvious problem.
- Another problem with the Oxford criteria is that it is likely to include a large percentage of patients who have a primary psychiatric diagnosis.
- The most severely affected ME/CFS patients were excluded from the trial.
- In one of his recruitment appeals to general practioners, lead study author Professor Peter White, asked them to refer anyone “whose main complaint is fatigue (or a synonym).”
Based on these inclusions and exclusions, it is doubtful that many of the participants actually even had ME/CFS.
There were no objective measures used to evaluate outcomes, as is necessary in sound scientific research. The original protocol included an actigraphy test, which measures rest and movement over time. Several thousand pounds was spent purchasing the equipment, however, it was dropped from the final protocol, which leaves us to surmise that the study designers didn't think the actigraph would yield the results they were looking for.
In the end, only subjective measures were used to evaluate the results. The participants self-reported how they were feeling by answering questionnaires. Since in two of the treatment arms (CBT and GET) patients were specifically encouraged to re-interpret their symptoms as normal responses to exercise rather than as disease symptoms, there is a good chance that their answers were less than accurate descriptions of how they felt.