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.
Then the researchers devised their own scale to measure the significance of the responses. They also conveniently redefined the meaning of the word “recovery” so it was no longer limited to the standard definition of regaining health after an illness.
It appears that trial therapists were taught to mislead participants. The therapists were told that there was no underlying pathology in CFS/ME. In other words, it is a psychological/behavioral disorder. However, the therapists were then instructed to assure participants that they believed their illness is “real” and to show empathy.
Other tactics, such as sending birthday cards to participants and encouraging them to share their threatment successes in a trial newsletter, were used to create a feeling of warmth and empathy that would help “maintain participation” in the trial. It could be argued that these tactics may have put psychological pressure on the participants to report more positive results that they were actually experiencing because they didn't want to disappoint the therapists who seemed to care so much for them.
Conflicts of Interest
Many of the Principal Investigators, including the lead Investigator Professor White, have financial links to the health insurance industry and a vested interest in the results of the trial.
In My Opinion...
Given the history behind the PACE trial and the multiple flaws in the trial itself, it doesn't take much of a leap to conclude that the desired results were determined first, then a trial was designed that would give those results.
What bothers me most about this study is that it can potetially cause great harm to patients.
- The 250,000 ME/CFS patients in the UK may be denied needed medical care because their illness is thought to be psychological and not biological.
- Despite the fact that many patients are incapacitated by ME/CFS, they could be denied disability benefits because officials think they just are not pushing themselves hard enough.
- CBT treatments may discourage patients from seeing medical care for their symptoms because they are told their symptoms are not real – they're just disordered thinking.
- GET is known to cause a worsening of symptoms for approximately 50% of ME/CFS. In some cases, this could lead to severe, even fatal, consequences.
- Governments and health insurance companies around the world may be tempted to use the PACE trial results as justification for denying medical treatment to ME/CFS patients.
The study flaws I've listed barely scratch the surface of all the problems and inconsistencies in the PACE trial. For a much more in-depth analysis, download and read Professor Hooper's paper “Magical Medicine: How to make a disease disappear.” I know it is a very long paper – not something you will likely read in one sitting. But the revelations it contains are incredible, albeit sometimes shocking. Within the paper, Hooper also ennumerates many of the biological abnormalities found in ME/CFS patients, which can be a useful tool for you and your doctor as you seek answsers and treatments for your own illness.
White PD, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Mar 5;377(9768):823-36.
Hooper, Malcom. Magical Medicine: How to make a disease disappear. University of Sunderland. February 12, 2010.
Published On: April 30, 2011