Who was included in the trial?
The original design of the study seemed poised to get some good answers. But problems started early during the recruitment process. It turned out to be more difficult to find appropriate patients who were interested in participating in the study than expected, and so the PACE researchers allowed patients with a higher level of physical function to enter the trial. This tweak was the first of many, each of which had the effect of improving measurements of success, regardless of how the patients fared.
Patients had to meet many criteria to be included in the trial, notably the following:
- Have chronic fatigue syndrome. Patients had to meet the Oxford criteria for CFS, which includes a broad range of people who feel very tired: Patients must suffer from severe and debilitating fatigue for over six months, and fatigue must be the main symptom of their problems. Depression, which can cause prolonged fatigue, was acceptable as a co-morbid condition, and was in fact quite common among the patients who were eventually included (33 percent). In addition, patients could not be diagnosed with another medical issue known to produce chronic fatigue, nor suffer from psychosis, bipolar disorder, substance misuse, an organic brain disorder, or an eating disorder.
- Have significant self-assessed fatigue. Fatigue was measured using the bimodal Chalder fatigue scale, which is discussed in some detail below. Patients had to score six or higher (out of 11) on this scale to enter the trial. The higher the number, the more fatigue a patient experiences.
- Have poor self-assessed physical function. Physical function was measured using the the short form-36 physical function subscale. For entry to the study during the first 11 months, one had to score 60 or below out of 100; this threshold was changed to 65 or below during the trial, to recruit more patients. The lower the score, the worse physical function a patient has.
- Be able to travel to the hospital for treatment. This simple rule immediately excluded some of the sickest patients from participating in the trial, thus making any results generalizable only to the more functional patients with CFS.
The first issue with these criteria, as Tuller noted
in the New York Times back in 2011 when he first started looking at PACE more closely, is their use of the Oxford definition, which requires no symptoms specific to the illness beyond fatigue. Most importantly, it doesn’t require the symptom that most experts consider the hallmark of the disease: the exacerbation of all other symptoms after exercise, or post-exertional malaise. It also doesn’t require other symptoms such as cognitive, sleep, or blood pressure regulation problems, nor neurological or immune problems. The Institute of Medicine cites
several of these as “core symptoms” for ME/CFS. As a result, many specialists worry that PACE includes patients who suffer from other fatiguing illnesses but not ME/CFS, as described by other standard criteria.