By David Tuller, DrPH
When the PACE trial was published in early 2011, my New York Times editor sent it to me, along with the press release. As a non-staff contributor to the Times, I had started covering the debate over the mouse retrovirus hypothesis and science, but I’d heard nothing about anything called PACE or graded exercise therapy. I got a few hours to whip something up for the next day’s news coverage. Knowing nothing, I reported the findings as best I could. Unfortunately, I took them more or less at face value.
As I learned more about the trial and read comments from patients and others, I realized I’d screwed up. A couple of months later I wrote another story—about case definition as a tool in epidemiology, and the complications that can arise when case definitions vary. The article discussed the Oxford criteria used in PACE but failed to mention subgroup analyses of trial participants also defined using the Fukuda criteria and a separate ME case definition. That omission prompted a request for a correction from the PACE principal investigators.
If a patient is experiencing multiple symptoms, the Oxford criteria require that fatigue be the primary one. Neither Fukuda nor the ME case definition used in PACE include that requirement. For a CFS diagnosis under Fukuda, your primary symptom could be cognitive dysfunction or PEM, not fatigue. The ME definition also didn’t require the primary symptom to be six months of fatigue. Given this mismatch, it can’t be assumed that every person who would meet the other two definitions would have been screened in with the Oxford criteria; an unknown number would have been screened out.
Instead of running a correction, my Times editor allowed me to respond to the concerns raised by the PACE investigators. Below is their letter, and my response. This exchange ran on March 14, 2011. At that time, the PACE investigators were touting the “robust” evidence favoring CBT and GET for patients with CFS and ME, “however the illness is defined.”
To the Editor:
In “Defining an Illness Is Fodder for Debate” (March 8), your reporter David Tuller correctly noted that the way an illness is defined can often determine what is found in studies of it. He also suggested that this problem of definition had limited the interpretation of our trial of treatments for chronic fatigue syndrome, published recently in The Lancet. That is not the case.
The patients in this trial had a disabling chronic illness in which fatigue was their main symptom and for which no alternative had been found; that is the definition of the syndrome used in Britain. But we also assessed trial participants to see if they met two other definitions of the illness that are favored by some scientists.
We found that both cognitive behavior therapy and graded exercise therapy, when added to specialist medical care, were most effective not only in the whole sample but also in the participants who met these alternative criteria. In addition, these treatments were the most effective whether or not a patient was depressed, a not uncommon accompaniment to this chronic and misunderstood illness. The trial also found that these treatments were safe so long as they were provided by appropriate therapists trained to help patients with chronic fatigue syndrome.
So to Mr. Tuller’s question “Does the evidence from that study prove that these strategies would help patients identified as having chronic fatigue syndrome through very different criteria?,” the answer is “Yes, it does.” Patients and their doctors now have robust evidence that there are two safe treatments that can improve both symptoms and quality of life, however the illness is defined.
P. D. White
London and Edinburgh
The writers are the principal investigators of the PACE trial.
David Tuller replies: The article asked whether findings among a population defined by one set of criteria would apply to populations defined by “very different criteria.” In this study, all participants were first defined, identified and selected not by different criteria but by the same criteria, the so-called Oxford criteria used in Britain. Subgroups within that already screened population who also meet secondary criteria are not easily compared to patients who have not been screened, since an unknown number who met the secondary criteria might not have met the study’s criteria for inclusion. The gold standard for making comparisons across groups of patients identified by three varying case definitions would be a study with three completely separate cohorts, not one large sample with two embedded subgroups.