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A 2011 <i>The Lancet</i> paper examining treatments for chronic fatigue syndrome is still causing controversy.

A 2011 The Lancet paper examining treatments for chronic fatigue syndrome is still causing controversy.

The Lancet

Criticism mounts of a long-controversial chronic fatigue study

The authors of a controversial 2011 trial that showed that exercise and behavioral therapy could help treat chronic fatigue syndrome (CFS) today released a follow-up study that supports their original findings. But the new report comes on the heels of a lengthy and highly critical examination of the original trial by a journalist.

At issue is an $8 million trial run in the United Kingdom, dubbed PACE, which examined a number of treatments for CFS, a disease also known as myalgic encephalomyelitis (ME) that has no known cause. In The Lancet, the PACE researchers reported that patients with CFS/ME experienced “moderate improvements” in their symptoms if they did a program of graded exercise or cognitive behavior therapy. Two other interventions tested, so-called specialist medical care and adaptive pacing therapy, did not help.

The Lancet study drew immediate fire from patient groups, with some complaining that it appeared to suggest that CFS/ME is a psychological, rather than physical, disorder. Many researchers, meanwhile, argued that some of the study’s methods were seriously flawed. As The Lancet itself noted in an editorial a few months after publishing the 2011 study, the “response to the trial’s publication was swift and damning.”

On 21 October, journalist David Tuller, who helps oversee a journalism program at the University of California (UC), Berkeley, published the first installment of a four-part series re-examining the trial. The series, “Trial by Error,” appears on the virology blog run by Columbia University microbiologist Vincent Racaniello.

Tuller writes that after the PACE results were published, people with CFS/ME “bristled with offense at the suggestion they would get better if only they could change their perceptions about their condition.” And “pushing themselves to be more active not only wasn’t helpful, they insisted, but could trigger a serious and extended relapse.”

Tuller quotes several scientists lambasting the PACE study for everything from its methodology and outcome measures to alleged conflicts of interest involving its authors. He reports that the authors did not reply to his inquiries. Comments about his series are flooding websites run by CFS/ME groups.

The authors of the PACE study today added fuel to the fire, releasing an online paper in The Lancet Psychiatry that reports on a long-term follow-up of trial participants. It concludes that the benefits of the interventions were maintained.

In the follow-up, a team led by psychiatrist Michael Sharpe of the University of Oxford in the United Kingdom sent questionnaires to 604 of the trial participants and asked them to self-rate their health. The 481 participants who responded reflected a statistically valid sample of the patients who received the four interventions.

After analyzing the responses, the researchers concluded that the benefits reported in the original study, which assessed participants at 1 year, were maintained for at least another 1.5 years. But the participants randomized to receive the two interventions that initially did nothing also improved, and there “was little evidence of differences in outcomes” when compared with the people in the other treatment groups. The authors suggest that this is because the people in the ineffective groups later decided to seek out graded exercise and cognitive behavior therapy.

“These are not magic cures,” said Sharpe at a press conference in London today. “This is just the only game in town really in terms of an evidence-based treatment if you have got this condition to get yourself improved.”

Rona Moss-Morris, a psychologist at King’s College London who was not involved in the study, said, “I think this is a robust study with some limitations that the authors have been clear about.”

But in Tuller’s takedown of the PACE study, Arthur Reingold, an epidemiologist at UC Berkeley, is sharply critical of the original trial’s design. “Under the circumstances, an independent review of the trial conducted by experts not involved in the design or conduct of the study would seem to be very much in order,” Reingold asserts. University College London Neurologist Jonathan Edwards told Tuller that the PACE data are “a mass of uninterpretability” and said “the issues with the trial are extremely worrying.”

At the press conference, Sharpe said he doesn’t think there’s “a growing army of people upset about this,” and he stressed that their findings are not suggesting that CFS/ME is a mental illness. “It’s sometimes quite hard to understand what motivates the very vocal minority that gets so upset about this apparently benign bit of moderately helpful treatment,” he said.