TRIAL BY ERROR: The Troubling Case of the PACE Chronic Fatigue Syndrome Study (final installment)

By David Tuller, DrPH

David Tuller is academic coordinator of the concurrent masters degree program in public health and journalism at the University of California, Berkeley. 

A few years ago, Dr. Racaniello let me hijack this space for a long piece about the CDC’s persistent incompetence in its efforts to address the devastating illness the agency itself had misnamed “chronic fatigue syndrome.” Now I’m back with an even longer piece about the U.K’s controversial and highly influential PACE trial. The $8 million study, funded by British government agencies, purportedly proved that patients could “recover” from the illness through treatment with one of two rehabilitative, non-pharmacological interventions: graded exercise therapy, involving a gradual increase in activity, and a specialized form of cognitive behavior therapy. The main authors, a well-established group of British mental health professionals, published their first results in The Lancet in 2011, with additional results in subsequent papers.

Much of what I report here will not be news to the patient and advocacy communities, which have produced a voluminous online archive of critical commentary on the PACE trial. I could not have written this piece without the benefit of that research and the help of a few statistics-savvy sources who talked me through their complicated findings. I am also indebted to colleagues and friends in both public health and journalism, who provided valuable suggestions and advice on earlier drafts. Today’s Virology Blog installment is the final quarter; the first and second installment were published previously. I was originally working on this piece with Retraction Watch, but we could not ultimately agree on the direction and approach. 

After this article was posted, the PACE investigators replied, and in turn I responded to their criticisms. All the articles can be found at the ME/CFS page.

SUMMARY

This examination of the PACE trial of chronic fatigue syndrome identified several major flaws:

*The study included a bizarre paradox: participants’ baseline scores for the two primary outcomes of physical function and fatigue could qualify them simultaneously as disabled enough to get into the trial but already “recovered” on those indicators–even before any treatment. In fact, 13 percent of the study sample was already “recovered” on one of these two measures at the start of the study.

*In the middle of the study, the PACE team published a newsletter for participants that included glowing testimonials from earlier trial subjects about how much the “therapy” and “treatment” helped them. The newsletter also included an article informing participants that the two interventions pioneered by the investigators and being tested for efficacy in the trial, graded exercise therapy and cognitive behavior therapy, had been recommended as treatments by a U.K. government committee “based on the best available evidence.” The newsletter article did not mention that a key PACE investigator was also serving on the U.K. government committee that endorsed the PACE therapies.

*The PACE team changed all the methods outlined in its protocol for assessing the primary outcomes of physical function and fatigue, but did not take necessary steps to demonstrate that the revised methods and findings were robust, such as including sensitivity analyses. The researchers also relaxed all four of the criteria outlined in the protocol for defining “recovery.” They have rejected requests from patients for the findings as originally promised in the protocol as “vexatious.”

*The PACE claims of successful treatment and “recovery” were based solely on subjective outcomes. All the objective measures from the trial—a walking test, a step test, and data on employment and the receipt of financial information—failed to provide any evidence to support such claims. Afterwards, the PACE authors dismissed their own main objective measures as non-objective, irrelevant, or unreliable.

*In seeking informed consent, the PACE authors violated their own protocol, which included an explicit commitment to tell prospective participants about any possible conflicts of interest. The main investigators have had longstanding financial and consulting ties with disability insurance companies, having advised them for years that cognitive behavior therapy and graded exercise therapy could get claimants off benefits and back to work. Yet prospective participants were not told about any insurance industry links and the information was not included on consent forms. The authors did include the information in the “conflicts of interest” sections of the published papers.

Top researchers who have reviewed the study say it is fraught with indefensible methodological problems. Here is a sampling of their comments:

Dr. Bruce Levin, Columbia University: “To let participants know that interventions have been selected by a government committee ‘based on the best available evidence’ strikes me as the height of clinical trial amateurism.”

Dr. Ronald Davis, Stanford University: “I’m shocked that the Lancet published it…The PACE study has so many flaws and there are so many questions you’d want to ask about it that I don’t understand how it got through any kind of peer review.”

Dr. Arthur Reingold, University of California, Berkeley: “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.”

Dr. Jonathan Edwards, University College London: “It’s a mass of un-interpretability to me…All the issues with the trial are extremely worrying, making interpretation of the clinical significance of the findings more or less impossible.”

Dr. Leonard Jason, DePaul University: “The PACE authors should have reduced the kind of blatant methodological lapses that can impugn the credibility of the research, such as having overlapping recovery and entry/disability criteria.”

************************************************************************

PART FOUR:

The Publication Aftermath

Publication of the paper triggered what The Lancet described in an editorial as “an outpouring of consternation and condemnation from individuals or groups outside our usual reach.” Patients expressed frustration and dismay that once again they were being told to exercise and seek psychotherapy. They were angry as well that the paper ignored the substantial evidence pointing to patients’ underlying biological abnormalities.

Even Action For ME, the organization that developed the adaptive pacing therapy with the PACE investigators, declared in a statement that it was “surprised and disappointed” at “the exaggerated claims” being made about the rehabilitative therapies. And the findings that the treatments did not cause relapses, noted Peter Spencer, Action For ME’s chief executive officer, in the statement, “contradict the considerable evidence of our own surveys and those of other patient groups.”

Many believed the use of the broad Oxford criteria helped explain some of the reported benefits and lack of adverse effects. Although people with psychosis, bipolar disorder, substance “misuse,” organic brain disorder, or an eating disorder were screened out of the PACE sample, 47 percent of the participants were nonetheless diagnosed with “mood and anxiety disorders,” including depression. But just as cognitive and behavioral interventions have proven successful with people suffering from primary depression, as DePaul psychologist Leonard Jason had noted, the increased activity was also unlikely to harm such participants if they did not also experience the core ME/CFS symptom of post-exertional malaise.

Others, like Tom Kindlon, speculated that many of the patients in the two rehabilitative arms, even if they had reported subjective improvements, might not have significantly increased their levels of exertion. To bolster this argument, he noted the poor results from the six-minute walking test, which suggested little or no improvement in physical functioning.

“If participants did not follow the directives and did not gradually increase their total activity levels, they might not suffer the relapses and flare-ups that patients sometimes report with these approaches,” said Kindlon.

During an Australian radio interview, Lancet editor Richard Horton denounced what he called the “orchestrated response” from patients, based on “the flimsiest and most unfair allegations,” seeking to undermine the credibility of the research and the researchers. “One sees a fairly small, but highly organized, very vocal and very damaging group of individuals who have, I would say, actually hijacked this agenda and distorted the debate so that it actually harms the overwhelming majority of patients,” he said.

In fact, he added, “what the investigators did scrupulously was to look at chronic fatigue syndrome from an utterly impartial perspective.”

In explaining The Lancet’s decision to publish the results, Horton told the interviewer that the paper had undergone “endless rounds of peer review.” Yet the ScienceDirect database version of the article indicated that The Lancet had “fast-tracked” it to publication. According to current Lancet policy, a standard fast-tracked article is published within four weeks of receipt of the manuscript.

Michael Sharpe, one of the lead investigators, also participated in the Australian radio interview. In response to a question from the host, he acknowledged that only one in seven participants received a “clinically important treatment benefit” from the rehabilitative therapies of graded exercise therapy and cognitive behavior therapy—a key data point not mentioned in the Lancet paper.

“What this trial isn’t able to answer is how much better are these treatments than really not having very much treatment at all,” Sharpe told the radio host in what might have been an unguarded moment, given that the U.K. government had spent five million pounds on the PACE study to find out the answer. Sharpe’s statement also appeared to contradict the effusive “recovery” and “back-to-normal” news stories that had greeted the reported findings.

***

In correspondence published three months after the trial, the PACE authors gave no ground. In response to complaints about changes from the protocol, they wrote that the mid-trial revisions “were made to improve either recruitment or interpretability” and “were approved by the Trial Steering Committee, were fully reported in our paper, and were made before examining outcome data to avoid outcome reporting bias.” They did not mention whether, since it was an unblinded trial, they already had a general sense of outcome trends even before examining the actual outcome data. And they did not explain why they did not conduct sensitivity analyses to measure the impact of the protocol changes.

They defended their post-hoc “normal ranges” for fatigue and physical function as having been calculated through the “conventional” statistical formula of taking the mean plus/minus one standard deviation. As in the Lancet paper itself, however, they did not mention or explain the unusual overlaps between the entry criteria for disability and the outcome criteria for being within the “normal range.” And they did not explain why they used this “conventional” method for determining normal ranges when their two population-based data sources did not have normal distributions, a problem White himself had acknowledged in his 2007 study.

The authors clarified that the Lancet paper had not discussed “recovery” at all; they promised to address that issue in a future publication. But they did not explain why Chalder, at the press conference, had declared that patients got “back to normal.”

They also did not explain why they had not objected to the claim in the accompanying commentary, written by their colleagues and discussed with them pre-publication, that 30 percent of participants in the rehabilitative arms had achieved “recovery” based on a “strict criterion” —especially since that “strict criterion” allowed participants to get worse and still be “recovered.” Finally, they did not explain why, if the paper was not about “recovery,” they had not issued public statements to correct the apparently inaccurate news coverage that had reported how study participants in the graded exercise therapy and cognitive behavior therapy arms had “recovered” and gotten “back to normal.”

The authors acknowledged one error. They had described their source for the “normal range” for physical function as a “working-age” population rather than what it actually was–an “adult” population. (Unlike a “working-age” population, an “adult” population includes elderly people and is therefore less healthy. Had the PACE participants’ scores on the SF-36 physical function scale actually been compared to the SF-36 responses of the working-age subset of the adult population used as the source for the “normal range,” the percentages achieving the “normal range” threshold of this healthier group would have been even lower than the reported results.)

Yet The Lancet did not append a correction to the article itself, leaving readers completely unaware that it contained—and still contains–a mistake that involved a primary outcome and made the findings appear better than they actually were. (Lancet policy calls for correcting “any substantial error” and “any numerical error in the results, or any factual error in interpretation of results.”)

***

A 2012 paper in PLoS One, on financial aspects of the illness, included outcomes for some additional objective measures. Instead of a decrease in financial benefits received by those in the rehabilitative therapy arms, as would be expected if disabled people improved enough to increase their ability to work, the paper reported a modest average increase in the receipt of benefits across all the arms of the study. There were also no differences among the groups in days lost from work.

The investigators did not include the promised information on wages. They also had still not published the results of the self-paced step-test, described in the protocol as a measure of fitness.

In another finding, the PLoS One paper argued that the graded exercise and cognitive behavior therapies were the most cost-effective treatments from a societal perspective. In reaching this conclusion, the investigators valued so-called  “informal” care—unpaid care provided by family and friends–at the replacement cost of a homecare worker. The PACE statistical analysis plan (approved in 2010 but not published until 2013) had included two additional, lower-cost assumptions. The first valued informal care at minimum wage, the second at zero compensation.

The PLoS One paper itself did not provide these additional findings, noting only that “sensitivity analyses revealed that the results were robust for alternative assumptions.”

Commenters on the PLoS One website, including Tom Kindlon, challenged the claim that the findings would be “robust” under the alternative assumptions for informal care. In fact, they pointed out, the lower-cost conditions would reduce or fully eliminate the reported societal cost-benefit advantages of the cognitive behavior and graded exercise therapies.

In a posted response, the paper’s lead author, Paul McCrone, conceded that the commenters were right about the impact that the lower-cost, alternative assumptions would have on the findings. However, McCrone did not explain or even mention the apparently erroneous sensitivity analyses he had cited in the paper, which had found the societal cost-benefit advantages for graded exercise therapy and cognitive behavior therapy to be “robust” under all assumptions. Instead, he argued that the two lower-cost approaches were unfair to caregivers because families deserved more economic consideration for their labor.

“In our opinion, the time spent by families caring for people with CFS/ME has a real value and so to give it a zero cost is controversial,” McCrone wrote. “Likewise, to assume it only has the value of the minimum wage is also very restrictive.”

In a subsequent comment, Kindlon chided McCrone, pointing out that he had still not explained the paper’s claim that the sensitivity analyses showed the findings were “robust” for all assumptions. Kindlon also noted that the alternative, lower-cost assumptions were included in PACE’s own statistical plan.

“Remember it was the investigators themselves that chose the alternative assumptions,” wrote Kindlon. “If it’s ‘controversial’ now to value informal care at zero value, it was similarly ‘controversial’ when they decided before the data was looked at, to analyse the data in this way. There is not much point in publishing a statistical plan if inconvenient results are not reported on and/or findings for them misrepresented.”

***

The journal Psychological Medicine published the long-awaited findings on “recovery” in January, 2013. In the paper, the investigators imposed a serious limitation on their construct of “recovery.” They now defined it as recovery solely from the most recent bout of illness—a health status generally known as  “remission,” not “recovery.” The protocol definition included no such limitation.

In a commentary, Fred Friedberg, a psychologist in the psychiatry department at Stony Brook University and an expert on the illness, criticized the PACE authors’ use of the term “recovery” as inaccurate. “Their central construct…refers only to recovery from the current episode, rather than sustained recovery over long periods,” he and a colleague wrote. The term “remission,” they noted, was “less prone to misinterpretation and exaggeration.”

Tom Kindlon was more direct. “No one forced them to use the word ‘recovery’ in the protocol and in the title of the paper,” he said. “If they meant ‘remission,’ they should have said ‘remission.’” As with the release of the Lancet paper, when Chalder spoke of getting “back to normal” and the commentary claimed “recovery” based on a “strict criterion,” Kindlon believed the PACE approach to naming the paper and reporting the results would once again lead to inaccurate news reports touting claims of “recovery.”

In the new paper, the PACE investigators loosened all four of the protocol’s required criteria for “recovery” but did not mention which, if any, oversight committees approved this overall redefinition of the term. Two of the four revised criteria for “recovery” were the Lancet paper’s fatigue and physical function “normal ranges.” Like the Lancet paper, the Psychological Medicine paper did not point out that these “normal ranges”—now re-purposed as “recovery” thresholds–overlapped with the study’s entry criteria for disability, so that participants could already be “recovered” on one or both of these two indicators from the outset.

The four revised “recovery” criteria were:

*For physical function, “recovery” required a score of 60 or more. In the protocol, “recovery” required a score of 85 or more. At entry, a score of 65 or less was required to demonstrate enough disability to be included in the trial. This entry threshold of 65 indicated better health than the new “recovery” threshold of 60.

*For fatigue, a score of 18 or less out of 33 (on the fatigue scale, a higher score indicated more fatigue). In the protocol, “recovery” required a score of 3 or less out of 11 under the original scoring system. At entry, a score of at least 12 on the revised scale was required to demonstrate enough fatigue to be included the trial. This entry threshold of 12 indicated better health than the new “recovery” threshold of 18.

*A score of 1 (“very much better”) or 2 (“much better”) out of 7 on the Clinical Global Impression scale. In the protocol, “recovery” required a score of 1 (“very much better” on the Clinical Global Impression scale; a score of 2 (“much better”) was not good enough. The investigators made this change, they wrote, because “we considered that participants rating their overall health as ‘much better’ represented the process of recovery.” They did not cite references to justify their post-protocol reconsideration of the meaning of the Clinical Global Impression scale, nor did they explain when and why they changed their minds about how to interpret it.

*The last protocol requirement for “recovery”—not meeting any of the three case definitions used in the study–was now divided into less and more restrictive sub-categories. Presuming participants met the relaxed fatigue, physical function, and Clinical Global Impression thresholds, those who no longer met the Oxford criteria were now defined as having achieved “trial recovery,” even if they still met one of the other two case definitions, the CDC’s chronic fatigue syndrome case definition and the ME definition. Those who fulfilled the protocol’s stricter criteria of not meeting any of the three case definitions were now defined as having achieved “clinical recovery.” The authors did not explain when or why they decided to divide this category into two.

After these multiple relaxations of the protocol definition of “recovery,” the paper reported the full data for the less restrictive category of “trial recovery,” not the more restrictive category of “clinical recovery.” The authors found that the odds of “trial recovery” in the cognitive behavior therapy and graded exercise therapy arms were more than triple those in the adaptive pacing therapy and specialist medical care arms. They did not report having conducted any sensitivity analyses to measure the impact of all the changes in protocol definition of “recovery.”

They acknowledged that the “trial recovery” rate from the two rehabilitative treatments, at 22 percent in each group, was low. They suggested that increasing the total number of graded exercise therapy and cognitive behavior therapy sessions and/or bundling the two interventions could boost the rates.

***

Like the Lancet paper, the “recovery” findings received uncritical media coverage—and as Tom Kindlon feared, the news accounts did not generally mention “remission.” Nor did they discuss the dramatic changes in all four of the criteria from the original protocol definition of “recovery.” Not surprisingly, the report drew fire from patients and advocacy groups.

Commenters on the journal’s website and on patient and advocacy blogs challenged the revised definition for “recovery,” including the use of the overlapping “normal ranges” for fatigue and physical function as two of the four criteria. They wondered why the PACE authors used the term “recovery” at all, given the serious limitation they had placed on its meaning. They also noted that the investigators were ignoring the Lancet paper’s objective results from the six-minute walking test in assessing whether people had recovered, as well as the employment and benefits data from the PLoS One paper—all of which failed to support the “recovery” claims.

In their response, White and his colleagues defended their use of the term “recovery” by noting that they explained clearly what they meant in the paper itself. “We were careful to give a precise definition of recovery and to emphasize that it applied at one particular point only and to the current episode of illness,” they wrote. But they did not explain why, given that narrow definition, they simply did not use the standard term “remission, ” since there was always the possibility that the word “recovery” would lead to misunderstanding of the findings.

Once again, they did not address or explain why the entry criteria for disability and the outcome criteria for the physical function and fatigue “normal ranges”—now redefined as “recovery” thresholds–overlapped. They again did not explain why they used the statistical formula to find “normal ranges” for normally distributed populations on samples that they knew were skewed. And they now disavowed the significance of objective measures they themselves had selected, starting with the walking test, which had been described as “an objective outcome measure of physical capacity” in the protocol.

“We dispute that in the PACE trial the six-minute walking test offered a better and more ‘objective’ measure of recovery,” they now wrote, citing “practical limitations” with the data.

For one thing, the researchers now explained that during the walking test, in deference to participants’ poor health, they did not verbally encourage them, in contrast to standard practice. For another, they did not have follow-up walking tests for more than a quarter of the sample, a significant data gap that they did not explain. (One possible explanation is that participants were too sick to do the walking test at all, suggesting that the findings might have looked significantly worse if they had included actual results from those missing subjects.)

Finally, the PACE investigators explained, they had only 10 meters of corridor space for conducting the test, rather than the standard of 30 to 50 meters–although they did not explain whether all six of their study centers around the country, or just some of them, suffered from this deficiency. “This meant that participants had to stop and turn around more frequently, slowing them down and thereby vitiating comparisons with other studies,” wrote the investigators.

This explanation raised further questions, however. The investigators had started assessing participants–and administering the walking-test–in 2005. Yet two years later, in the protocol published in BMC Neurology, they did not mention any comparison-vitiating problems; instead, they described the walking test as an “objective” measure of physical capacity. While the protocol itself was written before the trial started, the authors posted a comment on the BMC Neurology web page in 2008, in response to patient comments, that reaffirmed the six-minute walking test as one of “several objective outcome measures.”

In their response in the Psychological Medicine correspondence, White and his colleagues did not explain if they had recognized the walking test’s comparison-vitiating limitations by the time they published their protocol in 2007 or their comment on BMC Neurology’s website in 2008–and if not, why not.

In their response, they also dismissed the relevance of their employment and benefits outcomes, which had been described as “another more objective measure of function” in the protocol. “Recovery from illness is a health status, not an economic one, and plenty of working people are unwell, while well people do not necessarily work,” they now wrote. “In addition, follow-up at 6 months after the end of therapy may be too short a period to affect either benefits or employment. We therefore disagree…that such outcomes constitute a useful component of recovery in the PACE trial.”

In conclusion, they wrote in their Psychological Medicine response, cognitive behavior therapy and graded exercise therapy “should now be routinely offered to all those who may benefit from them.”

***

Each published paper fueled new questions. Patients and advocates filed dozens of freedom-of-information requests for PACE-related documents and data with Queen Mary University of London, White’s institutional home and the designated administrator for such matters.

How many PACE participants, patients wanted to know, were “recovered” according to the much stricter criteria in the 2007 protocol? How many participants were already “within the normal range” on fatigue or physical function when they entered the study? When exactly were the changes made to the assessment strategies promised in the protocol, what oversight committees approved them, and why?

Some requests were granted. One response revealed that 85 participants—or 13 percent of the total sample–were already “recovered” or “within the normal range” for fatigue or physical function even as they qualified as disabled enough for the study. (Almost all of these, 78 participants, achieved the threshold for physical function alone; four achieved it for fatigue, and three for both.)

But many other requests have been turned down. Anna Sheridan, a long-time patient with a doctorate in physics, requested data last year on how the patients deemed “recovered” by the investigators in the 2013 Psychological Medicine paper had performed on the six-minute walking test. Queen Mary University rejected the request as “vexatious.”

Sheridan asked for an internal review. “As a scientist, I am seeking to understand the full implications of the research,” she wrote. “As a patient, the distance that I can walk is of incredible concern…When deciding to undertake a treatment such as CBT and GET, it is surely not unreasonable to want to know how far the patients who have recovered using these treatments can now walk.”

The university re-reviewed the request and informed Sheridan that it was not, in fact, “vexatious.” But her request was again being rejected, wrote the university, because the resources needed to locate and retrieve the information “would exceed the appropriate limit” designated by the law. Sheridan appealed the university’s decision to the next level, the U.K. Information Commissioner’s Office, but was recently turned down.

The Information Commissioner’s Office also turned down a request from a plaintiff seeking meeting minutes for PACE oversight committees to understand when and why outcome measures were changed. The plaintiff appealed to a higher-level venue, the First-Tier Tribunal. The tribunal panel–a judge and two lay members—upheld the decision, declaring that it was “pellucidly clear” that release of the minutes would threaten academic freedom and jeopardize future research.

The tribunal panel defended the extensive protocol changes as “common to most clinical trials” and asserted that the researchers “did not engineer the results or undermine the integrity of the findings.” The panel framed the many requests for trial documents and data as part of a campaign of harassment against the researchers, and sympathetically cited the heavy time burdens that the patients’ demands placed on White. In conclusion, wrote the panel, the tribunal “has no doubt that properly viewed in its context, this request should have been seen as vexatious–it was not a true request for information–rather its function was largely polemical.”

To date, the PACE investigators have rejected requests to release raw data from the trial for independent analysis. Patients and other critics say the researchers have a particular obligation to release the data because the trial was conducted with public funds.

Since the Lancet publication, much media coverage of the PACE investigators and their colleagues has focused on what The Guardian has called the “campaign of abuse and violence” purportedly being waged by “militants…considered to be as dangerous and uncompromising as animal rights extremists.” In a news account in the BMJ, White portrayed the protestors as hypocrites. “The paradox is that the campaigners want more research into CFS, but if they don’t like the science they campaign to stop it,” he told the publication. While news reports have also repeated the PACE authors’ claims of treatment success and “recovery,” these accounts have not generally examined the study itself in depth or investigated whether patients’ complaints about the trial are valid.

Tom Kindlon has often heard these arguments about patient activists and says they are used to deflect attention away from the PACE trial’s flaws. “They’ve said that the activists are unstable, the activists have illogical reasons and they are unfair or prejudiced against psychiatry, so they’re easy to dismiss,” said Kindlon.

What patients oppose, he and others explain, is not psychiatry or psychiatrists, but being told that their debilitating organic disease requires treatments based on the hypothesis that they have false cognitions about it.

***

In January of this year, the PACE authors published their paper on mediators of improvement in The Lancet Psychiatry. Not surprisingly, they found that reducing participants’ presumed fears of activity was the main mechanism through which the rehabilitative interventions of graded exercise therapy and cognitive behavior therapy delivered their purported benefits. News stories about the findings suggested that patients with ME/CFS could get better if they were able to rid themselves of their fears of activity.

Unmentioned in the media reports was a tiny graph tucked into a page with 13 other tiny graphs: the results of the self-paced step-test, the fitness measure promised in the protocol. The small graph indicated no advantages for the two rehabilitative intervention groups on the step-test. In fact, it appeared to show that those in the other two groups might have performed better. However, the paper did not include the data on which the graph was based, and the graph was too small to extract any useful data from it.

After publication of the study, a patient filed a request to obtain the actual step-test results that were used to create the graph. Queen Mary University rejected the request as “vexatious.”

With the publication of the step-test graph, the study’s key “objective” outcomes—except for the still-unreleased data on wages–had now all failed to support the claims of “recovery” and treatment success from the two rehabilitative therapies. The Lancet Psychiatry paper did not mention this serious lack support for the study’s subjective findings from all its key objective measures.

Some scientific developments since the 2011 Lancet paper–such as this year’s National Institutes of Health and Institute of Medicine panel reports, the Columbia University findings of distinct immune system signatures, further promising findings from Norwegian research into the immunomodulatory drug [see correction below] pioneered by rheumatoid arthritis expert Jonathan Edwards, and a growing body of evidence documenting patients’ abnormal responses to activity–have helped shift the focus to biomedical factors and away from PACE, at least outside Great Britain.

In the U.K. itself, the Medical Research Council, in a modest shift, has awarded some grants for biomedical research, but the PACE approach remains the dominant framework for treatment within the national health system. Two years ago, the disparate scientific and political factions launched the CFS/ME Research Collaborative, conceived as an umbrella organization representing a range of views. At the collaborative’s inaugural two-day gathering in Bristol in September of 2014, many speakers presented on promising biomedical research. Peter White’s talk, called “PACE: A Trial and Tribulations,” focused on the response to his study from disaffected patients.

According to the conference report, White cited the patient community’s “campaign against the PACE trial” for recruitment delays that forced the investigators to seek more time and money for the study. He spoke about “vexatious complaints” and demands for PACE-related data, and said he had so far fielded 168 freedom-of-information requests. (He’d received a freedom-of-information request asking how many freedom-of-information requests he’d received.) This type of patient activity “damages” research efforts, he said.

Jonathan Edwards, the rheumatoid arthritis expert now working on ME/CFS, filed a separate report on the conference for a popular patient forum. “I think I can only describe Dr. White’s presentation as out of place,” he wrote. After White briefly discussed the trial outcomes, noted Edwards, “he then spent the rest of his talk saying how unreasonable it was that patients did not gratefully accept this conclusion, indicating that this was an attack on science…

“I think it was unfortunate that Dr. White suggested that people were being unreasonable over the interpretation of the PACE study,” concluded Edwards. “Fortunately nobody seemed to take offence.”

Correction: The original text referred to the drug as an anti-inflammatory. 

Comments on this entry are closed.

  • Thank you. Producing these reports must have been a massive undertaking.
    Your work is very much appreciated.

    Now hopefully medicine can move onwards with the real work of exploring the physiology behind ME, and the search for real treatment options.

  • Maik Speedy

    Thank You 4 dissecting the PACEtrial David and posting this on your site professor. Sounds like serious professional misconduct; more than time that the report is retracted by The Lancet …

  • Valentijn

    Even more interesting regarding the published step-test graph with missing values: someone ran it through a program which evaluates graphs to estimate values, and CBT and GET arms looked like they did quite a bit worse than the others arms. Maybe even statistically significantly worse, which could explain the authors’ reluctance to provide numerical values. It wouldn’t look very good if an objective measurement contradicted their carefully extracted questionnaire results, after all.

    Food for thought 🙂

  • Jo Best

    Thank you for a comprehensive investigative report on the various problems arising from misinterpretation of both the results, and of concerns following publication, of the PACE trial, and for the efforts of everyone involved in seek the actual results.

    May I add some information that may interest you. The MRC ring-fenced funding announced early 2011, ostensibly to investigate causes of this disease, was instigated by a patient with severe ME and her mother/carer and support from her MP.

    Membership of the UK CFS/ME Research Collaborative doesn’t include all disparate views regarding a model for research into this disease. Three UK patient organisations remain independent of it: The 25% M.E. Group representing severe ME;
    The Young ME Sufferers Trust representing children and young people and their families, which published ‘Behind the Scenes – Research Collaborative’;
    and Invest in ME (Research) which has been driving the direction of research in UK/Europe towards a strategy of translational research based on the biomedical model (WHO ICD-10 G93.3) as well as facilitating biomedical research and collaboration, notably through the past 10 years of international conference and 5 years of biomedical researchers into ME colloquium. Jonathan Edwards stated that his interest in ME/CFS was sparked by the charity’s invitation to its 8th Invest in ME Conference, following which he agreed to advise the charity on the B-cell / Rituximab Research.

    Thank you once again with best wishes, Jo Best.

  • pinklil

    Thank you David Tuller for exposing what I now tend to think of as the ‘White Noise’ …. the ‘drum drum’ and ‘fizz fizz’ and ‘blah blah’… of the PACE Trial. What is more concerning to me, like the good old Emperor of old, is the fact that the flaws within the whole dastardly concoction were transparent right from the off. I sincerely hope the miasma which blinds the powers that be; the supposedly discriminating and enlightened ‘free press’; the doctors who can only bear to read abstracts; and so on can be cleared by your reports as presented here over the last 3 days. I also hope this article finds its way to broadsheet outlets in the US and hopefully to all media portals (though clearly breaching the walls of the SMC ain’t ever going to happen) for worldwide dissemination. This bastardising of science with what most patients would consider to be a predetermined design to achieve a particular end result (and when that end result proved elusive a massaging of protocol and data to make it fit) must surely mean a full retraction of all papers associated with the PACE experiment? I’ve had enough of the White Noise, come one ..let the good guys run the show. We know who you are, the Davis’s, the Marshall-Gradisniks, the Lipkins, the Mellas and Fluges, the Montoyas. Time to get well.. …. time to live….

    Oh and did I say ‘thank you’? (Again!)

  • Sasha

    Thank you, David Tuller and Vince Racaniello, for this final instalment.

    It’s astonishing that for all these years this stark-naked emperor has been running down the street in full sight of everyone. Patients have been pointing and shouting, “He’s got no clothes on!” and the people whose job it is to watch out for naked emperors have been shouting, “No, stupid patients! He’s wearing a lovely suit of clothes!”

    The ability of PACE to hide its ludicrous, post-hoc, results-inflating analyses in plain sight has been just extraordinary.

    It’s time for the journals involved – The Lancet, and Psychological Medicine – to wake up and retract these findings and for Queen Mary, University of London to stop being complicit with the study authors in withholding the results as defined in the study protocol.

    UK taxpayers paid £5 million for this trial, and I’m one of them. We deserved a well-conducted trial. It’s not too late to at least get transparency about the pre-planned outcomes and recovery measures.

    I think we can pretty much guarantee they’ll be dismal.

  • Not this again

    Needless to say, great job. Massive undertaking. I wonder what will happen next! After all, there’s a good number of research papers that cite the initial paper…

    http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_citedin&from_uid=21334061

    including 4 systematic reviews…

    http://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_pmh_cited&from_uid=21334061

    With the Lancet needing a media relations officer…I’m sure David could refer them some qualified applicants!

  • disqus_Rv8tqVZbOP

    Why is this on a Virology blog?

    PACE trial was published several years ago. How is this newsworthy? These flaws and critiques of PACE have been put forth many times. Mainly a regurgitation of previous analyses.

    Why is Kindlon made out to be so prominent, when in reality he has been one of many who have exposed these problems, including many researchers and scientists?

    So what is the real point? PACE isn’t even cited in any US or CDC CFS material. A distraction? Seems to mainly lay more groundwork and further the bogus ME/CFS agenda, the fundamental problem with diagnosis and treatment. And although the study itself was deeply flawed, PACE is but a symptom.

  • fractal

    Approximated change from baseline to 52 weeks:

    Specialist medical care = +0.1875
    GET = +0.109375
    CBT = +0.09375
    Adaptive pacing = +0.40625

    None of the interventions could be said to be effective, but the ones claimed to be most effective by the authors actually produced the least improvement at follow up.

    The graph and data extraction is discussed here: http://forums.phoenixrising.me/index.php?threads/pace-trial-team-wont-release-data-theyve-already-published-in-graph-form.38978/

  • Doug

    PACE is absolutely cited in US material that affect patient treatment. The AHRQ cites it as evidence that CBT and GET are effective therapy for ME/CFS. UpToDate, which is used by many, if not most, doctors in the US cites it as evidence for GET as well. One of CDC’s CME also referenced it. Family physicians is the US were told that “Patients with poor social adjustment, a strong belief in an organic cause for fatigue, or some sort of sickness benefit (i.e., financial incentive) tend to have worse responses to therapy”, which was based on the PACE studies. http://www.aafp.org/afp/2012/1015/p741.html

  • disqus_Rv8tqVZbOP

    PACE has nothing to do with ME. And ALL has been reported and discussed before.

  • disqus_Rv8tqVZbOP

    Right. Because these are Me groups and this report is not about ME. Neither is “ME/CFS.”

  • Well the authors of PACE did nothing to correct the papers that applied all the PACE conclusions to ME. Also NICE guidelines on how to treat patients with ME are based largely on PACE outcomes. So sadly PACE does influence ME treatment.

  • disqus_Rv8tqVZbOP

    PACE is simply included in evidenced based reviews. There are many studies in the literature recommending CBT and exercise for CFS. It is on Medscape, Webmd etc, but hardly based solely on PACE. There is nothing in the CDC CME citing or even referencing PACE.
    Tobi M, 1982, Lancet 1:61-4; 1984 771:376-82; DuBois RE, Seeley JK, Brus I, Sakamoto K, Ballow M, Harada S; Chronic mononucleosis syndrome. South Med J. 1984 ;77:1376-82.

    Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985;102:1-7.

    Straus SE, Tosato G, Armstrong G, Lawley T, Preble OT, Henle W et al. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985;102:7-16.
    Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987; 257:2297-302.
    Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988;108:387-9.
    Holmes GP. Defining the chronic fatigue syndrome. Rev Infect Dis. 1991;13 Suppl 1:S53-5.
    Reyes M, Gary HE Jr, Dobbins JG, Randall B, Steele L, Fukuda K, et al. Surveillance for chronic fatigue syndrome: four U.S. cities, September 1989 through August 1993. MMWR CDC Surveill Summ. 1997; 461-13.

    Lawrie SM, Pelosi AJ. Chronic fatigue syndrome in the community: prevalence and associations. Br J Psychiatry. 1995;166:793-7.

    Steele L, Dobbins JG, Fukuda K, Reyes M, Randall B, Koppelman M, et al. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998;105:83S-90S.

    Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999;159:2129-37.
    HOMEBACKNEXT
    Tobi M, 1982, Lancet 1:61-4; 1984 771:376-82; DuBois RE, Seeley JK, Brus I, Sakamoto K, Ballow M, Harada S; Chronic mononucleosis syndrome. South Med J. 1984 ;77:1376-82.

    Jones JF, Ray CG, Minnich LL, Hicks MJ, Kibler R, Lucas DO. Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies. Ann Intern Med. 1985;102:1-7.

    Straus SE, Tosato G, Armstrong G, Lawley T, Preble OT, Henle W et al. Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection. Ann Intern Med. 1985;102:7-16.
    Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987; 257:2297-302.
    Holmes GP, Kaplan JE, Gantz NM, Komaroff AL, Schonberger LB, Straus SE, et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988;108:387-9.
    Holmes GP. Defining the chronic fatigue syndrome. Rev Infect Dis. 1991;13 Suppl 1:S53-5.
    Reyes M, Gary HE Jr, Dobbins JG, Randall B, Steele L, Fukuda K, et al. Surveillance for chronic fatigue syndrome: four U.S. cities, September 1989 through August 1993. MMWR CDC Surveill Summ. 1997; 461-13.

    Lawrie SM, Pelosi AJ. Chronic fatigue syndrome in the community: prevalence and associations. Br J Psychiatry. 1995;166:793-7.

    Steele L, Dobbins JG, Fukuda K, Reyes M, Randall B, Koppelman M, et al. The epidemiology of chronic fatigue in San Francisco. Am J Med. 1998;105:83S-90S.

    Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, et al. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999;159:2129-37.
    HOMEBACKNEXT

  • Beatrice Pham

    It’s newsworthy because the work continues to be cited by major medical resources such as Medscape/ UpToDate as well as by federal agencies like NIH and AHRQ. It has an impact on how physicians and other diagnose and care for patients.

    Aside from which, it is a fantastic example of how papers, even ones published in prominent journals that have undergone peer review, can have prominent flaws and twisted interpretations. As a scientist/ doctor myself who writes/ reviews articles and teaches, the value of such articles is they help teach younger/ new investigators how to read an article/ design better studies and remind more experienced ones to be skeptical.

    Another point, one of the principles of medicine is Listen to the patient. My mentor used to say — “If you can’t figure out what the patient has, re-take the history. Never say ‘the patient is a poor historian’; rather it reflects that you are a poor clinician.” Something’s truly wrong when many patients with a condition say that a treatment doesn’t work for them or it makes them worse. If patients with cancer, heart attacks, asthma or any other condition stated a treatment did not work for them, the reaction would not be to attack the patient or patient groups for not improving but rather to look for why not and for better treatments. Think about that.

  • Wendy Matthews

    Thank you David for writing about this in such a readable and comprehensive way.
    It amazes me that those who do not have ME/CFS or care for those that do, are so astounded at the “anger” that comes from patients and their advocates. If they were watching their sons, daughters or friends deal with a nasty illness, up night and day trying to nurse them, struggling to find a way to pay the bills, while being told that it was not that bad, all in their heads and they were being demanding when they wanted help and answers, they may get a tad upset too. It is a frightening reality for many as they watch loved ones suffer. To stay silent and no longer stand up for them, to turn and walk away and no longer be a voice for them, is not an option for people who care and want to see what they deal with every moment of every day validated. To take millions of dollars of research funding, to produce what is in effect mistruth is indefensible. What is worse is to produce and promote a treatment on flawed grounds, call it a cure, worsen patients with it and then take away their means of support e.g insurance claims and health benefits.Thank goodness for more recent, up to date reports that are unbiased, based on quality research, give some idea of what is really going on and deliver the hope of a biomarker and perhaps treatment. This may at last remove the totally undeserved stigma over this illness and patients can attend to what they really want to do, which is use their energies to quietly get well, instead of having to work so hard to just be believed.

  • Beatrice Pham

    The reason why PACE is important is not merely that it is cited but because it is a randomized double-blind placebo controlled trial with hundreds of patients, it is given more weight in evidence-based reviews than other studies. However if you subject PACE to standards such as CONSORT for clinical trials, it violates several principles. Supposedly, publications like Lancet use standards like CONSORT but as Tuller’s article shows, it’s not uniformly applied.

    (http://www.consort-statement.org/)

    (And the way “evidence-based medicine” is currently conceived is an issue in and of itself. I’m not against EBM — I teach it — but there are also limits to it. See Trish Greenlagh’s article here:

    http://www.biomedcentral.com/1741-7015/13/200)

    Also, I’m not sure what your agenda is but the bottom line is – regardless of how/ where, etc. the PACE trial is cited or not — it affects the care of millions here in the US and abroad. How do I know? I have a relative with this illness and have seen how she and other patients are treated. I also have worked in one of the largest healthcare systems in the US and seen how they use studies and evidence to make decisions about care so these studies have real-life implications for people.

  • disqus_Rv8tqVZbOP

    Right, there are many studies and evidence other than PACE. Nothing here that hasn’t been floated around for quite some time. We all know how patients are treated but PACE is only a small part of it. At this point if it were retracted it would not make much difference.

  • disqus_Rv8tqVZbOP

    I’ve seen nowhere that HHS/CDC/NIH/AHRQ quotes or references PACE in guidelines or treatment recommendations.

  • disqus_Rv8tqVZbOP

    This is not up to authors of a study to correct or complain about those who misapply results or misinterpret it. And many occurs due to the ME/CFS fraud, which is being promoted by ALL US so called patient groups.

  • disqus_Rv8tqVZbOP

    My agenda is not to go over the same things over and over that have relatively little importance, while ignoring and even contributing to the fundamental problems.

  • disqus_Rv8tqVZbOP

    And why is this on a virology blog?

  • halcyon

    That’s not true sadly. The 2011 PACE paper is littered with mentions of myalgic encephalomyelitis and the discussion states that “The PACE findings can be generalised to patients who also meet alternative diagnostic criteria for chronic fatigue syndrome and myalgic encephalomyelitis but only if fatigue is their main symptom.”

    Otherwise I’d be with you. Focus all effort on differentiating ME from CFS and the PACE trial and any other research on CFS goes away.

  • Valentijn

    It still sounds good enough for a PACE-style headline … “Definitive multi-million pound trial with hundreds of participants proves that pacing is four times more effective than CBT or GET!!!111!!!!ONE!11!!” 😀

    More seriously, that’s an approximated 0.4 point increase for pacing on a scale that only seems to go up to 3, compared to 0.1 increase for CBT or GET. That seems fairly big, at least if it’s not being presented on a graph which has been horizontally stretched to a ridiculous extent.

  • Valentijn

    I imagine in it’s on a virology blog for the reason that the PACE recovery paper was published in a psych journal. Because that’s where it got accepted. Until there’s a high-profile “Psychosomatic Hypotheses are Quackfests” blog, I’m afraid there won’t be a good home for debunking the massive amount of low-quality research from psychosomatic theorists.

  • Greg Crowhurst

    The PACE Trial was NOT about ME, as Peter White et al (2011) stated : “The PACE trial paper refers to chronic fatigue syndrome (CFS) which is operationally defined; it does not purport to be studying CFS/ME…..CFS defined simply as a principal complaint of fatigue that is disabling, having lasted six months, with no alternative medical explanation (Oxford criteria)”.http://www.investinme.org/Article427%20Initial%20response%20by%20Hooper%20to%20undated%20letter%20by%20White%20to%20Horton.htm

    ME is not CFS !!

    The anger, I feel, that for over two decades my wife, who has Very Severe ME, has suffered pain that you could never imagine, torment from the environment that is beyond any notion of comprehension, it is so removed from ordinary experience and a massive, multi-system physical dysfunction that tears me apart to observe,over and over again, all because a small body of psychiatrists, without a shred of evidence, but with massive influence and power, is able to perpetuate an oppressive toxic tissue of lies, deceit,manipulation, cover-up, of which the PACE Trial is a prime example, thank you David for your brilliant, cutting analysis, that denies my wife any investigation, treatment, hope or chance of a cure, that has reduced our life together to a daily coping and getting through and hoping not to fall into despair; that anger few know !

    Last night, the sadness on my wife’s face, that she might never get better, broke my heart, I gently tried to comfort her tortured, screamingly hypersensitive body, as I have done so many times before – since Bill Clinton was elected President, in 1993, that is how long it has been.

    Our struggle is here :

    http://stonebird.co.uk

  • disqus_Rv8tqVZbOP

    Right. So then it really belongs on a psychology blog. Nothing to do with Virology.
    So where should ME patients debunk the massive amount of “ME /CFS” misinformation, which is actually what brings in the psychs and low quality psych research?

  • disqus_Rv8tqVZbOP

    Yes, but thIs ME reference Is really a trap. Thrown In as more of a comorbIdIty. Because fatigue Is NOT the maIn symptom of true ME.
    So, like you saId, “Focus all effort on differentiating ME from CFS and the PACE trial and any other research on CFS goes away.” WhIch Is why thIs bogus “ME/CFS” Is so dangerous. CFS continues to brIng in all the psych stuff. Keep CFS and we’ll contInue to get the “treatments” associated wIth it. So we should not constantly act surprIsed and outraged.

  • Merry Speece

    You are magnificent, David Tuller. Brilliant goodness! Thanks also to Vincent Racaniello, a generous and gracious scientist, marvel of Nature. And thanks to the patients — activists, analysts, afflicted detectives — who persisted worrying the numbers.

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  • Doug

    The authors of the PACE trial have oversized power in the UK. They are the people holding back biomedical research. Having their paper retracted (as it should be) will be a huge stain on their career and will help lead to a change in guidelines, research, and care. A retraction is likely to make a big difference.

  • disqus_Rv8tqVZbOP

    No it is not psychiatrists that deny investigation. It is the mixing and misdiagnosis of ME as CFS, vis a vis ME/CFS. ME is not CFS. Tuller seems to ignore this and goes along with it, thus contributing to the main problem. And Kindlon has been a major proponent of the ME/CFS agenda.
    Separate ME from CFS and PACE and the fatigue fraud will not be misapplied to ME patients. The study authors stated as such that this was NOT ME. Don’t blame them.
    “ME/CFS” = promise everything, deliver nothing, blame everyone else. These ME/CFSers work against ME patients, then pretend to be ME advocates. Disgusting.

  • disqus_Rv8tqVZbOP

    Again, I agree that any flawed study should be retracted. And PACE was awful. However, I do not know about the UK, but it is just not a major consideration in the US. I have seen NO citation or reference to PACE in any US (HHS) information, despite claims to the contrary. These things often become way overinflated and serve as distractions from the larger issues. Keep patients busy and focused on the wrong things for the wrong reasons.

  • Jill

    Thanks as always Jill for your respectful, productive commentary. Do you get satisfaction from attacking house-bound patients? Did you bother reading anything Dr Tuller wrote or did you just cut-and-paste your usual comment?

  • Greg Crowhurst

    Yes, you emphasize very well the overwhelming need to separate ME from CFS. Yes a “ME/CFS” agenda only perpetuates the suffering. I have profound respect for Tom Kindlon , his outstanding commitment, his extraordinary campaigning and his masterful exposure of the PACE Trial; it is not good to attack individuals; we have had far too much of that in the ME Community ! I agree the power to change is with us – even up against seemingly overwhelming odds.

  • disqus_Rv8tqVZbOP

    No one is attacking anyone. Scrutinizing actions and positions and pointing out discrepancies and disagreements is necessary. Not everyone claiming to be advocates is actually helping OUR cause.
    There is a rift between the 2 agendas. Kindlon has been a prime proponent furthering and promoting the ME/CFS agenda. This is anathema to ME recognition. It is the opposite. These ME/CFSers work against us and claim to be ME advocates. It is disgusting.

  • disqus_Rv8tqVZbOP

    Do you get satisfaction from casting the usual baseless aspersions? Stick with issues. Criticizing and scrutinizing positions are not attacks. Those who see them as such should not be involved. We have every right to disagree. Actually this fake pretense of being attacked (read: anything you do not like or agree with) is a well known tactic to try to shut down debate.
    Actually it is sad that cut and paste would be very appropriate as the same issues are ignores or misrepresented constantly.

  • Nic

    It is a major, major, major consideration in the UK. Pretty much every national paper picked up the PACE ball and ran with it, and weren’t picky about the difference between ME and CFS. Same with the science journals. As you’d know if you read the article fully. So for us in the UK, this is a larger issue. One of the biggest issues there is.

    That’s because the PACE authors are the same group of people who first attempted to turn the CDC’s theoretical research title of “CFS” into the erasure of “ME” as a disease identity. (Small wonder many patients in the UK spontaneously started to insist on ME/CFS in the 1990s, as at the time it was the only way to maintain continuity of ME in the UK at all – no it wasn’t ideal, but if it was a choice between losing my diagnosis of ME completely with a new doctor that refused to use the name because she’d bought into the psych lobby, and self-identifying as ME(CFS) or ME/CFS? I’ll pick the compromise every time! You want to blame someone for the confusion between ME and CFS? Please blame it on the correct people, the research group who’ve spent thirty years trying to write ME out of history, not the people who’ve spent thirty years trying to simultaneously defend the continuity of the illness whilst advocating for accurate definitions, diagnoses, and subgroupings…and yes, even before the artificial creation of CFS, there was still the possibility of subgroups (infectious and non-infectious ME).)

    That research group have been successfully redefining medical terms ever since, in their efforts to change the conversation and erase ME – and convincing a surprisingly large amount of highly placed people that the medical terms they’ve redefined have always been that way – e.g. their use of “somatic” to mean not the opposite of “psychosomatic” but the continuation of it in a biopsychosocial model, and their use of “recovery” in the PACE paper to mean “minor improvement”…but only when they’re pressed on the incongruity of using the word “recovery”.

    And regardless of the focus, it’s a fundamental issue that bad science, biased researchers and a heterogeneous trial population should not be able to dominate the course of conversation across government, the media and all national science journals by falsely invoking patient emotionality and mental health stigma.

  • disqus_Rv8tqVZbOP

    That the PACE trial is a crap study and should be retracted is not in dispute. This was critiqued and analyzed years ago.

    How do we acknowledge the problems with and blame those for the confusion between ME and CFS and continue to promote ME/CFS? This is illogical on its face. Same excuses and illogical rhetoric.

    We do NOT need two names.

    ME/CFS is NOT a compromise. A compromise is where both sides get something. ME/CFS may help those with CFS but harms those with ME.

    ME/CFS is the psychs kryptonite, aided and abetted by these ME/CFSers. They study chronic fatigue and pretend to study ME. We have come full circle to these fake ME group/advocates that are REALLY about CFS and ME/CFS.

    Keep CFS in the mix and we’ll continue to get the “treatments” associated with it.

  • Sarah LaBelle

    I am astounded to learn that White gave a talk complaining about the reactions to his big research project, at a serious conference. So very unprofessional, unscientific.To do that rather than open his mind to the notion that some of the criticisms might be valid, I am sorry for him. Sorrier for all of us, of course, with the largest funded study ever being such a damaging exercise. I hope this analysis of the situation is read by more than patients, and has a huge effect on attitudes, funding, further research and treatments. And that the Lancet retracts publishing the trial, especially as fast track — maybe that speed failed to gain sufficiently qualified peers for the reviews. Instead, that review has been done now.

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  • J.A.

    MEActionNetwork has started a petition to have the PACE claims retracted. It’s been up for less than 12 hours and already has well over 1,000 signatures. Let’s show the PACE authors that we are not a vocal minority… sign and share and show how many we number!

    http://my.meaction.net/petitions/pace-trial-needs-review-now

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  • deboruth

    Well put Doug.

  • deboruth

    It is cited. Read the bibliography of the IOM report and much CDC work.

  • deboruth

    White et al say the results of the trial can be applied to ME, and in fact the NHS does apply CBT and GET to ME patients.

  • deboruth

    Three cheers and then some for David Tuller and Prof. Racaniello. There are two tragedies attendant on this story. First: how many of us have in effect lost our lives because of this outrageous fraud and its large influence on the CDC, perpetuated via Peter White’s weekly chats with former “CFS” chief William Reeves (which chats Reeves cited in a public meeting.) Secondly; how foolish and poisonous it has made British science seem, from the assent of the Lancet peer group in publishing the PACE trial’s travesty of research to the way every branch of the UK establishment — law courts, newspapers, academics, and medical professionals alike — has rallied round to defend and protect the pathetic and amateurish deception. Repeatedly the establishment rises noisily and en masse to defend White and colleagues from supposed “abuse,” such as the rest of the world might term “criticism,” or, at worst, “sniping.” Remarkably, such cry-baby tactics even persuaded the UK scientific powers-that-be to secure White’s colleague, the CBT/GET gang’s lead theoretician Simon Wessely, a knighthood from the Crown for enduring “abuse” and alleged “death threats,” the likes of which which Scotland Yard never located.

    All this reflects sadly on British science, limping anyway since the brain drain of the post-war years. The timing could not be worse. Following the re-election of UK Prime Minister David Cameron last spring, a new and tougher UK cabinet has been threatening the national budget for scientific research with a 40% across-the- board budget cut. Yet far from White and Wessely’s preserve of psychiatric make-believe one can still find troves of brilliance in British science; for example, youthful Cambridge Professor Clare Grey’s remarkable advance in battery chemistry, announced the other day, which may one day allow a car to drive across Texas with hardly a stop to re-charge.

  • deboruth

    Read bibliographies. IOM and many CDC papers.