Trial By Error, Continued: Did the PACE Trial Really Prove that Graded Exercise Is Safe?

By Julie Rehmeyer and David Tuller, DrPH

Julie Rehmeyer is a journalist and Ted Scripps Environmental Journalism Fellow at the University of Colorado, Boulder, who has written extensively about ME/CFS.

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

Joining me for this episode of our ongoing saga is my friend and colleague Julie Rehmeyer. In my initial series, I only briefly touched on the PACE trial’s blanket claim of safety. Here we examine this key aspect of the study in more detail, which is complicated and requires a deep dive into technicalities. Sorry about that, but the claim is too consequential to ignore.    

 

One of the most important and controversial claims from the PACE Trial was that graded exercise therapy is safe for patients with chronic fatigue syndrome (or ME/CFS, as U.S. government agencies now call it).

“If this treatment is done by skilled people in an appropriate way, it actually is safe and can stand a very good chance of benefiting [patients],” Michael Sharpe, one of the principal PACE investigators, told National Public Radio in 2011, shortly after The Lancet published the first results.

But to many in the ME/CFS community, this safety claim goes against the very essence of the disease. The hallmark of chronic fatigue syndrome, despite the name, is not actually fatigue but the body’s inability to tolerate too much exertion — a phenomenon that has been documented in exercise studies. All other symptoms, like sleep disorders, cognitive impairment, blood pressure regulation problems, and muscle pain, are exacerbated by physical or mental activity. An Institute of Medicine report this year even recommended that the illness be renamed to emphasize this central problem, choosing the name “systemic exertion intolerance disease,” or SEID. [see correction below]

A careful analysis shows that the PACE researchers’ attempts to prove safety were as flawed as their attempts to prove efficacy. However, while the trial reports gave enough information to establish that the treatments were not effective (in spite of the claims of success and “recovery”), they did not give enough information to establish whether they were safe (also in spite of their claims). We simply do not know.

“I would be very skeptical in recommending a blanket statement that GET is safe,” says Bruce Levin, a biostatistician at Columbia University, who has reviewed the PACE trial and found other methodological aspects indefensible. “The aphorism that absence of evidence is not evidence of absence applies here. There is real difficulty interpreting these results.”

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Assessing the PACE team’s safety claims is critical, because the belief that graded exercise is safe has had enormous consequences for patients. In the UK, graded exercise therapy is recommended for all mild to moderate ME/CFS patients by the National Institute for Health and Care Excellence, which strongly influences treatment across the country. In the US, the Centers for Disease Control and Prevention also recommends graded exercise.

Exertion intolerance—also called “post-exertional malaise”—presents ME/CFS patients with a quandary: They want to do as much as they can when they’re able, while not doing so much that they make themselves sicker later. Among themselves, they’ve worked out a strategy to accomplish that, which they call “pacing.” Because their energy levels fluctuate, they carefully monitor how they are feeling and adapt their activities to stay within the day’s “energy envelope.”  This requires sensitive attunement to their symptoms in order to pick up on early signs of exacerbation and avoid exceeding their limits.

But according to the hypothesis behind the PACE study, this approach is all wrong. Because the investigators believe physical deconditioning rather than an organic disease perpetuated the many symptoms, they theorized that the key to getting better was to deliberately exceed current limits, gradually training the body to adapt to greater levels of activity. Rather than being sensitively attuned to symptoms, patients should ignore them, on the grounds that they have become obsessed about sensations most people would consider normal. Any increase in symptoms from exertion was explained as expected, transient and unimportant—the result of the body’s current state of weakness, not an underlying disease.

Many patients in the UK have tested this theory, since graded exercise therapy, or GET, is one of the few therapies available to patients there. And patient reports on the approach are very, very bad. In May 2015, the ME Association, a British charity, released a survey of patients’ experiences with GET, cognitive behavioral therapy, and pacing. The results suggested that GET was far and away the most dangerous. Of patients who received GET, 74 percent said that it had made them worse. In contrast, 18 percent said they were worse after cognitive behavior therapy and only 14 percent after pacing.

The survey is filled with reports similar to this one: “My condition deteriorated significantly, becoming virtually housebound, spending most of my day in bed in significant pain and with extreme fatigue.”

Anecdotal reports, however, don’t provide the proof of a randomized clinical trial. So this was one of the central issues at stake in the PACE study: Is it safe for patients to increase their activity on a set schedule while ignoring their symptoms?

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In the 2011 Lancet article with the first PACE results, the researchers reported that eight percent of all participants experienced a “serious deterioration” and less than two percent experienced a “serious adverse reaction” over the course of the year, without significant differences between the arms of the trial.

For patients to have a “serious deterioration,” their physical function score needed to drop by at least 20 points and they needed to report that their overall health was “much worse” or “very much worse” at two consecutive assessment periods (out of a total of three).

To have a “serious adverse reaction,” the patient needed to experience a persistent “severe, i.e. significant deterioration,” which was not defined, or to experience a major health-related event, such as a hospitalization or even death. Furthermore, a doctor needed to determine that the event was directly caused by the treatment—a decision that was made after the doctor was told which arm of the trial the patient was in.

Subsequent “safety” results were published in a 2014 article in the Journal of Psychosomatic Research. And this paper revealed a critical detail unmentioned in the Lancet paper: the six centers around England participating in the study appear to have applied the methods for assessing safety differently. That raises questions about how to interpret the results and whether the overall claims of “safety” can be taken at face value.

Beyond that issue, a major problem with the PACE investigators’ reporting on harms from exercise is that it looks as though participants might not have actually done much exercise. While the researchers stated the ambitious goal that participants would exercise for at least 30 minutes five times a week, they gave no information on how much exercise participants in fact did.

The trial’s objective outcomes suggest it may not have been much. The exercise patients were only able to walk 11 percent further in a walking test at the end of the trial than patients who hadn’t exercised. Even with this minimal improvement, participants were still severely disabled, with a poorer performance than patients with chronic heart failure, severe multiple sclerosis, or chronic obstructive pulmonary disorder.

On top of that, almost a third of those in the exercise arm who finished other aspects of the trial never completed the final walking test; if they couldn’t because they were too sick, that would skew the results. In addition, the participants in GET showed no improvement at all on a step test designed to measure fitness. Presumably, if the trial’s theory that patients suffered from deconditioning was correct, participants who had managed to exercise should have become more fit and performed better on these tests.

Tom Kindlon, a long-time patient and an expert on the clinical research, suggests that even if those in the exercise arm performed more graded exercise under the guidance of trial therapists, they may have simply cut back on other activities to compensate, as has been found in other studies of graded activity. He also notes that the therapists in the trial were possibly more cautious than therapists in everyday practice.

“In the PACE Trial, there was a much greater focus on the issue of safety [than in previous studies of graded activity], with much greater monitoring of adverse events,” says Kindlon, who published an analysis of the reporting of harms from trials of graded activity in ME/CFS, including PACE. “In this scenario, it seems quite plausible that those running the trial and the clinicians would be very cautious about pushing participants to keep exercising when they had increased symptoms, as this could increase the chances the patients would say such therapies caused adverse events.”

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Had the investigators stuck to their original plan, we would have more evidence to evaluate participants’ activity levels.  Originally, participants were going to wear a wristwatch-sized ankle band called an actometer, similar to a FitBit, that would measure how many steps they took for a week at the beginning of the trial and for a week at the end.

A substantial increase in the number of steps over the course of the trial would have definitively established both that participants were exercising and that they weren’t decreasing other activity in order to do so.

But in reviewing the PACE Trial protocol, which was published in 2007, Kindlon noticed, to his surprise, that the researchers had abandoned this plan. Instead, they were asking participants to wear the actometers only at the beginning of the trial, but not at the end. Kindlon posted a comment on the journal’s website questioning this decision. He pointed out that in previous studies of graded activity, actometer measurements showed that patients were not moving more, even if they reported feeling better. Hence, the “exercise program” in that case in fact did not raise their overall activity levels.

In a posted response, White and his colleagues explained that they “decided that a test that required participants to wear an actometer around their ankle for a week was too great a burden at the end of the trial.” However, they had retained the actometer as a baseline measure, they wrote, to test as “a moderator of outcome”—that is, to determine factors that predicted which participants improved. The investigators also noted that the trial contained other objective outcome measures. (They subsequently dismissed the relevance of these objective measures after they failed to demonstrate efficacy.)

That answer didn’t make sense to Kindlon. “They clearly don’t find it that great a burden that they drop it altogether as it is being used on patients before the start,” he wrote in a follow-up comment. “If they feel it was that big of a burden, it should probably have been dropped altogether.”

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The other major flaws that make it impossible to assess the validity of their safety claims are related to those that affected the PACE trial as a whole.  In particular, problems related to four issues affected their methods for reporting harms: the case definition, changes in outcome measures after the trial began, lack of blinding, and encouraging participants to discount symptoms in a trial that relied on subjective endpoints.

First, the study’s primary case definition for identifying participants, called the Oxford criteria, was extremely broad; it required only six months of medically unexplained fatigue, with no other symptoms necessary. Indeed, 16% of the participants didn’t even have exercise intolerance—now recognized as the primary symptom of ME/CFS—and hence would not be expected to suffer serious exacerbations from exercise. The trial did use two additional case definitions to conduct sub-group analyses, but they didn’t break down the results on harms by the definition used. So we don’t know if the participants who met one of the more stringent definitions suffered more setbacks due to exercise.

Second, after the trial began, the researchers tightened their definition of harms, just as they had relaxed their methods of assessing improvement. In the protocol, for example, a steep drop in physical function since the previous assessment, or a slight decline in reported overall health, both qualified as a “serious deterioration.” However, as reported in The Lancet, the steep drop in physical function had to be sustained across two out of the trial’s three assessments rather than just since the previous one. And reported overall health had to be “much worse” or “very much worse,” not just slightly worse. The researchers also changed their protocol definition of a “serious adverse reaction,” making it more stringent.

The third problem was that the study was unblinded, so both participants and therapists knew the treatment being administered. Many participants were probably aware that the researchers themselves favored graded exercise therapy and another treatment, cognitive behavior therapy, which also involved increasing activity levels. Such information has been shown in other studies to lead to efforts to cooperate, which in this case could lead to lowered reporting of harms.

And finally, therapists were explicitly instructed to urge patients in the graded exercise and cognitive behavioral therapy arms to “consider increased symptoms as a natural response to increased activity”—a direct encouragement to downplay potential signals of physiological deterioration. Since the researchers were relying on self-reports about changes in functionality to assess harms, these therapeutic suggestions could have influenced the outcomes.

“Clinicians or patients cannot take from this trial that it is safe to undertake graded exercise programs,” Kindlon says. “We simply do not know how much activity was performed by individual participants in this trial and under what circumstances; nor do we know what was the effect on those that did try to stick to the programs.”

Correction: The original text stated that the Institute of Medicine report came out “this” year; that was accurate when it was written in late December but inaccurate by the time of publication.

Comments on this entry are closed.

  • RhymesWithElena

    Once again, thank you so much! Hugely valuable, very much appreciated. Keep up the good work.

  • clark ellis

    Thanks for this, really important issue to raise. How they get away with making the claim that it is safe without presenting sufficient evidence to back it up, is astonishing. With all the reports from the real world of harm from GET in ME/CFS this issue must be given the attention it deserves. I was personally harmed by GET and you can read my short story on that here: http://stories.meaction.net/2015/11/10/graded-exercise-therapy-ruined-me/

  • Graham

    Essentially then, the PACE trial was a test to see whether therapists
    could, over a dozen or more sessions, persuade patients to grade their
    symptoms more leniently, irrespective of how the symptoms really were,
    even if they deteriorated. Or, in my terms, to make patients wary of
    saying how ill they really were.

  • Mike Dean

    The tightening of adverse event reporting compared to the relaxation of outcome measurement is one of the more unethical aspects of PACE, so thanks for highlighting it. Patients were assessed at 12, 24 and 52 weeks. Under the more stringent criteria, adverse responses appearing shortly after the first assessment at 12 weeks then had to persist until week 52 to count. Imagine a pharmaceutical trial where a serious decline in overall health was ignored unless it lasted 9 to 10 months.

  • disqus_Rv8tqVZbOP

    Again, more misinformation and misrepresentation that continues Tuller and Rehmeyer’s made up narratives.
    It is curious that those with journalism and public health degrees cannot understand or accurately portray basic issues.
    The hallmark of CFS is not PEM, it is optional. That which is optional is not a hallmark. The hallmark or defining characteristic is fatigue. Look it up.
    PACE used the Oxford definition, which studies those with 6 months of fatigue. It does NOT include PEM. Clearly stated. They studied what they said they studied, not what YOU think it is or should be….
    Yes PACE was a bad or flawed study, but Tuller and Rehmeyer’s disingenuously tweaking and embellishing for whatever purposes only does us more harm. Does more harm in general than any one study, no matter how flawed.

  • Peter Kemp

    Patients with ME/CFS have often had every aspect of their lives shattered. They are quite simply desperate to improve and recover; to the extent that I imagine that many would determinedly undertake a treatment even if it carried a risk to their very life. The notion that patients struggling in the rubble of their former life, would baulk at enduring pain in exchange for recovery – is not just disrespectful; it is stupid and divorced from reality. Treating ‘deconditioning’ could not be simpler. Just about everyone does it for themselves, after ‘flu, glandular fever, a broken leg etc. At first it is hard to get back to normal, but in just a few days it gets easier. After months of GET, PACE participants that stuck to the regime should have been fully recovered if the deconditioning theory had any merit whatsoever.

  • H. Clay Johnson III

    Let me highlight one issue which tends to get lost in the detail. The PACE authors did a trial to see if Graded Exercise Therapy was both safe and effective, yet totally failed to measure the difference between total activity with and without therapy, or change in total activity after therapy.

    Do you need a PhD. in experimental design to detect a problem with this?

  • Stephen Wright

    yes and when you take into account that the actual objective measures were dropped and dismissed – the truly absurd reality of this study is exposed.

    When the primary treatment is to persuade patients they are not as ill as they think they are, you could only ever hope to get a useful result by using objective measures. You simply cannot try to brainwash patients, then get them to fill out a questionnaire – and call that science. Its time to end this nonsense.

  • Lou Corsius

    It may be obvious that your reaction is nothing more or less than your personal opinion.
    I, on the other hand, am very pleased with their findings and their efforts to let the public, the scientific world and doctors and psychologists know that PACE results cannot be taken serious in any way.

  • Thanks so much for this. In my reading of the PACE trial, I had known about their redefinition of recovery halfway through, but I hadn’t known about the simultaneous redefinition of harms. As someone who has been made permanently disabled by the UK’s Graded Exercise Therapy, I am very grateful for these flaws being made more widely known

  • Simone

    The IOM report released last Feb reviewed much of the literature, and concluded that PEM is a hallmark of ME/CFS. The IOM report’s recommended diagnostic criteria consists of 3 mandatory criteria: PEM is one of them. PEM is also a required symptom of the 2 most well-regarded definitions (CCC/ICC). That PEM is absent from, or not required, in other definitions, has been a criticism of them.

    The P2P report, released a few months before the IOM report, concluded that the Oxford definition is too broad, is impeding research progress and should be retired from the field. An examination of the definition used to select participants for a trial is an important part of any critique of any study.

    I don’t see any misinformation or misrepresentation here.

  • Nic

    Wow – that really brings it into perspective. It took me six months to get over the effort involved in filling in the ESA form for the first time, and that wouldn’t have counted as an adverse response. Imagine testing for allergies and deciding only full-blown anaphylactic shock counted?!

    In fact, I wouldn’t be madly surprised to find that any patient reporting that extreme persistence of adverse effect finds that it winds up being a permanent downturn in health. It would take something on the scale of my monumental collapse at the end of uni – following prolonged and massive systemic overstrain – to show up with those criteria. Certainly, as of ten years later, I still haven’t improved at all from my setback.

    (I had to split my final year in two to keep up with the workload as my health had deteriorated gradually under the strain of the university workload. Even with reasonable adjustments, there’s only so far you can pace yourself at uni. When my final project rolled around, I wasn’t given the lab help that I’d been told would be organised for me, so I had to run far too many lab tests myself and wound up spending a month away from the lab, confined mostly to bed apart from meals/bathroom. The academic staff finally (and grudgingly) organised the practical help I needed, and I got back into the lab and soldiered on, still putting too much effort on ignoring my symptoms to get it finished, because I’d already got worse enough over the past years that I knew I wouldn’t be well enough for a another shot at it. By the time the Easter hols came up, and only the analysis and write-up was left, I went home – and spent the entire hols, and weeks afterwards, on pretty strict bed rest. All available energy went to brainwork – I revised in bed, I dictated my reasoning and maths for the writeup in bed whilst my dad acted as amanuensis (him being a scientist with a very different specialty to mine was great, as he could be very helpful for overcoming my problems without needing to worry about crossing the line into doing the work for me), and when my brain was at its foggiest, I relied on him to suggest the words that I couldn’t find.

    And finally, when the deadlines got too close, I returned to uni, shoved my symptoms to the bottom of my brain and finished the course. …And then my uni had the cheek to suggest that because I’d had a lab helper for some of the lab time, they couldn’t be sure I knew how the various experimental techniques were performed, and demanded I sit an extra viva to prove my practical knowledge! …And then, once results were out, I went home again and pretty much crawled back into bed until it was time for graduation.

    But the end result was that my health never recovered to the state it was before my final year at university, let alone the state of health I was in before uni, when I would have been just about capable of holding down a part-time job.)

  • Nic

    Yes, and as we’ve told you before, the authors of PACE are very clear that THEY consider CFS and ME to be synonymous – some of them are, in fact the very people who originally championed the change of name and persuaded the UK medical profession to stop diagnosing ME and put all patients with those symptoms into the CFS diagnosis instead.

    Tuller and Rehmeyer are not being disingenuous; they are sticking up for all the ME patients who have been buried under the new name and mistreated as a result. Whatever the PACE authors say about the definition of the illness they’re studying, the fact remains that it is ME patients who are being harmed in their name, under their auspices.

  • cluecat

    Yeah, PACE is bs. Couch-to-5k has sedentary people conditioned to run 3 miles in two months. PACE can’t get participants get in better shape than heart failure patients in a year.

  • Sasha

    Many thanks for another informative and important post.

    The ditching of the actometers in this trial was a catastrophe. That was the best chance of getting objective data in this £5m trial and the experimenters decided that while it was fine to push patients through a walking test and a step fitness-test, it would be too much for them to wear an ankle bracelet for a week, which they would barely have known was there.

    Ridiculous.

  • disqus_Rv8tqVZbOP

    Peter White has stated that they were not studying ME. And we’ve told you and Tuller and Rehmeyer that ME and CFS are not synonymou.They are NOT sticking up for ME patients; they are furthering the ME/CFS misinformation and misrepresenting the issues. ME patients are harmed by ME/CFS misinformation, not PACE. PACE is on CFS, not ME. Get rid of CFS and PACE and the fatigue nonsense goes away.

  • disqus_Rv8tqVZbOP

    PEM is the hallmark of SEID (IOM). It is not the hallmark of CFS.
    So what if P2P said that Oxford def was too broad. This is still what PACE was studying. They can study what they want. However, to that end, this whole PACE frenzy is relatively moot in the US as HHS does not recognize or cite it in anything.

  • disqus_Rv8tqVZbOP

    Actually not my opinion, it is that the definitions are as written which Rehmeyer and Tuller misrepresent. Again it is not their finding, these flaws and criticisms were put forth years ago. And yes most already were well aware of the flaws with the PACE trial.

  • Helle Rasmussen

    Just one comment:
    Since we are on the other side of the New Year, I will suggest that “this year” is changed into “from 2015” in this sentence, just to be precise:
    “An Institute of Medicine report this year even recommended that the illness be renamed to emphasize this central problem, choosing the name “systemic exertion intolerance disease,” or SEID.”

    Thank you so much for another very important blog post!

  • acacia1

    Thanks for covering this issue, Julie. It has been bothering me. It struck me that PEM was defined out of existence in PACE. the Protocol covers ‘Non-serious adverse events and reactions’ and they say:
    ‘Non-serious adverse events or reactions
    will be assessed by the RN at each follow-up assessment interview (see 10 & 11). A risk assessment has been undertaken, and we have concluded that the therapies are of low risk to participants.’
    They determined this BEFORE they conducted PACE.
    ‘Examples of expected nonserious adverse events have been identified, and these include:

    • Development of new mood disorder
    • Musculoskeletal injuries – e.g. ankle
    sprains etc.,
    • Transient exacerbation of fatigue or
    pain, expected as a normal reaction to CBT or
    GET in patients with CFS/ME, which does
    not have significant impact upon function (see 14.1.1 (a))
    • Development of new sleep disturbance P66 ‘

    It is striking that ‘exacerbation of fatigue or pain’ are considered NORMALin these patients, unless they have significant effect on function. Presumably then they are considered serious? Much of PEM falls down a black hole with sleight of hand definitions.

    disqus_Rv8tqVZbOP, please note they say CFS/ME. not just ‘CFS’ as per Oxford criteria. At best the authors seem to have been confused about what condition they were investigating. The 2011 paper also states 51% of patients had
    PEM, (due to them meeting the London criteria which includes PEM). In the 2013 paper they generalise applicability of the findings to ME provided the major symptoom is fatigue. whatever that means.

  • Jimbobsky

    They were studying their own interpretation of the set of symptoms that are predominantly connected to Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and which are still related. This DID include PEM as the whole purpose of GET is to increase activity without bringing on the symptoms such as fatigue and post-exertional malaise that causes pain and suffering to the patient. To quote the actual protocol:

    ‘The chronic fatigue syndrome (CFS) is a condition characterised by chronic disabling fatigue and other symptoms, which are not better explained by an alternative diagnosis [1–3]. Myalgic encephalomyelitis/encephalopathy (ME) refers to a severe debilitating illness thought by some to be a separate illness, but by others to be synonymous with CFS [2–6]. In keeping with the MRC Research Advisory Group report and the CMO’s working group report, we will refer to the illness using both terms: CFS/ME [4, 6].’ (http://bmcneurol.biomedcentral.com/articles/10.1186/1471-2377-7-6).

    So they were treating the symptoms of BOTH illnesses. I am someone who has been diagnosed with CFS/ME (mostly ME with PEM and extreme pain), treated by a member of PACE/NICE guidelines teams, and ended up very ill because of it (unable to get out of bed without assistance ill!). I’ve said it before on this site – if one of the collaborators of the PACE trial and co-author of the NICE guidelines can’t make their own treatment work, then who can??

  • Nic

    Peter White has stated that they were not studying ME, because Peter White does not believe that ME is a separate illness from CFS, and the CFS name and definition is the only one that he acknowledges as existing.

    As long as he and his ilk control the perception of the situation in the UK media, those of us living in the UK have to accept that even if we have the most textbook case of classic epidemic ME ever written, our doctors are still going to call it CFS, and are still going to try to treat us with whatever Peter White and his friends say is good for CFS.

    You don’t live in the UK – good for you, you get the privilege of having your illness called by it’s true name – but we don’t! And we have to live with the consequences and fight the misinformation where it is actually happening! But pretending that White and co are not trying to treat people with ME because the name is different, is like sticking your fingers in your ears and your head in the sand.

  • disqus_Rv8tqVZbOP

    Then this makes no sense. If it’s just a name then he would say that he was studying ME (transitive property).
    Oh and gee, why do people call it CFS??? Because these bogus groups/advocates ALL go along with and promote the ME/CFS claptrap. Would AIDS people have simply gone along with GRID/AIDS or GayPlague/AIDS? It is ludicrous. Yet this is what we are expected to accept, while these so called groups ALL ban and censor anything other than their spin, misinformation (Rehmeyer, Coyne and Vastag ALL block/censor any discussion of issues on social media or that of THEIR ilk).

  • disqus_Rv8tqVZbOP

    They were treating some symptoms (of both illnesses). That is NOT the same as saying it is a treatment for the illness. What illness is fatigue not a symptom of? Actually this is the ME/CFS fraudsters and those pushing it constant disingenuous musings.

  • Jimbobsky

    They are saying it is the only evidence based treatment for the illness CFS/ME. Believe me when I say that the people who came up with GET, those who developed the programme and who provide it as a service to sufferers consider it not just a treatment but a means to be recovered from it to live a functional life. And that’s the problem – how to define a ‘functional’ life? It certainly isn’t back to full health or able to work full-time for me. I don’t believe I’m just chronically fatigued as this isn’t my main symptom. Muscle and joint pain, headaches, twitching limbs, exhaustion after doing very little – I had all these symptoms before knowing anything about advocacy groups, the PACE trial and issues with how it is named. All I know is that I’ve gone from being able to walk 7 miles a day with no issues to walking 7mins a day in substantial pain since having Glandular Fever. All I want is an answer to what’s going on inside my body.

  • disqus_Rv8tqVZbOP

    They measured fatigue. As stated. You cannot trash every trial for everything that they did not measure. No study could measure up.

  • disqus_Rv8tqVZbOP

    OK there is no actual illness CFS/ME, it is just a term with different meanings, so on it’s face is absurd.
    And yes, what is a functional life? This is so subjective as to be equally absurd. Hard to argue this.
    We will never get to the specific illness of ME if it is obscured by/as CFS.

  • Jimbobsky

    Agreed we won’t get to ME via CFS. But the truth is GET is being used to treat the chronically fatigued, ME sufferers, fibromyalgia, recovering from viruses, pain syndromes, chronic pain……based on just 2 trials that in real-life situations isn’t doing what was expected of it. So there must be questions asked because too many people ARE being harmed by this programme. If the same applied to cancer sufferers there would be a national outrage. Sadly, this is not the case for us and arguing doesn’t help. We just want answers.

  • disqus_Rv8tqVZbOP

    People who do not have what the study is not studying. This is the real problem. Should NOT apply to ME patients, but does, primarily due to CFS vis a vis the ME/CFS misinformation that Tuller Rehmeyer and ilk contribute to. So yes this is exactly what ME patients must argue.

  • H. Clay Johnson III

    Fatigue is both a subjective experience and an objective phenomenon measurable in several ways: reduced capacity for exercise, reduced activity, increased metabolic products of exercise, etc. The authors have never expressed interest in metabolic studies, but in their proposal for the study they not only said they were going to measure total activity and changes in this, but even requested funds for equipment to do this. Once they had these funds and that equipment they changed their minds about measuring changes in total patient activity. It might be that this was due to three other studies which had found patients were displacing activity from a fixed budget to participate in therapy, something the authors might wish to deny. The equipment required is equivalent to the popular “FitBit”, so can’t be considered seriously difficult for patients to use. By making all objective measures secondary to subjective ones, then making the remaining objective measures meaningless, the authors have managed to pull a “bait and switch” of the plans in their initial proposal.

  • Nic

    You know what…nope. I give up.

    Feel free to go off into your little delusional corner where the bad guys never have the social power to keep the conversation framed on their terms, and the good guys never have to compromise on small things (like names) in order to keep fighting the big issues (like lives).

    Meanwhile, I’ll be over here in the real world, trying to draw more people’s attention to the case of Karina Hansen and all the other people with ME who have been directly harmed by inappropriate applications of CBT/GET therapies.

    (If you haven’t heard of Karina, she’s a young Danish woman who was diagnosed with ME by several reputable doctors. In 2013, she was involuntarily and forcibly committed to a psychiatric hospital because a psychiatrist decided she ought to undergo a course of GET and she refused the offer. The Danish government have so far refused to recognise that her rights were violated because hey, medical people know best, right? And let me just point out that despite your assertion that he only treats CFS, Peter White is known to have been involved (as an advisor) with Karina’s forced treatment and convenient psych rediagnosis!)

  • A.B.

    With assessments at 12, 24 and 52 weeks (as posted by Mike Dean below), any steep deterioration of physical functioning occurring at 25 weeks or later would have been ignored.

    What kind safety study ignores deterioration of physical functioning in the second half of the study? That’s crazy.

  • A.B.

    Even worse, patients that report harm from GET usually describe it as cumulative harm accrued from many sessions. So it’s more likely to occur later in the program.

    Again the protocol looks like it was designed to make the favorite interventions of the investigators look good, with disrespect for the welfare of patients and good science.

  • Star Man

    I must strongly disagree that “this whole PACE frenzy is relatively moot in the US”.

    My HMO (Kaiser Permanente) in the US cites the PACE trial abundantly. Their website has patient info sections such as “Chronic Fatigue Syndrome: Using Graded Exercise to Get More Energy” and “Chronic Fatigue Syndrome: Using Healthy Thinking”.

    When I struggled with my physician prescribed exercise program, I was encouraged to push myself to exercise as much as I could. I was told my increasing stumbling, orthostatic intolerance, breathing difficulties, and other central nervous system problems were imaginary. I was prescribed various stimulants to continue working and exercising.

    A year ago, barely able to walk, I had to quit my job. I remain mostly housebound; dependent upon family and $200 per week of disability to survive.

    In the United States, real patient harm and utter destruction of lives continues to occur because of this scandalous study.

  • anniekim

    I think their argument is as Tuller says in the article some increased pain and fatigue after increased exertionwould be expected if deconditioned, but would be transient and so can be ignored. Of course people with this illness are not deconditioned and the cumulative effects of going beyond one’s limits can cause long term further disability.

  • disqus_Rv8tqVZbOP

    In spite of their hyperbole, it is not all about PACE. The US health agencies do not recognize it. And most are well aware of the the flaws. The OI, neuro, CNS stuff was not addressed or included in PACE, so you cannot blame the PACE trial. And this healthy positive attitude thing is foisted on almost everyone.

  • disqus_Rv8tqVZbOP

    Well sorry that you cannot think beyond the misinformation. That’s what they thrive on and ban and censor to try to control the dialogue.
    So the self righteous ploys to skew the argument always come out.
    Your ME/CFS nonsense allows him to say that he treats ME. That’s what happened to Karina.

  • disqus_Rv8tqVZbOP

    Or in the real world, PACE was not on ME so should not apply to or harm ME patients.

  • Star Man

    “Chronic Fatigue Syndrome: Using Graded Exercise to Get More Energy” cites several sources, including:

    White PD, et al. (2011). Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): A randomised trial. Lancet, 377(9768): 823–826.

    U.S. Department of Health and Human Services (2008). 2008 Physical Activity Guidelines for Americans (ODPHP Publication No. U0036). Washington, DC: U.S. Government Printing Office. Available online: http://www.health.gov/paguidelines/guidelines/default.aspx.

    Perhaps the US health agencies do not recognize PACE. But that’s meaningless if patients are still subjected to PACE.

  • disqus_Rv8tqVZbOP

    Right, Cites SEVERAL sources. Not just PACE. Thus they are not “subjected” to PACE.

  • etherspin

    so to make a crazy but valid analogy, if a study tested the ability of cream X to make hair grow faster it would be fine not to record the final length of the hair to compare to baseline growth rates, as long as we got reports about the level of shine and the number of split ends ?

    of course studies could measure up to these basic standards, these are absolutely crucial metrics for researchers who went on to publically state that GET is safe

  • etherspin

    PEM is almost universally considered non optional except for flawed criteria like the Oxford set – selecting this set is as ill advised as underestimating PEM.

  • disqus_Rv8tqVZbOP

    No this analogy is about effectiveness not safety.

  • Sasha

    David, may I ask when the 20-day response deadline is up for your FOI request for the PACE data?

  • disqus_Rv8tqVZbOP

    Again, they can study what they want using whatever criteria they want. This is how science works. What is ill advised is to combine and conflate it with ME viv a vis ME/CFS which will misinform and misdiagnose. This is what this blog (Tuller, Rehmeyer and ilk)
    seems to want to promote and make all kinds of excuses. Why is this even on a virology blog, and taking up this amount of space?

    So, one more time, PACE is not studying ME.

  • Valentijn

    Patients with ME/CFS are very much disabled by it. None of the patients I have ever heard from were particularly concerned with “fatigue”. We want to be able to sit up again all day, to go to school or work, to take a normal shower or bath. Fatigue endpoints do not matter to patients. The authors are lying when they claim that we do.

    They are also lying when they claim that subjective outcomes are appropriate because our symptoms are all subjective. Post-exertional malaise results in unique gene expression and VO2max results 24 hours after exertion. Tilt Table Tests show low blood pressure, low pulse pressure, and/or tachycardia in response to being upright for too long. Actometers, when used, show that our activity levels are shockingly low compared to sedentary controls. The 6 minute walking test shows that we’re badly disabled.

    The PACE trial did test for some of those, and avoided testing for others, despite that they are widely known to be relevant to ME/CFS patients. When those objective results showed no improvement, they were downplayed. ME/CFS patients did not become fitter. They did not get back to work. They did not get off of benefits. They just learned to say they were a bit less fatigued after a year of brainwashing.

  • Valentijn

    In the real world, that comes across as a weak argument, unfortunately. We can yell it all we want and try to ignore PACE as being irrelevant, but the fact is that doctors and government agencies see it as applying to all definitions of ME and/or CFS.

    It isn’t sufficient to pretend that we won that argument, even if we rationally should have won it. PACE obviously doesn’t apply to ME, but most people won’t believe that. On the other hand, there are many other glaring problems which even non-ME patients/experts/advocates can easily recognize as being problematic.

    We need to focus on the arguments that work, not just the ones that we feel are the most “right” or most relevant.

  • disqus_Rv8tqVZbOP

    Right. PACE never claimed to be relevant to “ME/CFS.” There is technically no such illness as ME/CFS, but you are defining or describing what it is, which is nonetheless not what PACE studied. So PACE is not relevant to this or many other things.

  • disqus_Rv8tqVZbOP

    But thing is, they don’t work. We should educate, not go along with these false beliefs??? That’s just lunacy. Drs do not put much stock in PACE, certainly not in any official US HHS realm. I think we should still stick with what is most right and most relevant, not play these same games that Tuller and ilk are fostering.

  • patrick holland

    Thanks for that, David. We need to move from social media to other forums offline to bring these matters to a more practical conclusion.There should be enough evidence now for patients to bring legal actions and court actions and government actions against these “researchers” and challenge them directly. Some people have proposed plans for this
    http://www.me-ireland.com/scientific/16.htm
    http://www.me-ireland.com/bogus.htm
    http://www.me-ireland.com/bogus.htm#sci