Back to list All Articles Archives Search RSS Terug naar lijst Alle artikelen Archieven Zoek RSS

Myth-busting a myth busting

Myth-busting a myth busting

Photographer:Fotograaf: Forbes.com

“Many ME-patients suffer from tremendous exhaustion for days after exercise, the so-called post-exertional malaise, or PEM. There were doubts as to whether the large British PACE trial was correct,” said professor of Internal Medicine and Immunology Jan Willem Cohen Tervaert, a couple of weeks ago in the Myth Busters- series of Observant. The professors Trudie Chalder, Michael Sharpe and Peter White, who led this PACE trail on the chronic fatigue syndrome, are convinced that cognitive behaviour therapy and graded exercise therapy “are moderately effective and safe for patients with CFS/ME. To suggest that this is not the case is to propagate a myth”.

Professor Cohen Tervaert states in his interview with Observant in “Myth: ME is a mental illness” that chronic fatigue syndrome (CFS), regarded as another name for ME, is a disabling and much misunderstood illness. Feeling worse after activity is a central feature, along with poor concentration, sleep problems and pain. We agree with these statements.  But, in his keenness to debunk the myth that such a serious illness can be readily dismissed as unreal or unimportant, he risks creating a new myth – that behavioural treatments do not help people with CFS.

We led the PACE trial, which was criticised by Professor Cohen Tervaert, and which found that such treatments are effective. The PACE trial was the largest trial of any treatments of the illness, in which 641 patients with CFS were randomly allocated to one of four treatments: specialist medical care or specialist medical care in addition to one of three therapies: adaptive pacing therapy (pacing activity to stay within the limits of the illness), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). The results clearly showed that CBT and GET improved both symptoms and disability more than the other two treatments. Equally importantly, the trial showed that all four treatments were safe. This trial added to the evidence from many previous trials showing the same thing; that CBT and GET safely helps people with CFS. At the same time, we emphasise what we said in our main paper: “The effectiveness of behavioural treatments does not imply that the condition is psychological in nature.” CBT and GET are useful treatments for many chronic and disabling physical conditions.

In a secondary analysis, we found that 22% of patients who had CBT or GET, met criteria for recovery, compared to 7% and 8% after the other two treatments. Our criteria for assessing recovery (all of which had to be met) included: being within the normal range for fatigue and physical function, no longer having CFS sufficiently badly to be eligible for the trial, and patients rating their own overall health as either “much better” or “very much better”.

As Professor Cohen Tervaert said, some data from the PACE trial were released last year under the UK Freedom of Information Act. Some patient activists, aided by two statisticians, re-analysed just the recovery data – not the main outcome results. They used more stringent thresholds for defining recovery, such as only counting people who were “very much better”.  Unsurprisingly, they found that smaller numbers of patients met their criteria for recovery. Using different thresholds to assess recovery will clearly result in different recovery rates. There is no universally agreed definition of recovery, so we cannot be sure which figures are most accurate, but previous trials and studies of patients found similar figures to ours.

However one chooses to define recovery, the main findings of the trial stand - that CBT and GET are both safe and effective in reducing fatigue and improving functioning. In such a chronic and disabling illness, it is good to have a hopeful message for patients that, like previous researchers, we found not one but two treatments that are moderately effective and safe for patients with CFS/ME. To suggest that this is not the case is to propagate a myth.

 

Professors Trudie Chalder, Michael Sharpe and Peter White, Kings College London, University of Oxford, Queen Mary University of London, UK

Read here the opinion article of Mark Vink, in Dutch

Read here the reaction of Mark Vink in English

Read here the reaction of David Tuller in English

Read here the reaction of Caroline Wilshire in English

Categories:Categorieën:
Tags:
me

CommentsReacties

2017-03-23: K
Thankfully readers can now freely access an independent reanalysis of the PACE trial data, showing that “PACE trial claims of recovery are not justified by the data”:

Full paper (free access) http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724

See also Wilshire et al’s response to the PACE authors’ criticism of their reanalysis:

https://www.researchgate.net/publication/315482747_PACE_trial_claims_of_recovery_are_not_justified_by_the_data_A_Rejoinder_to_Sharpe_Chalder_Johnson_Goldsmith_and_White_2017

and Lubet’s summary of what is wrong with the PACE trial (an easy-to-read blog post):
http://theconversation.com/how-a-study-about-chronic-fatigue-syndrome-was-doctored-adding-to-pain-and-stigma-74890

2017-03-23: Philosopher of Science
As a patiënt with severe ME i can say that CBT neither GET are safe treatments for ME/CFS patiënts. I did CBT with GET like The Pace trial and ended up in a wheelchair.
And i am not alone there are a lot of harmfull complaints from patiënts (1).

People like Chalder, Sharpe and White don't report this kind of harm in their publications, it is like public bias (Rosenthal).

The Pace trial is no science. It is politic, wishfull thinking and propaganda from a very arrogant elite group of people. This people are bad for the reputation of real science.

1. Neuro Endocrinol Lett. 2009;30(3):284-99. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Twisk FN1, Maes M.
2017-03-23: Thijs

As a patient with 10+ years of CFS, I never really understood this biopsychosocial (BPS) model for CFS.

Multiple doctors/psychologists explained it to me, but i never got a satisfying explanation. Their answers could be categorized as:

A) CFS is de-conditioning, and perpetuated by lack of activity

This seems highly unlikely to me. I have tried to improve my physical condition in the past. I used to do cycling. Progress was slow, but eventually I managed to cycle long distances. I even participated in a +100km tour. Although my fatigue was a bit less during this period, all other symptoms remained, and the activity level didn't turn out to be sustainable.


B) CFS is a variant of Central Sensitization Syndrome, and perpetuated by increased focus on symptoms.

This could be a possibility, however what about the physical abnormalities found in other studies? Reduced VO2 max after extortion, metabolism, immune abnormalities, etc.
I don't understand how a problem with "feeling" fatigue is supposed to affect these processes.


C) CFS is a chronic burnout, and perpetuated by stress/fear about activity (via cortisol).

Again this could be a possibility, but I can't recognize myself in it. I rarely feel stressed, and someone with fear of activity wouldn't participate in cycling tours.


D) Or, a combination of above.


I can only speak for myself, but if other CFS patients got the same answers as I did, I can understand why they are skeptical; This BPS model for CFS is incomprehensible for patients.

In my opinion the authors of these studies should come with a stronger hypothesis of what CFS is, and it should be able to explain the abnormalities found in other studies. Without this, the patients will probably remain skeptical, and I think they are right to do so.
2017-03-23: jimells
Regius Professor Sir Simon Wessely has publicly stated that the PACE trial "is a thing of beauty". And indeed it is. Like Thor's Hammer, it is being used by patient advocates and prominent academics to smash the "CFS" psycho-babble lobby to bits.

Instead of accolades, the "Wessely School" psychiatrists will soon be receiving subpoenas. Time to buy popcorn, sit back to enjoy the show, and write another check to Dr Ron Davis' research group in the U.S.
2017-03-23: adrian
Patients performing a reanalysis of the recovery claims used the definition of recovery that was taken from the PACE protocol. This was one that they thought was ok before they saw how the open label trial was going.

I would challenge anyone to look at the sf36 physical function questionnaire and try to come up with answers to the questions that have a score of 60 and where they can claim that such answers reflect someone who is recovered. Then do the same for the CFQ.

They also fail to mention that they changed the primary outcomes for their trial after its start and after they were forced to release data we discovered their changes massively overstated the results.

More seriously the whole protocol was flawed as they had some interventions aimed at changing how people thought about their symptoms and abilities and judged success by asking people about their abilities and symptoms,

Claims of safety are also not safe as they failed to monitor compliance with treatments. They also changed the protocol defined measures for serious adverse events

I find it hard to believe that the authors of PACE have failed to grasp the criticisms and what they have done wrong. They should releasing data and doing some serious thinking about how they have mislead patients.
2017-03-23: Teresa
How can anyone claim GET is safe for ME patients when the main defining symptom is PEM - post exertional malaise. Exercise for ME patients has been quoted as the equivalent of sugar for diabetics. Absolutely disgraceful and incorrect comments from the debunked PACE trial authors
2017-03-23: DSGG
"Some patient activists, aided by two statisticians, re-analysed just the recovery data – not the main outcome results. They used more stringent thresholds for defining recovery, such as only counting people who were “very much better”.

In their reply Chalder, White and Sharpe have neglected to mention that these 'more stringent thresholds' were in fact drawn up by the three of them (along with the rest of the PACE team) at the outset of the PACE trial and included in the pre-trial protocol - but they were then substantially loosened part way through the trial.

The PACE authors have previously insisted that they made this decision to relax the recovery definition after all the trial data had been collected but before they started analysing it. If this is true, perhaps Chalder, White and Sharpe can finally explain what happened mid-trial to persuade them that the original definition - which they chose, and clearly had sufficient confidence in to include in the trial protocol - was excessively stringent?

Given that Chalder, White and Sharpe acknowledge in the second paragraph of their response that PACE was "the largest trial of any treatments of the illness" it is highly unsatisfactory that the only justification they have offered for this change is that the revised recovery definition gave results consistent with earlier trials and studies. These earlier studies into GET and CBT were - by definition - smaller and less comprehensive, and the stated intent of PACE was to confirm (or disprove) the results of the earlier research into these treatments. Until they offer a better explanation Chalder, White and Sharpe seem to be essentially acknowledging that they looked at the earlier trials - whose results they were expecting to validate - and then tweaked their own trial methodology to ensure that they got the similar outcome they wanted.

It really shouldn't need saying, but this is not how good science is conducted. Good scientists don't start with the conclusion they want and then torture the data until it says what they want it to.
2017-03-23: Ashley Hinds
"Some patient activists, aided by two statisticians, re-analysed just the recovery data – not the main outcome results. They used more stringent thresholds for defining recovery, such as only counting people who were “very much better”. "

Everybody reading please take note that these 'patient activists' and the statisticians who re-analysed the data, did so using the PACE team's OWN published, pre-planned protocol for analysing the data.

Your team switched outcome measures, presumably to hide the embarrassing null result that invalidates your life's work.

The 'patient activists' merely did what your team committed to do before they performed the study.

Sunlight is the best disinfectant. Any reasonable person looking at these facts can see the truth.
2017-03-24: David Tuller
The PACE investigators continue in their refusal to actually address the key concerns raised about their study. First, they continue to refer to this as a "secondary" paper. While it is true that the PACE authors for reasons only they know designated "recovery" as a secondary outcome in the PACE protocol, "recovery" is surely not of secondary importance to patients, so dismissing the paper's significance is this way is unwarranted.

They dismiss the difference in recovery outcomes between their paper and the reanalysis as just a matter of opinion, because the reanalysis used stricter guidelines. They fail to mention that the reanalysis only used the specific criteria the PACE investigators outlined in their own protocol, and then abandoned in favor of ones that allowed them to report statistically significant recovery rates. They received absolutely no approval from oversight committees for this redefinition of recovery.

In their detailed protocol, they included four very clear criteria for recovery. In the paper as published, every one of these four criteria was significantly weakened, in ways documented by Wilshire et al. For two of the four criteria--physical function and fatigue--participants could get worse and yet still meet the "recovery" thresholds because that revised threshold represented worse health than then entry criteria. Thirteen percent of the trial participants met one or both of these "recovery" criteria at baseline.

They have referred to these thresholds as being within the normal range. Yet this is an utterly dishonest argument. They generated their absurdly expansive "normal ranges" by using the wrong calculation to calculate them. They applied the method of finding the normal range for normally distributed populations--the mean plus/minus one standard deviation--and applied it to population samples that they knew were highly skewed in a positive direction. Dr. White himself, in a 2007 paper he co-wrote, had explained how using this method to determine a purported "normal range" for the SF-36 physical function scale yielded distorted findings. This caveat was not included in the Lancet or Psychological Medicine papers.

The authors themselves know that what they are referring to as a "normal range" is not the standard statistical "normal range" that includes two-thirds of the values but a wildly generous "normal range" that includes upwards of 90 percent of all the population values. That's why they ended up with the absurd "normal range" of 60. The same strategy applies to the fatigue normal range--they developed in the same intellectually dishonest way, and yet continue to refer to it as a "normal range." They have never explained why they used the wrong statistical method to develop normal ranges from highly skewed samples. Moreover, Dr. Chalder has never explained why she referred to these absurd "normal ranges" as "getting back to normal" in the Lancet press conference.

They have recently argued, in response to Wilshire et al, that it doesn't matter that some participants were recovered on the physical function or the fatigue outcomes at baseline because there were other recovery criteria. This is truly a bizarre response for researchers to make. It is also a serious violation of the rules of honest scientific inquiry. It is unclear to me why we all have to waste so much intellectual time and energy simply to demonstrate that studies in which participants can be disabled and recovered simultaneously on key indicators should never have been published and, once published, need to be retracted immediately. The PACE authors have no scientific ground to stand on.
2017-03-24: Guido den Broeder
Can you all please drop ME from this discussion. Myalgic encephalomyelitis (G93.3) is a specific brain disorder with no relation to CFS (R53.82).

Guido den Broeder
ME Vereniging Nederland
2017-03-24: Robin
The PACE trial's objective outcomes have been largely buried and show that the patients were still severely disabled after a year of GET/CBT....

It is so easy to measure physical disability, the failure to do so by White, Sharpe, Chadler and Wessley is at odds with the claim that GET and CBT were effective.

Is there an other trial in which participants are simultaneously ill enough to enter a trial, able to worsen and be labelled recovered???

The reanalysis of the PACE data was done using the PACE authors original published trial protocol....

Can delusional mental health practitioners be directed to treatment?
2017-03-26: Carolyn Wilshire
I was the lead author on the recent critical commentary on recovery rates in the PACE trial.

Being relatively new to the field of Health Psychology research (my background is in Neuropsychology), I have been stunned by the absence of the kind of critical thinking that characterises most fields of Science. Many articles in Health Psychology present only one side of the story; they are written to highlight findings that support the investigators' prior beliefs, and to obscure those that do not. The PACE trial, despite being one of the most prominent and best-funded studies in this field, seems to be no exception.

In our critical commentary, we pointed out a number of major problems with key conclusions from the PACE trial (those regarding recovery). Yet the PACE investigators have still not accepted or acknowledged a single one. Instead, they have used every strategy they can to deflect criticisms or distract readers from the central problems.

This is not some arcane academic debate. Being wrong here has real consequences for very sick people. Patients are fed up with being fobbed off with treatments that simply don't work - or worse still, make them feel sicker - and they desperately need ones that really help.

I urge the PACE investigators to approach this debate more objectively. The first step is to acknowledge valid criticisms. Only then can we really start to move this field of research forward and find better treatments for patients.

Our critical commentary, and our reply to the PACE investigators' letter of defence, can be found here:

http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724
https://www.researchgate.net/publication/315482747_PACE_trial_claims_of_recovery_are_not_justified_by_the_data_A_Rejoinder_to_Sharpe_Chalder_Johnson_Goldsmith_and_White_2017

Carolyn Wilshire, PhD
School of Psychology
Victoria University of Wellington, New Zealand
2017-03-26: Sue Wilson
I greatly object to the word 'activists' that is clearly stated as a put down. They are ME patients who represent hundreds of thousnads of other ME patients. They are intelligent people with a knowledge of research.
I don't think there is a problem with the definition of recovery - clearly recovery means that patients are no longer ill and can return to all the activities of their life before they were ill. I am not aware any participant in the PACE Trial was able too o do this. There is however a problem with the definition of ME. I don't disagree that behaviour management techniques can help people recover from chronic fatigue related to other illnesses such as mental illnesses; I do not accept that the PACE Trial shows recovery for ME patients. It is not clear if everyone who participated had the neurological condition ME as defined by Ramsay in the 1980s or chronic fatigue related to other illnesses.
Sue Wilson, Speech and Language Therapist (HPCP registered) with knowledge and skills in Critical Appraisal of Research Papers
2017-03-30: jimells
Thank you Guido den Broeder for mentioning "CFS" vs. ME.

This is a critical point. The PACE People have long claimed that their results are applicable to anybody with any kind of fatigue from any cause. Their useless "Oxford Criteria" has but one symptom: fatigue lasting six months or more. This criteria was rejected by the Institute of Medicine 2015 report "Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness."

The PACE People in turn have rejected the IOM's conclusions. Likewise they have ignored or rejected the entire body of biomedical evidence developed over the past 60 years - that's well over 5000 studies. They are like little kids sticking fingers in ears and singing "La la la la - I can't hear you!" while covering eyes and thinking they are invisible.

They truly exist in their own little world, with their own public relations firm known as "Science Media Centre" and their own journals whose articles are reviewed by - who else - themselves, of course. They even seem to have their own permanent tap into the funding pipeline. It's all very cozy for them - and deadly for us.

But the problems caused by these psychiatrists go well beyond the ME patient population. They claim, with a straight face, that something like a quarter of ALL patients have so-called "psychosomatic symptoms" that only they can treat.

After 30 years of continuous struggle, ME patients have nearly thrown these kinds of people off our backs. Unfortunately they are already on the hunt for more victims to practice on.

If you have MS, fibromyalgia, irritable bowel syndrome, chronic pain, or any kind of chronic illness, you should be afraid, very afraid.

Post a Comment

Laat een reactie achter

Name (required)

Email (required)

CAPTCHA image
Enter the code shown above: