A large clinical trial might be said to resemble an ocean liner, which is leaving Southampton to sail to New York. It is a complicated system. There will be a captain on the bridge and a large crew. They will have filed a course some time before they set sail, but not everything can be foreseen in advance; the weather for example. Sometimes small corrections to the route will need to be made en voyage. These will be meticulously recorded, authorised by the ship’s owners, otherwise known as the Trial Steering Committee, which can overrule the captain if needed. Occasionally something happens; the vessel is seaworthy, the cabins are ready, and the band has started playing, but the ship never sets out, most often because they can’t get enough passengers on board to make the voyage worthwhile. Very occasionally there is a shipwreck, but this is very rare. Few trials suffer the fate of the Titanic, but sometimes the ship gets to the USA, but not to New York, but some other place; destination changed en route, which is considered bad form. In that case, people may debate for years afterwards what actually pushed them off course, and what that means. But most often the ship does eventually dock in New York, with satisfied passengers, and a tired but relieved crew.
Such a ship was the clinical trial known as PACE, standing for Pacing, graded Activity, and Cognitive behaviour therapy: a randomised Evaluation. It was a very large ship, one of the largest of its kind, and its voyage was undoubtedly one of the choppiest crossings ever. It certainly did make it to the other side, completing its voyage, with a full complement of passengers, and hardly any washed overboard (“lost to follow up”), but its troubles were not over. Indeed even safely in harbour it continues to be buffeted to this day. The question is whether or not it is still shipshape, and whether or not its voyage fulfilled its goals. Some claimed even before the ship had sailed that it should stay in port; one of the main patient organisations in this country campaigned for that before a single passenger got on board. Others have said that the ship struck an iceberg on the way, and even though it limped into New York, all the passengers and crew had a wasted voyage and nothing of benefit emerged.
In this blog I will argue that HMS PACE did make it successfully across the Atlantic. Small corrections to the route taken were made on the way, but these were of little significance. The fundamental mechanics of the ship remained water tight and at no time were the ship or its passengers in peril until it safely docked exactly where it was supposed to. Storms continue to buffet the ship even as it remains in harbour, but none of these have damaged the ship to impair its seaworthiness.
I was not on the ship, neither as passenger or crew. I helped recruit some patients to the study from our clinic, as did many doctors, but that was as far as it went. I am not an author on the ship’s log, but I am not a neutral observer. I know a lot about how these ships sail (Everitt and Wessely, 2003). I know a lot about the passengers, those with the illness known as chronic fatigue syndrome (CFS), because I have seen what must be a few thousand now as a doctor who used to research the illness and continues to see sufferers in the clinic. I have done a few voyages similar to the one undertaken by PACE (e.g. Deale et al, 1997), but not in such a large and complex boat, at least not for this illness. I also make no secret of the fact that I know some members of the crew well. I have worked happily with many of them over the years, and in particular I consider the most senior officers on board this particular ship to be personal friends. Do I have competing interests? Sure I do.
Back on dry land
So moving on from our nautical analogy, I am well informed about clinical trials in general, and about the issues that surround chronic fatigue syndrome in particular. I have previously made it clear that I think that PACE was a good trial; I once described it as a thing of beauty. In this blog I will describe why I still think that and I will try and avoid very technical issues, which have been addressed by the investigators on many occasions. Here is a recent response to criticisms, few of them new.
Nor will I drown the reader in the details of the trial itself, except where necessary. Again, here is a link to the main paper of the trial, so you can check what I say against the main record (White et al, 2011) and here is the follow-up paper published last week (Sharpe et al, 2015).
Finally I will not discuss some of the wider issues that the trial raises, or the wider debate on chronic fatigue syndrome. I will simply state that CFS is a genuine illness, can cause severe disability and distress, affects not just patients but their families and indeed wider society, as it predominantly affects working age adults, and its cause, or more likely causes, remains fundamentally unknown. I do not think that chronic fatigue syndrome is “all in the mind”, whatever that means, and nor do the PACE investigators. I do think that, as with most illnesses, of whatever nature, psychological and social factors can be important in understanding illness and helping patients recover. Like many of the PACE team, I have run a clinic for patients with chronic fatigue syndrome for many years. Like the PACE investigators, I have also in the past done research into the biological nature of the illness; research that has indicated some of the biological abnormalities that have been found repeatedly in CFS.
What was the PACE trial and what were the main results?
The PACE trial randomly allocated 641 patients with chronic fatigue syndrome, recruited in six clinics across the UK, into one of four treatments. Everyone received Specialist Medical Care (SMC), where specialist doctors gave advice on managing the illness and may have prescribed medication for symptoms.
- One group received SMC alone; the other three groups also received a therapy:
- Adaptive Pacing Therapy (APT) where patients adapt their lives to live better with the limits of their condition;
- Cognitive Behaviour Therapy (CBT) where the therapy aims to help patients explore different ways to understand their illness and cope actively; or
- Graded Exercise Therapy (GET) where patients receive help to gradually increase the time they are physically active and then the activity’s intensity. All were followed up until one year after they entered the trial.
What were its main findings? These were simple:
- That both cognitive behaviour therapy (CBT) and graded exercise therapy (GET) improved fatigue and physical function more than either adaptive pacing therapy (APT) or specialist medical care (SMC) a year after entering the trial.
- All four treatments were equally safe.
These findings are consistent with previous trials (and there are also more trials in the pipeline), but PACE, because of its sheer size, has attracted the most publicity, both good and bad. It has already been used as an example of how to conduct a large complex intervention, and has been cited 219 times in Scopus. But of course it has also been subjected to what in my experience is an unprecedented campaign of criticism, which sometimes has merged into something approaching vilification that goes well beyond a reasoned scientific critique.
Reading some of the criticism, I am struck that some of the critics are not familiar with the fundamental strengths of the randomised control trial, and why medicine continues to value it so highly. Likewise, some show unfamiliarity with the core methodological components that contribute to the integrity of a clinical trial, and whose violation calls into question the findings, as compared to what one might call secondary less important features. In other words, what distinguishes a good trial whose results are likely to be sound from one in which there is a definite risk of bias. And so returning to my nautical analogy, what are the main pitfalls that might occur from the moment the naval architects start to design the ship, to it coming safely to rest in New York harbour?
What makes a good trial and how does PACE measure up?
So what does the literature on randomised controlled trials tell us about the factors that are known to influence or bias the results of trials?
a. Allocation concealment
Far and away the most important is allocation concealment; the ability of investigators/patients to influence the randomisation process (a computer algorithm organised independently of the investigators). If trials are to be judged by one quality alone, there is agreement that it would be allocation concealment (Schultz & Grimes, 2002a and b). When this is violated, it calls into question all the findings of a trial, and considerably increases the risk of error. No one has criticised allocation concealment in PACE, it was exemplary.
Next comes power. A study needs to be big. If a study is small then it might well decide that a treatment is not effective when actually it is. Alternatively, it might do the opposite; find something works which doesn’t. Randomisation can’t overcome the chances of a maverick result in a small sample size. None of this applies to PACE. It was planned to recruit 600 patients to four arms and over recruited. Predetermined sample size calculations showed it had plenty of power to detect clinically significant differences. It was one of the largest behavioural or psychological medicine trials ever undertaken. No one has criticised its size.
c. Loss to follow-up
The next thing that can jeopardise the integrity of a trial is major losses to follow up, which would reduce the ability of a trial to deliver a significant result (i.e. loss of power). That is bad enough; it reduces the efficiency of a trial, and might mean that nothing much can be concluded from the results. But the situation would be worse if follow up is also biased by allocation. That would happen if people receiving one treatment were more likely to be followed up than those in a different arm. This would introduce bias, rather than waste, and can invalidate the results even if statistically significant. The key end point in PACE was pre-defined as the one year follow up. 95% of patients provided follow up data at this stage. I am unaware of any large scale behavioural medicine trial that has exceeded this. Again, no one has questioned this, and indeed one of the fiercest critics has specifically praised this. Even more importantly, what little loss to follow up there was did not differ between the treatment arms. So again, we can have confidence in the main results.
d. Treatment infidelity
Next comes treatment infidelity, which is where participants do not get the treatment they were allocated to. PACE had a series of checks on this, including therapy supervisors listening to randomly chosen audio-recordings during the trial, and providing feedback to therapists. At the end of the trial, two independent scrutineers, masked to treatment allocation, both rated over 90% of the randomly chosen 62 sessions they listened to as the allocated therapy. Only one session was thought by both scrutineers not to be the right therapy. Again, no criticism has been made on the basis of therapy infidelity.
e. Analytical bias
The analytical protocol was predetermined (before the analysis started) and published. Two statisticians were involved in the analysis, blind to treatment group until the analysis was completed and signed off. So again, the chances of bias being introduced at this stage are also negligible.
f. Post-hoc sub-group analysis (fishing for significant differences)
This often happens when investigators are frustrated when their main hypothesis is not supported. Especially in large trials, they can then go looking for particular sub-groups which might have responded to the treatment, even if overall there was no effect. A landmark paper on this is the classic analysis of a massive cardiology trial that showed there were significant differences in responses to treatment according to signs of the Zodiac (ISIS 2, 1998). The only sub-group analyses undertaken in the main PACE paper were pre-specified and showed that the outcomes were similar in those patients who met two other definitions of CFS. There were no post-hoc sub-group analyses in the main outcome paper. A couple of sub-group post-hoc analyses were done in follow up publications, and clearly identified as such and appropriate cautions issued. None concerned the main outcomes. Again, no one has raised the issue of sub-group analyses.
Trials can be rated as single, double or even triple blind. This means at the patients, clinicians and raters either know or don’t know which treatment is which. PACE was not blinded; the therapists and patients knew what treatments were being given, which would be hard to avoid. This has been raised by several critics, and of course is true. It could hardly be otherwise; therapists knew they were delivering APT, or CBT or whatever, and patients knew what they were receiving. This is not unique to PACE. It is true in any trial of a psychological, behavioural or surgical intervention for example. Indeed, it turns out to be true in many trials of drug treatments as well, since it is difficult and sometimes impossible to remove recognition of a treatment medicine because of the impact of side effects.
So patients knew what they were getting. This is what would happen in real life, which is what the PACE trial was trying to recreate. Did this matter? One way is to see whether there were differences in what patients thought of the treatment, to which they were allocated, before they started them. There might be problems if one treatment was thought to be better than another, whether rightly or wrongly. Expectations can influence the outcomes, especially in psychological treatments, which is why so called patient preference trials, in which patients chose the intervention they prefer – give results that can be difficult to interpret, which indeed is an issue around the longer term outcomes of PACE after the end of the formal follow up (see the references below). Randomisation removes the worst of this problem, since patients by definition cannot select what they get. But if they still have higher or lower expectations of one treatment over another, it can still matter. And that did happen in the PACE trial itself. One therapy was rated beforehand by patients as being less likely to be helpful, but that treatment was CBT. In the event, CBT came out as one of the two treatments that did perform better. If it had been the other way round; that CBT had been favoured over the other three, then that would have been a problem. But as it is, CBT actually had a higher mountain to climb, not a smaller one, compared to the others.
So far then, I would suggest that PACE has passed the main challenges to the integrity of a trial with flying colours. If we check it against any of the many rating scales that exist for randomised controlled trials, it comes out well, losing points only on the issue of blinding, as do most trials in surgery or psychiatry, and every trial in clinical psychology, social interventions or health psychology. For example, the two most recent systematic reviews in this field rated PACE as good quality, with a low risk of bias, much the same as numerous previous systematic reviews have rated PACE’s predecessors (Larun et al 2015: Smith et al, 2015).
Response to other criticisms of PACE
So now we move on to lesser issues. I say these are lesser issues because that is what the literature on randomised trials says. Not unimportant, but not likely to affect the fundamental integrity of a trial, nor the confidence with which we can view the results. The major criticisms that have been often repeated and can be crystallised as follows:
a. Entry criteria too broad
The criteria for deciding who had the illness were too broad and included people who did not have CFS
There is no “gold standard” definition of chronic fatigue syndrome. Some 20 definitions have been published. The PACE trial used the Oxford criteria. These are broad criteria, chosen to include as many clinic attenders with CFS as possible. Randomisation will have made sure that this had no impact on the main results of the trial. It might potentially influence what is known as generalisation; how much do the results of the trial apply to other populations? Measures taken during the trial allowed the authors to see if the results would have different if other narrower criteria had been used. The answer was no. However, because all patients were recruited in various clinics, those who could not attend clinics were not included. Although there are some case reports of, for example, bed bound patients receiving similar therapies to those tested in PACE, there is no suggestion that the results of PACE can be generalised to such patients. So the findings only apply to those patients who were able to attend clinic regularly, and not to bed-bound patients. The important point to remember is that the choice of criteria did influence generalizability (not to bed bound patients) but did not influence the key findings of the study.
The researchers also used stringent procedures to ensure that those people with another diagnosis that would explain their fatigue were excluded (White et al, 2007).
b. Incremental point change in entry criteria
There was a one incremental point change in the entry criteria for physical disability, introduced 11 months after starting the trial in order both to include those who would normally be offered treatment and in order to boost recruitment.
As before, randomisation would ensure that this would not have any impact on the main findings.
c. Patient newsletter
A patient newsletter sent during the trial included some positive feedback from patients that particularly affected expectations of CBT.
A PDF of the patient newsletter is freely available.
You can see there were six comments from patients, praising the trial, their therapy, their treatment and research staff. The important thing is that all four arms were represented and no treatment or therapy was named. There is a quote from Number 10, Downing Street praising the trial, with no treatments named, which was a response to a public petition to stop the trial, a reminder if one is needed of the external and unpleasant atmosphere. Finally there is a quote from a doctor praising a therapy “which I know is recommended for CFS”. The newsletter was written after all 641 patients had been recruited. At that time just 30 or so would have still been receiving CBT.
There is no way of knowing how many people actually read the newsletter; my own experience of similar newsletters is not encouraging. It is also rather implausible that reading brief anonymous feedback would really have had much influence over and above all the direct one to one sessions with trial therapists and all the other material provided to participants. Even if it did, again, that would be immaterial unless it specifically impacted on any particular therapeutic approach. This seems unlikely. The patient comments came from all four arms of the trial and no treatment or therapy was named, so it is very unlikely that any bias towards one arm or another would follow from this. Perhaps the quote from Downing Street had a positive influence on Labour supporters and the opposite on Conservative; that seems unlikely as well, but even more unlikely is that more Labour supporters were receiving CBT and so on. The medical quote could have referred to any of the therapies, since all three, including activity management and pacing, were recommended by NICE.
But frankly, it all seems far fetched. If a few encouraging anonymous sentences are all it takes to improve outcomes in CFS, then one wonders why we are bothering with all these complex treatments anyway. It is more plausible that there would have been a negative impact from some of the relentless negative publicity out there, some of it backed by one of the UK patient associations, and which was explicitly aimed against CBT and GET, and in favour of pacing, and some of it also specifically directed against PACE.
d. It’s good to talk
Non-specific effects of seeing a therapist (i.e. just having someone to talk to helps).
These are certainly important, but could only impact on the key results if they differed between the treatment groups. The team ensured that all therapists were well trained and supervised, and that the total number of treatment sessions and time offered was the same across all therapies. Patients reported that they were similarly satisfied after all three therapies (APT, CBT and GET). Independent scrutineers of audio-recordings of therapies reported that the therapies had been delivered as designed. So it seems improbable that the differences between the therapy groups could be due to non-specific effects.
e. Changes to original protocol
The researchers changed the way they scored and analysed the primary outcomes from the original protocol.
The actual outcome measures did not change, but it is true that the investigators changed the way that fatigue was scored from one method to another (both methods have been described before and both are regularly used by other researchers) in order to provide a better measure of change (one method gives a maximum score of 11, the other 33). How the two primary outcomes (fatigue and physical function) were analysed was also changed from using a more complex measure, which combined two ways to measure improvement, to a simple comparison of mean (average) scores. This is a better way to see which treatment works best, and made the main findings easier to understand and interpret. This was all done before the investigators were aware of outcomes and before the statisticians started the analysis of outcomes. The changes were approved by the two independent oversight committees. The very detailed analysis plan, including these changes, was published, and these changes and the reasons for them were also described in the main paper.
f. Interpreting the follow-up study
The 2.5 year follow up is hard to interpret because it was no longer randomised.
Correct. The study team has just published the results of the 2.5 year follow up (Sharpe et al 2015). It has been criticised because after the end of the main study (one year post-treatment) participants were then able to choose further treatments if they wished, thus breaking the randomisation. As those who do trials know, it is unethical (as well as impossible) to deny this and indeed this was mandated for PACE. The findings of the long term follow up are clear. There was no deterioration from the one year gains in patients originally allocated to CBT and GET. Meanwhile those originally allocated to SMC and APT improved so that their outcomes were now similar. What isn’t clear is why. It may be because many had CBT and GET after the trial, but it may not. Whatever the explanation for the convergence , it does seem that CBT and GET accelerate improvement, as the accompanying commentary pointed out (Moylan, 2015).
No trial is perfect. Nothing as complex as a multi-centre trial (there were six centres involved), that recruited 641 people, delivered thousands of hours of treatment, and managed to track nearly all of them a year later, can ever be without some faults. But this trial was a landmark in behavioural complex intervention studies. That is why it survived all the independent scrutiny as it progressed, survived the rigorous review processes of one of the world’s top medical journals, which rejects nearly all the papers it receives, and this is why it has already been cited in over 200 medical publications. But even then, one trial does not a summer make, and one needs to see it as part of the totality of similar trials before and since.
Were the results maverick? Did PACE report the opposite to what has gone before or happened since? The answer is no. It is a part of a jigsaw (admittedly the biggest piece) but the picture it paints fits with the other pieces. I think that we can have confidence in the principal findings of PACE, which to repeat, are that two therapies (CBT and GET) are superior to adaptive pacing or standard medical treatment, when it comes to generating improvement in patients with chronic fatigue syndrome, and that all these approaches are safe.
What does that mean? Is it important? Does it matter? That is a matter of judgement for you, the reader to decide. Here is my take; you are welcome to make your own. I think this trial is the best evidence we have so far that there are two treatments that can provide some hope for improvement for people with chronic fatigue syndrome. Furthermore the treatments are safe, so long as they are provided by trained appropriate therapists who are properly supervised and in a way that is appropriate to each patient. These treatments are not “exercise and positive thinking” as one newspaper unfortunately termed it; these are sophisticated, collaborative therapies between a patient and a professional. Having said that, there were a significant number of patients who did not improve with these treatments. Some patients deteriorated, but this seems to be the nature of the illness, rather than related to a particular treatment.
It would be nice to think that perhaps we can now all move on. We can accept that PACE was a good trial and we can have some confidence in its findings, for all the reasons outlined above. We can differ in our views as to whether this matters; whether it was all worth it. And then we can come together again and agree that PACE or no PACE, we need more research to provide treatments for those who do not respond to presently available treatments. The PACE trial will not be the last word. But it is the best we have for now.
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. The Lancet , Volume 377 , Issue 9768 , 823 – 836 doi:10.1016/S0140-6736(11)60096-2
Sharpe M et al. (2015) Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial. The Lancet Psychiatry 2015 28th October online. doi:10.1016/S2215-0366(15)00317-X
[Note: both of the above papers are free to access, but you may need to register on The Lancet website to download them].
Deale A, Chalder T, Marks I, Wessely S. A randomised controlled trial of cognitive behaviour therapy for chronic fatigue syndrome. Am J Psychiatry 1997; 154:408-414. [PubMed abstract]
Everitt B, Wessely S. Clinical Trials in Psychiatry. Oxford University Press, 2003.
ISIS-2 Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988; 2: 349–360. [PubMed abstract]
Larun L, Brurberg KG, Odgaard-Jensen J, Price JR. (2015) Exercise therapy for chronic fatigue syndrome. Cochrane Database of Systematic Reviews 2015, Issue 2. Art. No.: CD003200. DOI: 10.1002/14651858.CD003200.pub3.
Moylan, S et al. (2015) Chronic fatigue syndrome: what is it and how to treat? The Lancet Psychiatry commentary 27/10/15 doi:10.1016/S2215-0366(15)00475-7
Schultz K, Grimes D. (2002). Allocation concealment in randomised trials: defending against deciphering. Lancet 359: 614-618. doi:10.1016/S0140-6736(02)07750-4
Schultz, K. and D. Grimes (2002). Blinding in randomised trials: hiding who got what (PDF). Lancet 359: 696-700.
Smith MB et al. (2015) Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 162: 841-850. doi: http://dx.doi.org/10.7326/M15-0114.
White PD et al. (2007) Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol 7:6. doi: http://dx.doi.org/10.1186/1471-2377-7-6
The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/KP058ChXxm #MentalHealth
It is disappointing – and surprising – that Professor Wessely appears to remain blind to the nature and extent of the flaws in the PACE trial.
Six prominent scientists today published an open letter to The Lancet, which published the study, saying “the study suffered from major flaws that have raised serious concerns about the validity, reliability and integrity of the findings.”
Over 10,000 people have signed a petition calling for the misleading claims made in PACE to be retracted:
I suggest interested readers follow those links and get the facts.
Mental Elf, you owe patients an apology for publishing this biased and misleading article. How will you make this right?
Mental Elf, I was serious when I said “Mental Elf, you owe patients an apology for publishing this biased and misleading article. How will you make this right?”
Why haven’t you responded to my question? What are you going to do to make things right for ME/CFS patients to undo the damage caused by the biased article that you published?
How are you going to repair the damage to your own reputation as a source of unbiased information?
RT iVivekMisra The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/db4XgnYvrr #MentalHealth
Results of PACE trial for CFS/ME are reliable. People can & will disagree about importance/implication @Mental_Elf https://t.co/TtC9Wxxcsq
If you believe the results are reliable then surely the fact that CBT/GET are no better than no treatment at long-term follow-up is a concern?
CBT and GET were pretty similar to pacing and standard medical care at follow-up. Those were the 4 arms that were studied in the PACE trial. The trial did not include an arm that received no treatment.
“There is something I don’t understand about how the PACE trial is being reported. Reports say that there were 4 groups and all recieved some form of treatment but this isn’t true. There was a group that received nothing and I know this because I was on the trial and in this group.
“Wow…..it’s just dawned on me that they are classing the group that got nothing as having received ‘specialist medical care’……talk about spin. You got nothing, not even them saying ‘ok your GP will do a review with you, see if any medication can help’ which is the least I would expect to class this as a group that got ‘specialist medical care’. This was not a group that recieved SMC much more accurate to say there was no intervention. Also I was not contacted for a 2.5 year follow up.”
I thought the protocol specified a number of sessions with a doctor and more for the SMC group than others.
Did you get no contact at all?
You are mistaken: CBT, GET and APT all received SMC, as well as the SMC-only group. So at least SMC is effectively ‘no treatment’ compared to the others that had SMC as well.
@WesselyS @Mental_Elf Not for ME as no one has just restricted results to ME. ME is NOT same as CFS. Maybe same as PVFS. Believe me. Dr EMG
@WesselyS @Mental_Elf Sir Simon your lengthy defence of PACE is a masterclass in dogmatic ‘group think’,in response to independent criticism
@WesselyS @Mental_Elf I still don’t understand how the treatments are found safe yet contradict patient testimony. This needs explaining.
@HylomantisL @WesselyS @Mental_Elf Nothing to understand. #PACEtrial #FloggingAdeadHorse #QuestionsNotAnswered #MyalgicEncephalomyelitis
@HylomantisL @WesselyS @Mental_Elf Great analogy though. #PACEtrial is a #shipwreck.
@WesselyS @Mental_Elf Key concerns were:1)recovery claims, 2) reliance on subjective self report in nonblinded trial 3) objective results.
@WesselyS @Mental_Elf Dodged 1&3. 2:Semi-dodge.Expectations data of ltd use due to CBT/GET claims made during trial. https://t.co/Ewt2xHeE2k
@WesselyS @Mental_Elf Need evidence questionnaires used reliably asses impact on symptoms of psychosocial interventions in nonblinded trial.
@WesselyS @Mental_Elf Otherwise unethical to claim CBT/GET EBM for improving patients’ symptoms. Objective results indicate: worthless.
@WesselyS @Mental_Elf re safety: Need to replicate PACE safety-measures & controls in clinical practice, or outcomes could be different.
@WesselyS @Mental_Elf “It may be because many had CBT and GET after the trial” ? But paper’s own data indicated that CBT/GET made no dif.
@WesselyS @Mental_Elf PS: Should add 4th key concern about failure to release outcomes from trial protocol. Again, dealt with poorly imo.
@WesselyS @rcpsych @Mental_Elf My concern is that it will be condensed to a 1 size fits all treatment & blaming for ppl it doesn’t work for
@WesselyS @Firestormmer @Mental_Elf am sick of the whole melodrama :/
@WesselyS @Mental_Elf Overly broad Oxford (Indeterminate patient population) & unblinded trial & subjective measures = reliable? How? #MECFS
.@WesselyS @Mental_Elf PACE studied Oxford fatigue, a criteria widely discredited in diagnosing ME/CFS. And still no long-term improvement.
@WesselyS @Mental_Elf PACE changed primary outcomes and all four criteria for defining “recovery,” but did not include sensitivity analyses.
.@davidtuller1 @WesselyS @Mental_Elf @brianvastag UK psychiatrists lack the right skill-set says @NIHDirector https://t.co/p2X1SC5V4r #MEcfs
@WesselyS @Mental_Elf I salute your clarity & your loyalty here but I find PACE terribly unbalanced & therefore unsafe.
https://t.co/ekPouuqF1L This ignores the flaws.
Today @WesselyS on the PACE Trial for chronic fatigue syndrome https://t.co/h8mk95E7EJ
Why is a psychiatrist researching a physiological illness. Totally irrelevant and full of flaws.
.@Mental_Elf If #mecfs is not a mental health illness why is @Mental_Elf reporting on #PACEtrial @swessely?
Simon Wessely responds to criticism of the latest #PACETrial follow-up paper: https://t.co/uGqilcZbjr #mecfs #cfsme #MyE
@SonyaChowdhury @TomKindlon @davidtuller1 @CoyneoftheRealm
Any thoughts on PACE #CFS blog from @WesselyS?
The authors of the PACE trial never fail to amaze with the spin that they can put on null results. I am disappointed that you’re joining them, Professor Wessely. Your economy with the truth over the changes to the study protocol is extraordinary.
People with ME/CFS and their supporters – and anyone who cares about good science – will want to be aware of this important petition – 6,000 strong in only five days – calling for the retraction of misleading claims of recovery using cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome in the PACE trial.
Emeritus Professor Jonathan Edwards of University College London has called PACE “valueless”. The background pages to the petition make grim but fascinating reading for any scientist.
PACE’s authors abandoned all the main outcome and recovery analyses that had been specified in the trial’s protocol. In the new analyses, patients were considered to have recovered their physical function if they scored at similar levels to people with Class II congestive heart failure.
Please help ME/CFS patients free themselves of bad science and sign and forward the petition.
@AYME_UK @MEAssociation @actionforme
Any thoughts on PACE #CFS blog from @WesselyS?
Twitter have launched #hearts just in time for our @WesselyS blog on the #CFS PACE trial https://t.co/h8mk95E7EJ
It is notable that Simon Wessely does not address the biggest weakness of the trial, the one that makes the results uninterpretable: the reliance on self report questionnaires.
Self report questionnaires are not reliable during unblinded trials and especially with therapies designed to modify cognitions. It is likely that questionnaire answering behaviour changed (as patients were more optimistic) with little to no underlying change in disability or behaviour. We know this because similar studies of CBT/GET showed no difference on objective measures of functioning, despite improvement on self-report scores. In the PACE trial, there were no improvements in fitness, or employment status*, indeed patients were far more likely to be on welfare after the trial than before, regardless of the group they were randomised to.
If the the self-reporting is biased in the short term, then we would predict the difference between groups would disappear in the long term. That is exactly what was shown in the followup study.
Lastly, the published data does not suggest that treatments after the trial finished had any effect either.
One of the authors, Peter White stated “We chose (subjective) self-ratings as the primary outcomes, since we considered that the patients themselves were the best people to determine their own state of health.”
Here is the message loud and clear: The patient community does not believe that subjective self-reports are a vaild way to measure outcomes in an unblinded trial.
Such data would be considered invalid in a pharmacological trial, so why the double standard with non-pharmacological trials?
The patient community was consulted before the trial and proposed actigraphy as a key measure. It was the authors of the trial that rejected this suggestion as they decided it was too difficult. Other suggestions have been made, such as repeat exercise (2 day) testing (unfortunately only suitable for higher functioning patients) and neuropsychological testing.
* Several trials of CBT for CFS patients have been conducted during economic booms and found to have no effect on employment status.
“In 2015, Professor Wessely offered a spirited defense of the PACE trial that was couched in a ocean liner metaphor (unlike the ‘Oxford says ME not a chronic illness’ shock jocks). This followed a fortnight’s worth of intense criticism towards PACE from journalists and bloggers–but surely not his peers, as Sir Simon Wessely has no peer walking this earth. As he has never been wrong about anything since birth, this blog shall be taken as the ultimate in truth, and fact; so it is written.”
The PACE Trial for #mecfs @WesselyS in full damage control mode, nothing changed. @TheLancet: Retract. https://t.co/kzrwrxvz7L
@WesselyS Simon says: “Do I have competing interests? Sure I do.” We know, Simon, we know. #pwme #MyalgicE #SevereME https://t.co/CcetSiHF6B
PACE Trial sinks faster than Titanic! Fatal Flaws! https://t.co/CcetSiq4f3 @WesselyS #pwme #MyalgicE https://t.co/7E0EbotvpP
The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/57pyN1EtKW via @sharethis
The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/ZLjhAGFST4 via sharethis
The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/K9bPaRYdBK via sharethis
The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/OX40tpQArC
RT @WDaisyFL: CBT and GET are NOT safe for ME patients! Makes us much sicker! https://t.co/CcetSiq4f3 #PACEtrial #pwme #MyalgicE @WesselyS
@Tanith777 @Mental_Elf @CoyneoftheRealm @SonyaChowdhury @TomKindlon @davidtuller1 @WesselyS doesn’t bother me. Analysis important.
RT @PaulWhiteleyPhD: Via @Firestormmer The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/7vOKJB…
MT — HUH?
Twitter #hearts just in time 4 R @WesselyS blog on #CFS PACE trial https://t.co/uMIh2PAD18 ‘
RT @Firestormmer: Simon Wessely: The PACE Trial for #CFS: choppy seas but a prosperous voyage: https://t.co/9DpCFth9xy via @Mental_Elf #MEC…
@Tanith777 @Mental_Elf @CoyneoftheRealm @SonyaChowdhury @TomKindlon @davidtuller1 @WesselyS sure but it’s also happening.
CBT & graded exercise therapy improved fatigue & physical function in chronic fatigue syndrome https://t.co/h8mk95E7EJ
@Mental_Elf think u need to check ur facts on this one & not rely on sensationalist tabloid headlines GET causes PEM & harms #PWME#realstory
@Mental_Elf Hello, you do know that GET has caused worse disability in many pwME? Ask @TomKindlon https://t.co/gv2MiMxnoK
With all the errors in this trial and changing of protocol it’s not a trial at all! It needs drowning at sea!
Sir Simon, you fail to address the real question – why do a large number of sufferers fail to improve under these treatments? That is the main issue we have with PACE – it offers no real-life solutions and DOES cause harm to some. It is not robust enough to say ‘that’s the nature of the illness’ and then put people on programmes like CBT & GET without fully understanding what causes the relapses. I myself have been through GET, led by a member of the PACE team, and ended up bedridden, unable to recover quick enough to keep my job. Throughout my treatment I was continuously praised for the effort and mentality I had to get better and to push myself to do the low-level activity increments as suggested but when it ends up with your wife helping you out of bed (and still being told by the experts to push through the pain) it would be stupid of me to continue pushing. I have been told time and again by my GP & CFS clinic that I have all the skills to get better but it is a very slow process. I am now only just beginning to get back to the consistent level of (poor) health I had before GET, 1+ year on, able to do a few hours of activity a day at home, unable to drive very far and struggling to get about without symptoms increasing. I believe that allowing my body time to recover rather than pushing it beyond it’s capability is key. I wish the PACE trial was the massive success you claim it to be, but I am still left with no answers as to how I can beat this dreadful, soul destroying illness from a medical point of view. Until we have one, I’m afraid sufferers will continue to challenge the status quo, however unpleasant that may feel to the medical profession to be called into question. Too many people are now relying on people such as yourself to find real tangible answers, just as MS sufferers did 20-30 years ago.
Passionate, well-articulated but very differing views on the value of the PACE ME study: https://t.co/WktqOgeLuG and https://t.co/l4VPURBKSy
Patients scored worse than patients with heart failure and chronic lung disease in the PACE trial walking test:
The claims about recovery are bizarre nonsense.
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.”
Prof. Wessely says:
“The findings of the long term follow up are clear. There was no deterioration from the one year gains in patients originally allocated to CBT and GET. Meanwhile those originally allocated to SMC and APT improved so that their outcomes were now similar. What isn’t clear is why. It may be because many had CBT and GET after the trial, but it may not. “
The two core findings in the 2.5 year follow-up paper from PACE are:
1. There was no difference in therapeutic effect between all four trial arms.
2. There was no therapeutic advantage from adding CBT and/or GET to APT or SMC.
1 + 2 = no benefit from CBT and/or GET over APT or, much more importantly, over SMC (standard medical care).
This is a clear null result for the cognitive-behavioural model tested in PACE, and so assiduously promoted by Prof. Wessely for a quarter century now.
Yet, Prof. Wessely goes on to say:
“(CBT and GET) are superior to adaptive pacing or standard medical treatment, when it comes to generating improvement in patients with chronic fatigue syndrome,…“
No, they are not, and you should stop saying that they are, and accept that it is time to abandon the cognitive-behavioural model of CFS.
Wessely responds to #PACEtrial critics. Sidesteps “technical issues.” We think his Titanic analogy is apt. https://t.co/KqK8MqTNQy #mecfs
“A landmark trial on the management of CFS, known as the PACE Trial, was published recently in The Lancet. It tested four therapies:
table 1. Illness and disease
adaptive pacing therapy (APT), cognitive behavioural therapy (CBT), graded exercise therapy (GET) and standard medical care (SMC). Two treatments, graded exercise and CBT, clearly made a difference, although they certainly were not ‘magic bullets’. For those who appreciate these things, the trial is a thing of beauty, and the results confirm previous smaller studies and follow ups”
Simon Wessely, Dec 2011
“No trial is perfect”
Simon Wessely, Nov 4th 2015.
If #MECFS is not a psychological condition, why is @Mental_Elf covering it? https://t.co/HFXO4WwMx9 #PACEtrial
“A landmark trial on the management of CFS, known as the PACE Trial, was published recently in The Lancet. It tested four therapies:
table 1. Illness and disease
adaptive pacing therapy (APT), cognitive behavioural therapy (CBT), graded exercise therapy (GET) and standard medical care (SMC). Two treatments, graded exercise and CBT, clearly made a difference, although they certainly were not ‘magic bullets’. For those who appreciate these things, the trial is a thing of beauty, and the results confirm previous smaller studies and follow ups”
Simon Wessely, Dec 2011
“No trial is perfect”
Simon Wessely, Nov 4th 2015. http://www.nationalelfservice.net/?p=26374#comment-977903
@rebelcorbyn @WesselyS @rcpsych @Mental_Elf Yes. I have Fibro. Done a walking programme twice. Done everything required to do. Now iller.
@rebelcorbyn @WesselyS @rcpsych @Mental_Elf It is an issue. Assumption is I have failed somehow, rather than it just not worked for me.
sadly this is par for the course,I know about 10 people doing / finished one particular program adapted from the PACE trial and 2 are doing well on it, one is very over optimistic and always liked the deconditioning type model, the other in mid twenties ( where some CFS docs will take patients on because remission is most possible, teens to ~25) the other 8 are at best the same after the mini relapse they had doing the programme but most are worse since doing it and the most successful one tells them that its because they paced incorrectly, its a circular argument, it works as evidenced by who it worked for but despite being damaging to the majority this is because they paced in correctly… as evidenced by.. pacing being so effective!
A correct interpretation of the results would be that the PACE trial has proven beyond a doubt that CBT/GET is NOT beneficial to the targeted patient population. Despite all the attempts to rig the outcome, the result is a definite ‘nothing to see here’. It would take a good scientist to accept this, change their own false illness beliefs, and move on.
CFS is NOT a specific disease. It’s a label attached by researchers to patients that haven’t been properly examined yet. They have unexplained medical complaints. It is therefore very unlikely for any treatment to show significant effectiveness even in a well-designed and executed study, which PACE was not.
The first priority to help these patients must be to examine them better. Diseases like ME, Lyme, EDS, cardiomyopathy, Hashimoto, and many others, remain undiagnosed far too often. For most of these diseases, including ME, genuine treatments are available that can make the patient whole again.
What genuine treatment is available for M.E? I doing the Perrin technique but I don’t believe it to be a cure.
Jessica, there are several known treatments for ME, but their availability is limited. Medicinal treatment includes Valcyte, Vistide, CMX001, rituximab, Ampligen.
I’m sure you are aware of the results from our latest quantitative and qualitative report on ME/CFS on the acceptability, efficacy and safety of CBT, GET and Pacing
The results yet again confirm previous patient evidence indicating that CBT is often ineffective and that GET makes their condition worse
So please could you address the issue of why consistent and robust patient evidence over many years is just not consistent with the results from clinical trials involving these two treatments?
The MEA recommendations following on from this research are as follows:
Our part 1 recommendations are based on the full results from our survey in respect of the three main therapeutic approaches to illness management, and are as follows:
Cognitive Behavioural Therapy (CBT)
We conclude that CBT in its current delivered form should not be recommended as a primary intervention for people with ME/CFS.
CBT courses, based on the model that abnormal beliefs and behaviours are responsible for maintaining the illness, have no role to play in the management of ME/CFS and increase the risk of symptoms becoming worse.
The belief of some CBT practitioners that ME/CFS is a psychological illness was the main factor which led to less symptoms improving, less courses being appropriate to needs, more symptoms becoming worse and more courses being seen as inappropriate.
Our results indicate that graded exercise therapy should form no part of any activity management advice employed in the delivery of CBT, as this also led to a negative impact on outcomes.
There is a clear need for better training among practitioners. The data indicates that deemed lack of knowledge and experience had a direct effect on outcomes and remained a key factor even where courses were held in specialist clinics or otherwise given by therapists with an ME/CFS specialism.
However, our results did indicate that when used appropriately the practical coping component of CBT can have a positive effect in helping some patients come to terms with their diagnosis and adapt their lives to best accommodate it.
CBT was also seen to have a positive effect in helping some patients deal with comorbid issues – anxiety, depression, stress – which may occur at any time for someone with a long-term disabling illness.
An appropriate model of CBT – one that helps patients learn practical coping skills and/or manage co-morbid issues such as those listed above – could be employed, where appropriate, for ME/CFS as it is for other chronic physical illnesses such as multiple sclerosis, Parkinson’s disease, cancer, heart disease, and arthritis etc.; and we recommend all patients should have access to such courses as well as access to follow-up courses and/or consultations as and when required.
Graded Exercise Therapy (GET)
We conclude that GET should be withdrawn with immediate effect as a primary intervention for everyone with ME/CFS.
One of the main factors that led to patients reporting that GET was inappropriate was the very nature of GET itself, especially when it was used on the basis that there is no underlying physical cause for their symptoms, and that patients are basically ill because of inactivity and deconditioning.
A significant number of patients had been given advice on exercise and activity management that was judged harmful with symptoms having become worse or much worse and leading to relapse.
And it is worth noting that, despite current NICE recommendations, a significant number of severe-to-very severe patients were recommended GET by practitioners and/or had taken part in GET courses.
The other major factor contributing to poor outcomes was the incorrect belief held by some practitioners that ME/CFS is a psychological condition leading to erroneous advice that exercise could overcome the illness if only patients would ‘push through’ worsening symptoms.
We recognise that it is impossible for all treatments for a disease to be free from side-effects but, if GET was a licensed medication, we believe the number of people reporting significant adverse effects would lead to a review of its use by regulatory authorities.
As a physical exercise-based therapy, GET may be of benefit to a sub-group who come under the ME/CFS umbrella and are able to tolerate regular and progressive increases in some form of aerobic activity, irrespective of their symptoms. However, identifying a patient who could come within that sub-group is problematic and is not possible at present.
Some patients indicated that they had been on a course which had a gentle approach of graded activity rather than a more robust and structured approach of graded physical exercise. There were some reports that patients were told they should not exercise when they felt too unwell to do so. These led, for some, to an improvement in symptoms or to symptoms remaining unaffected.
However, we conclude that GET, as it is currently being delivered, cannot be regarded as a safe and effective form of treatment for the majority of people with ME/CFS. The fact that many people, including those who consider themselves severely affected, are being referred to specialist services for an intervention that makes them either worse or much worse is clearly unacceptable and in many cases dangerous.
GET should therefore be withdrawn by NICE and from NHS specialist services as a ‘one size fits all’ recommended treatment with immediate effect for everyone who has a diagnosis of ME/CFS. This advice should remain until there are reliable methods for determining which people who come under the ME/CFS umbrella are likely to find that GET is a safe and effective form of management.
Pacing was consistently shown to be the most effective, safe, acceptable and preferred form of activity management for people with ME/CFS and should therefore be a key component of any illness management programme.
The benefit of Pacing may relate to helping people cope and adapt to their illness rather than contributing to a significant improvement in functional status. Learning coping strategies can help make courses more appropriate to needs even if they do not lead to immediate or even longer term improvement in symptoms.
For some, improvement may be a slow process so, whilst they may be somewhat better by the end of the course, the improvement is not enough to take them into a better category of severity for some time, perhaps not until they have self-managed their illness for a few years.
Pacing can be just as applicable to someone who is severely affected, as to someone who is mildly or moderately affected, although additional measures need to be taken to ensure that a person who is severely affected has equal access to services.
However, proposed increases in activity, both mental and physical, must be gradual, flexible and individually tailored to a patient’s ability and circumstance, and not progressively increased regardless of how the patient is responding.
There must be better training for practitioners who are to deliver such management courses and all patients should have access to suitable courses, follow-up courses and/or consultations as and when required.
The full MEA report can be read here:
Wessely says of the long-term follow-up paper: “There was no deterioration from the one year gains in patients originally allocated to CBT and GET. Meanwhile those originally allocated to SMC and APT improved so that their outcomes were now similar.”
Which is a rather convoluted way of saying that there were no useful differences between treatment arms at follow-up, and so no treatment benefits were seen for any intervention.
To clarify: CBT and GET had no benefit at 2.5 year follow-up.
Wessely then claims that “it does seem that CBT and GET accelerate improvement”.
However, the trial was not designed to test this hypothesis, so it doesn’t seem sensible to make that claim. It could equally be said that CBT and GET impaired spontaneous improvement after 52 weeks.
RT @Mental_Elf: What makes a good randomised controlled trial and how does the PACE #CFS study measure up? https://t.co/h8mk95E7EJ
@MEawareness @Mental_Elf I know. But that hasn’t stopped clinicians treating it as if it still is.
@_Lucibee @Mental_Elf Interesting how #MEcfs could be perceived as a surreptitious mental health diagnosis.Why wouldn’t the Dr tell us?
@_Lucibee @Mental_Elf Perhaps more the fact it’s perceived as MH for agenda purposes?And what now SNOMED CT have removed it from MH? #MEcfs
@_Lucibee @Mental_Elf Is the media gonna report of this change of tact?If not,perhaps it reinforces the agenda to report #MEcfs deceitfully.
Excellent, readable summary of the PACE study (with a nice metaphor for RCTs) by @WesselyS https://t.co/eihitek1DV
RT @Mental_Elf: Chronic fatigue syndrome, clinical trials and good science from @WesselyS https://t.co/h8mk95E7EJ < Unmissable PACE blog
Wessely says that: “There were no post-hoc sub-group analyses in the main outcome paper.”
This may be correct, however that does not address the major concerns that have been raised in relation to post-hoc changes to the trial’s primary outcomes.
Wessely acknowledges a post-hoc change to the primary outcomes, as follows: “The researchers changed the way they scored and analysed the primary outcomes from the original protocol.”
This change to the scoring methods of one of the primary outcome measures is a significant post-hoc change that should not be overlooked or underplayed. It may possibly have significantly altered the main reported outcomes.
Wessely seems to underplay the significance of the change, saying: “This was all done before the investigators were aware of outcomes and before the statisticians started the analysis of outcomes.”
But, whether or not the changes were made before formal analysis, this was an open-label trial, so there may have been an indication that e.g. outcomes may be borderline, after the trial had started but before formal analysis.
Wessely also acknowledges that there were other important post-hoc changes to the primary endpoints: “How the two primary outcomes (fatigue and physical function) were analysed was also changed from using a more complex measure, which combined two ways to measure improvement, to a simple comparison of mean (average) scores.”
Wessely does not mention another post-hoc change in the 2011 paper: The definition of the clinically useful difference is another significant post-hoc amendment to the original protocol.
These post-hoc changes are possibly the most important element of the complaints made against the PACE trial, and they leave the authors open to accusations of cherry-picking. Wessely has done little to address the concerns, other than confirming that the complaints are factually correct.
In ME/CFS CBT and Graded Exercise Therapy are used in accordance with a theory in which cognitive and behavioural factors interact with physical factors to produce symptoms and that there is no underlying physical cause for ME patients symptoms. Patients are told that their fear that exercise will make their illness worse is unjustified. However the science now supports what the patients have been saying all along and that unlike in other illnesses exercise does makes ME patients worse. And there is indeed biomedical evidence of this and some indication of the biology behind it.
Perhaps the readers may like to look at the following
Clinical exercise testing in CFS/ME research and treatment – Professor Christopher Snell
Snell CR, et al. Discriminative validity of metabolic and workload measurements for identifying people with Chronic Fatigue Syndrome. (Phys Ther. 2013 Nov;93(11):1484-92.)
Gene Expression Biomarkers for Chronic Fatigue and Fibromyalgia Syndromes – Latest Developments – Professor Alan light
Light AR, et al – Moderate exercise increases expression for sensory, adrenergic and immune genes in chronic fatigue syndrome patients, but not in normal subjects (J Pain. 2009 October ; 10(10): 1099–1112)
McCully KK, et al. Impaired oxygen delivery to muscle in Chronic Fatigue Syndrome. (Clin Sci. 1999;97:603–608.)
Jones DE, et al. Loss of capacity to recover from acidosis on repeat exercise in Chronic Fatigue Syndrome: a case-control study. (Eur J Clin Investig. 2012;42:186–194.)
Paul L, et al. Demonstration of delayed recovery from fatiguing exercise in Chronic Fatigue Syndrome.(Eur J Neurol. 1999 Jan;6(1):63-9.)
Brown AE, et al – Abnormalities of AMPK Activation and Glucose Uptake in Cultured Skeletal Muscle Cells from Individuals with Chronic Fatigue Syndrome (PLoS One. 2015 Apr 2;10(4):e0122982)
The Biopsychosocial model is a busted flush and no matter how much its proponents try to spin to prop it up and what elaborate constructs that they come up with to try to support it, it will not change the fact that it is a myth that is busted.
The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/0G5fxpZ0Pj via @sharethis PACE IS the Titanic
@WesselyS I’m a patient, good news if true.But made no diff to nonCBT/GET bods post-trial. Response bias @1yr likely https://t.co/pFRCzgMQ8x
RT @SympoPsychiatry: The PACE Trial for chronic fatigue syndrome. https://t.co/kJRQn3fXtB by @NatElfService top shared link among psychiatr…
I saw the effects of exercise work to increase mobility in a trial where they only cared about weight loss. I think the media spin of making PACE look like a cure for all persons with CFS is overstated. I would hope that for those that do not respond to this intervention that they will not be cut off from other alternatives or just told all they need is to respond to counseling and get some exercise. Be great to see some post trial qualitative research with patients who did/did not respond as maybe there would be ways to increase the benefits
I think this is a very helpful article which shows that most if not all criticisms of the PACE trial are unfounded, where there were limitations these have already been acknowledged by the trial authors, as an M.E. sufferer I am very pleased that there has been such an extensive trial and that it has shown treatments that can help some patients .It makes me feel less alone and more hopeful, and properly read and understood I think the PACE trial should contribute to increased understanding for patients from the medical profession. I think there is a lot of misunderstanding of the trial among M.E. patients partly due to incorrect information about it being disseminated through careless reporting in the media , through patient groups and through some professionals who have become involved in the M.E. debate but really seem to have a limited understanding of it themselves.
This is a CFS study, not a ME study at all. Patients with ME should avoid CBT/GET entirely, as they would risk major permanent damage.
NEW CANARD PASSENGER LINE
Southampton to New York in 5 days
Canard has announced the successful first voyage of its flagship, the Queen Mary Pace. Built in Oxford to rigorous specifications, this sleek and sophisticated liner, with the latest engines built with Graduated Energy Transmission, has taken the world by storm with the first crossing in just 5 days.
Setting out from Southampton on 18th March, 2005, amid cheers from admiring crowds in the medical enclosure, it left harbour looking every inch the awesome and standard-setting giant that it is.
With everyone settled in and enjoying the cruise, the captain called together his senior crew and decided to make some minor adjustments to the course plotted. Informing the management back at Canard, these quickly took place, and a mere 5 days later, passengers found themselves at the quayside in Dublin.
“All changes were rigorously discussed with the senior crew,” explained the captain. “It was felt important to make changes that truly reflected the potential of the new engine arrangement. Dublin is an entirely normal destiny for cruise liners.”
A number of passengers complained, but, as management at Canard explained, “There are always vexatious passengers on any cruise. All decisions were taken in their interests, and, naturally, it would be inappropriate for passengers unfamiliar with the ways of the sea to be allowed to comment on such matters. The crew had unusually tranquil seas and clement weather to contend with: it is too easy to criticize from the sidelines.” The UK government, which invested heavily in this engineering miracle, recommends that everyone should experience this very effective service.
When questioned, 22% of the passengers said that they thought Dublin was much better or even very much better than they had realized: but another analysis showed that, actually, none of them ever ended up in New York, even two years later.
Don’t miss: The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/h8mk95E7EJ #EBP
After Wessely gave high marks to #PACEtrial @Mental_Elf new critical post from @davidtuller1 on recovery claims. https://t.co/J779mLSVaf
The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage https://t.co/4Eer9OBydX via @WesselyS
Top story: The PACE Trial for chronic fatigue syndrome https://t.co/7cn6PRygjC, see more https://t.co/oT5ZtD4hhQ
RT @Mental_Elf: Big thanks to @WesselyS for his PACE #CFS blog today https://t.co/MES7A4x7uX
RT @Mental_Elf: @juliaoftoronto @picardonhealth @AllenFrancesMD
Any thoughts on PACE #CFS blog from @WesselyS?
Um I thought this must be a spoof post – a prosperous voyage. We are talking about people with ME here? It reads like a Goons take off – but then I realised this is serious stuff. Very serious if you happen to be a patient and not living in the lofty realms of intellectual justification.
Unfortuantely no-one has told the emperor that he has no clothes. Please Mental Elf if you are serious about unbiased reporting of factual evidence do your homework. ME is not CFS, nor post-viral fatigue syndrome, nor fatigue.
A random question – why did the Occupational Health Doctors exclude all research into ME when they came up with their guidelines for treatment on ME / CFS? Only the terms CFS or CF were used. Who is covering up what? If you are really looking for unbiased science take a look …
The emperor’s nakedness has been pointed out to him on many occasions, but he is an incorrigible exhibitionist.
This is excellent & well worth reading RT @Mental_Elf: Big thanks to @WesselyS for his PACE #CFS blog today https://t.co/iXANT9gdpe
I very much enjoyed your comparison of PACE with the Titantic. We all know how that voyage ended, and PACE is headed for the same fate. In fact, it has already struck a giant iceberg in the form of David Tuller’s analysis.
Perhaps you haven’t realized yet that the U.S. National Institutes of Health threw you overboard last week when it announced an intramural research program of actual biomedical research, along with a promise of a substantial increase in the extramural funding.
I just have one question for you:
How long can you tread water??
Simon, or should that be Captain Simon, I ponder whether you may have been a politician in a previous life, such is your ability to avoid answering all the important questions. You refer to the trial as ‘prosperous’ (interesting choice of word) prosperous for whom? For those conducting the trial, or for the patients? Could you please tell us where are the records of the patients who have been made worse by participating? The patient groups, and no doubt the PACE authors know full well there are a number of people who have been adversely affected, some severely, one or two have commented on here, one wonders how many others are too sick to do so. Records must be kept of patients made worse by these treatments, not just during the trial, but ongoing, for all patients receiving these treatments.
RT @alansarchives: Nope, this ship sunk because the captain was mad! ‘The PACE Trial for chronic fatigue syndrome:a prosperous voyage’ http…
If this is the ‘best’ of British research into CFS then I would rather go back to the 80’s when I could get help for my neurological condition.
Me too Vikki, I was diagnosed in 1991 by a very nice NHS doctor at the Royal Free Hospital in London and treated with the utmost respect by GP’s. Contrary to the belief of many outsiders, we aren’t usually self diagnosed. They saw a young woman who was desperate to get her life back and keep her job, friends, social life etc. Later I suffered from Trigeminal Neuralgia and saw an Oral surgeon on the advice of my dentist. This man laughed at me in front of a group of junior doctors, saying the medication for the neuralgia was ‘obviously’ only working due to the ‘placebo’affect’ and that it was obvious that I was suffering from depression. My GP was really angry and ignored this ignorant man. I was referred to a neurologist and diagnosed with the TN. Just a brief insight into how we are sometimes treated with ME. I’ve been in a state of collapse in A&E with tachycardia and the doctor assigned to me didn’t have a clue what ME is. I asked my GP to refer me to a cardiologist, it turned out that I also have a heart condition. Can you see how dangerous it can be if doctors don’t ‘believe’ or aren’t trained?
I got a diagnosis of PVF in 97 after 12 separate infections and numerous virus’s . At the same time I started to experience excruciating back pain and referred to an Orthopaedic surgeon who decided based on medical records and diagnosis of PVF which he turned into CFS that I was suffering from a somatisation disorder and packed off with some paracetomol. Presumably a placebo for the pain. Jump forwards 3 years and I could not move without pain, sit, stand, walk nothing. My partner decided enough was enough and demanded an MRI where I was finally four years after initial presentation diagnosed with Degenerative Disc disease, Lateral Recess Spinal Stenosis, osteophyte formation on facet joints, Nerve root impingement and sciatica. I was offered a 3 level spinal fusion but and here’s the big one, the Neurosurgeon wasn’t sure my facets were stable enough to be able to hold the pins and would do nothing to alleviate the back pain i.e. damage done.
I know who I blame for the delay in diagnosis
Like many I long for the day when responsibility will have to be taken and apology’s will have to be given but it will in no way make up for the damage and harm inflicted on so many.
As for this shipwreck of an analysis of his mates research it is nothing more than what I have come to expect from this cabal of UK psychiatrists, insurance companies and the UK government who fund this sort of not fit for purpose research.
.@IsabelHardman “I do not think that chronic fatigue syndrome is “all in the mind” (…) nor do PACE investigators” https://t.co/DTTJ7V5Zqx
Taken from the comments attached to Simon Wessely’s blog in Mental Elf yesterday: https://t.co/Azncjl3a8L
@Mental_Elf @TheLancetPsych lancetpsy pushing one dogmatic perspective via retweets and tweets remarkable example of #lack of independence
Having read your report, I find it hard to reconcile your findings when I have a 31 year old daughter who is virtually bedridden through ME and fibromyalgia. Car has been introduced in the past when she was more able bodied than she is now, and as for exercise, it would be impossible for her to even attempt when for example, just getting up and brushing her teeth (with an electric toothbrush) exhausts her. This is the only time in the day when she is “up” as she cannot manage more than this tiny exercise. It is heartbreaking to know that so little, if anything, can be done, especially as a mother watching her child suffer so much. Heartfelt!.
Quite a few people with ME are (re-/)having success with antiretrovirals once they clear any co-infections first.Perhaps those with Gulf War Army ME Syndrome Disease and their affected autistic and ME family members should try to seek out such therapies too front line to neutralise bacterial and exogenous retroviral signal.This might shell shock some but appears to be a horrific reality that is quickly starting to get out now.There seems to be a common putative transmissible man-made pathogen at work here which can’t be a endogenous herv and people are working it out for themselves and many are taking treatments before it is too late for them to be effective(under strict medical surveillance only of course).And the Band plays on…We must accept what has happened and deal with this global crisis and screen and protect future generations.War casualties while away and when coming home too..Some people had a duty to inform but failed to do so. All we are left with is the observation of the human catastrophy unravelling before our eyes.
New world of hope.
New paradigm. Treatable with ARV’s.
CBT & graded exercise therapy improved fatigue & physical function in chronic fatigue syndrome https://t.co/7iOYxzxMXx
The PACE Trial for chronic fatigue syndrome https://t.co/yxmMrFyrI1
I think it was very kind of the government to spend so much money on a study which started with the clear idea that ME has no physical basis when they are having so many problems with cutting sickness benefits. It is also refreshing to see a major study dealing with an organized and informed patient group that so readily dismissed their concerns and experience, and in fact continue to do so. Now I am fairly familiar with how CBT can be usefully employed in helping people suffering a range of physical symptoms. The very pragmatic approach to helping people understand their condition and develop a range of coping skills can be really useful. I was however surprised to see that the manualised CBT offered appeared to be based on a model of the condition that the patients beliefs about the cause of their condition and their ability to assess their own symptoms were based on abnormal beliefs. Despite this, the study was of course reliant on patient self reports. As a working model of the illness this is inadequate and has no empirical support, in fact based on earlier work I didn’t think anyone considered it useful and some people viewed it as damaging.
Now despite this study providing weak evidence of a possible sort term effect there is an important lessen we can all learn. In any study when you do your baseline measures if it looks as if the criteria set in the research protocol for judgeing how effective an intervention might be, then change them. For example in the Physical function subscale you might have described certain score cut off points like this,
100 healthy physical function
85 or above recovery threshold
65 or below Disabled enough to enter the trial
0 most extreme disability
The simple expedient of disguarding the 85 recovery threshold and replacing it with a threshold of 60 or above instantly gives you something to talk about. If more research adopted this technique we probably wouldn’t need to bother patients at all. Like many studies of this nature critics have been subject to insults and personal attacks, there is an avoidence of addressing the issues properly, it seems there is a consensus of support and its settled science. Its still amazes me that there appears to be a growing crisis of confidence in “science”. I’m sorry I’ll stop at this point I’ve just noticed I’m knawing through my own arm and the stub of my scarcasm pencil is nearly finished.
[…] elf: The PACE Trial for chronic fatigue syndrome: choppy seas but a prosperous voyage [Simon Wessely Nov 4] A defence of the trial results […]
Most popular blog this week? It’s @WesselyS on the PACE Trial for chronic fatigue syndrome https://t.co/h8mk95E7EJ
For someone no longer involved with ME, Simon does seem, well, awfully involved.
Interesting analogy: the trial ship steered by the PIs on a preordained journey to a predetermined destination. It’s how many patients view PACE. It’s a point Simon fails to address: all the PIs have reputational, professional and
financial interests in the particular model tested, as of course does Simon himself. It’s an obvious problem. It’s perfectly possible to point out the clear danger of group-think and cognitive bias, without casting aspersions on the
personal integrity of the people involved.
Naturally, Simon wants to concentrate on the good points of PACE, but it’s a curate’s egg-defence. He ignores the bad, which poison the whole study.
‘I was not on the ship, neither as passenger or crew. I helped recruit some patients to the study from our clinic, as did many doctors, but that was as far as it went.’
In the PACE protocol ( http://www.biomedcentral.com/1471-2377/7/6 ) he is listed under ‘centre leaders and co-leaders’, one of only 8.
‘I have done a few voyages similar to the one undertaken by PACE (e.g. Deale et al, 1997)’.
A few suggests more than one. I know of only one RCT for ME/CFS which Simon has ever carried out, one with a relatively small number of patients, all from his own (psychiatric) clinic (years after he had become a controversial
figure in the field) and selecting patients on the broadest possible criteria. Perhaps Simon could upload to his website the other RCTs he has carried out on ME/CFS.
‘I do not think that chronic fatigue syndrome is “all in the mind”, whatever that means, and nor do the PACE investigators.’
Simon has recently stated to me that he still considers ME to be a neurasthenia (listed as a psychological illness by the WHO, which categorizes ME as neurological), a functional somatoform syndrome, ‘simply a belief’. The PIs
have all made it clear they do not consider there to be an ongoing biological cause of the illness. I accept Simon would not, and has never used, such an expression as ‘all in the mind’, but his view of the illness is exactly what is
generally understood by the term.
‘That both cognitive behaviour therapy (CBT) and graded exercise therapy (GET) improved fatigue and physical function more than either adaptive pacing therapy (APT) or specialist medical care (SMC) a year after entering the trial.’
This is blatant cherry-picking. The current debate has been spurred by the follow-up study looking at outcomes after ‘at least 2 years’ which found ‘little difference in outcomes’.
‘Expectations can influence the outcomes.’
Yet he then dimisses any possible impact from the newsletter. It is true that CBT and GET are not named in the newsletter, but: First, there is a clear bias toward ‘treatment’ and therapy. Second, whatever you call pacing, however
you dress it up, it is simply pacing; it is not a treatment or therapy. Third, the newsletter is a blatant plug of the PIs’ model. It says: First, that the biological approach has failed (HHHV6 and coxsackie studies). Second, that fatigue is a ‘persistent unexplained symptom’ similar to Irritable Bowel Syndrome (other funding by MRC). Third, that ‘chronic fatigue’ is not in fact a distinct illness but the far end of the spectrum of human experience, linked to ‘sleep deprivation and overwork’ (Japanese study). Fourth, that this fatigue can be overcome (Japanese study). Fifth, the treatment and therapy offered by the study is an effective way of overcoming it (patients’ and doctor’s feedback). And sixth, that the treatment in question is CBT and GET, as endorsed by NICE (link to NICE guidelines). It’s so biased as to be comically amateur. They may just as well have written CBT and GET will make you better.
‘There is no way of knowing how many people actually read the newsletter.’
Indeed, but a properly run trial would not have taken the risk anyone would have read such absurd propaganda.
‘So it seems improbable that the differences between the therapy groups could be due to non-specific effects.’
This is a key point which Simon dismisses far too airily. Patients in one group were told for 6 months that their illness was down to their false beliefs and that if they changed these beliefs they would feel better. They were then asked if they felt better. It is known that subjective perception can be changed without affecting objective outcomes. There is a clear danger that the study is only measuring changes in subjective perception. It is why critics of PACE have pointed to the lack of difference in objective outcomes and the failure to use actimeters. It is not sufficient to claim as the PIs have done that ‘patients are the best judge of how they feel’. First, of course, we know that in such trials and under such conditions, they are not always. This may have been particularly true since patients were selected from treatment centres and so by definition thought treatment possible (and ‘expectations can influence the outcomes’). Patients like me, who know that no treatment is available and would not waste our time and energy going to treatment centres set up for CBT and GET, were excluded. Second, this claim is in itself revealing bias: it is defining ME as a subjective illness. (And of course it is rather odd to say that patients are the best judge when the CBT model is based on the theory the illness is one of false belief.)
‘Those originally allocated to SMC and APT improved so that their outcomes were now similar. What isn’t clear is why. It may be because many had CBT and GET after the trial, but it may not.’
That is simply untrue. We know from the study itself, which shows that whether they had CBT and GET after the trial made absolutely no difference whatsoever. It’s another null finding.
‘I think that we can have confidence in the principal findings of PACE, which to repeat, are that two therapies (CBT and GET) are superior to adaptive pacing or standard medical treatment, when it comes to generating improvement in patients with chronic fatigue syndrome.’
1.That may be what Simon thinks, but that’s not what the evidence shows. What PACE found was that those who received CBT made no greater improvement on any of the objective measurements, and indeed did a little worse on some. The patients in the CBT and GET groups made a slightly better showing on subjective measurements, but this moderate superiority may well have been down to the non-specific effect of contact with a therapist and in any case the groups did not maintain the advantage over a longer period. The patients in the GET group showed up slightly better in one objective measure, the 6-minute step test, but we do not know if this was due to being ‘coached to the test’ and/or at a cost to other activity, as neither actimeters nor the 2-day test were used. Since the GET group did not show any improvement in the fitness tests the latter seems likely.
2.That is not what the PIs claim and that is not how the study is reported. The PIs claim that CBT and GET lead to ‘recovery’ and are ‘effective treatments’. The evidence does not support either contention, however it is interpreted.
‘That is a matter of judgement for you, the reader to decide.’
We would like to make this judgment informed by the data, but the PACE PIs refuse to release great chunks of it, including, absurdly, data on which they based a graph they have used. Perhaps Simon would join us in calling for the data to be released, or explain why he will not.
There is a lot of good criticism above. I will not repeat it.
PACE was conducted by PIs all of whom were massively invested in the model being tested. The selection of participants was biased in favour of the interventions. Patients were sent newsletters which amounted to little more than propaganda for CBT and GET. The protocols were changed; the analyses were done in the most favourable way. And in the end what did they find? ‘Little difference in outcomes’. Null finding. Case closed. There is no evidence CBT and GET treat ME.
[…] outline the current backdrop to this post, there’s much heated debate for and against the reliability/validity of the PACE trial methodology. The depth and details of this […]
“I am disappointed that after building a reputation on your logo of “No bias. No misinformation. No spin.”, you have greatly damaged if not destroyed that reputation by asking a vested party to report on this topic. SWessely has partnered with the PACE authors on papers, and other ventures, and defended PACE in the past. This is no independent evaluation.
My understanding is that you had followed up on James C. Coyne’s offer to debate the PACE authors, and maybe SWessely as well as that offer was also made, after David Tuller’s article and James C. Coyne’s blog, ‘Uninterpretable: Fatal flaws in PACE Chronic Fatigue Syndrome follow-up study’, on a few of the problems with PACE and were looking at hosting a live webinar debate.
I can’t understand why, when the PACE authors declined, that you decided to post a blog from a PACE defender.
To try to save your reputation, and present a balanced view of PACE, may I suggest that you ask David Tuller, James C. Coyne and Prof Keith Laws to respond to the SWessely piece.”
[…] this as a co-ordinated attack in response to Tuller’s critique. Some might have been surprised by Wessley’s article in particular, as he had previously announced his retirement from the field of ME following the […]
An Open Letter To Richard Horton and the Lancet
Somehow I suspect this was not a development Professor Wessely will be pleased to see. He shall, however, triumph over all, to the betterment of mankind. Such a sweet man.
What I don’t understand is the level of hostility shown by many people living with CFS/ME to any type of research looking at the psychological aspects of the condition.
It is such a blinkered, knee-jerk, reaction.
The NHS News story we ran on the PACE trial (http://www.nhs.uk/news/2015/10October/Pages/Exercise-and-therapy-useful-for-chronic-fatigue-syndrome.aspx)
has been given 33 one star ratings.
Not because it is a bad article – but because it offends people’s world view.
Some of the CFS community attempts to shut down debates about research amounts to censorship – you are only free to publish if you say CFS is viral
To the person who made the comment about the NHS article, it’s interesting that fault is directed towards patients rather than the inaccurate and problematic contents of the NHS article. It’s an interesting tactic to blame the victims of hideously unbalanced reporting rather than blame the reporting itself for the overwhelming negative response from the public. Distract from the actual issue of bad reporting by demonizing a patient community. Great style.
How about engaging with the patient community and asking what the issues are, from their point of view, rather than making provocative, ignorant and ill considered remarks?
The NHS article misrepresents the PACE study outcomes, starting with the title: “Exercise and therapy ‘useful for chronic fatigue syndrome'”. (Never mind the fact that the PACE trial did not investigate ‘exercise’ – but thanks for the dangerous misrepresentation). If the actual data had been considered, rather than regurgitating the spin from the Oxford press release, then patients might be more grateful for the reporting. But they’re hardly going to thank you for perpetuating untruths and misinformation about a very important issue that affects their lives.
Why didn’t the NHS article simply say that there was no difference between treatment arms in the trial, and so the therapies were shown to be ineffective? Why not explain that when CBT or GET were added to basic medical care, there was no clinical benefit? Why not explain that patients would have the same level of health whether or not they had received CBT or GET two years earlier? Any of those simple statements would have sufficed.
Why regurgitate that nonsense about the benefits of CBT & GET being ‘maintained’? If you’re going to go down a rabbit hole, and ignore the basic methodology of a clinical trial by reporting in-group changes, then you need to balance it out by saying that CBT & GET inhibited improvements beyond 52 weeks. But why on earth would you refer to in-group changes in the first place, as if they are indicative clinical benefit? The fact that the article made a basic error re trial methodology but then didn’t say that CBT & GET inhibited improvements beyond 52 weeks, clearly demonstrates that the article was regurgitating spin in an embarrassing case of churnalism, on the NHS website of all places.
It is not the fact that the research is psychological that is the problem. Indeed some researchers who have done psychological studies, such as Leonard Jason are very popular amongst the patient and advocate community.
The difference is that Leonard Jason actively listens to the community, conducts high quality research and does not exaggerate or spin the results of his studies.
It is the quality and context of the research that is being questioned. That is why the likes of James Coyne etc. have joined the debate.
Isn’t it in fact the case that you are shutting down debate by claiming that those who criticise particular trials are shutting down debate? Aren’t trials supposed to be dissected and debated?
I disliked it because it’s an extremely bad example of an article. It’s far from “balanced” as you claim and merely regurgitates the authors’ PR which has been shown to be completely unsubstantiated.
Btw, you really showed your true colours in your abusive tweets against patients.
In writing twitter_gezblair that,
‘What I don’t understand is the level of hostility shown by many people living with CFS/ME to any type of research looking at the psychological aspects of the condition.’
my answer would be that you don’t seem to understand that what really irks people with CFS/ME is what we feel has been the major bias towards the funding and reporting (and far too often misreporting) of psychological research for decades now, of which your NHS News story on the PACE trial is I feel a prime example.
‘What were the basic results?’ you asked.
‘The results of the original study found people who had CBT or GET had, on average, lower levels of fatigue and were able to function better physically at the end of the study year.’
Yes on average they did, but as Table D. in the ‘Supplementary appendix’ of the PACE trial long-term follow up paper(1) shows, the long-term outcome for 48% of the patients who were given CBT and 47% of those given GET was that there was ‘no change’ in their condition from the start of the trial, and that 10% who received CBT and 6% who received GET said they experienced negative perceived health and impairment of daily activities, defined in the notes of Table D. as being ‘much worse’, or ‘very much worse’ respectively.
Professor Wessely writes,
‘. . . there were a significant number of patients who did not improve with these treatments.’
A ‘significant number’ comes across as a minority to me, but from the published results, the majority, a total of 58% who received CBT, and 53% who received GET, said they experienced ‘no change’ or got ‘much worse’ or ‘very much worse’.
‘The follow-up study showed these results persisted, so people in these groups either stayed the same or improved slightly after the first year.’
Table D. shows that the number of those who experienced negative changes after receiving CBT and felt much worse, or very much worse, increased from 6% at the end of the trial year to 10% at the long-term follow-up.
‘People who had specialised medical care alone, or with APT, had less positive results at the end of the study year, although everyone improved somewhat.’
This is not what Table D. records. 66% who were given SMC experienced ‘no change’ during the study year, and 9% experienced negative change, and were either much worse, or very much worse, so far from it being the case that everyone improved somewhat, 75% given SMC alone either experienced no change or negative change in the first year, and while there was a post-trial reduction, 58% of the SMC group continued to say they had no change or negative change at follow up.
In the APT group, 70% said they had experienced no change or negative change at the end of the first year, 62% were still saying there had been no change or negative change at follow-up.
‘How did the researchers interpret the results?
The researchers say that the most important result was that, “The beneficial effects of CBT and GET seen at one year were maintained at long-term follow-up” two or more years after the trial started.’
Yes, but only for a minority of the total involved in the trial, 42% of the SMC group, 38% of the APT group, 42% of the CBT group and 48% of the GET group were improved two or more years after the trial started.
‘Conclusion . . .
. . . As the researchers themselves say, some people in this study didn’t get any better regardless of which treatment they had.’
To me ‘some people’ makes it sound like a minority didn’t get any better. As the PACE trials own results show, the majority either didn’t get any better, or got worse.
‘We know CBT and GET don’t help everyone, even if they seem to help more people than other currently available treatments.’
That these treatments ‘don’t help everyone’ I feel makes it sound like they help the majority, but by the trials own results, neither SMC, APT, CBT or GET help the majority with CFS/ME.
‘We still need better treatments for this complicated and disabling condition.’
The majority of people who took part in this study and I suggest many others with CFS/ME don’t just need ‘better treatments’, by the evidence of this trial there is no treatment that works for the majority, rather the results seem to show that in the long term, for a minority with CFS/ME, very gradually taking longer regular walks (GET) to consult your doctor (SMC) could be as effective as anything.
Especially in the current funding squeeze I feel it is especially important that reports of medical research that are likely to inform many thousands of patient/doctor consultations across the world, are described in as crystal clear, balanced manner as possible without bias or spin, to prevent the expenditure of many millions of pounds on unnecessary, unwarranted treatments.
Its critically important I feel that General Practitioners GP’s, other providers and CFS/ME patients are given the clear ‘take home’ message that on the evidence of the PACE trial, if all the CFS/ME patients in this country were prescribed either APT, CBT or GET, at least half of the money spent on these treatments would be wasted, for at least half of the patients treated would either not improve, or get worse.
When I heard PACE trial author Professor Sharpe talking about the PACE trial on ABC National Radio, Australia on the 18th April 2011 I think it was, if I transcribed it correctly he said,
‘So the differences we’re looking at here are clinically useful but they’re not actually enormous.’
but felt he might have qualified his words by saying, ‘. . . are clinically useful for a minority of patients, but they’re not actually enormous’.
What I don’t understand is why the reportedly, at least £5 million UK taxpayer funded PACE trial and its spin-off reports that describes what for me are less than unimpressive results, has been so often reported and misreported across the media for years now until many CFS/ME patients like me are very tired of hearing about it, but that what I understand to be far less generously largely charity funded, ground breaking British biomedical objective research(2) at Newcastle University and the Newcastle Hospitals, NHS Foundation Trust, Newcastle upon Tyne reported earlier this year, that described the enzyme AMPK they had observed operating in electrically stimulated cultured samples of the skeletal muscle of healthy controls, was not operating at all in the skeletal muscle of any of the CFS patients, seems to have been largely ignored by the media.
If this is proven in repeat studies by independent researchers, it could I suggest be one of the biggest, if not the biggest ever breakthroughs in CFS research across the world to date, bringing hope to millions of desperate sufferers across the world.
As so many times in the past, it didn’t seem to get widely reported, it’s not psychological research, psychiatrists don’t see any profit in it, and the media our families and friends read and listen to can’t spin it to imply for the thousandth time that all CFS/ME sufferers really need to do to recover is get help to think differently, and get a bit more exercise.
I sense it is human nature to wish to put an upbeat positive slant on things, to make things seem better than they are, but when this repeatedly distorts and minimises the truth of medical research studies such as the PACE trial that prove the treatments trialled don’t help the majority, I feel it’s corrosive, and really doesn’t help patients or anyone else.
CBT as I understand it, in part at least aims at giving people a reality check. I feel reports of medical research also need to engage in a reality check, and reflect the reality of the research, not a partial, distorted reality.
With medical research, even on something as little researched as CFS//ME, for most, including many doctors and especially Professors of Medicine working in their closeted specialisms, it seems to me that it is very difficult to actually read and digest all, or even part of the total medical research on an illness and produce a balanced view of the nature of it for patients and their families.
I’m just a layman, but someone who I feel may have succeeded in producing a more balanced view than most of CFS, is Professor Anthony L. Komaroff who supplying information for ‘Ten Discoveries about the Biology of CFS’ at,
and in his 2014 Stanford University presentation, ‘The Biology of Chronic Fatigue Syndrome’ at,
The question I think many with CFS/ME would like to ask Professor Wessely is what is his opinion of Professor Komaroff’s summary of research from across the world? Is this a reasonable description of the nature of this illness as medical research understands it so far, fit for people with CFS/ME to share with all their family and friends across the world, or if not, in what way does he not agree with it?
If I haven’t got all of this data and information entirely correct please forgive me, I’m far from well.
1 – Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial, M. Sharpe et al, Lancet Psychiatry 2015;2:1067-74, published online, October 28th 2015.
2 – Abnormalities of AMPK Activation and Glucose Uptake in Cultured Skeletal Muscle Cells from Individuals with Chronic Fatigue Syndrome, journals,plos.org, J. Newton et al., published April 2nd, 2015.
As a severe ill patient for almost 20 years now i really get tired of the CBT/GET and mental issues. It is so clear to me that a subgroup (30%) of CFS patiënts (Oxford, Fukua criteria) have a positive respons to CBT/GET. The other 70% don’t respond or deteriorated by CBT/GET. I would like to know why? Acknowledge this and find out the real cause. Don’t blame the patiënts for not reponding. Lets find out the right therapy for the right patiënt rahter than starting ‘a war’
about a devastating illness. Start looking for somatic causes rather than only spend money on psychologal therapies. It is very strange to see al that money is going only to psychiatrists isn’t it? Sauce for the goose is sauce for the gander!
[…] information website National Elf Service, the “no bias” site instead publishes a 4,500-word article praising the study by Professor Sir Simon Wessely, who describes the PACE authors as “personal […]
[…] National Elf Service when the authors declined a debate and the site instead published a long article by Professor Sir Simon Wessely praising the […]
[…] website National Elf Service when the authors declined a debate and the site instead published a long article by Professor Sir Simon Wessely praising the […]
[…] trial written by its organizers, Peter White, Trudie Chalder, and Michael Sharpe, and also to this post of his from November, coming to the defense of the much-maligned PACE […]
I was not on the ship, neither as passenger or crew. I helped recruit some patients to the study from our clinic, as did many doctors, but that was as far as it went.
Professor Simon Wessely from King’s College London, who believes there may be viral triggers for the disease but who pioneered the psychosocial therapies, ran the studies on which Nice’s guidance is based
Please read the above article with the following in mind:
Top researchers who have reviewed the PACE Trial say it is fraught with indefensible methodological problems. Here is a sample 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.”
42 research scientists and clinicians have signed an open letter to the Lancet asking for the data to be released and reanalysed outside of the UK (outside of the reach of the PACE Trial authors and numerous cohorts.)
On March 8th, 2016, a petirion with 12,000+ signatures was sent to Richard Horton of the Lancet:
This is unprecedented!!
[…] According to Simon Wessely, Professor of Psychiatry at Kings College London,“Small corrections to the route taken were made on the way, but these were of little significance.” Yet it seems that some of these corrections had such a major impact that they might have altered the results so as to be significantly more beneficial to patients than would have been found using the original criteria. Let’s take a look at how that works. […]
Dr Younger has published studies on CFS, Fibromyalgia and pain.
It appears that this ship was torpedoed when the principal investigators saw that the passengers weren’t responding to the “treatment” as they had proposed. The relaxation of the outcomes was absurd- to have a trial where people can be worse at the end than at the start is a nonsense. This article needs to be retracted and or severely amended…the GET and CBT were ineffective as per the original trial protocol.
This article explains why Simon Wessleys article is false.
Where you go wrong, Simon, is in the very beginning. You say that CFS is a disease. It is not, it’s a category of unexplained fatigue and malaise (R53.82 in the ICD-10-CM) and that’s all it is.
There are many different diseases that can cause symptoms like the ones found in CFS criteria. CFS patients are likely to suffer from one of them, they just haven’t been fully diagnosed yet. As soon as they are, their symptoms aren’t unexplained anymore, and the CFS label no longer applies.
The logical consequence of all this is that CFS has no treatment. You will never find one, no matter how many millions are spent on research. CBT/GET does not heal CFS patients, but neither does anything else.
If you have CFS patients, please continue to medically examine them. The odds are good that they have an underlying disease that can be treated effectively. You just haven’t found what it is yet. For a small subset it will be ME (I was fortunate to get properly diagnosed without having to go through CFS); for most, something else entirely.
When there is only the label CFS, management in the form of CBT/GET makes no sense. You simply don’t know enough about the patient, so you don’t know which thought process or behaviour is working for or against them. Common wisdom says: pace yourself, rest, and that is usually best.
[…] A large clinical trial might be said to resemble an ocean liner…Very occasionally there is a shipwreck – Simon Wessely […]
[…] you point to your own blog post, which ironically undermines your very point. You compare the PACE Trial to an ocean liner […]
So can we now do the same CBT/PACE trial for AIDS patients, cancer patients, or any other chronic illness. etc etc.
Does nothing to fix the actual illness, but it may help you cope with it.
[…] Geraghty begins his editorial citing Simon Wessely: ‘Science is not always plain sailing and sometimes the voyage is across an angry sea’. This quote gives an excellent picture of real world science and its challenges. Unfortunately, the […]
Wessley at it again a scientific trial is not meant to be tweaked to ensure that it gets the authors preferred pre-determined result result which is very different to a ship that needs to be adjusted to get to its set port. Wessley’s analogy under scores the key problem with the PACE trial it was a trial designed, developed and implemented to confirm the authors false belief system. When the results were at odds with their beliefs all manner or tweaks were applied, outcome measures relaxed, objective measures dropped, the 6 minute walking test buried. What seems to being missed is that the VO2 max test described in the PACE manual but not reported on, (or preferably a 2-day CPET test as per Staci protocol) would have 100% objectively demonstrated the physical functional disability of the patients). Lacking objective biomarkers and outcomes are a hallmark of the PACE authors and their supporters. They are well aware of HR abnormalities and abnormal VO2 max results – White a principal investigator included these in a 1997 paper. No data on the impact of the trials arms on the resting heart rate of the participants has been provided despite this being part of the trial. The failure to design, develop, implement a trial that looks at and uses common, cheap and readily accessible physiological markers is at odds with a real effort to help patients and/or understand this disease. Wessley continues to flog a dead horse, presumably as this is extremely lucrative- the cost of the insurance industry of recognising CFS as a physical disease is enormous.
Carol Monaghan, SNP secured a Debate on the PACE Trial in the House of Commons Westminster Hall on February 20, 2018.
Carol Monaghan (Glasgow North West) (SNP), “I think that when the full details of the trial become known, it will be considered one of the biggest medical scandals of the 21st century.”
PACE Trial: People with ME 20 February 2018
Volume 636, Column 28WH
Official Hansard Record:
Thanks Suzy. That is exactly the quote which stood out for me too when I watched the debate. The latest is that primary investigator of the PACE trial retired shortly after the latest FOI request for all the trial data. Queen Mary UL are saying they have no staff who know how to retrieve it so that’s (apparently) that. PACE is more like the Titanic then…we’ll have to send the divers in! The whole thing is indeed a scandal.
If the PACE trial was such a success, why has it, along with most of the other research that claims to show that GET and CBT help people with ME recover, been ranked as either poor or very poor in terms of scientific validity? And why has Nice removed recommendations for the two so- called treatments? And why do people with ME so regularly state that GET in particular has done them great harm? I just don’t understand why anyone who claims to be remotely rational would continue to support such a study. There is a module in a course at the University of California called ‘How not to conduct a research study’ which uses PACE as an exemplar.