A general thread on the PACE trial!

[Barry]

I seem to recall that when this was raised the PACE trial authors claimed this wasn't an objective measure because of possible changes in the employment market.

Although there is some validity to that, I should have thought the changes could have been normalised to a fair degree, given that employment market changes would be pretty well understood.

To me if I'm recovered, I'm able to come off benefits, work full time, do my house work and have a life.

But when I said this he [PDW] asked me: "Do you want to go back to the life that gave you ME?"

That's a cop out.

It's way beyond a cop-out. It's a blatant admission of the presumption that a person's lifestyle and attitude to their life is the cause of their ME.

He said,'Do you think it's down to you?' On my report he has written: "[name] is making good progress. [Name]'s only remaining barriers are [name]'s illness beliefs"

That, surely, is good anecdotal evidence of supportive care being withheld from a patient due to wilful misdiagnosis, and thereby risk of harm.

 

[BruceInOz]

But when I said this he asked me: "Do you want to go back to the life that gave you ME?"

That's a cop out.

I think that's called gaslighting.

 

[Barry]

Although there has been media coverage of 'the flaws in the PACE trial' it has been nothing compared to the headlines of '60% of pwME recover with CBT/GET' style reporting (even though the 60% was 'improvement')

The move from 60% to 21% should surely have been a big enough revelation, even without all the other ins and outs of the trial, to warrant equally sensational headlines(?)

Am I right in thinking that even those numbers took no account of the (notional) control arm results, effectively inflating those numbers still further?

 

[Barry]

This is probably the best indicator of how fatally flawed it is to have the word "fatigue" as part of the condition's name. And why this group of people were so determined to have PwME labelled as having Chronic Fatigue Syndrome ... all about patients' perceptions of their illness, thereby allowing people like these to discount other measures that don't fit with their closed belief system.

 

[JohnTheJack]

Do you think that was the case? Because the many patient surveys indicate that quite a lot of people with ME have tried GET and I know that some important ME advocates did as well. In the early stages of ME you do not know for sure what disease you have and how your body will respond. So if doctors propose a treatment that might help you without there being an alternative then it’s not easy to say no, especially if you’re desperate. So I’m not sure that most ME patients will refuse GET, especially in the years 2000 when knowledge about the harms of GET was less well known and criticism was less prominent.

I do think that was the case. It may be true that newly diagnosed patients would be willing to try anything including GET, but ME is not a new illness and there were many who had been ill for years or decades by the time the trial started. We knew there was no treatment, so wouldn't have wasted our time and energy going to 'treatment clinics' and knew that neither CBT or GET is effective so wouldn't have bothered taking part in a trial of them.

There is no question that the sample was biased: by the criteria it used, by taking participants from treatment centres and by testing interventions many patients already knew were worthless and potentially harmful.

 

[dave30th]

Am I right in thinking that even those numbers took no account of the (notional) control arm results, effectively inflating those numbers still further?

Yes, in the comparison arms the rate of "improvement" was about 45%, so there was a marginal 15 % improvement for CBT/GET. When "improvement" dropped to around 20 %, the comparison arms had around 10%.

 

[Barry]

Yes, in the comparison arms the rate of "improvement" was about 45%, so there was a marginal 15 % improvement for CBT/GET. When "improvement" dropped to around 20 %, the comparison arms had around 10%.

So a 10% difference on subjective outcomes for improvement, from unblinded treatments.

 

[Unable]

So a 10% difference on subjective outcomes for improvement, from unblinded treatments.

And that might be roughly the reporting bias, you might expect from patients knowing they are getting “the treatment” ! (Actually I’d have guessed it would be higher, but there you go )

 

[ME/CFS Skeptic]

I do think that was the case.

Ok, but there are still some things that don’t add up.

The patients in the trial were given very cautious instructions to increase their activity level. GET used a safe baseline, small increases with a mutual agreed planning, heart rate monitoring and 15 sessions of oversight by a trained supervisor. I suspect that in most illnesses this would help patients to get a little better or at least to increase their fitness.That didn’t happen in the patients in the PACE trial and they reported to be severely disabled at follow-up.

So what prevented them from increasing their fitness if they were merely chronically fatigued? I find it hard to believe that would have simply refused to follow the treatment plan. If you are part of such a big treatment trial, receive detailed instruction and meet 15 times with a therapist who checks up on you, I suspect the majority of participant would have honestly tried to increase their activity level.

To me, the failure to achieve increased activity is an indication that most of these patients had ME/CFS. Around 85% of them indicated they had post-exertional malaise at baseline.

Also: why isn't there an indication of a subgroup of patients doing worse (the 'real ME' patients) and a larger group making some small improvements (the chronically fatigued)? Wilshere indicated that the data did not show this to be the case. The argument that there were basically no 'real ME' patients in the trial seems a bit unlikely: all around the world ME patients report to be harmed by GET, but this large trial would have somehow excluded them all?

 

[Dolphin]

Regarding their claim that an average lack of employment improvements might be down to the economy in the 2000s (a questionable claim as the trial recruited over 4 or 5 years): the Collin & Crawley 2017 paper on English CFS clinic patients (who would have got GET and/or CBT mainly) also didn’t find an improvement using this measure.

 

[Sean]

All one can say is given the inherent built in bias the only surprise is that the results were so poor. Demonstrating that, regardless of the hypothesis as to causes, this treatment doesn't seem to work for anyone within the staggeringly broad criteria.

I think that is the real finding from PACE: it disproved their own model.

----------------------

To me if I'm recovered, I'm able to come off benefits, work full time, do my house work and have a life.

But when I said this he asked me: "Do you want to go back to the life that gave you ME?"

That's a cop out.

I think that's called gaslighting.

I would even describe it as cowardice and fraud.

Either that or he is so incompetent that he should not be allowed near a piece of wet tissue.

 

[TrixieStix]

That quote is quite revealing in terms of the cognitive dissonance it arose from. It makes no sense. If a person is recovering then a discrepancy between their aspirations and their lifestyle is not an obstacle - as it would have been before recovery. And why do you need a psychodynamic theorist to describe someone wanting to work but not being able to? I suspect the psychodynamic theorists talked about people secretly wanting to keep their lazy lifestyle.

I can understand how healthy people could mistakenly believe that not having to work due to disability sounds like a 'perk' of being disabled. Most healthy people have only ever experienced very short periods of not working (due to either temporary illness, vacation, etc). To them such short periods off from work are often welcome and/or enjoyable, and they know that it's only temporary.

 

[EzzieD]

I can understand how healthy people could mistakenly believe that not having to work due to disability sounds like a 'perk' of being disabled. Most healthy people have only ever experienced very short periods of not working (due to either temporary illness, vacation, etc). To them such short periods off from work are often welcome and/or enjoyable, and they know that it's only temporary.

Yes. A good friend who is a kind, sympathetic and understanding person, is currently unemployed and having problems finding a good job as opposed to terrible ones his Job Centre tries to foist on him. Feeling stressed out he said to me "You're lucky you don't have to work." After getting over my shock, I explained that no, I was not lucky, I'd rather be working, even at a less than ideal job, than sitting at home with incapacitating scary neurological symptoms. It then took yet further explanation to get him to sort of understand. When our own friends we've known for years are unable to grasp what's like to be in our situation, no wonder the general public (and certain medical professionals) think it's no big deal and that we're even 'lucky'.

 

[Mithriel]

The problem with the term "post exertional malaise" is that it can be wrongly interpreted. WE know what we mean but it is easy to make it simply feeling worse with exercise, that is walking too far, getting achey or having to sit down for a while, not the complex and abnormal experience we have.

As John says, at the time they were recruiting for the trial, people in the ME community would not go to the clinics. Partly because we avoided doctors so did not get referred and we knew how bad the clinics were. Then they used the Oxford criteria which excludes neurological problems. At the time we tried to find out exactly how they did that but they refused, were sarcastic actually, yet a postive Romberg test is widespread in ME as is paralysis, speech problems and other neurological things. They only took 600 from something like 3000 available candidates (memory!) without ever saying what the criteria were.

Now the trial may have included patients with actual ME, but only at the milder end and there was a high drop out rate for GET. While they were recruiting and setting up the trial we believed that they were selecting for post viral fatigue rather than ME which seemed to be the case for the previous trials especially as they do not believe the conditions are different. Exercise does not help that as deconditioning is not a factor there either.

In other studies, actigraphy has shown that patients with CFS (possibly even ME!) rearranged their activity so they can do the walking. Even when I was getting worse, I could have managed a walk every day if someone else had fed the kids and washed the dishes. The trial was doomed to failure when they did not measure total activity and that could be why people with actual ME could take it.

 

[JohnTheJack]

Ok, but there are still some things that don’t add up.

The patients in the trial were given very cautious instructions to increase their activity level. GET used a safe baseline, small increases with a mutual agreed planning, heart rate monitoring and 15 sessions of oversight by a trained supervisor. I suspect that in most illnesses this would help patients to get a little better or at least to increase their fitness.That didn’t happen in the patients in the PACE trial and they reported to be severely disabled at follow-up.

So what prevented them from increasing their fitness if they were merely chronically fatigued? I find it hard to believe that would have simply refused to follow the treatment plan. If you are part of such a big treatment trial, receive detailed instruction and meet 15 times with a therapist who checks up on you, I suspect the majority of participant would have honestly tried to increase their activity level.

To me, the failure to achieve increased activity is an indication that most of these patients had ME/CFS. Around 85% of them indicated they had post-exertional malaise at baseline.

Also: why isn't there an indication of a subgroup of patients doing worse (the 'real ME' patients) and a larger group making some small improvements (the chronically fatigued)? Wilshere indicated that the data did not show this to be the case. The argument that there were basically no 'real ME' patients in the trial seems a bit unlikely: all around the world ME patients report to be harmed by GET, but this large trial would have somehow excluded them all?

But that raises another question. As you say, although the GET cohort did slightly more on the 6-minute walk test, they didn't raise their fitness, which suggests they weren't actually more active.

So did they actually have GET? The distinguishing (from pacing) feature of GET is that there is a planned increase in activity that happens regardless of symptoms. But the investigators kept no record of how many patients actually stuck to the plan. It's quite possible that patients saw the therapist to improve marginally their subjective 'fatigue' and they switched their attention to one activity (the walk) at the expense of others. But they didn't actually increase their exercise levels. In the controlled environment of a clinical trial where the therapists were desperate to ensure no harms occur that might spoil their cause, they may well have actually followed the patients' lead. So it wasn't really GET. It was just another form of pacing.

I would add as well and I think @Mark Vink has done some work on this: the only types of harm measured in PACE were fairly extreme events, so perhaps there's no surprise none/little was recorded.

 

[ME/CFS Skeptic]

It's quite possible that patients saw the therapist to improve marginally their subjective 'fatigue' and they switched their attention to one activity (the walk) at the expense of others. But they didn't actually increase their exercise levels

Ok. But to be honest this doesn’t convince me. It’s a possibility but why would the patients do that?

If you suppose they didn’t have ME and could have increased their activity level if they tried, why would they refuse to do so after signing up for a research study? Why would they covertly refuse to grade their exercises as they are being encouraged/monitored to do GET, a treatment that could actually help them get a little better?

If you suppose they (a majority) did have ME, why did all the patients in the study switched their attention to GET at the expense of other activities, while there are so many reports of ME patients being harmed by GET? The patients in those surveys did not lessen their activities while doing GET which makes sense as that would be contrary to the whole idea of GET. If you’re willing to do this treatment and sign up for it, then I suppose you actually believe there’s some chance that GET will improve your health. So I expect these ME patients to try it out and ignore any setbacks they might have along the way. We all know how easy it is to overdo things and how serious a relapse can be for ME patients even after trivial overexertion. So why would we suppose that the ME patients who naively signed up for a GET trial somehow managed to pace themselves perfectly at a time they received instructions by a trained physiotherapist to do just the opposite?

 

[Lucibee]

To be fair, we don't whether they increased their exercise levels because actigraphy was dropped. Some might have managed to. Others might have paced carefully so that they could complete the test and demonstrate they were doing OK (even at the cost of being wiped out for the next few days).

This comment was left by someone in the GET group:



Source:

 

[Barry]

Pretty sure there was a comment on social media by a PACE participant (cannot remember where now though), which said they backed off from some of their normal daily life activities, in order to try and save their energy for the trial's activities. Which would make a mockery of GET anyway. Without measuring overall daily-living-activity, but only the trial's selected highlights, yet analysing that data on the assumption it represents all-inclusive activity, then you must end up with a skewed, artificially favourable interpretation. The person was saying that their overall activity level did not change, just the mix, so they could do their GET activities.

 

[Snowdrop]

Pretty sure there was a comment on social media by a PACE participant (cannot remember where now though), which said they backed off from some of their normal daily life activities, in order to try and save their energy for the trial's activities. Which would make a mockery of GET anyway. Without measuring overall daily-living-activity, but only the trial's selected highlights, yet analysing that data on the assumption it represents all-inclusive activity, then you must end up with a skewed, artificially favourable interpretation. The person was saying that their overall activity level did not change, just the mix, so they could do their GET activities.

I also saw this comment on twitter. And I can well imagine that someone would just naturally reduce other activity in order to do well on the test. It may not make sense. Not everything in life does. They had committed to the research and now were invested.

 

[Barry]

I also saw this comment on twitter. And I can well imagine that someone would just naturally reduce other activity in order to do well on the test. It may not make sense. Not everything in life does. They had committed to the research and now were invested.

Yes, and I think that is the point. Trial participants are not themselves likely to be familiar with scientific methodologies. The primary objective that was drilled into them was to do well, and I strongly suspect that the focus for that was to do well within the context of the trial itself. A well run trial would have emphasised the need to capture overall activities, but I bet that did not happen for PACE. The treatment was in a sense self indulgent - the emphasis on participants being motivated by the therapy itself, to show how well the therapy was benefiting them. Some (maybe most) participants may never have realised the biasing effects of swapping out some of their normal daily activities in order to fulfil GET activities, and the PACE mindset might well have been to not enlighten them!