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"News" 8 Sep 2016: PACE trial team analyse main outcome measures according to the original protocol

Messages
65
Location
UK
Esther12 said:
I doubt that the data from PACE is going to show a significant problem with CBT/GET causing harm.

And:



By worsers I'm meaning more those who got worse but not to the degree of dropping out or being classed as adverse events.

Those whose health and ability to function worsened to a greater or lesser degree with CBT/GET.

That doesn't seem to have been adequately assessed?

Getting 'worse' should show up, for example in the 6 minute walking test. I distinctly remember I did far fewer setps in the second and third ones than the original one. Same for the tramping up and down a set of mini stairs. But they didn't do the ankle braclet more than once, so that has a starting figure, but not an ending figure.

The question is, whether or not the data requested under the FOI is for starting and say the last one - for comparison.

I'm pretty sure that deterioriation in functionality during the Trial in terms of physical capability will show up in the walking and mini stairs thing.

As to the questionnaires, where you put how you 'felt' about symptoms etc. Not so sure, cos the variables are greater, for example, I walked fewer steps, had to give up most of my life, so was grieving for that, but also my symptoms got a bit less overall. I can't remember what I put on teh scales, but I do remember finding it hard cos it wasn't a linear progression and lots of elements were included in my working out my answer.

And as far as earnings went, I happened to work fewer hours, for the same money (payrises in effect) and as I recall, taht scenario wasn't one they'd envisaged happening. I think they thought people would not have that correlation between hours worked and hourly rate. Cos most people, do fewer hours and have less money.

I'm looking forwards to seeing the results once the data has been released to Alem and analysed according to the original protocols.
 
Messages
65
Location
UK
Hmmm I've now read teh rest. I'd completely forgotten what the questionannaires actually asked. Yes they may have asked if you can do certain things physically.

As to the question about 'do you have trouble starting things' - I don't have any cogent proof as to why I think this, but in my mind, this question was about depression type behaviours I think.

To be honest it's all so long ago, nearly a decade, it's all a bit of a blur!
 

anciendaze

Senior Member
Messages
1,841
I've only skimmed this thread to see if anyone had made the point I had in mind. If you did, and I missed it, I will apologize in advance.

Remember that the original intake of patients considered as CFS patients by primary care physicians was 3158. Of these some 640 were chosen, and chose to participate. None of those who participated could have been housebound. The entire study only applied to about 20% of the population of "CFS" patients per NHS labels.

This group was randomized into 4 study arms, so we are talking about around 160 in each arm. Now we come to the question of how many of these were "improved" by this therapy, which is currently being claimed as roughly 22%. Oh, by the way, the "control group" experienced half that improvement.

The difference between their controls and preferred therapies now depends on results from about 16 individuals. (Does anyone with experience in statistics see a problem with calling this a "massive study" supporting those therapies?)

My point for the UK government is that the problem seen by their own medical professionals is scarcely affected by a therapy which applies to a few percent of the original 3158. This never was any kind of solution to the public medical problem.

I'm sure there will be a spirited defense of these results. This must necessarily depend on the unsupported assertion that these patients are fully representative of the entire 3158. Is there something I have not seen to suggest that the study cohort was the result of anything except "cherry picking" patients who seemed likely to improve?

This, possibly picking patients who were less ill to begin with, is always a problem in any study of the benefits of exercise, and I am so far unaware that anyone has controlled for the effect in any medical study of any condition. There have been studies which judged severity of illness by objective measures, but the problem of controlling for the selection effect I'm describing without such objective standards does not appear to have been addressed.
 

Dolphin

Senior Member
Messages
17,567
Getting 'worse' should show up, for example in the 6 minute walking test. I distinctly remember I did far fewer setps in the second and third ones than the original one. Same for the tramping up and down a set of mini stairs. But they didn't do the ankle braclet more than once, so that has a starting figure, but not an ending figure.

The question is, whether or not the data requested under the FOI is for starting and say the last one - for comparison.

I'm pretty sure that deterioriation in functionality during the Trial in terms of physical capability will show up in the walking and mini stairs thing.

As to the questionnaires, where you put how you 'felt' about symptoms etc. Not so sure, cos the variables are greater, for example, I walked fewer steps, had to give up most of my life, so was grieving for that, but also my symptoms got a bit less overall. I can't remember what I put on teh scales, but I do remember finding it hard cos it wasn't a linear progression and lots of elements were included in my working out my answer.

And as far as earnings went, I happened to work fewer hours, for the same money (payrises in effect) and as I recall, taht scenario wasn't one they'd envisaged happening. I think they thought people would not have that correlation between hours worked and hourly rate. Cos most people, do fewer hours and have less money.

I'm looking forwards to seeing the results once the data has been released to Alem and analysed according to the original protocols.
Thanks @Amused.

Can you remember anything about the long-term follow-up study? There was the main study where it were some assessments at 12 weeks, 24 weeks and 52 weeks. The last time one saw the therapist was at around 36 weeks.

However I am interested in a study they did after 52 weeks: a minimum of 2 years after starting the trial. Did they ask about hours worked at that stage? They haven't published on it but I vaguely recall seeing something which suggested they might look for this data. It is interesting if they collected the data but haven't published it.

Please keep track of what they ask you in another long-term follow-up study that they recently have got funding for. Again it will be interesting to see what data they collect compared to what they publish and.
 

anciendaze

Senior Member
Messages
1,841
Here's a more concrete example of the selection effect I was describing above, and the way it impacts a debate on public policy.

Assume you, as a doctor with a preferred intervention, have 50 patients referred to you as having a particular condition. (You can call this condition CFS, but it could be anything with dicey diagnoses.)

After examining all 50 patients, you decide that 10 of them are suitable for treatment. After treating these for a year you proclaim that 2 are "improved", neglecting to mention that a group of 10 who did not receive your special treatment sauce had one patient with the same improvement. (You also avoid emphasizing the fact that you yourself couldn't distinguish patients who benefited from your intervention from all others in long-term follow-up.)

If this is used to determine national policy, what happens to the other 48 patients?

When favorable response rates are this low, and transient, it is hard to reject treatments based on accupuncture, aromatherapy, biofields, Rolfing, Shamanism, etc.
Should we now expect to see trials for these alternatives?
 
Messages
65
Location
UK
Thanks @Amused.

Can you remember anything about the long-term follow-up study? There was the main study where it were some assessments at 12 weeks, 24 weeks and 52 weeks. The last time one saw the therapist was at around 36 weeks.

However I am interested in a study they did after 52 weeks: a minimum of 2 years after starting the trial. Did they ask about hours worked at that stage? They haven't published on it but I vaguely recall seeing something which suggested they might look for this data. It is interesting if they collected the data but haven't published it.

Please keep track of what they ask you in another long-term follow-up study that they recently have got funding for. Again it will be interesting to see what data they collect compared to what they publish and.

I wish I'd paid more attention at the time now! and kept copies of stuff. But I didn't.
I was on the CBT arm. I remember at the end there was a final therapist session, and a session of signoff for the end of the Trial. This I remember vividly cos I thought it was the promised SMC that I'd never had (supposed to be given alongside) and the guy who did the signoff tried to do that and my questions about painkillers & symptom control in a physical way. But failed horribly. If only both of us had realised and instead of him trying to hlep me there and do 2 things, the medical bit had been rescheduled. But not.... There were lots of questionnaires. And a step test (where I did really badly compared to the beginning) and the mini stairs (again reduced number).

I was late onto the Trial, 2007 to 2008 by the time neurology got their ducks in a row and gave me the all clear, so I think the 2 year followup was in 2010 when I'd moved from London to Northubmerland. I remember it being one of those carbon copy type questionnaires. But nothing about it. At the time I wasn't working cos of the recession. But looking for work.

I'm very interested in being included in any followup they've got funding for - not only cos I think it's good to do, but also I've gone severe, which they said wouldn't happen if I followed the CBT Manual. I ahve followed the manual and I have gone severe! So I'd like an opportunity to slot that into their findings! My going severe thankfully doesn't appear to be the progressive sort. I appear to be rehabbing at a glacially slow pace just by wombling around the house and immediately outside it. I got a cripple chariot a fortnight ago (aka mobility scooter) and am trundling around on that a bit (at a cost) and starting to do more 'practicing' of being in the car with family driving. Taking forever with more steps backwards tahn forwards, but it is slowly slowly getting stronger. Of course my relapses happen over a period of months of thinking I'm doing ok but pushing too far then crashing. So who knows! but I digress.

I did happen to speak to one of the 3 first named researchers last week, who was very kind and helpful, and explained what data I ought to be asking for from my PACE centre. I want to use it as a benchmark to aim for, now my severe seems to have stabilised. I'm thinking of asking for the stuff we discussed in that telecon specifically, but also for everything (except the taped CBT sessions. those I never want to hear, I remember mostly wailing and crying about giving stuff up). cos it'll be useful to help me remember and useful I think for me having a framework of whatever results fall out from whatever Alem's going to be able to analyse.

Finally, as to participants being 'cherry picked'. To a certain extent there was a lot of occasions where patients wouldn't get that far to start with:
1. GP doesn't believe in ME/CFS and/or won't refer to a consultant
2. Consultant doesn't think to refer patient to the Trial.
3. Patient doesn't live close enough to be able to turn up.
4. Patient is trying to hold down a job and can't take time off or can take time off but is too knackered to work AND participate. I was very lucky I was on a 6 week contract, got ill, boss told me to reduce my hours AND find out what was wrong with me, and kept me on that contract for 2.5 years, with fewer hours but the same money. I would imagine most people in a job without a supportive boss, wouldn't ahve been able to participate. I do remember the therapist saying I was the only, or one of the few on the Trial who had carried on working. I got the feeling people had carried on with the Trial but given up work for example.
5. Patient has other things wrong with them so by the time those are fixed (with Nhs waiting lists and delays) the Trial may have been closed.

I can't remember which thread I said it on, or maybe it was on MEAction's site, but for me, they ran the bloodtests and also did MRI and various neurology stuff before I got to the CFS Unit. Then at the Unit they did psychological assessments etc and said that if they found people had other things, they'd be referred off to other depts, like mental health or erm I dunno, but say a neurology thing. So I know people are concerned (rightly) about the Oxford criteria being used, but within the context of the NHS conveyor belt system of dealing with issues then passing you onto the next dept for the next issues and the 'hurdles' one had to clear to get to be considered for the Trial, at least at the hospital I was at, I'm pretty sure the people who participated weren't just a 'little bit tired for a week' or had other obvious issues that would explain it. Obviously I have no idea about other centres, and also I only saw a few other patient type people who did look bloody ill and knackered! even though there was parking close to the building and a lift and not enormously long corridors to get to reception.

Sorry I'm so fluffy on the details, I thought I'd be on the Trial, fixed and it would help others. I didn't realise it would be so important a decade later!
 
Messages
65
Location
UK
Here's a more concrete example of the selection effect I was describing above, and the way it impacts a debate on public policy.

Assume you, as a doctor with a preferred intervention, have 50 patients referred to you as having a particular condition. (You can call this condition CFS, but it could be anything with dicey diagnoses.)

After examining all 50 patients, you decide that 10 of them are suitable for treatment. After treating these for a year you proclaim that 2 are "improved", neglecting to mention that a group of 10 who did not receive your special treatment sauce had one patient with the same improvement. (You also avoid emphasizing the fact that you yourself couldn't distinguish patients who benefited from your intervention from all others in long-term follow-up.)

If this is used to determine national policy, what happens to the other 48 patients?

When favorable response rates are this low, and transient, it is hard to reject treatments based on accupuncture, aromatherapy, biofields, Rolfing, Shamanism, etc.
Should we now expect to see trials for these alternatives?


Sorry I've just realised the cherry picking thing was responding to what you said. What I'm trying to say is that to a certain extent participants picked themselves. Or rather self excluded themselves. It's pure supposition but I'd imagine only moderately or mildly affected people could have done it, not the severely affected (wisely cos it was a big committment) and of those, many would have needed to prioritise the ability to keep working or at least that would be a driver at first. Many of those would have families or other commitments. Which I didn't. I only needed to stay working and as I said above my boss was really supportive and I only had myself to worry about. Not other people.

So from what I can remember (which is fluffy) yes you had to 'tick' certain boxes in the preliminary screening, but once you did, it was up to you whether you joined it or not. So in my eyes, as the boxes were fairly wide, it's more patient self selection than the researchers picking people likely to improve. They were very keen to get MORE people not fewer was my impression. And I didn't get the impression they were looking at my capacity to improve, cos their belief is/was that if you follow xyz you do improve. Their 'worldview' encompasses relapses, but that these are only temporary and can be recovered from. So if one is researching on that basis, with that belief, one wouldn't exclude any of the 'walking wounded' - because the severe ones can't join in anyway. If that makes sense?

Not sure it does - I was feckless and went paddling on Sunday (with parentals help and my rollator for resting on every 2 metres) PEM is beginning to kick in with a vengeance and I'm not making sense with my carer or family today. Anyway if that is gobbledegook, that's why!
 

anciendaze

Senior Member
Messages
1,841
Sorry I've just realised the cherry picking thing was responding to what you said. What I'm trying to say is that to a certain extent participants picked themselves. Or rather self excluded themselves. It's pure supposition but I'd imagine only moderately or mildly affected people could have done it, not the severely affected (wisely cos it was a big committment) and of those, many would have needed to prioritise the ability to keep working or at least that would be a driver at first. Many of those would have families or other commitments. Which I didn't. I only needed to stay working and as I said above my boss was really supportive and I only had myself to worry about. Not other people.

So from what I can remember (which is fluffy) yes you had to 'tick' certain boxes in the preliminary screening, but once you did, it was up to you whether you joined it or not. So in my eyes, as the boxes were fairly wide, it's more patient self selection than the researchers picking people likely to improve. They were very keen to get MORE people not fewer was my impression. And I didn't get the impression they were looking at my capacity to improve, cos their belief is/was that if you follow xyz you do improve. Their 'worldview' encompasses relapses, but that these are only temporary and can be recovered from. So if one is researching on that basis, with that belief, one wouldn't exclude any of the 'walking wounded' - because the severe ones can't join in anyway. If that makes sense?

Not sure it does - I was feckless and went paddling on Sunday (with parentals help and my rollator for resting on every 2 metres) PEM is beginning to kick in with a vengeance and I'm not making sense with my carer or family today. Anyway if that is gobbledegook, that's why!
You are making considerable sense, but you are also trying to make a distinction I did not. I was worried about selection effects, not trying to establish something like criminal intent by researchers. It doesn't matter if patients are self-selected or not, particularly when the criteria on preliminary questionnaires are chosen by study authors. The validity of the study would be questionable any time there is room for a huge selection effect, and positive response rates are low.

I've looked at other medical research not directly related to "CFS", like the effect of exercise on recovery from surgery. Where there is objective evidence of degree of impairment you can argue that your protocol was not simply selecting patients who were in better condition at the outset. Without this kind of measure to tell how sick patients are it is entirely possible a result indicating people who exercised improved was due to a self-selection effect caused by people who feel better being more likely to exercise. You don't have to call this any kind of therapy, just an observation of an association between exercise and later health. There has been surprisingly little concern in medicine for this kind of confounding effect.

Purely as an illustration consider a study of walking as therapy for sprained ankles. People with mild sprains may benefit, while people with more serious sprains will refuse to walk, making them non-compliant.
 

JES

Senior Member
Messages
1,320
You are making considerable sense, but you are also trying to make a distinction I did not. I was worried about selection effects, not trying to establish something like criminal intent by researchers. It doesn't matter if patients are self-selected or not, particularly when the criteria on preliminary questionnaires are chosen by study authors. The validity of the study would be questionable any time there is room for a huge selection effect, and positive response rates are low.

PACE was a randomized trial, meaning that once the trial participants were determined, they were randomly assigned to one of the treatment groups (SMC, APT, GET or CBT). This, from my understanding, should avoid any selection effects within the trial participants.

Another matter is that the trial authors should have always compared CBT and GET improvers against SMC improvers (SMC was their so called "placebo group"). In their latest revised analysis from last week, CBT actually did not provide a statistically significant improvement over SMC, and GET was just barely significant. So the 20% reported improvement was more like 10% when you compare it against SMC.
 

anciendaze

Senior Member
Messages
1,841
@JES,

I fully agree with you concerning the use of SMC as both a control group and a form of therapy. If it was a control group, gains in that group should have been subtracted from the results of different therapies. This is an example of misrepresentation of results which seems deliberate. I believe the reason even their "control group" improved was due to the selection effect I've been talking about.

The Oxford fallback position now seems to be that CFS will likely go away on its own if you wait long enough. (Decades?) Note that there has been no randomized controlled test of SMC, which is deemed beyond question. (Why?)

PACE was partly randomized, and sort of controlled. The selection of trial participants was anything but random. Why is this important? The assumption of normal distributions on which parametric statistics depend is not met by the population distribution from which they are selecting patients. This takes us into fairly esoteric territory governed by the central limit theorem to establish that groups in the study were normally distributed as a result of random sampling. I am on record as predicting that this was not true, based on a number of strange aspects of this research already reported. (When all groups show an increase in variance/standard deviation you should look carefully at the assumption of normality, the bell-shaped curve at the beginning may be no more stable than a pile of marbles. If the distribution is not stable, you are well outside parametric statistics.) This is a particular concern when there are changes in entrance criteria which leave sample groups clustered near the upper bound of 60 or 65. A tiny random variation could push them back into "health".

If the groups are not normally distributed, then two parameters (mean and standard deviation) are not sufficient to describe them. This gets to the heart of the dispute over trial data. If only a few outliers were responsible for the shift in mean values we have to deal with questions of errors in diagnosis. After dismissing CFS diagnoses by other NHS doctors as in error 30% of the time, in another paper, these authors apparently assumed they were never in error. We have good reason to doubt their diagnostic acuity, based on the variety of divergent criteria they have claimed to have satisfied. If results from a handful of patients could change the outcome substantially this is a definite concern.

On the other hand, if all patients changed by very modest amounts the results were not clinically significant. We can't tell without seeing more information about those distributions.

We have every reason to believe the authors chose those patients they believed were most likely to respond to their preferred interventions. This is revealed by the biased claims made during the trial, and distributed to patients before any results were tabulated. This may not count as a placebo effect, but it will certainly bias responses on questionnaires when those running the trial are authority figures with input to agencies controlling benefits. Patients who were immune to such influences self-selected themselves out of the trial at the beginning.

In trials of medication similar weak results are often attributed to placebo effect. We can't be certain what is going on inside patients' minds because we may also be dealing with a publication bias toward trials which favor a particular intervention. Eliminate the negative reports and the drug looks promising.
 

BruceInOz

Senior Member
Messages
172
Location
Tasmania
PACE was partly randomized, and sort of controlled.
It wasn't controlled. There is too much difference in the therapist contact time between SMC and the active arms for SMC to be considered an effective control. This is implicitly acknowledged in the 2011 Lancet paper where the first sentence of the Methods section says:
PACE was a parallel, four group, multicentre, randomised trial, ...
No mention of the word "controlled". If i recall, that was slipped in in later papers.
 

anciendaze

Senior Member
Messages
1,841
Above I've again raised the question of how representative the patients in the PACE trial were of the entire intake of patients referred for treatment. This is basically an assertion unsupported by evidence, and it is crucial to the question of setting public policy.

Now, I want to take aim at a different problem: how representative are the responders in arms of the PACE trial of the entire cohort in that arm? If 60% responded you might say they were representative, with only a minority of patients somehow being different. Adjust that number to 10% and it becomes clear that the responders do not even represent the bulk of those treated with the preferred intervention.

At this point my questions about diagnostic error become especially pertinent. If you manage to get diagnostic error for any psychiatric condition down to only 10% you are doing well. When results of treatment are at the same level it is very appropriate to consider that you may have a mixed cohort created by faulty diagnoses.

This is an internal contradiction in the idea that the disease is primarily a mental illness needing counseling taken together with the revised results. My own answer is to reject the assumption of primary mental illness, but I have no idea how the authors would deal with such a contradiction. They have literally wasted years denying that internal contradictions even exist.

Pharmaceutical companies are well aware of such problems, and for good financial reasons. If a drug, say to treat anxiety, only produces a response in 10% of patients it will never be approved, and would fail in the marketplace if it were approved. On the other hand, if it turned out all the patients treated for anxiety who responded should actually have been diagnosed with obsessive-compulsive disorder (OCD), then new prospects open up. A drug which benefits a high percentage of patients with OCD should be marketable.

This is not a far-fetched scenario. The history of modern pharmacology is filled with examples of drugs which were developed for one purpose, but ended up being effective for another after a disappointing trial for the original condition.

My point is that all the responders in the PACE trial may have been suffering from a different condition from non-responders. The question then becomes: did the PACE authors correctly diagnose 80% of the patients, for which their preferred therapies were ineffective, or did they correctly diagnose 10% for which their therapies were somewhat effective, and misdiagnose the 80%? (I'm leaving 10% uncertain.)

These are serious scientific questions, and failure to address them after five years of controversy is telling.
 

Dolphin

Senior Member
Messages
17,567
I wish I'd paid more attention at the time now! and kept copies of stuff. But I didn't.
I was on the CBT arm. I remember at the end there was a final therapist session, and a session of signoff for the end of the Trial. This I remember vividly cos I thought it was the promised SMC that I'd never had (supposed to be given alongside) and the guy who did the signoff tried to do that and my questions about painkillers & symptom control in a physical way. But failed horribly. If only both of us had realised and instead of him trying to hlep me there and do 2 things, the medical bit had been rescheduled. But not.... There were lots of questionnaires. And a step test (where I did really badly compared to the beginning) and the mini stairs (again reduced number).

I was late onto the Trial, 2007 to 2008 by the time neurology got their ducks in a row and gave me the all clear, so I think the 2 year followup was in 2010 when I'd moved from London to Northubmerland. I remember it being one of those carbon copy type questionnaires. But nothing about it. At the time I wasn't working cos of the recession. But looking for work.

I'm very interested in being included in any followup they've got funding for - not only cos I think it's good to do, but also I've gone severe, which they said wouldn't happen if I followed the CBT Manual. I ahve followed the manual and I have gone severe! So I'd like an opportunity to slot that into their findings! My going severe thankfully doesn't appear to be the progressive sort. I appear to be rehabbing at a glacially slow pace just by wombling around the house and immediately outside it. I got a cripple chariot a fortnight ago (aka mobility scooter) and am trundling around on that a bit (at a cost) and starting to do more 'practicing' of being in the car with family driving. Taking forever with more steps backwards tahn forwards, but it is slowly slowly getting stronger. Of course my relapses happen over a period of months of thinking I'm doing ok but pushing too far then crashing. So who knows! but I digress.

I did happen to speak to one of the 3 first named researchers last week, who was very kind and helpful, and explained what data I ought to be asking for from my PACE centre. I want to use it as a benchmark to aim for, now my severe seems to have stabilised. I'm thinking of asking for the stuff we discussed in that telecon specifically, but also for everything (except the taped CBT sessions. those I never want to hear, I remember mostly wailing and crying about giving stuff up). cos it'll be useful to help me remember and useful I think for me having a framework of whatever results fall out from whatever Alem's going to be able to analyse.

Finally, as to participants being 'cherry picked'. To a certain extent there was a lot of occasions where patients wouldn't get that far to start with:
1. GP doesn't believe in ME/CFS and/or won't refer to a consultant
2. Consultant doesn't think to refer patient to the Trial.
3. Patient doesn't live close enough to be able to turn up.
4. Patient is trying to hold down a job and can't take time off or can take time off but is too knackered to work AND participate. I was very lucky I was on a 6 week contract, got ill, boss told me to reduce my hours AND find out what was wrong with me, and kept me on that contract for 2.5 years, with fewer hours but the same money. I would imagine most people in a job without a supportive boss, wouldn't ahve been able to participate. I do remember the therapist saying I was the only, or one of the few on the Trial who had carried on working. I got the feeling people had carried on with the Trial but given up work for example.
5. Patient has other things wrong with them so by the time those are fixed (with Nhs waiting lists and delays) the Trial may have been closed.

I can't remember which thread I said it on, or maybe it was on MEAction's site, but for me, they ran the bloodtests and also did MRI and various neurology stuff before I got to the CFS Unit. Then at the Unit they did psychological assessments etc and said that if they found people had other things, they'd be referred off to other depts, like mental health or erm I dunno, but say a neurology thing. So I know people are concerned (rightly) about the Oxford criteria being used, but within the context of the NHS conveyor belt system of dealing with issues then passing you onto the next dept for the next issues and the 'hurdles' one had to clear to get to be considered for the Trial, at least at the hospital I was at, I'm pretty sure the people who participated weren't just a 'little bit tired for a week' or had other obvious issues that would explain it. Obviously I have no idea about other centres, and also I only saw a few other patient type people who did look bloody ill and knackered! even though there was parking close to the building and a lift and not enormously long corridors to get to reception.

Sorry I'm so fluffy on the details, I thought I'd be on the Trial, fixed and it would help others. I didn't realise it would be so important a decade later!
Thanks for sharing all of that. Very sorry to hear you have become more severe.

All the details for the first 12 months of the trial should have been fairly well covered in this document: http://evaluatingpace.phoenixrising.me/PACE_Protocol.pdf

However for any of the longer follow-up, there is no protocol that I know of so questionnaires et cetera might be dropped if someone doesn't keep track of it. So please if you can keep a record of what you receive