The draft scope for the NICE guideline on ME/CFS is now out for consultation, June 2018

I can understand wanting to come at the data with no preconceptions but having done so, there's every reason to look at what others have done in order to see if someone has already reported the same findings; has mentioned such findings but has critiqued them with arguments that you haven't thought of; or did other analyses that make your findings irrelevant or cast them in a different light.

If you don't do that, you have no way of knowing whether you're adding to the literature or muddying the waters.

 

@Peter Kemp , thanks for the graphs: I love looking at the way different analyses can be presented. What puzzles me though is what your horizontal axis represents. You'll find that in our "evaluatingpace" webpages we analysed the changes in fatigue levels in a different way.

 

Dear Adrian, did you look at the charts? They represent actual data, not how it was interpreted or reported, but how it actually is. It has nothing to do with reporting bias. I am disappointed (and in fact find it unlikely) that anyone involved in campaigning would be unaware of the repeatedly expounded problems caused by including 'fatigue' patients in ME/CFS research. In fact I consider it so unlikely that I think your question is vexatious. The charts show what I would expect to see in a mixed cohort of fatigue and bona fide M.E. patients. As I have already stated, there is no data to correlate with the alternative criteria for M.E. and Reeves et al CFS so these cannot be verified.

 

'Vexatious' is a rather politically charged term in this context. This is the second time in this thread you've accused others of having sinister motives. Might I suggest that you consider such feedback constructively, rather than as an attack on you?

Your numbers are certainly very interesting, but I think comparing your results with those of others would only make them stronger, not weaker.

 

Dear @Peter Kemp,

I agree with a lot of what you say but these are issues we have discussed at length on the forums and I think are pretty much covered by what people have published. As Sasha says, if you want to publish the you need to cite other people who have published on the topic. There are lots of people with ME here who have been working on this as long as you have so it is hard to see why it should be difficult to find people to collaborate with.

I agree that it is likely that the recruitment to PACE could have favoured selecting people without typical ME that might have been more likely to improve. But since the improvement you mention occurs in all groups it cannot be evidence of being more likely to benefit from CBT and GET, but rather a likelihood of improving over the trial period in some sort of therapeutic context. The SMC arm subjects got pretty little as far as I can tell so the prima facie evidence is that they selected people who were rather likely to improve spontaneously.

Moreover, I am not yet convinced that the improvements are unusual for a trial like this. There are several reasons why people tend to improve in trials irrespective of treatments. One is regression to the mean for a relapsing remitting condition - where people get recruited at their worst and then return to average. Another is the placebo effect - which may not have operated much in the SMC group so might not fit. Then there is the 'reverse placebo' effect of people saying they are better when placed in the social role of being a therapy beneficiary. (I have recently emphasised this in my submission to the Scottish Parliament that they have published online.) There are probably other mechanisms. Major improvements across trials are common enough, especially if the trials are unblinded.

You are clearly wanting to hang your argument on the idea that evidence from PACE is weak because the 'wrong patients' were recruited. That is possible but I don't think we can prove it. Moreover, in real life nobody is a 'wrong patient'. Everyone deserves to be in a trial. For me the more persuasive argument is that as unblinded trials with subjective outcomes none of these trials of therapist-delivered treatments produce any valid data. There is no reliable evidence that anything in any of the treatment arms makes a real difference to any group of people.

We also have a problem in arguing in the context of NICE that maybe people with 'other fatigue' might benefit from therapist-delivered treatments. That is that NICE has to cover these people, for pragmatic reasons. So we end up with a suggestion that some groups might have CBT and GET and others not. That to me is the worst case situation because it takes us back to where we are now. In theory people for whom GET is unsuitable should not be having it even now. But they are. If the service providers are not that convinced that there are clear distinctions between patient groups we slip back into BPS mindset.

It is a pity that you have not been in on the debate longer because you have clearly thought about this a lot.

 

That is the nub of it surely. PACE purported to show them effective, and instead proved them ineffective. NICE CG53 has been perpetuated based on the former, and the new guideline must take much more heed of the latter. Do we need to confuse things beyond this.

 

I don't understand this. The "actual data" is in fact data that was acquired from self-reports, so any reporting bias will inescapably be intrinsic to it. "How it actually is" is simply how it was actually reported, incorporating any reporting bias that affected that data.

 

Dear Sasha, I accept what you say, the problem is finding the time and energy. I had no intention of contributing to a substantial stakeholder response to NICE. I never even meant to write one for the Lyme guideline or all the BMJ rapid responses I have written since. But the situation is just too bad to ignore. I have had M.E. for over 40 years and for the past 3-4 years have just wanted to stop and have some peace. But it is for kids, like Graham's son, that I keep going. I was lucky, I was 21 years old before my life as I knew it came to an end. Yes, 'lucky'. I had some fun, got some memories and even all these years later they give me something good to look back upon. I breaks my heart when I hear about children that get M.E. or Lyme disease because I have heard of too many that have been ill right through their childhood and into adulthood up to the present. This cannot be allowed to go on. Parents do not bring children into the world to suffer - God knows how they cope.

A few weeks ago I visited a very dear friend on her 87th birthday. Since she retired and up until 2 years ago, she was a 24/7 carer for her adult daughter with M.E. Then my friend's whole body just packed-up and she is now confined to bed downstairs, whilst her daughter is confined to bed upstairs - where she has been stuck for 17 years now. Whilst I was with my friend, one of the carers came in with a message from the daughter, 'Do you know if there are any new treatments, please let me know?' I am sick to my heart with that question because there was nothing I could say except that I would have a look around and let her know. The only tiny consolation is that like me, she got a childhood and young adulthood, knows what it is like to have a job-career, romance, holidays hopes and dreams that could come true... So it is really for kids that I am motivated to keep going beyond my limits and keep doing what I can, even though illness has deprived me of every having any of my own. It is for them and what lies ahead for them, that gives me the strength to withstand the strain and indeed the ignorant and frustrated people that the battered remnants of a fighting spirit always seems to attract (or perhaps it's just me).

So excuse that I have not done everything that perhaps I should and excuse the moan.

Best Wishes,
Peter

 

Hi Trish and Graham, the horizontal of the chart is the count of individual participants. As I remarked, each diamond represents an individual participant. I think what made it confusing is that all the participants were sorted left to right with those with the lowest amount of change on the left and highest on the right. If you just look at one diamond, its colour tells you which trial arm that participant was in, then look at the left-hand scale, that tells you how much their ratings changed with the outcome measure. You will see that there were around 15% who deteriorated, a whole lot who improved a bit, and around 10 to 15% who improved significantly (some of these, spectacularly). You can also see the small difference between CBT and GET compared to APT and CBT.

 

I can understand being short on time and energy. I hope that some of the comments on this thread will be helpful.

(Sorry for my short reply to your long post - having a bit of a rough day!)

 

Maybe, maybe not. If it is accepted as given that the PACE trial disproves GET and CBT all well and good. I do not get the impression that it is accepted, but please correct me if I am wrong. As I have explained, if the PACE trial was withdrawn completely, it would not guarantee that GET and CBT will not be in the next NICE guideline, and in fact NICE might be obliged to include them. It is all in my earlier post.

 

Adrian, I agree with most of what you write and have written along these same lines myself. But your conclusion is not completely sound to me because it implies that subjective measures are unreliable per se. There are some huge discrepancies between the POM's and the walk test data, and other discrepancies like participant's CFQ and SF-36 scores contradicting each other. How much of these and other changes can be put down to placebo, optimism, deference, gratitude etc, I am not sure about. As I already mentioned, nearly half GET/CBT participants rated improvement which meets the 'minimum detectable change' thresholds for the measures. These ratings are from one year, and months after their therapy sessions had finished. I guess, weeks or months after most had met their therapist. In my experience deference does not hang around very long - especially for clients who did not gain any practical benefit from a therapy. So to me, whilst bias can explain the level of improvement for a lot of participants, it is inadequate to explain all changes.

Those registering significant improvement cannot be ignored. This is what I have got from looking at individual data - which I expect is what you have done also. Some of the changes would be nothing short of spectacular if those participants were bona fide M.E. or CFS patients. As I remarked in my bit about NNT's, 7 is quite good. But if the authors had settled for 15 or 20 they could produce astounding figures for improvement, with only the control group to rescue the situation for patients. So I would say that the control group is vital to our case, but so is selection bias.

Frankly, I am rather stunned to find that an admin's approach is that 'chronic fatigue' is a legitimate selection criteria for ME/CFS research. Perhaps I misunderstood your remarks on this. If this represents the group's position, I'm going back to Kansas.

 

The complaint is not that subjective measures are unreliable per se, but that the combination of subjective measures and an unblinded trial are problematic.

Regarding significant improvement in PACE. The general improvement in the PACE trial for CBT / GET compared to the other arms was insignificant enough, that if the authors had just followed their original protocol they would have had a null result. I do not consider this to be a significant improvement.

Secondly. In addition to the problem of subjective measures and an unblinded trial. You don't only have to take the placebo and the therapist effect into account. The CBT and GET manuals explicitly stated that it was essential that patients were told to ignore negative symptoms, that patients should be told how effective the treatments given were, and how strong the scientific evidence for treatment was. The CBT and GET treatments are basically built to change the patients perception about their own health and illness. To me, this makes the exclusive use of subjective measurements as primary outcome measures seem like insanity. one of the things that surprises me the most about the results of the PACE trial is that the improvements in self reported outcomes weren't in fact higher in the CBT / GET arms than they were. Something that probably surprised the authors themselves.

 

Dear Jonathan,

Thank you for your remarks, I also agree with a lot of what yourself and others have said on this topic, though I find it interesting that I seem to be coming from a perspective where our views do not automatically meet.

I assure you that I am not hanging on to an argument, to me, the selection problem is actually a side-issue (which I happily ignored for years) compared to the numerous issues which show that the PACE trial report is unreliable and that GET and CBT are not treatments.

However, patient selection could become an issue and forewarned is forearmed as they say, but it has not worked here. Not only have my warnings gone unheeded, some people seem to be resistant to the idea. Perhaps this is because they believe that participant selection does not and will not matter and that might be true - I hope so.

I have only just learned that this group considers that 'fatigue' patients are legitimate participants in M.E. and CFS research, and that it is prepared to accept 'fatigue' patients in a NICE guideline for 'ME/CFS' patients. This is not something we are going to agree on. It is the VIRAS position that M.E. and critically defined CFS are distinct from chronic fatigue and that they can and should be differentiated for the purposes of diagnosis and treatment/management.

I think I am correct in thinking that yourself and your colleagues are tightly focussed on eliminating GET and CBT from the NICE guideline. That aim VIRAS certainly share, but not to the extent of watering-down diagnosis. The current NICE guideline at least limits who should be offered GET or CBT and NICE have listened to complaints of coercion. The current guideline also has PEM as an obligatory symptom for diagnosis - correctly IMO. If 'fatigue' patients are accommodated in the guideline there is a risk that PEM will be eliminated and only fatigue of a particular severity and duration will be required for diagnosis.

For reasons which I have set out, I am concerned that your group are placing great hopes in the influence on NICE of discrediting the PACE Trial. But I have my doubts about just how far that will go towards eliminating GET and CBT as 'treatments' for ME/CFS. Someone did recognise (sorry cannot remember who) using the PACE Trial data to prove that GET and CBT are not treatments - and therefore the theories behind them are wrong. That would be great. But there is also a risk that the PACE Trial was such an almighty cock-up that the data cannot be used to prove the opposite of what the authors claimed.

You seem to suggest that yourself, Jonathan: "the more persuasive argument is that as unblinded trials with subjective outcomes none of these trials of therapist-delivered treatments produce any valid data". If you are correct, then it would seem that the PACE Trial data cannot be used to disprove the author's theories.

Damned complicated stuff.

Good Luck with your goals,
Peter