This podcast was part of the PACE Trial Press Conference held at the Science Media Centre on the 17^th February 2011

Listen to the podcast here:  PACE Press Conference

Richard Lane (press officer, Lancet,UK):  Hello and welcome to the Lancet podcast, Richard Lane here with you on Friday, February the 18^{th. .}

This week, chronic fatigue syndrome, commonly known as ME, a controversial syndrome. This syndrome, which is quite prevalent, for example around a quarter of a million sufferers in the United Kingdom alone, is controversial in terms of how or if it can be treated.

On Friday, February the 18^th we published online a randomised trial to shed light on this issue. Let’s now hear from two of the authors of the study speaking at the press conference held at London, Michael Sharpe, who is Professor of Psychological Medicine a the University of Edinburgh and Trudie Chalder, who is Professor of Cognitive  Behaviour Therapy at King’s College London.

(00:45) Professor Sharpe: We want to outline for you today a randomised trial of treatments for the condition that’s referred to as CFS/ME and what I’m going to do is set a little bit of background explaining why the trial is important say just a little bit about how it was carried out and then  going to pass over to Trudie who is going to tell you what we found and what we think the findings mean, what the implications are.

 Some of you will be very familiar with this topic, some maybe less so. CFS/ME, as it has been come to be called, is a condition that is relatively common, estimates vary but around a quarter of a million people in the UK and if you have this condition you are likely to suffer from severe disabling fatigue which is bad enough to prevent you leading a normal life and as well as that there are common associations or difficulties with memory and concentration and other symptoms such as disturbed sleep, widespread pains.

Now there is an issue with some people regard CFS and ME as separate conditions and we’ll come back to that at the end of the trial. I think probably the majority view is that people regard them as the same or certainly overlapping conditions.

(02:22) So why did we do this trial?

Well clearly from what I’ve told you about the condition there is obviously a need for effective treatments to address this level of disability in so many people and there have been previous treatment trials and the best evidence is for two rehabilitative sort of treatments, one called CBT or cognitive behaviour therapy and one called GET or graded exercise therapy, and I’ll be telling you a little bit more about what they are in a minute. However the evidence that of those treatments is mainly from small trials and it’s proved to be very controversial.

The two main UK patient organisations have both done large surveys of members and as a result of that have expressed a view that these treatments are not helpful, and indeed actually expressed strong views that they harm people.

(3.21)  As an alternative they’ve expressed a preference for something called Adaptive Pacing Therapy, APT, and I’ll come onto what this is but this is essentially a none rehabilitative treatment which helps the person to live within the limits imposed by the illness.

The other treatment which they’ve expressed a preference for is to see a doctor, a hospital doctor who is a specialist in this area. So there actually, if you’ve actually been part of this field you realise that there’s actually been tremendous controversy about this.

Are CBT and GET really effective?  Do they harm people?

Is APT effective and what is just seeing a specialist doctor really as good as anything else?

So  to address that question we have conducted with a large scale clinical trial across the UK to compare these four different treatments and to find out how relatively effective they are and how relatively safe they are and that trial’s called  PACE and that’s what we’re talking about today.

(4:29) There were six hundred and forty patients randomised in this trial so for a trial of none drug treatment this is a large trial and it was conducted in I don’t know six or seven centres Trudie?

Professor Chalder : Six

Professor Sharpe: Six centres, one of the centres amalgamated, six centres and so its also a large sample of patients across many places.

Just to summarise, the treatments the patients were randomised to were randomly allocated to one of these four treatments: SMC, means specialist medical care, that’s seeing a hospital specialist experienced in a condition so everybody that went into the trial got that so nobody in the trial got nothing so that’s important to bear in mind so our comparisons are all based on everyone getting at least that.

And then the three other groups they had six months of approximately weekly sessions with a therapist  giving something as well as the specialist medical care and those three things are listed  here as APT, CBT and GET.

(05:30) So briefly we can talk about this more later if it’s not clear, APT is adaptive pacing therapy so that’s seeing a therapist regularly to help you optimally adapt to the energy problems that you have as a result of an illness, to help make sure you get the best rest, to help make sure you prioritise things to do the things you want to do but not to try and overdo it, not to try necessarily and push what you can do unless you feel able to do it. So that’s pacing, it’s pacing your activities and adapting to the illness.

Cognitive behaviour therapy you may be more familiar with, this again involves seeing a therapist who works with the patient again in a collaborative relationship and helps them examine how their thinking about their symptoms and how they are responding to the symptoms in their behaviour and then helps them test out whether trying to do more actually will work, if they do it in a gradual way can they find they can actually do that.

(06:30) Graded exercise therapy is again seeing a therapist this time a physiotherapist or exercise therapist to do a very graduated, tailored programme of increasing activity with  heart rate monitoring, monitoring how the patient feels, it’s done in a very tailored, gradual way again to help the patient increase what they can do.

So you’ve got specialist medical care they all get, APT is adapting to the illness, CBT and GET are both trying to see if you can overcome the limits imposed by the illness by trying to do more, working closely with a therapist in a graduated way.

Just a few words about the trial, as I’ve said, this was a fairly large trial and it was done to the Medical Research Council have quite rigorous guidelines to how trials should be conducted and these were followed so the trial has an independent steering committee which scrutinises all the procedures of the trial, it had an independent data monitoring and ethics committee which scrutinised the data through the trial to make sure we weren’t causing harms we were unaware of during the trial and also oversaw handling of the data so there was a ot of independent scrutiny of procedures of the trial which is important because in some areas this trial will be seen as very controversial.

(08:00) The therapies, very important to get the therapy right and there were detailed manuals which I think are going to be available to you on the website of how each therapy should be delivered and all the therapies, therapy sessions were audio recorded and ten percent of them were checked to make sure that the therapy was given as it should have been. Importantly the safety issues are important so all the safety, all the reports patients made of feeling less well or possible reactions to treatments were then scrutinised by our completely independent panel of doctors for them to decide whether they could be reactions to the treatment.

So I hope that is enough by way of introduction to why we did the trial and what it was like, I’m going to pass on to Trudie Chalder now for the exciting bit, which is what we actually found.

(8:52) Professor Trudie Chalder: OK, so we had two primary outcomes, they were fatigue which is obviously the main symptom that people are complaining of and physical functioning and I’m going to talk about both these outcomes.

So this graph illustrates change over time, naught is start of treatment and 24 weeks is where the treatment  largely ended and then the follow up period started, so the follow up period occurred  between twenty four weeks  and fifty two weeks. You can see that the results in terms of fatigue, they largely separated into two groups, with CBT and graded exercise therapy which is the green and the blue lines at the bottom, oh sorry CBT and GET which is the green and purple ones at the bottom, slightly different, and the APT and specialist medical care at the top with a clear difference being shown between CBT, graded exercise therapy and the other two groups, specialist medical care and APT so the bottom line there is that graded exercise therapy and cognitive behaviour therapy show better, more improvement than the other two groups. As I say the main outcome was at 52 weeks at the follow up period.

(10:23) So just moving on to physical functioning, this might be slightly confusing because it is the other, the scale goes the other way round to the fatigue scale so a higher score means better functioning. Again the results are largely divided into two groups with graded exercise therapy and cognitive behaviour therapy doing better than adaptive pacing therapy and specialist medical care.

You may be able to see from the graph that actually specialist medical care did slightly better, it looks as though it did slightly better than APT but actually there’s no statistical difference there, but there was a statistical difference between graded exercise therapy, CBT and the other two groups. So again we can see the same pattern of results with CBT and graded exercise therapy doing better than the other two groups at fifty-two weeks.

(11:25) So if you take those two outcomes together, that is fatigue and physical functioning, again you see the same pattern of results with graded exercise therapy and cognitive behaviour therapy doing better than specialist medical care and adaptive pacing therapy and if you think about the number of people who get back to normal levels of functioning and fatigue then you see twice as many people in the graded exercise therapy and cognitive behaviour therapy group improving and getting back to normal compared the other two groups.

 In terms of safety as Michael has already said we monitored safety very carefully in the trial because we wanted to ensure that the treatments that we were offering people were not causing any harm, and in fact if you look at the percentages there was no difference between any of the groups in terms of those people who reported that they had seriously deteriorated, all those individuals who reported any serious adverse reaction, if you see, if you look at the serious deterioration we measured that in a whole number of different ways which we can talk about later if you are interested in the details, but actually it is a very small percentage...

(12:50) Professor Sharpe interjects: Trudie, just a second, they are not percentage,  they are absolute numbers, so tiny percentages.

Professor Chalder:  Yes, yes, yes they are small percentages for there absolute numbers out of six hundred and forty and in terms of the serious adverse reactions again the numbers were miniscule, and again those serious adverse reactions were what independent scrutineers decided could have been related to the actual treatment that they received.

So to conclude then, cognitive behaviour therapy and graded exercise therapy are more effective than both specialist medical care alone and adaptive pacing therapy. Adaptive pacing therapy was no different from specialist medical care alone and you have to bear in mind that these are all comparisons that we’re talking about at fifty-two weeks. The effects of cognitive behaviour therapy and graded exercise therapy is moderate, that the effect that we see in terms of the improvements was similar across all of the outcomes that we measured.

(13:58) The effect was the same or very similar if we looked at people who were operationally defined as having chronic fatigue syndrome, that was the six hundred and forty patients, but of those there was a percentage of these who fulfilled operational criteria for ME and again we saw exactly the same pattern of results so we can be quite confident that that pattern of results is fairly robust across different definitions, or different ways of defining the illness.

 The treatments are safe and serious adverse outcomes of any sort were extremely uncommon in this trial and again were similar across the treatments so some, any of the serious adverse reactions or events could not be attributed to the actual treatment.

And we’d just like to acknowledge the funders, the primary funder was the Medical Research Council and the Department of Health and Chief Scientist Office in Scotland actually funded the actual therapists who delivered the treatments, thank you for them too.

Richard Lane: Well many thanks to both speakers for their insight into this interesting paper and to you for listening, see you next time.