The Pace Trial 2011 - can we GET any better?
On 18/12/10 a study was published in the Lancet that compared the effectiveness of different therapies on patients diagnosed with CFS. It concluded that Cognitive Behaviour Therapy and Graded Exercise Therapy can safely be added to specialist medical care to moderately improve outcomes for chronic fatigue syndrome. Headlines suggested that the use of GET and CBT for treating ME/CFS had been justified: the actual report makes it clear that the use of GET and CBT should be continued.
The PACE trial had 4 groups, each with around 160 patients: the members of one group had specialist medical care about 5 times over the year: the other three groups had specialist medical care 3 or 4 times as well, but also had an additional 12 to 15 sessions of Graded Exercise Therapy (GET), or of Cognitive Behaviour Therapy (CBT), or of Adaptive Pacing Therapy (APT). Their progress was tracked in a variety of ways, and was measured at the start, after 12 weeks, after 24 weeks and after 52 weeks.
It cost over £4 million: the report is complex and often unclear. I feel sorry for any medical practitioner trying to understand the whole picture: it takes hours.
We are just looking at two aspects of those results - they are typical of the general pattern of results, so they will give you a pretty clear idea of the whole balance of the study.
First let us look at the way that GET is claimed "to moderately improve" the fatigue levels of patients. We will focus on their assessment of fatigue using the "continuous" Chalder scale, which runs from 0 points to 33 points, where 33 points represents utter exhaustion (in the true sense of the term - not just feeling very tired). Patients were assessed at the start of the trial, after 12, after 24 and after 52 weeks. A drop in score therefore represents a drop in fatigue: an improvement in health.
(The animation below has a commentary.)
The GET line is actually flattening out: it is roughly taking twice as long for each drop of 0.8 points on the fatigue scale. It isn't sensible to try to predict very far, but it would suggest that it might take another year to drop another one point, then another 2 years to drop another point... That is a daft thing to speculate, but it does emphasise that, speaking realistically, the improvement is about as good as it gets. I would call this a very minimal improvement, and hardly cost-effective.
It leaves me with two questions. As most of us are lucky to get even one appointment with an M.E. specialist, and that is generally to confirm diagnosis, wouldn't it have been appropriate for the authors of this trial, if anything, to suggest that patients with M.E. should have more sessions with a specialist, since this gave the greatest improvement? (Although it is important to remember that the overall improvement was not great).
Also, I wonder how much of the initial overall improvement was due simply to "settling down" and getting used to the study (the biggest improvement in all groups came in the first interval between tests, after 12 weeks). I know myself how much it takes out of me to go somewhere new and participate in new activities. It isn't possible to guess this, because for some reason, the authors of the study chose not to allow for such initial stresses. It is my guess that if the study had been set up with a "settling down" period giving patients time to familiarise themselves with the location, situation and testing procedures, before actually embarking on the therapies, then this initial improvement would have been very much reduced.
We would have been able to estimate this, and any placebo effect, if there had been a proper control group, where the patients had not had the benefits of specialist medical care or therapies but did have an equal amount of support time, but the authors of the study chose not to do this.
Now we would like to explain our concerns about the variability in these results. Again we are concentrating on the improvement in fatigue caused by GET alone. Obviously we do not have the raw data, so all we can do is to give you a sort of picture of what could be happening here, but we have tried hard to be realistic and fair to the information that we do have. This is not intended to be an accurate graph: it is intended to illustrate how such a small average improvement has major implications on the mixture of recovery patterns that we could see.
Why haven't we been told how many patients did really well under GET? How many improved a little? How many made no change or actually got worse? We are often told by experts that many people with ME do recover and go on to enjoy a full and productive life. Did this trial support those claims? Are we now able to say what sort of patient will improve with GET? After all, giving absolutely everyone in a doctor's waiting room a course of antibiotics would improve the overall average health by a little, but who would advocate that? Just like the patients in the waiting room, we know that patients diagnosed with CFS represent a range of conditions. With each patient in the study having at least 4 hours of specialist medical care, surely there is enough information to distinguish between the different subsets, and to see which groups actually showed a worthwhile improvement.
We, as taxpayers, have paid for a lot of data. Isn't it about time that someone analysed it in a fair and useful manner?
Click on this link http://www.meetup.org.uk/pacedownload.html if you would like to dowload a pdf file that covers the content of this blog, but adds a little more depth and detail.
This analysis was a joint effort between Graham, Bob and Ian: click here to contact us by email.