Thursday, March 17, 2016

2: Unfit and afraid?

Generally psychiatrists avoid any discussion of what actually sets off ME in the first place, but a small core argue that the reason that the condition continues is purely psychological. A very small minority of people with ME take offence at this, thinking it is a way of trivialising the condition, but that would be wrong and unfair. Anyone with any experience of depression, or any other condition labelled as "mental illness", is only too aware of how devastating and difficult such conditions are. Sadly, many psychiatrists also confuse that wrong attitude, held by a very small minority, with the scientific scepticism of many others about the validity of their suggestions. Unfortunately, others in society, including much of the media and some doctors, have taken the opinions of those psychiatrists to mean that ME is relatively trivial, and is simply a result of a lack of will-power: I am not convinced that the psychiatrists who put forward these ideas have done enough to counter that misunderstanding.

One of the ideas held by this small group of psychiatrists is that it is our fear that is holding us back: they believe that for some reason we have a deep dread of pushing ourselves, and any natural aches and pains that would normally occur on the road to recovery, are taken as confirmation that we are still very ill. They argue that such an attitude can also make us more sensitive to such pains. Again, it is important to realise that this is not an attempt to judge us, any more than it would for people suffering from post-traumatic disorder.

Their other idea is simply that we are deconditioned: too unfit to do much without getting tired. Actually they are linked, because the first one implies that the fear itself would make us become deconditioned.

Of course, fear and deconditioning can be part of any illness. I'm sure if anyone went down with food poisoning after eating a dodgy kebab, fear might well be something that holds them back from repeating the experience: and, of course, many older folk lose their confidence if they start to fall over regularly. Anyone who is in bed with a vicious bug for a week or more will be a little deconditioned, and if someone has a broken leg, it will take a while to get back to normal. Some will have their confidence shaken: some will wonder if they are quite ready to get back to work.

But this is very, very different here: the argument is not that some sessions of CBT can help us adjust to ME, but that most or all of our symptoms are due purely to fear or deconditioning. They are not talking about the way that CBT can help some people cope with heart conditions, asthma, MS etc. They mean that the level of fear and deconditioning described must very severe and deep-rooted, in order to be the sole reason for our symptoms.

These two suggestions have been described as hypotheses, but that really rankles with me from a scientific point of view. When a scientist has an idea or a theory that fits the known facts, it doesn't command any respect until it can be tested by predicting something that is previously untested and that fits specifically with that theory.

Here's a silly example, just to explain what I mean. Suppose you have a little electronic number pad, and when you press 2 the answer 4 pops up. When you press 4 the answer 8 pops up. Pretty obviously it is just doubling the number you pressed. But I could come up with the suggestion that it takes 2 from the number, squares that, then adds 4 to it. They both give the same results, but doubling predicts that pressing 3 will give a 6, but my method would give a 5. So trying it with a 3 is a test that would show the difference between the suggestions.

That is, of course, a silly example, and is so easy to test, but think of scientists puzzling about climate change. They cannot perform experiments, so when they come up with ideas, they must find ways to show that their idea is a good one: they have to come up with something new to be measured that would distinguish their new idea from existing ones: something that clearly shows that they are on the right track. Anything worthy of being called a hypothesis must add something new to the understanding, and, most importantly, predict something that has yet to be tested that will confirm its unique ideas.

Now contrast that with these two "hypotheses" about ME. It could be argued that they add some deeper insight into the condition. But it is easy to speculate about what ME could be. I could offer a suggestion that ME is caused when some of the millions of neutrinos, that pass through our bodies every minute, hit and disturb processes within our cells: it is simply that some of us are more sensitive to these disturbances than others. Would you like to have a go producing one? What do you fancy? How about childhood abuse, stresses at work, chemical additives to chicken, electromagnetic radiation from the sun, visits by the tooth fairy, or imbalances of cosmic energies? None of these would deserve to be called hypotheses: they are just ideas. Some might be educated ideas, some random, and some downright weird, but that's all they are

So how have they tested the fear hypothesis? Getting people to fill in a questionnaire to measure their fear isn't going to impress anyone. Some people get confused and think that measuring whether CBT helps actually tests the hypothesis. It doesn't, for two good reasons. The first is that CBT does not only address fear, and there is no proof that it addresses fear efficiently: if CBT worked brilliantly for ME it would not confirm the fear factor, and if it was utterly ineffective it wouldn't disprove it either, any more than taking aspirin would.

It's not up to me to suggest a test, but I'll give it a go. I would expect that, if fear is such a major factor in ME, when people with ME suffer from another health problem it will show up very clearly in their recovery. Remember that we aren't talking about the apprehension many people feel after a really bad illness: we are talking about fear so strong that many patients become housebound: they lose contact with most of their friends, and are often shunned by their own families. So when, for example, 6 years ago I fell over and broke my hip, fear of putting weight back on it during the recovery process should have been a significant problem. (In case you are wondering, it wasn't. In fact the biggest problem was not beating people about the head with my crutches when they were being really sympathetic, trying to get them to understand that in comparison with ME, a broken hip was just a temporary inconvenience.)

What about deconditioning? Here the suggestion is that there is no difference between people with ME and people who are very deconditioned. Now obviously anyone who has been ill for a while becomes deconditioned. The important part about this suggestion is not that we are deconditioned, but that that is our only problem. Not only that, but this is the case for all patients caught by the Oxford Criteria for Chronic Fatigue Syndrome, which, in effect, means medically unexplained fatigue for 6 months or more.

There have been a large number of small studies over the years looking at muscles that have shown a variety of interesting and relevant results: if you try this link and click on "Documented muscle abnormalities" in the Contents page, it will give you a lot to look at. More recently, studies carried out with Julia Newton at Newcastle showed that, when exercised, the muscles of people with ME produce on average 20 times as much acid as healthy folk. This almost contradicts the supposition of deconditioning being the simple cause of fatigue, but a pedantic sort (like me) would say that strictly speaking patients with ME have to be compared, not with the healthy, but with those who really are deconditioned – with couch potatoes. To prove their point, perhaps supporters of this "deconditioning hypothesis" should demonstrate that people who are simply deconditioned display the same (inconsistent) range of abnormalities in these tests as people with ME. Now that would be an unexpected and untested prediction.

This is where the recent run of "2-day treadmill exercise" tests could come in but unfortunately these tests are hard to set up, and carry out consistently. What is more, they are normally matched with relatively healthy volunteers: I can imagine that it would be quite difficult to get some very deconditioned people to volunteer.

You could argue that if our only problem was deconditioning, then Graded Exercise Therapy should do the trick. That still doesn't satisfy my requirements though, because many studies fail to see whether patients are actually exercising more, or simply doing less of other things to fit in the required exercises. On the few occasions that pedometers were used to track patients, it was found that the overall level of activity didn't increase. But then, a large number of people with ME report that GET harmed them.

So there aren't any studies that actually confirm these suppositions, and, strictly speaking, there aren't any that prove they are false: but then surely the important question, before bothering to test whether they are true or false, is whether the suppositions actually match the facts. No scientist would waste her or his time testing something that didn't match known events. I would find it very hard to fit these suppositions to my situation. I went down with ME very abruptly after an infection in 1999. I changed virtually overnight from being able to cycle the 8 (very hilly) miles to work and back twice a week, to struggling to walk a couple of hundred metres to the staffroom.

But without a diagnosis, and with none of the standard tests showing any abnormalities, I had to carry on working for two-and-a-half years. It was terrible. Fortunately I was in a brilliant, supportive, and very concerned department. I am certainly not the only one who has been in that sort of situation. How could the assumption of fear or deconditioning be applied in cases like that? Could I become that deconditioned so quickly? Could I stay deconditioned for two-and-a-half years while still struggling to work? How could the concept of fear be applied here? If the explanations cannot fit the situations, then how can they even be worth considering?

These two suppositions certainly don't deserve to be called hypotheses, and that fact that some doctors choose to claim they are true simply indicate that these are, in fact, belief systems; belief systems that feed on people's bigotry. The fact that they don't even cover many circumstances make it even more of a "faith above reality" situation. What difference is there between doctors saying that they believe these to be true, based on their "clinical experience" then advocating treatment that, of course, helps pay their salary, and a preacher that assures you that he has talked with God and knows that He wants you to hand over your money to his particular church?

So the next time that a doctor suggests that deconditioning is your problem, and that CBT or GET would solve your problem, point out that you are an atheist, Buddhist, Methodist,... and that you do not subscribe to his particular form of unquestioning faith in the god-like wisdom of the medical hierarchy. Unless of course he can produce the hard evidence. In which case, please let me know and I will rewrite this blog (with apologies).

Monday, February 22, 2016

Scientific analysis and ME psychosocial research:

will they ever meet?

I get frustrated by the endless recycling of unsubstantiated claims and opinions about ME, and can fully understand why many people get quite angry about it. So I intend to write a short series of blogs looking at the claims that some people make and studies that people believe support them. It will involve a certain amount of statistics, but I do not intend to get bogged down in the numbers: you only need common sense and logic to see where these studies fall down. I used to teach maths, and I get very annoyed with researchers who use what I call “spreadsheet statistics.” In the old days (my youth), before even calculators were around, we had to think very, very carefully about which forms of analysis to use, because the calculations involved took ages. Now researchers just click on a function button on a spreadsheet and get all sorts of complex calculations performed.
I could instruct a spreadsheet to work out the average of my height, weight, shoe size, age, waist measurement, and house number. It doesn't know such a calculation is meaningless: press the button, it will do it. But if the researchers involved do not understand the fundamental assumptions behind any statistical technique and exactly what they are dealing with, then they might just as well be predicting the future with animal entrails. It's just a shame that journalists don't check the original sources any more, and are happy to take the word of people who have financial interests in their interpretations being printed as fact.

1: “Those who report a diagnosis of CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms.”

This quote comes from a study, by Harvey, Wadsworth, Wessely and Hotopf, published online in 2007 ( At first it sounds a pretty impressive investigation, with a total of 3035 subjects, using terminology like “There was a dose–response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME,” or “Logistic regression analysis was then used to calculate odds ratios (ORs) corrected for known sociodemographic confounders, such as gender.” No wonder few people dig into it to find out what is really going on.

What happened was that there were 5362 subjects selected for the Medical Research Council National Survey of Health and Development in one week of March 1946. In 1999, 3035 of these, by then aged 53, were followed up. But only 34 of them had ME/CFS. So this wasn't some enormous study, but one on a mere 34 patients. Now in my book, a survey of 34 people just isn't worth doing, no matter how fancy a set of statistical spreadsheet buttons you have. But, let's go with it. 

Roughly the expected number of those 34 had not had any previous psychiatric or psychological problems, and again the expected number had some prior lesser psychiatric or psychological problems, such as more moderate depression or anxiety. But instead of finding 2 people in the group with severe psychiatric problems, there were 6. From a statistical point of view, that is quite unexpected: it is significant. But is it significant in the real world sense?

The key part is a little more buried: these were not diagnoses of ME/CFS, but were simply notes made by the interviewing nurses that the subjects said that they had ME/CFS. So, in essence, all of this hinges on a statement by 4 people, who had suffered severe psychiatric problems in the past, that they now had ME/CFS.

The explanation by the authors here is interesting. “Clinical experience suggests that it is uncommon for a patient to complain of CFS or ME and to not have sufficiently severe symptoms to warrant the diagnosis.” It is interesting to note the faith that these authors have of the validity of patients' self assessments of their symptoms. Presumably patients are much better at this than GPs, with reports coming out from Newcastle and London ME centres saying that around half of the patients sent to them with suspected ME/CFS in fact were suffering from a different condition that their GP had not detected.

So, out of an original sample of 3035 people, the certainty that Those who report a diagnosis of CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms,” is based on the statement by those 4 subjects. Those 4 subjects who told the nurse that they had ME/CFS, but no attempt was made to check that diagnosis. Notice too that 30 out of the 34 patients “with ME/CFS” were not at all out of the ordinary, but the conclusion was applied to all.
In science, it is important to aim for the simplest explanation that covers the facts. A large proportion of the sample of patients with ME had no background of psychological problems: the conclusion cannot be appropriate for them. The simplest and most logical conclusion to draw from these results is that, if indeed all 34 patients had a diagnosis of ME/CFS (which is questionable), the criteria generally used to define the condition are not sufficiently good enough to exclude those whose primary problems are psychological.

This study was useless right from the start. No statistician could resurrect anything worthwhile from it. Who would dream of repeating its conclusions?

Tuesday, June 19, 2012

OK, it's been a long time, but a group of us have now completed a fuller analysis of the PACE trial. You can find it at

There is also an introductory Youtube video at

It may have taken a while, but last year's PACE publication was only meant to be the first part. There is still no word about when the rest of the analysis will be available, and the authors are resisting requests to release the data for others to analyse, despite the fact that we all paid for it. We still do not have any data on whether any of the patients managed to sustain a return to full or part-time work.

Last year, Richard Horton of The Lancet issued a challenge to patient groups to engage in a proper discussion of the PACE trial, but although we contacted him on 15th May this year, and the assistant editor on the 25th, neither has replied. I wonder what he had in mind when he invited us to engage in discussion? Perhaps we need to qualify as doctors first.

However, Janelle spoke at the CFSAC meeting last week, and introduced our analysis there. Phoenix Rising are hosting the site and members contributed greatly to its production, and we are continuing to try to have our findings recognised.

If you have any suggestions, or would like to spread the word, please feel free to contact me via the website.

Sunday, March 13, 2011

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.

Part One

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.

Part Two

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 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.