David Tuller: Trial By Error: The Cochrane Controversy

They show any exercise that crosses the anaerobic threshold is damaging, and that in us the anaerobic threshold is very very low, and we can cross it without even getting out of bed according to a few reports. If the GET research wants to show this is not the case they can use this technology and get hard data. They do not do so.

PS Just recently it was announced that one patient had a 44% decline in energy after some brief exercise to tolerance, within twenty four hours. I hope I am not misremembering. That is nearly a fifty percent decline in one day, and not for prolonged or difficult exercise. No other disease is known that does that.

 

@alex3619, like @Esther12 I am not aware of any studies that show actual harm, in the sense of long term deterioration being shown to be caused by exercise. A decrease in exercise capacity in response to exertion over a two day period does not indicate harm. Training with eccentric muscle usage (muscle contraction while lengthening) in normal people produces a deterioration in muscle function in the short term but in the long term is not harmful. An elite tennis player will be less good at winning the day after a long match but that does not mean that playing tennis does them harm.

 

I once attended a lecture by Lillebeth Larun for health care personell. She talked about her work on going through ME research and finding the best research to summarise.

She gave a tip to the audience when searching information about the illness; use "CFS" and not "ME", because "ME" also means "me" so the search results becomes very large. "CFS" doesn't mean anything other than "CFS" so will take you right to what you are looking for.

As those with BPS approach tend to use CFS, and those with biomedical approach tend to use ME, I believe just a simple thing like that could be enough to skew results a little bit. Perhaps without even being aware of it.

 

Holy crap, that's awful. If ME throws up too many unrelated search results, then the answer is to then use Myalgic Encephalomyelitis, not to abandon it altogether.

 

I think "CFS" is used in most research publications? But if you use only CFS in order to keep up with media articles, debates etc, you definitely risk loosing out on key information.

 

The trouble with studying harms of GET, are that:

- Those who believe GET causes no harm can carry out studies, but they are not careful about looking for harms, because they don’t think they exist. (And patients don’t trust them to properly record harms).

- Those who believe GET causes harm, cannot ethically conduct studies to discover and document that harm.

So we are left in the Catch 22 of “no evidence of harm”. At least no evidence beyond large patient surveys, and reports from some PACE participants that the harms they described were not documented.

So where do we go from here?

 

there was a similar problem raised with the NICE guidelines committee in 2007 re searches
on GET:
""Just one example of this is GET; the question posed by the York team looked for papers on ‘GET and ME/CFS’, it did not however search for papers on ‘Exercise and ME/CFS’, and this meant that the many papers showing the potential harm of exercise on the bodies of people with ME/CFS, and that people with ME/CFS react adversely to exercise were not picked up, "

see also problems with PACE reporting of harms:
https://www.s4me.info/threads/pace-trial-graphs-and-gifs.4860/page-2#post-87743

 

I have not only not disputed there are no studies showing long term harm from GET, I have said so myself.

The problem is this is completely irrelevant.

There are no adequate studies showing its safety either. PACE does not do so.

If this were a drug, with zero proper safety studies, then would it be acceptable to defend it on the basis that no studies show the long term harm?

I am reminded of the published and somewhat satirical commentary that there are no double blind placebo controlled studies of parachute efficacy either.

In drugs we have long term monitoring of side effects through various mechanisms. GET does not. Nor do psychotherapeutic strategies.
We do however have patient surveys showing about half the patients report harm. Some of the GET studies also show a decline in activity levels overall. That is a harm in my view.

We also have studies showing massive declines in physical capacity. Someone at Workwell has said they will not do a long term GET study ala PACE as its highly unethical, though I forget who. They have however many cases of patients who have been tracked with various exercise programs. There are patients who show long term decline in energy output. They are themselves working on ways to engage with exercise to help manage ME better but they are not doing anything like GET is considered to be.

In ME and CFS I personally regard loss of energy in the long term as a harm, regardless of other considerations and risks. If a person is down to a low percentage functional capacity, and your therapy slashes that, how is that not harm?

My point in the original comment is this is an angle we need to work on in advocacy, that there is abundant evidence of harm, and that we need to find ways to emphasise this.

Finally there are many patient reports of harm, and sometimes severe harm. This has not been adequately investigated, so there are no large studies supporting this.

The tobacco lobby spent decades saying there was no definitive proof of harm from tobacco smoke. They were right. Yet there was lots of evidence.

The onus of proving lack of harm with pharmaceuticals is on the manufacturer/owner/developer. It should be the same with therapies when there is highly pervasive anecdotal evidence of harm, including many medically investigated cases.

I regard GET for ME as an accepted but dangerous therapy. There are no good studies showing otherwise. There is lots of physiological data backing this.

If we need a large dbpcRCT to show PACE style training is safe, using advanced physiological testing, something is deeply broken with medical research. Which might well be the case, especially in psychiatry.

 

I think I'd agree more with the point that it's worrying that we do not have good evidence of safety, rather than that there is abundant evidence of harm. I think that there is good reason to be critical of people making exaggerated claims about the safety of GET.

I think that a vital part of effective ME/CFS advocacy is to push against people making exaggerated claims about the evidence, and that means it's worth us also being cautious in claims that are made about possible harm from GET when the evidence here is still really disputable. From what I've seen, strong claims about GET leading to harm are not a useful tactic for advocacy attempts aimed at those who want to check the evidence for themselves.

 

Another crack in the dam the water is spouting through.

 

Quite. Which is why I feel that where there are documented cases of suspected harm, albeit anecdotal at that point, if a more rigorous study were to follow those up, and try to apply some scientific investigations into them, maybe something might come of that. I mean, what happens if a drug starts getting widely reported as causing severe subjective side effects? Is that just ignored? What is done in such cases, that could not be done here?

 

There is a particular difficulty if a potential side effect of a treatment is exacerbation of the pre-existing problem. For most drug side effects the effect is something rather rarely encountered in the treated population. Most people with a cough do not have a widespread itchy rash suddenly appear so it is relatively easy to suspect that an antibiotic was the cause. It is even easier if the side effect is rare, like bone marrow failure.

If the unwanted effect is an exacerbation of a fluctuating condition then the only way to gather evidence is to show that the pattern of the worsening is different in a treated population from a non-treated population, using statistical analysis. That need not be confined to mean levels. A different pattern of variance would be important. Thus a scatter plot of the untreated group might show after a certain period of time that the individuals' levels had wandered around but the spread of levels was the same. For the treated group after a period of time there might be a slight upward trend as whole but 10% of cases might dip way below the previous range.

That is why we really need scatter plots for all these studies, to see changes in variance patterns. Maybe the data for PACE exist somewhere on a computer, but drop outs would need to be addressed too.

 

When discussing GET, I've generally referred to it as "possibly harmful" or something along those lines. And I've also indicated that it is contra-indicated if the cardinal symptom, per IOM and others, is PEM or "exertion intolerance" or whatever it's called. I have also cited the surveys that more people report harms than improvements. In other words, I've tried to find ways to suggest that there is a risk of long-term harm, based on all the data, without stating declaratively that this is the case. It's possible one could find places where I wasn't so careful, but that's how I've tried to approach it when reporting on it.

 

Interesting and important. At first, the layman in me really calls for solid distinctions and accuracy. What is GET and what is PACE style GET? These terms need to be defined. If being the devils Advocate, I think we have to acknowledge that the long-term harmful effect of GET not is well documented- here defining GET as the very mildest form of physical activity. At the same time - GET is of little use and benefit, may come out as pretty neutral. The problematic part then, is overselling GET as some kind of treatment, that is just not right.

Then there is “activity/training”, something that for pedagogical purposes, simply can be defined as a step above GET. What we are sure of; there are a vast number of testimonies and experiences of how activity/training harms. If you gather such testimonies and systemize them, they become something else and of some sort of value. You have patient surveys. Unfortunately they won’t count much in a the hierarchy of the medical world, which in general and here very specific, must be said to have a somewhat vulgar cochranised approach.

It is a fact that many patients have experienced long-term harm of exercise/training early on. That could be seen as a wild speculation, one could argue that it wouldn’t play any difference long-term. I personally think it has great influence on an anecdotal level, and then again, if the anecdotes are many, it is something else. Maybe not an authoritative source, but knowledge of value. With all reasonable and relevant reservations, I’m quite sure that many have ruined their prognosis the described way. But how to pin down the connection in a scientific way? We need really clever scientists with good ideas on studies. But to prove in retrospect the connection of to much activity/training early on and long-term harm, may be, in its nature and without a clear marker, almost impossible?

But if we can’t argue very strong against the long-time harm of GET, we can, and it may be even more important, highlight the real danger of activity/training early on and the impact it often has on long-term prognosis.

Interesting but difficult.

 

Depends what we is meant by ‘training effect’.
For aerobic exercise, “training effect” sounds like aerobic conditioning, meaning that your capacity to do it increases after doing it for a period of time. This takes place over a period of weeks with the shortest time to observe a change being maybe about five days.

The increase in Endurance actually happens while you are resting, the exercise triggers the body to adapt to it. For people in normal health the difference can be dramatic; one can go from being winded and sore after running a mile to being able to continue for 10

But you may have meant something entirely different.

 

I think we are arguing the wrong issue. I am preparing a further comment, it will take some time, but I think the crux of this issue is this - what constitutes unjustifiable harm?

 

If you want to search for ME, and avoid every blog that uses "me", put it in square brackets [ME], and that carries out an exact search. Well, at least it seems to do that for ME.

 

We are definitely caught in a Catch 22. Their is no precedent for our situation. I can see why a side effect that is an exacerbation of our condition is hard to detect statistically, but the real problem is that "doctors" are using a treatment without watching to see what happens.

Imagine a treatment for asthma which is in as much use as GET is for ME. If patients went back to their GPs and said they couldn't climb a flight of stairs for a fortnight after each session they would not need to show a randomised controlled trial of 200 patients and controls with a decent p value before they were believed.

Would a fortnight feeling worse be classed as a harm, would it have to be a year, or death before the GP refused to send anymore patients?

Step back and look at it. How many patients have to claim to be harmed before a treatment is looked at with caution? Even if the surveys are self selected the bare numbers should be enough. How many patients and how long a relapse before it is seen as wrong?

What other treatments in medicine leave the patient bed bound, even if only for a few weeks? The ones that do, such as chemotherapies, have obvious, overwhelming evidence that they are successful in the long run. We deserve the same.

 

I agree with @Mithriel but I think there is another aspect of harm which is often overlooked. It is indisputable that CBT and GET have caused many ME patients a great deal of distress, both directly and indirectly. If a treatment doesn’t work and makes many patients feel more stressed, anxious or depressed, it is harmful. Period. That such treatments are devised and delivered by mental health professionals who appear to be disinterested or dismissive of such negative psychological effects is deeply concerning.

Thankfully, I have never been subjected to GET, and I was lucky to be subjected to a more sympathetic form of CBT than that which is recommended by PACE, but the promotion of these therapies and the assumptions upon which they are based has been enormously stressful (ie harmful) for me in many ways, including damaging relationships with friends and family, and preventing me from being able to access appropriate support to help me deal with both the psychological and physical challenges of being so unwell and disabled for so long.

Another important indirect harm is the impact that false claims about the efficacy of CBT/GET have had on inhibiting other avenues of research etc.

I don’t know if any of this is what @alex3619 was alluding to.

[Edit - typos]