PACE trial TSC and TMG minutes released

It's a relief to know then, that these BPS folk are all in a state of equipoise when running their clinical trials. Heaven forbid anyone should be concerned they might have preconceived ideas of where their ship might be bound for. Hmmm, "HMS Equipoise" has a ring to it.

 

This piece talks about a state of scientific "equipoise" between antidepressants and psychotherapeutic interventions.

Whether or not that's correct - that there is genuinely equal evidence for the efficacy of both treatments - I don't know. But people so quickly forget that there's a huge elephant in the room when you try to directly compare drugs and talking therapies. The drugs are trialled in fully blinded trials, whereas the talking therapies are trialled non-blinded studies, so outcomes are likelt to benefit enormously from expectancy effects.

Not a fair competition.

What does it take for people to notice that elephant in the room?

 

Is this clinical trial design a fair comparison of a parmacological intervention and CBT?

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

https://www.ncbi.nlm.nih.gov/pubmed/8430715

 

Are there any "immune or metabolic treatments" that are commonly used in other countries for ME/CFS? I'm just wondering why they mentioned them at all, if they really do deny any involvement of immune or metabolic processes in the disease?

 

It seems better than most, I like the way they had a "clinical" control, that was designed to incorporate all the nonspecific effects you might get alongside CBT, such as support, validation, etc. Good find!

But there are no manuals or details given, you just have to trust the authors that they made the "clinical" control condition to be as persuasive as possible. In this instance, there was no significant difference between the treatment arms, but if there had been a difference, you'd need to know more about what was actually done in the "clinical" control to make sense of it.

 

"These results contrast with our uncontrolled study reporting substantial benefits of CBT..."

They might as well have said, "these results contrast with our highly biased study reporting substantial benefits of CBT."

 

Could Wessely and co possibly have been referring to the "study" of which he said, after MS called it a "well conducted case series",

"You were in fact too kind to our study, Dr Sharpe. This was not a study at all; we were just trying to treat people (Butler et al 1991)We started this treatment at a time when the view was that CFS patients are untreatable; not only that but this kind of approach was considered harmful. We did everything we could, in a completely uncontrolled fashion using antidepressant drugs, and behaviour and cognitive therapy, just to demonstrate that something would work. This enabled us to get funding for a controlled trial."

I think it was. Strange how often this "study" was quoted.

 

Yea:

The powerful placebo
HK Beecher - Journal of the American Medical Association, 1955 - jamanetwork.com
Cited by 2257

I can't think of any other medical ones, but there's this from Psychology:

The Stanford Prison experiment:
Interpersonal dynamics in a simulated prison
C Haney, C Banks, P Zimbardo - 1972 - dtic.mil
Cited by 1591
(participants were assigned to the role of guard or prisoner, and the study reports the guards became cruel and the prisoners hopeless. The study was supposed to have shown that people act according to their group identity, but it turns out the researchers instructed the guards to be cruel!).

 

Yesterday I read that one of the prisoners admitted that he had faked an emotional breakdown (or a similar event, I don't remember the details).

 

Good spot! They cannot claim equipoise if the hypotheses are unidirectional.

 

I had not come across this equipoise term before but from what I have read recently I think you can have equipoise even if you have a hypothesis that favours one treatment. As I understand it equipoise is about the ethics of a trial. For a trial to be ethical there has to be genuine doubt, amongst those expected to know, whether A is better than B (or nothing). I think there remains genuine doubt for the PACE treatments since we still do not know. The problem with having a hypothesis the alters body language and thereby biases outcomes is, I think, separate.

 

So this quote from Sharpe could just mean he's not 100% certain CBT/GET are better than nothing?

"Furthermore, I would like to take this opportunity to emphasise that despite my previous research into particular treatment approaches, I am in a position of equipoise as regards the relative efficacy of the treatments being evaluated in this trial."

Given the difficulty of being certain about anything, is 'equipoise' between trial arms something that can be claimed for almost anything?

As it's a bit relevent to the discussion, I thought I'd also post the assumptions about efficacy from the full PACE trial protocol: Final version 5.0, 01.02.2006

 

Surely those are predictions, not assumptions. And if they are assumptions, they can't claim to be in "a position of equipoise".

So it's basically, previous trials showed this, so we'll repeat them, make all the same mistakes and assumptions and get the same result. Bingo!

 

They were from the Sample Size section of the full protocol and led into their power analyses:

I don't really know how these things should be best described.

 

Sample size calcs should be based on what would be considered clinically important, not just statistically significant. They seem to have based it on the results that previous trials got, and haven't looked at whether any of that was clinically relevant or not.

I would have thought that for true equipoise, they should have stated that this is how much one (unspecified) treatment should be better than all the other (unspecified) treatments, and on that basis (of meaningful clinical difference) this is what their power calcs should look like. I really don't think they can claim equipoise and then state which treatments they are expecting to do best, and by how much.

If I were them, I would have kept the trial as simple as possible and done a straight comparison between what is offered in the clinic and what patients say works for them. They "controlled" it in completely the wrong way by expecting pts to attend clinic for their "pacing" intervention. But that just shows how poorly they understand the condition.