A general thread on the PACE trial!

"An elite athlete may run miles before their body switches from aerobic respiration to anaerobic respiration. That’s the point when the body’s cells stop converting glucose for energy and start producing lactic acid as a byproduct, it’s less efficient and uses more energy"

I thought that was the point when the body starts converting glucose for energy? when it's not getting enough oxygen from the lungs.
 
John Mac said:
"An elite athlete may run miles before their body switches from aerobic respiration to anaerobic respiration. That’s the point when the body’s cells stop converting glucose for energy and start producing lactic acid as a byproduct, it’s less efficient and uses more energy"

I thought that was the point when the body starts converting glucose for energy? when it's not getting enough oxygen from the lungs.
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It's badly phrased, in both ana and aerobic respiration glucose is turned into pyruvate. Without oxygen the pyruvate ends up as lactate, with oxygen it can enter the Kreb's cycle.
 
PACE has essentially been debunked: the initial definition of ME/CFS used in the study was overly broad, endpoints were changed mid-stream and after data had been collected, objective measures of patient improvement (or lack thereof) were removed from the study.

One of the objective measures – actimeters – was not used at outcome. It is particularly critical as it would not only have measured therapeutic benefit (or lack of it), but also therapeutic compliance, and possible activity substitution by patients (simply swapping some or all of their usual activity for the treatment activity, without increasing overall activity levels).

The other objective outcomes – employment, welfare use, 6 Minute Walk Test, and Self-Paced Step Test – were reported but they did not show any clinically significant benefit on any measure, and were not given the due weight they should have been.

The Self-Paced Step Test, at least, was also inadequately reported in the form of a small graph. FOI requests for the more detailed data to reveal critical info, such as the scatter plots and correlations, were denied.
 
Sean said:
PACE has essentially been debunked
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I feel the need to again comment on what I consider PACE's greatest failure. Standard deviation of SF36PF data is improper manipulation of data. PDW wrote a paper showing he knew this in 2007. So its a knowing manipulation of data to derive their intended result, which included their "normal" threshold of 60 on SF36PF, and later used for their recovery claim. What do we call that? What does that mean about the work of people in this area that not only can they do that, they can ignore when other researchers do that? Papers have been retracted based on this kind of thing, careers have been destroyed, but somehow this has not happened with PACE.

You can cross check this with several data points. The base recovery threshold of 60 is about the value of average heart failure patients, or COPD. When you add SD to the mean for the general population you get an impossible result. Somehow this is never mentioned.

ETA What do we conclude when long term follow up data shows clear regression to the mean, with no benefit from their treatments, but this gets ignored? I eagerly await the new study showing no employment benefit, I hope I haven't missed it.
 
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As some of you may have seen on Graham’s thread, I’ve been playing with ChatGPT for the first time today. Out of interest I asked it to write 500 words on the PACE trial for ME/CFS. This was its answer:

“The PACE trial is a clinical trial conducted in the United Kingdom between 2005 and 2011, aimed at evaluating the effectiveness of cognitive-behavioral therapy (CBT) and graded exercise therapy (GET) for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The study was funded by the UK Medical Research Council, the Department of Health, and the Department for Work and Pensions and involved 641 participants recruited from NHS clinics. The trial's controversial nature has led to criticism from patients, advocacy groups, and researchers regarding its methodology, implementation, and reporting.

The PACE trial's design involved randomly assigning participants to one of four treatment arms: specialist medical care (SMC), CBT, GET, and adaptive pacing therapy (APT). SMC was considered the control group and received standard care from their general practitioner. CBT aimed to change participants' perceptions of their illness and encourage them to gradually increase their activity levels. GET aimed to increase participants' physical activity levels gradually, following a structured program. APT aimed to help patients manage their energy levels better without increasing their activity levels. The trial's primary outcome measure was self-reported fatigue and physical function.

One of the main criticisms of the PACE trial's design was the inclusion criteria, which allowed participants with less severe symptoms to be included in the study. This meant that the cohort of patients did not necessarily represent the typical ME/CFS population, and the results cannot be generalized to all patients with ME/CFS. Furthermore, the trial used subjective outcome measures, such as self-reported fatigue and physical function, which are prone to bias and have low reliability.

The implementation of the trial has also been criticized, particularly regarding the GET arm. Many ME/CFS patients experience post-exertional malaise (PEM), which is a worsening of symptoms after physical or mental exertion. The GET arm of the PACE trial encouraged participants to gradually increase their activity levels, regardless of their symptoms. This approach contradicts the hallmark of ME/CFS, and many patients reported feeling worse after engaging in the therapy. Moreover, the trial did not measure or report the frequency or severity of PEM in the GET arm, which is a crucial aspect of the disease's management.

Another criticism of the PACE trial was its reporting. The trial's authors selectively reported positive outcomes and ignored the negative findings. The original study claimed that CBT and GET were effective in improving patients' fatigue and physical function, based on the self-reported measures. However, a reanalysis of the trial's data by independent researchers found that the objective measures, such as the six-minute walking test, did not show any significant improvement in the CBT and GET groups compared to the control group. The selective outcome reporting has undermined the validity of the study's findings and raised doubts about the effectiveness of CBT and GET for ME/CFS.

The PACE trial's methodology and results have also faced ethical concerns. Patients were told that the study aimed to evaluate four different treatments, but the trial's registration only mentioned two interventions, CBT, and GET. Additionally, the trial's investigators had financial ties to the insurance companies, who had a vested interest in reducing the number of ME/CFS claims. These ethical concerns have raised questions about the study's integrity and the potential for bias in the interpretation of the results.

In conclusion, the PACE trial's methodology, implementation, and reporting have been extensively criticized by patients, advocates, and researchers. The study's flawed design, selective outcome reporting, potential harm to patients, and ethical concerns have undermined the validity of its findings and raised doubts about the effectiveness of CBT and GET for ME/CFS. The controversy surrounding the PACE trial has highlighted the need for robust and rigorous research methods in the field of ME.”

Better understanding than most journalists I’d say.
 
Robert 1973 said:
Better understanding than most journalists I’d say.
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Not just journalists, also better understanding than editors of learned medical journals, various senior professors, august members of various medical Royal Colleges and an army of BPS researchers and clinicians. The journalists have the partial excuse of uncritical reliance on high profile advocates for PACE, but those whose job is to understand what constitutes objective evidence and reliable experimental design have no excuse whatsoever.

[added - it is reassuring that there is now enough information out there for an AI system to sift and reach a balanced conclusion. Perhaps it would be interesting to see what the same process came up with if asked to justify GET/CBT as a curative treatment for ME, or if it would now struggle to do this?]
 
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Moreover, the trial did not measure or report the frequency or severity of PEM in the GET arm, which is a crucial aspect of the disease's management.
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Patients were told that the study aimed to evaluate four different treatments, but the trial's registration only mentioned two interventions, CBT, and GET.
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However, a reanalysis of the trial's data by independent researchers found that the objective measures, such as the six-minute walking test, did not show any significant improvement in the CBT and GET groups compared to the control group.
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I think these points need to be fact checked.
The controversy surrounding the PACE trial has highlighted the need for robust and rigorous research methods in the field of ME.
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Correct.
 
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