Bias due to a lack of blinding: a discussion

Thank you everybody for your replies.

Looking forward to reading hopefully soon but won't be able to engage in the discussion for a while, all the more happy if others find it worthwhile to engage.

Thought it's an interesting trial that's relevant to discussions on ME/CFS clinical trial design / outcome measures in several respects.

Also shows, once again, that the standards of research on 'established' diseases, especially if looking at symptoms like fatigue or pain and assessing therapist-delivered interventions, aren't necessarily better than in research on ME/CFS (even if for MS good drugs have been developed in the recent decades to modify the underlying disease, at least for the relapsing-remitting type).
 
ME/CFS Skeptic said:
New blog post: Problems with the MetaBLIND study



The MetaBLIND study is likely the largest study on the effect of blinding in randomized trials to date. Contrary to expectations, the study did not find a relationship between exaggerated treatment effects and lack of blinding of patients, healthcare providers, or observers. I’ve contacted the authors to obtain the dataset of one of the most important analyses of the study, namely the impact of blinding trial participants on patient-reported outcomes. After screening the blinded and unblinded trials that were compared to each other, it became clear that the MetaBLIND study suffers from serious flaws. Some of the analyses had little relevance to medical trials, others included trials that were wrongly labeled as blinded and in most cases trials were simply too different for a meaningful comparison.

https://mecfsskeptic.com/problems-with-the-metablind-study/
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I'm revisiting this. I still consider the MetaBLIND study the worst meta-analysis I have ever read by a long margin. Due to the errors and apples to computer mice type comparisons they made, combined with the fact that they hid all of this in the manuscript and did not publish as supplementary information.
 
GRADE is getting a big update and some parts are already available in this new book:
https://book.gradepro.org/

Unfortunately, it includes the following passage:
Although in theory it is possible to rate down by more than 1 level due lack of blinding, meta-epidemiological evidence and practical experience suggest that those situations are exceptional.
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The meta-epidemiological evidence refers to the MetaBLIND study.

This might explain why reviewers (such as those that wrote the CDC review) are reluctant to downgrade with 2 levels. This might also make it more difficult to get the issues with GET and CBT trials acknowledged because we have to argue that they are an exception.

In a way they are exceptions because of the close and long contact with therapists, the encouragements to be optimistic, emphasising progress, believing that you can recover, avoiding catastrophizing, stop thinking about fatigue etc. But these issues are I believe quite common in the medical literature, so sad to see it described as exceptional, that is possible 'in theory'.
 
ME/CFS Skeptic said:
GRADE is getting a big update and some parts are already available in this new book:
https://book.gradepro.org/
Click to expand...

"meta-epidemiological evidence and practical experience suggest"

Isn't that a very weak or even self-contradictory argument?

What is the role of "practical experience" in scholarly assessing evidence of clinical trials other than it needs some clinical practice to set up a trial in a way that will deliver robust evidence on the effects of a particular treatment for a particular disease?

Reminds of me the argument in the recent Busse et al review on CBT and exercise for LC where they say that you could downgrade the quality of evidence for an intervention's lack of plausibility of action mechanism.

Aren't these lines of reasoning apt to boost reviewers' own biases/ prejudices in the first place?
 
MSEsperanza said:
"meta-epidemiological evidence and practical experience suggest"
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Meta-epidemiological evidence that randomization and allocation concealment overestimate treatment effects is also weak.

Take for example this latest overview where Guyatt was senior author and where the overestimation because of lack of blinding was actually bigger than for randomization and allocation concealment:
Forty-one meta-epidemiological studies (34 of between-, 7 of within-trial comparisons) proved eligible. Inadequate random sequence generation (ROR 0.94, 95% confidence interval [CI] 0.90-0.97) and allocation concealment (ROR 0.92, 95% CI 0.88-0.97) probably lead to effect overestimation (moderate certainty). Lack of patients blinding probably overestimates effects for patient-reported outcomes (ROR 0.36, 95% CI 0.28-0.48; moderate certainty). Lack of blinding of outcome assessors results in effect overestimation for subjective outcomes (ROR 0.69, 95% CI 0.51-0.93; high certainty).
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Source: https://pubmed.ncbi.nlm.nih.gov/37939743/

So it doesn't make much sense to me. The meta-epidemiological approach also doesn't seem reliable enough to change basic scientific principles.
 
dave30th said:
Is this common, for NICE to recommend off-label use? I didn't realize off-label prescribing was much of a thing in UK. Does NHS pay for anything that's prescribed off-label?
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Off label prescribing on the NHS is fairly common for less common illnesses, especially for 'secondary problems'. Thus patients with systemic lupus are often treated with drugs that do not have a specific license for use in lupus.

But I think it must be quite unusual for NICE to endorse usage in. specific context for which there is no license or the license cannot reasonably be considered to stretch to the context. NHS providers would be entitled to deny paying for anything not licensed and might well do so but it could easily slip through as a prescription in primary care where the pharmacist is a high street drug store rather than a budget obsessed hospital unit.
 
Jonathan Edwards said:
Off label prescribing on the NHS is fairly common for less common illnesses, especially for 'secondary problems'. Thus patients with systemic lupus are often treated with drugs that do not have a specific license for use in lupus.

But I think it must be quite unusual for NICE to endorse usage in. specific context for which there is no license or the license cannot reasonably be considered to stretch to the context. NHS providers would be entitled to deny paying for anything not licensed and might well do so but it could easily slip through as a prescription in primary care where the pharmacist is a high street drug store rather than a budget obsessed hospital unit.
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Thanks. I assume each country. has its own ways of dealing with off-label prescribing. Very common over here. Whether health insurance will pay is another thing.
 
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