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).

 

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.

 

It might not be a surprise, but:

No firm evidence that lack of blinding affects estimates of mortality in randomized clinical trials of intensive care interventions: a systematic review and meta-analysis
https://www.sciencedirect.com/science/article/abs/pii/S0895435617313501

 

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:

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'.

 

"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?

 

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:

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.

 

Meta and antimeta.


...I'll get my coat.

 

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?

 

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.

 

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.

 

Makes me wonder whether metablind was cooked up to justify that aspect of GRADE... (yes I know it's a conspiracy theory)