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If we could get hold of the data, we could do this analysis ourselves and see if the result can be explained by sex and contraception. The paper states:

There was a massive sex difference between groups: 47% of controls were males compared to only 17% in the Canadian ME cohort. So what does frequency-matching mean in this context? Pretty much all of their measures were affected by sex, suggesting that the difference between ME and HC could be...

The emails are interesting. Garner and Flottorp appear very assertive and activitst-like. They try to get themselves on the committee and are very dismissive if guideline text doesn't mention psychological treatments and recovery, often suggesting that this will cause harm. They use COFFI and...

From the paper:

Don't quite understand why figure 32 (below) shows decreases in % change in zeta-potential in ME/CFS patients while on Figure 21 that Murph posted above, it seems that zeta-potential increased after 1.5 hours in the ME/CFS patients. Figure 32| Normalised ζ-potential data for PBMCs incubated...

Another questionnaire, The Revised Fibromyalgia Impact Questionnaire (FIQR, range 0-100), did show a significant difference between groups. The RLZ has a score of 62.3 (57.32 to 67.28) compared to 70.70 (64.90 to 76.50) in the control group, with lower scores being better. The p-value of the...

Using the CI of the means, I've tried to calculate the mean difference and its confidence interval and p-value. I got: 0.54 (-0.42, 1.50), p-value = 0.26. So it seems like the difference was not statistically significant and might be due to random variation.

The primary outcome was the Brief Pain Inventory Short Form (BPI-SF). The results show 41 participants analyzed in both groups with the following means: Placebo: 6.30 (5.59 to 7.01) RLZ: 5.76 (5.11 to 6.41)

This was a bit surprising: One might suspect that patients try more medications early after getting a diagnosis but then reduce them because most don't work. Perhaps those patients fall in the 1/3 group that doesn't take medication for ME/CFS symptoms anymore.

Not sure what you mean but if there are multiple trials on the same intervention/outcome then they are pooled using meta-analysis. They are added together so that there is one estimate and then the GRADE approach is only applied after that on that pooled estimate. If these are estimates of the...

I don't see an issue with the Vortioxetine rating but other estimates (from non-behavioral interventions such as hyperbaric oxygen or transcranial stimulation) were downgraded with two levels for imprecision. There seems to be an inconsistency where non-behavioral interventions were downgraded...

The conclusion would be: 'We are uncertain that treatment X improves symptoms' and 'Treatment Y probably has little or no effect on symptoms.' Agree. GRADE allows it (probably because it was the standard in the past) but it makes little or no sense. As a reviewer you want to determine if there...

Approach 3 is what they've done with Vortioxetine trial and it is possible to combine this with approach 1 for point estimates that are higher than the MID. So that would be ok. The thing that doesn't fit is that they themselves claim: "When the point estimate exceeded the MID, we rated...

Yes. GRADE calls it 'little or no effect'. It's a bit beside the point but is described in this paper: Rating certainty when the target threshold is the null and the point estimate is close to the null | BMJ Evidence-Based Medicine If the point estimate is lower than the MID, GRADE finds it...

Rating (im)precision is different from null-hypothesis testing though so wouldn't phrase it like that.

Here's my understanding of the GRADE approach: In study B the point estimate (0.8) is lower than the MID (1) so GRADE recommends rating the evidence of there being NO effect. In that case you cannot chose the null and have to compare to the MID. The confidence interval (0.5-1.1) includes values...

This also doesn't seem correct. The sample size in this CBT trial (114, or 57 per group) is so far of from what GRADE recommends as sufficient for good precision (800 or 400 per group) as a rule of thumb for continuous outcomes. So something has gone wrong here and I it's how they used the CIS...

Thanks for checking. I think Figure 5b. forms an illustrative example. The text says: Zeraatkar says: "we rated certainty of an important effect". That means that they should rate down for imprecision of the confidence intervals cross the MID. Zeraatkar, however, says that they didn't so...

I'm mostly interested in this issue of imprecision which I wrote a blog post on. The authors reply to this point by writing: Perhaps others can check but this seems like a contradiction to me. If you're rating the certainty of an important effect then this means not just any effect that is...

There is a new reply by first author Dena Zeraatkar to previous rapid responses but unfortunately it does not address most of the points raised. https://www.bmj.com/content/387/bmj-2024-081318/rr-12