Yann04
Senior Member (Voting Rights)
Is there ever a good reason for this? Their excuses seemed like fancy jargon that doesn’t mean much…
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Rapamune / Rapamycin/ mTOR
- Thread starter ScottTriGuy
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I don't fully understand the reason for not including the control, but it appears they are trialing primarily for the ATG13 response to Rapamycin, not ME/CFS response. It just happens that ME/CFS patients have higher level of ATG13 according to their previous investigation. I hope they don't promote Rapamycin as a valid treatment based on the result of this trial. They'll have to do another trial with a control arm if they are going to do that.
I think it could potentially be scientifically ok if they treat everyone, and in an independent blinded analysis, determine the status of each participant with respect to those two biomarkers. And then see if the 'responders' match up with the presence of their biomarkers.
The study won't accurately tell them if the drug is safe though. I would have thought it would be better to have a placebo arm as well, but their study has the potential to produce valid data.
Jonathan Edwards
Senior Member (Voting Rights)
I agree with @Hutan that this is a potentially valid way of doing a study. But there is a potential problem that they will not know whether the treatment made one group better or the other group worse - quite apart from safety in terms of other unwanted effects.
If the trial generated a 'placebo' response, in the broadest sense of a spurious reported improvement of 9 points on average then you might get results such as:
Group 1: 14 points better Group 2: 9 points better
Group 1: 9 points better Group 2: 5 points better
Since you have no idea that the placebo effect is 9 points (because there are no controls) you cannot interpret these differences one way or the other.
If the trial generated a 'placebo' response, in the broadest sense of a spurious reported improvement of 9 points on average then you might get results such as:
Group 1: 14 points better Group 2: 9 points better
Group 1: 9 points better Group 2: 5 points better
Since you have no idea that the placebo effect is 9 points (because there are no controls) you cannot interpret these differences one way or the other.
Why not just trial properly for the ME/CFS responses if they are trialing for ME/CFS? We don't know if the intermediate markers are actually biomarkers for ME/CFS symptoms till their previous study is replicated. Even if they are the actual biomarkers, reducing the biomarkers doesn't necessarily mean reducing the symptoms, so they'll have to re-trial for ME/CFS symptoms anyway.
'significant percentage of patients were considered responders'. The question is responders to what? - the drug or hope?
Jonathan Edwards
Senior Member (Voting Rights)
Actually this is quite clever way to do a valid control. You take a population and treat with X. You find those with highY all get better but those with lowY do not. That implies that getting better was due to X in the presence of a context marked by highY. The lowY's act like a placebo group.
It doesn't matter if Y is totally epiphenomenal. We have already established that those with highY did improve symptomatically so that does not need repeating. The next step is to try and work out why highY is a marker for benefit from X but there are lots of situations in medicine (the majority) where such questions are not yet settled but the treatments are working fine.
The problem, as mentioned, is that you don't know if highYs do better because X plus lowY is actually poisonous.
I had to think about this for a sec since all population (ME/CFS) in their trial presumably have highY (high ATG13) to start with. But then, it occurred to me that Y can indeed serve as the control since (lower Y AND symptom improvement) after X could imply the efficacy of X. So, I agree it's a clever way to test Y's role in ME/CFS and X's efficacy at the same time. But I'd think they'll have to prove the correlation between Y and symptom improvement after X, not just lower Y or symptom improvement in order to validate their hypothesis.
Edit: added "(high ATG13)" for clarification; removed "without healthy control", an unnecessary appendage.
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I went through previous threads on ATG13 to see if I missed something. All I could find was pretty much what's on this thread: high ATG13 in ME/CFS patients and ATG13 turned microglia inflammatory. How do you mean "highY did improve symptomatically"?
Utsikt
Senior Member (Voting Rights)
I believe he meant if people with high Y improved after treatment, not that high Y leads to improvement itself.
Any idea where I can find (HighY vs LowY) after X? I'm presuming Y is ATG13 and X is Rapamycin.
Murph
Senior Member (Voting Rights)
Today on reddit I found a blurry poster that apparnetly reports preliminary findings from the Avik Roy, Maureen Hanson, Gottschalk Rapamycin study. They've put 40 people through their 3-month study of weekly rapamycin dosing and the preliminary results are good.
In the charts in the middle you can see results at four timepoints: baseline and three later points. The first chart, A, the Bell Score, is rising, and significant when comparing the last timepoint to the baseline.
There's four charts under B, which are symptom scores, fatigue and disturbed sleep. YOu can see a lot of lines indicating they are all significant.
Theres 6 charts under C which are the fatigue inventory, a few of them are significant.
There's 6 charts under D which is the SF 36 health survey, you see those bars rising and a fair few statistically significant findings. A full paper is set to follow.
Yes I did look for a non-blurry version and no I couldn't find it!
In the charts in the middle you can see results at four timepoints: baseline and three later points. The first chart, A, the Bell Score, is rising, and significant when comparing the last timepoint to the baseline.
There's four charts under B, which are symptom scores, fatigue and disturbed sleep. YOu can see a lot of lines indicating they are all significant.
Theres 6 charts under C which are the fatigue inventory, a few of them are significant.
There's 6 charts under D which is the SF 36 health survey, you see those bars rising and a fair few statistically significant findings. A full paper is set to follow.
Yes I did look for a non-blurry version and no I couldn't find it!
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From reading a lot of the patient stories and hearing what the researchers say it seems like some people benefit a lot but most don't respond or not much.
So it could be that when the full study is published we see big responders and non responders averaging out here.
Or it could just be placebo.
Yann04
Senior Member (Voting Rights)
I really feel weird when I see so many people celebrating studies like these on social media. I don’t wanna be a party pooper, but like it pains me to see people be convinced we’ve found a treatment when the chances are very low.
I don't understand. Wasn't the whole point of the trial to look at pATG13 (and some other things) before, during and after treatment? I can't find those on the poster. The subjective reports in people going to Dr Kaufmann to take this drug in an unblinded trial are as we all know, without much value. I suppose the pATG13 might still take some time, but is there any point of doing a poster beforehand?
Utsikt
Senior Member (Voting Rights)
Utsikt
Senior Member (Voting Rights)
The time frame for the primary outcomes (subjective) were 1 year, and 1.5 years for the secondary (objective).
Maybe they only have the subjective ones now?
I suppose my preference would have been to wait another 6 months (but since it's just a poster, no problem in having something to discuss with colleagues). At least it means we shouldn't have to wait long for someone to post those results either.
The poster was taken from Stephanie Grach's Twitter account where she posted it (https://twitter.com/user/status/1907915204656300387
).
Utsikt
Senior Member (Voting Rights)
I agree!