4 ms·

This is absolute corruption of the FDA's mission to accurately label and appropriately market drugs. The evidence is from a study with N=40. Not 40,000. 40.

by dsr_ 1y ago

metalcrow 1y ago
Can you link to the study? The release implies there are multiple but doesn't link to any
- bunderbunder 1y ago
  Here's a PubMed search. https://pubmed.ncbi.nlm.nih.gov/?term=leucovorin+cerebral+folate+deficiency https://pubmed.ncbi.nlm.nih.gov/?term=leucovorin+cerebral+fo... It's worth noting that, in the absence of pre-registration, one should should assume that the body of literature (and any systematic review or meta-analysis that relies on it) could be significantly influenced by the file drawer effect. Anyway, I looked at a recent systematic review from those search results (https://pmc.ncbi.nlm.nih.gov/articles/PMC8622150/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8622150/), and it found exactly one double-blind RCT (https://pmc.ncbi.nlm.nih.gov/articles/PMC5794882/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5794882/) that seemed to support what the FDA is saying here. It had a fairly short duration (12 weeks) and a small cohort (48). I'm not medical expert but I do read medical literature as an amateur, and I'm pretty sure this is nowhere close to the standard of evidence for establishing safety and efficacy that the FDA used to demand. It feels like we may be reverting all the way back to the evidentiary standards that allowed crap like thalidomide onto the market.
  - metalcrow 1y ago
    Thank you! That's useful. And yeah i agree, this and the aducanumab scandal make it seem the FDA is going away from "too strict" back to "too loose".
OkayPhysicist 1y ago
Sample size doesn't tell you everything about a study. You don't need to throw 40,000 people out of an airplane to determine it's safer with a parachute.
- yibg 1y ago
  This gets brought up often and while true isn't very useful. We know jumping out of plane is dangerous because we have a good understanding of the physics and we have many many comparable examples (jumping out of buildings etc). We understand the mechanism of action of parachutes, so we also know for example a tiny little parachute made of paper towel won't work, and we don't need to test it to know that. Do we understand the cause of autism or how this supposed cure works?
  - OkayPhysicist 1y ago
    The key is effect size. We didn't know the exact method of action when we started injecting comatose diabetic children with insulin, but when the coma patient sits up and starts chatting with you, you can establish that a drug is effective with very small sample sizes.
    - yibg 1y ago
      Sure, but even there you need some reasonable sample size. i.e. a sample of 1 won't be sufficient and more importantly it needs to be reproducible. Inject 1 patient and they wake up, but if you inject 10 others and nothing happens and it may not be effective (not that it's definitely not effective). This would require a then a larger sample size.
    - thaw13579 1y ago
      Autism isn't as cut and dry as this. Falling out of planes and diabetic comas are truly black-and-white outcomes, but ASD assessment involves behavioral testing of social and verbal ability, which has high variability between and within individuals. The linked studies about folinic acid are not finding a binary conversion of of ASD kids from non-verbal to verbal, rather they are detecting X% increase in Y behavioral test, which is subtle and something that is found with behavioral treatment. I would love to live in a world where we discover a treatment for ASD that is as clearly successful as insulin for diabetes, but we're not there yet.

This is absolute corruption of the FDA's mission to accurately label and appropriately market drugs. The evidence is from a study with N=40. Not 40,000. 40.

by dsr_ 1y ago

This is absolute corruption of the FDA's mission to accurately label and appropriately market drugs. The evidence is from a study with N=40. Not 40,000. 40.

metalcrow 1y ago

Can you link to the study? The release implies there are multiple but doesn't link to any

bunderbunder 1y ago
Here's a PubMed search. https://pubmed.ncbi.nlm.nih.gov/?term=leucovorin+cerebral+folate+deficiency https://pubmed.ncbi.nlm.nih.gov/?term=leucovorin+cerebral+fo... It's worth noting that, in the absence of pre-registration, one should should assume that the body of literature (and any systematic review or meta-analysis that relies on it) could be significantly influenced by the file drawer effect. Anyway, I looked at a recent systematic review from those search results (https://pmc.ncbi.nlm.nih.gov/articles/PMC8622150/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8622150/), and it found exactly one double-blind RCT (https://pmc.ncbi.nlm.nih.gov/articles/PMC5794882/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5794882/) that seemed to support what the FDA is saying here. It had a fairly short duration (12 weeks) and a small cohort (48). I'm not medical expert but I do read medical literature as an amateur, and I'm pretty sure this is nowhere close to the standard of evidence for establishing safety and efficacy that the FDA used to demand. It feels like we may be reverting all the way back to the evidentiary standards that allowed crap like thalidomide onto the market.
- metalcrow 1y ago
  Thank you! That's useful. And yeah i agree, this and the aducanumab scandal make it seem the FDA is going away from "too strict" back to "too loose".

OkayPhysicist 1y ago

Sample size doesn't tell you everything about a study. You don't need to throw 40,000 people out of an airplane to determine it's safer with a parachute.

yibg 1y ago
This gets brought up often and while true isn't very useful. We know jumping out of plane is dangerous because we have a good understanding of the physics and we have many many comparable examples (jumping out of buildings etc). We understand the mechanism of action of parachutes, so we also know for example a tiny little parachute made of paper towel won't work, and we don't need to test it to know that. Do we understand the cause of autism or how this supposed cure works?
- OkayPhysicist 1y ago
  The key is effect size. We didn't know the exact method of action when we started injecting comatose diabetic children with insulin, but when the coma patient sits up and starts chatting with you, you can establish that a drug is effective with very small sample sizes.
  - yibg 1y ago
    Sure, but even there you need some reasonable sample size. i.e. a sample of 1 won't be sufficient and more importantly it needs to be reproducible. Inject 1 patient and they wake up, but if you inject 10 others and nothing happens and it may not be effective (not that it's definitely not effective). This would require a then a larger sample size.
  - thaw13579 1y ago
    Autism isn't as cut and dry as this. Falling out of planes and diabetic comas are truly black-and-white outcomes, but ASD assessment involves behavioral testing of social and verbal ability, which has high variability between and within individuals. The linked studies about folinic acid are not finding a binary conversion of of ASD kids from non-verbal to verbal, rather they are detecting X% increase in Y behavioral test, which is subtle and something that is found with behavioral treatment. I would love to live in a world where we discover a treatment for ASD that is as clearly successful as insulin for diabetes, but we're not there yet.