42 ms·

I think the study is somewhat more robust than you're letting on, since it compares HCQ against an alternative rheumatoid arthritis drug - Methotrexate. It's po

by ummonk 4y ago

I think the study is somewhat more robust than you're letting on, since it compares HCQ against an alternative rheumatoid arthritis drug - Methotrexate. It's possible that the choice of prescribed drug itself is correlated with some other confounding factor, but it's certainly less likely to be so compared to HCQ vs nothing. Also, the study itself is clear about the amount of evidence needed to validate whether HCQ actually reduces Alzheimer's risk: "This hypothesis merits testing through adequately powered clinical trials in at-risk individuals during preclinical stages of disease progression."

loosescrews 4y ago
In that case, couldn't it be that Methotrexate makes the risk worse rather than Hydroxychloroquine reducing the risk?
travisp 4y ago
Methotrexate is standard of care, considered “strongly recommended” over hydroxychloroquine (source: https://onlinelibrary.wiley.com/doi/epdf/10.1002/acr.24596 https://onlinelibrary.wiley.com/doi/epdf/10.1002/acr.24596 ) for rheumatoid arthritis. If I read the paper right, hydroxychloroquine may be favored in “low disease” states. So I would certainly expect some sort of difference in patient population. It would suggest those initiated on hydroxychloroquine would normally have less severe rheumatoid arthritis (or have some other difference that their doctor would choose to not use methotrexate by default), although I don’t know if that’s the case in reality.
- carbocation 4y ago
  Not having prescribed either since I was a PCP years ago, I would just say that I agree with this line of inquiry. If both drugs were equally good and were pretty much used at random, then they could be good instruments. But if there is confounding by indication, then it’s harder to get value out of an analysis that compares them. It doesn’t mean the conclusions are wrong (and nor does my comment above), it just tempers my interpretation.
  - elcritch 4y ago
    You could try and reduce the possible effect by controlling for disease severity. If it reduced the effect a large amount it'd strengthen the case that the effect is actually due to RA disease severity. Actually I'd be a bit surprised if the authors didn't do that for an observational study.
    - carbocation 4y ago
      Agreed. I didn't see it described in their methods, although it seemed that the main focus of this paper (based on length dedicated to the material) was the biological/model data rather than the EHR data.

by ummonk 4y ago

loosescrews 4y ago

In that case, couldn't it be that Methotrexate makes the risk worse rather than Hydroxychloroquine reducing the risk?

travisp 4y ago

Methotrexate is standard of care, considered “strongly recommended” over hydroxychloroquine (source: https://onlinelibrary.wiley.com/doi/epdf/10.1002/acr.24596 https://onlinelibrary.wiley.com/doi/epdf/10.1002/acr.24596 ) for rheumatoid arthritis. If I read the paper right, hydroxychloroquine may be favored in “low disease” states. So I would certainly expect some sort of difference in patient population. It would suggest those initiated on hydroxychloroquine would normally have less severe rheumatoid arthritis (or have some other difference that their doctor would choose to not use methotrexate by default), although I don’t know if that’s the case in reality.

carbocation 4y ago
Not having prescribed either since I was a PCP years ago, I would just say that I agree with this line of inquiry. If both drugs were equally good and were pretty much used at random, then they could be good instruments. But if there is confounding by indication, then it’s harder to get value out of an analysis that compares them. It doesn’t mean the conclusions are wrong (and nor does my comment above), it just tempers my interpretation.
- elcritch 4y ago
  You could try and reduce the possible effect by controlling for disease severity. If it reduced the effect a large amount it'd strengthen the case that the effect is actually due to RA disease severity. Actually I'd be a bit surprised if the authors didn't do that for an observational study.
  - carbocation 4y ago
    Agreed. I didn't see it described in their methods, although it seemed that the main focus of this paper (based on length dedicated to the material) was the biological/model data rather than the EHR data.