cmonsen

1) First, required reading for anyone interpreting medical studies: http://jama.jamanetwork.com/article.aspx?.articleid=201218 TLDR; is that ~40% of _randomized_ (generally considered highest level of quality) studies and maybe more are proven wrong by subsequent ones resulting from publication bias. Consider that this would not have been published in a high profile journal if it showed no effect, hence pub bias. In other words, we're not seeing the similarly large analyses that show no effect because they're not published.

2) The adjusted analyses have confidence intervals on the odds ratio that overlap with 1.0 except for the highest dose group. There is evidence of a dose response relationship, but there is a problem in how they measure dose response. Cumulative dose biases towards people who have been on medications for a long time. People who are able to take medications (ie are older) for a long time are at greater risk for dementia.

3) It is problematic that they assume any effect on their endpoint is a class effect (ie true of all anticholinergics). The relationship with one medication may be driving this effect entirely. I would like to see, for example, oxybutynin pulled out of the analysis which is never prescribed for allergies and more often for neurological conditions, which could be an unmeasured confounder depending on how they modeled the comorbidities.

4) Controlled analyses are difficult to do well. Most of the time it controls for linear effects, meaning synergistic effects (which are probably involved in development of dementia) are not captured unless explicitly modeled. I do not see that they did this here.

5) I am further suspicious of the way they obtained fill data. As you are noting, many OTC anticholinergics are not "dispensed" in a way typical of prescription anti-cholinergics. If I bought Benadryl at CVS or even if I bought the pre-packaged bottle at the Group Health pharmacy, it's pretty clear to me that neither of these would be reflected in the data. This skews heavily toward prescription anti-cholinergics, which tend to be given for psych/neuro indications which themselves have an association (though likely not a causal one) with dementia. Again, unclear if they modeled all of these.

Overall, I share the sentiment that medical literature needs to be more open. I think it's unfortunate that current state makes it hard to confirm analyses like these with a great degree of certainty.