How to Read a Research Paper: An Exercise in Critical Thinking in the Context of an Epidemiologic Study on Tamsulosin and the Risk of Dementia.

A recent study of the relationship between tamsulosin and dementia found that, in propensity score-matched analyses that adjusted for measured risk factors for dementia, the use of tamsulosin to treat benign prostatic hyperplasia (BPH) was associated with a small but significant increase in the risk of incident dementia relative to untreated BPH, BPH treated with the 5α-reductase inhibitors dutasteride and finasteride, and BPH treated with the α adrenoceptor blockers doxazosin, terazosin, and alfuzosin. The choice of control groups addressed confounding by indication, confounding by disease severity, and confounding by pharmacologic drug class. The authors of the study provided a wealth of detail in their main paper and in supplementary materials, allowing an almost forensic examination of the findings. This article discusses the study from the perspective of whether the hypothesis relating tamsulosin to dementia was set a priori or emerged after an exploratory exercise; whether tamsulosin crosses the blood-brain barrier for dementia as the event of interest to be attributable to treatment; whether the action of tamsulosin is plausibly related to dementia as a possible outcome; whether confounding was adequately addressed in the analyses; whether the duration of follow-up was sufficient for the event of interest to be attributable to tamsulosin; whether the absolute increase in the rate of incident dementia was clinically significant; and what the curiosities in the dose-dependence and subgroup analysis findings could imply. These matters provide considerable food for thought. Thus, this article is intended to serve as an example of how to read a paper critically and how to think about what the findings might suggest.