Commentary on “Health economics and the value of therapy in Alzheimer's disease.” Cholinesterase inhibitors in Alzheimer's disease—Evidence‐based or evidence‐biased?

s T e c t m n i a t r d m r b s t a w c d l t r m The value of cholinesterase inhibitors in the treatment of lzheimer’s disease has been hotly debated. Whereas clincal guidelines recommend that these medications should be onsidered [1–6], this endorsement by clinicians is not eflected in reviews by policymakers [7] and others evaluting economic impact [7–9]. The same evidence has alterately been rated as “level 1” (strong clinical evidence elatively free from bias) by expert clinicians [1,3–6], and ismissed by others as “non-evidence-based fluff” [10] or ow quality [11]. How has such a situation arisen, given the uge database of clinical trials evaluating the efficacy and afety of cholinesterase inhibitors for Alzheimer’s disease? he answer lies in the disparate evidence required by frontine clinicians and policymakers. Clinicians require evidence about efficacy and safety to etermine whether they should prescribe a medication to an ndividual patient. From an evidence-based medicine perpective, where the goal is to minimize the influence of bias, he gold standard for drug evaluation is a systematic review f evidence from randomized, controlled clinical trials. eta-analyses of cholinesterase inhibitor trials, either on ndividual drugs [8,12–16] or on drug groups [3,11,17–21], ere used to broadly summarize treatment effects. The esults show that cholinesterase inhibitors have a significant hough modest effect on important outcomes, including lobal measures and function [3,8,11–17,19–21]. Despite he consistent findings of these meta-analyses, there has een controversy on the value of the conclusions that can be rawn on the basis of these randomized, controlled trials. iscrepancies arise over the interpretation of treatment efect size [8,18], the quality of trials [11,16], and clinical