The IQWiG and cholinesterase inhibitors: early September the Institute for Quality and Economy in Healthcare (IQWiG), an institution with function comparable to NICE, published its preliminary report on the benefit of cholinesterase inhibitors in ALZHEIMER's disease. The Institute knows how to spring surprises - it comes to a basically positive conclusion. A benefit "with regard to the treatment aim of improvement or preservation of cognitive performance" is said to be confirmed for donepezil (ARICEPT), galantamine (REMINYL) and rivastigmine (EXELON). In addition, the authors claim that there is "evidence of benefit with regard to the treatment aim of improvement or prevention of impairment of the activities of daily life" for all three drugs. The authors find no evidence of an influence on the quality of life of patients and their relatives and on admission to nursing homes or mortality (http://www.iqwig.de/index.403.html). The results and conclusions of the report have caused dissent (DEGAM: http://www.degam.de/presse/sep_06_b.html), as the included studies, which were conducted almost exclusively by the manufacturers, are largely of poor methodological quality. In addition, they only investigated changes on various test scales, but no clinical outcome. The AD2000 study, the only one that investigated a clinically relevant end point, namely, the incidence of admission to nursing homes - without showing benefit (a-t 2004; 35: 67-8) -, is not taken into account by IQWiG because of its methodological weaknesses. In contrast, all of the studies - eight out of 22 - originally classified as "insufficient" in the preliminary report are included in the evaluation. High drop-out rates and uncertainty if the allocation of patients was concealed and the end points recorded by blinded investigators are regular flaws of the included studies. Moreover, the positive evaluation is based particularly on an advantage of an average of 3 out of 70 points on a cognitive performance scale (ADAS-cog) compared to placebo. It is not explained, what this means in practice and it is presumably far from any practical relevance. Specifically, it may mean the reproduction of three additional terms in one memory test belonging to the ADAS-cog. Is that relevant? Side effects are common with dementia drugs. 5% to 40% of patients are affected by gastrointestinal complaints. However, the risk/benefit ratio is discussed insufficiently in the preliminary report. If at least 4 points on the ADAS-cog scale are defined as "response", ten patients must be treated in order to reach this goal (number needed to treat) according to data from a meta-analysis that analysed 16 studies. However, this corresponds roughly to the increase in side effects calculated in the same meta-analysis (number needed to harm = 12; LANCTÔT, K.L. et al.: CMAJ 2003; 169: 557-64). Healthcare resources must be distributed reasonably to measures of proven benefit. There is still no proof of the benefit of cholinesterase inhibitors. -Ed.