Methodology, results and quality of clinical trials of tacrine in the treatment of Alzheimers-disease: a systematic review of the literature

CRD COMMENTARY: The authors clearly stated their research question and the inclusion and exclusion criteria. There was also a quality scoring for the included trials. The literature search was limited to two databases of published literature and it was not reported whether there were any language restrictions. It is unclear whether additional unpublished or published, non-English studies may have been missed. The review included non-randomised and randomised trials. It was not possible to combine the trials with a statistical analysis because of heterogeneity between the trials. The RCTs included trials of a crossover design which are not appropriate for the study of a progressive illness such as AD; this is confirmed in a Cochrane review (see Other Publications of Related Interest no.5). Thirteen of the twenty-one RCTs were therefore questionable inclusions in the narrative analysis. The authors stated that they did not combine the trials because of heterogeneity, but how that decision was made was not reported or discussed. There was also a very large number of drop-outs from the trials due to the adverse effects of tacrine. The authors' conclusions should be viewed with caution because of the poor methodological quality of the included trials.