PLoS Medicine | www.plosmedicine.org0456Randomized controlled trials (RCTs) are generally considered to be a robust form of evidence, free from bias, and the trial results are often used as a powerful tool to promote new drugs [1,2]. However, because the inclusion criteria for many RCTs are often very restrictive (for example, trials generally exclude patients with serious concomitant illnesses) and because patients in trials tend to receive better care than those in standard-care settings, clinicians should be careful about generalizing RCT results to their own patients. Unfortunately, many drug treatments are widely used in clinical practice, sometimes beyond the approved indications, even when doubts remain about whether the results of RCTs of these drugs should be generalized. In this article, we discuss the use of cholinesterase inhibitors in patients with a variety of types of dementia and cognitive impairment, looking critically at the clinical trial evidence on these drugs.If the results of these trials are not carefully evaluated, together with evaluating the methodological quality of the studies, this could lead to inappropriate prescribing of cholinesterase inhibitors. Drug companies have invested heavily in developing treatments for Alzheimer disease, and then were actively involved in expanding the market to other forms of dementia. In the last decade, donepezil, galantamine, and
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