to an "average" duration or population size. There are also basic mathematical constraints, i.e., it is not appropriate to calculate confidence intervals in crossover studies, and the mean NNT for several studies is actually the reciprocal of the arithmetic mean of the individual weighted absolute risk reductions and not the average of all weighted NNT's. If the end points move in the same direction for both placebo and drug, NNT's might be overestimated. Finally, the validity of meta-analyses should be questioned if the reduction in RR exceeds 20% between studies.

Use of the aforementioned methods with an awareness of their caveats might ensure that treatment on a robust evidence base is advocated as opposed to the current situation, where a number of national and international guidelines still recommend tricyclic antidepressants as first line treatment for painful diabetic neuropathy. This is despite the fact that studies assessing the efficacy of amitriptyline are limited to five small clinical trials with heterogeneous patient groups, end points and analyses, which have never enabled it to secure an indication for diabetic neuropathy (1).

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