The value of the number-needed-to-treat method in antiepileptic drug trials

There is controversy between clinicians and statisticians on the appropriateness of the number needed to treat (NNT) as a summary statistic to report the effectiveness of a treatment. We examine the two viewpoints and make proposals concerning the reporting of clinical trial results.

In the context of antiepileptic treatments, we explain the two different viewpoints and illustrate the use of the odds ratio, relative risk, absolute difference, and NNT on the results of randomized clinical trials with topiramate (TPM). Special attention is paid to the use of these summary statistics in meta-analyses. Here, the NNT is the expected number of patients one would need to treat to achieve a single occurrence of a specified good outcome (e.g., 50% reduction in seizure rate) in comparison to no (or placebo) treatment.

Although the NNT is readily interpretable in some instances, it exhibits undesirable statistical behavior in other cases. In particular, confidence intervals for the NNT may split into two intervals and extend to positive and negative infinity when treatment efficacy is not clearly established by the data. Meta-analyses cannot be sensibly conducted directly on the NNT scale.

Although other measures, such as the odds ratio, have been more commonly used in the context of meta-analyses, clinicians prefer the NNT because it gives them a clearer clinical interpretation of the effectiveness of a (new) treatment. On the other hand, statisticians do not recognize the value of the NNT, as it has undesirable statistical properties. Some reconciliation between the two views could be achieved when the clinicians acknowledge the weak aspects of the NNT and when statisticians realize that statistical appropriateness is not the same as clinical relevance. It is suggested that the NNT be used as a secondary reporting tool not on an equal footing with the classic scales.