Background Several recent trials in chronic obstructive pulmonary disease (COPD) have assessed the effectiveness of the fluticasone–salmeterol combination inhaler in preventing COPD exacerbations, while finding an increased risk of pneumonia. The number needed to treat (NNT) is a simple measure to perform the comparative benefit–risk impact, but its calculation involving repeated outcome events such as COPD exacerbations has been incorrect. We describe the proper methods to calculate the NNT and, using data from published trials, apply them to evaluate the relative impact of fluticasone–salmeterol treatment on exacerbations and pneumonias in patients with COPD.

Methods We review the fundamental definition of NNT and quantify it for situations with varying follow-up times. We review the ‘event-based’ NNT, proposed and used for repeated event outcomes, show its inaccuracy, describe its proper use and provide an approximate formula for its application.

Results We show that a 1-year trial of the fluticasone–salmeterol combination versus salmeterol used the incorrect event-based approach to calculate the NNT as two patients that need to be treated for 1 year to prevent one COPD exacerbation, when the proper calculation results in a NNT of 14. In contrast, 20 patients need to be treated to induce one pneumonia case. For the TORCH trial, the NNT is 44 patients treated for 3 years with fluticasone–salmeterol versus salmeterol to prevent one exacerbation compared with 16 patients to induce one pneumonia case.

Conclusions The NNT is a useful measure of the effect of drugs, but its proper calculation is essential to prevent misleading clinical practice guidelines.