The number needed to treat (NNT) statistic was developed to facilitate the
practice of evidence-based medicine. Placebo was assumed to be
therapeutically inert when the NNT was originally conceived, but more recent
data for conditions such as major depressive disorder (MDD) suggest that the
placebo control condition can have considerable therapeutic effects.
Complications arise because the NNT calculated from randomised controlled
trials (RCTs) reflects a comparison between medication plus clinical
management and placebo plus clinical management, whereas, in the clinical
setting, physicians choose between prescribing open medication, observing a
patient over time with a supportive approach, and doing nothing. Thus, NNTs
derived from clinical trials are not directly relevant to clinical
decision-making, because they are based on control conditions that do not
exist in standard practice. Additional difficulties may arise when using
NNTs to compare alternative treatments for MDD, such as medication and
psychotherapy, since these comparisons require the control conditions upon
which the respective NNTs are based to be similar. Whereas pill placebo
conditions include intensive clinical management and elicit expectations of
improvement, attention control conditions for psychotherapy research are
less well developed. Often the effects of psychotherapy are gauged against a
wait-list control condition, which has substantially fewer therapeutic
components than a pill placebo control condition. To improve the clinical
utility of NNTs for the treatment of MDD, we advocate effectiveness studies
that include treatment conditions resembling actual clinical practice,
rather than using placebo-controlled RCTs for this purpose. Until such
studies are performed, the effect of bias in comparing NNTs across
treatments can be controlled by ensuring that the RCT control conditions
upon which the NNTs are based are comparable.