Impact of benefit of erlotinib in one subpopulation vs harm in another: Despite substantial benefit in one subpopulation, a randomized trial may conclude that an agent is ineffective if it causes harm in a different subpopulation. Erlotinib vs placebo were added to chemotherapy in NSCLC,  and the curves overlapped suggesting no impact of erlotinib (two center curves, redrawn from Herbst et al. ). However, on molecular assessment, erlotinib was associated with potential benefit in the 13% of patients with an EGFR mutation (p=0.09), but was associated with harm in the 21% of patients with KRAS mutations (p=0.03) (curves resynthesized using component parts from Eberhard et al. ).