Sufficiently important difference: Expanding the framework of clinical significance

Background. It is generally agreed that randomized controlled trials should be powered to detect small but clinically significant treatment effects. Toward these ends, minimal important difference (MID) was proposed as a benchmark for designing trials and for interpreting health-related quality-of-life instrument scores. MID was defined in 1989 as the smallest difference in score in the domain of interest which patients perceive as beneficial and which would mandate, in the absence of troubling side effects and excessive cost, a change in the patient's management.Objective. 1) To expand the idea of minimal clinically important difference so as to take into account harms as well as benefits. 2) To propose concepts and methods with which to do so. Summary. The authors define sufficiently important difference (SID) as the smallest amount of patient-valued benefit that an intervention would require to justify associated costs, risks, and other harms. As a means toward estimation of SID, the authors propose benefit-harm tradeoff methods, in which domains of benefit and harm are systematically traded off against each other and assessed in relation to the global decision of whether a treatment choice is worthwhile. Specific SID estimates can be used to power and interpret clinical trials or to inform health services research and/or public health policy. This article briefly describes the evolution of the important difference concept and outlines similarities and differences between MID and SID.