- To provide additional evidence regarding the plausible range of the differences in health-related quality of life (HRQL) questionnaire scores within which the minimal important difference (MID) falls, we reviewed the results of 32 randomized controlled trials in individual subjects (N of 1 RCTs) with chronic diseases. These trials had been conducted to establish whether a patient was obtaining more good than harm from a medication. Each N of 1 RCT included a series of pairs of treatment periods, one period on active drug, and one on placebo or alternative drug. We examined the relationship between small (MID), medium, and large differences between periods within pairs, as indicated by Global Ratings and differences between these same periods according to HRQL questionnaires. The results showed a mean difference of 0.29 points per question in HRQL questionnaire scores corresponded to the MID. Differences of approximately 0.66 points per question corresponded to a moderate difference as ranked by the Global Rating; difference of about 1.09 points per question represented marked difference.