The natural history, prognosis, and clinical significance of chronic hepatitis C are highly variable and somewhat controversial. The purpose of this study was to evaluate the effect of chronic hepatitis C infection on patients' perceptions of health-related quality of life (HRQOL) and to evaluate whether treatment with interferon improves HRQOL. A total of 642 patients with compensated liver disease who were enrolled in a multicenter trial of interferon therapy for chronic hepatitis C had evaluation of HRQOL using the SF-36 and other instruments derived from the Medical Outcomes Study (MOS). These instruments were self-administered by patients at baseline and at the end of a 24-week post-treatment observation period after 24 weeks of interferon treatment. Patients with chronic hepatitis C were compared with healthy controls (n ‫؍‬ 750) selected from a representative sample of adults in the United States. Unadjusted and age/gender-adjusted results were similar, as were analyses using parametric or nonparametric methods. Compared with healthy controls, patients with chronic hepatitis C at baseline had lower HRQOL on all eight scales of the SF-36 (P F .001 for all). Patients without cirrhosis (n ‫؍‬ 284 ) showed similar although slightly smaller differences. The differences were highly significant, clinically and socially relevant, and greatest for those scales that were more reflective of physical than mental or emotional disease. Patients who had a sustained viral response to interferon therapy (n ‫؍‬ 41) exhibited marked improvements in HRQOL, and these improvements exceeded those of nonresponders on 13 of 14 HRQOL scales (8 were statistically significant). Similar improvements were noted in patients with sustained biochemical re-

It is generally believed that small differences in health-related quality of life (HR-QOL) may be statistically significant yet clinically unimportant. The concept of the minimal clinically meaningful difference (MCID) has been proposed to refer to the smallest difference in a HR-QOL score that is considered to be worthwhile or clinically important. However, there is danger in oversimplification in asking the question: what is the MCID on this HR-QOL instrument? We argue that the attempt to define a single MCID is problematic for a number of reasons and recommend caution in the search for the MCID holy grail. Specifically, absolute thresholds are suspect because they ignore the cost or resources required to produce a change in HR-QOL. In addition, there are several practical problems in estimating the MCID, including: (i) the estimated magnitude varies depending on the distributional index and the external standard or anchor; (ii) the amount of change might depend on the direction of change; and (iii) the meaning of change depends on where you start (baseline value).

Etanercept therapy improves PROs in patients with psoriasis and makes a meaningful difference to their lives. These results support the efficacy profile of physician-reported clinical measures while providing a more complete understanding of the benefits experienced by patients with psoriasis treated with etanercept.