ANALYTIC DIFFICULTIES IN APPLYING QUALITY-OF-LIFE OUTCOMES TO CLINICAL-TRIALS OF THERAPY FOR HIV DISEASE

Despite considerable enthusiasm for the concept, quality-of-life or he alth status outcomes are seldom employed in clinical trials. The failu re of common analytic procedures to meet key requirements may have con tributed to this limited acceptance. In particular, (1) results of cli nical trials must be expressed in terms that clinicians, regulators, a dministrators, and patients find useful, (2) reasonable means of summa rizing outcomes should be available a priori, (3) scale units should h ave real world meaning, (4) unwarranted assumptions regarding scale pr operties should be avoided, and (5) adequate methods for handling attr ition due to death or drop-out are necessary. Our group has developed approaches to these problems. We summarize overall outcome using a wei ghted sum of scores for scales covering several domains and weights de rived from regressions of scale scores on a reference variable. Our mu ltistate survival analysis, an extension of standard survival analysis attempts to circumvent some of the difficulties with attrition and po or scale properties of health status/quality of life measures. Multist ate survival analysis has two components, a description of survival-in -state, and significance test based on transitions-from-state. In surv ival-in-state analysis, we generalize the usual survival analysis to c onsider the proportions of participants with a health or quality statu s which is at least equal to that indicated by specified ordered state s. In transition-from-states analysis, we generalize the Mantel-Haensz el procedure to simultaneously consider upward and downward transition s from previous health or quality state to improved or worsened states . These approaches incorporate mortality without requiring specificati on of a score value for death, allow reasonable handling of attrition, give results denominated in proportions or time units rather than sco re values, and allow assessment of net changes in status for individua l participants between evaluations.