Because many randomized clinical trials (RCTs) study several important outcome variables that may respond to treatment, evaluation of efficacy is often difficult. Objective algorithms that combine information from all relevant variables may not capture satisfactorily the total experience of patients. Therefore, a computer program that implements a flexible, subjective, and blinded ranking of patients using their entire medical history during the RCT has important commercial application for organizations that perform RCTs. This project describes a new procedure for endpoint determination. Raters, blinded to treatment assignment, independently rank outcomes of participants in the RCT. The procedure pools ranks across raters to determine a final "global outcome rank". A rank procedure, e.g., the Mann-Whitney statistic, tests treatment effect. Phase I, which stresses applications to cardiovascular disease, has three aims: (a) Investigation of feasibility of the approach by reanalyzing the SHEP (I) data. The rating assessments will incorporate different lengths of follow-up and varied severity of events. Phase I will (i) evaluate agreement between raters, (ii) study approaches for rating large numbers of RCT participants, and (iii) compare tests of treatment differences using subjective endpoints to standard methods; (b) Consideration of general methodological issues related to statistical power in subjective rankings; (c) Preliminary design of the prototype software package.Awardee's statement of the potential commercial applications of the research:The research aims eventually to produce computer programs to implement subjective endpoints in randomized clinical trials. The modules will be add-ons to commonly used computer statistical packages. They will be marketed to drug companies and other organizations conducting clinical trials. Some drug companies and academic institutions have already expressed interest in such programs.National Institute of General Medical Sciences (NIGMS)
