title: Reducing unnecessary measurements in clinical trials with multiple primary endpoints.
abstract: Clinical trials often involve two or more primary endpoints. However, observing or measuring high-cost endpoints often reduces the efficiency of the study because of high medical costs, highly invasive measurements, or long-term follow-up. Further, the individual powers to demonstrate the overall efficacy of a new intervention for the multiple endpoints often differ under a given sample size. We propose an efficient clinical trial design in which the sample size for each of the endpoints is individually determined, taking into consideration both the cost and the individual power for each endpoint. We compared the efficiency of the proposed design with that of the conventional design using three variables: (1) the number of participants in the study, (2) the total number of measurements for all endpoints, and (3) the cost of enrolling the participants and obtaining the measurements for all endpoints. We extended the proposed design to a group-sequential design. Numerical examples show that the proposed design can reduce unnecessary measurements and adjust the individual powers for the endpoints, especially when the individual power for one endpoint is relatively higher than that for other endpoints in a study with multiple co-primary endpoints.
authors.affiliation: a Department of Management Science , Faculty of Engineering, Tokyo University of Science , Tokyo , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sozu
authors.affiliation: b Hirosaki University Graduate School of Science and Technology , Aomori , Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Sugimoto
authors.affiliation: c Office of Biostatistics and Data Management, National Cerebral and Cardiovascular Center , Osaka , Japan.|d Department of Innovative Clinical Trials and Data Science, Osaka University Graduate School of Medicine , Osaka , Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Hamasaki
mesh_terms: D002986:Clinical Trials as Topic; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D006801:Humans; D012107:Research Design; D018401:Sample Size
keywords: Cost; drug development; efficiency; group-sequential design; multiplicity; sample size