title: Longitudinal data analysis in medical device clinical studies.
abstract: Several statistical approaches are discussed for analysis of longitudinal clinical data from a two independent groups, randomized, prospective, multicenter study of patients with benign prostate hyperplasia (BPH) who are treated with either a new transurethral microwave thermotherapy device (TUMT, n = 147) or sham control (n = 73) at baseline and at 1, 3, and 6 months follow up. The primary clinical endpoint, based on the American Urological Association (AUA) symptom score from 7 questions (each scored 0-5) with 35 as the worst total score, is illustrated in this paper. The primary effectiveness null hypothesis is no treatment effect at any follow-up time against the alternative hypothesis of a favorable treatment effect at one or more follow-up times. Based on the prespecified clinical input of TUMT improvement in AUA mean score as a possible early effect, the expected change of slope between baseline to month 1 (baseline slope) and from month 1 to the end of month 6 (longitudinal slope), with knot at one month, were analyzed. The primary effectiveness endpoint was analyzed by a piecewise linear spline regression model with knot at month 1. Statistically significant lower mean AUA score was found in the TUMT group compared to the sham group at month 3 (P = 0.01) and at month 6 (P < 0.0001) follow-up; no significant difference in mean AUA score was found at baseline or at month 1 follow-up, after an overall statistically significant difference in mean AUA score (P = 0.004) was found between the TUMT and sham groups.
authors.affiliation: Division of Biostatistics, Office of Surveillance and Biostatistics, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Rockville, Maryland 20850, USA. chang.lao@fda.hhs.gov
authors.forename: Chang S
authors.initials: CS
authors.lastname: Lao
authors.forename: Harry F
authors.initials: HF
authors.lastname: Bushar
mesh_terms: D004864:Equipment and Supplies / Q000706:statistics & numerical data*; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data / Q000639:trends; D011470:Prostatic Hyperplasia / Q000453:epidemiology / Q000628:therapy; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data* / Q000639:trends*; D013223:Statistics as Topic / Q000379:methods / Q000639:trends