Clinical Trials

❘❙❚■ IndexHhazard function, definition, 279hazard ratioadjusted vs unadjusted, 290two-arm trial, 250health-economic endpoint see endpointshigh-order crossover trials, 95histograms, 171, 175, 409, 416–418, 417, 423hormone replacement trial, 297–298data, 297sample selection, 297hypothesis testing see significance testsIincidence rates, two-arm trial, 249–250incomplete crossover trials, 94incomplete factorial design, 109institutional review boards, 160intention-to-treat analysis (ITT), 62, 255–263bias control, 62definition, 10, 256–257, 454example, 256–257, 257, 260–261trial profile, 256see also pre-eclampsia study; vitamin Asupplementation trialimplementation, 262justification, 257–258limitations, 258–259per-protocol analysis vs, 259reporting, 262, 372interaction testing, 305–316classification, 307–308confounding vs, 303definition, 306effect modification, 306evaluation, 308examples, 306, 311–313crossover trials, 315multicenter trials, 313–314, 314treatment-by-center, 313–314, 314treatment-by-period, 315see also Gruppo Italiano per lo Studiodella Streptochinasi nell’InfartoMiocardico (GISSI)-Prevenzione trialfactorial design, 110–111, 111linear regression model, 309–311, 310qualitative, 307–308, 308quantitative, 307–308, 308, 310, 314subgroup analysis, 269timing, 306intercept, definition, 276interim analysesmulticenter trials, 161multiplicity, 333, 337interim monitoring, 353–362Candesartan in Heart failure – Assessmentof Reduction in Mortality and morbidity(CHARM), 10definition, 354early trial termination, 360–361procedures, 355purposes, 354statistical methods, 356, 356–360, 357O’Brien-Fleming analysis, 358, 359, 359Pocock analysis, 358, 359usage, 354–355internal validity, report interpretation, 368International Conference on Harmonizationguidelines for Good Clinical Practice(ICH-GCP), 24introductions, 370reports, 367inverse normal plot (quantile-quantile plot),normal distribution assessment, 183investigators, patient selection, 49–50ITT see intention-to-treat analysis (ITT)KKaplan-Meier plot, 239–242, 240, 241, 398definition, 456limitations, 242by treatment group, 241Lλ, bioequivalence trials, 123–124, 124landmark study, 3last observation carried forward, bias control, 62Latin square design, 126–127, 127linear regression, multiple see regression analysislinear regression model, 292, 423line graphs, 418–420, 420literature search, meta-analysis, 442logistic regression see regression analysislog-rank test, 242–244, 244limitations, 244survival curves, 242–244472