Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Mmain clinical effect, definition, 309Mann-Whitney (two-sample Wilcoxon rank-sum)test, 210–212, 212, 214maximum, repeated measurements, 322–323, 323meanscomparison of, 197–216example, 198–200see also chronic airways limitation(CAL)multiple group comparisons, 213two-sample Wilcoxon rank-sum(Mann-Whitney) test, 210–212, 212, 214two-sample Z-test, 210, 214see also t-testsdefinition, 172repeated measurements, 321–322, 322median, definition, 172Medicines and Healthcare Products RegulatoryAgency (MHRA), 25meta-analysis, 86, 439–451aims, 440data extraction and quality assessment, 443definition, 440examples, 441, 446, 448fixed-effects model, 445, 445–446limitations/concerns, 449–450literature search, 442objectives, 449publication bias, 443random-effects model, 446–448, 447statistics, 444, 445–449study question formulation, 440study selection, 442–443methods section, 367, 370minimization randomization, 72, 72–73missing at random (MAR) data, 340–341missing completely at random (MCAR)data, 340–341missing data, 339–351, 340–341common types, 340–341datasets with, 347datasets with missing values, 348, 349dealing with, 342–344analysis of all available data, 342analysis of complete cases only, 342comparison of techniques, 344–350datasets with missing values, 346last observation carried forward, 342–343multiple imputation, 343–344definition, 340potential effects, 341simulation model, 344–346statistical analysis, 348–350, 350missing not at random (MNAR) data, 340–341dealing with, 344mode, definition, 172multicenter clinical trials, 153–163advantages, 154–156definition, 3–4, 154examples, 155financial considerations, 162institutional review boards, 160interaction, treatment-by-center, 313,313–314, 314‘life cycle’, 158organization, 156–159center selection, 161coordinating team, 156–157ethics approval, 160–161facilitating collaboration, 157–159interim analyses, 161randomization, 161publication policy, 162recruitment targets, 159timeline, 157multiple endpoints, 332multiple group comparisons, 213multiple imputationbias control, 62missing data, 343–344multiple linear regression see regression analysismultiple treatments, 332multiplicity, 329–338, 337definition, 330design incorporation, 333–335outcome definition, 334–335post trial manipulation, 335P-value changes, 333–334interim analyses, 333, 337multiple endpoints, 332, 335–337, 337combination, 335–336composite endpoints, 336multivariate approach, 336specification, 335multiple treatments, 332, 337occurrence in clinical trials, 332–333repeated measurements, 332–333473