Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘types, 38–39enrolment process, protocol development, 31equivalence trials, 4, 113–119between-subject variability, 115–116definition, 114design issues, 115–116features, 117purposes, 114result interpretation, 116–117types, 115bioequivalence see bioequivalence trialsclinical equivalence see clinicalequivalence trialsnoninferiority studies see noninferioritytrialswithin-subject variability, 115–116ethicsapproval, multicenter trials, 160–161cluster randomized trials, 148–149patient selection, 52–53protocol development, 32EU Clinical Trials Directive (EUCTD), 24executive committee, protocol development, 35expected event rate calculation, 83exploratory trial, 4external validitydefinition, 48report interpretation, 368Ffacilitating collaboration, multicentertrials, 157–159factorial design, 101–112advantages, 110–111analysis, 105–106, 106compliance, 111complicated, 109–110cost, 110definition, 102example, 102–103, 103incomplete/partial, 109interactions, 110–111intervention number, 107limitations, 111notations, 108randomization, 104sample size, 104–105, 110treatment interaction, 105–106trial profile, 381types, 106–110unbalanced, 109use of, 103–104factorial trials, definition, 3false-negative results (type II error) see type II(beta) errorsfigures, 407–425example, 409, 409, 410graphs, 408–409, 410–424bar charts, 410–411, 411, 423box plots, 414–416, 416, 423column chart, 412dot plots, 412–413, 414, 423forest plots, 421–423, 422, 423funnel plots, 423, 424, 444histograms, 416–418, 417, 423line graphs, 418–420, 420, 423pie charts, 411–412, 413, 423scatter plots, 418, 419, 423spaghetti plots, 420, 421stem and leaf plots, 413–414, 415, 423three variables, 423, 424Fisher’s exact test, 225fixed-effects model, meta-analysis, 445, 445–446follow-upprotocol development, 31tables, 401footnotes, tables, 402forest plots, 421–423, 422, 423frequency, definition, 170funnel plots, 423, 424, 444GGaussian distribution see normal distributiongeneralizability, definition, 48GISSI see Gruppo Italiano per lo Studio dellaStreptochinasi nell’Infarto Miocardico (GISSI)-Prevenzione trialGlobal Registry of Acute Coronary Events(GRACE), 278–279graphs see figuresGruppo Italiano per lo Studio dellaStreptochinasi nell’Infarto Miocardico(GISSI)-Prevenzione trial, 106, 309–311,311, 311–313data, 306logistic regression model, 312primary endpoint rate, 312471