Clinical Trials

❘❙❚■ Indexsignificance effects, 331subgroup analysis, 333, 337multivariate analysisdefinition, 455multiplicity, 336myocardial infarction trial, 218–219contingency table, 219statistical inferences, 221outcome predictor identification, regressionanalysis, 282outcomesCONSORT statement, 369critical appraisal of reports, 433–435definition, 454protocol development, 31tables, 401Nnegative confounding, 300negative trials, critical appraisal of reports, 432–433negative values, tables, 403non-ignorable missing data, 340–341noninferiority trials, 4, 116, 131–140analysis, 137–138definition, 114, 132example, 132, 133, 134, 136–137, 138, 138, 139features, 117margin choice, 134biocreep, 135patient population, 138–139result interpretation, 116–117sample size calculation, 135–137, 136use of, 133–134normal distribution, 175–184, 176area under the curve calculation, 179–182lower tail, 181two sided symmetric tails, 181–182upper tail, 179, 180, 180within user defined range, 181assessment, 182–184inverse normal plot (quantile-quantileplot), 182, 183definition, 175–176fitted curves, 175histograms, 178importance, 177–178properties, 176–177standard normal distribution, 178–179number needed to treat (NNT), definition, 455OO’Brien-Fleming analysis, 358, 359, 359odds ratiodefinition, 455two-arm trial, 228–229, 249one sample t-test see t-testsopen (unblinded) studies, 77Ppaediatric trials, 52paired t-test see t-testspancreatic cancer trial, 236data, 237log-rank test, 244survival curves, 241–242by treatment group, 241survival data, analysis, 251parallel design studiescrossover trials vs, 95–96trial profile, 380, 381parallel trials, definition, 92partial factorial design, 109patient population, noninferiority trials, 138–139patient selection, 47–54centers, 49–50critical appraisal of reports, 430disease status, 51–52eligibility criteria, 50–51, 51ethical issues, 52–53example, 48exclusion of eligible patients, 53investigators, 49–50paediatric trials, 52source of, 49‘period effect,’ crossover trials, 97–98per-protocol analysisdefinition, 456intention-to-treat analysis vs, 259pharmacodynamics, Phase II clinical trials, 3pharmacokineticsexamples, 58, 59Phase II clinical trials, 3phases (of trials), 3pie charts, 171, 411–412, 413, 423placebo, 2, 10Pocock analysis, 358, 358, 359pooled odds ratio estimate, 445population, significance tests, 186474