Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘positive confounding, 300post hoc analysis, subgroup analysis, 269–270postmarketing study, 3post randomization exclusions, bias, 62powercalculation, 9critical appraisal of reports, 433sample size, 84PRAIS- UK (Prospective Registry of AcuteIschaemic Syndromes in the UK), 280pre-eclampsia study, 256–257analysis, 257trial profile, 256prerandomization run-in periods, reporting, 373primary biliary cirrhosis trial, 288–290adjusted vs unadjusted hazards ratios, 290data, 289primary endpoints, 38tabulation, 394primary hypothesis, protocol development, 29procedures, protocol development, 31prognostic factor identification, regressionanalysis, 282–283PROMIS (Prospective Registry of Outcomes andManagement in Acute Ischaemic Syndromes), 144proportions, comparison of, 217–235, 232endpoint comparison, 230–231, 231example, 218–219contingency table, 219see also myocardial infarction trialFisher’s exact test, 225statistical inferences, 219–222, 221two-arm trial, 226–230, 229odds ratio, 228–229, 232odds ratio vs risk ratio, 230risk difference, 226–230, 232risk ratio, 226–227, 232risk ratio vs odds ratio, 229between two groups, 222–226see also Chi-squared (χ 2 ) testtwo-sample Z-test, 225–226Prospective Registry of Acute IschaemicSyndromes in the UK(PRAIS-UK), 280, 280–281Prospective Registry of Outcomes andManagement in Acute Ischaemic Syndromes(PROMIS), 144, 145protocol development, 23–36abbreviations, 26administrative considerations, 32background and rationale, 28–29case record form (CRF), 34definition, 24eligibility criteria, 30–31enrolment process, 31ethics, 32flow chart, 28follow-up, 31guideline implications, 25intervention information, 29investigational plan, 29, 29key components, 26objectives, 25, 29outcome measures/endpoints, 31primary hypothesis, 29procedures, 31protocol information page, 26publication policy, 33qualities of a good protocol, 25randomization, 31references, 34regulatory requirements, 32sample size, 31–32secondary hypothesis, 29statistics, 32study timetable, 33table of contents, 26, 27treatments, 31trial committees, 34–35clinical event review committee, 35data and safety monitoring boardor committee, 35executive committee, 35steering committee, 35trial design, 30trial monitoring, 33trial summary/synopsis, 28writing, 24–25publication bias, 62–63bias, 62–63meta-analysis, 443reporting, 372publication policymulticenter trials, 162protocol development, 33P-valuesmultiplicity, 333–334tables, 403475