SAMPLE SIZE CALCULATIONS IN CLINICAL RESEARCH

By SUSAN MILLER

CONTENTS INTRODUCTION REGULATORY REQUIREMENT BASIC CONSIDERATIONS PROCEDURES FOR SAMPLE SIZE CALCULATION AIMS AND STRUCTURE OF THE BOOK CONSIDERATIONS PRIOR TO SAMPLE SIZE CALCULATION CONFOUNDING AND INTERACTION ONE-SIDED TEST VERSUS TWO-SIDED TEST CROSSOVER DESIGN VERSUS PARALLEL DESIGN SUBGROUP/INTERIM ANALYSES DATA TRANSFORMATION PRACTICAL ISSUES COMPARING MEANS ONE-SAMPLE DESIGN TWO-SAMPLE PARALLEL DESIGN TWO-SAMPLE CROSSOVER DESIGN MULTIPLE-SAMPLE ONE-WAY ANOVA MULTIPLE-SAMPLE WILLIAMS DESIGN LARGE SAMPLE TESTS FOR PROPORTIONS ONE-WAY ANALYSIS OF VARIANCE WILLIAMS DESIGN RELATIVE RISK—PARALLEL DESIGN RELATIVE RISK—CROSSOVER DESIGN EXACT TESTS FOR PROPORTIONS BINOMIAL TEST FISHER’S EXACT TEST OPTIMAL MULTIPLE-STAGE DESIGNS FOR SINGLE ARM TRIALS FLEXIBLE DESIGNS FOR MULTIPLE-ARM TRIALS REMARKS TESTS FOR GOODNESS-OF-FIT AND CONTINGENCY TABLES TESTS FOR GOODNESS-OF-FIT TEST FOR INDEPENDENCE—SINGLE STRATUM TEST FOR INDEPENDENCE—MULTIPLE STRATA TEST FOR CATEGORICAL SHIFT CARRY-OVER E?ECT TEST COMPARING TIME-TO-EVENT DATA BASIC CONCEPTS EXPONENTIAL MODEL COX’S PROPORTIONAL HAZARDS MODEL WEIGHTED LOG-RANK TEST GROUP SEQUENTIAL METHODS POCOCK’S TEST O’BRIEN AND FLEMING’S TEST WANG AND TSIATIS’ TEST INNER WEDGE TEST BINARY VARIABLES TIME-TO-EVENT DATA ALPHA SPENDING FUNCTION SAMPLE SIZE RE-ESTIMATION CONDITIONAL POWER 8 10 PRACTICAL ISSUES COMPARING VARIABILITIES COMPARING INTRA-SUBJECT VARIABILITIES COMPARING INTRA-SUBJECT CVS COMPARING INTER-SUBJECT VARIABILITIES COMPARING TOTAL VARIABILITIES 10 BIOEQUIVALENCE TESTING 10 1 BIOEQUIVALENCE CRITERIA 10 2 AVERAGE BIOEQUIVALENCE 10 3 POPULATION BIOEQUIVALENCE 10 4 INDIVIDUAL BIOEQUIVALENCE 10 5 IN VITRO BIOEQUIVALENCE 11 DOSE RESPONSE STUDIES 11 1 CONTINUOUS RESPONSE 11 2 BINARY RESPONSE 11 3 TIME-TO-EVENT ENDPOINT 11 4 WILLIAMS’ TEST FOR MINIMUM E?ECTIVE DOSE (MED) 11 5 COCHRAN-ARMITAGE’S TEST FOR TREND 11 6 DOSE ESCALATION TRIALS 11 7 CONCLUDING REMARKS 12 MICROARRAY STUDIES 12 1 LITERATURE REVIEW 12 2 FALSE DISCOVERY RATE (FDR) CONTROL 12 3 FAMILY-WISE ERROR RATE (FWER) CONTROL 12 4 CONCLUDING REMARKS 13 BAYESIAN SAMPLE SIZE CALCULATION 13 1 POSTERIOR CREDIBLE INTERVAL APPROACH 13 2 POSTERIOR ERROR APPROACH 13 3 THE BOOTSTRAP-MEDIAN APPROACH 13 4 CONCLUDING REMARKS 14 NONPARAMETRICS 14 1 VIOLATION OF ASSUMPTIONS 14 2 ONE-SAMPLE LOCATION PROBLEM 14 3 TWO-SAMPLE LOCATION PROBLEM 14 4 TEST FOR INDEPENDENCE 14 5 PRACTICAL ISSUES 15 SAMPLE SIZE CALCULATION IN OTHER AREAS 15 1 QT/QTC STUDIES WITH TIME-DEPENDENT REPLICATES 15 2 PROPENSITY ANALYSIS IN NON-RANDOMIZED STUDIES 15 3 ANOVA WITH REPEATED MEASURES 15 4 QUALITY OF LIFE 15 5 BRIDGING STUDIES 15 6 VACCINE CLINICAL TRIALS