{"text_format":"2","workbook":"xls","n_sheets":1,"sheets":["report2"],"not_rendered":{"charts":0,"images":0,"macros":0,"external_links":1,"defined_names":1,"comments":0,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"run_cost":"one","rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900","formulas":"cached_only"}

{"sheet":"report2","index":0,"n_rows":32,"n_cols":5,"rows_kept":32,"cut":false,"hidden":false,"merged":[[0,2,0,3],[0,4,0,5],[1,2,1,3],[1,4,1,5],[2,2,2,3],[2,4,2,5],[3,2,3,3],[4,2,4,3],[12,2,12,3],[13,2,13,3],[14,2,14,3],[15,2,15,3],[18,2,18,3],[19,2,19,3],[22,2,22,3]],"flags":["formulas_cached_only"]}
[null,"1.","Record Nr.",null,"UNINA9910822202603321"]
[null,null,"Autore",null,"Chow Shein-Chung <1955->"]
[null,null,"Titolo",null,"Design and analysis of clinical trials : concepts and methodologies / / Shein-Chung Chow, Jen-pei Liu"]
[null,null,"Pubbl/distr/stampa",null,"Hoboken, New Jersey, : Wiley, [2014]"]
[null,null,"ISBN",null,"9781118458099"]
[{"$nulls":4},"1118458095"]
[{"$nulls":4},"9781118458167"]
[{"$nulls":4},"1118458168"]
[{"$nulls":4},"9781118458143"]
[{"$nulls":4},"1118458141"]
[{"$nulls":4},"9781118458136"]
[{"$nulls":4},"1118458133"]
[null,null,"Edizione",null,"[3rd ed.]"]
[null,null,"Descrizione fisica",null,"1 recurso en línea (893 páginas)"]
[null,null,"Collana",null,"Wiley series in probability and statistics"]
[null,null,"Soggetti",null,"Biometría"]
[{"$nulls":4},"Estudios clínicos - Métodos estadísticos"]
[{"$nulls":4},"Estudios clínicos - Métodología"]
[null,null,"Lingua di pubblicazione",null,"Inglese"]
[null,null,"Formato",null,"Materiale a stampa"]
[null,null,null,"Livello bibliografico","Monografia"]
[null,null,null,"Nota di bibliografia","Índice. Bibliografía"]
[null,null,"Nota di contenuto",null,"Intro -- Design and Analysis of Clinical Trials -- Contents -- Preface -- PART I Preliminaries -- CHAPTER 1 Introduction -- 1.1 WHAT ARE CLINICAL TRIALS? -- 1.2 HISTORY OF CLINICAL TRIALS -- 1.3 REGULATORY PROCESS AND REQUIREMENTS -- 1.3.1 The Food and Drug Administration -- 1.3.2 FDA Regulations for Clinical Trials -- 1.3.3 Phases of Clinical Development -- 1.4 INVESTIGATIONAL NEW DRUG APPLICATION -- 1.4.1 Clinical Trial Protocol -- 1.4.2 Institutional Review Board -- 1.4.3 Safety Report -- 1.4.4 Treatment IND -- 1.4.5 Withdrawal and Termination of an IND -- 1.4.6 Communication with the FDA -- 1.5 NEW DRUG APPLICATION -- 1.5.1 Expanded Access -- 1.5.2 Abbreviated New Drug Application -- 1.5.3 Supplemental New Drug Application -- 1.5.4 Advisory Committee -- 1.6 CLINICAL DEVELOPMENT AND PRACTICE -- 1.6.1 Clinical Development Plan -- 1.6.2 Good Clinical Practice -- 1.7 AIMS AND STRUCTURE OF THE BOOK -- CHAPTER 2 Basic Statistical Concepts -- 2.1 INTRODUCTION -- 2.2 UNCERTAINTY AND PROBABILITY -- 2.2.1 Uncertainty -- 2.2.2 "]
[{"$nulls":4},"Probability -- 2.3 BIAS AND VARIABILITY -- 2.3.1 Bias -- 2.3.2 Variability -- 2.4 CONFOUNDING AND INTERACTION -- 2.4.1 Confounding -- 2.4.2 Interaction -- 2.5 DESCRIPTIVE AND INFERENTIAL STATISTICS -- 2.6 HYPOTHESES TESTING AND p-VALUES -- 2.6.1 p-Values -- 2.6.2 One-Sided Versus Two-Sided Hypotheses -- 2.7 CLINICAL SIGNIFICANCE AND CLINICAL EQUIVALENCE -- 2.8 REPRODUCIBILITY AND GENERALIZABILITY -- 2.8.1 Reproducibility -- 2.8.2 Generalizability -- CHAPTER 3 Basic Design Considerations -- 3.1 INTRODUCTION -- 3.2 GOALS OF CLINICAL TRIALS -- 3.3 TARGET POPULATION AND PATIENT SELECTION -- 3.3.1 Eligibility Criteria -- 3.3.2 Patient Selection Process -- 3.3.3 Ethical Considerations -- 3.4 SELECTION OF CONTROLS -- 3.4.1 Placebo Concurrent Control -- 3.4.2 Dose-Response Concurrent Control -- 3.4.3 Active (Positive) Concurrent Control."]
[{"$nulls":4},"3.4.4 No Treatment Concurrent Control -- 3.4.5 Historical Control -- 3.5 STATISTICAL CONSIDERATIONS -- 3.5.1 Efficacy and Safety Assessment -- 3.5.2 Sample Size Estimation -- 3.5.3 Interim Analysis and Data Monitoring -- 3.5.4 Statistical and Clinical Inference -- 3.6 OTHER ISSUES -- 3.6.1 Single Site Versus Multisites -- 3.6.2 Treatment Duration -- 3.6.3 Patient Compliance -- 3.6.4 Missing Value and Dropout -- 3.7 DISCUSSION -- CHAPTER 4 Randomization and Blinding -- 4.1 INTRODUCTION -- 4.2 RANDOMIZATION MODELS -- 4.2.1 Population Model -- 4.2.2 Invoked Population Model -- 4.2.3 Randomization Model -- 4.2.4 Stratification -- 4.3 RANDOMIZATION METHODS -- 4.3.1 Complete Randomization -- 4.3.2 Permuted-Block Randomization -- 4.3.3 Adaptive Randomization -- 4.4 IMPLEMENTATION OF RANDOMIZATION -- 4.4.1 Generation, Labeling, and Packaging -- 4.4.2 Random Assignment -- 4.5 GENERALIZATION OF CONTROLLED RANDOMIZED TRIALS -- 4.6 BLINDING -- 4.7 DISCUSSION -- PART II Designs and Their Classifications -- CHAPTER 5 Designs for Clinical Trials -- 5.1 INTRODUCTION -- 5.2 PARALLEL GROUP DESIGNS -- 5.2.1 Run-in Periods -- 5.2.2 Examples of Parallel Group Design in Clinical Trials -- 5.3 CLUSTERED RANDOMIZED DESIGNS -- 5.4 CROSSOVER DESIGNS -- 5.4.1 Higher-Order Crossover Designs -- 5.4.2 Williams Designs -- 5.4.3 Balanced Incomplete Block Design -- 5.4.4 Examples of Crossover Design in Clinical Trials -- 5.5 TITRATION DESIGNS -- 5.5.1 Standard Titration Design -- 5.5.2 Forced Dose-Escalation Design -- 5.6 ENRICHMENT DESIGNS -- 5.7 GROUP SEQUENTIAL DESIGNS -- 5.8 PLACEBO-CHALLENGING DESIGNS -- 5.8.1 Statistical Model and Inferences -- 5.9 BLINDED READER DESIGNS -- 5.10 DISCUSSION -- CHAPTER 6 Designs for Cancer Clinical Trials -- 6.1 INTRODUCTION -- 6.2 GENERAL CONSIDERATIONS FOR PHASE ICANCER CLINICAL TRIALS -- 6.3 SINGLE-STAGE UP-AND-DOWN PHASE I DESIGNS."]
[{"$nulls":4},"6.3.1 Design A-Standard Dose-Escalation Design -- 6.3.2 Design B -- 6.3.3 Design D -- 6.4 TWO-STAGE UP-AND-DOWN PHASE I DESIGNS -- 6.4.1 Design BD -- 6.4.2 Accelerated Titration Designs -- 6.5 CONTINUAL REASSESSMENT METHOD PHASE I DESIGNS -- 6.6 OPTIMAL AND FLEXIBLE MULTIPLE-STAGE DESIGNS -- 6.6.1 Single-Arm Trials -- 6.6.2 Multiple-Arm Trials -- 6.7 RANDOMIZED PHASE II DESIGNS -- 6.8 DISCUSSION -- CHAPTER 7 Classification of Clinical Trials -- 7.1 INTRODUCTION -- 7.2 MULTICENTER TRIALS -- 7.2.1 Treatment-by-Center Interaction -- 7.2.2 Practical Issues -- 7.3 SUPERIORITY TRIALS -- 7.4 ACTIVE CONTROL AND EQUIVALENCE/NONINFERIORITY TRIALS -- 7.4.1 Primary Objectives -- 7.4.2 Issues in Active Control Equivalence Trials -- 7.4.3 Interpretation of the Results of Active Control Trials -- 7.4.4 Equivalence/Noninferiority Limits -- 7.4.5 Statistical Methods -- 7.5 DOSE-RESPONSE TRIALS -- 7.5.1 "]
[{"$nulls":4},"Randomized Parallel Dose-Response Designs -- 7.5.2 Crossover Dose-Response Design -- 7.5.3 Forced Titration (Dose-Escalation) Design -- 7.5.4 Optional Titration Design (Placebo-Controlled Titration to Endpoint) -- 7.6 COMBINATION TRIALS -- 7.6.1 Fixed-Combination Prescription Drugs -- 7.6.2 Multilevel Factorial Design -- 7.6.3 Global Superiority of Combination Drugs -- 7.6.4 Method of Response Surface -- 7.7 BRIDGING STUDIES AND GLOBAL TRIALS -- 7.7.1 Introduction -- 7.7.2 Ethnic Sensitivity and Necessity of Bridging Studies -- 7.7.3 Types of Bridging Studies -- 7.7.4 Assessment of Similarity Based on Bridging Evidence -- 7.8 VACCINE CLINICAL TRIALS -- 7.8.1 Basic Design and Statistical Considerations -- 7.8.2 Types of Vaccine Immunogenicity Trials -- 7.8.3 Statistical Methods -- 7.9 QT STUDIES -- 7.9.1 Study Designs and Models -- 7.9.2 Power and Sample Size Calculation -- 7.9.3 Allocation Optimization -- 7.9.4 Remarks -- 7.10 DISCUSSION."]
[{"$nulls":4},"PART III Analysis of Clinical Data -- CHAPTER 8 Analysis of Continuous Data -- 8.1 INTRODUCTION -- 8.2 ESTIMATION -- 8.3 TEST STATISTICS -- 8.3.1 Paired t Test -- 8.3.2 Two-Sample t Test -- 8.4 ANALYSIS OF VARIANCE -- 8.4.1 One-Way Classification -- 8.4.2 Simultaneous Confidence Intervals -- 8.4.3 Two-Way Classification -- 8.5 ANALYSIS OF COVARIANCE -- 8.6 NONPARAMETRIC METHODS -- 8.6.1 Wilcoxon Signed Rank Test -- 8.6.2 Wilcoxon Rank Sum Test -- 8.6.3 Kruskal-Wallis Test -- 8.7 REPEATED MEASURES -- 8.7.1 Assessment of Overall Average Effect Across Time -- 8.7.2 Detection of Time Effect -- 8.7.3 Treatment-by-Time Interaction -- 8.7.4 Method of Generalized Estimating Equations (GEEs) -- 8.8 DISCUSSION -- CHAPTER 9 Analysis of Categorical Data -- 9.1 INTRODUCTION -- 9.2 STATISTICAL INFERENCE FOR ONE SAMPLE -- 9.3 INFERENCE OF INDEPENDENT SAMPLES -- 9.4 ORDERED CATEGORICAL DATA -- 9.5 COMBINING CATEGORICAL DATA -- 9.6 MODEL-BASED METHODS -- 9.7 REPEATED CATEGORICAL DATA -- 9.8 DISCUSSION -- CHAPTER 10 Censored Data and Interim Analysis -- 10.1 INTRODUCTION -- 10.2 ESTIMATION OF THE SURVIVAL FUNCTION -- 10.3 COMPARISON BETWEEN SURVIVAL FUNCTIONS -- 10.4 COX'S PROPORTIONAL HAZARD MODEL -- 10.5 CALENDAR TIME AND INFORMATION TIME -- 10.6 GROUP SEQUENTIAL METHODS -- 10.7 DISCUSSION -- CHAPTER 11 Sample Size Determination -- 11.1 INTRODUCTION -- 11.2 BASIC CONCEPT -- 11.2.1 Study Objectives and Hypotheses -- 11.2.2 Type I and Type II Errors -- 11.2.3 Precision Analysis -- 11.2.4 Power Analysis -- 11.3 TWO SAMPLES -- 11.3.1 One-Sample Test for Mean -- 11.3.2 Two-Sample Test for Comparing Means -- 11.4 MULTIPLE SAMPLES -- 11.4.1 Sample Size Calculations for Analysis of Variance Models -- 11.4.2 Sample Size Calculations for Generalized Linear Models -- 11.5 CENSORED DATA -- 11.6 DOSE-RESPONSE STUDIES -- 11.6.1 Dose-Response Relationship."]
[{"$nulls":4},"11.6.2 Minimum Effective Dose -- 11.7 CROSSOVER DESIGNS -- 11.7.1 Point Hypotheses for Equality -- 11.7.2 Interval Hypotheses for Equivalence -- 11.7.3 Higher-Order Crossover Designs -- 11.8 EQUIVALENCE AND NONINFERIORITY TRIALS -- 11.8.1 Independent Binary Endpoints -- 11.8.2 Paired Binary Endpoints -- 11.8.3 Independent Censored Endpoints -- 11.9 MULTIPLE-STAGE DESIGN IN CANCER TRIALS -- 11.10 MULTINATIONAL TRIALS -- 11.10.1 Selection of the Number of Sites -- 11.10.2 Sample Size Calculation and Allocation -- 11.11 COMPARING VARIABILITIES -- 11.11.1 Comparing Intrasubject Variabilities -- 11.11.2 Comparing Intersubject Variabilities -- 11.12 DISCUSSION -- PART IV Issues in Evaluation -- CHAPTER 12 Issues in Efficacy Evaluation -- 12.1 INTRODUCTION -- 12.2 BASELINE COMPARISON -- 12.3 INTENTION-TO-TREAT PRINCIPLE "]
[{"$nulls":4},"AND EFFICACY ANALYSIS -- 12.4 ADJUSTMENT FOR COVARIATES -- 12.5 MULTICENTER TRIALS -- 12.6 MULTIPLICITY -- 12.6.1 Multiple Comparisons -- 12.6.2 Multiple Endpoints -- 12.6.3 Subgroup Analysis -- 12.7 DATA MONITORING -- 12.7.1 Definition and Objectives -- 12.7.2 Regulatory Concerns -- 12.7.3 Early and Late Stages of Drug Development -- 12.7.4 Administrative Interim Analyses -- 12.7.5 Data Monitoring Committee -- 12.8 USE OF GENETIC INFORMATION FOR EVALUATION OF EFFICACY -- 12.9 SAMPLE SIZE REESTIMATION -- 12.10 DISCUSSION -- CHAPTER 13 Safety Assessment -- 13.1 INTRODUCTION -- 13.2 EXTENT OF EXPOSURE -- 13.2.1 Risk of Exposure -- 13.2.2 Absorbing Events -- 13.2.3 Recurring Events with Negligible Duration -- 13.2.4 Recurring Events with Nonnegligible Duration -- 13.2.5 Laboratory Data -- 13.3 CODING OF ADVERSE EVENTS -- 13.3.1 Definitions of Adverse Events -- 13.3.2 COSTART -- 13.3.3 MedDRA -- 13.3.4 Common Toxicity Criteria -- 13.4 ANALYSIS OF ADVERSE EVENTS -- 13.4.1 Adverse Event Data Listing -- 13.4.2 Summary Tables of Adverse Events."]
[{"$nulls":4},"13.4.3 Graphical Presentation."]
[null,null,null,"Sommario/riassunto","Praise for the Second Edition:   \"...a grand feast for biostatisticians. It stands ready to satisfy the appetite of any pharmaceutical scientist with a respectable statistical appetite.\" -Journal of Clinical Research Best Practices   The Third Edition of Design and Analysis of Clinical Trials provides complete, comprehensive, and expanded coverage of recent health treatments and interventions. Featuring a unified presentation, the book provides a well-balanced summary of current regulatory requirements and recently developed statistical methods as well as an overview of the various designs and analyses that are utilized at different stages of clinical research and development. Additional features of this Third Edition include:   • New chapters on biomarker development and target clinical trials, adaptive design, trials for evaluating diagnostic devices, statistical methods for translational medicine, and traditional Chinese medicine   • A balanced overview of current and emerging clinical issues as well as newly developed statistical methodologies   • Practical examples of clinical trials that demonstrate everyday applicability, with illustrations and examples to explain key concepts   • New sections on bridging studies and global trials, QT studies, multinational trials, comparative effectiveness trials, and the analysis of QT/QTc prolongation   • A complete and balanced presentation of clinical and scientific issues, statistical concepts, and methodologies for bridging clinical and statistical disciplines   • An update of each chapter that reflects changes in regulatory requirements for the drug review and approval process and recent developments in statistical design and methodology for clinical research and development   Design and Analysis of Clinical Trials, Third Edition continues to be an ideal clinical research reference for academic, pharmaceutical, medical, and regulatory scientists/researchers, statisticians, and graduate-level students."]