Description

Book Synopsis

Biostatistics Decoded covered a large number of statistical methods that are mainly applied to clinical and epidemiological research, as well as a comprehensive discussion of study designs for observational research and clinical trials,two important concerns for the clinical researcher.

In this second edition, new material is included covering statistical methods and study designs that are used to analyse research. Following the same methodology used in the first edition, the chapters are presented in two levels of detail, one for the reader who wishes only to understand the rationale behind each statistical method, and one for the reader who wishes to understand the computations

Key features include:

  • Extensive coverage of the design and analysis of experiments for basic science research
  • Experimental designs are presented together with the statistical methods
  • The rationale of all forms of ANOVA is explained with simple mathematics<

    Table of Contents

    Preface xi

    1 Populations and Samples 1

    1.1 The Object of Biostatistics 1

    1.2 Scales of Measurement 3

    1.3 Central Tendency Measures 5

    1.4 Sampling 8

    1.5 Inferences from Samples 11

    1.6 Measures of Location and Dispersion 14

    1.7 The Standard Deviation 15

    1.8 The n − 1 Divisor 16

    1.9 Degrees of Freedom 18

    1.10 Variance of Binary Variables 19

    1.11 Properties of Means and Variances 20

    1.12 Descriptive Statistics 22

    1.13 Sampling Variation 25

    1.14 The Normal Distribution 27

    1.15 The Central Limit Theorem 29

    1.16 Properties of the Normal Distribution 30

    1.17 Probability Distribution of Sample Means 32

    1.18 The Standard Error of the Mean 33

    1.19 The Value of the Standard Error 35

    1.20 Distribution of Sample Proportions 37

    1.21 Convergence of Binomial to Normal Distribution 39

    2 Descriptive Studies 41

    2.1 Designing a Research 41

    2.2 Study Design 42

    2.3 Classification of Descriptive Studies 44

    2.4 Cross-sectional Studies 45

    2.5 Inferences from Means 47

    2.6 Confidence Intervals 48

    2.7 Statistical Tables 49

    2.8 The Case of Small Samples 51

    2.9 Student’s t Distribution 54

    2.10 Statistical Tables of the t Distribution 56

    2.11 Inferences from Proportions 58

    2.12 Statistical Tables of the Binomial Distribution 60

    2.13 Sample Size Requirements 61

    2.14 Longitudinal Studies 63

    2.15 Incidence Studies 65

    2.16 Cohort Studies 66

    2.17 Inference from Incidence Studies 70

    2.18 Standardization 72

    2.19 Time-to-Event Cohort Studies 75

    2.20 The Actuarial Method 76

    2.21 The Kaplan–Meier Method 79

    2.22 Probability Sampling 82

    2.23 Simple Random Sampling 84

    2.24 Replacement in Sampling 85

    2.25 Stratified Sampling 87

    2.26 Multistage Sampling 92

    3 Analytical Studies 97

    3.1 Objectives of Analytical Studies 97

    3.2 Measures of Association 98

    3.3 Odds, Logits, and Odds Ratios 99

    3.4 Attributable Risk 101

    3.5 Classification of Analytical Studies 103

    3.6 Uncontrolled Analytical Studies 104

    3.7 Comparative Analytical Studies 105

    3.8 Hybrid Analytical Studies 109

    3.9 Non-probability Sampling in Analytical Studies 111

    3.10 Comparison of Two Means 111

    3.11 Comparison of Two Means from Small Samples 114

    3.12 Comparison of Two Proportions 116

    4 Statistical Tests 121

    4.1 The Null and Alternative Hypotheses 121

    4.2 The z-Test 122

    4.3 The p-Value 125

    4.4 Student’s t-Test 126

    4.5 The Binomial Test 128

    4.6 The Chi-Square Test 130

    4.7 The Table of the Chi-Square Distribution 134

    4.8 Analysis of Variance 135

    4.9 Partitioning the Sum of Squares 139

    4.10 Statistical Tables of the F Distribution 142

    4.11 The ANOVA Table 143

    5 Aspects of Statistical Tests 145

    5.1 One-Sided Tests 145

    5.2 Power of a Statistical Test 149

    5.3 Sample Size Estimation 150

    5.4 Multiple Comparisons 153

    5.5 Scale Transformation 155

    5.6 Non-parametric Tests 156

    6 Cross-sectional Studies 161

    6.1 Linear Regression 161

    6.2 The Least Squares Method 163

    6.3 Linear Regression Estimates 166

    6.4 Regression and Correlation 171

    6.5 The F-Test in Linear Regression 173

    6.6 Interpretation of Regression Analysis Results 176

    6.7 Multiple Regression 177

    6.8 Regression Diagnostics 180

    6.9 Selection of Predictor Variables 184

    6.10 Independent Nominal Variables 185

    6.11 Interaction 188

    6.12 Nonlinear Regression 190

    7 Case–Control Studies 193

    7.1 Analysis of Case–Control Studies 193

    7.2 Logistic Regression 194

    7.3 The Method of Maximum Likelihood 196

    7.4 Estimation of the Logistic Regression Model 198

    7.5 The Likelihood Ratio Test 201

    7.6 Interpreting the Results of Logistic Regression 202

    7.7 Regression Coefficients and Odds Ratios 203

    7.8 Applications of Logistic Regression 204

    7.9 The ROC Curve 205

    7.10 Model Validation 208

    8 Cohort Studies 213

    8.1 Repeated Measurements 213

    8.2 The Paired t-Test 213

    8.3 McNemar’s Test 215

    8.4 Generalized Linear Models 216

    8.5 The Logrank Test 219

    8.6 The Adjusted Logrank Test 222

    8.7 The Incidence Rate Ratio 224

    8.8 The Cox Proportional Hazards Model 225

    8.9 Assumptions of the Cox Model 229

    8.10 Interpretation of Cox Regression 230

    9 Measurement 233

    9.1 Construction of Clinical Questionnaires 233

    9.2 Factor Analysis 234

    9.3 Interpretation of Factor Analysis 237

    9.4 Factor Rotation 239

    9.5 Factor Scores 241

    9.6 Reliability 242

    9.7 Concordance 248

    9.8 Validity 253

    9.9 Validation of Diagnostic Tests 255

    10 Experimental Studies 257

    10.1 Main Design Features and Classification 257

    10.2 Experimental Controls 260

    10.3 Replicates 261

    10.4 Classification of Experimental Designs 262

    10.5 Completely Randomized Design 263

    10.6 Interaction 268

    10.7 Full Factorial Design 269

    10.8 The Random Effects Model 274

    10.9 Components of Variance 275

    10.10 ANOVA Model II and Model III 278

    10.11 Rules for the Definition of the Error Terms 282

    10.12 ANOVA on Ranks 284

    11 Blocking 285

    11.1 Randomized Block Design 285

    11.2 Generalized Randomized Block Design 288

    11.3 Incomplete Block Design 291

    11.4 Factorial Design with Randomized Blocks 292

    11.5 Latin and Greco-Latin Square Design 293

    12 Simultaneous Inference 297

    12.1 Multiple Comparisons 297

    12.2 Generalist Methods 298

    12.3 Multiple Comparisons of Group Means 303

    12.4 Pairwise Comparison of Means 304

    12.5 Different Variances 312

    12.6 Comparison to a Control 313

    12.7 Comparison of post hoc Tests 315

    12.8 Complex Comparisons 316

    12.9 Tests of Multiple Contrasts 320

    12.10 A posteriori Contrasts 324

    12.11 The Size of an Experiment 326

    13 Factorial ANOVA 329

    13.1 The n-Way ANOVA 329

    13.2 The 2k Factorial Design 331

    13.3 The 2k Factorial Design with Blocking 335

    13.4 The Fractional Factorial Design 337

    14 Nested Designs 339

    14.1 Split–Plot Design 339

    14.2 Nested (Hierarchical) Design 343

    14.3 Mixed Model Nested ANOVA 345

    14.4 Mixed Model Nested ANOVA with Three Sublevels 349

    14.5 Pure Model II Nested ANOVA 352

    15 Repeated Measures 355

    15.1 Repeated Measures ANOVA 355

    15.2 Repeated Measures ANOVA with Two Factors 359

    15.3 ANOVA with Several Repeated Measures 361

    15.4 Multivariate Tests 362

    16 Clinical Trials 363

    16.1 Classification of Clinical Trials 363

    16.2 The Clinical Trial Population 365

    16.3 The Efficacy Criteria 366

    16.4 Controlled Clinical Trials 367

    16.5 The Control Group 369

    16.6 Blinding 370

    16.7 Randomization 371

    16.8 Non-comparative Clinical Trials 375

    16.9 Regression Toward the Mean 378

    16.10 Non-randomized Controlled Clinical Trials 379

    16.11 Classical Randomized Clinical Trial Designs 381

    16.12 Alternative Clinical Trial Designs 385

    16.13 Pragmatic Clinical Trials 387

    16.14 Cluster Randomized Trials 389

    16.15 The Size of a Clinical Trial 393

    16.16 Non-inferiority Clinical Trials 398

    16.17 Adaptive Clinical Trials 403

    16.18 Group Sequential Plans 405

    16.19 The Alpha Spending Function 407

    16.20 The Clinical Trial Protocol 409

    16.21 The Data Record 411

    17 Analysis of Clinical Trials 413

    17.1 General Analysis Plan 413

    17.2 Data Preparation 414

    17.3 Study Populations 415

    17.4 Primary Efficacy Analysis 418

    17.5 Analysis of Multiple Endpoints 420

    17.6 Secondary Analyses 423

    17.7 Safety Analysis 424

    18 Meta-analysis 427

    18.1 Purpose of Meta-analysis 427

    18.2 Measures of Effect 428

    18.3 The Inverse Variance Method 429

    18.4 The Random Effects Model 435

    18.5 Heterogeneity 439

    18.6 Publication Bias 442

    18.7 The Forest Plot 444

    References 447

    Index 455

Biostatistics Decoded

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    A Hardback by A. Gouveia Oliveira

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      Publisher: John Wiley & Sons Inc
      Publication Date: 08/10/2020
      ISBN13: 9781119584209, 978-1119584209
      ISBN10: 1119584205

      Description

      Book Synopsis

      Biostatistics Decoded covered a large number of statistical methods that are mainly applied to clinical and epidemiological research, as well as a comprehensive discussion of study designs for observational research and clinical trials,two important concerns for the clinical researcher.

      In this second edition, new material is included covering statistical methods and study designs that are used to analyse research. Following the same methodology used in the first edition, the chapters are presented in two levels of detail, one for the reader who wishes only to understand the rationale behind each statistical method, and one for the reader who wishes to understand the computations

      Key features include:

      • Extensive coverage of the design and analysis of experiments for basic science research
      • Experimental designs are presented together with the statistical methods
      • The rationale of all forms of ANOVA is explained with simple mathematics<

        Table of Contents

        Preface xi

        1 Populations and Samples 1

        1.1 The Object of Biostatistics 1

        1.2 Scales of Measurement 3

        1.3 Central Tendency Measures 5

        1.4 Sampling 8

        1.5 Inferences from Samples 11

        1.6 Measures of Location and Dispersion 14

        1.7 The Standard Deviation 15

        1.8 The n − 1 Divisor 16

        1.9 Degrees of Freedom 18

        1.10 Variance of Binary Variables 19

        1.11 Properties of Means and Variances 20

        1.12 Descriptive Statistics 22

        1.13 Sampling Variation 25

        1.14 The Normal Distribution 27

        1.15 The Central Limit Theorem 29

        1.16 Properties of the Normal Distribution 30

        1.17 Probability Distribution of Sample Means 32

        1.18 The Standard Error of the Mean 33

        1.19 The Value of the Standard Error 35

        1.20 Distribution of Sample Proportions 37

        1.21 Convergence of Binomial to Normal Distribution 39

        2 Descriptive Studies 41

        2.1 Designing a Research 41

        2.2 Study Design 42

        2.3 Classification of Descriptive Studies 44

        2.4 Cross-sectional Studies 45

        2.5 Inferences from Means 47

        2.6 Confidence Intervals 48

        2.7 Statistical Tables 49

        2.8 The Case of Small Samples 51

        2.9 Student’s t Distribution 54

        2.10 Statistical Tables of the t Distribution 56

        2.11 Inferences from Proportions 58

        2.12 Statistical Tables of the Binomial Distribution 60

        2.13 Sample Size Requirements 61

        2.14 Longitudinal Studies 63

        2.15 Incidence Studies 65

        2.16 Cohort Studies 66

        2.17 Inference from Incidence Studies 70

        2.18 Standardization 72

        2.19 Time-to-Event Cohort Studies 75

        2.20 The Actuarial Method 76

        2.21 The Kaplan–Meier Method 79

        2.22 Probability Sampling 82

        2.23 Simple Random Sampling 84

        2.24 Replacement in Sampling 85

        2.25 Stratified Sampling 87

        2.26 Multistage Sampling 92

        3 Analytical Studies 97

        3.1 Objectives of Analytical Studies 97

        3.2 Measures of Association 98

        3.3 Odds, Logits, and Odds Ratios 99

        3.4 Attributable Risk 101

        3.5 Classification of Analytical Studies 103

        3.6 Uncontrolled Analytical Studies 104

        3.7 Comparative Analytical Studies 105

        3.8 Hybrid Analytical Studies 109

        3.9 Non-probability Sampling in Analytical Studies 111

        3.10 Comparison of Two Means 111

        3.11 Comparison of Two Means from Small Samples 114

        3.12 Comparison of Two Proportions 116

        4 Statistical Tests 121

        4.1 The Null and Alternative Hypotheses 121

        4.2 The z-Test 122

        4.3 The p-Value 125

        4.4 Student’s t-Test 126

        4.5 The Binomial Test 128

        4.6 The Chi-Square Test 130

        4.7 The Table of the Chi-Square Distribution 134

        4.8 Analysis of Variance 135

        4.9 Partitioning the Sum of Squares 139

        4.10 Statistical Tables of the F Distribution 142

        4.11 The ANOVA Table 143

        5 Aspects of Statistical Tests 145

        5.1 One-Sided Tests 145

        5.2 Power of a Statistical Test 149

        5.3 Sample Size Estimation 150

        5.4 Multiple Comparisons 153

        5.5 Scale Transformation 155

        5.6 Non-parametric Tests 156

        6 Cross-sectional Studies 161

        6.1 Linear Regression 161

        6.2 The Least Squares Method 163

        6.3 Linear Regression Estimates 166

        6.4 Regression and Correlation 171

        6.5 The F-Test in Linear Regression 173

        6.6 Interpretation of Regression Analysis Results 176

        6.7 Multiple Regression 177

        6.8 Regression Diagnostics 180

        6.9 Selection of Predictor Variables 184

        6.10 Independent Nominal Variables 185

        6.11 Interaction 188

        6.12 Nonlinear Regression 190

        7 Case–Control Studies 193

        7.1 Analysis of Case–Control Studies 193

        7.2 Logistic Regression 194

        7.3 The Method of Maximum Likelihood 196

        7.4 Estimation of the Logistic Regression Model 198

        7.5 The Likelihood Ratio Test 201

        7.6 Interpreting the Results of Logistic Regression 202

        7.7 Regression Coefficients and Odds Ratios 203

        7.8 Applications of Logistic Regression 204

        7.9 The ROC Curve 205

        7.10 Model Validation 208

        8 Cohort Studies 213

        8.1 Repeated Measurements 213

        8.2 The Paired t-Test 213

        8.3 McNemar’s Test 215

        8.4 Generalized Linear Models 216

        8.5 The Logrank Test 219

        8.6 The Adjusted Logrank Test 222

        8.7 The Incidence Rate Ratio 224

        8.8 The Cox Proportional Hazards Model 225

        8.9 Assumptions of the Cox Model 229

        8.10 Interpretation of Cox Regression 230

        9 Measurement 233

        9.1 Construction of Clinical Questionnaires 233

        9.2 Factor Analysis 234

        9.3 Interpretation of Factor Analysis 237

        9.4 Factor Rotation 239

        9.5 Factor Scores 241

        9.6 Reliability 242

        9.7 Concordance 248

        9.8 Validity 253

        9.9 Validation of Diagnostic Tests 255

        10 Experimental Studies 257

        10.1 Main Design Features and Classification 257

        10.2 Experimental Controls 260

        10.3 Replicates 261

        10.4 Classification of Experimental Designs 262

        10.5 Completely Randomized Design 263

        10.6 Interaction 268

        10.7 Full Factorial Design 269

        10.8 The Random Effects Model 274

        10.9 Components of Variance 275

        10.10 ANOVA Model II and Model III 278

        10.11 Rules for the Definition of the Error Terms 282

        10.12 ANOVA on Ranks 284

        11 Blocking 285

        11.1 Randomized Block Design 285

        11.2 Generalized Randomized Block Design 288

        11.3 Incomplete Block Design 291

        11.4 Factorial Design with Randomized Blocks 292

        11.5 Latin and Greco-Latin Square Design 293

        12 Simultaneous Inference 297

        12.1 Multiple Comparisons 297

        12.2 Generalist Methods 298

        12.3 Multiple Comparisons of Group Means 303

        12.4 Pairwise Comparison of Means 304

        12.5 Different Variances 312

        12.6 Comparison to a Control 313

        12.7 Comparison of post hoc Tests 315

        12.8 Complex Comparisons 316

        12.9 Tests of Multiple Contrasts 320

        12.10 A posteriori Contrasts 324

        12.11 The Size of an Experiment 326

        13 Factorial ANOVA 329

        13.1 The n-Way ANOVA 329

        13.2 The 2k Factorial Design 331

        13.3 The 2k Factorial Design with Blocking 335

        13.4 The Fractional Factorial Design 337

        14 Nested Designs 339

        14.1 Split–Plot Design 339

        14.2 Nested (Hierarchical) Design 343

        14.3 Mixed Model Nested ANOVA 345

        14.4 Mixed Model Nested ANOVA with Three Sublevels 349

        14.5 Pure Model II Nested ANOVA 352

        15 Repeated Measures 355

        15.1 Repeated Measures ANOVA 355

        15.2 Repeated Measures ANOVA with Two Factors 359

        15.3 ANOVA with Several Repeated Measures 361

        15.4 Multivariate Tests 362

        16 Clinical Trials 363

        16.1 Classification of Clinical Trials 363

        16.2 The Clinical Trial Population 365

        16.3 The Efficacy Criteria 366

        16.4 Controlled Clinical Trials 367

        16.5 The Control Group 369

        16.6 Blinding 370

        16.7 Randomization 371

        16.8 Non-comparative Clinical Trials 375

        16.9 Regression Toward the Mean 378

        16.10 Non-randomized Controlled Clinical Trials 379

        16.11 Classical Randomized Clinical Trial Designs 381

        16.12 Alternative Clinical Trial Designs 385

        16.13 Pragmatic Clinical Trials 387

        16.14 Cluster Randomized Trials 389

        16.15 The Size of a Clinical Trial 393

        16.16 Non-inferiority Clinical Trials 398

        16.17 Adaptive Clinical Trials 403

        16.18 Group Sequential Plans 405

        16.19 The Alpha Spending Function 407

        16.20 The Clinical Trial Protocol 409

        16.21 The Data Record 411

        17 Analysis of Clinical Trials 413

        17.1 General Analysis Plan 413

        17.2 Data Preparation 414

        17.3 Study Populations 415

        17.4 Primary Efficacy Analysis 418

        17.5 Analysis of Multiple Endpoints 420

        17.6 Secondary Analyses 423

        17.7 Safety Analysis 424

        18 Meta-analysis 427

        18.1 Purpose of Meta-analysis 427

        18.2 Measures of Effect 428

        18.3 The Inverse Variance Method 429

        18.4 The Random Effects Model 435

        18.5 Heterogeneity 439

        18.6 Publication Bias 442

        18.7 The Forest Plot 444

        References 447

        Index 455

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