Biostatistics DecodedISBN: 9781119953371
346 pages
September 2013

Study design and statistical methodology are two important concerns for the clinical researcher. This book sets out to address both issues in a clear and concise manner. The presentation of statistical theory starts from basic concepts, such as the properties of means and variances, the properties of the Normal distribution and the Central Limit Theorem and leads to more advanced topics such as maximum likelihood estimation, inverse variance and stepwise regression as well as, timetoevent, and eventcount methods. Furthermore, this book explores sampling methods, study design and statistical methods and is organized according to the areas of application of each of the statistical methods and the corresponding study designs. Illustrations, working examples, computer simulations and geometrical approaches, rather than mathematical expressions and formulae, are used throughout the book to explain every statistical method.
Biostatisticians and researchers in the medical and pharmaceutical industry who need guidance on the design and analyis of medical research will find this book useful as well as graduate students of statistics and mathematics with an interest in biostatistics.
Biostatistics Decoded:
 Provides clear explanations of key statistical concepts with a firm emphasis on practical aspects of design and analysis of medical research.
 Features worked examples to illustrate each statistical method using computer simulations and geometrical approaches, rather than mathematical expressions and formulae.
 Explores the main types of clinical research studies, such as, descriptive, analytical and experimental studies.
 Addresses advanced modeling techniques such as interaction analysis and encoding by reference and polynomial regression.
Preface ix
1 Introduction 1
1.1 The object of biostatistics 1
1.2 Defining the population 4
1.3 Study design 4
1.4 Sampling 6
1.5 Inferences from samples 9
2 Basic concepts 15
2.1 Data reduction 15
2.2 Scales of measurement 15
2.3 Tabulations of data 18
2.4 Central tendency measures 19
2.5 Measures of dispersion 20
2.6 Compressing data 21
2.7 The standard deviation 23
2.8 The n1 divisor 24
2.9 Properties of means and variances 26
2.10 Common frequency distributions 28
2.11 The normal distribution 29
2.12 The central limit theorem 31
2.13 Properties of the normal distribution 31
2.14 Statistical tables 34
3 Statistical inference 37
3.1 Sampling distributions 37
3.2 The normal distribution of sample means 39
3.3 The standard error of the mean 40
3.4 The value of the standard error 42
3.5 Inferences from means 43
3.6 Confidence intervals 45
3.7 The case of small samples 46
3.8 Student’s t distribution 48
3.9 Statistical tables of the t distribution 51
3.10 Estimation with binary variables 53
3.11 The binomial distribution 54
3.12 Inferences from proportions 55
3.13 Statistical tables of the binomial distribution 58
3.14 Sample size requirements 59
4 Descriptive studies 63
4.1 Classification of descriptive studies 63
4.2 Probability sampling 64
4.3 Simple random sampling 66
4.4 Replacement in sampling 67
4.5 Stratified sampling 70
4.6 Multistage sampling 74
4.7 Prevalence studies 77
4.8 Incidence studies 78
4.9 The personyears method 80
4.10 Nonprobability sampling in descriptive studies 81
4.11 Standardization 82
5 Analytical studies 87
5.1 Design of analytical studies 87
5.2 Nonprobability sampling in analytical studies 91
5.3 The investigation of associations 92
5.4 Comparison of two means 93
5.5 Comparison of two means from small samples 96
5.6 Comparison of two proportions 98
5.7 Relative risks and odds ratios 100
5.8 Attributable risk 102
5.9 Logits and log odds ratios 104
6 Statistical tests 107
6.1 The null hypothesis 107
6.2 The ztest 108
6.3 The pvalue 111
6.4 Student’s ttest 112
6.5 The binomial test 115
6.6 The chisquare test 116
6.7 Degrees of freedom 121
6.8 The table of the chisquare distribution 122
6.9 Analysis of variance 123
6.10 Statistical tables of the F distribution 129
7 Issues with statistical tests 131
7.1 Onesided tests 131
7.2 Power of a statistical test 135
7.3 Sample size estimation 136
7.4 Multiple comparisons 139
7.5 Scale transformation 142
7.6 Nonparametric tests 143
8 Longitudinal studies 147
8.1 Repeated measurements 147
8.2 The paired Student’s ttest 147
8.3 McNemar’s test 150
8.4 Analysis of events 151
8.5 The actuarial method 151
8.6 The Kaplan–Meier method 155
8.7 The logrank test 159
8.8 The adjusted logrank test 161
8.9 The Poisson distribution 163
8.10 The incidence rate ratio 166
9 Statistical modeling 169
9.1 Linear regression 169
9.2 The least squares method 171
9.3 Linear regression estimates 174
9.4 Regression and correlation 179
9.5 The Ftest in linear regression 180
9.6 Interpretation of regression analysis results 183
9.7 Multiple regression 185
9.8 Regression diagnostics 188
9.9 Selection of predictor variables 192
9.10 Regression, ttest, and anova 194
9.11 Interaction 196
9.12 Nonlinear regression 199
9.13 Logistic regression 201
9.14 The method of maximum likelihood 204
9.15 Estimation of the logistic regression model 206
9.16 The likelihood ratio test 208
9.17 Interpreting the results of logistic regression 209
9.18 Regression coefficients and odds ratios 211
9.19 Applications of logistic regression 211
9.20 The ROC curve 213
9.21 Model validation 216
9.22 The Cox proportional hazards model 219
9.23 Assumptions of the Cox model 223
9.24 Interpretation of Cox regression 225
10 Measurement 229
10.1 Construction of clinical questionnaires 229
10.2 Factor analysis 230
10.3 Interpretation of factor analysis 234
10.4 Factor rotation 236
10.5 Factor scores 238
10.6 Reliability 239
10.7 Concordance 245
10.8 Validity 251
11 Experimental studies 253
11.1 The purpose of experimental studies 253
11.2 The clinical trial population 255
11.3 The efficacy criteria 256
11.4 Noncomparative clinical trials 258
11.5 Controlled clinical trials 261
11.6 Classical designs 262
11.7 The control group 266
11.8 Blinding 267
11.9 Randomization 268
11.10 The size of a clinical trial 272
11.11 Noninferiority clinical trials 277
11.12 Adaptive clinical trials 284
11.13 Group sequential plans 286
11.14 The alpha spending function 288
11.15 The clinical trial protocol 291
11.16 The data record 292
12 The analysis of experimental studies 295
12.1 General analysis plan 295
12.2 Data preparation 296
12.3 Study populations 297
12.4 Primary efficacy analysis 301
12.5 Analysis of multiple endpoints 303
12.6 Secondary analyses 307
12.7 Safety analysis 308
13 Metaanalysis of clinical trials 311
13.1 Purpose of metaanalysis 311
13.2 Measures of treatment effect 312
13.3 The inverse variance method 313
13.4 The random effects model 316
13.5 Heterogeneity 317
13.6 Publication bias 319
13.7 Presentation of results 322
Further reading 325
Index 327