Principles of Biostatistics

Principles of Biostatistics
Third Edition

Marcello Pagano
Kimberlee Gauvreau
Heather Mattie
Third edition published 2022
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Library of Congress Cataloging-in-Publication Data

Names: Pagano, Marcello, 1945- author. | Gauvreau, Kimberlee, 1963- author.
| Mattie, Heather, author.
Title: Principles of biostatistics / Marcello Pagano, Kimberlee Gauvreau,
Heather Mattie.
Description: Third edition. | Boca Raton : CRC Press, 2022. | Revised
edition of: Principles of biostatistics / Marcello Pagano, Kimberlee
Gauvreau. 2nd ed. c2000. | Includes bibliographical references and
index.
Identifiers: LCCN 2021057073 (print) | LCCN 2021057074 (ebook) | ISBN
9780367355807 (hardback) | ISBN 9781032252445 (paperback) | ISBN
9780429340512 (ebook)
Subjects: LCSH: Biometry.
Classification: LCC QH323.5 .P34 2022 (print) | LCC QH323.5 (ebook) | DDC
570.1/5195--dc23/eng/20211223
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LC ebook record available at https://lccn.loc.gov/2021057074

ISBN: 978-0-367-35580-7 (hbk)

ISBN: 978-1-032-25244-5 (pbk)
ISBN: 978-0-429-34051-2 (ebk)

DOI: 10.1201/9780429340512

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 This book is dedicated with love to
Phyllis, Marisa, John-Paul, Camille and Ivy,
Neil and Eliza,
Ali, Bud, Connie, Nanette, Steve, Katie and Buddy
Contents

Preface xiii

1 Introduction 1
1.1 Why Study Biostatistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Difficult Numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 Overview of the Text . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3.1 Part I: Chapters 2–4 Variability . . . . . . . . . . . . . . . . . . . . . . . 4
1.3.2 Part II: Chapters 5–8 Probability . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.3 Part III: Chapters 9–22 Inference . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.4 Computing Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.4 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

I Variability 13
2 Descriptive Statistics 15
2.1 Types of Numerical Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.1 Nominal Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.2 Ordinal Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.3 Ranked Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.1.4 Discrete Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
2.1.5 Continuous Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
2.2 Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.2.1 Frequency Distributions . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
2.2.2 Relative Frequency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.3 Graphs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3.1 Bar Charts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3.2 Histograms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.3.3 Frequency Polygons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.3.4 Box Plots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2.3.5 Two-Way Scatter Plots . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.3.6 Line Graphs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
2.4 Numerical Summary Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.4.1 Mean . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
2.4.2 Median . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.4.3 Mode . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2.4.4 Range . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
2.4.5 Interquartile Range . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
2.4.6 Variance and Standard Deviation . . . . . . . . . . . . . . . . . . . . . . . 39
2.5 Empirical Rule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
2.6 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
2.7 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

vii
viii Contents

3 Rates and Standardization 67

3.1 Rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
3.2 Adjusted Rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
3.2.1 Direct Standardization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
3.2.2 Indirect Standardization . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
3.3 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
3.4 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84

4 Life Tables 89
4.1 Historical Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
4.2 Life Table as a Predictor of Longevity . . . . . . . . . . . . . . . . . . . . . . . . 95
4.3 Mean Survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
4.4 Median Survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.5 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
4.6 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106

II Probability 109
5 Probability 111
5.1 Operations on Events and Probability . . . . . . . . . . . . . . . . . . . . . . . . 111
5.2 Conditional Probability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
5.3 Total Probability Rule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
5.4 Relative Risk and Odds Ratio . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
5.5 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
5.6 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

6 Screening and Diagnostic Tests 135

6.1 Sensitivity and Specificity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136
6.2 Bayes’ Theorem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
6.3 Likelihood Ratios . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
6.4 ROC Curves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
6.5 Calculation of Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
6.6 Varying Sensitivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
6.7 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151
6.8 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

7 Theoretical Probability Distributions 159

7.1 Probability Distributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159
7.2 Binomial Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161
7.3 Poisson Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
7.4 Normal Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
7.5 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
7.6 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

8 Sampling Distribution of the Mean 191

8.1 Sampling Distributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
8.2 Central Limit Theorem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
8.3 Applications of the Central Limit Theorem . . . . . . . . . . . . . . . . . . . . . 193
8.4 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198
8.5 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
Contents ix

III Inference 207

9 Confidence Intervals 209
9.1 Two-Sided Confidence Intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
9.2 One-Sided Confidence Intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
9.3 Student’s t Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
9.4 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
9.5 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222

10 Hypothesis Testing 227

10.1 General Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
10.2 Two-Sided Tests of Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
10.3 One-Sided Tests of Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
10.4 Types of Error . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
10.5 Power . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
10.6 Sample Size Estimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
10.7 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
10.8 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

11 Comparison of Two Means 253

11.1 Paired Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
11.2 Independent Samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
11.2.1 Equal Variances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
11.2.2 Unequal Variances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
11.3 Sample Size Estimation for Two Means . . . . . . . . . . . . . . . . . . . . . . . 266
11.4 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
11.5 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274

12 Analysis of Variance 279

12.1 One-Way Analysis of Variance . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
12.1.1 The Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
12.1.2 Sources of Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
12.2 Multiple Comparisons Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . 286
12.3 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
12.4 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293

13 Nonparametric Methods 297

13.1 Sign Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
13.2 Wilcoxon Signed-Rank Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
13.3 Wilcoxon Rank Sum Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
13.4 Kruskal-Wallis Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
13.5 Advantages and Disadvantages of Nonparametric Methods . . . . . . . . . . . . . 311
13.6 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
13.7 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318

14 Inference on Proportions 323

14.1 Normal Approximation to the Binomial Distribution . . . . . . . . . . . . . . . . 324
14.2 Sampling Distribution of a Proportion . . . . . . . . . . . . . . . . . . . . . . . . 326
14.3 Confidence Intervals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
14.4 Hypothesis Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
14.5 Sample Size Estimation for One Proportion . . . . . . . . . . . . . . . . . . . . . 330
14.6 Comparison of Two Proportions . . . . . . . . . . . . . . . . . . . . . . . . . . . 332
x Contents

14.7 Sample Size Estimation for Two Proportions . . . . . . . . . . . . . . . . . . . . 335

14.8 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
14.9 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345

15 Contingency Tables 351

15.1 Chi-Square Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
15.1.1 2 × 2 Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
15.1.2 r × c Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
15.2 McNemar’s Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358
15.3 Odds Ratio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
15.4 Berkson’s Fallacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
15.5 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
15.6 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373

16 Correlation 381
16.1 Two-Way Scatter Plot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
16.2 Pearson Correlation Coefficient . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
16.3 Spearman Rank Correlation Coefficient . . . . . . . . . . . . . . . . . . . . . . . 387
16.4 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389
16.5 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395

17 Simple Linear Regression 399

17.1 Regression Concepts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
17.2 The Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 402
17.2.1 Population Regression Line . . . . . . . . . . . . . . . . . . . . . . . . . 402
17.2.2 Method of Least Squares . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
17.2.3 Inference for Regression Coefficients . . . . . . . . . . . . . . . . . . . . 408
17.2.4 Inference for Predicted Values . . . . . . . . . . . . . . . . . . . . . . . . 410
17.3 Evaluation of the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 413
17.3.1 Coefficient of Determination . . . . . . . . . . . . . . . . . . . . . . . . . 413
17.3.2 Residual Plots . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
17.3.3 Transformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
17.4 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
17.5 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425

18 Multiple Linear Regression 431

18.1 The Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
18.1.1 Least Squares Regression Equation . . . . . . . . . . . . . . . . . . . . . 432
18.1.2 Inference for Regression Coefficients . . . . . . . . . . . . . . . . . . . . 434
18.1.3 Indicator Variables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
18.1.4 Interaction Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
18.2 Model Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438
18.3 Evaluation of the Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
18.4 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
18.5 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451

19 Logistic Regression 455

19.1 The Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 455
19.1.1 Logistic Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457
19.1.2 Fitted Equation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
19.2 Indicator Variables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460
19.3 Multiple Logistic Regression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 464
Contents xi

19.4 Simpson’s Paradox . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466

19.5 Interaction Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 467
19.6 Model Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 468
19.7 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469
19.8 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474

20 Survival Analysis 479

20.1 Life Table Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 481
20.2 Product-Limit Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487
20.3 Log-Rank Test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
20.4 Cox Proportional Hazards Model . . . . . . . . . . . . . . . . . . . . . . . . . . 495
20.5 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 496
20.6 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505

21 Sampling Theory 509

21.1 Sampling Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511
21.1.1 Simple Random Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . 512
21.1.2 Systematic Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 514
21.1.3 Stratified Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 515
21.1.4 Cluster Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 519
21.1.5 Ratio Estimator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521
21.1.6 Two-Stage Cluster Sampling . . . . . . . . . . . . . . . . . . . . . . . . . 523
21.1.7 Design Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 526
21.1.8 Nonprobability Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . 527
21.2 Sources of Bias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 528
21.3 Further Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 530
21.4 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535

22 Study Design 537

22.1 Randomized Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538
22.1.1 Control Groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
22.1.2 Randomization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
22.1.3 Blinding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 540
22.1.4 Intention to Treat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541
22.1.5 Crossover Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541
22.1.6 Equipoise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541
22.2 Observational Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
22.2.1 Cross-Sectional Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
22.2.2 Longitudinal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543
22.2.3 Case-Control Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 543
22.2.4 Cohort Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 544
22.2.5 Consequences of Design Flaws . . . . . . . . . . . . . . . . . . . . . . . . 544
22.3 Big Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 544
22.4 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 546

Bibliography 547

Glossary 569

Statistical Tables 583

Index 601
Preface

This book was written for students of the health sciences and serves as an introduction to the study
of biostatistics – the use of numbers and numerical techniques to extract information from data and
facts, and to then use this information to communicate scientific results. However, just as one can lie
with words, one can also lie with numbers. Indeed, numbers and lies have been linked for quite some
time; there is even a book titled How to Lie with Statistics. This association may owe its origin – or
its affirmation at the very least – to the British Prime Minister Benjamin Disraeli. Disraeli is credited
by Mark Twain as having said, “There are three kinds of lies: lies, damned lies, and statistics.” One
has only to observe any modem political campaign to be convinced of the abuse of statistics. But
enough about lies; this book adopts the position of Professor Frederick Mosteller, who said, “It is
easy to lie with statistics, but it is easier to lie without them.”

Background
Principles of Biostatistics is aimed at students in the biological and health sciences who wish to learn
traditional research methods. The first edition was based on a required course for graduate students
at the Harvard T.H. Chan School of Public Health, which is also attended by a large number of health
professionals from the Harvard medical area. The course is as old as the school itself, which attests
to its importance. It spans 16 weeks of lectures and laboratory sessions; the lab sessions reinforce
the material covered in lectures and introduce the computer into the course. We have included a
selection of lab materials – either additional examples, or a different perspective on the material
covered in a chapter – in the sections called Further Applications. These sections are designed to
provoke discussion, although they are sufficiently complete for an individual who is not using the
book as a course text to benefit from reading them.
The book includes a range of biostatistical topics, the majority of which can be covered at some
depth in one semester in an American university. However, there is enough material to allow the
instructor some flexibility. For example, some instructors may choose to omit the sections covering
the calculation of prevalence (Section 6.5) or the Poisson distribution (Section 7.3), or the chapter
on analysis of variance (Chapter 12), if they consider these concepts to be less important than others.

Structure
Some say that statistics is the study of variability and uncertainty. We believe there is truth to this
adage, and have used it as a guide to divide the book into three parts covering the basic principles
of vip: (1) variability, (2) inference, and (3) probability. For pedagogical purposes, inference and
probability are covered in reverse order in the text. Chapters 2 through 4 deal with the variability
inherent in collections of numbers, and the ways in which to summarize, explore, and explain
them. Chapters 5 through 8 focus on probability, and serve as an introduction to the tools needed
for the subsequent investigation of uncertainty. In Chapter 8 we distinguish between populations
and samples and begin to examine the variability introduced by sampling from a population, thus
progressing to inference in the book’s remaining chapters. We think that this modular introduction
to the quantification of uncertainty is justified by the success achieved by our students. Postponing

xiii
xiv Preface

the slightly more difficult concepts until a solid foundation has been established makes it easier for
the reader to comprehend and retain them.

Datasets and Examples

Throughout the text we have used data drawn from published studies to illustrate biostatistical
concepts. Not only is real data more meaningful, it is usually more interesting as well. Of course, we
do not wish to use examples in which the subject matter is too esoteric or too complex. To this end,
we have been guided by the backgrounds and interests of our students – primarily topics in public
health and clinical research – to choose examples that best demonstrate the concepts at hand.
There is some risk involved in using published data. We cannot guarantee that all of the examples
are honest and that the data were properly collected; for this we must rely on the reputations of our
sources. We do not belittle the importance of this consideration. The value of our inference depends
critically on the worth of the data, and we strongly recommend that a good deal of effort be expended
on evaluating its quality. We assume that this is understood by the reader.
In some cases we have used examples in which the population of the United States is broken
down along racial lines. In reporting these official statistics we follow the lead of the government
agencies that release them. We do not wish to rectify this racial categorization, since the observed
differences may well be due to socioeconomic factors rather than the implied racial ones. One option
would be to ignore these statistics; however, this would hide inequities which exist in our health
system – inequities that need to be eliminated. We focus attention on the problem in the hope of
stimulating interest in promoting solutions.
We have minimized the use of mathematical notation because of its well-deserved reputation of
being the ultimate jargon. If used excessively, it can intimidate even the most ardent scholar. We
do not wish to eliminate it entirely, however; it has been developed over the ages to be helpful in
communicating results. In this third edition, mathematical notation and important formulas used in
the text have also been included in summary boxes at the ends of relevant sections.

Computing
There is something about numbers – maybe a little magic – that makes them fun to study. The fun
is in the conceptualization more than the calculations, however, and we are fortunate that we have
the computer to do the drudge work. This allows students to concentrate on the concepts. In other
words, the computer allows the instructor to teach the poetry of statistics and not the plumbing.
To take advantage of the computer, one needs a good statistical package. We use Stata, a product
of the Stata Corporation in College Station, Texas, and also R, a software environment available for
free download. Stata is user-friendly, accurate, powerful, reasonably priced, and works on a number
of different platforms, including Windows, Unix, and Macintosh. R is available on an open-source
license, and also works on a number of platforms. It is a versatile and efficient programming language.
Other statistical packages are available, and this book can be supplemented by any one of them. We
strongly recommend that some statistical package be used for calculations.
Some of the review exercises in the text require the use of a computer. The required datasets
are available on the book’s companion website at https://github.com/Principles-of-Biostatistics/3rd-
Edition. There are also many exercises that do not require the computer. As always, active learning
yields better results than passive observation. To this end, we cannot stress enough the importance
of the review exercises, and urge the reader to attempt as many as time permits.
Preface xv

New to the Third Edition

The third edition continues in the spirit of the first edition, but has been updated to reflect some
of the advances of the last 30 years. It includes revised and expanded discussions on many topics
throughout the book. Major revisions include:
• The chapters on Data Presentation and Numerical Summary Measures from the second edition
have been streamlined and combined into a single chapter titled Descriptive Statistics.
• The chapter on Life Tables has been rewritten, and detailed calculations for the life table have
been moved into the Further Applications section.

• The material on Screening and Diagnostic Tests – formerly contained within the Probability
chapter – has been given its own chapter. This new chapter includes sections on likelihood ratios
and the concept of varying sensitivities.
• New sections on sample size calculations for two-sample tests on means and proportions, the
Kruskal-Wallis test, and the Cox proportional hazards model have been added to existing chapters.
• Concepts previously covered in a chapter titled Multiple 2 × 2 Tables have now been moved into
the Logistic Regression chapter.
• The chapter on Sampling Theory has been greatly expanded.
• A new chapter introducing the basic principles of Study Design has been added at the end of the
text.
• Datasets used in the text and those needed for selected review exercises are now available on the
book’s companion website at https://github.com/Principles-of-Biostatistics/3rd-Edition.
• The companion website also contains the Stata and R code used to produce the computer output
displayed in the text’s Further Applications sections, as well as introductory material describing
the use of both statistical packages.
• A glossary of definitions for important statistical terms has been added at the back of the book.
• As previously mentioned, mathematical notation and formulas used in the text have been included
in summary boxes at the end of each section for ease of reference.
• Additional review exercises have been included in each chapter.
In addition to these changes in content, previously used data have been updated whenever possible
to reflect more current public health information. As its name suggests, Principles of Biostatistics
covers topics which are fundamental to an introduction to biostatistics. Of course we have had to limit
the material presented, and some important topics have not been included. Decisions about what to
exclude were difficult, especially as the field of biostatistics and data science continues to evolve. No
small role in this evolution is played by the computer; the capacity of statistical software seems to
increase limitlessly, providing new and exciting inferential tools. However, to truly appreciate these
tools and to be able to utilize them properly requires a strong foundation in traditional statistical
principles. Those laid out in this text are still essential and will be useful to the reader both today
and in the future.
xvi Preface

Acknowledgments
A debt of gratitude is owed to a number of people: former Harvard University President Derek
Bok for providing the support which got the first edition of this book off the ground, Dr. Michael
K. Martin for performing the calculations for the Statistical Tables section, John-Paul Pagano for
assisting in the editing of the first edition, and the individuals who reviewed the manuscript. We
thank the teaching assistants who have helped us teach our courses over the years and who have
made many valuable suggestions. Probably the most deserving of thanks are our students, who have
tolerated us as we learned how to best teach the material. We are still learning.

Marcello Pagano
Kimberlee Gauvreau
Heather Mattie

Boston, Massachusetts
1
Introduction

CONTENTS
1.1 Why Study Biostatistics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 Difficult Numbers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3 Overview of the Text . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.3.1 Part I: Chapters 2–4 Variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3.2 Part II: Chapters 5–8 Probability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.3 Part III: Chapters 9–22 Inference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
1.3.4 Computing Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.4 Review Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

In 1903, H.G. Wells hypothesized that statistical thinking would one day be as necessary for good
citizenship as the ability to read and write. Wells was correct, and today statistics play an important
role in many decision-making processes. For example, before any new drug or medical device can
be marketed legally in the United States, the United States Food and Drug Administration (fda)
requires that it be subjected to a clinical trial, an experimental study involving human subjects. The
data from this study is compiled and analyzed to determine not only whether the drug is effective,
but also if it is safe. How is this determined? As another example, the United States government’s
decisions regarding Social Security and public health programs rely in part on the longevity of the
nation’s population; the government must therefore be able to accurately predict the number of years
each individual will live. How does it do this? If the government incorrectly forecasts human life
expectancy, it could render itself insolvent and endanger the well-being of its citizens.
There are many other issues that must be addressed as well. Where should a government invest
its resources if it wishes to reduce infant mortality? Should a mastectomy always be recommended
to a patient with breast cancer? Should a child play football? What factors increase the risk that an
individual will develop coronary heart disease? Will we be able to afford our health care system in
the future? Does global warming impact the sea level? Our health? What effect would a particular
change in policy have on longevity? To answer these questions and others, we rely on the methods
of biostatistics.

1.1 Why Study Biostatistics

The study of statistics explores the collection, organization, analysis, and interpretation of numerical
data. The concepts of statistics may be applied to a number of fields, including business, psychology,
and agriculture. When focus is on the biological and health sciences, we use the term biostatistics.
Historically, statistics have been used to tell a story with numbers. Numbers often communicate
ideas more succinctly than do words. For example, the World Health Organization (who) defines
maternal mortality as “the death of a woman while pregnant or within 42 days of termination of

DOI: 10.1201/9780429340512-1 1
2 Principles of Biostatistics

FIGURE 1.1
Maternal mortality per 100,000 live births, 1990–2015

pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or
aggravated by the pregnancy or its management but not from accidental or incidental causes” [1].
Therefore, when presented with the graph in Figure 1.1 [2, 3], someone concerned with maternal
mortality might react with alarm at the reported striking behavior of the United States and research
the issue further.
How useful is the study of biostatistics? Biostatistics are certainly ubiquitous in the health
sciences. The Centers for Disease Control and Prevention (cdc) reports that “During the 20th century,
the health and life expectancy of persons residing in the United States improved dramatically. Since
1900, the average lifespan of persons in the United States has lengthened by greater than 30 years;
25 years of this gain are attributable to advances in public health” [4–6]. They go on to list what they
consider to be ten great achievements:

– Vaccination – Motor vehicle safety

– Safer workplaces – Control of infectious diseases
– Healthier mothers and babies – Safer and healthier foods
– Fluoridation of drinking water – Family planning
– Decline in deaths from coronary – Recognition of tobacco use
heart disease and stroke as a health hazard

When one reads the recounting of these achievements in subsequent Mortality and Morbidity Weekly
Reports, it is evident that biostatistics played an important role in every one of them.
Notwithstanding these societal successes, work still needs to be done. The future with its exabytes
of data – known as big data – providing amounts of information which are orders of magnitude larger
than was previously available is a new challenge. But if we are to progress responsibly, we cannot
ignore the lessons of the past [7]. A case in point is our failure to control the number of deaths from
guns that has led to a public health crisis in the United States. The statistic blared from a headline in
Introduction 3

The New York Times in 2018 [8]: “nearly 40,000 people died from guns in u.s. last year, highest in
50 years.” This crisis looks even worse when one considers what is happening with mass shootings
in schools. The United States is experiencing a remarkable upward trend in the number of casualties
involved. There have been more school shooting deaths in the first 18 years of the 21st century (66)
than in the last 60 years of the 20th century (55). The same is true for injuries due to guns, with 260
and 81 in each of these two time periods, respectively [9]. A summary of this situation is made more
pithy by the statistics.

1.2 Difficult Numbers

The numbers needed to tell a story are not always easy to come by – examples include attempts
to investigate the volume of illicit human trafficking [10], or to measure the prevalence of female
genital mutilation [11] – but are indispensable for communicating important ideas. The powerful use
of statistics in this argument against continued restrictions on the drug mifepristone’s distribution is
clear [12]:
Since its approval in 2000, more than 3.7 million women have used mifepristone to end an
early pregnancy in the United States — it is approved for use up to 70 days into a pregnancy.
Nearly two decades of data on its use and effects on patients provide significant new insights
into its safety and efficacy. Mifepristone is more than 97% effective. Most adverse effects
are mild, such as cramping or abdominal pain, and the rate of severe adverse events is
very low: such events occur in less than 0.5% of patients, according to the fda. Many drugs
marketed in the United States have higher adverse event rates and are not subject to restricted
distribution.
In this example, the numbers provide a concise summary of the situation being studied. They, of
course, must be both accurate and precise if we are to trust any conclusions based on them.
The examples described deal with complex situations, yet the numbers convey essential informa-
tion. A word of caution: we must remain realistic in our expectations of what statistics can achieve.
No matter how powerful it is, no statistic will convince everyone that a given conclusion is true.
The data on gun deaths in the United States mentioned above are often brushed away with some
variant of the aphorism, “Guns don’t kill people, people do.” This should not come as a surprise.
After all, there are still deniers of global warming, people who believe that the vaccine for measles,
mumps, and rubella causes autism, and members in the Flat Earth Society, whose website states:
“This website is dedicated to unravelling the true mysteries of the universe and demonstrating that
the earth is flat and that Round Earth doctrine is little more than an elaborate hoax” [13].

1.3 Overview of the Text

The aim of a study using biostatistics is to analyze and present data in a transparent, interpretable,
and coherent manner to effectively communicate results and to help lead policy makers to the best
informed decisions. This text book, as its title states, covers the principles of biostatistics. The
21 chapters beyond this one can be arranged into three parts to cover the tenets of biostatistics:
(1) variability, (2) inference, and (3) probability. We list them in this order so students can easily
remember the acronym vip. For pedagogical reasons, however, we present them in a different order:
4 Principles of Biostatistics

FIGURE 1.2
Racial breakdown of COVID-19 cases in the United States through May 28, 2020

(1) Chapters 2–4 discuss variability, (2) Chapters 5–8 cover probability, and (3) Chapters 9–22 cover
inference.

1.3.1 Part I: Chapters 2–4 Variability

If we wish to study the effects of a new diet, we might place a group of individuals on that diet and
measure changes in their body mass over time. Similarly, if we want to investigate the success of an
innovative therapy for treating pancreatic cancer, we might record the lengths of time that patients
treated with this therapy survive beyond their initial diagnosis. These numbers, however, can display
a great deal of variability from one person to another. They are generally not very informative
until we begin combining them in some way. Descriptive statistics, the topic of Chapter 2, are
methods for organizing and summarizing a set of measurements. They help us to better understand
the attributes of a group or population. For instance, to support the premise that there was racial
inequity in who was afflicted by the coronavirus, reporters from The New York Times collected data
and displayed it not only in a table, but also as a graph similar to Figure 1.2 [14]. To dig deeper into
their analysis and show the impact by age group, they also included Figure 1.3 [14]. This example
demonstrates the power of a picture to tell a story. The graphical capabilities of computers make
this type of summarization feasible even for the most modest analyses, and use of both tables and
graphs to summarize information enables scientists and policy makers to formulate hypotheses that
then require further investigation.
By definition, a summary captures only a particular aspect of the data being studied; consequently,
it is important to have an idea of how well the summary represents the set of measurements as a
whole. For example, we might wish to know how long hiv/aids patients survive after diagnosis with
one of the opportunistic infections that characterize the disease. If we calculate an average survival
time, is this average representative of all patients? Furthermore, how useful is it for planning future
health service needs? In addition to tables and graphs, Chapter 2 examines numerical summary
measures that help answer questions such as these. The chapter includes an introduction to the mean
and standard deviation; the former tells us where the measurements are centered, and the latter how
dispersed they are. The chapter ends with the splendid empirical rule, which quantifies the metaphor
“the apple does not fall far from the tree.”
Measurements that take on only two distinct values require special attention. In the health
sciences, one of the most common examples of this type of data is the categorization of being
alive or dead. If we denote survival by 0 and death by 1, we are able to classify each member
of a group of individuals using these numbers and then average the results. In this way, we can
summarize the mortality associated with the group. Chapter 3 deals exclusively with measurements
Introduction 5

FIGURE 1.3
Racial breakdown of COVID-19 cases in the United States in 2020, by age

that assume only two values. The notion of dividing a group into smaller subgroups or classes based
on a characteristic such as age or sex is also introduced. Grouping individuals into smaller, more
homogeneous subgroups decreases variability, thus allowing better prognosis. For example, it might
make sense to determine the mortality of females separately from that of males, or the mortality of
20- to 29-year-olds separately from 80- to 89-year-olds. Chapter 3 also investigates techniques that
allow us to make valid comparisons among populations whose compositions may differ substantially.
Chapter 4 introduces the classical life table, one of the most important numerical summary
techniques available in the health sciences. Life tables are used by public health professionals
to characterize the well-being of a population, and by insurance companies to predict how long
individuals will live. In this chapter, the study of mortality begun in Chapter 3 is extended to
incorporate the actual time to death for each individual, resulting in a more refined analysis.
Together, Chapters 2 through 4 demonstrate that the extraction of information from a collection
of measurements is not precluded by the variability among those measurements. Despite their vari-
ability, the data often exhibit a certain regularity as well. For example, here are the birth rates in the
United States among women 15–19 years of age over the 5-year time span shown [15]:

Year : 2011 2012 2013 2014 2015

Birth rate per 1000 : 31.3 29.4 26.5 24.2 22.3

Are the numbers showing a natural variability around a constant rate over time – think of how many
mistakes can go into the reporting of such numbers – or is this indicative of a real downward trend?
This question deserves better than a simple choice between these two options. To answer it properly,
we need to apply the principles of probability and inference, the subjects covered in the next two
sections of the text.
6 Principles of Biostatistics

1.3.2 Part II: Chapters 5–8 Probability

Probability theory resides within what is known as an axiomatic system; we start with some basic
truths (axioms), and then build up a logical system around them. In its purest form, this theoretical
system has no practical value. Its practical importance comes from knowing how to use the theory to
yield useful approximations. An analogy can be drawn with geometry, a subject that most students
are exposed to relatively early in their schooling. Although it is impossible for an ideal straight line
to exist other than in our imaginations, that has not stopped us from constructing some wonderful
buildings, based on geometric calculations; including some that have lasted thousands of years. The
same is true of probability theory. Although it is not practical in its pure form, its basic principles –
which we investigate in Chapter 5 – can be applied to provide a means of quantifying uncertainty.
An important application of probability theory arises in medical screening and diagnostic testing,
as we see in Chapter 6. Uncertainty is present because, despite some manufacturers’ claims, no
biological test is perfect. This leads to complicated findings, which are sometimes unintuitive, even
in the simple situation where the test is diagnosing the presence or absence of a medical condition.
Before performing the test, we consider each of four possible classifications: the test result is correct
or not, and the person being tested has the condition or not. The relationship between the results
of the test and the truth gives rise to important practical questions. For instance, can we conclude
that every blood sample that tests positive for hiv actually harbors the virus? All the units in the
Red Cross blood supply have tested negative for hiv; does this mean that there are no contaminated
samples? If there are contaminated samples, how many might there be? To address questions such
as these, we study the average or long-term behavior of diagnostic tests by using probability theory.
Chapters 7 and 8 extend probability theory and introduce some common probability distributions
used to describe the variability in a set of measurements. These mathematical models are useful as
a basis for the inferential methods covered in the remainder of the text.

1.3.3 Part III: Chapters 9–22 Inference

The Cambridge Dictionary defines inference as a guess that is made or an opinion that is formed
based on the information available. The paradigm we use in this text is that the inference we make
about a population is based on a sample of observations selected from that much larger population.
On the basis of the sample, we draw conclusions about the entire population, including the part of
the population we did not measure – those not in the sample. Humans are much more similar to
each other than dissimilar, and we capitalize on this fact to add credibility to our inference. However,
knowing how the sample is chosen and whom the sample represents are also of critical importance
for making inference.
An analogy can be made with the way in which traveling salesmen in the late 19th and early 20th
centuries in the United States were able to sell their goods to potential customers. Rather than carry
all the goods to be sold – including big items such as stoves – they would transport miniature models
of the products they were selling; see Figure 1.4 for an example. These replicas were very carefully
crafted, so as to convey an honest likeness, albeit a much smaller version of the sale item [16].
Although these are also called samples, this is where the analogy ceases to be useful; to make
realistic models, the manufacturers had the real item as a guide. When we sample in biostatistics, it
is because we do not know what the measurements look like for the entire target population.
Suppose we want to know whether a new drug is effective in lowering high blood pressure. Since
the population of all people in the world who have high blood pressure is very large, it is implausible
to think we would have either the time or the resources necessary to locate and examine each and
every person with this condition who might be a candidate to use the drug. Out of necessity, we
must rely on a sample of people drawn from the population. The limits to our subsequent inference
– which are always there – are determined by both the population that we sample, and by how well
the sample represents that population.
Introduction 7

FIGURE 1.4
Boxed salesman’s sample set of glass bottles, containing samples from the Crocker company (Buffalo,
New York) (photo courtesy of Judy Weaver Gonyeau) [16]

The ability to generalize results from a sample to a population is the bedrock of empirical
research, and a central issue in this book. One requirement for credible inference is that it be based
on a representative sample. In any particular study, do we truly have a representative sample? If we
answer yes, this leads to a logical conundrum. To truly judge that we have a representative sample we
need to know the entire population. And if we know the entire population, why then focus only on a
sample? If we do not have the ability to study an entire population, the best solution available is to
utilize a simple random sample of the population. This means, amongst other things, that everyone in
the population has an equal chance of being selected into the sample. It ensures us that, on average,
we have a representative sample. A pivotal side benefit of a simple random sample is that it also
provides an estimate of the possible inaccuracy of our inference.
It can often be difficult to obtain a simple random sample. The consequences of mistakenly
thinking that a sample is representative when in fact it is not lead to invalid inferences. A case
in point is provided by the behavioral sciences, where empirical results are often derived from
individuals sampled from western, educated, industrialized, rich, and democratic (weird) societies.
An example of this is the undergraduate students who make a few extra dollars by volunteering to
be a subject for an on-campus study. Since most of these studies are done in the United States, we
can see the problem. Clearly the results will reflect the pool from which the subjects came. Use of
the label weird implies a certain contempt for a large number of published findings attacked in an
article by Henrich and colleagues [17]. They investigate results in the domains of visual perception,
fairness, cooperation, spatial reasoning, categorization and inferential induction, moral reasoning,
reasoning styles, self-concepts and related motivations, and the heritability of iq. They conclude
that “members of weird societies, including young children, are among the least representative
populations one could find for generalizing about humans.” Yet the researchers who published the
original results presumably believed that their samples were random and representative.
8 Principles of Biostatistics

We have repeated this mistake in the bio-medical sciences, where the consequences can be even
more severe. For example, we do not perform as many clinical trials on children as on adults [18].
Trials of adults, even randomized clinical trials, are not representative of children. Children are not
small adults who simply require a modification in dosage. Some conditions – such as prematurity
and many of its sequelae – occur only in infants and children [19]. Certain genetic conditions such
as phenylketonuria (pku) will, if untreated, lead to severe disability or even death in childhood. The
diagnosis, prevention, and treatment of these conditions cannot be adequately investigated without
studying children. Other conditions such as influenza and certain cancers and forms of arthritis
also occur in both adults and children, but their pathophysiology, severity, course, and response to
treatment may be quite different for infants, children, and adolescents. Treatments that are safe and
effective for adults may be dangerous or ineffective for children.
There are many more examples where certain groups have been largely ignored by researchers.
The lack of trials in women [20] and people of color led Congress, in 1993, to pass the National
Institutes of Health Revitalization Act, which requires the agency to include more people from these
groups in their research studies. Unfortunately, success in the implementation of this law has been
slow [21]. The headline in Scientific American on September 1, 2018 – 25 years after the Act was
passed – was clinical trials have far too little racial and ethnic diversity; it’s unethical
and risky to ignore racial and ethnic minorities [22].
This problem extends beyond clinical trials. The 21st century has seen the mapping of the human
genome. Genome wide association studies (gwas) have identified thousands of genetic variants
identified with human traits and diseases. This exciting source of information is unfortunately
restricted, so inference is constrained or biased. A 2009 study showed that 96% of participants in
gwas studies were of European descent [23]. Seven years later this had decreased to 80%, largely
due to studies carried out in China and Japan; the Asian content has increased, but the representation
of other groups has not. Since gwas studies are the basis for precision medicine, this has raised the
fear that precision medicine will exacerbate racial health disparities [24]. This, of course, is a general
trait of artificial intelligence systems: they reflect the information that goes into them.
As an example of the value of inference, we can consider a group of investigators who were
interested in evaluating whether, at the time of their study, there was a difference in how analgesics
were administered to male versus female patients with acute abdominal pain. It would be impossible
to investigate this issue by observing every person in the world with acute abdominal pain, so they
designed a study of a smaller group of individuals with this ailment so they could, on the basis of
the sample, infer what was happening in the population as a whole. How far their inference should
reach is not our focus right now, but it is important to take notice of what they say. Here is a copy of
the abstract from the published article [25]:
objectives: Oligoanalgesia for acute abdominal pain historically has been attributed to the
provider’s fear of masking serious underlying pathology. The authors assessed whether a
gender disparity exists in the administration of analgesia for acute abdominal pain.
methods: This was a prospective cohort study of consecutive nonpregnant adults with
acute nontraumatic abdominal pain of less than 72 hours duration who presented to an urban
emergency department (ed) from April 5, 2004, to January 4, 2005. The main outcome mea-
sures were analgesia administration and time to analgesic treatment. Standard comparative
statistics were used.
results: Of the 981 patients enrolled (mean age standard deviation [sd] 41 17 years;
65% female), 62% received any analgesic treatment. Men and women had similar mean pain
scores, but women were less likely to receive any analgesia (60% vs. 67%, difference 7%,
95% confidence interval (ci) = 1.1% to 13.6%) and less likely to receive opiates (45% vs.
56%, difference 11%, 95% ci = 4.1% to 17.1%). These differences persisted when gender-
specific diagnoses were excluded (47% vs. 56%, difference 9%, 95% ci = 2.5% to 16.2%).
After controlling for age, race, triage class, and pain score, women were still 13% to 25%
Introduction 9

less likely than men to receive opioid analgesia. There was no gender difference in the receipt
of nonopioid analgesia. Women waited longer to receive their analgesia (median time 65
minutes vs. 49 minutes, difference 16 minutes, 95% ci = 3.5 to 33 minutes).
conclusions: Gender bias is a possible explanation for oligoanalgesia in women who
present to the ed with acute abdominal pain. Standardized protocols for analgesic adminis-
tration may ameliorate this discrepancy.

This is a fairly typical abstract in the health sciences literature – it reports on a clinical study and
uses statistics to describe the findings – so we look at it more closely. First consider the objectives
of the study. We are told that the goal is to discover whether there is a gender disparity in the
administration of drugs. This is not whether there was a difference in administering the drugs
between genders in this particular study – that question is easy to answer – but rather a more
ambitious finding; namely, is there something in this study that allows us to generalize the findings
to a broader population?
The abstract goes on to describe the methods utilized in the study, and then its results. We first
learn that the researchers studied a group of 981 patients. To allow the reader to get an understanding
of who these 981 patients are, they provide some descriptive statistics about the patients’ ages and
genders. This is done to lay the groundwork for generalizing the results of the study to individuals
not included in the study sample.
The investigators then start generalizing their results. We are told that even though men and
women suffered similar amounts of pain, women were less likely – 7% less likely – to receive any
analgesia. This difference of 7% is clearly study specific. Had they chosen fewer than 981 patients or
more, or even a different group of 981 patients, they likely would have observed a difference other
than 7%. How to quantify this potential variability from sample to sample – even though we have
observed only a single sample – and how to accommodate it when making inference, is answered
by the most useful and effective result in the book. It is an application of the theory covered in
Chapter 8, and is known as the central limit theorem.
An application of the central limit theorem allows the study investigators to construct a 95%
confidence interval for the difference in proportions, 1.1% to 13.6%. One way to interpret this
interval is to appeal to a thought experiment and repetition: If we were to sample repeatedly from
the underlying population, each sample might result in a difference other than 7%, and a confidence
interval other than 1.1% to 13.6%. However, 95% of these intervals from repeated sampling will
include the true population difference between the genders, whatever its value. The interpretations for
all the other confidence intervals in the abstract are similar. More general applications of confidence
intervals are introduced in Chapter 9, and examples appear throughout the text.
For a study to be of general interest and usefulness, we must be able to extrapolate its findings
to a larger population. By generalizing in this manner, however, we inevitably introduce uncertainty.
There are various ways to measure and convey this uncertainty, and we cover two such inferential
methods in this book. One is to use confidence intervals, as we just saw in the abstract, and the other is
to use hypothesis testing. The latter is introduced in Chapter 10. The two methods are consistent with
each other, and will lead to the same action following a study. There are some questions, however,
that are best answered in the hypothesis testing framework.
As an example, consider the way we monitor the water supply for lead contamination [26].
In 1974, the United States Congress passed the Safe Drinking Water Act, and its enforcement is
a responsibility of the Environmental Protection Agency (epa). The epa determines the level of
contaminants in drinking water at which no adverse health effects are likely to occur, with an
adequate margin of safety. This level for lead is zero, and untenable. As a result, the epa established
a treatment technique, an enforceable procedure which water systems must follow to ensure control
of a contaminant. The treatment technique regulation for lead – referred to as the Lead and Copper
Rule [27] – requires water systems to control the corrosivity of water. The regulation stipulates that
to determine whether a system is safe, health regulators must sample taps in the system that are
10 Principles of Biostatistics

more likely to have plumbing materials containing lead. The number of taps sampled depends on
the size of the system served. To accommodate aberrant local conditions, if 10% or fewer of the
sampled taps have no more than 15 parts per billion (ppb) of lead, the system is considered safe. If
not, additional actions by the water authority are required. We can phrase this monitoring procedure
in a hypothesis testing framework: We wish to test the hypothesis that the water has 15 ppb or fewer
of lead. The action we take depends on whether we reject this hypothesis, or not. According to the
Lead and Copper Rule, the decision depends on the measured tap water samples. If more than 10%
of the water samples have more than 15 ppb, we reject the hypothesis and take corrective action.
Just as with diagnostic testing in Chapter 6, we have the potential to make the wrong decision
when conducting a hypothesis test. The chance of such an error is influenced by the way in which
the samples are chosen, how many samples we take, and the 10% cutoff rule. In 2015, the city of
Flint, Michigan, took water samples in order to check the level of lead in the water [28]. According
to the Lead and Copper Rule, they were supposed to take 100 samples from houses most likely to
have a lead problem. They did not. First, they took only 71 samples; second, they chose the 71 in
what seemed like a random fashion. Setting aside these contraventions, they found that 8 of the 71
samples had more than 15 ppb. This is more than 10% of the samples, and thus they were required to
alert the public and take corrective action. Instead, the State of Michigan forced Flint to drop two of
the water samples, both with more than 15 ppb of lead. This meant that there were only 69 samples,
and 6 had more than 15 ppb of lead. Thus fewer than 10% crossed the threshold, and the authorities
felt free to tell the residents of Flint that their water was fine. This is yet another example of ignoring
the message produced by the scientific method and having catastrophe follow [29]. It seems like the
lead problem is repeating itself, only this time in Newark, New Jersey [30].
In Chapter 10 we apply hypothesis testing techniques to statements about the mean of a single
population, and in Chapter 11 extend these techniques to the comparison of two population means.
They are further generalized to the comparison of three or more means in Chapter 12. Chapter 13
continues the development of hypothesis testing concepts, but introduces techniques that allow the
relaxation of some of the assumptions necessary to carry out the tests. Chapters 14 and 15 develop
inferential methods that can be applied to enumerated data or counts – such as the numbers of cases
of sudden infant death syndrome among children put to sleep in various positions – rather than
continuous measurements.
Inference can also be used to explore the relationships among a number of different attributes,
with the underlying motivation being to reduce variability. If a full-term infant whose gestational age
is 39 weeks is born weighing 4 kilograms, or 8.8 pounds, no one would be surprised. If the infant’s
gestational age is only 22 weeks, however, then their weight would be cause for alarm. Why? We
know that birth weight tends to increase with gestational age, and, although it is extremely rare to
find a baby weighing 4 kilograms at 22 weeks, it is not uncommon at 39 weeks. There is sufficient
variability in birth weights to not be surprised to hear that an infant weighs 4 kilograms at birth,
but when the gestational age of the child is known, there is much less variability among infants of a
particular gestational age, and 4 kilograms may seem out of place. In other words, our measurements
have a more precise interpretation the more information we have about the measurement.
The study of the extent to which two factors are related is known as correlation analysis; this is
the topic of Chapter 16. If we wish to predict the outcome of one factor based on the value of another,
then regression is the appropriate technique. Simple linear regression is investigated in Chapter 17,
and is extended to the multiple regression setting – where two or more factors are used to predict
a single outcome – in Chapter 18. If the outcome of interest can take on only two possible values,
such as alive or dead, then an alternative technique must be applied; logistic regression is explored
in Chapter 19.
In Chapter 20, the inferential methods appropriate for life tables are introduced. These techniques
enable us to draw conclusions about the mortality of a population based on the experience of a sample
of individuals drawn from the population. This is common in clinical trials, especially in randomized
Introduction 11

clinical trials, when the purpose of the trial is to study whether a patient’s survival has been prolonged
by a treatment [31].
Chapter 21 is devoted to surveys and inference in finite populations. These techniques are very
popular around election time in democracies, but also find many uses in public health. For example,
the United States Census Bureau supplements the decennial census with an annual survey called
the American Community Survey; its purpose is to help “local officials, community leaders, and
businesses understand the changes taking in their communities. It is the premier source for detailed
population and housing information about our nation” [32]. In 2017, 2,145,639 households were
interviewed. Once again, the mainstay that enables us to make credible inference about the entire
United States population, 325.7 million people in 2017, is the simple random sample. We take that
as our starting point, and build on it with more refined designs. Practical examples are given by the
National Centers for Health Statistics within the cdc [33].
Once again it would be helpful if we could control variability and lessen its effect. Some survey
designs help in this regard. For example, if we can divide a population into strata where we know
the size of each stratum, we can take advantage of that extra information – the size of the strata – to
estimate the population characteristics more accurately via stratified sampling. If on the other hand
we wish to lower the cost of the survey, we can turn to cluster sampling. Of course, we can combine
these ideas and utilize both in a single survey. These design considerations and some of the issues
raised are addressed in this chapter.
The last chapter, Chapter 22, could have been the first. Even though it is foundational, one needs
the material developed in the rest of the book to appreciate its content. It is here that we bolster the
belief that it is not just the numbers that count, but what they represent, and how they are obtained.
This was made quite clear during the covid-19 pandemic. The proper monitoring of a viral epidemic
and its course requires an enumeration of people infected by the virus. This, unfortunately, did
not happen. Miscounting of covid-19 cases occurred across the world [34], including the United
States [35,36]. One cannot help but think that this disinformation contributed to the resultant damage
from the pandemic.
Chapter 22 explores how best to design studies to take advantage of the methods described in
this book. It also should whet your appetite to study biostatistics further, as the story gets even more
fascinating. To quote what George Udny Yule wrote almost a century ago [37]:
When his work takes an investigator out of the field of the nearly perfect experiments, in
which the influence of disturbing causes is practically negligible, into the field of imperfect
experiment (or a fortiori of pure observation) where the influence of disturbing causes is
important, the first step necessary for him is to get out of the habit of thinking in terms of
the single observation and to think in terms of the average. Some seem never to get beyond
this stage. But the next state is even more important, viz., to get out of the habit of thinking
in terms of the average, and think in terms of the frequency distribution. Unless and until he
does this, his conclusions will always be liable to fallacy.

1.3.4 Computing Resources

In addition to Stata output, R output is presented for all examples in the Further Applications
sections of each chapter. In addition, all Stata and R code is available online, and can be accessed at
https://github.com/Principles-of-Biostatistics/3rd-Edition.
12 Principles of Biostatistics

1.4 Review Exercises

1. Design a study aimed at investigating an issue you believe might influence the health of
the world. Briefly describe the data you will require, how you will obtain them, how you
intend to analyze the data, and the method you will use to present your results. Keep this
study design and reread it after you have completed the text.

2. Suppose it is stated that in a given year, 512 million people around the world were
malnourished, up from 460 million just five years prior [38].
(a) Suppose that you sympathize with the point being made. Justify the use of these
numbers.
(b) Are you sure that the numbers are correct? Do you think it is possible that 513 million
people were malnourished during the year in question rather than 512 million?

3. In addition to stating that “the Chinese have eaten pasta since 1100 b.c.,” the label on
a box of pasta shells claims that “Americans eat 11 pounds of pasta per year,” whereas
“Italians eat 60 pounds per year.” Do you believe that these statistics are accurate? Would
you use these numbers as the basis for a nutritional study?
References
WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division, “Maternal Mortality:
Levels and Trends 2000–2017,” 2019, https://www.who.int/reproductivehealth/publications/maternal-mortality-
2000-2017/en.
Martin N, Montagne R, “US Has the Worst Rate of Maternal Deaths in the Developed World,” Propublica, May
12, 2017, https://www.npr.org/2017/05/12/528098789/us-has-the-worst-rate-of-maternal-deaths-in-the-
developed-world.
GBD 2015 Maternal Mortality Collaborators, “Global, Regional, and National Levels of Maternal Mortality,
1990–2015: A Systematic Analysis for the Global Burden of Disease Study 2015,” The Lancet, Volume 388,
10053, 1775–1812, October 8, 2016.
“Ten Great Public Health Achievements – United States, 1900–1999,” Morbidity and Mortality Weekly Report,
Volume 48, Number 12, April 2, 1999, 241–243.
“Ten Great Public Health Achievements – United States, 2001–2010,” Morbidity and Mortality Weekly Report,
Volume 60, Number 19, May 20, 2011, 619–623.
“Ten Great Public Health Achievements – Worldwide, 2001–2010,” Morbidity and Mortality Weekly Report,
Volume 60, Number 24, June 24, 2011, 814–818.
O'Neil C, Weapons of Math Destruction: How Big Data Increases Inequity and Threatens Democracy, New
York: Crown Random House, 2016.
Mervosh S, “Nearly 40,000 People Died From Guns in US Last Year, Highest in 50 Years,” The New York
Times, December 18, 2018, https://www.nytimes.com/2018/12/18/us/gun-deaths.html.
Katsiyannis A, Whitford DK, Ennis RP, “Historical Examination of United States Intentional Mass School
Shootings in the 20th and 21st Centuries: Implications for Students, Schools, and Society,” Journal of Child and
Family Studies, Volume 27, 2018, 2562.
Nemeth JM, Fraga Rizo C, “Estimating the Prevalence of Human Trafficking: Progress Made and Future
Directions,” American Journal of Public Health, Volume 109, Number 10, 2019, 1318–1319.
“Female Genital Mutilation/Cutting: A Global Concern,” UNICEF, 2016,
https://www.unicef.org/media/files/FGMC_2016_brochure_final_UNICEF_SPREAD.pdf.
Henney JE, Gayle HD, “Time to Reevaluate US Mifepristone Restrictions,” The New England Journal of
Medicine, Volume 381, 2019, 597–598.
The Flat Earth Society, 2013-2021, https://www.tfes.org.
Richard A, Oppel RA, Gebeloff R, Lai KKR, Wright W, Smith M, “The Fullest Look Yet at the Racial Inequity of
Coronavirus,” The New York Times, July 5, 2020.
National Center for Health Statistics, Health, United States, 2016: With Chartbook on Long-Term Trends in
Health, 2017.
Carter-Lome M, “Artfully Small Examples of the Real Thing,” The Journal of Antiques and Collectibles,
Sturbridge, Massachusetts, November 13, 2019.
Henrich J, Heine SJ, Norenzayan A, “Beyond WEIRD: Towards a Broad-Based Behavioral Science,”
Behavioral and Brain Sciences, Volume 33, 2010, 111–135.
Bavdekar SB, “Pediatric Clinical Trials,” Perspectives in Clinical Research, Volume 4, Number 1, 2013, 89–99.
Field MJ, Behrman RE, editors, Institute of Medicine (US) Committee on Clinical Research Involving Children,
“Ethical Conduct of Clinical Research Involving Children,” The Necessity and Challenges of Clinical Research
Involving Children, Washington, DC: National Academies Press, Volume 2, 2004,
https://www.ncbi.nlm.nih.gov/books/NBK25553.
Liu KA, Mager NA, “Women's Involvement in Clinical Trials: Historical Perspective and Future Implications,”
Pharmacy Practice (Granada), Volume 14, Number 1, 2016, 708, doi:10.18549/PharmPract.2016.01.708.
Oh SS, Galanter J, Thakur N, Pino-Yanes M, Barcelo NE, White MJ, de Bruin DM, Greenblatt RM, Bibbins-
Domingo K, Wu AHB, Borrell LN, Gunter C, Powel NR, Burchard EG, “Diversity in Clinical and Biomedical
Research: A Promise Yet to Be Fulfilled,” PLoS Medicine, Volume 12, Number 12, December 15, 2015,
e1001918.
“Clinical Trials Have Far Too Little Racial and Ethnic Diversity: It's Unethical and Risky to Ignore Racial and
Ethnic Minorities,” Scientific American, September 1, 2018.
Popejoy AB, Fullerton SM, “Genomics is Failing on Diversity,” Nature, Volume 538, Number 7624, October 13,
2016, 161–164.
Martin AR, Kanai M, Kamatani Y, Okada Y, Neale BM, Daly MJ, “Clinical Use of Current Polygenic Risk Scores
May Exacerbate Health Disparities,” Nature Genetics, Volume 51, 2019, 584–591.
Chen EH, Shofer FS, Dean AJ, Hollander JE, Baxt WG, Robey JL, Sease KL, Mills AM, “Gender Disparity in
Analgesic Treatment of Emergency Department Patients with Acute Abdominal Pain,” Academic Emergency
Medicine, Volume 15, Number 5, 2008, 414–418.
“Basic Information about Lead in Drinking Water,” Environmental Protection Agency, Drinking Water
Requirements for Lead, 2021, https://www.epa.gov/ground-water-and-drinking-water/basic-information-about-
lead-drinking-water#regs.
Lead and Copper Rule, Environmental Protection Agency, Drinking Water Requirements for Lead, 2021,
https://www.epa.gov/dwreginfo/lead-and-copper-rule.
Brush M, “Expert Says Michigan Officials Changed a Flint Lead Report to Avoid Federal Action,” National
Public Radio, November 5, 2015, https://www.michiganradio.org/post/expert-says-michigan- officials-changed-
flint-lead-report-avoid-federal-action.
Michigan Civil Rights Commission, The Flint Water Crisis: Systemic Racism Through the Lens of Flint, 2017.
Leyden L, “In Echo of Flint, Michigan, Water Crisis Now Hits Newark,” The New York Times, October 30, 2018.
Rich JT, Neely JG, Paniello RC, Voelker CCJ, Nussenbaum B, Wang EW, “A Practical Guide to Understanding
Kaplan-Meier Curves,” Otolaryngology – Head and Neck Surgery, Volume 143, Number 3, 2010, 331–336.
American Community Survey, https://www.census.gov/programs-surveys/acs.
Surveys and Data Collection Systems, National Center for Health Statistics,
https://www.cdc.gov/nchs/surveys.html.
Michaels D, “Extent of COVID-19 Deaths Failed to Be Captured by Most Countries” Wall Street Journal, May
28, 2020.
Bernstein L, “US Reports 66,000 More Deaths Than Expected So Far This Year,” The Washington Post, April
29, 2020.
Rossen LM, Branum AM, Ahmad FB, Sutton P, Anderson RN, “Excess Deaths Associated with COVID-19, by
Age and Race and Ethnicity – United States, January 26 – October 3, 2020,” Morbidity and Mortality Weekly
Report, Volume 69, 2020, 1522–1527.
Yule GU, The Function of Statistical Methods in Scientific Investigation, London: Medical Research Council
Industrial Fatigue Research Board, 1924.
United Nations Population Fund, “Family Planning: Saving Children, Improving Lives,” New York: Jones &
Janello, 1990.
Centers for Disease Control and Prevention, HIV/AIDS Surveillance Report, Volume 5, Number 4, 1994.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP, “Toxicity and Response
Criteria of the Eastern Cooperative Oncology Group,” American Journal of Clinical Oncology, Volume 5,
December 1982, 649–655.
Heron M, National Center for Health Statistics, National Vital Statistics Report, Volume 67, Number 6, July 26,
2018.
Wang TW, Kenemer B, Tynan MA, Singh T, King B, “Consumption of Combustible and Smokeless Tobacco –
United States, 2000-2015,” Morbidity and Mortality Weekly Report, Volume 65, Number 48, December 2016.
Fulwood R, Kalsbeek W, Rifkind B, Russell-Briefel R, Muesing R, LaRosa J, Lippel K, “Total Serum Cholesterol
Levels of Adults 20–74 Years of Age: United States, 1976–1980,” Vital and Health Statistics, Series 11,
Number 236, May 1986.
“Longterm Health Conditions,” National Health Survey: First Results 2014-15, Australian Bureau of Statistics,
August 2015, https://www.abs.gov.au/statistics/health/health-conditions-and-risks/national-health-survey-first-
results.
Spear ME, Charting Statistics, New York: McGraw-Hill, 1952.
National Center for Health Statistics, Centers for Disease Control and Prevention Compressed Mortality File,
1999–2016, CDC WONDER Online Database, June 2017, https://wonder.cdc.gov.
Tukey JW, Exploratory Data Analysis, Reading, Massachusetts: Addison-Wesley, 1977.
Bethel RA, Sheppard D, Geffroy B, Tam E, Nadel JA, Boushey HA, “Effect of 0.25 ppm Sulphur Dioxide on
Airway Resistance in Freely Breathing, Heavily Exercising, Asthmatic Subjects,” American Review of
Respiratory Disease, Volume 31, April 1985, 659–661.
Adams DA, Thomas KR, Jajosky RA, Foster L, Baroi G, Sharp P, Onweh DH, Schley AW, Anderson WJ, for the
Nationally Notifiable Infectious Conditions Group, “Summary of Notifiable Infectious Diseases and Conditions —
United States, 2015,” Morbidity and Mortality Weekly Report, Volume 64, Number 53, August 2017.
“National Health Expenditure Data: Historical,” Centers for Medicare & Medicaid Services, December 11, 2018,
www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-
Reports/NationalHealthExpendData.
“National Health Expenditure Trends, 1975 to 2018,” Canadian Institute for Health Information, Ottawa, Ontario:
CIHI, 2018.
Tufte ER, The Visual Display of Quantitative Information, Cheshire, Connecticut: Graphics Press, 1983.
“Causes of Death 2013,” Statistics South Africa, Pretoria, South Africa: 2016, http://www.statssa.gov.za.
Koenig JQ, Covert DS, Hanley QS, Van Belle G, Pierson WE, “Prior Exposure to Ozone Potentiates
Subsequent Response to Sulfur Dioxide in Adolescent Asthmatic Subjects,” American Review of Respiratory
Disease, Volume 141, February 1990, 377–380.
Prial FJ, “Wine Talk,” The New York Times, December 25, 1991, 29.
Framingham Heart Study Teaching Dataset, Biologic Specimen and Data Repository Information Coordinating
Center, National Heart, Lung, and Blood Institute, https://biolincc.nhlbi.gov/teaching.
McGuill D, “Does the United States Have a Lower Death Rate From Mass Shootings Than European
Countries?,” March 9, 2018, https://www.snopes.com.
“Ten Leading Causes of Injury Death by Age Group, Highlighting Unintentional Injury Deaths, United States –
2017,” National Center for Health Statistics, Centers for Disease Control and Prevention Injury Statistics Query
and Reporting System, 2019, https://www.cdc.gov/injury/wisqars/.
Natality Public Use Data 2007-2016, CDC WONDER Online Database, February 2018, https://wonder.cdc.gov.
“World Health Statistics 2018: Monitoring Health for the SDGs, Sustainable Development Goals,” Global Health
Observatory Data, Geneva: World Health Organization, 2018.
The Health Consequences of Smoking: 50 Years of Progress: A Report of the Surgeon General, Atlanta,
Georgia: Centers for Disease Control and Prevention, 2014,
https://www.cdc.gov/tobacco/data_statistics/sgr/50th-anniversary/index.htm.
Molfino NA, Nannini LJ, Martelli AN, Slutsky AS, “Respiratory Arrest in Near-Fatal Asthma,” The New England
Journal of Medicine, Volume 324, January 31, 1991, 285–288.
Nelson C, “Office Visits to Cardiovascular Disease Specialists, 1985,” Vital and Health Statistics, Advance Data
Report Number 171, June 23, 1989.
“Summary of Notifiable Diseases, United States, 1989,” Morbidity and Mortality Weekly Report, Volume 38,
October 5, 1990.
Kuntz T, “Killings, Legal and Otherwise, Around the US,” The New York Times, December 4, 1994, 3.
Wagenknecht LE, Burke GL, Perkins LL, Haley NJ, Friedman GD, “Misclassification of Smoking Status in the
CARDIA Study: A Comparison of Self-Report with Serum Cotinine Levels,” American Journal of Public Health,
Volume 82, January 1992, 33–36.
Yassi A, Cheang M, Tenenbein M, Bawden G, Spiegel J, Redekop T, “An Analysis of Occupational Blood Lead
Trends in Manitoba, 1979 Through 1987,” American Journal of Public Health, Volume 81, June 1991, 736–740.
Wynder EL, Graham EA, “Tobacco Smoking as a Possible Etiologic Factor in Bronchiogenic Carcinoma: A
Study of 684 Proved Cases,” Journal of the American Medical Association, Volume 143, 329–336.
Ochmann S, Roser M, “Smallpox,” Our World in Data, 2019, https://ourworldindata.org.
Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD, “Seizures and Other Neurologic Sequelae of Bacterial
Meningitis in Children,” The New England Journal of Medicine, Volume 323, December 13, 1990, 1651–1656.
Jacobus CH, Holick MF, Shao Q, Chen TC, Holm IA, Kolodny JM, Fuleihan GEH, Seely EW, “Hypervitaminosis
D Associated with Drinking Milk,” The New England Journal of Medicine, Volume 326, April 30, 1992,
1173–1177.
Gwirtsman HE, Kaye WH, Obarzanek E, George DT, Jimerson DC, Ebert MH, “Decreased Caloric Intake in
Normal-Weight Patients with Bulimia: Comparison with Female Volunteers,” American Journal of Clinical
Nutrition, Volume 49, January 1989, 86–92.
“Infant Mortality Rate,” The State of the World's Children, United Nations Children's Fund, 2013,
https://undata.org.
“Live Births by Month of Birth,” Demographic Statistics Database, United Nations Statistics Division, February
2019, https://undata.org.
Fulwood R, Johnson CL, Bryner JD, Gunter EW, McGrath CR, “Hematological and Nutritional Biochemistry
Reference Data for Persons 6 Months–74 Years of Age: United States, 1976–1980,” Vital and Health Statistics,
Series 11, Number 232, December 1982.
Bansal A, Garg C, Pakhare A, Gupta S, “Selfies: A Boon or Bane,” Journal of Family Medicine and Primary
Care, Volume 8, 2018, 828–831.
“Low Birthweight: Country, Regional and Global Estimates,” United Nations Children's Fund and World Health
Organization, New York: UNICEF, 2004.
Health, United States, 2016: With Chartbook on Long-term Trends in Health. Hyattsville, Maryland: National
Center for Health Statistics, May 2017, 1217–1232.
Kaiserman MJ, Rickert WS, “Carcinogens in Tobacco Smoke: Benzo[a]pyrene from Canadian Cigarettes and
Cigarette Tobacco,” American Journal of Public Health, Volume 82, July 1992, 1023–1026.
Ferdos J, Rahman M, “Maternal Experience of Intimate Partner Violence and Low Birth Weight of Children: A
Hospital-Based Study in Bangladesh,” PLoS ONE, 2017, 12:e0187138.
Leviton A, Fenton T, Kuban KCK, Pagano M, “Labor and Delivery Characteristics and the Risk of Germinal
Matrix Hemorrhage in Low Birth Weight Infants,” Journal of Child Neurology, Volume 6, October 1991, 35–40.
Kochanek KD, Murphy SL, Xu J, Arias E, “Deaths: Final Data for 2017,” National Vital Statistics Reports,
Volume 68, Number 6, June 24, 2019.
Scholl L, Seth P, Kariisa M, Wilson N, Baldwin G, “Drug and Opioid-Involved Overdose Deaths — United
States, 2013–2017,” Morbidity and Mortality Weekly Reports, ePub: December 21, 2018.
“Child Mortality – Number of Deaths,” Global Health Observatory, World Health Organization,
https://www.who.int/healthinfo/mortality_data/en/.
“Perinatal Mortality Rates by Country, 2000,” World Health Organization (2006) Neonatal and Perinatal
Mortality: Country, Regional and Global Estimates, Geneva: World Health Organization, 2006,
https://apps.who.int/iris/handle/10665/43444.
“Under-Five Mortality,” Global Health Observatory, World Health Organization,
https://www.who.int/gho/child_health/mortality/mortality_under_five_text/en/.
“Health Indicators, 2000,” Statistics Canada, Statistique Canada, Catalogue Number 82-221-XIE,
https://www150.statcan.gc.ca/n1/pub/82-221-x/4149077-eng.htm.
“Health,” The World Bank, 2020, https://data.worldbank.org/topic/8.
“2018 Global Reference List of 100 Core Health Indicators (plus health-related SDGs),” World Health
Organization, Geneva: World Health Organization, 2018. https://apps.who.int/iris/handle/10665/259951
Xu JQ, Murphy SL, Kochanek KD, Arias E, “Mortality in the United States, 2018,” National Center for Health
Statistics Data Brief, Number 355, Hyattsville, MD: National Center for Health Statistics, 2020.
Dimick JB, Staiger DO, Birkmeyer, J.D., “Ranking Hospitals on Surgical Mortality: The Importance of Reliability
Adjustment,” Health Services Research, Volume 45, Number 6, 2020, 1614–1629.
“A Look at the 1940 Census,” United States Census Bureau,
https://www.census.gov/newsroom/cspan/1940census/CSPAN_1940slides.pdf.
Vital Statistics of the United States, 1940, Washington: United States Government Printing Office, 1943,
https://www.cdc.gov/nchs/data/vsus/vsus_1940_1.pdf.
Murphy S, Xu J, Kochanek KD, “Deaths: Final Data for 2010,” National Vital Statistics Reports, Volume 61,
Number 4, May 8, 2013, https://www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_04.pdf.
Shalala, DE, “HHS Policy for Changing the Population Standard for Age Adjusting Death Rates, 8/26/98,”
United States Department of Health and Human Services, 1998, https://aspe.hhs.gov/hhs-policy-
changingpopulation-standard-age-adjusting-death-rates-82698.
Krieger N, Williams DR, “Changing to the 2000 Standard Million: Are Declining Racial/Ethnic and
Socioeconomic Inequalities in Health Real Progress or Statistical Illusion?,” American Journal of Public Health,
August 2001, Volume 91, Number 8, 1209–1213.
“Cancer Facts & Figures 2020,” American Cancer Society, Atlanta, Georgia: American Cancer Society,
https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2020.html.
Tate J, Jenkins J, Rich S, “Fatal Force,” The Washington Post,
http://www.washingtonpost.com/graphics/investigations/police-shootings-database.
Roser M, Ritchie H, “Cancer,” Our World in Data, 2015, https://ourworldindata.org/cancer.
Centers for Disease Control and Prevention, “National Diabetes Statistics Report, 2020,” Atlanta, Georgia:
Centers for Disease Control and Prevention, United States Department of Health and Human Services, 2020.
Ely DM, Driscoll AK, “Infant Mortality in the United States, 2018: Data from the Period Linked Birth/Infant Death
File,” National Vital Statistics Reports, Volume 69, Number 7, 2020.
Ely DM, Driscoll AK, “Infant Mortality in the United States, 2017: Data From the Period Linked Birth/Infant Death
File,” National Vital Statistics Reports, Volume 68, Number 10, 2019.
“Massachusetts Department of Public Health, Registry of Vital Records and Statistics,” Massachusetts Births
2017, November 2019, https://www.mass.gov/doc/2017-birth-report-updated.
“Massachusetts Department of Public Health, Registry of Vital Records and Statistics,” Massachusetts Deaths
2017, October 2019, https://www.mass.gov/doc/2017-death-report-updated.
Ely DM, Gregory EEW, Drake P, “Infant Mortality by Maternal Prepregnancy Body Mass Index: United States,
2017–2018,” National Vital Statistics Reports, Volume 69, Number 9, 2020.
Foreman J, “Making Age Obsolete: Scientists See Falling Barriers to Human Longevity,” The Boston Globe,
September 27, 1992, 1, 28–29.
Dell AJ, Kahn AJ, “Geographical Maldistribution of Surgical Resources in South Africa: A Review of the Number
of Hospitals, Hospital Beds and Surgical Beds,” South African Medical Journal, Volume 107, Number 12, 2017,
1099–1105.
Meier P, “Polio Trial: An Early Efficient Clinical Trial,” Statistics in Medicine, Volume 9, Number 1/2,
January–February 1990, 13–16.
National Center for Health Statistics, Vital Statistics Rates in the United States, 1900–1940, Chapters I–IV,
reprinted 1972.
Gardner JF, Wiedemann T, The Roman Household: A Sourcebook, New York: Routledge, Taylor and Francis
Group, 2013.
Graunt J, Natural and Political Observations Mentioned in a Following Index, and Made Upon the Bills of
Mortality, Fifth Edition, Much Enlarged, 1676.
Halley E, “An Estimate of the Degrees of the Mortality of Mankind, Drawn from Curious Tables of the Births and
Funerals at the City of Breslaw; with an Attempt to Ascertain the Price of Annuities upon Lives,” Philosophical
Transactions, Volume 17, 1693, 596–610.
Arias E, Xu J, Kochanek KD, “United States Life Tables, 2016,” National Vital Statistics Reports, Volume 68,
Number 4, May 7, 2019.
Arias E, “United States Life Tables, 2006,” National Vital Statistics Reports, Volume 58, Number 21, June 28,
2010.
Vandenbroucke JP, “Survival and Expectation of Life from the 1400s to the Present: A Study of the Knighthood
Order of the Golden Fleece,” American Journal of Epidemiology, Volume 122, December 1985, 1007–1015.
Organization for Economic Cooperation and Development, “Life Expectancy at Birth (Indicator),” OECD Data,
2020, doi: 10.1787/27e0fc9d-en.
Holden C, “Why Do Women Live Longer Than Men?,” Science, Volume 238, 1987, 158–160.
Eskes T, Haanen C, “Why Do Women Live Longer Than Men?,” European Journal of Obstetrics & Gynecology
and Reproductive Biology, Volume 133, Number 2, August 2007, 126–133.
Xirocostas ZA, Everingham SE, Moles AT, “The Sex with the Reduced Sex Chromosome Dies Earlier: A
Comparison Across the Tree of Life,” Biology Letters, Volume 16, Number 3, 2020, 20190867.
Woolhandler S, Himmelstein DU, Ahmed S, Bailey Z, Bassett MT, “Public Policy and Health in the Trump Era,”
The Lancet, February 11, 2021, https://doi.org/10.1016/S0140-6736(20)32545-9.
Wilkins R, Adams OB, “Health Expectancy in Canada, Late 1970s: Demographic, Regional, and Social
Dimensions,” American Journal of Public Health, Volume 73, September 1983, 1073–1080.
Arias E, Xu J, “United States Life Tables, 2017,” National Vital Statistics Reports, Volume 68, Number 7, June
24, 2019.
National Academies of Sciences, Engineering, and Medicine, The Growing Gap in Life Expectancy by Income:
Implications for Federal Programs and Policy Responses, Washington, DC: The National Academies Press,
2015, doi.org/10.17226/19015.
Medawar P, The Strange Case of the Spotted Mice, and Other Classic Essays on Science, Oxford: Oxford
University Press, 1996.
Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, “Births: Final Data for 2018,” National Center for Health
Statistics, National Vital Statistics Reports, Volume 68, Number 13, November 27, 2019.
Howden LM, Meyer JA, “Age and Sex Composition: 2010,” United States Census Bureau, May 2011.
Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB, Burke JR, Hurd MD, Potter GG,
Rodgers WL, Steffens DC, Willis RJ, Wallace RB, “Prevalence of Dementia in the United States: The Aging,
Demographics, and Memory Study,” Neuroepidemiology, Volume 29, 2007, 125–132.
Carter CL, Jones DY, Schatzkin A, Brinton LA, “A Prospective Study of Reproductive, Familial, and
Socioeconomic Risk Factors for Breast Cancer Using NHANES I Data,” Public Health Reports, Volume 104,
January–February 1989, 45–49.
Garfinkel L, Silverberg E, “Lung Cancer and Smoking Trends in the United States Over the Past 25 Years,”
Ca—A Cancer Journal for Clinicians, Volume 41, May/June 1991, 137–145.
Hennekens CH, Speizer FE, Lipnick RJ, Rosner B, Bain C, Belanger C, Stampfer MJ, Willett W, Peto R, “A
Case-Control Study of Oral Contraceptive Use and Breast Cancer,” Journal of the National Cancer Institute,
Volume 72, January 1984, 39–42.
Colditz GA, Hankinson SE, Hunter DJ, Willett WC, Manson JE, Stampfer MJ, Hennekens C, Rosner B, Speizer
FE, “The Use of Estrogens and Progestins and the Risk of Breast Cancer in Postmenopausal Women,” The
New England Journal of Medicine, Volume 332, June 15, 1995, 1589–1593.
American Cancer Society, Breast Cancer Facts & Figures 2017–2018, Atlanta, Georgia: American Cancer
Society, 2017.
American Cancer Society, Colorectal Cancer Facts & Figures 2017–2019, Atlanta, Georgia: American Cancer
Society, 2017.
Morales M, Joseph E, “Blacks and Latinos are Overwhelmingly Ticketed by NYPD for Social Distancing
Violations,” CNN, May 9, 2020, https://www.cnn.com/2020/05/08/us/social-distancing-stats-nyc/index.html.
Greer S, Naidoo M, Hinterland K, Archer A, Lundy de la Cruz N, Crossa A, Gould LH, “Health of Latinos in New
York City,” NYC Health, 2017, 1–32.
Freeman WJ, Weiss AJ, Heslin KC, “Overview of U.S. Hospital Stays in 2016: Variation by Geographic
Region,” Healthcare Cost and Utilization Project (HCUP) Statistical Briefs, December 18, 2018.
Berchick ER, Barnett JC, Upton RD, “Health Insurance Coverage in the United States, 2018,” United States
Census Bureau, November 8, 2019.
Sundaram A, Vaughan B, Kost K, Bankole A, Finer L, Singh S, Trussell J, “Contraceptive Failure in the United
States: Estimates from the 2006-2010 National Survey of Family Growth,” Perspectives on Sexual and
Reproductive Health, Volume 49, Number 1, February 28, 2017, 7–16.
Margolis PA, Greenberg RA, Keyes LL, LaVange LM, Chapman RS, Denny FW, Bauman KE, Boat BW, “Lower
Respiratory Illness in Infants and Low Socioeconomic Status,” American Journal of Public Health, Volume 82,
August 1992, 1119–1126.
“US and World Population Clock,” United States Census Bureau, May 25, 2020,
https://www.census.gov/popclock.
“Coronavirus Resource Center: COVID-19 Case Tracker,” Johns Hopkins University & Medicine, May 2020,
https://coronavirus.jhu.edu/map.html.
Maxim LD, Niebol R, Utell MJ, “Screening Tests: A Review with Examples,” Inhalation Toxicology, Volume 26,
Number 13, 2014, 811–820.
Mayrand MH, Duarte-Franco E, Rodrigues I, Walter SD, Hanley J, Ferenczy A, Ratnam S, Coutlee F, Franco
EL, “Human Papillomavirus DNA versus Papanicolaou Screening Tests for Cervical Cancer,” The New England
Journal of Medicine, Volume 357, Number 16, October 18, 2007, 1579–1588.
Kumar N, Bhargava SK, Agrawal CS, George K, Karki P, Baral D, “Chest Radiographs and Their Reliability in
the Diagnosis of Tuberculosis,” Journal of Nepal Medical Association, Volume 44, Number 160, 2005, 138–142.
Skerrett PJ, “Doctor Groups List Top Overused, Misused Tests, Treatments, and Procedures,” Harvard Health
Publishing, Harvard Medical School, April 5, 2012, www.health.harvard.edu/blog/doctor-groups-list-top-
overused-misused-tests-treatments-and-procedures-201204054570.
DeLong ER, Vernon WB, Bollinger RR, “Sensitivity and Specificity of a Monitoring Test,” Biometrics, Volume
41, December 1985, 947–958.
World Health Organization, “Preventive Chemotherapy in Human Helminthiasis: Coordinated Use of
Athelminthic Drugs in Control Interventions: A Manual for Health Professionals and Programme Managers,”
ISBN 978 92 4 154710 9, 2006.
Novick LF, Glebatis DM, Stricof RL, MacCubbin PA, Lessner L, Berns DS, “Newborn Seroprevalence Study:
Methods and Results,” American Journal of Public Health, Volume 81, May 1991, 15–21.
Gurevich R, “When to Take a Pregnancy Test: Understanding How Pregnancy Tests Really Work,”
https://www.verywellfamily.com/when-is-the-best-time-to-take-an-early-pregnancy-test-1960163.
Ransohoff DF, Feinstein AR, “Problems of Spectrum and Bias in Evaluating the Efficacy of Diagnostic Tests,”
The New England Journal of Medicine, Volume 299, Number 17, October 26, 1978, 926–930.
Hajian-Tilaki KO, Gholizadehpasha AR, Bozorgzadeh S, Hajian-Tilaki E, “Body Mass Index and Waist
Circumference are Predictor Biomarkers of Breast Cancer Risk in Iranian Women,” Medical Oncology, Volume
28, 2011, 1296–1301.
Kwon C, Farrell PM, “The Magnitude and Challenge of False-Positive Newborn Screening Test Results,”
Archives of Pediatrics and Adolescent Medicine, Volume 154, Number 7, 2000, 714–718.
“Screening Mammography Sensitivity, Specificity, and False Negative Rate,” Breast Cancer Surveillance
Consortium, March 23, 2017, https://www.bcsc-research.org/statistics/screening-performance-
benchmarks/screening-sens-spec-false-negative.
Katz JN, Larson MG, Fossel AH, Liang MH, “Validation of a Surveillance Case Definition of Carpal Tunnel
Syndrome,” American Journal of Public Health, Volume 81, February 1991, 189–193.
Begg CB, McNeil BJ, “Assessment of Radiologic Tests: Control of Bias and Other Design Considerations,”
Radiology, Volume 167, May 1988, 565–569.
Schroder FH, Kranse R, “Verification Bias and the Prostate-Specific Antigen Test – Is There a Case for a Lower
Threshold for Biopsy,” The New England Journal of Medicine, Volume 349, Number 4, July 24, 2003, 393–395.
Bortheiry AL, Malerbi DA, Franco LJ, “The ROC Curve in the Evaluation of Fasting Capillary Blood Glucose as
a Screening Test for Diabetes and IGT,” Diabetes Care, Volume 17, November 1994, 1269–1272.
Current Population Survey, “Households by Size, 1960 to Present,” United States Census Bureau, November
2018, https://census.gov.
Centers for Disease Control and Prevention, “Current Cigarette Smoking Among Adults in the United States,”
Fast Facts and Fact Sheets: Smoking & Tobacco Use, February 4, 2019, https://www.cdc.gov.
Wilson R, Crouch EAC, “Risk Assessment and Comparisons: An Introduction,” Science, Volume 236, April 17,
1987, 267–270.
National Center for Health Statistics, Drizd T, Dannenberg AL, Engel A, “Blood Pressure Levels in Persons
18–74 Years of Age in 1976–1980, and Trends in Blood Pressure From 1960 to 1980 in the United States,”
Vital and Health Statistics, Series 11, Number 234, July 1986.
Castelli WP, Anderson K, “Antihypertensive Treatment and Plasma Lipoprotein Levels: The Associations in
Data from a Population Study,” American Journal of Medicine Supplement, Volume 80, February 14, 1986,
23–32.
Tye L, “Many States Tackling Issue of AIDS-Infected Health Care Workers,” The Boston Globe, May 27, 1991,
29–30.
Centers for Disease Control, “Summary of Notifiable Diseases, United States, 1989,” Morbidity and Mortality
Weekly Report, Volume 39, October 5, 1990.
Najjar MF, Rowland M, “Anthropometric Reference Data and Prevalence of Overweight: United States,
1976–1980,” Vital and Health Statistics, Series 11, Number 238, October 1987.
Woodwell D, “Office Visits to Pediatric Specialists, 1989,” Vital and Health Statistics, Advance Data Report
Number 208, January 17, 1992.
National Center for Health Statistics, Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P, “Births:
Final Data for 2016,” National Vita Statistics Report, Volume 67, Number 1, 2018.
American Diabetes Association, “Overall Numbers, Diabetes and Prediabetes,” Statistics About Diabetes,
March 22, 2018, https://www.diabetes.org.
Youth Risk Behavior Surveillance System, “Adolescent and School Health, 2017,” National Center for
HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, August 22, 2018.
Gibbons RD, Clark DC, Fawcett J, “A Statistical Method for Evaluating Suicide Clusters and Implementing
Cluster Surveillance,” American Journal of Epidemiology Supplement, Volume 132, July 1990, 183–191.
Arias E, Xu J, “United States Life Tables, 2015,” National Vital Statistics Report, Volume 67, Number 7,
November 13, 2018.
MacMahon SW, MacDonald GJ, “A Population at Risk: Prevalence of High Cholesterol Levels in Hypertensive
Patients in the Framingham Study,” American Journal of Medicine Supplement, Volume 80, February 14, 1986,
40–47.
Lindgren BW, Statistical Theory, New York: Macmillan, 1976.
Snedecor GW, Cochran WG, Statistical Methods, Ames, Iowa: Iowa State University Press, 1980.
Scully RE, McNeely BU, Mark EJ, “Case Record of the Massachusetts General Hospital: Weekly
Clinicopathological Exercises,” The New England Journal of Medicine, Volume 314, January 2, 1986, 39–49.
Ostro BD, Lipsett MJ, Wiener MB, Selner JC, “Asthmatic Responses to Airborne Acid Aerosols,” American
Journal of Public Health, Volume 81, June 1991, 694–702.
Wilcox AJ, Skjærven R, “Birth Weight and Perinatal Mortality: The Effects of Gestational Age,” American
Journal of Public Health, Volume 82, March 1992, 378–382.
Loenen Hmja, Eshuis H, Lowik MRH, Schouten EG, Hulshof Kfam, Odink J, Kok FJ, “Serum Uric Acid
Correlates in Elderly Men and Women with Special Reference to Body Composition and Dietary Intake (Dutch
Nutrition Surveillance System),” Journal of Clinical Epidemiology, Volume 43, Number 12, 1990, 1297–1303.
Kaplan NM, “Strategies to Reduce Risk Factors in Hypertensive Patients Who Smoke,” American Heart
Journal, Volume 115, January 1988, 288–294.
Clark M, Royal J, Seeler R, “Interaction of Iron Deficiency and Lead and the Hematologic Findings in Children
with Severe Lead Poisoning,” Pediatrics, Volume 81, February 1988, 247–253.
Tsou VM, Young RM, Hart MH, Vanderhoof JA, “Elevated Plasma Aluminum Levels in Normal Infants
Receiving Antacids Containing Aluminum,” Pediatrics, Volume 87, February 1991, 148–151.
Streissguth AP, Aase JM, Clarren K, Randels SP, LaDue RA, Smith DF, “Fetal Alcohol Syndrome in
Adolescents and Adults,” Journal of the American Medical Association, Volume 265, April 17, 1991,
1961–1967.
Tirosh E, Elhasid R, Kamah SCB, Cohen A, “Predictive Value of Placebo Methylphenidate,” Pediatric
Neurology, Volume 9, Number 2, 1993, 131–133.
Klein BEK, Klein R, Moss SE, “Blood Pressure in a Population of Diabetic Persons Diagnosed After 30 Years of
Age,” American Journal of Public Health, Volume 74, April 1984, 336–339.
Ahmed T, Garrigo J, Danta I, “Preventing Bronchoconstriction in Exercise-Induced Asthma with Inhaled
Heparin,” The New England Journal of Medicine, Volume 329, July 8, 1993, 90–95.
Longaker MT, Golbus MS, Filly RA, Rosen MA, Chang SW, Harrison MR, “Maternal Outcome After Open Fetal
Surgery,” Journal of the American Medical Association, Volume 265, February 13, 1991, 737–741.
Saudek CD, Selam JL, Pitt HA, Waxman K, Rubio M, Jeandidier N, Turner D, Fischell RE, Charles MA, “A
Preliminary Trial of the Programmable Implantable Medication System for Insulin Delivery,” The New England
Journal of Medicine, Volume 321, August 31, 1989, 574–579.
Campbell S, Nash D, “The CDC's Gun Injury Data Is Becoming Even More Unreliable,” The Trace, March 11,
2019.
Bellinger DC, Jonas RA, Rappaport LA, Wypij D, Wernovsky G, Kuban KCK, Barnes PD, Holmes GL, Hickey
PR, Strand RD, Walsh AZ, Helmers SL, Constantinou JE, Carrazana EJ, Mayer JE, Hanley FL, Castaneda AR,
Ware JH, Newburger JW, “Developmental and Neurologic Status of Children After Heart Surgery with
Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass,” The New England Journal of Medicine,
Volume 332, March 2, 1995, 549–555.
Gauvreau K, Pagano M, “Why 5%?,” Nutrition, Volume 10, 1994, 93–94.
Wasserstein R, on behalf of the American Statistical Association, “ASA Statement on Statistical Significance
and P-Values,” The American Statistician, Volume 70, 2016, 129–133.
“Firm Admits Using Rival's Drug in Tests,” The Boston Globe, July 1, 1989, 41.
Davidson JW, Lytle MH, After the Fact: The Art of Historical Detection, Third Edition, Volume 1, New York:
McGraw-Hill, Inc., 1992, 26.
“Child Abuse – and Trial Abuse,” The New York Times, January 20, 1990, 24.
Appel BR, Guirguis G, Kim I, Garbin O, Fracchia M, Flessel CP, Kizer KW, Book SA, Warriner TE, “Benzene,
Benzo(a)Pyrene, and Lead in Smoke from Tobacco Products Other Than Cigarettes,” American Journal of
Public Health, Volume 80, May 1990, 560–564.
Rohrbach BW, Harkess JR, Ewing SA, Kudlac J, McKee GL, Istre GR, “Epidemiologic and Clinical
Characteristics of Persons with Serologic Evidence of E. canis Infection,” American Journal of Public Health,
Volume 80, April 1990, 442–445.
Feskens EJM, Kromhout D, “Cardiovascular Risk Factors and the 25 Year Incidence of Diabetes Mellitus in
Middle-Aged Men,” American Journal of Epidemiology, Volume 130, December 1989, 1101–1108.
Meade TW, Cooper JA, Peart WS, “Plasma Renin Activity and Ischemic Heart Disease,” The New England
Journal of Medicine, Volume 329, August 26, 1993, 616–619.
Burkholz H, The FDA Follies, New York: Basic Books, 1994, 107–113.
Packard FR, The Life and Times of Ambroise Paré, 1510–1590, New York: Paul B. Hoeber, 1921.
Rhodes J, Curran TJ, Camil L, Rabideau N, Fulton DR, Gauthier NS, Gauvreau K, Jenkins KJ, “Impact of
Cardiac Rehabilitation on the Excercise Function of Children with Serious Congenital Heart Disease,”
Pediatrics, Volume 116, 2005, 1339–1345.
Krasnoff JB, Vintro AQ, Ascher NL, Bass NM, Paul SM, Dodd MJ, Painter PL, “A Randomized Trial of Exercise
and Dietary Counseling After Liver Transplantation,” Americal Journal of Transplantation, Volume 6, 2006,
1896–1905.
Markowski CA, Markowski EP, “Conditions for the Effectiveness of a Preliminary Test of Variance,” The
American Statistician, Volume 44, November 1990, 322–326.
Moser BK, Stevens GR, “Homogeneity of Variance in the Two-Sample Means Test,” The American Statistician,
Volume 46, February 1992, 19–21.
Satterthwaite FW, “An Approximate Distribution of Estimates of Variance Components,” Biometrics Bulletin,
Volume 2, December 1946, 110–114.
SHEP Cooperative Research Group, “Prevention of Stroke by Antihypertensive Drug Treatment in Older
Persons with Isolated Systolic Hypertension: Final Results of the Systolic Hypertension in the Elderly Program
(SHEP),” Journal of the American Medical Association, Volume 265, June 26, 1991, 3255–3264.
Allred EN, Bleecker ER, Chaitman BR, Dahms TE, Gottlieb SO, Hackney JD, Hayes D, Pagano M, Selvester
RH, Walden SM, Warren J, “Acute Effects of Carbon Monoxide Exposure on Individuals with Coronary Artery
Disease,” Health Effects Institute Research Report Number 25, November 1989.
Kien CL, Liechty EA, Mullett MD, “Effects of Lactose Intake on Nutritional Status in Premature Infants,” Journal
of Pediatrics, Volume 116, March 1990, 446–449.
Wolff MS, Toniolo PG, Lee EW, Rivera M, Dubin N, “Blood Levels of Organochlorine Residues and Risk of
Breast Cancer,” Journal of the National Cancer Institute, Volume 85, April 21, 1993, 648–652.
DiGiusto E, Eckhard I, “Some Properties of Saliva Cotinine Measurements in Indicating Exposure to Tobacco
Smoking,” American Journal of Public Health, Volume 76, October 1986, 1245–1246.
Venkataraman PS, Duke JC, “Bone Mineral Content of Healthy, Full-term Neonates: Effect of Race, Gender,
and Maternal Cigarette Smoking,” American Journal of Diseases of Children, Volume 145, November 1991,
1310–1312.
Schiff E, Barkai G, Ben-Baruch G, Mashiach S, “Low-Dose Aspirin Does Not Influence the Clinical Course of
Women with Mild Pregnancy-Induced Hypertension,” Obstetrics and Gynecology, Volume 76, November 1990,
742–744.
Tramo MJ, Loftus WC, Green RL, Stukel TA, Weaver JB, Gazzaniga MS, “Brain Size, Head Size, and
Intelligence Quotient in Monozygotic Twins,” Neurology, Volume 50, Number 5, May 1998, 1246–1252.
Anderson JW, Spencer DB, Hamilton CC, Smith SF, Tietyen J, Bryant CA, Oeltgen P, “Oat-Bran Cereal Lowers
Serum Total and LDL Cholesterol in Hypercholesterolemic Men,” American Journal of Clinical Nutrition, Volume
52, September 1990, 495–499.
Stoline MR,“The Status of Multiple Comparisons: Simultaneous Estimation of All Pairwise Comparisons in One-
Way ANOVA Designs,” The American Statistician, Volume 35, Number 3, 1981, 134–141.
Wood PD, Stefanick ML, Dreon DM, Frey-Hewitt B, Garay SC, Williams PT, Superko HR, Fortmann SP, Albers
JJ, Vranizan KM, Ellsworth NM, Terry RB, Haskell WL, “Changes in Plasma Lipids and Lipoproteins in
Overweight Men During Weight Loss Through Dieting as Compared with Exercise,” The New England Journal
of Medicine, Volume 319, November 3, 1988, 1173–1179.
Chase HP, Garg SK, Marshall G, Berg CL, Harris S, Jackson WE, Hamman RE, “Cigarette Smoking Increases
the Risk of Albuminuria Among Subjects with Type I Diabetes,” Journal of the American Medical Association,
Volume 265, February 6, 1991, 614–617.
Fowkes FGR, Housley E, Riemersma RA, Macintyre CCA, Cawood EHH, Prescott RJ, Ruckley CV, “Smoking,
Lipids, Glucose Intolerance, and Blood Pressure as Risk Factors for Peripheral Atherosclerosis Compared with
Ischemic Heart Disease in the Edinburgh Artery Study,” American Journal of Epidemiology, Volume 135,
February 15, 1992, 331–340.
Wheeler JRC, Fadel H, D'Aunno TA, “Ownership and Performance of Outpatient Substance Abuse Treatment
Centers,” American Journal of Public Health, Volume 82, May 1992, 711–718.
Spicher V, Roulet M, Schutz Y, “Assessment of Total Energy Expenditure in Free-Living Patients with Cystic
Fibrosis,” Journal of Pediatrics, Volume 118, June 1991, 865–872.
Knowles MR, Church NL, Waltner WE, Yankaskas JR, Gilligan P, King M, Edwards LJ, Helms RW, Boucher
RC, “A Pilot Study of Aerosolized Amiloride for the Treatment of Lung Disease in Cystic Fibrosis,” The New
England Journal of Medicine, Volume 322, April 26, 1990, 1189–1194.
Hollander M, Wolfe DA, Nonparametric Statistical Methods, New York: Wiley, 1973.
Wrona RM, “A Clinical Epidemiologic Study of Hyperphenylalaninemia,” American Journal of Public Health,
Volume 69, July 1979, 673–679.
Burch KD, Covitz W, Lovett EJ, Howell C, Kanto WP, “The Significance of Ductal Shunting During
Extracorporeal Membrane Oxygenation,” Journal of Pediatric Surgery, Volume 24, September 1989, 855–859.
Morrison NJ, Abboud RT, Ramadan F, Miller RR, Gibson NN, Evans KG, Nelems B, Müller NL, “Comparison of
Single Breath Carbon Monoxide Diffusing Capacity and Pressure-Volume Curves in Detecting Emphysema,”
American Review of Respiratory Disease, Volume 139, May 1989, 1179–1187.
Abdelrahman I, Elmasry M, Olofsson P, Steinvall I, Fredrikson M, Sjoberg F, “Division of Overall Duration of
Stay into Operative Stay and Postoperative Stay Improves the Overall Estimate as a Measure of Quality of
Outcome in Burn Care,” PLoS ONE, Volume 12, March 2017, e0174579.
Lee LA, Kimball TR, Daniels SR, Khoury P, Meyer RA, “Left Ventricular Mechanics in the Preterm Infant and
their Effect on the Measurement of Cardiac Performance,” The Journal of Pediatrics, Volume 120, January
1992, 114–119.
Walker AM, Jick H, Perera DR, Thompson RS, Knauss TA, “Diphtheria–Tetanus–Pertussis Immunization and
Sudden Infant Death Syndrome,” American Journal of Public Health, Volume 77, August 1987, 945–951.
Jeffery RW, Forster JL, French SA, Kelder SH, Lando HA, McGovern PG, Jacobs DR, Baxter JE, “The Healthy
Worker Project: A Work-Site Intervention for Weight Control and Smoking Cessation,” American Journal of
Public Health, Volume 83, March 1993, 395–401.
Ayanian JZ, Kohler BA, Abe T, Epstein AM, “The Relation Between Health Insurance Coverage and Clinical
Outcomes Among Women with Breast Cancer,” The New England Journal of Medicine, Volume 329, July 29,
1993, 326–331.
Nuland SB, Doctors: The Biography of Medicine, New York: Vintage Books, 1989.
“Lung Cancer Survival Rates,” American Cancer Society, January 9, 2020, https://cancer.org/cancer/lung-
cancer/detection-diagnosis-staging.
Liu M, Cai X, Yu W, Lv C, Fu X, “Clinical Significance of Age at Diagnosis Among Young Non-Small Cell Lung
Cancer Patients Under 40 Years Old: A Population-Based Study,” Oncotarget, Volume 6, 2015, 44963–44970.
Brown LD, Cai TT, DasGupta A, “Interval Estimation for a Binomial Proportion,” Statistical Science, Volume 16,
2001, 101–133.
Wilson EB, “Probable Inference, the Law of Succession, and Statistical Inference,” Journal of the American
Statistical Association, Volume 22, 1927, 209–212.
Rosner B, Fundamentals of Biostatistics, Seventh Edition, Boston, Massachusetts: Brooks/Cole, Cengage
Learning, 2011.
Osberg JS, DiScala C, “Morbidity Among Pediatric Motor Vehicle Crash Victims: The Effectiveness of Seat
Belts,” American Journal of Public Health, Volume 82, March 1992, 422–425.
Hack M, Breslau N, Weissman B, Aram D, Klein N, Borawski E, “Effect of Very Low Birth Weight and
Subnormal Head Size on Cognitive Abilities at School Age,” The New England Journal of Medicine, Volume
325, July 25, 1991, 231–237.
Sheehan WJ, Mauger DT, Paul IM, Moy JN, Boehmer SJ, Szefler SJ, Fitzpatrick AM, Jackson DJ, Bacharier
LB, Cabana MD, “Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma,” The New
England Journal of Medicine, Volume 375, August 18, 2016, 619–630.
Sanchis-Gomar F, Perez-Quilis C, Leischik R, Lucia A, “Epidemiology of Coronary Heart Disease and Acute
Coronary Syndrome,” Annals of Translational Medicine, Volume 4, July 2016, 256.
Tsai J, Hoff RA, Harpaz-Rotem I, “One-Year Incidence and Predictors of Homelessness Among 300,000 US
Veterans Seen in Specialty Mental Health Care,” Psychological Services, Volume 14, 2017, 203–207.
Magruder KM, Frueh BC, Knapp RG, Davis L, Hamner MB, Martin RH, Gold PB, Arana GW, “Prevalence of
Posttraumatic Stress Disorder in Veterans Affairs Primary Care Clinics,” General Hospital Psychiatry, Volume
27, 2005, 169–179.
Peyron R, Aubeny E, Targosz V, Silvestre L, Renault M, Elkik F, Leclerc P, Ulmann A, Baulieu E, “Early
Termination of Pregnancy with Mifepristone (RU 486) and the Orally Active Prostaglandin Misoprostol,” The
New England Journal of Medicine, Volume 328, May 27, 1993, 1509–1513.
Folsom AR, Grim RH, “Stop Smoking Advice by Physicians: A Feasible Approach?,” American Journal of Public
Health, Volume 77, July 1987, 849–850.
Christianson JB, Lurie N, Finch M, Moscovice IS, Hartley D, “Use of Community-Based Mental Health
Programs by HMOs: Evidence from a Medicaid Demonstration,” American Journal of Public Health, Volume 82,
June 1992, 790–796.
Graham NMH, Nelson KE, Solomon L, Bonds M, Rizzo RT, Scavotto J, Astemborski J, Vlahov D, “Prevalence
of Tuberculin Positivity and Skin Test Anergy in HIV-1-Seropositive and -Seronegative Intravenous Drug
Users,” Journal of the American Medical Association, Volume 267, January 15, 1992, 369–373.
Wijnen M, Olsson DS, van den Heuvel-Eibrink MM, Hammarstrand C, Janssen Jamjl, van der Lely AJ,
Johannsson G, Neggers Sjcmm, “The Metabolic Syndrome and its Components in 178 Patients Treated for
Craniopharyngioma after 16 Years of Follow-up,” European Journal of Endocrinology, Volume 178, 2018,
11–22.
Juul SE, Comstock BA, Wadhawan R, Mayock DE, Courtney SE, Robinson T, Ahmad KA, Bendel-Stenzel E,
Baserga M, LaGamma EF, “A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants,” The
New England Journal of Medicine, Volume 382, January 16, 2020, 233–243.
Thompson RS, Rivara FP, Thompson DC, “A Case-Control Study of the Effectiveness of Bicycle Safety
Helmets,” The New England Journal of Medicine, Volume 320, May 25, 1989, 1361–1367.
Cochran WG, “Some Methods for Strengthening the Common χ2 Test,” Biometrics, Volume 10, December
1954, 417–451.
Grizzle JE, “Continuity Correction in the χ2 Test for 2×2 Tables,” The American Statistician, Volume 21,
October 1967, 28–32.
Schottenfeld D, Eaton M, Sommers SC, Alonso DR, Wilkinson C, “The Autopsy as a Measure of Accuracy of
the Death Certificate,” Bulletin of the New York Academy of Medicine, Volume 58, December 1982, 778–794.
Coulehan JL, Lerner G, Helzlsouer K, Welty TK, McLaughlin J, “Acute Myocardial Infarction Among Navajo
Indians, 1976–1983,” American Journal of Public Health, Volume 76, April 1986, 412–414.
McCusker J, Harris DR, Hosmer DW, “Association of Electronic Fetal Monitoring During Labor with Cæsarean
Section Rate and with Neonatal Morbidity and Mortality,” American Journal of Public Health, Volume 78,
September 1988, 1170–1174.
Roberts RS, Spitzer WO, Delmore T, Sackett DL, “An Empirical Demonstration of Berkson's Bias,” Journal of
Chronic Diseases, Volume 31, February 1978, 119–128.
Gross TP, Conde JG, Gary GW, Harting D, Goeller D, Israel E, “An Outbreak of Acute Infectious Nonbacterial
Gastroenteritis in a High School in Maryland,” Public Health Reports, Volume 104, March–April 1989, 164–169.
Kirscht JP, Brock BM, Hawthorne VM, “Cigarette Smoking and Changes in Smoking Among a Cohort of
Michigan Adults, 1980-82,” American Journal of Public Health, Volume 77, April 1987, 501–502.
Engs RC, Hanson DJ, “University Students' Drinking Patterns and Problems: Examining the Effects of Raising
the Purchase Age,” Public Health Reports, Volume 103, November–December 1988, 667–673.
Tilyard MW, Spears GFS, Thomson J, Dovey S, “Treatment of Postmenopausal Osteoporosis with Calcitriol or
Calcium,” The New England Journal of Medicine, Volume 326, February 6, 1992, 357–362.
Liberati A, Apolone G, Nicolucci A, Confalonieri C, Fossati R, Grilli R, Torri V, Mosconi P, Alexanian A, “The
Role of Attitudes, Beliefs, and Personal Characteristics of Italian Physicians in the Surgical Treatment of Early
Breast Cancer,” American Journal of Public Health, Volume 81, January 1991, 38–42.
Kircher T, Nelson J, Burdo H, “The Autopsy as a Measure of Accuracy of the Death Certificate,” The New
England Journal of Medicine, Volume 313, November 14, 1985, 1263–1269.
Siscovick DS, Strogatz DS, Weiss NS, Rennert G, “Retirement and Primary Cardiac Arrest in Males,” American
Journal of Public Health, Volume 80, February 1990, 207–208.
Lilienfeld AM, Graham S, “Validity of Determining Circumcision Status by Questionnaire as Related to
Biological Studies of Cancer of the Cervix,” Journal of the National Cancer Institute, Volume 21, October 1958,
713–720.
Haahtela T, Marttila O, Vilkka V, Jappinen P, Jaakkola JJK, “The South Karelia Air Pollution Study: Acute
Health Effects of Malodorous Sulphur Air Pollutants Released by a Pulp Mill,” American Journal of Public
Health, Volume 82, April 1992, 603–605.
Nischan P, Ebeling K, Schindler C, “Smoking and Invasive Cervical Cancer Risk: Results from a Case-Control
Study,” American Journal of Epidemiology, Volume 128, July 1988, 74–77.
Coste J, Job-Spira N, Fernandez H, Papiernik E, Spira A, “Risk Factors for Ectopic Pregnancy: A Case-Control
Study in France, with Special Focus on Infectious Factors,” American Journal of Epidemiology, Volume 133,
May 1, 1991, 839–849.
Armstrong BG, McDonald AD, Sloan M, “Cigarette, Alcohol, and Coffee Consumption and Spontaneous
Abortion,” American Journal of Public Health, Volume 82, January 1992, 85–87.
Smith PF, Mikl J, Truman BI, Lessner L, Lehman JS, Stevens RW, Lord EA, Broaddus RK, Morse DL, “HIV
Infection Among Women Entering the New York State Correctional System,” American Journal of Public Health
Supplement, Volume 81, May 1991, 35–40.
Chassin MR, Kosecoff J, Park RE, Winslow CM, Kahn KL, Merrick NJ, Keesey J, Fink A, Solomon DH, Brook
RH, “Does Inappropriate Use Explain Geographic Variations in the Use of Health Care Services?,” Journal of
the American Medical Association, Volume 258, November 13, 1987, 2533–2537.
King A, “Enhancing the Self-Report of Alcohol Consumption in the Community: Two Questionnaire Formats,”
American Journal of Public Health, Volume 84, February 1994, 294–296.
Rea TD, Fahrenbruch C, Culley L, Donohoe RT, Hambly C, Innes J, Bloomingdale M, Subido C, Romines S,
Eisenberg MS, “CPR with Chest Compression Alone or with Rescue Breathing,” The New England Journal of
Medicine, Volume 363, July 29, 2010, 423–432.
“Children, Food, and Nutrition: Growing Well in a Changing World,” The State of the World's Children 2019,
New York: UNICEF, 2019.
Tefft BC, “Rates of Motor Vehicle Crashes, Injuries and Deaths in Relation to Driver Age, United States, 2014-
2015,” AAA Foundation for Traffic Safety, June 2017.
Cominacini L, Zocca I, Garbin U, Davoli A, Compri R, Brunetti L, Bosello O, “Long-Term Effect of a Low-Fat,
High-Carbohydrate Diet on Plasma Lipids of Patients Affected by Familial Endogenous Hypertriglyceridemia,”
American Journal of Clinical Nutrition, Volume 48, July 1988, 57–65.
Miller PF, Sheps DS, Bragdon EE, Herbst MC, Dalton JL, Hinderliter AL, Koch GG, Maixner W, Ekelund LG,
“Aging and Pain Perception in Ischemic Heart Disease,” American Heart Journal, Volume 120, July 1990,
22–30.
Dean HT, Arnold FA, Elvove E, “Domestic Water and Dental Caries,” Public Health Reports, Volume 57, August
7, 1942, 1155–1179.
Wolfe SM, Williams C, Zaslow A, “Public Citizen Health Research Group Ranking of the Rate of State Medical
Boards' Serious Disciplinary Actions, 2009–2011,” Public Citizen, May 17, 2012.
Rollins JD, Collins JS, Holden KR, “United States Head Circumference Growth Reference Charts,” Journal of
Pediatrics, Volume 156, 2010, 907–913.
Kleinbaum DG, Kupper LL, Muller KE, Applied Regression Analysis and Other Multivariable Methods, Boston,
Massachusetts: PWS-Kent, 1988.
State of the World's Children 2019. Children, Food, and Nutrition: Growing Well in a Changing World, New
York: UNICEF, 2019.
Wyatt JS, Edwards AD, Cope M, Delpy DT, McCormick DC, Potter A, Reynolds EOR, “Response of Cerebral
Blood Volume to Changes in Arterial Carbon Dioxide Tension in Preterm and Term Infants,” Pediatric
Research, Volume 29, June 1991, 553–557.
Ahmadian HR, Sclafani JJ, Emmons EE, Morris MJ, Leclerc KM, Slim AM, “Comparison of Predicted Exercise
Capacity Equations and the Effect of Actual versus Ideal Body Weight among Subjects Undergoing
Cardiopulmonary Exercise Testing,” Cardiology Research and Practice, Volume 2013, ID 940170.
Weeks JL, Fox M, “Fatality Rates and Regulatory Policies in Bituminous Coal Mining, United States,
1959–1981,” American Journal of Public Health, Volume 73, November 1983, 1278–1280.
Agongo G, Nonterah EA, Debpuur C, Amenga-Elego L, Ali S, Oduro A, Crowther NJ, Ramsey M, “The Burden
of Dyslipidaemia and Factors Associated with Lipid Levels Among Adults in Rural Northern Ghana: An AWI-
Gen Sub-Study,” PLoS ONE, Volume 13, 2018, e0206326.
Gapminder, Data, 2005, www.gapminder.org/data.
Van Horn L, Moag-Stahlberg A, Liu K, Ballew C, Ruth K, Hughes R, Stamler J, “Effects on Serum Lipids of
Adding Instant Oats to Usual American Diets,” American Journal of Public Health, Volume 81, February 1991,
183–188.
Almond CSD, Shin AY, Fortescue EB, Mannix RC, Wypij D, Binstadt BA, Duncan CN, Olson DP, Salerno AE,
Newburger JW, Greenes DS, “Hyponatremia among Runners in the Boston Marathon,” The New England
Journal of Medicine, Volume 352, April 14, 2005, 1550–1556.
Hosmer DW, Lemeshow S, Applied Logistic Regression, New York: Wiley, 1989.
Hoagland PM, Cook EF, Flatley M, Walker C, Goldman L, “Case-Control Analysis of Risk Factors for the
Presence of Aortic Stenosis in Adults (Age 50 Years or Older),” American Journal of Cardiology, Volume 55,
March 1, 1985, 744–747.
Zweig MS, Singh T, Htoo M, Schultz S, “The Association Between Congenital Syphilis and Cocaine/Crack Use
in New York City: A Case-Control Study,” American Journal of Public Health, Volume 81, October 1991,
1316–1318.
Holtzman D, Anderson JE, Kann L, Arday SL, Truman BI, Kohbe LJ, “HIV Instruction, HIV Knowledge, and
Drug Injection Among High School Students in the United States,” American Journal of Public Health, Volume
81, December 1991, 1596–1601.
Rosenberg L, Palmer JR, Kelly JP, Kaufman DW, Shapiro S, “Coffee Drinking and Nonfatal Myocardial
Infarction in Men Under 55 Years of Age,” American Journal of Epidemiology, Volume 128, September 1988,
570–578.
Martinez FD, Cline M, Burrows B, “Increased Incidence of Asthma in Children of Smoking Mothers,” Pediatrics,
Volume 89, January 1992, 21–26.
Pearl R, “Tobacco Smoking and Longevity,” Science, Volume 87, March 4, 1938, 216–217.
Ragni MV, Kingsley LA, “Cumulative Risk for AIDS and Other HIV Outcomes in a Cohort of Hemophiliacs in
Western Pennsylvania,” Journal of Acquired Immune Deficiency Syndromes, Volume 3, July 1990, 708–713.
Brown BW, “Estimation in Survival Analysis: Parametric Models, Product-Limit and Life Table Methods,”
Statistics in Medical Research, New York: Wiley, 1982.
Hosmer DW, Lemeshow S, Applied Survival Analysis: Regression Modeling of Time to Event Data, New York:
John Wiley, 1999.
Shapiro CL, Henderson IC, Gelman RS, Harris JR, Canellos GP, Frei E, “A Randomized Trial of
Cyclophosphamide, Methotrexate, and Fluorouracil Versus Methotrexate, Fluorouracil Adjuvant Chemotherapy
in Moderate Risk Breast Cancer Patients,” Proceedings of the American Association for Cancer Research,
Volume 31, March 1990, 185.
Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, Markesbery WR, MacDonald JS,
Young B, “A Randomized Trial of Surgery in the Treatment of Single Metastases to the Brain,” The New
England Journal of Medicine, Volume 322, February 22, 1990, 494–500.
Ash RC, Casper JT, Chitambar CR, Hansen R, Bunin N, Truitt RL, Lawton C, Murray K, Hunter J, Baxter-Lowe
LA, Gottschall JL, Oldham K, Anderson T, Camitta B, Menitove J, “Successful Allogeneic Transplantation of T-
Cell Depleted Bone Marrow from Closely HLA-Matched Unrelated Donors,” The New England Journal of
Medicine, Volume 322, February 22, 1990, 485–494.
Laine L, Bonacini M, Sattler F, Young T, Sherrod A, “Cytomegalovirus and Candida Esophagitis in Patients with
AIDS,” Journal of Acquired Immune Deficiency Syndromes, Volume 5, June 1992, 605–609.
Hviid A, Hansen JV, Frisch M, Melbye M, “Measles, Mumps, Rubella Vaccination and Autism: A Nationwide
Cohort Study,” Annals of Internal Medicine, Volume 170, 2019, 513–520.
Kotler DP, “Cytomegalovirus Colitis and Wasting,” Journal of Acquired Immune Deficiency Syndromes, Volume
4, Supplement 1, 1991, S36–S41.
Wei LJ, Lin DY, Weissfeld L, “Regression Analysis of Multivariate Incomplete Failure Time Data by Modeling
Marginal Distributions,” Journal of the American Statistical Association, Volume 84, December 1989,
1065–1073.
Ahmad T, Munir A, Bhatti SH, Aftab M, Raza MA, “Survival Analysis of Heart Failure Patients: A Case Study,”
PLoS ONE, Volume 12, 2017, e0181001.
National Health Interview Survey, National Center for Health Statistics, Centers for Disease Control and
Prevention, 2021, https://www.cdc.gov/nchs/nhis.
NCHS Fact Sheets, National Center for Health Statistics, Centers for Disease Control and Prevention, 2021,
https://www.cdc.gov/nchs/about/fact_sheets.htm.
“Data Collection Systems,” National Center for Health Statistics, Centers for Disease Control and Prevention,
2021, https://www.cdc.gov/nchs/index.htm.
The Demographic and Health Surveys Program, https://dhsprogram.com.
Judiciary and Judicial Procedure, Part V, “Chapter 121: Juries, Trials by Jury,” Legal Information Institute,
United States Government Publishing Office, 2012, https://www.govinfo.gov/content/pkg/USCODE-2012-title28-
partV-chap121.html.
Chernoff NW, “No Records, No Right: Discovery & the Fair Cross-Section Guarantee,” Iowa Law Review,
Volume 101, 2016, 1719–1786.
Rao RU, Samarasekera SD, Nagodavithana KC, Punchihewa MW, Ranasinghe USB, Weil GJ, “Systematic
Sampling of Adults as a Sensitive Means of Detecting Persistence of Lymphatic Filariasis Following Mass Drug
Administration in Sri Lanka,” PLoS Neglected Tropical Diseases, Volume 13, April 22, 2019,
https://doi.org/10.1371/journal.pntd.0007365.
Nelson RK, Winling L, Marciano R, Connolly N, “Mapping Inequality,” American Panorama, ed. Nelson RK,
Ayers EL, https://dsl.richmond.edu/panorama/redlining.
Statistical Release P0302 Mid-Year Population Estimates, Statistics South Africa, Republic of South Africa,
2019.
Dell A, Kahn D, “Geographical Maldistribution of Surgical Resources in South Africa: A Review of the Number
of Hospitals, Hospital Beds and Surgical Beds,” South African Medical Journal, Volume 107, 2017, 1099–1105.
Laplace, PS, “Sur les Naissances, les Mariages et les Morts,” Mémoires de l'Académie Royale des Sciences de
Paris, 1783, 693–702.
Lohr SL, Sampling Design and Analysis, Second Edition, New York: Chapman and Hall/CRC, 2019.
Henderson RE, Davis H, Eddins D, Foege W, “Assessment of Vaccination Coverage, Vaccination Scar Rates,
and Smallpox Scarring in Five Areas of West Africa,” Bulletin of the World Health Organization, Volume 48,
1973, 183–194.
Henderson RE, Sundaresan T, “Cluster Sampling to Assess Immunization Coverage: A Review of Experience
with a Simplified Sampling Method,” Bulletin of the World Health Organization, Volume 60, 1982, 253–260.
“The Immunization Programme that Saved Millions of Lives,” Bulletin of the World Health Organization, Volume
92, 2014, 314–315.
Otte MJ, Gumm ID, “Intra-Cluster Correlation Coefficients of 20 Infections Calculated from the Results of
Cluster-Sample Surveys,” Preventive Veterinary Medicine, Volume 31, 1997, 147–150.
Gatrell N, Herman J, Olarte S, Feldstein M, Localio R, “Psychiatrist–Patient Sexual Contact: Results of a
National Survey, Prevalence,” American Journal of Psychiatry, Volume 143, September 1986, 1126–1131.
Owen K, “Honesty No Longer Assumed Where Religion is Concerned,” The Owensboro Messenger–Inquirer,
January 16, 1999.
Weissman AN, Steer RA, Lipton DS, “Estimating Illicit Drug Use Through Telephone Interviews and the
Randomized Response Technique,” Drug and Alcohol Dependence, Volume 18, 1986, 225–233.
Zuckerman B, Frank DA, Hingson R, Amaro H, Levenson SM, Kayne H, Parker S, Vinci R, Aboagye K, Fried
LE, Cabral H, Timperi R, Bauchner H, “Effects of Maternal Marijuana and Cocaine Use on Fetal Growth,” The
New England Journal of Medicine, Volume 320, June 1989, 762–768.
Hatziandreu EJ, Pierce JP, Fiore MC, Grise V, Novotny TE, Davis RM, “The Reliability of Self-Reported
Cigarette Consumption in the United States,” American Journal of Public Health, Volume 79, August 1989,
1020–1023.
Silverman H, “Ethical Issues during the Conduct of Clinical Trials,” Proceedings of the American Thoracic
Society, Volume 4, 2007, 180–184.
Talbot TR, Stapleton JT, Brady RC, Winokur PL, Bernstein DI, Germanson T, Yoder SM, Rock MT, Crowe JE,
Edwards KM, “Vaccination Success Rate and Reaction Profile with Diluted and Undiluted Smallpox Vaccine,”
Journal of the American Medical Association, Volume 292, September 2004, 1205–1212.
Best M, Neuhauser D, Slavin L, “Evaluating Mesmerism, Paris, 1784: The Controversy Over the Blinded
Placebo Controlled Trials has not Stopped,” Quality and Safety in Health Care, Volume 12, 2003.
Rosner F, “The Ethics of Randomized Clinical Trials,” American Journal of Medicine, Volume 82, 1987,
283–290.
Collins R, Bowman L, Landray M, Peto R, “The Magic of Randomization versus the Myth of Real-World
Evidence,” The New England Journal of Medicine, Volume 382, February 13, 2020, 674–678.