Bayesian Methods in Epidemiology, 1st Edition

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 Bayesian
Methods in
Epidemiology
 Editor-in-Chief

Shein-Chung Chow, Ph.D.

Professor
Department of Biostatistics and Bioinformatics
Duke University School of Medicine
Durham, North Carolina

Series Editors

Byron Jones Jen-pei Liu

Biometrical Fellow Professor
Statistical Methodology Division of Biometry
Integrated Information Sciences Department of Agronomy
National Taiwan University
Novartis Pharma AG
Taipei, Taiwan
Basel, Switzerland

Karl E. Peace Bruce W. Turnbull

Georgia Cancer Coalition Professor
Distinguished Cancer Scholar School of Operations Research
Senior Research Scientist and and Industrial Engineering
Professor of Biostatistics Cornell University
Jiann-Ping Hsu College of Public Health Ithaca, New York
Georgia Southern University
Statesboro, Georgia
Adaptive Design Methods in Biostatistics: A Computing Approach
Clinical Trials, Second Edition Stewart J. Anderson
Shein-Chung Chow and Mark Chang Causal Analysis in Biomedicine and
Adaptive Design Theory and Epidemiology: Based on Minimal
Implementation Using SAS and R Sufficient Causation
Mark Chang Mikel Aickin
Advanced Bayesian Methods for Medical Clinical Trial Data Analysis using R
Test Accuracy Ding-Geng (Din) Chen and Karl E. Peace
Lyle D. Broemeling Clinical Trial Methodology
Advances in Clinical Trial Biostatistics Karl E. Peace and Ding-Geng (Din) Chen
Nancy L. Geller Computational Methods in Biomedical
Applied Meta-Analysis with R Research
Ding-Geng (Din) Chen and Karl E. Peace Ravindra Khattree and Dayanand N. Naik
Basic Statistics and Pharmaceutical Computational Pharmacokinetics
Statistical Applications, Second Edition Anders Källén
James E. De Muth Confidence Intervals for Proportions and
Bayesian Adaptive Methods for Related Measures of Effect Size
Clinical Trials Robert G. Newcombe
Scott M. Berry, Bradley P. Carlin, Controversial Statistical Issues in
J. Jack Lee, and Peter Muller Clinical Trials
Bayesian Analysis Made Simple: An Excel Shein-Chung Chow
GUI for WinBUGS Data and Safety Monitoring Committees
Phil Woodward in Clinical Trials
Bayesian Methods for Measures of Jay Herson
Agreement Design and Analysis of Animal Studies in
Lyle D. Broemeling Pharmaceutical Development
Bayesian Methods in Epidemiology Shein-Chung Chow and Jen-pei Liu
Lyle D. Broemeling Design and Analysis of Bioavailability and
Bayesian Methods in Health Economics Bioequivalence Studies, Third Edition
Gianluca Baio Shein-Chung Chow and Jen-pei Liu
Bayesian Missing Data Problems: EM, Design and Analysis of Bridging Studies
Data Augmentation and Noniterative Jen-pei Liu, Shein-Chung Chow,
Computation and Chin-Fu Hsiao
Ming T. Tan, Guo-Liang Tian, Design and Analysis of Clinical Trials with
and Kai Wang Ng Time-to-Event Endpoints
Bayesian Modeling in Bioinformatics Karl E. Peace
Dipak K. Dey, Samiran Ghosh, Design and Analysis of Non-Inferiority
and Bani K. Mallick Trials
Biosimilars: Design and Analysis of Mark D. Rothmann, Brian L. Wiens,
Follow-on Biologics and Ivan S. F. Chan
Shein-Chung Chow
Difference Equations with Public Health Multiple Testing Problems in
Applications Pharmaceutical Statistics
Lemuel A. Moyé and Asha Seth Kapadia Alex Dmitrienko, Ajit C. Tamhane,
DNA Methylation Microarrays: and Frank Bretz
Experimental Design and Statistical Optimal Design for Nonlinear Response
Analysis Models
Sun-Chong Wang and Arturas Petronis Valerii V. Fedorov and Sergei L. Leonov
DNA Microarrays and Related Genomics Randomized Clinical Trials of
Techniques: Design, Analysis, and Nonpharmacological Treatments
Interpretation of Experiments Isabelle Boutron, Philippe Ravaud, and
David B. Allison, Grier P. Page, David Moher
T. Mark Beasley, and Jode W. Edwards Randomized Phase II Cancer Clinical
Dose Finding by the Continual Trials
Reassessment Method Sin-Ho Jung
Ying Kuen Cheung Sample Size Calculations in Clinical
Elementary Bayesian Biostatistics Research, Second Edition
Lemuel A. Moyé Shein-Chung Chow, Jun Shao
Frailty Models in Survival Analysis and Hansheng Wang
Andreas Wienke Statistical Design and Analysis of
Generalized Linear Models: A Bayesian Stability Studies
Perspective Shein-Chung Chow
Dipak K. Dey, Sujit K. Ghosh, Statistical Evaluation of Diagnostic
and Bani K. Mallick Performance: Topics in ROC Analysis
Handbook of Regression and Modeling: Kelly H. Zou, Aiyi Liu, Andriy Bandos,
Applications for the Clinical and Lucila Ohno-Machado, and Howard Rockette
Pharmaceutical Industries Statistical Methods for Clinical Trials
Daryl S. Paulson Mark X. Norleans
Interval-Censored Time-to-Event Data: Statistics in Drug Research:
Methods and Applications Methodologies and Recent
Ding-Geng (Din) Chen, Jianguo Sun, Developments
and Karl E. Peace Shein-Chung Chow and Jun Shao
Joint Models for Longitudinal and Time- Statistics in the Pharmaceutical Industry,
to-Event Data: With Applications in R Third Edition
Dimitris Rizopoulos Ralph Buncher and Jia-Yeong Tsay
Measures of Interobserver Agreement Survival Analysis in Medicine and
and Reliability, Second Edition Genetics
Mohamed M. Shoukri Jialiang Li and Shuangge Ma
Medical Biostatistics, Third Edition Translational Medicine: Strategies and
A. Indrayan Statistical Methods
Meta-Analysis in Medicine and Health Dennis Cosmatos and Shein-Chung Chow
Policy
Dalene Stangl and Donald A. Berry
Monte Carlo Simulation for the
Pharmaceutical Industry: Concepts,
Algorithms, and Case Studies
Mark Chang
 Bayesian
Methods in
Epidemiology

Lyle D. Broemeling
Broemeling and Associates
Medical Lake, Washington, USA
CRC Press
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Contents

1. Introduction to Bayesian Methods in Epidemiology...............................1

1.1 Introduction............................................................................................ 1
1.2 Review of Statistical Methods in Epidemiology...............................1
1.3 Preview of the Book...............................................................................4
1.3.1 Chapter 2: A Bayesian Perspective of Association
between Risk Exposure and Disease..................................... 4
1.3.2 Chapter 3: Bayesian Methods of Adjustment of Data..........9
1.3.3 Chapter 4: Regression Methods for Adjustment................ 16
1.3.4 Chapter 5: A Bayesian Approach to Life Tables................. 21
1.3.5 Chapter 6: A Bayesian Approach to Survival Analysis..... 27
1.3.6 Chapter 7: Screening for Disease.......................................... 32
1.3.7 Chapter 8: Statistical Models for Epidemiology................. 36
1.4 Preview of the Appendices................................................................. 45
1.4.1 Appendix A: Introduction to Bayesian Statistics............... 45
1.4.2 Appendix B: Introduction to WinBUGS.............................. 47
1.5 Comments and Conclusions............................................................... 48
Exercises........................................................................................................... 48
References........................................................................................................ 49

2. A Bayesian Perspective of Association between Risk

Exposure and Disease................................................................................... 53
2.1 Introduction.......................................................................................... 53
2.2 Incidence and Prevalence for Mortality and Morbidity.................54
2.3 Association between Risk and Disease in Cohort Studies............ 57
2.4 Retrospective Studies: Association between Risk and
Disease in Case–Control Studies������������������������������������������������������ 61
2.5 Cross-Sectional Studies.......................................................................65
2.6 Attributable Risk.................................................................................. 69
2.7 Comments and Conclusions............................................................... 73
Exercises........................................................................................................... 75
References........................................................................................................80

3. Bayesian Methods of Adjustment of Data............................................... 81

3.1 Introduction.......................................................................................... 81
3.2 Direct Adjustment of Data.................................................................. 82
3.3 Indirect Standardization Adjustment...............................................90
3.3.1 Introduction............................................................................. 90
3.3.2 Indirect Standardization........................................................ 91
3.3.3 Bayesian Inferences for Indirect Adjustment..................... 92
3.3.4 Example of Indirect Standardization................................... 93

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viii Contents

3.4 Stratification and Association between Disease and

Risk Exposure�������������������������������������������������������������������������������������� 96
3.4.1 Introduction............................................................................. 96
3.4.2 Interaction and Stratification................................................. 97
3.4.3 An Example of Stratification............................................... 101
3.5 Mantel–Haenszel Estimator of Association................................... 103
3.6 Matching to Adjust Data in Case–Control Studies....................... 107
3.7 Comments and Conclusions............................................................. 109
Exercises......................................................................................................... 110
References...................................................................................................... 120

4. Regression Methods for Adjustment....................................................... 121

4.1 Introduction........................................................................................ 121
4.2 Logistic Regression............................................................................ 123
4.2.1 Introduction........................................................................... 123
4.2.2 An Example of Heart Disease............................................. 124
4.2.3 An Example with Several Independent Variables........... 131
4.2.4 Goodness of Fit...................................................................... 133
4.3 Linear Regression Models................................................................ 134
4.3.1 Introduction........................................................................... 134
4.3.2 Simple Linear Regression.................................................... 135
4.3.3 Another Example of Simple Linear Regression............... 138
4.3.4 More on Multiple Linear Regression................................. 141
4.3.5 An Example for Public Health............................................ 146
4.4 Weighted Regression......................................................................... 149
4.5 Ordinal and Other Regression Models........................................... 156
4.6 Comments and Conclusions............................................................. 156
Exercises......................................................................................................... 158
References...................................................................................................... 168

5. A Bayesian Approach to Life Tables........................................................ 169

5.1 Introduction........................................................................................ 169
5.2 Basic Life Table................................................................................... 170
5.2.1 Life Table Generalized......................................................... 174
5.2.2 Another Generalization of the Life Table.......................... 177
5.3 Disease-Specific Life Tables.............................................................. 178
5.4 Life Tables for Medical Studies........................................................ 181
5.4.1 Introduction........................................................................... 181
5.4.2 California Tumor Registry 1942–1963................................ 183
5.5 Comparing Survival.......................................................................... 187
5.5.1 Introduction........................................................................... 187
5.5.2 Direct Bayesian Approach for Comparison of Survival....188
5.5.3 Indirect Bayesian Comparison of Survival....................... 190
5.5.3.1 Introduction........................................................... 190
5.5.3.2 Mantel–Haenszel Odds Ratio.............................. 191

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Contents ix

5.6 Kaplan–Meier Test............................................................................. 194

5.7 Comments and Conclusions............................................................. 201
Exercises......................................................................................................... 202
References...................................................................................................... 210

6 A Bayesian Approach to Survival Analysis........................................... 213

6.1 Introduction........................................................................................ 213
6.2 Notation and Basic Table for Survival............................................. 214
6.3 Kaplan–Meier Survival Curves........................................................ 217
6.3.1 Introduction........................................................................... 217
6.3.2 Bayesian Kaplan–Meier Method......................................... 221
6.3.3 Kaplan–Meier Plots for Recurrence of Leukemia
Patients...................................................................................225
6.3.4 Log-Rank Test for Difference in Recurrence Times......... 226
6.4 Survival Analysis............................................................................... 232
6.4.1 Introduction........................................................................... 232
6.4.2 Parametric Models for Survival Analysis......................... 233
6.4.3 Cox Proportional Hazards Model...................................... 248
6.4.4 Cox Model with Covariates................................................. 253
6.4.5 Testing for Proportional Hazards in the Cox Model....... 257
6.5 Comments and Conclusions............................................................. 261
Exercises......................................................................................................... 263
References...................................................................................................... 276

7 Screening for Disease................................................................................. 279

7.1 Introduction........................................................................................ 279
7.2 Principles of Screening...................................................................... 280
7.3 Evaluation of Screening Programs.................................................. 281
7.3.1 Introduction........................................................................... 281
7.3.2 Classification Probabilities.................................................. 283
7.3.3 Predictive Values................................................................... 286
7.3.4 Diagnostic Likelihood Ratios.............................................. 287
7.3.5 ROC Curve............................................................................. 288
7.3.6 UK Trial for Early Detection............................................... 292
7.4 HIP Study (Health Insurance Plan of Greater New York)........... 296
7.4.1 Introduction........................................................................... 296
7.4.2 Descriptive Statistics............................................................ 299
7.4.3 Estimating the Lead Time...................................................304
7.4.4 Estimating and Comparing Survival................................. 309
7.4.4.1 Life Tables...............................................................309
7.4.4.2 Survival Models.................................................... 322
7.5. Comments and Conclusions............................................................. 330
Exercises......................................................................................................... 333
References......................................................................................................340

© 2008 Taylor & Francis Group, LLC

x Contents

8 Statistical Models for Epidemiology.......................................................343

8.1 Introduction........................................................................................343
8.2 Review of Models for Epidemiology...............................................343
8.3 Categorical Regression Models........................................................346
8.4 Nonlinear Regression Models.......................................................... 355
8.5 Repeated Measures Model............................................................... 365
8.6 Spatial Models for Epidemiology.................................................... 375
8.7 Comments and Conclusions............................................................. 396
Exercises......................................................................................................... 398
References......................................................................................................404

Appendix A: Introduction to Bayesian Statistics......................................... 407

Appendix B: Introduction to WinBUGS........................................................ 437

© 2008 Taylor & Francis Group, LLC

1
Introduction to Bayesian Methods
in Epidemiology

1.1 Introduction
Our journey to Bayesian methods for epidemiology begins with this chapter.
This chapter consists of two parts: a review of the statistical methods used in
epidemiology, and a preview of the other seven chapters and two appendices.
Statistical methods in epidemiology appear in two ways: in those books that
more or less center around statistics, and those epidemiology books that have
some data analysis methods. A brief review of statistics books with methods
for epidemiology and of epidemiology books with statistical methods will be
conducted. The latter part of the chapter presents a detailed preview of the fol-
lowing chapters, and the last section contains some comments on the future of
statistics in epidemiology, with an emphasis on Bayesian methods.

1.2 Review of Statistical Methods in Epidemiology

Two types of books will be reviewed as to their content relating to statistical
methods for epidemiology: (1) statistics books whose aim is to provide statis-
tical methods for epidemiology and (2) books whose main aim is epidemiol-
ogy but also include statistical methods.
In the first category, Kahn and Sempos1 provided the author with much
material with their emphasis on statistical methods (non-Bayesian). For the
“usual” problems in epidemiology, I used some of their material, but gave it
a Bayesian flavor. The book begins with a review of the elementary notions
of mean and variance formulas for grouped data and attribute data. Various
forms of sampling are presented, including simple random sampling, strati-
fied random sampling, and systematic and cluster sampling. The following
chapter of the book introduces methods to estimate the association between
exposure to various risk factors, with a focus on the case–control and cohort

© 2008 Taylor & Francis Group, LLC 1

2 Bayesian Methods in Epidemiology

designs. The two types of design use different ways to estimate the associa-
tion, namely, the odds ratio for the case–control design and relative risk for
cohort studies. An important aspect of epidemiology is the so-called adjust-
ment of data with two approaches, the direct and indirect methods.
To compare two groups with different age distributions, direct and
­indirect adjustment techniques allow the user to make a fair comparison.
For example, the mortality of two states, say California and Florida, are to
be compared over several age intervals, but the states have quiet different age
distributions. To make a fair comparison, the mortality is compared relative
to a common age distribution, the so-called standard. The standard could
be the age distribution of the total U.S. population or some other s­ tandard,
and Kahn and Sempos1 explain various approaches to choosing the s­ tandard.
Many examples illustrate direct and indirect ways to adjust the data.
For establishing an association between disease and risk exposure, regres-
sion analysis is another approach to adjust data, and to this end, simple and
multiple regression for normally distributed dependent variables (which
measure disease or disease morbidity) are fully portrayed. When the depen-
dent variable is binary, simple and multiple logistic regression is employed
to establish an association between exposure and disease, adjusted for vari-
ous risk factors.
Life table techniques were developed by epidemiologists to relate the sur-
vival experience of a group of subjects and to compare the survival experience
of two or more groups of subjects, and Kahn and Sempos1 supply a detailed
exposition of the subject. The simplest life table observes a group of subjects
over several time intervals, and for each interval records the number who enter
each interval alive and the number who die in each interval. Various general-
izations of the life table to more complex scenarios are introduced and depicted
with several examples. One such scenario is when dropouts or withdrawals
are taken into account in estimating the survival experience. Another gener-
alization is reported by using person-years as the main end point of survival,
and estimating survival by descriptive techniques. Of course, when using
­person-years, statistical models can be utilized, and the authors briefly men-
tion the Cox proportional hazards model for estimating survival. As will be
seen, epidemiology books vary widely in their treatment of statistical methods.
For example, Selvin2 does not discuss life tables but does depict topics
not presented by Kahn and Sempos1 and does report on some topics not
reported by the former. For example, he introduces the student to maximum
likelihood estimation, a somewhat advanced topic. He then discusses odds
ratios for 2 by 2 and 2 by l tables for case–control studies. Continuing, he
puts a lot of stress on regression models including linear logistic and Poisson
regression. His presentation to regression analysis is somewhat similar to the
Kahn and Sempos1 approach, but Kahn and Sempos report more examples
applicable to epidemiology, namely, regression techniques to adjust the asso-
ciation between exposure and disease. Some advanced techniques such as
nonparametric regression and classification techniques are also portrayed.

© 2008 Taylor & Francis Group, LLC

Introduction to Bayesian Methods in Epidemiology 3

One of the better statistical books with a focus on epidemiology is by

Jewell,3 who defines the disease process and measures of disease prevalence
and incidence. This is followed by an in-depth study of probability and its
relevance to epidemiology and appears to be unique among such books. As
with Kahn and Sempos1 and Selvin,2 Jewell provides techniques for the esti-
mation of the association between disease and risk exposure through rela-
tive risk and odds ratios for cohort and case–control designs, respectively.
Regression models such as the logistic and log-linear are also meticulously
narrated. In summary, one can say with confidence that the three books
reviewed so far vary a lot, but with some common epidemiology themes.
Now to be reviewed are primarily epidemiology books that contain some
statistical methods, and the first is the popular book by Rothman, Greenland,
and Lash.4 With regard to statistical techniques, they present case–control
and cohort designs with the corresponding odds ratio and relative risk as
measures of association between exposure and disease occurrence, which
is followed by issues of cause and effect and estimation of interaction for
stratified studies. Also presented are regression models for surveillance,
using secondary data; ecologic studies; and environmental, genetic, and
molecular epidemiology.
A more traditional epidemiology book is Mausner and Kramer,5 which
is a good book for introducing epidemiology to the statistician. Traditional
topics are (1) epidemiologic concepts, (2) measurement of mortality and
­morbidity, (3) sources of data on community health, (4) selected indices of
health, (5) descriptive epidemiology, (6) analytical studies, (7) screening in
the ­detection of disease, (8) population dynamics and health, (9) ­occupational
­epidemiology, and (10) selected statistical topics.
Selected statistical topics introduce the beginning student to survival anal-
ysis, adjustment rates, cohort analysis of mortality, and sample size determi-
nation. As can be seen, most of the emphasis is on epidemiology with little in
the way of statistics. I recommend this book for the statistician who has little
knowledge of epidemiology.
Spatial epidemiology is a way to discover disease etiology by mapping the
relative risk of disease and exposure over distinct geographic units. It is a
very powerful tool for epidemiology, and the following references play an
important role in the last chapter of this book. Two books on spatial epide-
miology will be reviewed. The first by Elliot, Wakefield, Best, and Briggs6,
which is a good introduction to the subject and includes the following topics:
(1) use of population data for spatial epidemiology, (2) bias and ­confounding,
(3) ­ overview of statistical methods, (4) Bayesian approach, (5) d ­ etecting
­clusters, (6) spatial variation and correlation, (7) geostatistical methods, (8) the
­history of disease mapping, (9), mapping mortality data, (10) e­ xposure assess-
ment, (11) ­geographical studies of risk assessment, and (12) water q ­ uality and
health. Another quite relevant book is Bayesian by Lawson7 with the follow-
ing content: (1) Bayesian inference and modeling, (2) computational issues
including a description of the Monte Carlo Markov chain (MCMC), Gibbs

© 2008 Taylor & Francis Group, LLC

4 Bayesian Methods in Epidemiology

sampling, and the Metropolis–Hasting algorithm, (3) residuals and goodness

of fit, (4) ­disease mapping and reconstructing relative risk, (5) disease cluster
detection, (6) ecological analysis, (7) multivariate disease analysis, (8) spatial
survival and longitudinal studies, and (9) spatial-temporal disease mapping.
The preceding discussion is a brief review of statistical references for
epidemiology, and the present work is based on most of them, but with a
Bayesian approach for the statistical analysis of epidemiologic data.

1.3 Preview of the Book

At this point, Chapters 2–8 will be reviewed followed by a review of the
two appendices. Chapters 2–8 present the reader with a review of those
Bayesian methods that apply to epidemiology. Recall that epidemiology is
the study (or the science of the study) of the patterns, causes, and effects of
health and disease conditions in defined populations. It is the cornerstone of
public health that influences policy decisions and evidence-based medicine
by identifying risk factors for disease and targets for preventive medicine.
Epidemiologists help with study design, collection, and statistical analysis of
data, and interpretation and dissemination of results (including peer review
and occasional systematic review). Epidemiology has developed methodol-
ogy used in clinical research, public health studies, and, to some extent, basic
research in the biological sciences.
From the preceding discussion, one sees the role of statistical methodology
in various aspects of epidemiology. For example, in public health studies
and clinical research, life table methods were developed to compare various
therapies for the study of disease treatment.
Major areas of epidemiological study include disease etiology, outbreak
investigation, disease surveillance and screening, biomonitoring, and com-
parisons of treatment effects such as in clinical trials. Epidemiologists rely
on other scientific disciplines like biology to better understand disease
­processes, statistics to make efficient use of the data and draw a­ ppropriate
conclusions, social sciences to better understand proximate and distal causes,
and engineering for exposure assessment.
Of special importance for disease etiology, epidemiologists and statisti-
cians have developed spatial models to draw disease maps, which more
clearly reveals the association between exposure and disease etiology.

1.3.1 Chapter 2: A Bayesian Perspective of Association

between Risk Exposure and Disease
A formal beginning for statistical methods in epidemiology is Chapter 2,
which relays information about the association between exposure to risk

© 2008 Taylor & Francis Group, LLC