EPIDEMIOLOGY
Volume 160
Number 4
August 15, 2004
SPECIAL ARTICLE
Model-based Estimation of Relative Risks and Other Epidemiologic Measures in
Studies of Common Outcomes and in Case-Control Studies
Sander Greenland
From the Departments of Epidemiology and Statistics, University of California, Los Angeles, Los Angeles, CA.
Received for publication November 7, 2003; accepted for publication May 27, 2004.
Some recent articles have discussed biased methods for estimating risk ratios from adjusted odds ratios when
the outcome is common, and the problem of setting confidence limits for risk ratios. These articles have
overlooked the extensive literature on valid estimation of risks, risk ratios, and risk differences from logistic and
other models, including methods that remain valid when the outcome is common, and methods for risk and rate
estimation from case-control studies. The present article describes how most of these methods can be subsumed
under a general formulation that also encompasses traditional standardization methods and methods for
projecting the impact of partially successful interventions. Approximate variance formulas for the resulting
estimates allow interval estimation; these intervals can be closely approximated by rapid simulation procedures
that require only standard software functions.
absolute risk; case-control studies; clinical trials; cohort studies; logistic regression; odds ratio; relative risk; risk
assessment
In 1989, Holland (3) proposed an adjusted risk difference using the same biased risk-ratio formula rediscovered
Correspondence to Dr. Sander Greenland, Departments of Epidemiology and Statistics, University of California, Los Angeles, Los Angeles, CA
90095-1772 (e-mail: lesdomes@ucla.edu).
301
Am J Epidemiol 2004;160:301305
302 Greenland
RR
10 = 1.56, and RD 10 = 0.133 if the log-linear model fit by
binomial maximum likelihood is used; and R 1 = 0.383, R 0 =
0.235, RR
10 = 1.63, and RD 10 = 0.148 if log-linear Poisson
regression is used. The Mantel-Haenszel estimates (5, p.
271) are RR
10 = 1.62 and RD 10 = 0.166. Thus, all the valid
approximations yield similar results, as expected given the
sample size and good fit of the models.
In contrast, the odds-ratio estimate exp(b1) from the
logistic model is 2.51, and the Zhang-Yu risk-ratio estimate
Am J Epidemiol 2004;160:301305
TABLE 1. Data relating receptor level (low, high) and stage (I, II, III) to 5-year breast
cancer mortality (23), observed and model-based estimates of average risk (incidence
proportion) by receptor level and stage, and distributions for standardizing receptorlevel comparisons to total-cohort stage distribution
Stage I
Stage II
Stage III
Low
High
Low
High
Low
High
Deaths
17
12
Survivors
10
50
13
57
Total
12
55
22
74
14
15
Observed*
167
91
409
230
857
600
Logistic
190
86
422
226
816
639
Binomial
148
95
376
242
870
558
Poisson
153
94
386
237
905
555
p1(x)
0.349
0.500
0.151
p0(x)
0.349
0.500
0.151
Estimates of 5-year
mortality risk
(per 1,000)
Comparison distributions
0.023, 0.312 for RD10 using logistic regression; 1.05, 2.30 for
RR10 and 0.023, 0.312 for RD10 using binomial log-linear
regression; and 1.07, 2.47 for RR10 and 0.021, 0.299 for RD10
using Poisson regression.
CASE-CONTROL STUDIES
304 Greenland
ACKNOWLEDGMENTS
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