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2005 Hopkins Epi-Biostat Summer Institute1 Module 3: An Example of a Two-stage Model; NMMAPS Study Francesca Dominici Michael Griswold The Johns Hopkins University Bloomberg School of Public Health
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2005 Hopkins Epi-Biostat Summer Institute2 NMMAPS Example of Two-Stage Hierarchical Model National Morbidity and Mortality Air Pollution Study (NMMAPS) Daily data on cardiovascular/respiratory mortality in 10 largest cities in U.S. Daily particulate matter (PM10) data Log-linear regression estimate relative risk of mortality per 10 unit increase in PM10 for each city Estimate and statistical standard error for each city
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2005 Hopkins Epi-Biostat Summer Institute3 Semi-Parametric Poisson Regression Season weather Log-relative rate splines Log-Relative Rate Splines Season Weather
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2005 Hopkins Epi-Biostat Summer Institute4 Relative Risks* for Six Largest Cities CityRR Estimate (% per 10 micrograms/ml Statistical Standard Error Statistical Variance Los Angeles0.250.13.0169 New York1.40.25.0625 Chicago0.600.13.0169 Dallas/Ft Worth0.250.55.3025 Houston0.450.40.1600 San Diego1.00.45.2025 Approximate values read from graph in Daniels, et al. 2000. AJE
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2005 Hopkins Epi-Biostat Summer Institute5
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6 Notation
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8 City
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2005 Hopkins Epi-Biostat Summer Institute9 City
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2005 Hopkins Epi-Biostat Summer Institute10 City
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2005 Hopkins Epi-Biostat Summer Institute11 City
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2005 Hopkins Epi-Biostat Summer Institute12 Notation
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2005 Hopkins Epi-Biostat Summer Institute13 Estimating Overall Mean Idea: give more weight to more precise values Specifically, weight estimates inversely proportional to their variances
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2005 Hopkins Epi-Biostat Summer Institute14 Estimating the Overall Mean
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2005 Hopkins Epi-Biostat Summer Institute15 Calculations for Empirical Bayes Estimates CityLog RR (bc) Stat Var (vc) Total Var (TVc) 1/TVcwc LA0.25.0169.099410.1.27 NYC1.4.0625.1456.9.18 Chi0.60.0169.099410.1.27 Dal0.25.3025.3852.6.07 Hou0.45.160,2434.1.11 SD1.0.2025.2853.5.09 Over- all 0.6537.31.00 =.27* 0.25 +.18*1.4 +.27*0.60 +.07*0.25 +.11*0.45 + 0.9*1.0 = 0.65 Var = 1/Sum(1/TVc) = 0.164^2
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2005 Hopkins Epi-Biostat Summer Institute16 Software in R beta.hat <-c(0.25,1.4,0.50,0.25,0.45,1.0) se <- c(0.13,0.25,0.13,0.55,0.40,0.45) NV <- var(beta.hat) - mean(se^2) TV <- se^2 + NV tmp<- 1/TV ww <- tmp/sum(tmp) v.alphahat <- sum(ww)^{-1} alpha.hat <- v.alphahat*sum(beta.hat*ww)
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2005 Hopkins Epi-Biostat Summer Institute17 Two Extremes Natural variance >> Statistical variances Weights wc approximately constant = 1/n Use ordinary mean of estimates regardless of their relative precision Statistical variances >> Natural variance Weight each estimator inversely proportional to its statistical variance
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2005 Hopkins Epi-Biostat Summer Institute19 Estimating Relative Risk for Each City Disease screening analogy Test result from imperfect test Positive predictive value combines prevalence with test result using Bayes theorem Empirical Bayes estimator of the true value for a city is the conditional expectation of the true value given the data
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2005 Hopkins Epi-Biostat Summer Institute20 Empirical Bayes Estimation
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2005 Hopkins Epi-Biostat Summer Institute21 Calculations for Empirical Bayes Estimates CityLog RR Stat Var (vc) Total Var (TVc) 1/TVcwcRR.EBse RR.EB LA0.25.0169.099410.1.27.830.320.17 NYC1.4.0625.1456.9.18.571.10.14 Chi0.60.0169.099410.1.27.830.610.11 Dal0.25.3025.3852.6.07.210.560.12 Hou0.45.160,2434.1.11.340.580.14 SD1.0.2025.2853.5.09.290.750.13 Over- all 0.651/37.3= 0.027 37.31.000.650.16
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2005 Hopkins Epi-Biostat Summer Institute24 Maximum likelihood estimates Empirical Bayes estimates
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2005 Hopkins Epi-Biostat Summer Institute26 Key Ideas Better to use data for all cities to estimate the relative risk for a particular city Reduce variance by adding some bias Smooth compromise between city specific estimates and overall mean Empirical-Bayes estimates depend on measure of natural variation Assess sensitivity to estimate of NV
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2005 Hopkins Epi-Biostat Summer Institute27 Caveats Used simplistic methods to illustrate the key ideas: Treated natural variance and overall estimate as known when calculating uncertainty in EB estimates Assumed normal distribution or true relative risks Can do better using Markov Chain Monte Carlo methods – more to come
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