1. Introduction to logistic regression and Generalized Linear Models July 14, 2011 Introduction to Statistical Measurement and Modeling Karen Bandeen-Roche, PhD Department of Biostatistics Johns Hopkins University

2. Data motivation  Osteoporosis data  Scientific question : Can we detect osteoporosis earlier and more safely?  Some related statistical questions :  How does the risk of osteoporosis vary as a function of measures commonly used to screen for osteoporosis?  Does age confound the relationship of screening measures with osteoporosis risk?  Do ultrasound and DPA measurements discriminate osteoporosis risk independently of each other?

3. Outline  Why we need to generalize linear models  Generalized Linear Model specification  Systematic, random model components  Maximum likelihood estimation  Logistic regression as a special case of GLM  Systematic model / interpretation  Inference  Example

4. Regression for categorical outcomes  Why not just apply linear regression to categorical Y’s?  Linear model (A1) will often be unreasonable.  Assumption of equal variances (A3) will nearly always be unreasonable.  Assumption of normality will never be reasonable

5. Introduction: Regression for binary outcomes  Y i = 1{event occurs for sampling unit i} = 1 if the event occurs = 0 otherwise.  p i = probability that the event occurs for sampling unit i := Pr{Y i = 1}  Begin by generalizing random model (A5):  Probability mass function: Bernoulli Pr{Y i = 1} = p i ; Pr{Y i = 0} = 1-p i all other y i occur with 0 probability

6. Binary regression  By assuming Bernoulli: (A3) is definitely not reasonable  Var(Y i ) = p i (1-p i )  Variance is not constant: rather a function of the mean  Systematic model  Goal remains to describe E[Y i |x i ]  Expectation of Bernoulli Y i = p i  To achieve a reasonable linear model (A1): describe some function of E[Y i |x i ] as a linear function of covariates  g(E[Y i |x i ]) = x i ’ β  Some common g: log, log{p/(1-p)}, probit

7. General framework: Generalized Linear Models  Random model  Y~a density or mass function, f Y, not necessarily normal  Technical aside: f Y within the “exponential family”  Systematic model  g(E[Y i |x i ]) = x i ’ β = η i  “g” = “link function”; “x i ’ β ” = “linear predictor”  Reference: Nelder JA, Wedderburn RWM, Generalized linear models, JRSSA 1972; 135:370-384.

8. Types of Generalized Linear Models Model (link function) ResponseDistributionRegression Coef Interp Linear ContinuousGaussianChange in ave(Y) per unit change in X Logistic BinaryBinomialLog odds ratio Log-linear Times to events/counts PoissonLog relative rate Proportional hazards Times to events Semi- parametric Log hazard

9. Estimation  Estimation: maximizes L( β,a;y,X) =  General method: Maximum likelihood (Fisher)  Given {Y 1,...,Y n } distributed with joint density or mass function f Y (y; θ ), a likelihood function L( θ ;y) is any function (of θ ) that is proportional to f Y (y; θ ).  If sampling is random, {Y 1,...,Y n } are statistically independent, and L( θ ;y) α product of individual f.

10. Maximum likelihood  The maximum likelihood estimate (MLE),, maximizes L( θ ;y):  Under broad assumptions MLEs are asymptotically  Unbiased (consistent)  Efficient (most precise / lowest variance)

11. Logistic regression  Y i binary with p i = Pr{Y i = 1}  Example: Y i = 1{person i diagnosed with heart disease}  Simple logistic regression (1 covariate)  Random Model: Bernoulli / Binomial  Systematic Model: log{p i /(1- p i )}= β 0 + β 1 x i  log odds; logit(p i )  Parameter interpretation  β 0 = log(heart disease odds) in subpopulation with x=0  β 1 = log{p x+1 /(1-p x+1 )}- log{p x /(1-p x )}

12. Logistic regression Interpretation notes  β 1 = log{p x+1 /(1-p x+1 )}- log{p x /(1-p x )} =  exp( β 1 ) = = odds ratio for association of prevalent heart disease with each (say) one year increment in age = factor by which odds of heart disease increases / decreases with each 1-year cohort of age

13. Multiple logistic regression  Systematic Model: log{p i /(1- p i )}= β 0 + β 1 x i1 + … + β p x ip  Parameter interpretation  β 0 = log(heart disease odds) in subpopulation with all x =0  β j = difference in log outcome odds comparing subpopulations who differ by 1 on x j, and whose values on all other covariates are the same  “Adjusting for,” “Controlling for” the other covariates  One can define variables contrasting outcome odds differences between groups, nonlinear relationships, interactions, etc., just as in linear regression

14. Logistic regression - prediction  Translation from η i to p i  log{p i /(1- p i )}= β 0 + β 1 x i1 + … + β p x ip  Then = logistic function of η i  Graph of p i versus η i has a sigmoid shape

15. GLMs - Inference  The negative inverse Hessian matrix of the log likelihood function characterizes Var( ) (adjunct)  SE( ) obtained as square root of the jth diagonal entry  Typically, substituting for β  “Wald” inference applies the paradigm from Lecture 2  Z = is asympotically ~ N(0,1) under H 0 : β j = β 0j  Z provides a test statistic for H 0 : β j = β 0j versus H A : β j ≠ β 0j  ± z (1- α /2) SE{ } =(L,U) is a (1- α )x100% CI for β j  {exp(L),exp(U)} is a (1- α )x100% CI for exp( β j )

16. GLMs: “Global” Inference  Analog: F-testing in linear regression  The only difference: log likelihoods replace SS  Hypothesis to be tested is H 0 : β j1 =...= β jk = 0  Fit model excluding x j1,...,x jp j : Save -2 log likelihood = L s  Fit “full” (or larger) model adding x j1,...,x jp j to smaller model. Save -2 log likelihood = L L  Test statistic S = L s - L L  Distribution under null hypothesis: χ 2 p j  Define rejection region based on this distribution  Compute S  Reject or not as S is in rejection region or not

17. GLMs: “Global” Inference  Many programs refer to “deviance” rather than -2 log likelihood  This quantity equals the difference in -2 log likelihoods between ones fitted model and a “saturated model”  Deviance measures “fit”  Differences in deviances can be substituted for differences in -2 log likelihood in the method given on the previous page  Likelihood ratio tests have appealing optimality properties

18. Outline: A few more topics  Model checking: Residuals, influence points  ML can be written as an iteratively reweighted least squares algorithm  Predictive accuracy  Framework generalizes easily

19. Main Points  Generalized linear modeling provides a flexible regression framework for a variety of response types  Continuous, categorical measurement scales  Probability distributions tailored to the outcome  Systematic model to accommodate  Measurement range, interpretation  Logistic regression  Binary responses (yes, no)  Bernoulli / binomial distribution  Regression coefficients as log odds ratios for association between predictors and outcomes

20. Main Points  Generalized linear modeling accommodates description, inference, adjustment with the same flexibility as linear modeling  Inference  “Wald” - statistical tests and confidence intervals via parameter estimator standardization  “Likelihood ratio” / “global” – via comparison of log likelihoods from nested models