Interpretation of linear, logistic and Poisson regression models with transformed variables and its implementation in the R package tlm

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Interpretation of linear, logistic and Poisson regression models with transformed variables and its implementation in the R package tlm Jose Barrera-Gómez a jbarrera@creal.cat a Centre for Research in Environmental Epidemiology http://www.creal.cat Barcelona, October 24, 2013

Introduction Variables in a linear regression model are frequently transformed (e.g., homogeneity of variance, normality of errors, linearization, homogeneity of predictors). Researchers in health sciences are familiar with such transformations but less is known on how to interpret and report the effects in the original scale of the variables. The logarithmic transformation is especially important (e.g., adequacy of the lognormal distribution to describe ferritin, calcium, immunoglobulin, triglyceride or cotinine levels). J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 2 / 22

Aims Illustrate the interpretation of effects, in the original scale, under a linear model with transformed variables. Pay particular attention to the logarithmic transformation but also consider other transformations. Consider transformations of the explanatory variable in the logistic and Poisson regression models. Provide the R package tlm, which produces both numerical and graphical outputs. J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 3 / 22

Concepts Linear model Supose that we are interested in estimating the effect of an explanatory variable X on a response variable Y, based on the multiple linear regression model 9 E(Ỹ ) = β X + K = K = β 0 + β 2X 2 + + β px p (1) ; Ỹ and X are transformations of Y and X Assumptions 1 Monotonic bijective transformations. Specifically, Ỹ = f a(y ) and X = f b (Y ), where f p(u) = j log(u) if p = 0 U p if p 0, U > 0. (2) 2 The modeled variable, Ỹ (or Y if the response variable is untransformed), is normally distributed conditional on the explanatory variables, and therefore, symmetric. J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 4 / 22

Transforming means The generalized mean If we calculate the (arithmetic) mean in the transformed space and then undo the transformation, we obtain the generalized mean: f 1 p (f p(y )) = Pi Y p «1/p i. n Particular cases Harmonic mean if p = 1 Geometric mean if p = 0 (log) Arithmetic mean if p = 1 (no transformation) Quadratic mean if p = 2 The median Under the assumption of symmetry ( normality) and the family f p(), the generalized mean is equal to the median. J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 5 / 22

Intepretation of linear models with transformed response Under assumptions required for a linear model fitting and the family of transformations f p(): If no transformations Measure for the position of Y X and effect of X on Y : expected (adjusted) mean. Effect size does not depend on X (nor K): X = 1 E(Y ) = β. Additive-additive relationship. Under transformations f p() Measure for the position of Y X and effect of X on Y : expected (adjusted) median or generalized mean (geometric, harmonic or quadratic in some cases). Effect size does depend on X (and K): it can not be summarized by (a function of) β. Exception: log transformation in Y and/or X... J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 6 / 22

Linear models with log transformations (a) Example of Y = β 0 + β X (b) Example of Y = β 0 + β log(x) y+8 y+4 y+6 y+3 y+4 +1 +2 y+2 2 fold +1 y+2 y+1 y y x x+1 x+2 x+3 x+4 x 2x 4x 8x 16x (c) Example of log(y) = β 0 + β X (d) Example of log(y) = β 0 + β log(x) 16y 81y 8y 4y 2y y +1 2 fold 27y 9y 3y y 2 fold 3 fold x x+1 x+2 x+3 x+4 x 2x 4x 8x 16x J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 7 / 22

Linear models with log transformations (a1) IMT vs. Age Age (years) Intima media thickness (mm) 30 40 50 60 70 80 0.5 1.0 1.5 2.0 (b1) Weight vs. Cotinine Cotinine (ng/ml) Weight (kg) 0 200 400 600 800 2.0 2.5 3.0 3.5 4.0 4.5 (c1) Living room vs. Mattress alergen Mattress (µg/g) Room (µg/g) 0 50 100 150 200 0 500 1000 1500 2000 2500 (a2) IMT (log) vs. Age Age (years) Intima media thickness (mm) 30 40 50 60 70 80 0.5 1.0 1.5 2.0 (b2) Weight vs. Cotinine (log) Cotinine (ng/ml) Weight (kg) 0.5 5 50 500 2.0 2.5 3.0 3.5 4.0 4.5 (c2) Living room vs. Mattress alergen (log log) Mattress (µg/g) Room (µg/g) 0.01 0.1 1 10 50 0.01 0.1 1 10 100 1000 3000 (a): intima media thickness (IMT) and age. (b): birth weight and cord serum cotinine. (c): cat allergen levels in the home, measured in the living room and in the bed mattress. J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 8 / 22

Intepretation of linear models with log transformations Interpretation and size of the (adjusted) effect of X on Y under linear models with log transformed variables. In the transformed model, β is the regression coefficient associated to X. Model Log Effect size Effect interpretation Linear none E d = ˆβc Additive change in the mean of Y when adding c units to X Y M% d = 100 e ˆβc 1 % Relative change in the median of Y when adding c units to X X E d = ˆβ log(q) Additive change in the mean of Y when multiplying X by q X, Y M% d = 100 q ˆβ 1 % Relative change in the median of Y when multiplying X by q Logistic none OR c = e ˆβc Odds ratio for Y when adding c units to X X OR c = q ˆβ Odds ratio for Y when multiplying X by q Poisson none d E % = 100(e ˆβc 1)% Relative change in the mean of Y when adding c units to X X d E % = 100(q ˆβ 1)% Relative change in the mean of Y when multiplying X by q : (1 α)% confidence interval is obtained when replacing ˆβ i by ˆβ i ± z 1 α/2 bse( ˆβ i ). : Equivalently, geometric mean. : If X is binary, c = 1. J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 9 / 22

Intepretation of linear models with log transformations Approximate interpretation of the regression coefficient β under linear models with log transformed variables as the effect for a 1 unit or a 1% increase in the quantitative explanatory variable of interest, X. The last column indicates the error in the approximation. Log Interpretation Approximation error none ˆβ units change in the mean of Y for unit increase in X none Y 100 ˆβ% change in the median of Y for unit increase in X < 10% if ˆβ < 0.2; < 5% if ˆβ < 0.1 X ˆβ/100 units change in the mean of Y for 1% increase in X 0.5% for any ˆβ X, Y ˆβ% change in the median of Y for 1% increase in X < 10% if ˆβ < 20; < 5% if ˆβ < 10 : (1 α)% confidence interval is obtained when replacing ˆβ i by ˆβ i ± z 1 α/2 bse( ˆβ i ). : Percentage error relative to the true value of the effect. : Equivalently, geometric mean. : Also valid in the Poisson regression model with log transformed X. J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 10 / 22

Intepretation of linear models with other transformations Expected adjusted median of the response Y where ˆM(x) = fa 1 ( ˆβf b (x) + b K), b K = ˆβ 0 + ˆβ 2 X 2 + + ˆβ p X p. Expected adjusted effect of X (X = u 1 X = u 2) on the median of the response Y Additive change in the median of Y : d M = ˆM(u 2) ˆM(u 1) = f 1 a ( ˆβf b (u 2) + b K) f 1 ( ˆβf b (u 1) + b K). a Percent change in the median of Y : d M % = 100 ˆM(u 2) ˆM(u 1) % = 100 ˆM(u 1) For binary X, u 1 = 0 and u 2 = 1, and b = 1. " fa 1 ( ˆβf b (u 2) + b K) fa 1 ( ˆβf b (u 1) + b K) 1 # %, J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 11 / 22

Software implementation The R package tlm We are developing the R package tlm which allows to interpret and display adjusted effects both graphically and numerically. Main functions tlm: fits the model in the transformed space. Specific methods print and summary provide additional information on the transformations done. Specific method plot (original space, transformed space and graphical diagnosis). predict: computes the expected adjusted median of Y (or the adjusted mean of f a(y ), in the transformed space) as a function of X. Confidence intervals are based on parametric bootstrap. effectinfo: provides information about how to interpret effects in the original scale. effect: computes the expected change in the adjusted median of Y associated to a given change in X. J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 12 / 22

Example: cat allergen levels in the home Cat allergen levels measured in the living room (Y ) and in the bed mattress (X ): Original scale log log scale 2500 2000 Cat at home: no yes 3000 1000 100 Cat at home: no yes Room (µg/g) 1500 1000 Room (µg/g) 10 1 0.1 500 0.01 0 0 50 100 150 200 Mattress (µg/g) 0.01 0.1 1 10 50 Mattress (µg/g) J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 13 / 22

Example: cat allergen levels in the home > head(cat) id bed room cat logbed logroom 1 30001 0.3781000 8.004959 Yes -0.9725966 2.0800612 2 30002 0.2546667 0.216320 No -1.3677996-1.5309965 3 30004 0.2888511 20.437040 Yes -1.2418439 3.0173489 4 30005 0.0718000 0.384000 No -2.6338708-0.9571127 5 30006 0.0916053 0.192640 No -2.3902661-1.6469321 6 30007 0.0860870 0.103600 No -2.4523969-2.2672179 > library(tlm) > catmodel <- tlm(y = logroom, x = logbed, z = cat, ypow = 0, xpow = 0, data = cat) > catmodel Linear regression fitted model in the transformed space ------------------------------------------------------- Transformations: In the response variable: log In the explanatory variable: log Call: lm(formula = logroom ~ logbed + cat, data = cat) Coefficients: (Intercept) logbed catyes -0.1282 0.5913 1.4296 J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 14 / 22

Example: cat allergen levels in the home > summary(catmodel) Linear regression fitted model in the transformed space ------------------------------------------------------- Transformations: In the response variable: log In the explanatory variable: log Call: lm(formula = logroom ~ logbed + cat, data = cat) Residuals: Min 1Q Median 3Q Max -5.2453-0.9784-0.0585 0.7937 5.4805 Coefficients: Estimate Std. Error t value Pr(> t ) (Intercept) -0.1282 0.1183-1.083 0.279 logbed 0.5913 0.0483 12.242 < 2e-16 *** catyes 1.4296 0.2199 6.500 2.06e-10 *** --- Signif. codes: 0 *** 0.001 ** 0.01 * 0.05. 0.1 1 Residual standard error: 1.555 on 468 degrees of freedom Multiple R-squared: 0.3853, Adjusted R-squared: 0.3827 F-statistic: 146.7 on 2 and 468 DF, p-value: < 2.2e-16 J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 15 / 22

Example: cat allergen levels in the home > plot(catmodel, xname = "Mattress levels", yname = "room levels") Geometric mean of room levels 0 10 20 30 40 50 0 50 100 150 200 Mattress levels J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 16 / 22

Example: cat allergen levels in the home > plot(catmodel, xname = "Mattress levels", yname = "room levels", type = "transform", + observed = T) 4 2 0 2 4 6 4 2 0 2 4 6 8 Log(Mattress levels) Mean of log(room levels) J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 17 / 22

Example: cat allergen levels in the home > plot(catmodel, type = "diagnosis") 2 0 2 4 6 2 2 4 6 Fitted values Residuals Residuals vs Fitted 472 300 441 3 2 1 0 1 2 3 2 0 2 4 Theoretical Quantiles Standardized residuals Normal Q Q 472 300 441 2 0 2 4 0.0 0.5 1.0 1.5 Fitted values Standardized residuals Scale Location 472 300 441 0.00 0.01 0.02 0.03 0.04 4 2 0 2 4 Leverage Standardized residuals Cook's distance Residuals vs Leverage 92 465 167 J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 18 / 22

Example: cat allergen levels in the home > predict(catmodel) # Default: 10 points in arithmetic progression in the given space Estimated adjusted geometric mean of the response variable (original space): logbed Estimate lower95% upper95% 1 0.0045004 0.04428898 0.03007509 0.06522055 2 23.6706670 7.02358298 4.37193843 11.28348871 3 47.3368336 10.58127923 6.18328755 18.10743384 4 71.0030003 13.44793578 7.57129183 23.88588115 5 94.6691669 15.94152405 8.74040687 29.07555596 6 118.3353335 18.18996420 9.76974271 33.86729902 7 142.0015001 20.26055599 10.69984419 38.36412211 8 165.6676668 22.19406780 11.55478448 42.62966967 9 189.3338334 24.01748931 12.35024206 46.70676004 10 213.0000000 25.74982227 13.09710344 50.62595329 Several options... > predict(catmodel, x = quantile(cat$room, probs = 0:4/4)) > predict(catmodel, npoints = 100, space = "transformed", level = 0.99) J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 19 / 22

Example: cat allergen levels in the home > effectinfo(catmodel) The effect of X on Y can be summarized with a single number as follows: - Change in X: multiplicative of factor q (equivalently, adding an r = 100 * (q - 1)% to X) - Type of effect on Y: percent change in the geometric mean of Y - Effect size: 100 * (q^beta - 1)% beta coefficient estimate: Estimate Std. Error t value Pr(> t ) logbed 0.5913161 0.04830168 12.24214 4.354439e-30 Further details can be obtained using effect(), providing either the multiplicative ('q') or the percent ('r') change in X, and the level for the confidence interval, 'level'. > effect(catmodel) Percent change in the geometric mean of Y when changing X from the 1st to the 3rd quartile: 192.8697 95% confidence interval: (146.4713, 248.0028) Several options... > effect(object, x1 = NULL, x2 = NULL, c = NULL, q = NULL, r = NULL, npoints = NULL, + level = 0.95, nboot = 5000, seed = 4321) J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 20 / 22

Example: cat allergen levels in the home > catmodel2 <- tlm(y = logroom, x = cat, z = logbed, ypow = 0, data = cat) > effectinfo(catmodel2) The effect of X on Y can be summarized with a single number as follows: - Change in X: changing X from its reference, 'No', to the alternative level - Type of effect on Y: percent change in the geometric mean of Y - Effect size: 100 * [exp(beta) - 1]% beta coefficient estimate: Estimate Std. Error t value Pr(> t ) 1.429615e+00 2.199399e-01 6.500025e+00 2.061135e-10 Further details can be obtained using effect() and providing the level for the confidence interval, 'level'. > predict(catmodel2) Estimated adjusted geometric mean of the response variable (original space): cat Estimate lower95% upper95% 1 No 0.3405043 0.2919107 0.3971872 2 Yes 1.4223169 0.9575328 2.1127059 > effect(catmodel2) Adjusted change in the geometric mean of the response variable when the explanatory variable changes from its reference level, 'No', to an alternative level. Confidence interval for the difference was computing based on 5000 bootstrap samples: EstimateDiff lower95% upper95% EstimatePercent lower95% upper95% No -> Yes 1.081813 0.6127211 1.757564 317.7089 171.1285 543.5352 Further information about interpreting the effect using effectinfo() J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 21 / 22

Example: cat allergen levels in the home > plot(catmodel2, xname = "Cat at home", yname = "allergen leveles in the room", + las = 1, col = c("forestgreen", "red")) Geometric mean of allergen leveles in the room 2.0 1.5 1.0 0.5 No Yes Cat at home J. Barrera-Gómez (CREAL) Interpreting linear models with transformed variables Barcelona, October 24, 2013 22 / 22

Centre for Research in Environmental Epidemiology Parc de Recerca Biomèdica de Barcelona Doctor Aiguader, 88 08003 Barcelona (Spain) Tel. (+34) 93 214 70 00 Fax (+34) 93 214 73 02 info@creal.cat www.creal.cat

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