Cox s proportional hazards/regression model - model assessment

Size: px

Start display at page:

Download "Cox s proportional hazards/regression model - model assessment"

Sherilyn Marsh
5 years ago
Views:

1 Cox s proportional hazards/regression model - model assessment Rasmus Waagepetersen September 27, 2017

2 Topics: Plots based on estimated cumulative hazards Cox-Snell residuals: overall check of fit Martingale residuals: assessment of functional form of covariate Deviance residuals: detection of outliers Score-process residual: check of proportional hazards for each covariate Detection of influential observations.

3 Why not just proceed as for linear normal models? Issues: censoring. for Cox ph model we do not have a fully specified model - thus we do not know distribution of residuals. Generally, residual analysis is a bit tricky not only for survival data but for non-normal data in general - residuals tend to look ugly even if the model is correct.

4 Model with one factor Suppose we have observations (t ij, δ ij ) i = 1,..., K and model for the ith group h i (t ij ) = h 0 (t ij ) exp(β i ) Compute a cumulative hazard estimate Ĥ i for each group. Recall H i (t) = H 0 (t) exp(β i ) log H i (t) = log H 0 (t) + β i Various types of plots can be considered 1. log Ĥ i (t) s against t 2. log Ĥ i vs log Ĥ j 3. Ĥ i vs Ĥ j 4. log Ĥ i (t) log Ĥ 1 (t) s vs t. The last three alternatives require a bit of programming since the estimates are not obtained for the same ts.

5 Stratified Cox process Suppose we have several covariates and the first is a factor dividing subjects into K groups. Then a stratified Cox model is specified by h i (t z) = h 0i (t) exp(z T 1β 1 ) where h i ( z 1 ) is the hazard for a subject in the ith group with remaining covariate vector z 1 = (z 2,..., z p ) T. That is, a separate baseline hazard h 0i for each group/strata. If proportional hazards holds for the factor used for stratification then H 0i (t) = H 0 (t) exp(β 1 ). So we can make plots similar to those on the previous slide to assess proportional hazards for the factor considered. If we want to assess ph for a quantitative covariate then we can initially discretize it into a factor variable.

6 Martingale residuals Martingale residuals: r M i = δ i Ĥ0(t i ) exp(z T i ˆβ) Very skewed with values in interval ], 1]. Not useful for detecting outliers. May be used for assessing functional form of covariate by computing ri M for model without covariate and plotting ri M against the omitted covariate. Curve fitted to scatter plot may give indication of possible transformation of covariate. Reason for terminology will be more clear when we later on discuss counting processes and martingales.

7 Cox-Snell Cox-Snell residuals based on results for continuous random variable X with survivor function S and cumulative hazard and H: S(X ) Unif(]0, 1[) H(X ) Exp(1). Cox-Snell residual: r C i = Ĥ 0 (t i ) exp(z T i ˆβ) = δ i r M i Cox-Snell residuals should look like censored sample of unit-rate exponential random variables which have H(t) = t. This can be checked by considering estimated cumulative hazard for r C i. Cox-Snell residuals may be used for checking overall fit of model - but see reservations in practical notes in KM page

8 Deviance residuals Deviance residuals are obtained by applying symmetrizing transformation to martingale residuals: r D i = sign(ri M )[ 2(ri M + δ i log(δ i ri M ))] 1/2. These residuals should look (approximately) like a sample of iid normal random variables if model correct. However, if heavy censoring distribution becomes bimodal. May be useful for spotting outliers.

9 Schoenfeld residuals and score process Let x 1,..., x n denote the set of death times (where we only observe x i if δ i = 1) and let R 1,..., R n denote the associated ranks. Recall score function u(β) for Cox s partial likelihood is a sum of terms (p-dimensional vectors) u (i) (β) = δ (i) (z (i) E[z R(i) H i ]) = δ (i) [z (i) e((i))] The components of these terms are also known as Schoenfeld residuals (KM page 376). We can define the score process (KM page 376) as u(β, t) = l D: t l t u l (β) By definition u( ˆβ, t) = 0 for t greater than the maximal observed death time.

10 KM suggest to plot score process u( ˆβ, t) against time and compare with 95% boundaries of Brownian bridge process. Martinussen and Scheike (2006) Dynamic regression models for survival data, suggest to compare with simulations of score process under assumed model. The score process can also be expressed as n u(β, t) = δ i (z i e(i)) exp(zi T β) i=1 l D: t l t (z l e(l)) k R(t l ) exp(zt k β) (we will see later why, when considering counting processes and martingales). The score residuals are given by the components of u(β, t i ), i = 1,..., n. These are also available from the residuals function and can be cumulated to obtain score process.

11 Assessment of timevarying effects Suppose that we do not have proportional hazards for the jth covariate in the sense that the true effect of z j is timevarying: β j (t) = β j + γ j g(t). Let r S j,i be Schoenfeld residual scaled with the covariance matrix of ˆβ. Then the expected value of r S j,i is approximately equal to γ j g(t i ). Thus a plot of scaled Schoenfeld residuals versus time may reveal deviations from proportional hazards. Implemented in the cox.zph procedure. This is not covered in KM. See e.g. book by Collett.

12 Influential observations Do some observations have unusually large influence on estimation of β? Let ˆβ and ˆβ i denote estimates of β based on full data set and data with ith observation omitted. Want to look for i where ˆβ ˆβ i is an outlier. Based on score process residuals it is possible to compute approximation of ˆβ i - i.e. we do not need to fit Cox model for all datasets obtained by omitting one observation. These estimates are called dfbeta in the residual function for coxph objects.

13 Use of formal testing? KM note 5 page on 380 advocates use of graphical checks rather than formal tests. This is because we know that any statistical model is just an approximation and thus is bound to be rejected if the sample size is large enough. Remember the famous quote by Box: all models are wrong but some are useful Graphical checks may reveal if there are any serious deviations between model and data and possibly also hint to the cause of such deviations.

Survival Analysis Math 434 Fall 2011

Survival Analysis Math 434 Fall 2011 Part IV: Chap. 8,9.2,9.3,11: Semiparametric Proportional Hazards Regression Jimin Ding Math Dept. www.math.wustl.edu/ jmding/math434/fall09/index.html Basic Model Setup