[R] Interperting results of glmnet and coxph plot, Brier score and Harrel's C-Index - am I doing something wrong ???

Frank Harrell f.harrell at vanderbilt.edu
Sat Sep 28 16:48:38 CEST 2013


This entire procedure is not valid.  You cannot use a penalized method for
selecting variables then use an unpenalized procedure on those selected.

Frank

David Winsemius wrote
> On Sep 28, 2013, at 2:39 AM, E Joffe wrote:
> 
>> Hi all,
>>
>> I am using COX LASSO (glmnet / coxnet) regression to analyze a  
>> dataset of
>> 394 obs. / 268 vars.
>> I use the following procedure:
>> 1.	Construct a coxnet on the entire dataset (by cv.glmnet)
>> 2.	Pick the significant features by selecting the non-zero coefficient
>> under the best lambda selected by the model
>> 3.	Build a coxph model with bi-directional stepwise feature selection
>> limited to the coxnet selected features.
> 
> I was a bit puzzled by the third step. Once you had a reduced model  
> from glmnet, what was the statistical basis for further elimination of  
> variables?
> 
> (Quite apart from the statistical issues, I was rather surprised that  
> this procedure even produced results since the 'step' function is not  
> described in the 'stats' package as applying to 'coxph' model objects.)
> 
>> 	
>> To validate the model I use both Brier score (library=peperr) and  
>> Harrel's [Harrell]
>> C-Index (library=Hmisc) with a bootstrap of 50 iterations.
>>
>>
>> MY QUESTION :  I am getting fairly good C-Index (0.76) and Brier  
>> (0.07)
>> values for the models however per the coxnet the %Dev explained by  
>> the model
>> is at best 0.27 and when I plot the survfit of the coxph the plotted
>> confidence interval is very large.
> 
> How many events did you have?  (The width of CI's is most importantly  
> dependent on event counts and not particularly improved by a high case  
> count. The power considerations are very similar to those of a  
> binomial test.)
> 
> 
>> What am I missing here ?
> 
> Perhaps sufficient events? (You also seem to be missing a description  
> of the study goals.)
> 
> 
> -- 
> David.
> 
>>
>> %DEV=27%
>>
>>
>>
>> Brier score - 0.07  ($ipec.coxglmnet -> [1] 7.24)
>> C-Index - 0.76 ($cIndex -> [1] 0.763)
>>
>>
>>
>> DATA: [Private Health Information - can't publish] 394 obs./268 vars.
>>
>> CODE (need to define a dataset with 'time' and 'status' variables):
>>
>> library("survival")
>> library ("glmnet")
>> library ("c060")
>> library ("peperr")
>> library ("Hmisc")
>>
>>    #creat Y (survival matrix) for glmnet
>>    surv_obj <- Surv(dataset$time,dataset$status)
>>
>>
>>    ## tranform categorical variables into binary variables with  
>> dummy for
>> dataset
>>    predict_matrix <- model.matrix(~ ., data=dataset,
>>                                   contrasts.arg = lapply
>> (dataset[,sapply(dataset, is.factor)], contrasts))
>>
>>    ## remove the statu/time variables from the predictor matrix (x)  
>> for
>> glmnet
>>    predict_matrix <- subset (predict_matrix, select=c(-time,-status))
>>
>>    ## create a glmnet cox object using lasso regularization and cross
>> validation
>>    glmnet.cv <- cv.glmnet (predict_matrix, surv_obj, family="cox")
>>
>>    ## get the glmnet model on the full dataset
>>    glmnet.obj <- glmnet.cv$glmnet.fit
>>
>>    # find lambda index for the models with least partial likelihood
>> deviance (by cv.glmnet)
>>    optimal.lambda <- glmnet.cv$lambda.min    # For a more parsimoneous
>> model use lambda.1se
>>    lambda.index <- which(glmnet.obj$lambda==optimal.lambda)
>>
>>
>>    # take beta for optimal lambda
>>    optimal.beta  <- glmnet.obj$beta[,lambda.index]
>>
>>    # find non zero beta coef
>>    nonzero.coef <- abs(optimal.beta)>0
>>    selectedBeta <- optimal.beta[nonzero.coef]
>>
>>    # take only covariates for which beta is not zero
>>    selectedVar   <- predict_matrix[,nonzero.coef]
>>
>>    # create a dataframe for trainSet with time, status and selected
>> variables in binary representation for evaluation in pec
>>    reformat_dataSet <- as.data.frame(cbind(surv_obj,selectedVar))
>>
>>    # glmnet.cox only with meaningful features selected by stepwise
>> bidirectional AIC feature selection
>>    glmnet.cox.meaningful <- step(coxph(Surv(time,status) ~
>> .,data=reformat_dataSet),direction="both")
>>
>>
>>
>>
>> ##--------------------------------------------------------------------------
>> -----------------------------
>>    ##                                    MODEL PERFORMANCE
>>
>> ##--------------------------------------------------------------------------
>> -----------------------------
>>    ##
>>
>>
>>    ## Calculate the Brier score - pec does its own bootstrap so this
>> function runs on i=51 (i.e., whole trainset)
>>
>>        ## Brier score calculation to cox-glmnet
>>        peperr.coxglmnet <- peperr(response=surv_obj, x=selectedVarCox,
>>                                fit.fun=fit.coxph, load.all=TRUE,
>>                                 
>> indices=resample.indices(n=nrow(surv_obj),
>> method="boot", sample.n=50))
>>
>>        # Get error predictions from peperr
>>        prederr.coxglmnet <- perr(peperr.coxglmnet)
>>
>>        # Integrated prediction error Brier score calculation
>>        ipec.coxglmnet<-ipec(prederr.coxglmnet,
>> eval.times=peperr.coxglmnet$attribute, response=surv_obj)
>>
>>
>>  ## C-Index calculation 50 iter bootstrapping
>>
>>  for (i in 1:50){
>>        print (paste("Iteration:",i))
>>        train <- sample(1:nrow(dataset), nrow(dataset), replace =  
>> TRUE) ##
>> random sampling with replacement
>>        # create a dataframe for trainSet with time, status and  
>> selected
>> variables in binary representation for evaluation in pec
>>        reformat_trainSet <- reformat_dataSet [train,]
>>
>>
>>        # glmnet.cox only with meaningful features selected by stepwise
>> bidirectional AIC feature selection
>>        glmnet.cox.meaningful.test <- step(coxph(Surv(time,status) ~
>> .,data=reformat_dataSet),direction="both")
>>
>>        selectedVarCox   <-
>> predict_matrix[,attr(glmnet.cox.meaningful.test$terms,"term.labels")]
>>        reformat_testSet <-  
>> as.data.frame(cbind(surv_obj,selectedVarCox))
>>        reformat_testSet <- reformat_dataSet [-train,]
>>
>>
>> #     compute c-index (Harrell's) for cox-glmnet models
>>        if (is.null(glmnet.cox.meaningful)){
>>          cIndexCoxglmnet <- c(cIndexCoxglmnet,NULL)
>>        }else{
>>          cIndexCoxglmnet <- c(cIndexCoxglmnet,
>> 1-rcorr.cens(predict(glmnet.cox.meaningful,
>> reformat_testSet),Surv(reformat_testSet$time,reformat_testSet 
>> $status))[1])
>>        }
>>  }
>>
>>  #Get average C-Index
>>  cIndex<- mean (unlist(cIndexCoxglmnet),rm.na=TRUE)
>>
>>  #create a list of all the objects generated
>>
>> assign 
>> (name,c(eval(parse(text=name)),glmnet.cv=list(glmnet.cv),glmnet.obj=li
>> st(glmnet.obj),
>>
>> selectedVar=list(colnames(selectedVar)),glmnet.cox=list(glmnet.cox),
>>
>> glmnet 
>> .cox.meaningful=list(glmnet.cox.meaningful),ipec.coxglmnet=list(ipec.c
>> oxglmnet),
>>                cIndex=cIndex))
>>
>>  # save image of the workspace after each iteration
>>    save.image("final_subgroup_analysissubgroup_analysis.RData")
>>
>>
>> ______________________________________________
>> 

> R-help@

>  mailing list
>> https://stat.ethz.ch/mailman/listinfo/r-help
>> PLEASE do read the posting guide
>> http://www.R-project.org/posting-guide.html
>> and provide commented, minimal, self-contained, reproducible code.
> 
> David Winsemius, MD
> Alameda, CA, USA
> 
> ______________________________________________

> R-help@

>  mailing list
> https://stat.ethz.ch/mailman/listinfo/r-help
> PLEASE do read the posting guide
> http://www.R-project.org/posting-guide.html
> and provide commented, minimal, self-contained, reproducible code.





-----
Frank Harrell
Department of Biostatistics, Vanderbilt University
--
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