简 介
失效时间数据
根据生存结局的发生情况，生存分析的数据资料常常分为终点事件(如死亡)和删失(其他生存结局)两类。
生存分析不同类型的数据包括：
完全数据(Complete data)
删失数据(Censoring data)
删失数据通常在其右上角标记"+"号，表示真实的生存时间未知，只知道比观察到的删失时间要长。在生存分析中，发生终点事件记为“1” ，删失记为"0” 。
删失的类型包括：
(1) 右删失(Right censored)
I型删失(Type I censoring)
II型删失(Type II censoring)
III型删失(Type II censoring)
(注:图中X表示发生终点事件，O示删失)
(2) 左删失(Left censored)
(3) 区间删失(Interval censored)
生存分析方法分类
1. 参数法--survreg()
假定生存时间服从某个特定的分布，然后根据分布的特点对生存时间进行分析，常用方法有指数分布法、weibull分步法、对数正态回归分布法等。参数法通过估计的参数得到生存率的估计值，对于两组及多组的样本可根据参数估计对其进行统计推断。早期应用于武器使用寿命的研究等。
2. 半参数法--coxph()
只规定了影响因素和生存状况间的关系，但是没对时间（和风险函数）的分布情况加以限定。这种方法主要用于分析生存率的影响因素，属于多因素分析方法，典型方法是cox比例风险模型。Cox模型分析法以风险率函数作为应变量，以与生存时间可能有关的协变量或交互项作为自变量来分析生存率。
3. 非参数法--survdiff()
根据样本的顺序统计量对生存率进行估计，常用的方法有log-rank检验、似然比检验，对于两个及多个生存率的比较，其零假设为两组或多组总体生存时间分布相同，而不对其具体的分布形式及参数进行推断。常用于随访资料医学研究。
缺失类型-Surv()
缺失类型选择可以通过surv()函数中的type参数来选择：
type=c('right', 'left', 'interval', 'counting', 'interval2', 'mstate'),
character string specifying the type of censoring. Possible values are "right", "left", "counting", "interval", "interval2" or "mstate".
今天介绍的是拟合参数生存回归模型的构建--survreg()。
软件包安装
if(require(survival))
install.packages("survival")数据读取
数据说明：
futime: survival or censoring time
fustat: censoring status
age: in years
resid.ds: residual disease present (1=no,2=yes)
rx: treatment group
ecog.ps: ECOG performance status (1 is better, see reference)
data(cancer, package="survival")
head(ovarian)## futime fustat age resid.ds rx ecog.ps
## 1 59 1 72.3315 2 1 1
## 2 115 1 74.4932 2 1 1
## 3 156 1 66.4658 2 1 2
## 4 421 0 53.3644 2 2 1
## 5 431 1 50.3397 2 1 1
## 6 448 0 56.4301 1 1 2实例操作
参数说明：
survreg(formula, data, weights, subset,
na.action, dist="weibull", init=NULL, scale=0,
control,parms=NULL,model=FALSE, x=FALSE,
y=TRUE, robust=FALSE, cluster, score=FALSE, ...)
formula
a formula expression as for other regression models. The response is usually a survival object as returned by the Surv function. See the documentation for Surv, lm and formula for details.
data
a data frame in which to interpret the variables named in the formula, weights or the subset arguments.
weights
optional vector of case weights
subset
subset of the observations to be used in the fit
na.action
a missing-data filter function, applied to the model.frame, after any subset argument has been used. Default is options()\$na.action.
dist
assumed distribution for y variable. If the argument is a character string, then it is assumed to name an element from survreg.distributions. These include "weibull", "exponential", "gaussian", "logistic","lognormal" and "loglogistic". Otherwise, it is assumed to be a user defined list conforming to the format described in survreg.distributions.
parms
a list of fixed parameters. For the t-distribution for instance this is the degrees of freedom; most of the distributions have no parameters.
init
optional vector of initial values for the parameters.
scale
optional fixed value for the scale. If set to <=0 then the scale is estimated.
control
a list of control values, in the format produced by survreg.control. The default value is survreg.control()
model, x, y
flags to control what is returned. If any of these is true, then the model frame, the model matrix, and/or the vector of response times will be returned as components of the final result, with the same names as the flag arguments.
score
return the score vector. (This is expected to be zero upon successful convergence.)
robust
Use robust sandwich error instead of the asymptotic formula. Defaults to TRUE if there is a cluster argument.
cluster
Optional variable that identifies groups of subjects, used in computing the robust variance. Like model variables, this is searched for in the dataset pointed to by the data argument.
...
other arguments which will be passed to survreg.control.构建模型
根据说明ovarian数据集，构建模型:
library(survival)
fit <- survreg(Surv(futime, fustat) ~ ., ovarian, dist = "weibull", scale = 1)
summary(fit)
##
## Call:
## survreg(formula = Surv(futime, fustat) ~ ., data = ovarian, dist = "weibull",
## scale = 1)
## Value Std. Error z p
## (Intercept) 12.7826 2.5137 5.09 3.7e-07
## age -0.0875 0.0338 -2.59 0.0096
## resid.ds -0.7659 0.7411 -1.03 0.3014
## rx 0.6269 0.6162 1.02 0.3090
## ecog.ps -0.2523 0.6061 -0.42 0.6772
##
## Scale fixed at 1
##
## Weibull distribution
## Loglik(model)= -90.6 Loglik(intercept only)= -98
## Chisq= 14.78 on 4 degrees of freedom, p= 0.0052
## Number of Newton-Raphson Iterations: 5
## n= 26筛选最优模型
若要找到最佳模型，可以进行变量选择，采用逐步回归法进行分析,最后找到age显著。
library(MASS)
stepVar <- stepAIC(fit, direction = "both")
## Start: AIC=191.29
## Surv(futime, fustat) ~ age + resid.ds + rx + ecog.ps
##
## Df AIC
## - ecog.ps 1 189.46
## - rx 1 190.31
## - resid.ds 1 190.39
## <none> 191.29
## - age 1 198.05
##
## Step: AIC=189.46
## Surv(futime, fustat) ~ age + resid.ds + rx
##
## Df AIC
## - resid.ds 1 188.42
## - rx 1 188.44
## <none> 189.46
## + ecog.ps 1 191.29
## - age 1 196.73
##
## Step: AIC=188.42
## Surv(futime, fustat) ~ age + rx
##
## Df AIC
## - rx 1 187.56
## <none> 188.42
## + resid.ds 1 189.46
## + ecog.ps 1 190.39
## - age 1 198.95
##
## Step: AIC=187.56
## Surv(futime, fustat) ~ age
##
## Df AIC
## <none> 187.56
## + rx 1 188.42
## + resid.ds 1 188.44
## + ecog.ps 1 189.55
## - age 1 198.06summary(stepVar)
##
## Call:
## survreg(formula = Surv(futime, fustat) ~ age, data = ovarian,
## dist = "weibull", scale = 1)
## Value Std. Error z p
## (Intercept) 13.9339 2.1030 6.63 3.5e-11
## age -0.1185 0.0339 -3.50 0.00047
##
## Scale fixed at 1
##
## Weibull distribution
## Loglik(model)= -91.8 Loglik(intercept only)= -98
## Chisq= 12.51 on 1 degrees of freedom, p= 0.00041
## Number of Newton-Raphson Iterations: 5
## n= 26optFit <- survreg(Surv(futime, fustat) ~ age, ovarian, dist = "weibull", scale = 1)一致性
C_index <- data.frame(Cindex = as.numeric(summary(coxph(Surv(futime, fustat) ~ age,
data = ovarian))$concordance[1]))
C_index
## Cindex
## 1 0.7844037生存分析
根据最优解，模型中只有age这个变量，所以直接做生存分析即可：
library(survminer)
ovarian$age = ifelse(ovarian$age > median(ovarian$age), "High", "Low")
f <- survfit(Surv(futime, fustat) ~ age, data = ovarian)
ggsurvplot(f, data = ovarian, surv.median.line = "hv", legend.title = "Risk Group",
legend.labs = c("High Risk", "Low Risk"), pval = TRUE, ggtheme = theme_bw())
验证
ovarian$resposnse <- predict(optFit, newdata = ovarian, type = "response")绘制ROC曲线
library(pROC)
roc <- roc(ovarian$fustat, ovarian$resposnse, legacy.axes = T, print.auc = T, print.auc.y = 45)
roc$auc
## Area under the curve: 0.6548plot(roc, legacy.axes = T, col = "red", lwd = 2, main = "ROC curv")
text(0.2, 0.2, paste("AUC: ", round(roc$auc, 2)))
Reference
Kalbfleisch, J. D. and Prentice, R. L., The statistical analysis of failure time data, Wiley, 2002.
基于机器学习构建临床预测模型
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MachineLearning 4. 癌症诊断方法之 K-邻近算法（KNN）
MachineLearning 5. 癌症诊断和分子分型方法之支持向量机（SVM)
MachineLearning 6. 癌症诊断机器学习之分类树（Classification Trees)
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MachineLearning 8. 癌症诊断机器学习之随机森林（Random Forest)
MachineLearning 9. 癌症诊断机器学习之梯度提升算法（Gradient Boosting)
MachineLearning 10. 癌症诊断机器学习之神经网络（Neural network)
MachineLearning 11. 机器学习之随机森林生存分析（randomForestSRC）
MachineLearning 12. 机器学习之降维方法t-SNE及可视化(Rtsne)
MachineLearning 13. 机器学习之降维方法UMAP及可视化 (umap)
MachineLearning 14. 机器学习之集成分类器(AdaBoost)
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MachineLearning 19. 机器学习之神经网络分类器(NNET)
MachineLearning 20. 机器学习之袋装分类回归树(Bagged CART)
MachineLearning 21. 机器学习之临床医学上的生存分析(xgboost)
MachineLearning 22. 机器学习之有监督主成分分析筛选基因(SuperPC)
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MachineLearning 26. 机器学习之弹性网络算法应用于生存分析(Enet)
MachineLearning 27. 机器学习之逐步Cox回归筛选变量(StepCox)
MachineLearning 28. 机器学习之偏最小二乘回归应用于生存分析(plsRcox)
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MachineLearning 36. 机器学习之基于神经网络的Cox比例风险模型 (Deepsurv)
MachineLearning 37. 机器学习之倾斜随机生存森林 (obliqueRSF)
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MachineLearning 39. 机器学习之基于条件随机森林的生存分析临床预测 (CForest)
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