gcefg {gcerisk}

Fit Generalized Competing Event Model Based on Fine Gray Regression

Description

Fit a generalized competing event model by using Fine Gray regression model with crr function in cmprsk package.

Usage

gcefg(Time, Ind, Cov, N, M, t)

Arguments

Time

survival time for event(s) of interest.

Ind

the status indicators including the primary event(s) of interest, competing event(s) of interest, and all kind of event(s) of interest, normally 0 = alive, 1 = dead from the specific event(s) of interest.

Cov

a data frame containing all covariates.

N

the number of bootstrap replicates

M

the number of bins for \omega or \omega+ plots.

t

survival time point for \omega or \omega+ plots.

Details

The gcerisk package is designed to help investigators optimize risk-stratification methods for competing risks data, such as described in Carmona R, Gulaya S, Murphy JD, Rose BS, Wu J, Noticewala S, McHale MT, Yashar CM, Vaida F, Mell LK. Validated competing event model for the stage I-II endometrial cancer population. Int J Radiat Oncol Biol Phys. 2014;89:888-98. Standard risk models typically estimate the effects of one or more covariates on either a single event of interest (such as overall mortality, or disease recurrence), or a composite set of events (e.g., disease-free survival, which combines events of interest with death from any cause). This method is inefficient in stratifying patients who may be simultaneously at high risk for the event of interest but low risk for competing events, and who thus stand to gain the most from strategies to modulate the event of interest. Compared to standard risk models, GCE models better stratify patients at higher (lower) risk for an event of interest and lower (higher) risk of competing events. GCE models focus on differentiating subjects based on the ratio of the cumulative hazard (or cumulative hazard of the subdistribution) for the event of interest to the cumulative hazard (or cumulative hazard of the subdistribution) for all events (\omega), and the ratio of the cumulative hazard (or cumulative hazard of the subdistribution) for the event of interest to the cumulative hazard (or cumulative hazard of the subdistribution) for competing events (\omega+).

The gcefg function produces model estimates and confidence intervals from a generalized competing event model based on the Fine-Gray model for subdistribution hazards. In the subdistribution hazards model, the function H(t)= -log(1-F(t)) represents the cumulative hazard of the subdistribution for the cumulative distribution function F(t). The model assumes proportional subdistribution hazards for the composite set of events.

The function returns \omega and \omega+ ratio estimates for the chosen covariates, with 95% confidence intervals, and plots \omega and \omega+ at time t within M ordered subsets of subjects as a function of increasing risk (based on the linear predictor, i.e. the inner product of a subject's data vector and the coefficient vector).

Value

$coef1

generalized competing event model coefficients (log (\omega ratio))

$coef2

generalized competing event model coefficients (log (\omega+ ratio))

$result1

result table for generalized competing event model containing exponential of coefficients (\omega ratio) and 95% confidence intervals

$result2

result table for generalized competing event model containing exponential of coefficients (\omega+ ratio) and 95% confidence intervals

$omegaplot1

\omega plot for generalized competing event model

$omegaplot2

\omega+ plot for generalized competing event model

$omegaplot3

plot of \omega vs time

$riskscore1

predicted risk scores for \omega

$riskscore2

predicted risk scores for \omega+

Author(s)

Hanjie Shen, Ruben Carmona, Loren Mell

References

• Carmona R, Gulaya S, Murphy JD, Rose BS, Wu J, Noticewala S, McHale MT, Yashar CM, Vaida F, Mell LK. (2014) Validated competing event model for the stage I-II endometrial cancer population. Int J Radiat Oncol Biol Phys.89:888-98.

• Carmona R, Green GB, Zakeri K, Gulaya S, Xu B, Verma R, Williamson C, Rose BS, Murphy JD, Vaida F, Mell LK. (2015) Novel method to stratify elderly patients with head and neck cancer. J Clin Oncol 33 (suppl; abstr 9534).

• Carmona R, Zakeri K, Green GB, Triplett DP, Murphy JD, Mell LK. (2015) Novel method to stratify elderly patients with prostate cancer. J Clin Oncol 33 (suppl; abstr 9532).

Examples

# sample data to test
data(Sample)
test <- Sample
d <- trunc(dim(test)[1]*0.1)
set.seed(seed=2017)
s <- sample(dim(test)[1],d,replace = FALSE)
test <- test[s,]
rm(list=setdiff(ls(), "test"))
test <- transform(test, LRF_OR_DF_FLAG = as.numeric(test$LRFFLAG | test$DFFLAG))
test <- transform(test, LRF_OR_DF_MO = pmin(test$LRFMO, test$DFMO))
test <- transform(test, CMFLAG = as.numeric(test$OSFLAG & !test$LRFFLAG & !test$DFFLAG))
test <- transform(test, ACMFLAG = as.numeric(test$LRF_OR_DF_FLAG | test$CMFLAG))
test <- transform(test, ACM_MO = pmin(test$LRF_OR_DF_MO, test$OSMO))

cod1 <- test$ACMFLAG
cod1[test$LRF_OR_DF_FLAG == 1] <- 1
cod1[test$CMFLAG == 1] <- 2
cod2 <- test$ACMFLAG
Ind <- data.frame(cod1 = cod1, cod2 = cod2)
Time <- test$OSMO/12
Cov <- test[,c(3,4,6,15)]

N <- 50
M <- 5
t <- 5

fit <- gcefg(Time, Ind, Cov, N, M, t)