[R] CoxPH multivariate frailty model with coxph (survival)

Denise b den|@e@je@ne@b @end|ng |rom gm@||@com
Fri Jul 19 19:19:41 CEST 2019


 Dear R users,

I am interested in estimating the effects of a treatment on two
time-to-event traits (on simulated data), accounting for the dependency
between the two time-to-event outcomes.

I precise that the events are NOT recurrent, NOT competitive, NOT ordered.
The individuals are NOT related and can have 0, 1 or the 2 events (in any
ordered).

So, I specified a time-to-event model with one Cox PH hazard function for
each outcome.
The two hazard functions are linked by a common subject-specific frailty
term (gamma distribution) to account for the dependency. The likelihood
function of that model would include two risks sets (1 for eachoutcome)
connected via the shared frailty term.

To fit that model, I used the coxph function (survival R package, T.
Thernaud):
coxph( Surv(Time, Status) ~ treatment*Event_type + strata(Event_type) +
frailty(ID), data=example)
- where example is my dataset, with 2*N individuals (2 rows for each
individual, corresponding to each time-to-event outcome)
- Time = c(Time_outcome1, Time_outcome2)
- Status=c(Event_outcome1, Event_outcome2)
- Event_type=c(rep(0,length(Time_outcome1)),rep(1,length(Time_outcome2))
- ID=c(ID,ID)

So, the model implies different baseline hazard function for each outcome
(argument strata) and estimate a treatment effect for each event type(
treatment*Event_type).

Although the model returns some estimates close to what I expected
(simulation study), the problem is that most of the examples I found with
this type of formulation are for competitive time-to-event models (as
presented in Therneau's and Grambush's book "Modeling survival
data"  (pages 240-260 and 175-185) and also in some info I found on
internet).

So, I am wondering if some of you have the same or different interpretation
of mime.
Otherwise do you have other functions to recommend me to fit the desired
model, such as coxme...? I also checked the package " mets" which also
describes several examples for competitive time-to-event traits, but not
for NON competitive events.

Thanks in advance for your help,
Denise

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