[R] A question on time-dependent covariates in the Cox model.

2005-06-22 Thread Marianne dk
I have a dataset with

event=death
time (from medical examination until death/censoring)
dose (given at examination time)

Two groups are considered, a non-exposed group (dose=0), an exposed group 
(dose between 5 and 60).

For some reason there is a theory of the dose increasing its effect over 
time (however it was only given (and measured) once = at the time of 
examination).

I tested a model:

coxph(Surv(time,dod)~dose + dose:time)

Previously I tested the model in SAS:

proc phreg data=test;
model time*dod(0)=dose dosetime /rl ties=efron;
dosetime=time*dose;
run;

Without the interaction terms I get the same results for the two models. By 
including the interaction terms I do not. The model in R gives a negative 
coefficient for the interaction term which is expected to be positive (and 
is so in SAS). The LRTs are also completely different.

TWO QUESTIONS:

1) Is it reasonable to bring in an interaction term when dose is only 
measured once?

2) If yes, can anyone give a hint on explaining the difference between the 
models in R and SAS?

Thanx in advance,
marianne

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Re: [R] A question on time-dependent covariates in the Cox model.

2005-06-22 Thread Peter Dalgaard
"Marianne dk" <[EMAIL PROTECTED]> writes:

> I have a dataset with
> 
> event=death
> time (from medical examination until death/censoring)
> dose (given at examination time)
> 
> Two groups are considered, a non-exposed group (dose=0), an exposed group 
> (dose between 5 and 60).
> 
> For some reason there is a theory of the dose increasing its effect over 
> time (however it was only given (and measured) once = at the time of 
> examination).
> 
> I tested a model:
> 
> coxph(Surv(time,dod)~dose + dose:time)
> 
> Previously I tested the model in SAS:
> 
> proc phreg data=test;
>   model time*dod(0)=dose dosetime /rl ties=efron;
>   dosetime=time*dose;
>   run;
> 
> Without the interaction terms I get the same results for the two models. By 
> including the interaction terms I do not. The model in R gives a negative 
> coefficient for the interaction term which is expected to be positive (and 
> is so in SAS). The LRTs are also completely different.
> 
> TWO QUESTIONS:
> 
> 1) Is it reasonable to bring in an interaction term when dose is only 
> measured once?
> 
> 2) If yes, can anyone give a hint on explaining the difference between the 
> models in R and SAS?

I don't know what SAS does, maybe it second-guesses your intentions,
but R will definitely get it completely wrong. If you use time as a
covariate, the same time (of death/censoring) will be applied at all
death times. Pretty obviously, long observation times tend to be
associated with low mortalities! With interactions you get, er,
similarly incorrect effects.

To do coxph with time-dependent variables, you need to split data
into little time segments, according to the death time of every death,
inserting a new variable (ntime, say) which is the time of the
endpoint of the interval. 

-- 
   O__   Peter Dalgaard Øster Farimagsgade 5, Entr.B
  c/ /'_ --- Dept. of Biostatistics PO Box 2099, 1014 Cph. K
 (*) \(*) -- University of Copenhagen   Denmark  Ph: (+45) 35327918
~~ - ([EMAIL PROTECTED])  FAX: (+45) 35327907

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Re: [R] A question on time-dependent covariates in the Cox model.

2005-06-22 Thread Jacob Etches
This is a question about time-varying effects rather than time-varying 
covariates, even if the SAS method tests for the former by using the 
latter.  SAS evaluates the line

>> dosetime=time*dose;

for all observations at each event time as it estimates the model, such 
that you are not using future information.  It has the effect of 
testing for a linear change in the magnitude of the effect of dose over 
time.  I believe Paul Allison's survival book recommends this as a 
quick and dirty test for constancy of effect.  Had you put that line in 
a datastep prior to PHREG, rather than in PHREG, you'd get a completely 
different (and uninformative) result (probably the same as R is giving 
you), because each observation's total survival time would be used to 
create a single value for the interaction term.  You could manually 
replicate SAS's behaviour in R if you wanted, but every observation 
would have to start a new time interval whenever any other observation 
has an event, as Peter explained below.

You might also want to look at Aalen's additive survival model for 
non-linear changes in effect over time:
http://www.med.uio.no/imb/stat/addreg/

hope that helps,
Jacob Etches


On 2005/06/22, at 06:34, Peter Dalgaard wrote:

> "Marianne dk" <[EMAIL PROTECTED]> writes:
>
>> I have a dataset with
>>
>> event=death
>> time (from medical examination until death/censoring)
>> dose (given at examination time)
>>
>> Two groups are considered, a non-exposed group (dose=0), an exposed 
>> group
>> (dose between 5 and 60).
>>
>> For some reason there is a theory of the dose increasing its effect 
>> over
>> time (however it was only given (and measured) once = at the time of
>> examination).
>>
>> I tested a model:
>>
>> coxph(Surv(time,dod)~dose + dose:time)
>>
>> Previously I tested the model in SAS:
>>
>> proc phreg data=test;
>>  model time*dod(0)=dose dosetime /rl ties=efron;
>>  dosetime=time*dose;
>>  run;
>>
>> Without the interaction terms I get the same results for the two 
>> models. By
>> including the interaction terms I do not. The model in R gives a 
>> negative
>> coefficient for the interaction term which is expected to be positive 
>> (and
>> is so in SAS). The LRTs are also completely different.
>>
>> TWO QUESTIONS:
>>
>> 1) Is it reasonable to bring in an interaction term when dose is only
>> measured once?
>>
>> 2) If yes, can anyone give a hint on explaining the difference 
>> between the
>> models in R and SAS?
>
> I don't know what SAS does, maybe it second-guesses your intentions,
> but R will definitely get it completely wrong. If you use time as a
> covariate, the same time (of death/censoring) will be applied at all
> death times. Pretty obviously, long observation times tend to be
> associated with low mortalities! With interactions you get, er,
> similarly incorrect effects.
>
> To do coxph with time-dependent variables, you need to split data
> into little time segments, according to the death time of every death,
> inserting a new variable (ntime, say) which is the time of the
> endpoint of the interval.
>
> -- 
>O__   Peter Dalgaard Øster Farimagsgade 5, Entr.B
>   c/ /'_ --- Dept. of Biostatistics PO Box 2099, 1014 Cph. K
>  (*) \(*) -- University of Copenhagen   Denmark  Ph: (+45) 
> 35327918
> ~~ - ([EMAIL PROTECTED])  FAX: (+45) 
> 35327907
>
> __
> R-help@stat.math.ethz.ch mailing list
> https://stat.ethz.ch/mailman/listinfo/r-help
> PLEASE do read the posting guide! 
> http://www.R-project.org/posting-guide.html

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