**From: michel.tod@avc.ap-hop-paris.fr (tod michel)
Subject: Time-to-event**
Date: Mon, 30 Nov 1998 11:52:29 +0100

Dear NONMEM users,

I have some questions about the analysis of time-to-event data with Weibull distribution using NONMEM version IV and the code described at the PKPD server:

pkpd.icon.palo-alto.med.va.gov/nonmem.dir/NON_CONTINUOUS.DIR/

1- What are the key assumptions that must be met when using the Weibull distribution for time-to-event? In other words, can this model be used, at least as an approximation, for all this kind of data type? (I recognize the restriction given by LB Sheiner that covariates have to be time-independent).

2- Are there restrictions about the value of Gamma (the exponent of (T/Tmedian))? Has it to be greater than 1?

3- Is the subroutine CCONTR identical to that used for random logistic regression (given in the same directory /NON_CONTINUOUS.DIR/)?

4- How can I simulate data for a working exemple of time-to-event data? Could anyone show me a control file for simulation of these kind of data?

Thank you for your help.

Michel Tod, PhD

Dpt of Pharmacotoxicology

Hopital Avicenne

93009 Bobigny

FRANCE

****

**From: LSheiner <lewis@c255.ucsf.edu>
Subject: Re: Time-to-event**
Date: Mon, 30 Nov 1998 09:24:44 -0800

I can respond to some of your questions ...

tod michel wrote:

>

> Dear NONMEM users,

>

> I have some questions about the analysis of time-to-event data with

> Weibull distribution using NONMEM version IV and the code described at

> the PKPD server:

> pkpd.icon.palo-alto.med.va.gov/nonmem.dir/NON_CONTINUOUS.DIR/

>

> 1- What are the key assumptions that must be met when using the Weibull

> distribution for time-to-event? In other words, can this model be used,

> at least as an approximation, for all this kind of data type? (I

> recognize the restriction given by LB Sheiner that covariates have to be

> time-independent).

The same assump6ions as when using the Weibull for survival analysis in a more classical context, wqith teh single additiontaht the random effect is distributed normally. You might findit useful to read about survival analysis in some textbook, for example, Kalbfleisch & Prentice, "The statistical analysis of failure time data", Wiley, 1980.

>

> 2- Are there restrictions about the value of Gamma (the exponent of

> (T/Tmedian))? Has it to be greater than 1?

No, restrictions - as the exponent changes, the shape of the hazard changes.

>

> 3- Is the subroutine CCONTR identical to that used for random logistic

> regression (given in the same directory /NON_CONTINUOUS.DIR/)?

You should no longer be using CCONTR or CONTR. NONMEM V includes the LIKELIHOOD or -2LOGLIKELIHOOD option on the $ESTIM record. Your $PRED should supply the likeihood (probability) of the observation, or -2log likelihood, respectively, and NONMEM takes care of the rest.