R help - Oct 2006 - [OT] Survival and Function as co-primary endpoints in clinical trials. How to simulate in R ?

Dear R-Helpers,

Apologies in advance as this is partly (widely ?) OT. Not sure where to
ask, R is my favorite computer tool (no kidding) and there are plenty of
knowledgable and helpful people on the list.  

Background: There are discussions among experts and regulatory
authorities (cf guideline
http://www.emea.europa.eu/pdfs/human/ewp/056598en.pdf) that, in for
example Amyotrophic Lateral Sclerosis, a functional endpoint
(respiratory function, muscular testing, rating scale) should be
associated (co-primary, 2 primaries etc..) to survival in drug trials.

My problem: I wish to illustrate that from my point of view and when you
have a drug that improves survival this is not what you should do for
the following reasons: - Death leads to missing data on function (sic)
                   - This does not occur at random if the drug impacts
                   survival
                   - The assessment of function is biased in defavor of
                   the drug improving survival (keeping alive patients
                   with poor function)
                     and in favor of the placebo group (those who
                     survive have better function)

The questions: 1-Would some one please suggest litterature where this is
discussed or examples of similar situations
               2-  I would like to simulate the process in R ie generate
               survival (exponential for a start although Weibull may be
               be more  appropriate) data with several drug effects on
               survival (I can do this), and also simulate various
               effects on function (for example vital capacity) which
               would be correlated to the effect on survival (not sure I
               know what Ineed to do and how to do it...).

 I realize this is not clear language and a clear question but to help
 formulate the question better I would appreciate pointers to relevant
 litterature/scripts on simulation of clinical trials in general or more
 specific to my problem in R. 

Please answer to me directly to avoid OT inconvenience to the list and
so that I am not black listed...I'll be happy to summarize if relevant
to the list.

Best regards, Jean-Louis     
Jean-Louis Abitbol, MD
Chief Medical Officer
Trophos SA, Parc scientifique de Luminy, Case 931
Luminy Biotech Entreprises
13288 Marseille Cedex 9 France
Email: jlabitbol at trophos.com ---- Backup Email: abitbol at sent.com
Cellular: (33) (0)6 24 47 59 34
Direct Line: (33) (0)4 91 82 82 73-Switchboard: (33) (0)4 91 82 82 82  
Fax: (33) (0)4 91 82 82 89