On 01/01/2013 05:00 AM, r-help-requ...@r-project.org wrote:
Dear all,
Is there an implementation of Simon&  Makuch method of plotting the survival 
function with time-dependent variables. I?m only able to find event.chart in Hmisc 
for the purpose and I would prefer the Simon and Makuch method. I believe stata has 
it implemented for this purpose, but I cannot find it on CRAN.


Simon R, Makuch RW. A non-parametric graphical representation of the 
relationship between survival and the occurrence of an event: application to 
responder versus non-responder bias.  Statistics in Medicine 1984; 3: 35-44.
Short answer: it's easy, but I don't think the result is a survival curve.

Long answer:
1. Write out your data in (start, stop] form, exaclty as you would for a time-dependent Cox model. For example:
    id   time1  time2  status  response
     1     0      24      1      0
     2     0      15      0      0
     2    15      43      1      1
     3     0      31      0      0
  ...

Subject 1 has died without response at time 24. Subject 2 responded at time 15 and then died at time 45. Subject 3 is censored at 31 and has as yet not responded, etc.

The time dependent Cox model is
     fit <- coxph(Surv(time1, time2, status) ~ response, data=yourdata).
Everyone agrees that this is the right model, and if you read the "score test" line of summary(fit) you will have the test discussed in equation 1 and 2 of the Simon and Makuch paper. (Well almost- if there are 2 deaths tied on the same day there is an n-1 vs n-2 disagreement between authors with respect to the variance formula, but the effect is trivial.)

2. Hazard functions make sense for time dependent covariates. It is what the Cox model is founded on and we all agree. Simon and Makuck now make the argument
   a. Hazard functions are nice, but my clients are used to survival curves
b. When there aren't time-dependent covariates S(t) = exp(-H(t)) where S=survival and H=hazard
   c. Let's pretend that the formula in b still makes sense for this case, and 
apply it.

The R solution for c is trivial: replace "coxph" with "survfit" in the code above. You will get their curves (with proper confidence intervals) and can make plots in the usual way.

3. I don't agree with the argument. On the positive side, if H1 = H2 (no impact of response) then the Cox model will say "nothing here" and the Simon curves will give a picture that agrees, as opposed to some of the more boneheaded (but common in the medical literature) curves that they show in their figures 2b and 3b.

The problem is that the result is not a survival curve --- I've never figured out exactly WHAT it is. For something to be interpreted as a survival curve there needs to be a set of subjects for whom I could hold up the graph and say "this is your future". Put another way, assume that you have the above curves in hand and there is a new patient sitting across the desk from you. What is your answer when he/she says "Doc, which curve am I?".

I tend to view these curves as "primum non nocere", if faced with a client who absolutely won't bend when told the truth that there is no good survival curve for time-dependent covariates.

Terry Therneau

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