/* PubH 7450
Exampel 9.1: A stratified Cox PHM for the bone marrow transplant data; 
             see p.297-303. 
*/

options ls=80 center pagesize=60 number label;
goptions device = PS;  
         /* graphs are saved in a file names sasgraph.ps */

/*
g--Disease Group
1-ALL
2-AML Low Risk
3-AML High Risk

T1 -- Time To Death Or On Study Time

T2 --Disease Free Survival Time (Time To Relapse, Death Or End Of Study)

d1 -- Death Indicator
1-Dead 0-Alive

d2 -- Relapse Indicator
1-Relapsed, 0-Disease Free

d3--Disease Free Survival Indicator
1-Dead Or Relapsed, 0-Alive Disease Free)

TA--Time To Acute Graft-Versus-Host Disease

dA--Acute GVHD Indicator
1-Developed Acute GVHD 0-Never Developed Acute GVHD)

TC--Time To Chronic Graft-Versus-Host Disease

dC--Chronic GVHD Indicator
1-Developed Chronic GVHD 0-Never Developed Chronic GVHD

TP--Time To Return of Platelets to Normal Levels

dP--Platelet Recovery Indicator
1-Platelets Returned To Normal, 0-Platelets Never Returned to Normal

Z1--Patient Age In Years

Z2--Donor Age In Years

Z3--Patient Sex
1-Male, 0-Female

Z4--Donor Sex
1-Male, 0-Female

Z5--Patient CMV Status
1-CMV Positive, 0-CMV Negative

Z6--Donor CMV Status
1-CMV Positive, 0-CMV Negative

 Z7--Waiting Time to Transplant In Days

Z8--FAB
1-FAB Grade 4 Or 5 and AML, 0-Otherwise

Z9--Hospital
1-The Ohio State University, 2-Alferd , 3-St. Vincent, 4-Hahnemann

Z10--MTX Used as a Graft-Versus-Host- Prophylactic
1-Yes 0-No
*/

data bmt;
infile '/home/merganser/weip/public_html/course/7450/data/bmt.txt'
       firstobs=87;
input grp T1 T2 d1 d2 d3 Ta da Tc dc Tp dp V1-V10;
if grp=2 then Z1=1; /* AML Low Risk*/
  else Z1=0;
if grp=3 then Z2=1; /* AML High Risk*/
  else Z2=0;
Z3=V8; /* FAB */
Z4=V1-28; /* patient age */
Z5=V2-28; /* donor age */
Z6=Z4*Z5;

/* By Table 9.5 on p.304: the PH does NOT hold for MTX; 
   as an alternative, fit a stratified PHM.
   see Table 9.7 on p.309.
*/
proc phreg data=bmt;
model T2*d3(0) = Z1 Z2 Z3 Z4 Z5 Z6 Zp ;
strata V10;
if dp=0 or T2<Tp then Zp=0;
if dp=1 and T2>=Tp then Zp=1;
title 'A stratified PH model with Zp(t) and other fixed factors';

/* the corresponding PHM: */
proc phreg data=bmt;
model T2*d3(0) = Z1 Z2 Z3 Z4 Z5 Z6 Zp V10;
if dp=0 or T2<Tp then Zp=0;
if dp=1 and T2>=Tp then Zp=1;
title 'A standard PHM with Zp(t) and other fixed factors';

            A stratified PH model with Zp(t) and other fixed factors           1

               Summary of the Number of Event and Censored Values
                                                                  Percent
      Stratum    V10            Total       Event    Censored    Censored

            1    0                 97          57          40       41.24
            2    1                 40          26          14       35.00
      -------------------------------------------------------------------
        Total                     137          83          54       39.42

                             Model Fit Statistics
 
                                     Without           With
                    Criterion     Covariates     Covariates

                    -2 LOG L         644.652        606.379
                    AIC              644.652        620.379
                    SBC              644.652        637.311

                    Testing Global Null Hypothesis: BETA=0
 
            Test                 Chi-Square       DF     Pr > ChiSq

            Likelihood Ratio        38.2728        7         <.0001
            Score                   44.6457        7         <.0001
            Wald                    40.3675        7         <.0001

                    Analysis of Maximum Likelihood Estimates
 
                   Parameter     Standard                               Hazard
  Variable   DF     Estimate        Error   Chi-Square   Pr > ChiSq      Ratio

  Z1          1     -0.99030      0.36658       7.2980       0.0069      0.371
  Z2          1     -0.36327      0.37138       0.9568       0.3280      0.695
  Z3          1      0.89203      0.28347       9.9024       0.0017      2.440
  Z4          1      0.00954      0.01984       0.2314       0.6305      1.010
  Z5          1     -0.00141      0.01791       0.0062       0.9373      0.999
  Z6          1      0.00255    0.0009364       7.4245       0.0064      1.003
  Zp          1     -1.00334      0.34453       8.4810       0.0036      0.367

              A standard PHM with Zp(t) and other fixed factors               3

                             Model Fit Statistics
 
                                     Without           With
                    Criterion     Covariates     Covariates

                    -2 LOG L         746.719        705.816
                    AIC              746.719        721.816
                    SBC              746.719        741.166

                    Testing Global Null Hypothesis: BETA=0
 
            Test                 Chi-Square       DF     Pr > ChiSq

            Likelihood Ratio        40.9033        8         <.0001
            Score                   48.5572        8         <.0001
            Wald                    43.4747        8         <.0001

                    Analysis of Maximum Likelihood Estimates
 
                   Parameter     Standard                               Hazard
  Variable   DF     Estimate        Error   Chi-Square   Pr > ChiSq      Ratio

  Z1          1     -0.95769      0.36386       6.9278       0.0085      0.384
  Z2          1     -0.36425      0.37364       0.9504       0.3296      0.695
  Z3          1      0.82122      0.28394       8.3648       0.0038      2.273
  Z4          1      0.00590      0.01986       0.0883       0.7663      1.006
  Z5          1      0.00520      0.01785       0.0849       0.7708      1.005
  Z6          1      0.00287    0.0009292       9.5310       0.0020      1.003
  Zp          1     -0.95691      0.33948       7.9456       0.0048      0.384
  V10         1      0.23239      0.25780       0.8126       0.3674      1.262