Statistical Analysis¶

Dependent Variable (All Endpoints)¶

For each endpoint, the dependent variable will be Change from Vehicle, defined for each animal and time interval on Dosing Day 3 (including baseline) as:

[ \text{Change from Vehicle} = \big(\text{Value at Day 3, time } t\big) - \big(\text{Value at Vehicle Day 1, same time } t\big) ]

Study-Day Phases¶

Data will be analyzed by study-day phase:

  • Phase 1: Hours 1–6 (six 1-hour subphases)
  • Phase 2: Hours 7–12 (six 1-hour subphases)
  • Phase 3: Hours 13–18 (six 1-hour subphases)
  • Phase 4: Hours 19–24 (six 1-hour subphases)

Model (Within Phase)¶

Within each phase, a repeated-measures ANCOVA (RANCOVA) will be fit using PROC MIXED, with:

  • Fixed effects: TRT, TIME, and TRT×TIME
  • Covariate: baseline Change from Vehicle
  • Repeated effect: TIME
  • Subject: SUBJID

The covariance structure will be selected using AICC across candidate covariance structures.

Hypothesis Testing¶

For each treatment group, the null hypothesis will be tested at the 0.05 significance level at each time interval:

[ H_0: \text{Change from Vehicle} = 0 ]

Macro: RANCOVA_PARALLEL¶

Objective¶

Run a repeated-measures ANCOVA / MMRM in PROC MIXED for each PARAMCD and PHASE, using a user-specified within-subject covariance structure, and save key outputs to datasets for easy comparison across covariance types.

Model (fixed effects)¶

[ \text{CHANGE} = \text{BASE} + \text{DOSE} + \text{SUBPHASE} + (\text{DOSE} \times \text{SUBPHASE}) ]

Key questions answered¶

  1. Is there evidence of a treatment-by-time interaction?
    Type 3 test for DOSE*SUBPHASE
  2. What are the model-based means over time by dose?
    LSMeans for DOSE*SUBPHASE
  3. Which covariance structure fits best?
    AICC from FitStatistics (used for comparing TYPE choices)

Parameters¶

  • type=
    Covariance structure for the REPEATED statement.
    Examples: CS, CSH, AR(1), ARH(1), UN, TOEP, SP(POW), etc.
    Note: Parentheses in type are removed for dataset naming
    (e.g., SP(POW) → SPPOW).

  • random=
    Optional RANDOM statement(s) inserted verbatim into PROC MIXED.
    Use for random intercept/slope models when appropriate.
    Example: random intercept / subject=subjid;
    Leave blank to fit a pure repeated-measures model.

Input data requirements (MYDATA)¶

Your dataset must contain:

  • PARAMCD, PHASE (BY variables)
  • SUBJID (subject identifier)
  • DOSE (treatment/dose group)
  • SUBPHASE (visit/time variable)
  • CHANGE (response)
  • BASE (baseline covariate)

Sorting requirement:
Because BY-processing is used, the data must be sorted by:

  • PARAMCD, PHASE

Outputs (ODS OUTPUT datasets)¶

For each covariance structure type, the macro creates:

  • <type>.TESTS
    Type 3 tests filtered to the interaction (DOSE*SUBPHASE), plus TYPE label

  • <type>.LSM
    LSMeans for DOSE*SUBPHASE, plus TYPE label

  • <type>.FIT
    FitStatistics filtered to AICC, plus TYPE label

Notes¶

  • type is “cleaned” (parentheses removed) after the PROC MIXED step to ensure valid dataset names.
  • The Type 3 filter uses Effect="*SUBPHASE" which matches "DOSE*SUBPHASE".
  • The fit row retained is: AICC (Smaller is Better).
    You can switch to AIC/BIC by changing the `WHER
In [ ]:
In [48]:
options nonotes nosource nosource2 nomprint nomlogic nosymbolgen;

/***********Format for p values*************************************************/
proc format;
   picture psignif (round) low-0.001='<.001*' (noedit) 0.001<-<0.05='0009.999*' 0.05-1='0009.999';
run;


proc format; 
   invalue param (notsorted) "HR" = 1 "PP" = 2 "SAP"= 3 "DAP"= 4 "MAP"= 5; 
     value dayx (notsorted) 1 = "Day 1"  3= "Day 3"; 
run;

*  Format used *****************************************;
%let STATFMT0D=12.;
%let STATFMT1D=%sysevalf(&STATFMT0D + 0.1);
%let STATFMT2D=%sysevalf(&STATFMT1D + 0.1);
%let STATFMT3D=%sysevalf(&STATFMT2D + 0.1);
%let STATFMT4D=%sysevalf(&STATFMT3D + 0.1);
%let STATFMT5D=%sysevalf(&STATFMT4D + 0.1);


* rounding *********************************************;
%let round1 =0.1;
%let round2 =%sysevalf(0.1*&round1);
%let round3 =%sysevalf(0.1*&round2);
%let round4 =%sysevalf(0.1*&round3);
%let round5 =%sysevalf(0.1*&round4);

%put &STATFMT1D &STATFMT2D &STATFMT3D &STATFMT4D &STATFMT5D 
     &round1 &round2 &round3 &round4 &round5;

/*******************************************************/

12.1 12.2 12.3 12.4 12.5       0.1 0.01 0.001 0.0001 0.00001

Read ADSX from SASDATA library into WORK and print first 10 rows

In [4]:
libname sasdata "/export/viya/homes/alpha@alphatraore.com/toydata";

data adsx;
    set sasdata.adsx;
run;

proc print data =adsx (obs=10); run;
SAS Output

The SAS System

Obs SUBJID PARAMCD PERIOD PHASE SUBPHASE TIME DOSE VALUE VEHICLE CHANGE BASE
1 4429843 HR 1 0 1 0 1 59.803 59.740 0.063 .
2 4429843 HR 1 1 1 1 1 136.792 70.102 66.690 0.063
3 4429843 HR 1 1 2 2 1 146.995 51.557 95.438 0.063
4 4429843 HR 1 1 3 3 1 144.255 62.700 81.555 0.063
5 4429843 HR 1 1 4 4 1 131.402 56.043 75.359 0.063
6 4429843 HR 1 1 5 5 1 133.367 56.759 76.608 0.063
7 4429843 HR 1 1 6 6 1 118.239 48.994 69.245 0.063
8 4429843 HR 1 2 1 7 1 99.816 61.676 38.140 0.063
9 4429843 HR 1 2 2 8 1 104.273 47.869 56.404 0.063
10 4429843 HR 1 2 3 9 1 107.491 50.444 57.047 0.063

Exclude baseline (TIME=0) and sort by PARAMCD and PHASE for BY-group analyses

In [ ]:
/* Baseline dataset (TIME=0) and Sort for BY paramcd phase */ */
data mybase;
     set adsx;
     where time=0;
run;
proc sort; by paramcd phase  ;  run;


/* Baseline LSMeans by DOSE within PARAMCD/PHASE */
proc mixed data=mybase;
        by paramcd phase;
        class dose;
        model CHANGE = DOSE ;
        LSMEANS DOSE;
        ods output
        LSMeans = lsm_base
        ;
run;

/* Add baseline subphase flag */
data baselsm;
        set lsm_base;
        SUBPHASE=1;
run;
In [ ]:
In [56]:
/* Create analysis dataset excluding baseline (TIME ≠ 0) */
data mydata;
     set adsx;
     where time^=0;
run;

/* Sort for subsequent BY-group analyses (PARAMCD, PHASE) */
proc sort; by paramcd phase  ;  run;

%macro RANCOVA_PARALLEL(type=, random= );

proc mixed data=mydata;
       by paramcd phase ; 
       class subjid dose subphase; 

       model change = base dose subphase dose*subphase; 
       &random
       repeated SUBPHASE / type=&type sub=subjid;
       lsmeans DOSE*SUBPHASE ;
       %let type = %sysfunc(compress(%superQ(type),%str(%(%))));

       ods output
       Tests3 =&type.tests (where=(Effect="*SUBPHASE"))
       LSMeans = &type.lsm
       FitStatistics =&type.Fit
;
run;

data &type.Fit (drop=Descr);
     set &type.Fit;
     length type $15;
     /*    where=(Descr="AIC (Smaller is Better)");*/
     where Descr="AICC (Smaller is Better)";
     type="&type.   ";
run;


data &type.tests ;
     set &type.tests;
     length type $15;
     type="&type.   ";
run;

data &type.lsm ;
     set &type.lsm;
     length type $15;
     type="&type.   ";
run;

%mend RANCOVA_PARALLEL;
























In [58]:



     


ods results off;
ods select none;
ods exclude all;
ods graphics off;

/***************************************************************/
%RANCOVA_PARALLEL(type=CS)
%RANCOVA_PARALLEL(type=CSH)

%RANCOVA_PARALLEL(type=AR(1) , random=%str(random subjid;))
%RANCOVA_PARALLEL(type=ARH(1), random=%str(random subjid;) )

ods results on; 
ods select all; 
ods exclude none; 
ods graphics on;



     




















    
    











SAS Output













































In [59]:



     


/****************** Checking the fit to select the best model****/
data fitdata;
     set Csfit Cshfit Ar1fit  Arh1fit;
run;

proc sort data=fitdata; by paramcd phase value; run;

data bestfit;
     set fitdata;
    by paramcd phase value;
     if first.phase;
run;
proc sort; by paramcd phase type; run;

/*************Stack the data and select the best************/
data lsm; set Cslsm Cshlsm Ar1lsm Arh1lsm ; run;
proc sort; by paramcd phase  type; run;

data lsm_s;
     merge lsm (in=a) bestfit (in=b);
     by paramcd phase  type;
     if  a and b;
run;

data A_lsm_s;
     set lsm_s baselsm;
run;


proc sort data=A_lsm_s; by paramcd   phase SUBPHASE; run;

data report_lsm_ (rename=(dose=trtn SUBPHASE=atptn));
     set A_lsm_s;
     length rownum 8 rowlbl $40 cell $20; 
     retain  rownum;
     by paramcd   phase SUBPHASE;
     rownum =4;
          rowlbl = 'LSM';
          if abs(Estimate) < 10 then cell   = strip(put(round(Estimate,&round4), &STATFMT4D));
          else if 10 =< abs(Estimate) < 100 then cell   = strip(put(round(Estimate,&round3), &STATFMT3D));
          else if 100 =< abs(Estimate) < 1000 then cell   = strip(put(round(Estimate,&round2), &STATFMT2D));
          else if abs(Estimate) =< 1000 then cell   = strip(put(round(Estimate,&round1), &STATFMT1D));
     output;
     rownum +1;
          rowlbl = 'LSM s.e.';
          if abs(Estimate) < 10 then cell   = strip(put(round(StdErr,&round5), &STATFMT5D));
          else if 10 =< abs(Estimate) < 100 then cell   = strip(put(round(StdErr,&round4), &STATFMT4D));
          else if 100 =< abs(Estimate) < 1000 then cell   = strip(put(round(StdErr,&round3), &STATFMT3D));
          else if abs(Estimate) =< 1000 then cell   = strip(put(round(StdErr,&round2), &STATFMT2D));
     output;
     keep paramcd PHASE DOSE SUBPHASE rownum rowlbl cell;
run;

data report_lsm;
     set report_lsm_;
     if missing(atptn) then atptn=999;
run;



     




















    
    





























In [61]:



     


proc sort data=A_lsm_s (rename=(dose=trtn SUBPHASE=atptn)) out=A_lsm_ss ; by paramcd phase  atptn trtn ; run;

data report_lsmPv ;
     set A_lsm_ss;
     length rownum 8 rowlbl $40 cell $20; 
     retain  rownum;
     
     by paramcd phase  atptn trtn ;
     rownum =6;
          rowlbl = 'LSM = 0 p-value     ';
          cell   = strip(strip(put(Probt,psignif.)));
     output;
     keep paramcd phase  rownum rowlbl cell atptn trtn;
run;



     




















    
    





























In [63]:



     


ods results off;
ods select none;
ods exclude all;
ods graphics off;

/********************************************************/
*  Create the statistics for Section 1 of the report;
proc summary print data=adsx missing stackods 
             n mean std;
  class paramcd  dose phase SUBPHASE;
  var CHANGE;
  ods output Summary=bySUBPHASE;
run; quit;

proc summary print data=adsx (where=(PHASE^=0)) missing stackods   
             n mean std;
  class subjid paramcd  dose phase;
  var CHANGE;
  ods output Summary=tempsum;
run; quit;


proc summary print data=tempsum missing stackods    
             n mean std;
  class paramcd  dose phase;
  var Mean;
  ods output Summary=overall;
run; quit;

data summary;
     set bySUBPHASE overall;
     if missing(SUBPHASE) then SUBPHASE=999;
run;

proc sort data=summary; by paramcd  dose phase SUBPHASE; run;  

*;
*  Create a separate row from specific column values of the 
*  Summary data - Section 1.
*;

data report_summary_ (rename=(SUBPHASE=atptn dose=trtn));
     set work.summary;
     length rownum 8 rowlbl $40 cell $20; 
     retain  rownum;
     section = 1;
     by paramcd  dose phase SUBPHASE;
     rownum =1;
          rowlbl = 'Mean Change from Vehicle';
          if abs(mean) < 10 then cell   = strip(put(round(mean,&round4), &STATFMT4D));
          else if 10 =< abs(mean) < 100 then cell   = strip(put(round(mean,&round3), &STATFMT3D));
          else if 100 =< abs(mean) < 1000 then cell   = strip(put(round(mean,&round2), &STATFMT2D));
          else if abs(mean) =< 1000 then cell   = strip(put(round(mean,&round1), &STATFMT1D));
     output;
     rownum +1;
          rowlbl = 'SD';
          if abs(mean) < 10 then cell   = strip(put(round(StdDev,&round5), &STATFMT5D));
          else if 10 =< abs(mean) < 100 then cell   = strip(put(round(StdDev,&round4), &STATFMT4D));
          else if 100 =< abs(mean) < 1000 then cell   = strip(put(round(StdDev,&round3), &STATFMT3D));
          else if abs(mean) =< 1000 then cell   = strip(put(round(StdDev,&round2), &STATFMT2D));
     output;

     rownum +1;
     rowlbl = 'N';
     cell   = strip(put(N, &STATFMT0D));
     output;

     keep paramcd phase  rownum rowlbl cell SUBPHASE dose; ;
run;
data report_summary;
     set report_summary_;
     if atptn=999 and rownum=2 then cell="NA";
run;


/*****************Stack for report *********************/

data tempdata1 (where=(phase^=0));
     set Report_lsmPv Report_lsm report_summary;
     if missing(atptn) then atptn=999;
     paramn=input(paramcd,param.);
run;

proc sort ; by paramcd paramn phase  trtn rownum rowlbl atptn;run;


*  Transpose the data to get the layout needed for the report for post dose ;

proc transpose data=tempdata1 prefix=time_
               out=report_post (drop=_name_);
  by paramcd paramn phase  trtn rownum rowlbl;
  var cell;
  id atptn;
run; 


/***********base****************/
data tempdata2 (where=(phase=0));
     set Report_lsmPv Report_lsm report_summary;
     paramn=input(paramcd,param.);
     atptn=0;
run;

proc sort ; by paramcd paramn phase  trtn rownum rowlbl atptn;run;


*  Transpose the data to get the layout needed for the report for pre dose;

proc transpose data=tempdata2 prefix=time_
               out=report_base_ (drop=_name_);
  by paramcd paramn phase  trtn rownum rowlbl;
  var cell;
  id atptn;
run; 

data report_base;
     set report_base_;
     phase=1;
run;

/******all the table ***********************/

data reportfinal;
     merge report_base report_post;
     by paramcd paramn phase  trtn rownum rowlbl;
run;

ods results on; 
ods select all; 
ods exclude none; 
ods graphics on; 

proc print data=reportfinal; run;



     




















    
    











SAS Output


























Obs
PARAMCD
paramn
PHASE
trtn
rownum
rowlbl
time_0
time_1
time_2
time_3
time_4
time_5
time_6
time_999






1
HR
1
1
1
1
Mean Change from Vehicle
-5.6808
32.887
65.620
62.210
62.277
50.920
51.484
54.233




2
HR
1
1
1
2
SD
5.35020
26.4502
22.4734
14.2521
10.7755
18.2817
12.4820
NA




3
HR
1
1
1
3
N
4
4
4
4
4
4
4
4




4
HR
1
1
1
4
LSM
-5.6808
33.494
66.227
62.817
62.885
51.528
52.091
  




5
HR
1
1
1
5
LSM s.e.
3.53068
9.4020
8.6803
6.5935
6.3018
7.3207
4.3766
  




6
HR
1
1
1
6
LSM = 0 p-value
0.142
<.001*
<.001*
<.001*
<.001*
<.001*
<.001*
  




7
HR
1
1
2
1
Mean Change from Vehicle
0.4820
2.8933
30.080
28.284
21.067
21.256
15.926
19.917




8
HR
1
1
2
2
SD
8.79171
18.32200
16.4893
13.7110
13.1081
7.0977
3.4467
NA




9
HR
1
1
2
3
N
4
4
4
4
4
4
4
4




10
HR
1
1
2
4
LSM
0.4820
2.7469
29.933
28.137
20.920
21.109
15.779
  




11
HR
1
1
2
5
LSM s.e.
3.53068
9.29278
8.5619
6.4368
6.1377
7.1799
4.1368
  




12
HR
1
1
2
6
LSM = 0 p-value
0.894
0.769
0.001*
<.001*
0.001*
0.005*
<.001*
  




13
HR
1
1
3
1
Mean Change from Vehicle
3.0553
-10.479
24.696
23.208
22.907
29.218
20.813
18.394




14
HR
1
1
3
2
SD
6.60833
12.5510
16.7581
14.0077
13.3197
12.5136
2.3645
NA




15
HR
1
1
3
3
N
4
4
4
4
4
4
4
4




16
HR
1
1
3
4
LSM
3.0553
-10.940
24.235
22.747
22.446
28.757
20.351
  




17
HR
1
1
3
5
LSM s.e.
3.53068
9.3530
8.6273
6.5235
6.2285
7.2577
4.2704
  




18
HR
1
1
3
6
LSM = 0 p-value
0.409
0.248
0.007*
0.001*
<.001*
<.001*
<.001*
  




19
HR
1
2
1
1
Mean Change from Vehicle
  
21.215
40.394
45.012
28.181
39.603
32.725
34.522




20
HR
1
2
1
2
SD
  
13.3448
11.3117
8.6502
15.2532
16.0131
13.4334
NA




21
HR
1
2
1
3
N
  
4
4
4
4
4
4
4




22
HR
1
2
1
4
LSM
  
25.729
44.907
49.526
32.695
44.116
37.238
  




23
HR
1
2
1
5
LSM s.e.
  
6.0514
3.7927
2.9337
7.5557
5.8270
5.3551
  




24
HR
1
2
1
6
LSM = 0 p-value
  
<.001*
<.001*
<.001*
<.001*
<.001*
<.001*
  




25
HR
1
2
2
1
Mean Change from Vehicle
  
1.8203
12.587
15.388
15.828
20.142
6.5480
12.052




26
HR
1
2
2
2
SD
  
9.84040
5.4118
7.9559
8.1258
4.0932
6.66645
NA




27
HR
1
2
2
3
N
  
4
4
4
4
4
4
4




28
HR
1
2
2
4
LSM
  
0.7328
11.499
14.300
14.740
19.054
5.4605
  




29
HR
1
2
2
5
LSM s.e.
  
5.93683
3.6072
2.6896
7.4643
5.7080
5.22531
  




30
HR
1
2
2
6
LSM = 0 p-value
  
0.902
0.003*
<.001*
0.054
0.002*
0.302
  




31
HR
1
2
3
1
Mean Change from Vehicle
  
1.7793
17.523
12.252
25.109
29.862
29.819
19.391




32
HR
1
2
3
2
SD
  
11.12709
8.5156
5.7771
12.6284
9.3523
9.2791
NA




33
HR
1
2
3
3
N
  
4
4
4
4
4
4
4




34
HR
1
2
3
4
LSM
  
-1.6469
14.097
8.8256
21.683
26.436
26.392
  




35
HR
1
2
3
5
LSM s.e.
  
6.00010
3.7104
2.82648
7.5147
5.7738
5.2971
  




36
HR
1
2
3
6
LSM = 0 p-value
  
0.785
<.001*
0.003*
0.006*
<.001*
<.001*
  




37
HR
1
3
1
1
Mean Change from Vehicle
  
27.859
27.505
23.308
24.550
20.126
19.665
23.835




38
HR
1
3
1
2
SD
  
8.6534
6.6541
6.2420
9.5938
11.1809
6.0945
NA




39
HR
1
3
1
3
N
  
4
4
4
4
4
4
4




40
HR
1
3
1
4
LSM
  
29.810
29.456
25.258
26.500
22.076
21.615
  




41
HR
1
3
1
5
LSM s.e.
  
3.4445
3.4445
3.4445
3.4445
3.4445
3.4445
  




42
HR
1
3
1
6
LSM = 0 p-value
  
<.001*
<.001*
<.001*
<.001*
<.001*
<.001*
  




43
HR
1
3
2
1
Mean Change from Vehicle
  
9.3565
-1.9355
1.7350
0.4398
-2.4290
-1.0460
1.0201




44
HR
1
3
2
2
SD
  
7.65104
8.17044
4.23825
10.18202
3.74822
2.86982
NA




45
HR
1
3
2
3
N
  
4
4
4
4
4
4
4




46
HR
1
3
2
4
LSM
  
8.8866
-2.4054
1.2651
-0.0301
-2.8989
-1.5159
  




47
HR
1
3
2
5
LSM s.e.
  
3.31740
3.31740
3.31740
3.31740
3.31740
3.31740
  




48
HR
1
3
2
6
LSM = 0 p-value
  
0.010*
0.472
0.705
0.993
0.387
0.650
  




49
HR
1
3
3
1
Mean Change from Vehicle
  
21.028
16.797
13.002
3.8520
7.8570
12.371
12.484




50
HR
1
3
3
2
SD
  
7.9806
4.4917
6.5361
4.56616
3.95595
7.0126
NA




51
HR
1
3
3
3
N
  
4
4
4
4
4
4
4




52
HR
1
3
3
4
LSM
  
19.547
15.316
11.522
2.3715
6.3765
10.890
  




53
HR
1
3
3
5
LSM s.e.
  
3.3879
3.3879
3.3879
3.38788
3.38788
3.3879
  




54
HR
1
3
3
6
LSM = 0 p-value
  
<.001*
<.001*
0.001*
0.488
0.066
0.002*
  




55
HR
1
4
1
1
Mean Change from Vehicle
  
20.720
16.689
18.946
13.566
7.0670
-2.5748
12.402




56
HR
1
4
1
2
SD
  
4.6006
6.4045
7.8181
9.8952
9.91546
11.55177
NA




57
HR
1
4
1
3
N
  
4
4
4
4
4
4
4




58
HR
1
4
1
4
LSM
  
22.507
18.476
20.733
15.353
8.8541
-0.7876
  




59
HR
1
4
1
5
LSM s.e.
  
3.6550
3.6550
3.6550
3.6550
3.65504
3.65504
  




60
HR
1
4
1
6
LSM = 0 p-value
  
<.001*
<.001*
<.001*
<.001*
0.020*
0.830
  




61
HR
1
4
2
1
Mean Change from Vehicle
  
-0.4255
-7.6510
-4.3090
-7.0170
-11.966
-11.977
-7.2242




62
HR
1
4
2
2
SD
  
6.44556
7.24202
5.87769
4.53746
7.5879
5.5382
NA




63
HR
1
4
2
3
N
  
4
4
4
4
4
4
4




64
HR
1
4
2
4
LSM
  
-0.8561
-8.0816
-4.7396
-7.4476
-12.397
-12.407
  




65
HR
1
4
2
5
LSM s.e.
  
3.50066
3.50066
3.50066
3.50066
3.5007
3.5007
  




66
HR
1
4
2
6
LSM = 0 p-value
  
0.808
0.026*
0.183
0.039*
<.001*
<.001*
  




67
HR
1
4
3
1
Mean Change from Vehicle
  
10.387
1.8443
2.8940
10.559
0.2448
4.1975
5.0209




68
HR
1
4
3
2
SD
  
5.3319
7.01487
4.68906
9.4706
6.68270
7.02022
NA




69
HR
1
4
3
3
N
  
4
4
4
4
4
4
4




70
HR
1
4
3
4
LSM
  
9.0299
0.4877
1.5374
9.2019
-1.1118
2.8409
  




71
HR
1
4
3
5
LSM s.e.
  
3.58641
3.58641
3.58641
3.58641
3.58641
3.58641
  




72
HR
1
4
3
6
LSM = 0 p-value
  
0.015*
0.892
0.670
0.014*
0.758
0.432
  



































In [65]:



     


proc format; 
	 invalue param (notsorted) "HR" = 1 "PP" = 2 "SAP"= 3 "DAP"= 4 "MAP"= 5; 
     invalue dayff "Day 1"=1  "Day 3"=1; 
run;

data reportdata;
  set reportfinal;
  trt=cats(trtn);
/*  dayn=input(day,dayff.); */
run;

proc sort ; by paramn paramcd phase trtn trt rownum rowlbl;run;

data reportdatapg;
  set reportdata;
  by paramn paramcd phase trtn trt rownum rowlbl;
  if first.phase then page+1;;
/*  if trt="100" then trt="INTN ";*/
run;




/*==============================================================================
  PURPOSE:
    Create TFL-style PROC REPORT tables by PARAMCD (HR, SAP, DAP, MAP, PP),
    split across 4 analysis phases (1–4) with different time windows per page,
    and add a footer line describing the covariance structure used.
==============================================================================*/

/*--- Global listing layout / print formatting options ---*/
options missing=' ' nodate nonumber nocenter orientation=landscape
        pagesize=46 linesize=133
        formchar='|_---|+|---+=|-/\<>*';

/*--- Standard footnotes for all tables ---*/
footnote1 "-----------------------------------------------------------------------------------------------------------------------------------";
footnote2 "* : Statistically significant at the 0.05 level.                                                                                   ";
footnote3 "LSM = 0 p-value : Within dose level comparison with study day 1 vehicle.                                                           ";

/*--- Table titles (one per endpoint) ---*/
%let title1 = "Table 3.1: Analysis Summary Table for Change from Vehicle: Heart Rate";
/*%let title2 = "Table 3.2: Analysis Summary Table for Change from Vehicle: Systolic Arterial Pressure";*/
%let title3 = "Table 3.3: Analysis Summary Table for Change from Vehicle: Diastolic Arterial Pressure";
%let title4 = "Table 3.4: Analysis Summary Table for Change from Vehicle: Mean Arterial Pressure";
%let title5 = "Table 3.5: Analysis Summary Table for Change from Vehicle: Pulse Pressure";

/*--- Footer macros: print covariance structure note after each page ---*/
%macro cs;   compute after page; line @1 ' '; line @1 'Analysis Covariance Structure: Compound Symmetric'; endcomp; %mend;
%macro csh;  compute after page; line @1 ' '; line @1 'Analysis Covariance Structure: Compound Symmetric Heterogeneous'; endcomp; %mend;
%macro ar;   compute after page; line @1 ' '; line @1 'Analysis Covariance Structure: Autoregressive Order 1'; endcomp; %mend;
%macro arh;  compute after page; line @1 ' '; line @1 'Analysis Covariance Structure: Autoregressive Heterogeneous Order 1'; endcomp; %mend;

/*--- Column definitions per “phase page” (baseline + hours 1–6, then 7–12, 13–18, 19–24) ---*/
%macro def1;
   define page   / noprint order;
   define trtn   / noprint order;
   define trt    / "Dose|Level" left width=6 order;
   define rowlbl / "Statistic" left width=30;
   define rownum / noprint order;
   define time_0 / display "Baseline" right width=9;
   define time_1 / display "1|hour"   right width=9;
   define time_2 / display "2|hour"   right width=9;
   define time_3 / display "3|hour"   right width=9;
   define time_4 / display "4|hour"   right width=9;
   define time_5 / display "5|hour"   right width=9;
   define time_6 / display "6|hour"   right width=9;
   break after trtn / skip;
   break after page / page;
%mend;

%macro def2;
   define page   / noprint order;
   define trtn   / noprint order;
   define trt    / "Dose|Level" left width=6 order;
   define rowlbl / "Statistic" left width=30;
   define rownum / noprint order;
   define time_1 / display "7|hour"   right width=9;
   define time_2 / display "8|hour"   right width=9;
   define time_3 / display "9|hour"   right width=9;
   define time_4 / display "10|hour"  right width=9;
   define time_5 / display "11|hour"  right width=9;
   define time_6 / display "12|hour"  right width=9;
   break after trtn / skip;
   break after page / page;
%mend;

%macro def3;
   define page   / noprint order;
   define trtn   / noprint order;
   define trt    / "Dose|Level" left width=6 order;
   define rowlbl / "Statistic" left width=30;
   define rownum / noprint order;
   define time_1 / display "13|hour"  right width=9;
   define time_2 / display "14|hour"  right width=9;
   define time_3 / display "15|hour"  right width=9;
   define time_4 / display "16|hour"  right width=9;
   define time_5 / display "17|hour"  right width=9;
   define time_6 / display "18|hour"  right width=9;
   break after trtn / skip;
   break after page / page;
%mend;

%macro def4;
   define page   / noprint order;
   define trtn   / noprint order;
   define trt    / "Dose|Level" left width=6 order;
   define rowlbl / "Statistic" left width=30;
   define rownum / noprint order;
   define time_1 / display "19|hour"  right width=9;
   define time_2 / display "20|hour"  right width=9;
   define time_3 / display "21|hour"  right width=9;
   define time_4 / display "22|hour"  right width=9;
   define time_5 / display "23|hour"  right width=9;
   define time_6 / display "24|hour"  right width=9;
   break after trtn / skip;
   break after page / page;
%mend;

/*--- Reporting macros:
      Each macro prints 4 PROC REPORTs (phase=1..4), changing the hour window and covariance note. ---*/
%macro report1(paramcd=, title=);
  title1 &title;

  /* Phase 1: Baseline + hours 1–6 */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl time_0
           ('[--------------------------Analysis Phase 1-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=1;
    %def1
    %arh
  run;

  /* Phase 2: hours 7–12 */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 2-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=2;
    %def2
    %arh
  run;

  /* Phase 3: hours 13–18 */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 3-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=3;
    %def3
    %cs
  run;

  /* Phase 4: hours 19–24 */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 4-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=4;
    %def4
    %ar
  run;
%mend;

%macro report2(paramcd=, title=);
  title &title;
  /* All phases use CS note here */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl time_0
           ('[--------------------------Analysis Phase 1-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=1;
    %def1
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 2-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=2;
    %def2
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 3-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=3;
    %def3
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 4-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=4;
    %def4
    %cs
  run;
%mend;

%macro report3(paramcd=, title=);
  title &title;
  /* Same structure as report2; phase 1 header text slightly shorter */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl time_0
           ('[---------------------Analysis Phase 1--------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=1;
    %def1
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 2-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=2;
    %def2
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 3-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=3;
    %def3
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 4-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=4;
    %def4
    %cs
  run;
%mend;

%macro report4(paramcd=, title=);
  title &title;
  /* All phases use CS note here */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl time_0
           ('[--------------------------Analysis Phase 1-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=1;
    %def1
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 2-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=2;
    %def2
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 3-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=3;
    %def3
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 4-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=4;
    %def4
    %cs
  run;
%mend;

%macro report5(paramcd=, title=);
  title &title;
  /* Mixed covariance notes (ARH for phase 1; CS for phases 2–3; AR for phase 4) */
  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl time_0
           ('[--------------------------Analysis Phase 1-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=1;
    %def1
    %arh
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 2-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=2;
    %def2
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 3-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=3;
    %def3
    %cs
  run;

  proc report data=reportdatapg nowd nowindows headskip split='|' missing spacing=1;
    columns page trtn trt trtn rownum rowlbl
           ('[--------------------------Analysis Phase 4-------------------------]' time_1-time_6);
    where paramcd=&paramcd and phase=4;
    %def4
    %ar
  run;
%mend;

/*--- Route LISTING output to an external .lst file ---*/
proc printto new print="&path.\SAS\OUTPUT\COR1043_tables_&SYSDATE9..lst";

/*--- Generate each table by endpoint ---*/
%report1(paramcd='HR',  title=&title1);
%report2(paramcd='SAP', title=&title2);
%report3(paramcd='DAP', title=&title3);
%report4(paramcd='MAP', title=&title4);
%report5(paramcd='PP',  title=&title5);

/*--- Clear titles/footnotes and restore default output destination ---*/
title;
footnote;
proc printto new print=print;
run;



     




















    
    











SAS Output








Table 3.1: Analysis Summary Table for Change from Vehicle: Heart Rate 














 
[--------------------------Analysis Phase 1-------------------------]




Dose
Level		
Statistic
Baseline
1
hour		
2
hour		
3
hour		
4
hour		
5
hour		
6
hour		






1
Mean Change from Vehicle
-5.6808
32.887
65.620
62.210
62.277
50.920
51.484




 
SD
5.35020
26.4502
22.4734
14.2521
10.7755
18.2817
12.4820




 
N
4
4
4
4
4
4
4




 
LSM
-5.6808
33.494
66.227
62.817
62.885
51.528
52.091




 
LSM s.e.
3.53068
9.4020
8.6803
6.5935
6.3018
7.3207
4.3766




 
LSM = 0 p-value
0.142
<.001*
<.001*
<.001*
<.001*
<.001*
<.001*




2
Mean Change from Vehicle
0.4820
2.8933
30.080
28.284
21.067
21.256
15.926




 
SD
8.79171
18.32200
16.4893
13.7110
13.1081
7.0977
3.4467




 
N
4
4
4
4
4
4
4




 
LSM
0.4820
2.7469
29.933
28.137
20.920
21.109
15.779




 
LSM s.e.
3.53068
9.29278
8.5619
6.4368
6.1377
7.1799
4.1368




 
LSM = 0 p-value
0.894
0.769
0.001*
<.001*
0.001*
0.005*
<.001*




3
Mean Change from Vehicle
3.0553
-10.479
24.696
23.208
22.907
29.218
20.813




 
SD
6.60833
12.5510
16.7581
14.0077
13.3197
12.5136
2.3645




 
N
4
4
4
4
4
4
4




 
LSM
3.0553
-10.940
24.235
22.747
22.446
28.757
20.351




 
LSM s.e.
3.53068
9.3530
8.6273
6.5235
6.2285
7.2577
4.2704




 
LSM = 0 p-value
0.409
0.248
0.007*
0.001*
<.001*
<.001*
<.001*




 

Analysis Covariance Structure: Autoregressive Heterogeneous Order 1		












----------------------------------------------------------------------------------------------------------------------------------- 


* : Statistically significant at the 0.05 level. 


LSM = 0 p-value : Within dose level comparison with study day 1 vehicle. 












Table 3.1: Analysis Summary Table for Change from Vehicle: Heart Rate 














 
[--------------------------Analysis Phase 2-------------------------]




Dose
Level		
Statistic
7
hour		
8
hour		
9
hour		
10
hour		
11
hour		
12
hour		






1
Mean Change from Vehicle
21.215
40.394
45.012
28.181
39.603
32.725




 
SD
13.3448
11.3117
8.6502
15.2532
16.0131
13.4334




 
N
4
4
4
4
4
4




 
LSM
25.729
44.907
49.526
32.695
44.116
37.238




 
LSM s.e.
6.0514
3.7927
2.9337
7.5557
5.8270
5.3551




 
LSM = 0 p-value
<.001*
<.001*
<.001*
<.001*
<.001*
<.001*




2
Mean Change from Vehicle
1.8203
12.587
15.388
15.828
20.142
6.5480




 
SD
9.84040
5.4118
7.9559
8.1258
4.0932
6.66645




 
N
4
4
4
4
4
4




 
LSM
0.7328
11.499
14.300
14.740
19.054
5.4605




 
LSM s.e.
5.93683
3.6072
2.6896
7.4643
5.7080
5.22531




 
LSM = 0 p-value
0.902
0.003*
<.001*
0.054
0.002*
0.302




3
Mean Change from Vehicle
1.7793
17.523
12.252
25.109
29.862
29.819




 
SD
11.12709
8.5156
5.7771
12.6284
9.3523
9.2791




 
N
4
4
4
4
4
4




 
LSM
-1.6469
14.097
8.8256
21.683
26.436
26.392




 
LSM s.e.
6.00010
3.7104
2.82648
7.5147
5.7738
5.2971




 
LSM = 0 p-value
0.785
<.001*
0.003*
0.006*
<.001*
<.001*




 

Analysis Covariance Structure: Autoregressive Heterogeneous Order 1		












----------------------------------------------------------------------------------------------------------------------------------- 


* : Statistically significant at the 0.05 level. 


LSM = 0 p-value : Within dose level comparison with study day 1 vehicle. 












Table 3.1: Analysis Summary Table for Change from Vehicle: Heart Rate 














 
[--------------------------Analysis Phase 3-------------------------]




Dose
Level		
Statistic
13
hour		
14
hour		
15
hour		
16
hour		
17
hour		
18
hour		






1
Mean Change from Vehicle
27.859
27.505
23.308
24.550
20.126
19.665




 
SD
8.6534
6.6541
6.2420
9.5938
11.1809
6.0945




 
N
4
4
4
4
4
4




 
LSM
29.810
29.456
25.258
26.500
22.076
21.615




 
LSM s.e.
3.4445
3.4445
3.4445
3.4445
3.4445
3.4445




 
LSM = 0 p-value
<.001*
<.001*
<.001*
<.001*
<.001*
<.001*




2
Mean Change from Vehicle
9.3565
-1.9355
1.7350
0.4398
-2.4290
-1.0460




 
SD
7.65104
8.17044
4.23825
10.18202
3.74822
2.86982




 
N
4
4
4
4
4
4




 
LSM
8.8866
-2.4054
1.2651
-0.0301
-2.8989
-1.5159




 
LSM s.e.
3.31740
3.31740
3.31740
3.31740
3.31740
3.31740




 
LSM = 0 p-value
0.010*
0.472
0.705
0.993
0.387
0.650




3
Mean Change from Vehicle
21.028
16.797
13.002
3.8520
7.8570
12.371




 
SD
7.9806
4.4917
6.5361
4.56616
3.95595
7.0126




 
N
4
4
4
4
4
4




 
LSM
19.547
15.316
11.522
2.3715
6.3765
10.890




 
LSM s.e.
3.3879
3.3879
3.3879
3.38788
3.38788
3.3879




 
LSM = 0 p-value
<.001*
<.001*
0.001*
0.488
0.066
0.002*




 

Analysis Covariance Structure: Compound Symmetric		












----------------------------------------------------------------------------------------------------------------------------------- 


* : Statistically significant at the 0.05 level. 


LSM = 0 p-value : Within dose level comparison with study day 1 vehicle. 












Table 3.1: Analysis Summary Table for Change from Vehicle: Heart Rate 














 
[--------------------------Analysis Phase 4-------------------------]




Dose
Level		
Statistic
19
hour		
20
hour		
21
hour		
22
hour		
23
hour		
24
hour		






1
Mean Change from Vehicle
20.720
16.689
18.946
13.566
7.0670
-2.5748




 
SD
4.6006
6.4045
7.8181
9.8952
9.91546
11.55177




 
N
4
4
4
4
4
4




 
LSM
22.507
18.476
20.733
15.353
8.8541
-0.7876




 
LSM s.e.
3.6550
3.6550
3.6550
3.6550
3.65504
3.65504




 
LSM = 0 p-value
<.001*
<.001*
<.001*
<.001*
0.020*
0.830




2
Mean Change from Vehicle
-0.4255
-7.6510
-4.3090
-7.0170
-11.966
-11.977




 
SD
6.44556
7.24202
5.87769
4.53746
7.5879
5.5382




 
N
4
4
4
4
4
4




 
LSM
-0.8561
-8.0816
-4.7396
-7.4476
-12.397
-12.407




 
LSM s.e.
3.50066
3.50066
3.50066
3.50066
3.5007
3.5007




 
LSM = 0 p-value
0.808
0.026*
0.183
0.039*
<.001*
<.001*




3
Mean Change from Vehicle
10.387
1.8443
2.8940
10.559
0.2448
4.1975




 
SD
5.3319
7.01487
4.68906
9.4706
6.68270
7.02022




 
N
4
4
4
4
4
4




 
LSM
9.0299
0.4877
1.5374
9.2019
-1.1118
2.8409




 
LSM s.e.
3.58641
3.58641
3.58641
3.58641
3.58641
3.58641




 
LSM = 0 p-value
0.015*
0.892
0.670
0.014*
0.758
0.432




 

Analysis Covariance Structure: Autoregressive Order 1		












----------------------------------------------------------------------------------------------------------------------------------- 


* : Statistically significant at the 0.05 level. 


LSM = 0 p-value : Within dose level comparison with study day 1 vehicle. 































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