***************************************************************************************************
*   CLIENT NAME:  ModernaTX, Inc.
*   PROTOCOL:  mRNA-1273-P201
*   PURPOSE:  Create Inferential Statistical Analysis Macro
*
*   INPUT FILES:  ADB.*
*   OUTPUT FILES: 
*   USAGE NOTES:   
************************************************************************* 
*  Copyright 2020 PPD
*  All Rights Reserved. 
*************************************************************************;


%macro clopper (datain=, vac=, sar=,sec=, subset=, crit=, dataout=);

%if &datain. ^=ADIS %then %do;

%if &datain.=ADARSUM %then %do;
  data &datain.;
  set adb.&datain.;
  where &sar.='Y' and ATPTREF in &vac. and PARAMCD not in ('WRASH', 'LYMOCCYN');
  run;
  
  data temp;
  set &datain.;
  length trt $20;
  trt=trt01a;
  output;
  if index(trt01a, 'mRNA-1273') then trt='mRNA-1273 Total';
  output;
  run;

  data temp1;
  set temp;
  length cohort $20;
  cohort=AGEGR1;
  output;
  if AGEGR1^='' then cohort='Overall';;
  output;
  run;

  %if &sec.='AR' %then %do;
    proc sort data=temp1 out=n1 nodupkey;
    by subjid trt cohort;
    where (paramcd^='RASHOCYN' and ATOXGRN^=.) or (paramcd='RASHOCYN' and AVALC^='');
    run;

    proc sort data=temp1 out=any nodupkey;
    by subjid trt cohort;
    where (paramcd^='RASHOCYN' and ATOXGRN>0) or (paramcd='RASHOCYN' and AVALC='Y');
    run;
  %end;

 %if &sec.='LAR' %then %do;
    proc sort data=temp1 out=n1 nodupkey;
    by subjid trt cohort;
    where parcat1='LOCAL' and ATOXGRN^=.;
    run;

    proc sort data=temp1 out=any nodupkey;
    by subjid trt cohort;
    where parcat1='LOCAL' and ATOXGRN>0;
    run;
  %end;

  %if &sec.='SAR' %then %do;
    proc sort data=temp1 out=n1 nodupkey;
    by subjid trt cohort;
    where (parcat1='SYSTEMIC' and ATOXGRN^=.) or (paramcd='RASHOCYN' and AVALC^='');
    run;

    proc sort data=temp1 out=any nodupkey;
    by subjid trt cohort;
    where (parcat1='SYSTEMIC' and ATOXGRN>0) or (paramcd='RASHOCYN' and AVALC='Y');
    run;
  %end;

  proc freq data=n1 noprint;
  table trt*cohort/norow nocol nopercent nocum out=denom;
  run;


  proc freq data=any;
  table trt*cohort/norow nocol nopercent nocum out=num;
  run;


  data ar;
  merge denom(rename=count=denom drop=percent) num(rename=count=n drop=percent);
  by trt cohort;
  run;

  data ar;
  set ar;
  if n=. then n=0;
  run;

  data clopper;
  set ar;
  n1=denom-n;
  rename n=Y n1=N;
  run;

  proc transpose data=clopper out=clopper_ar;
  by trt cohort;
  var y n;
  run;

  proc freq data=clopper_ar;
  ods output binomialcls=ci;
  by trt cohort;
  tables _name_/ nocum norow binomial (LEVEL="Y" ALL);;
  weight col1 / zeros;
  run;

  data &dataout.;
  set ci;
  lowercl=lowercl*100;
  uppercl=uppercl*100;
  where type='Clopper-Pearson (Exact)';
  drop table proportion type;
  run;

%end;
   

%if &datain.=ADAR %then %do;
  data &datain.;
  set adb.&datain.;
  where &sar.='Y' and ATPTREF in &vac. and PARAMCD not in ('RASH', 'LYMPHOCC') and ANL01FL='Y';
  run;

  
  data temp;
  set &datain.;
  length trt $20;
  trt=trt01a;
  output;
  if index(trt01a, 'mRNA-1273') then trt='mRNA-1273 Total';
  output;
  run;

  data temp1;
  set temp;
  length cohort $20;
  cohort=AGEGR1;
  output;
  if AGEGR1^='' then cohort='Overall';;
  output;
  run;

  %if &sec.='AR' %then %do;
    proc sort data=temp1 out=n1 nodupkey;
    by subjid trt cohort atptgr1;
    where (paramcd^='RASHOCC' and ATOXGRN^=.) or (paramcd='RASHOCC' and AVALC^='');
    run;

    proc sort data=temp1 out=any nodupkey;
    by subjid trt cohort atptgr1;
    where (paramcd^='RASHOCC' and ATOXGRN>0) or (paramcd='RASHOCC' and AVALC='Y');
    run;
  %end;

 %if &sec.='LAR' %then %do;
    proc sort data=temp1 out=n1 nodupkey;
    by subjid trt cohort atptgr1;
    where parcat1='LOCAL' and ATOXGRN^=.;
    run;

    proc sort data=temp1 out=any nodupkey;
    by subjid trt cohort atptgr1;
    where parcat1='LOCAL' and ATOXGRN>0;
    run;
  %end;

  %if &sec.='SAR' %then %do;
    proc sort data=temp1 out=n1 nodupkey;
    by subjid trt cohort atptgr1;
    where (parcat1='SYSTEMIC' and ATOXGRN^=.) or (paramcd='RASHOCC' and AVALC^='');
    run;

    proc sort data=temp1 out=any nodupkey;
    by subjid trt cohort atptgr1;
    where (parcat1='SYSTEMIC' and ATOXGRN>0) or (paramcd='RASHOCC' and AVALC='Y');
    run;
  %end;

  proc freq data=n1 noprint;
  table trt*cohort*atptgr1/norow nocol nopercent nocum out=denom;
  run;


  proc freq data=any;
  table trt*cohort*atptgr1/norow nocol nopercent nocum out=num;
  run;


  data ar;
  merge denom(rename=count=denom drop=percent) num(rename=count=n drop=percent);
  by trt cohort atptgr1;
  run;

  data ar;
  set ar;
  if n=. then n=0;
  run;

  data clopper;
  set ar;
  n1=denom-n;
  rename n=Y n1=N;
  run;

  proc transpose data=clopper out=clopper_ar;
  by trt cohort atptgr1;
  var y n;
  run;

  proc freq data=clopper_ar;
  ods output binomialcls=ci;
  by trt cohort atptgr1;
  tables _name_/ nocum norow binomial (LEVEL="Y" ALL);
  weight col1 / zeros;
  run;

  data &dataout.;
  set ci;
  lowercl=lowercl*100;
  uppercl=uppercl*100;
  where type='Clopper-Pearson (Exact)';
  drop table proportion type;
  run;

%end;
%end;

%if &datain. =ADIS %then %do;
  data &datain.;
  set adb.&datain.;
  where &subset.;
  run;

  data temp;
  set &datain.;
  length trt $20;
  trt=trt01p;
  output;
  if index(trt01p, 'mRNA-1273') then trt='mRNA-1273 Total';
  output;
  run;

  data temp1;
  set temp;
  length cohort $20;
  cohort=AGEGR1;
  output;
  if AGEGR1^='' then cohort='Overall';;
  output;
  run;

  proc sort data=temp1 out=n1 nodupkey;
  by subjid trt cohort avisit paramcd;
  run;

  proc sort data=temp1 out=any nodupkey;
  by subjid trt cohort avisit paramcd;
  where &CRIT. ='Y';
  run;

  proc freq data=n1 noprint;
  table trt*cohort*paramcd*avisit/norow nocol nopercent nocum out=denom;
  run;


  proc freq data=any;
  table trt*cohort*paramcd*avisit/norow nocol nopercent nocum out=num;
  run;


  data sc;
  merge denom(rename=count=denom drop=percent) num(rename=count=n drop=percent);
  by trt cohort paramcd avisit;
  run;

  data sc;
  set sc;
  if n=. then n=0;
  if avisit='Baseline' then delete;
  run;

  data clopper;
  set sc;
  n1=denom-n;
  rename n=Y n1=N;
  run;

  proc transpose data=clopper out=clopper_sc;
  by trt cohort paramcd avisit;
  var y n;
  run;

  proc freq data=clopper_sc;
  ods output binomialcls=ci;
  by trt cohort paramcd avisit;
  tables _name_/ nocum norow binomial (LEVEL="Y" ALL);
  weight col1 / zeros;
  run;

  data &dataout.;
  set ci;
  lowercl=lowercl*100;
  uppercl=uppercl*100;
  where type='Clopper-Pearson (Exact)';
  drop table proportion type;
  run;


%end;
   
%mend clopper;