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204_cox_model.do
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204_cox_model.do
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********************************************************************************
*
* Do-file: cox model
* Project: Sotrovimab-Paxlovid-Molnupiravir
* Date: 06/4/23
* Programmed by: Katie Bechman
* Description: run cox models
* Data used: main.dta
* Data created: coxoutput
* Other output: logfiles, printed to folder $Logdir
* User installed ado: (place .ado file(s) in analysis folder)
****************************************************************************************************************
// global projectdir "C:\Users\k1635179\OneDrive - King's College London\Katie\OpenSafely\Safety mAB and antivirals\Safety-Sotrovimab-Paxlovid-Molnupiravir"
global projectdir `c(pwd)'
di "$projectdir"
capture mkdir "$projectdir/output/data"
capture mkdir "$projectdir/output/figures"
capture mkdir "$projectdir/output/tables"
global logdir "$projectdir/logs"
di "$logdir"
* Open a log file
cap log close
log using "$logdir/cox_model.log", replace
*Set Ado file path
adopath + "$projectdir/analysis/ado"
* SET Index date
global indexdate = "01/03/2020"
use "$projectdir/output/data/main.dta", clear
* Models
global crude i.drug
global agesex i.drug age i.sex
global adj i.drug age i.sex i.region_nhs i.imdq5 White 1b.bmi_group ///
paxlovid_contraindicated i.vaccination_status diabetes chronic_cardiac_disease chronic_respiratory_disease hypertension ///
downs_syndrome solid_cancer haem_disease renal_disease liver_disease imid_on_drug immunosuppression hiv_aids organ_transplant rare_neuro
global adj2 i.drug age i.sex i.region_nhs i.imdq5 White 1b.bmi_group
global adj3 i.drug age i.sex i.region_nhs i.imdq5 White 1b.bmi_group ///
paxlovid_contraindicated i.vaccination_status diabetes chronic_cardiac_disease chronic_respiratory_disease hypertension
global adj4 i.drug age i.sex i.region_nhs i.imdq5 White 1b.bmi_group ///
paxlovid_contraindicated i.vaccination_status diabetes chronic_cardiac_disease chronic_respiratory_disease hypertension ///
downs_syndrome solid_cancer haem_disease renal_disease liver_disease imid_on_drug immunosuppression hiv_aids organ_transplant rare_neuro ///
dementia care_home serious_mental_illness
* Outcome
global ae_disease ae_diverticulitis ///
ae_diarrhoea ///
ae_taste ///
ae_rash ///
ae_bronchospasm ///
ae_contactderm ///
ae_dizziness ///
ae_nausea_vomit ///
ae_headache ///
ae_anaphylaxis ///
ae_drugreaction ///
ae_ra ///
ae_sle ///
ae_psorasis ///
ae_psa ///
ae_axspa ///
ae_ibd
global ae_disease_serious ae_diverticulitis_serious ///
ae_diarrhoea_serious ///
ae_taste_serious ///
ae_rash_serious ///
ae_contactderm_serious ///
ae_dizziness_serious ///
ae_nausea_vomit_serious ///
ae_headache_serious ///
ae_anaphylaxis_serious ///
ae_drugreaction_serious ///
ae_ra_serious ///
ae_sle_serious ///
ae_psorasis_serious ///
ae_psa_serious ///
ae_axspa_serious ///
ae_ibd_serious
global ae_combined ae_all ///
ae_all_serious ///
ae_spc_all ///
ae_spc_serious ///
ae_drug_all ///
ae_drug_serious ///
ae_imae_all ///
ae_imae_serious
*******************************************************************************************************************
** MAIN ANALYSIS **
tab drug covid_test
tab eligible
tab drug pre_drug_test
tab drug paxlovid_contraindicated
*** Graphs - Schoenfeld Residual & log-log plot
foreach fail in $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
stcox i.drug
estat phtest,de
estat phtest, plot(1.drug) ytitle("Scaled Schoenfeld Residual, Sotrovimab", size(small)) name(schoenfeld_sot_`fail', replace)
estat phtest, plot(2.drug) ytitle("Scaled Schoenfeld Residual, Paxlovid",size(small)) name(schoenfeld_pax_`fail', replace)
estat phtest, plot(3.drug) ytitle("Scaled Schoenfeld Residual, Molnupiravir",size(small)) name(schoenfeld_mol_`fail', replace)
graph combine schoenfeld_sot_`fail' schoenfeld_pax_`fail' schoenfeld_mol_`fail', title("Schoenfeld Residual `fail'") saving("$projectdir/output/figures/schoenfield_`fail'", replace)
graph export "$projectdir/output/figures/schoenfield_`fail'.svg", as(svg) replace
stphplot, by(drug) legend(order(1 "Control" 2 "Sotrovimab" 3 "Paxlovid" 4 "Molnupiravir") symxsize(*0.4) size(small)) title ("log-log plot `fail'") saving("$projectdir/output/figures/loglog_plot_`fail'", replace)
graph export "$projectdir/output/figures/loglog_plot_`fail'.svg", as(svg) replace
}
*** Hazard of events
tempname cox_model_summary
postfile `cox_model_summary' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_summary", replace
foreach fail in $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
foreach model in crude agesex adj adj2 adj3 adj4{
stcox $`model', vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_summary' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_summary'
tempname cox_model_disease
postfile `cox_model_disease' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_disease", replace
foreach fail in $ae_diseaseae_ $ae_disease_serious {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
foreach model in crude agesex adj {
stcox $`model', vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_disease' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_disease'
*** Rates of events
tempname coxoutput_rates
postfile `coxoutput_rates' str20(failure) ///
all_ptime all_events all_rate all_lci all_uci ///
control_ptime control_events control_rate control_lci_ control_uci ///
sot_ptime sot_events sot_rate sot_lci sot_uci ///
pax_ptime pax_events pax_rate pax_lci pax_uci ///
mol_ptime mol_events mol_rate mol_lci mol_uci ///
using "$projectdir/output/tables/cox_model_rates", replace
foreach fail in $ae_disease $ae_disease_serious $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
stptime
local all_rate = `r(rate)'
local all_ptime = `r(ptime)'
local all_lci = `r(lb)'
local all_uci = `r(ub)'
local all_events = `r(failures)'
stptime if drug == 0
local control_rate = `r(rate)'
local control_ptime = `r(ptime)'
local control_lci = `r(lb)'
local control_uci = `r(ub)'
local control_events = `r(failures)'
display "no drug"
stptime if drug == 1
local sot_rate = `r(rate)'
local sot_ptime = `r(ptime)'
local sot_lci = `r(lb)'
local sot_uci = `r(ub)'
local sot_events = `r(failures)'
display "sotrovimab"
stptime if drug == 2
local pax_rate = `r(rate)'
local pax_ptime = `r(ptime)'
local pax_lci = `r(lb)'
local pax_uci = `r(ub)'
local pax_events = `r(failures)'
display "paxlovid"
stptime if drug == 3
local mol_rate = `r(rate)'
local mol_ptime = `r(ptime)'
local mol_lci = `r(lb)'
local mol_uci = `r(ub)'
local mol_events = `r(failures)'
display "molnupavir"
post `coxoutput_rates' ("`fail'") (`all_ptime') (`all_events') (`all_rate') (`all_lci') (`all_uci') ///
(`control_ptime') (`control_events') (`control_rate') (`control_lci') (`control_uci') ///
(`sot_ptime') (`sot_events') (`sot_rate') (`sot_lci') (`sot_uci') ///
(`pax_ptime') (`pax_events') (`pax_rate') (`pax_lci') (`pax_uci') ///
(`mol_ptime') (`mol_events') (`mol_rate') (`mol_lci') (`mol_uci')
}
postclose `coxoutput_rates'
*** Redact and save
use "$projectdir/output/tables/cox_model_summary", clear
save "$projectdir/output/tables/cox_model_summary", replace
export delimited using "$projectdir/output/tables/cox_model_summary.csv", replace
use "$projectdir/output/tables/cox_model_disease", clear
save "$projectdir/output/tables/cox_model_disease", replace
export delimited using "$projectdir/output/tables/cox_model_disease.csv", replace
use "$projectdir/output/tables/cox_model_rates", clear
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates", replace
export delimited using "$projectdir/output/tables/cox_model_rates.csv", replace
use "$projectdir/output/tables/cox_model_rates", clear
foreach var of varlist *events *ptime {
gen `var'_midpoint = (ceil(`var'/6)*6) - (floor(6/2) * (`var'!=0))
}
foreach var in all control sot pax mol {
gen `var'_rate_midpoint = (`var'_events_midpoint/`var'_ptime_midpoint)*1000
gen `var'_lci_midpoint = (invpoisson(`var'_events_midpoint,.975)/`var'_ptime_midpoint)*1000
gen `var'_uci_midpoint = (invpoisson(`var'_events_midpoint,.025)/`var'_ptime_midpoint)*1000
}
keep failure *midpoint
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_round", replace
export delimited using "$projectdir/output/tables/cox_model_rates_round.csv", replace
*******************************************************************************************************************
** SENSITIVITY ANALYSIS 1 = Treatment group start date on treatment date. Control group start date delayed by median delay between test and treat in treat group **
use "$projectdir/output/data/sensitivity_analysis.dta", clear
tab median_delay_all
gen start_date_delay = start_date + median_delay_all if drug==0
count if date_treated==. &drug>0
replace start_date_delay = date_treat if drug>0
*** Hazard of events
tempname cox_model_summary_sens_1
postfile `cox_model_summary_sens_1' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_summary_sens_1", replace
foreach fail in $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date_delay) enter(time start_date_delay) failure(fail_`fail'==1)
foreach model in crude agesex adj {
stcox $`model', vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_summary_sens_1' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_summary_sens_1'
tempname cox_model_disease_sens_1
postfile `cox_model_disease_sens_1' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_disease_sens_1", replace
foreach fail in $ae_diseaseae_ $ae_disease_serious {
stset stop_`fail', id(patient_id) origin(time start_date_delay) enter(time start_date_delay) failure(fail_`fail'==1)
foreach model in crude agesex adj {
stcox $`model', vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_disease_sens_1' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_disease_sens_1'
*** Rates of events
tempname coxoutput_rates_sens_1
postfile `coxoutput_rates_sens_1' str20(failure) ///
all_ptime all_events all_rate all_lci all_uci ///
control_ptime control_events control_rate control_lci_ control_uci ///
sot_ptime sot_events sot_rate sot_lci sot_uci ///
pax_ptime pax_events pax_rate pax_lci pax_uci ///
mol_ptime mol_events mol_rate mol_lci mol_uci ///
using "$projectdir/output/tables/cox_model_rates_sens_1", replace
foreach fail in $ae_disease $ae_disease_serious $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date_delay) enter(time start_date_delay) failure(fail_`fail'==1)
stptime
local all_rate = `r(rate)'
local all_ptime = `r(ptime)'
local all_lci = `r(lb)'
local all_uci = `r(ub)'
local all_events = `r(failures)'
stptime if drug == 0
local control_rate = `r(rate)'
local control_ptime = `r(ptime)'
local control_lci = `r(lb)'
local control_uci = `r(ub)'
local control_events = `r(failures)'
display "no drug"
stptime if drug == 1
local sot_rate = `r(rate)'
local sot_ptime = `r(ptime)'
local sot_lci = `r(lb)'
local sot_uci = `r(ub)'
local sot_events = `r(failures)'
display "sotrovimab"
stptime if drug == 2
local pax_rate = `r(rate)'
local pax_ptime = `r(ptime)'
local pax_lci = `r(lb)'
local pax_uci = `r(ub)'
local pax_events = `r(failures)'
display "paxlovid"
stptime if drug == 3
local mol_rate = `r(rate)'
local mol_ptime = `r(ptime)'
local mol_lci = `r(lb)'
local mol_uci = `r(ub)'
local mol_events = `r(failures)'
display "molnupavir"
post `coxoutput_rates_sens_1' ("`fail'") (`all_ptime') (`all_events') (`all_rate') (`all_lci') (`all_uci') ///
(`control_ptime') (`control_events') (`control_rate') (`control_lci') (`control_uci') ///
(`sot_ptime') (`sot_events') (`sot_rate') (`sot_lci') (`sot_uci') ///
(`pax_ptime') (`pax_events') (`pax_rate') (`pax_lci') (`pax_uci') ///
(`mol_ptime') (`mol_events') (`mol_rate') (`mol_lci') (`mol_uci')
}
postclose `coxoutput_rates_sens_1'
*** Redact and save
use "$projectdir/output/tables/cox_model_summary_sens_1", clear
save "$projectdir/output/tables/cox_model_summary_sens_1", replace
export delimited using "$projectdir/output/tables/cox_model_summary_sens_1.csv", replace
use "$projectdir/output/tables/cox_model_disease_sens_1", clear
save "$projectdir/output/tables/cox_model_disease_sens_1", replace
export delimited using "$projectdir/output/tables/cox_model_disease_sens_1.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_1", clear
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_sens_1", replace
export delimited using "$projectdir/output/tables/cox_model_rates_sens_1.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_1", clear
foreach var of varlist *events *ptime {
gen `var'_midpoint = (ceil(`var'/6)*6) - (floor(6/2) * (`var'!=0))
}
foreach var in all control sot pax mol {
gen `var'_rate_midpoint = (`var'_events_midpoint/`var'_ptime_midpoint)*1000
gen `var'_lci_midpoint = (invpoisson(`var'_events_midpoint,.975)/`var'_ptime_midpoint)*1000
gen `var'_uci_midpoint = (invpoisson(`var'_events_midpoint,.025)/`var'_ptime_midpoint)*1000
}
keep failure *midpoint
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_round_sens_1", replace
export delimited using "$projectdir/output/tables/cox_model_rates_round_sens_1.csv", replace
**************************************************************************************************************************************************************************************************************************************
** SENSITIVITY ANALYSIS 2 = time lag **
use "$projectdir/output/data/main.dta", clear
** Hazard of events with 1 day lag
tempname cox_model_summary_sens_2a
postfile `cox_model_summary_sens_2a' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_summary_sens_2a", replace
foreach fail in $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
foreach model in crude agesex adj {
stcox $`model' if _t>=2, vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_summary_sens_2a' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_summary_sens_2a'
** Hazard of events with 2 day lag
tempname cox_model_summary_sens_2b
postfile `cox_model_summary_sens_2b' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_summary_sens_2b", replace
foreach fail in $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
foreach model in crude agesex adj {
stcox $`model' if _t>=3, vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_summary_sens_2b' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_summary_sens_2b'
*** Redact and save
use "$projectdir/output/tables/cox_model_summary_sens_2a", clear
gen lag = 1
append using "$projectdir/output/tables/cox_model_summary_sens_2b"
replace lag =2 if lag==.
save "$projectdir/output/tables/cox_model_summary_sens_2", replace
export delimited using "$projectdir/output/tables/cox_model_summary_sens_2.csv", replace
*******************************************************************************************************************
** SENSITIVITY ANALYSIS 4 == restrict to eligible and pax contraindicated **
use "$projectdir/output/data/main.dta", clear
tab drug paxlovid_contraindicated
tab drug eligible
*** Hazard of events
tempname cox_model_summary_sens_4
postfile `cox_model_summary_sens_4' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_summary_sens_4", replace
foreach fail in $ae_combined {
stset stop_`fail' if eligible==1 & paxlovid_contraindicated==0, id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
foreach model in crude agesex adj{
stcox $`model', vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_summary_sens_4' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_summary_sens_4'
**** Rates of events
tempname coxoutput_rates_sens_4
postfile `coxoutput_rates_sens_4' str20(failure) ///
all_ptime all_events all_rate all_lci all_uci ///
control_ptime control_events control_rate control_lci_ control_uci ///
sot_ptime sot_events sot_rate sot_lci sot_uci ///
pax_ptime pax_events pax_rate pax_lci pax_uci ///
mol_ptime mol_events mol_rate mol_lci mol_uci ///
using "$projectdir/output/tables/cox_model_rates_sens_4", replace
foreach fail in $ae_disease $ae_disease_serious $ae_combined {
stset stop_`fail' if eligible==1 & paxlovid_contraindicated==0, id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
stptime
local all_rate = `r(rate)'
local all_ptime = `r(ptime)'
local all_lci = `r(lb)'
local all_uci = `r(ub)'
local all_events = `r(failures)'
stptime if drug == 0
local control_rate = `r(rate)'
local control_ptime = `r(ptime)'
local control_lci = `r(lb)'
local control_uci = `r(ub)'
local control_events = `r(failures)'
display "no drug"
stptime if drug == 1
local sot_rate = `r(rate)'
local sot_ptime = `r(ptime)'
local sot_lci = `r(lb)'
local sot_uci = `r(ub)'
local sot_events = `r(failures)'
display "sotrovimab"
stptime if drug == 2
local pax_rate = `r(rate)'
local pax_ptime = `r(ptime)'
local pax_lci = `r(lb)'
local pax_uci = `r(ub)'
local pax_events = `r(failures)'
display "paxlovid"
stptime if drug == 3
local mol_rate = `r(rate)'
local mol_ptime = `r(ptime)'
local mol_lci = `r(lb)'
local mol_uci = `r(ub)'
local mol_events = `r(failures)'
display "molnupavir"
post `coxoutput_rates_sens_4' ("`fail'") (`all_ptime') (`all_events') (`all_rate') (`all_lci') (`all_uci') ///
(`control_ptime') (`control_events') (`control_rate') (`control_lci') (`control_uci') ///
(`sot_ptime') (`sot_events') (`sot_rate') (`sot_lci') (`sot_uci') ///
(`pax_ptime') (`pax_events') (`pax_rate') (`pax_lci') (`pax_uci') ///
(`mol_ptime') (`mol_events') (`mol_rate') (`mol_lci') (`mol_uci')
}
postclose `coxoutput_rates_sens_4'
*** Redact and save
use "$projectdir/output/tables/cox_model_summary_sens_4", clear
save "$projectdir/output/tables/cox_model_summary_sens_4", replace
export delimited using "$projectdir/output/tables/cox_model_summary_sens_4.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_4", clear
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_sens_4", replace
export delimited using "$projectdir/output/tables/cox_model_rates_sens_4.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_4", clear
foreach var of varlist *events *ptime {
gen `var'_midpoint = (ceil(`var'/6)*6) - (floor(6/2) * (`var'!=0))
}
foreach var in all control sot pax mol {
gen `var'_rate_midpoint = (`var'_events_midpoint/`var'_ptime_midpoint)*1000
gen `var'_lci_midpoint = (invpoisson(`var'_events_midpoint,.975)/`var'_ptime_midpoint)*1000
gen `var'_uci_midpoint = (invpoisson(`var'_events_midpoint,.025)/`var'_ptime_midpoint)*1000
}
keep failure *midpoint
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_round_sens_4", replace
export delimited using "$projectdir/output/tables/cox_model_rates_round_sens_4.csv", replace
*******************************************************************************************************************
** SENSITIVITY ANALYSIS 5 == unrestricted to covid positive date. Start date for treatment is TREAT DATE **
use "$projectdir/output/data/sensitivity_analysis.dta", clear
tab drug pre_drug_test
tab drug paxlovid_contraindicated
tab drug eligible
*** Hazard of events
tempname cox_model_summary_sens_5
postfile `cox_model_summary_sens_5' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_summary_sens_5", replace
foreach fail in $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
foreach model in crude agesex adj{
stcox $`model', vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_summary_sens_5' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_summary_sens_5'
**** Rates of events
tempname coxoutput_rates_sens_5
postfile `coxoutput_rates_sens_5' str20(failure) ///
all_ptime all_events all_rate all_lci all_uci ///
control_ptime control_events control_rate control_lci_ control_uci ///
sot_ptime sot_events sot_rate sot_lci sot_uci ///
pax_ptime pax_events pax_rate pax_lci pax_uci ///
mol_ptime mol_events mol_rate mol_lci mol_uci ///
using "$projectdir/output/tables/cox_model_rates_sens_5", replace
foreach fail in $ae_disease $ae_disease_serious $ae_combined {
stset stop_`fail' if eligible==1 & paxlovid_contraindicated==0, id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
stptime
local all_rate = `r(rate)'
local all_ptime = `r(ptime)'
local all_lci = `r(lb)'
local all_uci = `r(ub)'
local all_events = `r(failures)'
stptime if drug == 0
local control_rate = `r(rate)'
local control_ptime = `r(ptime)'
local control_lci = `r(lb)'
local control_uci = `r(ub)'
local control_events = `r(failures)'
display "no drug"
stptime if drug == 1
local sot_rate = `r(rate)'
local sot_ptime = `r(ptime)'
local sot_lci = `r(lb)'
local sot_uci = `r(ub)'
local sot_events = `r(failures)'
display "sotrovimab"
stptime if drug == 2
local pax_rate = `r(rate)'
local pax_ptime = `r(ptime)'
local pax_lci = `r(lb)'
local pax_uci = `r(ub)'
local pax_events = `r(failures)'
display "paxlovid"
stptime if drug == 3
local mol_rate = `r(rate)'
local mol_ptime = `r(ptime)'
local mol_lci = `r(lb)'
local mol_uci = `r(ub)'
local mol_events = `r(failures)'
display "molnupavir"
post `coxoutput_rates_sens_5' ("`fail'") (`all_ptime') (`all_events') (`all_rate') (`all_lci') (`all_uci') ///
(`control_ptime') (`control_events') (`control_rate') (`control_lci') (`control_uci') ///
(`sot_ptime') (`sot_events') (`sot_rate') (`sot_lci') (`sot_uci') ///
(`pax_ptime') (`pax_events') (`pax_rate') (`pax_lci') (`pax_uci') ///
(`mol_ptime') (`mol_events') (`mol_rate') (`mol_lci') (`mol_uci')
}
postclose `coxoutput_rates_sens_5'
*** Redact and save
use "$projectdir/output/tables/cox_model_summary_sens_5", clear
save "$projectdir/output/tables/cox_model_summary_sens_5", replace
export delimited using "$projectdir/output/tables/cox_model_summary_sens_5.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_5", clear
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_sens_5", replace
export delimited using "$projectdir/output/tables/cox_model_rates_sens_5.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_5", clear
foreach var of varlist *events *ptime {
gen `var'_midpoint = (ceil(`var'/6)*6) - (floor(6/2) * (`var'!=0))
}
foreach var in all control sot pax mol {
gen `var'_rate_midpoint = (`var'_events_midpoint/`var'_ptime_midpoint)*1000
gen `var'_lci_midpoint = (invpoisson(`var'_events_midpoint,.975)/`var'_ptime_midpoint)*1000
gen `var'_uci_midpoint = (invpoisson(`var'_events_midpoint,.025)/`var'_ptime_midpoint)*1000
}
keep failure *midpoint
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_round_sens_5", replace
export delimited using "$projectdir/output/tables/cox_model_rates_round_sens_5.csv", replace
*******************************************************************************************************************
** SENSITIVITY ANALYSIS 6 == restricted to covid positive date, eligible and pax contraindicated - start date for treatment is TREAT DATE **
use "$projectdir/output/data/sensitivity_analysis.dta", clear
drop if pre_drug_test>5 & drug>0
tab drug pre_drug_test
tab drug paxlovid_contraindicated
tab drug eligible
*** Hazard of events
tempname cox_model_summary_sens_6
postfile `cox_model_summary_sens_6' str20(model) str20(failure) ///
hr_sot lc_sot uc_sot hr_pax lc_pax uc_pax hr_mol lc_mol uc_mol ///
using "$projectdir/output/tables/cox_model_summary_sens_6", replace
foreach fail in $ae_combined {
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
foreach model in crude agesex adj{
stcox $`model', vce(robust)
matrix b = r(table)
local hr_sot = b[1,2]
local lc_sot = b[5,2]
local uc_sot = b[6,2]
local hr_pax = b[1,3]
local lc_pax = b[5,3]
local uc_pax = b[6,3]
local hr_mol = b[1,4]
local lc_mol = b[5,4]
local uc_mol = b[6,4]
post `cox_model_summary_sens_6' ("`model'") ("`fail'") (`hr_sot') (`lc_sot') (`uc_sot') (`hr_pax') (`lc_pax') (`uc_pax') (`hr_mol') (`lc_mol') (`uc_mol')
}
}
postclose `cox_model_summary_sens_6'
**** Rates of events
tempname coxoutput_rates_sens_6
postfile `coxoutput_rates_sens_6' str20(failure) ///
all_ptime all_events all_rate all_lci all_uci ///
control_ptime control_events control_rate control_lci_ control_uci ///
sot_ptime sot_events sot_rate sot_lci sot_uci ///
pax_ptime pax_events pax_rate pax_lci pax_uci ///
mol_ptime mol_events mol_rate mol_lci mol_uci ///
using "$projectdir/output/tables/cox_model_rates_sens_6", replace
foreach fail in $ae_disease $ae_disease_serious $ae_combined {
stset stop_`fail' if eligible==1 & paxlovid_contraindicated==0, id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
stptime
local all_rate = `r(rate)'
local all_ptime = `r(ptime)'
local all_lci = `r(lb)'
local all_uci = `r(ub)'
local all_events = `r(failures)'
stptime if drug == 0
local control_rate = `r(rate)'
local control_ptime = `r(ptime)'
local control_lci = `r(lb)'
local control_uci = `r(ub)'
local control_events = `r(failures)'
display "no drug"
stptime if drug == 1
local sot_rate = `r(rate)'
local sot_ptime = `r(ptime)'
local sot_lci = `r(lb)'
local sot_uci = `r(ub)'
local sot_events = `r(failures)'
display "sotrovimab"
stptime if drug == 2
local pax_rate = `r(rate)'
local pax_ptime = `r(ptime)'
local pax_lci = `r(lb)'
local pax_uci = `r(ub)'
local pax_events = `r(failures)'
display "paxlovid"
stptime if drug == 3
local mol_rate = `r(rate)'
local mol_ptime = `r(ptime)'
local mol_lci = `r(lb)'
local mol_uci = `r(ub)'
local mol_events = `r(failures)'
display "molnupavir"
post `coxoutput_rates_sens_6' ("`fail'") (`all_ptime') (`all_events') (`all_rate') (`all_lci') (`all_uci') ///
(`control_ptime') (`control_events') (`control_rate') (`control_lci') (`control_uci') ///
(`sot_ptime') (`sot_events') (`sot_rate') (`sot_lci') (`sot_uci') ///
(`pax_ptime') (`pax_events') (`pax_rate') (`pax_lci') (`pax_uci') ///
(`mol_ptime') (`mol_events') (`mol_rate') (`mol_lci') (`mol_uci')
}
postclose `coxoutput_rates_sens_6'
*** Redact and save
use "$projectdir/output/tables/cox_model_summary_sens_6", clear
save "$projectdir/output/tables/cox_model_summary_sens_6", replace
export delimited using "$projectdir/output/tables/cox_model_summary_sens_6.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_6", clear
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_sens_6", replace
export delimited using "$projectdir/output/tables/cox_model_rates_sens_6.csv", replace
use "$projectdir/output/tables/cox_model_rates_sens_6", clear
foreach var of varlist *events *ptime {
gen `var'_midpoint = (ceil(`var'/6)*6) - (floor(6/2) * (`var'!=0))
}
foreach var in all control sot pax mol {
gen `var'_rate_midpoint = (`var'_events_midpoint/`var'_ptime_midpoint)*1000
gen `var'_lci_midpoint = (invpoisson(`var'_events_midpoint,.975)/`var'_ptime_midpoint)*1000
gen `var'_uci_midpoint = (invpoisson(`var'_events_midpoint,.025)/`var'_ptime_midpoint)*1000
}
keep failure *midpoint
order failure all* control* sot* pax* mol*
save "$projectdir/output/tables/cox_model_rates_round_sens_6", replace
export delimited using "$projectdir/output/tables/cox_model_rates_round_sens_6.csv", replace
*******************************************************************************************************************
** SENSITIVITY ANALYSIS 3 == time varying covariate **
use "$projectdir/output/data/main.dta", clear
** Hazard of events using stsplit
foreach fail in ae_all ae_spc_all ae_drug_all ae_imae_all {
preserve
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
stsplit time_`fail', at(1(1)5)
tab _t time_`fail'
foreach model in crude agesex adj {
bys time_`fail': stcox $`model', vce(robust)
}
restore
}
use "$projectdir/output/data/main.dta", clear
** Hazard of events using tvc
foreach fail in ae_all ae_spc_all ae_drug_all ae_imae_all {
preserve
stset stop_`fail', id(patient_id) origin(time start_date) enter(time start_date) failure(fail_`fail'==1)
stsplit time_`fail', at(1(1)5)
replace _t=1 if _t==0.75
foreach model in crude agesex adj {
stcox $`model', tvc(i.time_`fail') vce(robust)
}
restore
}
*** Graphs - Survival Risk & Survival Curve
/*foreach fail in $ae_combined {
sts graph, by(drug) tmax(28) ylabel(0(0.25)1) ylabel(,format(%4.3f)) xlabel(0(7)28) risktable(,title(" ")order(1 "Control " 2 "Sotrovimab " 3 "Paxlovid " 4 "Molnupiravir ") ///
size(small)justification(left) rowtitle(,size(small)justification(right))) legend(order(1 "Control" 2 "Sotrovimab" 3 "Paxlovid" 4 "Molnupiravir") symxsize(*0.4) size(small)) ///
xtitle("Analysis time (years)") ylabel(0.9(.025)1) ylabel(,angle(horizontal)) plotregion(color(white)) graphregion(color(white)) ytitle("Survival Probability" ) xtitle("Time (Days)") ///
title ("Kaplan Meier `fail'") saving("$projectdir/output/figures/survrisk_`fail'", replace)
graph export "$projectdir/output/figures/survrisk_`fail'.svg", as(svg) replace
stcurve, survival at1(drug=0) at2(drug=1) at3(drug=2) at4(drug=3) title("") range(0 28) xtitle("Analysis time (years)") legend(order(1 "Control" 2 "Sotrovimab" 3 "Paxlovid" 4 "Molnupiravir") ///
symxsize(*0.4) size(small)) ylabel(,angle(horizontal)) plotregion(color(white)) graphregion(color(white)) ytitle("Survival Probability" ) xtitle("Time (Days)") ///
title ("Survival Curve `fail'") saving("$projectdir/output/figures/survcurve_`fail'", replace)
graph export "$projectdir/output/figures/survcur_`fail'.svg", as(svg) replace
}
*/
log close