TY - JOUR
T1 - External adjustment for unmeasured confounders improved drug-outcome association estimates based on health care utilization data
AU - Corrao, Giovanni
AU - Nicotra, Federica
AU - Parodi, Andrea
AU - Zambon, Antonella
AU - Soranna, Davide
AU - Heiman, Franca
AU - Merlino, Luca
AU - Mancia, Giuseppe
PY - 2012/11
Y1 - 2012/11
N2 - Objectives: Health care utilization (HCU) databases are widespread sources of data for pharmacoepidemiologic investigations. Possible confounders are typically not measured in such databases. We show how to assess the impact of confounders in a study aimed at comparing cardiovascular (CV) risk according to drug regimen prescribed at starting antihypertensive therapy, nominally one agent (monotherapy) or a combination of agents in a unique tablet (fixed-dose combination) or in at least two distinct tablets (extemporaneous combination). Study Design and Settings: A nested case-control study was carried out by including the 209,650 patients from Lombardy (Italy) newly treated between 2000 and 2001. Cases were the 10,688 patients who were hospitalized for CV disease until 2007. Three controls were selected for each case. Logistic regression was used to model the CV risk associated with initial therapeutic regimen. A Monte Carlo sensitivity analysis was performed for accounting unmeasured confounders (hypertension severity and chronic disease score) by means of external adjustment with medical record (MR) data. Results: Compared with patients on fixed-dose combination, those on extemporaneous combination or monotherapy, respectively, had CV risk increased to 15% (95% confidence interval [CI]: 3%, 29%) or 17% (95% CI: 8%, 26%). External adjustment did not modify the risk associated with monotherapy. In contrast, the excess of risk associated with extemporaneous combination was annulled when external adjustment was applied. Conclusion: MR data can be used to assess confounding bias unmeasured from HCU database. Starting antihypertensive therapy with a combination of agents probably reduces the CV risk with respect to monotherapy, even in the setting of primary prevention.
AB - Objectives: Health care utilization (HCU) databases are widespread sources of data for pharmacoepidemiologic investigations. Possible confounders are typically not measured in such databases. We show how to assess the impact of confounders in a study aimed at comparing cardiovascular (CV) risk according to drug regimen prescribed at starting antihypertensive therapy, nominally one agent (monotherapy) or a combination of agents in a unique tablet (fixed-dose combination) or in at least two distinct tablets (extemporaneous combination). Study Design and Settings: A nested case-control study was carried out by including the 209,650 patients from Lombardy (Italy) newly treated between 2000 and 2001. Cases were the 10,688 patients who were hospitalized for CV disease until 2007. Three controls were selected for each case. Logistic regression was used to model the CV risk associated with initial therapeutic regimen. A Monte Carlo sensitivity analysis was performed for accounting unmeasured confounders (hypertension severity and chronic disease score) by means of external adjustment with medical record (MR) data. Results: Compared with patients on fixed-dose combination, those on extemporaneous combination or monotherapy, respectively, had CV risk increased to 15% (95% confidence interval [CI]: 3%, 29%) or 17% (95% CI: 8%, 26%). External adjustment did not modify the risk associated with monotherapy. In contrast, the excess of risk associated with extemporaneous combination was annulled when external adjustment was applied. Conclusion: MR data can be used to assess confounding bias unmeasured from HCU database. Starting antihypertensive therapy with a combination of agents probably reduces the CV risk with respect to monotherapy, even in the setting of primary prevention.
KW - Antihypertensive drugs
KW - Bias
KW - Combined therapy
KW - Monotherapy
KW - Monte Carlo sensitivity analysis
KW - Observational studies
KW - Pharmacoepidemiology
KW - Unmeasured confounding
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U2 - 10.1016/j.jclinepi.2012.03.014
DO - 10.1016/j.jclinepi.2012.03.014
M3 - Article
C2 - 23017636
AN - SCOPUS:84866843285
VL - 65
SP - 1190
EP - 1199
JO - American journal of syphilis, gonorrhea, and venereal diseases
JF - American journal of syphilis, gonorrhea, and venereal diseases
SN - 0895-4356
IS - 11
ER -