Use of Health Care Databases to Support Supplemental Indications of Approved Medications

JAMA Intern Med. 2018 Jan 1;178(1):55-63. doi: 10.1001/jamainternmed.2017.3919.

Abstract

Importance: Manufacturers of US Food and Drug Administration-approved prescription drugs often apply for additional indications based on randomized clinical trials. Real-world database analyses on a medication's use and outcomes in routine settings of care might help to inform decision making regarding such supplemental indications.

Objective: To examine whether longitudinal data from a health care database can support the results of a randomized clinical trial that led to a supplemental indication for telmisartan.

Design, setting, and participants: This cohort study of patients newly prescribed telmisartan or ramipril used insurance claims data from a nationwide health care database from January 1, 2003, through September 30, 2009, to compare patient outcomes. This study replicated the inclusion and exclusion criteria used in the Ongoing Telmisartan Alone and in Combination with Ramipril Global End-point Trial (ONTARGET) and used propensity score matching to balance 74 patient characteristics. Data analysis was performed from February 15, 2017, to May 24, 2017.

Exposures: Telmisartan use vs ramipril use.

Main outcomes and measures: The primary outcome was a composite of myocardial infarction, stroke, or hospitalization for congestive heart failure.

Results: Of the 640 951 patients included in the study, 48 053 were newly prescribed ramipril (mean [SD] age, 68.29 [9.52] years; 31 940 male [66.5%]) and 4665 were newly prescribed telmisartan (mean [SD] age, 69.43 [9.60] years; 2413 male [51.7%]). After propensity score matching, a total of 4665 patients were newly prescribed telmisartan (mean [SD] age, 69.43 [9.60] years; 2413 [51.7%]), and 4665 patients were newly prescribed ramipril (mean [SD] age, 69.36 [9.67] years; 2343 male [50.2%]). As seen in ONTARGET, the composite risk of stroke, myocardial infarction, and hospitalization for congestive heart failure was similar for the 2 medications (hazard ratio, 1.0; 95% CI, 0.9-1.1). In addition, the study found that telmisartan was associated with a substantially decreased risk of angioedema (hazard ratio, 0.1; 95% CI, 0.03-0.56) compared with ramipril.

Conclusions and relevance: Real-world data analyses of patients receiving routine care provided findings similar to those found in the randomized clinical trial that established telmisartan's supplemental indication. In certain situations, database studies may support supplemental applications for effectiveness for already approved medications.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Cardiovascular Diseases / prevention & control*
  • Clinical Trials as Topic / statistics & numerical data*
  • Delivery of Health Care / statistics & numerical data*
  • Drug Approval*
  • Drug Prescriptions / statistics & numerical data*
  • Follow-Up Studies
  • Humans
  • Ramipril / pharmacology*
  • Retrospective Studies
  • Telmisartan / pharmacology*
  • United States

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Ramipril
  • Telmisartan