A protocol for active surveillance of acute myocardial infarction in association with the use of a new antidiabetic pharmaceutical agent

Pharmacoepidemiol Drug Saf. 2012 Jan:21 Suppl 1:282-90. doi: 10.1002/pds.2337.

Abstract

Purpose: To describe a protocol for active surveillance of acute myocardial infarction (AMI) in users of a recently approved oral antidiabetic medication, saxagliptin, and to provide the rationale for decisions made in drafting the protocol.

Methods: A new-user cohort design is planned for evaluating data from at least four Mini-Sentinel data partners from 1 August 2009 (following US Food and Drug Administration's approval of saxagliptin) through mid-2013. New users of saxagliptin will be compared in separate analyses with new users of sitagliptin, pioglitazone, long-acting insulins, and second-generation sulfonylureas. Two approaches to controlling for confounding will be evaluated: matching by exposure propensity score and stratification by AMI risk score. The primary analyses will use Cox regression models specified in a way that does not require pooling of patient-level data from the data partners. The Cox models are fit to summarized data on risk sets composed of saxagliptin users and similar comparator users at the time of an AMI. Secondary analyses will use alternative methods including Poisson regression and will explore whether further adjustment for covariates available only at some data partners (e.g., blood pressure) modifies results.

Results: The results of this study are pending.

Conclusions: The proposed protocol describes a design for surveillance to evaluate the safety of a newly marketed agent as postmarket experience accrues. It uses data from multiple partner organizations without requiring sharing of patient-level data and compares alternative approaches to controlling for confounding. It is hoped that this initial active surveillance project of the Mini-Sentinel will provide insights that inform future population-based surveillance of medical product safety.

Publication types

  • Comparative Study

MeSH terms

  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Cohort Studies
  • Confounding Factors, Epidemiologic
  • Dipeptides / adverse effects*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Drug Approval
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / etiology
  • Poisson Distribution
  • Product Surveillance, Postmarketing / methods
  • Proportional Hazards Models
  • Regression Analysis
  • United States / epidemiology
  • United States Food and Drug Administration

Substances

  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • saxagliptin
  • Adamantane