Reproducing Protocol-Based Studies Using Parameterizable Tools-Comparison of Analytic Approaches Used by Two Medical Product Surveillance Networks

Clin Pharmacol Ther. 2020 Apr;107(4):966-977. doi: 10.1002/cpt.1698. Epub 2019 Dec 12.


The US Sentinel System and the Canadian Network for Observational Drug Effect Studies (CNODES) are two medical product safety surveillance networks. Using Sentinel's preprogrammed, parameterizable analytic tools, we reproduced two protocol-based studies conducted by CNODES to assess the risks of acute pancreatitis and heart failure (HF) associated with the use of incretin-based drugs, compared with use of ≥ 2 oral hypoglycemic agents. Results from the replication new-user cohort analyses aligned with those from the CNODES nested case-control studies. The adjusted hazard ratios were 0.95 (0.81-1.12; vs. 1.03 (0.87-1.22) in CNODES) for acute pancreatitis and 0.91 (0.84-1.00; vs. 0.82 (0.67-1.00) in CNODES) for HF among patients without HF history. The CNODES's common protocol approach allows studies tailored to specific safety questions, whereas the Sentinel's common data model plus pretested program approach enables more rapid analysis. Despite these differences, it is possible to obtain comparable results using both approaches.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Canada / epidemiology
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Heart Failure / chemically induced*
  • Heart Failure / epidemiology
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • Incretins / adverse effects*
  • Male
  • Middle Aged
  • Pancreatitis / chemically induced*
  • Pancreatitis / epidemiology
  • Product Surveillance, Postmarketing / methods*
  • Product Surveillance, Postmarketing / statistics & numerical data
  • Retrospective Studies
  • United States / epidemiology
  • Young Adult


  • Hypoglycemic Agents
  • Incretins