Methodologic considerations for noninterventional studies of switching from reference biologic to biosimilars

Pharmacoepidemiol Drug Saf. 2020 Jul;29(7):757-769. doi: 10.1002/pds.4809. Epub 2019 Jul 12.

Abstract

Purpose: As more biosimilars become available in the United States, postapproval noninterventional studies describing biosimilar switching and comparing effectiveness and/or safety between switchers and nonswitchers will play a key role in generating real-world evidence to inform clinical practices and policy decisions. Ensuring sound methodology is critical for making valid inferences from these studies.

Methods: The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) convened a workgroup consisting of academic researchers, industry scientists, and practicing clinicians to establish best practice recommendations for the conduct of noninterventional studies of biosimilar and reference biologic switching. The workgroup members participated in eight teleconferences between August 2017 and February 2018 to discuss specific topics and build consensus.

Results: This report provides workgroup recommendations covering five main considerations relating to noninterventional studies describing reference biologic to biosimilar switching and comparing reference biologic to biosimilars for safety and effectiveness in the presence of switching at treatment initiation and during follow-up: (a) selecting appropriate data sources from a range of available options including insurance claims, electronic health records, and registries; (b) study designs; (c) outcomes of interest including health care utilization and clinical endpoints; (d) analytic approaches including propensity scores, disease risk scores, and instrumental variables; and (e) special considerations including avoiding designs that ignore history of biologic use, avoiding immortal time bias, exposure misclassification, and accounting for postindex switching.

Conclusion: Recommendations provided in this report provide a framework that may be helpful in designing and critically evaluating postapproval noninterventional studies involving reference biologic to biosimilar switching.

Keywords: analytic methods; biosimilars; pharmacoepidemiology; study design; switching.

Publication types

  • Consensus Development Conference
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biosimilar Pharmaceuticals*
  • Guidelines as Topic*
  • Humans
  • Research Design*

Substances

  • Biosimilar Pharmaceuticals