The Impact of Generic Aromatase Inhibitors on Initiation, Adherence, and Persistence Among Women With Breast Cancer: Applying Multi-State Models to Understand the Dynamics of Adherence

Pharmacoepidemiol Drug Saf. 2020 May;29(5):550-557. doi: 10.1002/pds.4995. Epub 2020 Mar 20.


Purpose: Clinical trials have clearly documented the survival benefit of aromatase inhibitors (AIs); however, many women fail to initiate (primary nonadherence) or remain adherent to AIs (secondary nonadherence). Prior studies have found that costs impact secondary nonadherence to medications but have failed to examine primary nonadherence. The purpose of this study is to examine primary and secondary adherence following the reduction in copays due to the introduction of generic AIs.

Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified 50 054 women diagnosed with incident breast cancer between 2008 and 2013. We compare women whose copays would change and those whose would not, due to the receipt of cost-sharing subsidies before and after generics were introduced using a difference-in-difference (DinD) analysis. To examine primary and secondary nonadherence, we rely on a multistate model with four states (Not yet initiated, User, Not Using, and Death). We adjusted for baseline factors using inverse probability treatment weights and then simulated adherence for 36 months following diagnosis.

Results: The generic introduction of AIs resulted in patients initiating AIs faster (DinD = -4.7%, 95%CI = -7.0, -2.3; patients not yet initiating treatment at 6-months), being more adherent (DinD ranging in absolute increase of 8.1%-10.4%) and being less likely to not be using the therapy (DinD range in absolute decrease of 1.2% at 6 months to 8.8% at 24 months) for women that do not receive a subsidy after generics were available.

Conclusions: Introduction of generic alternatives to AIs significantly reduced primary and secondary nonadherence.

Keywords: adherence; breast cancer; copayment; endocrine therapy; generic; multi-state model; pharmacoepidemiology; survival analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural