Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Mar;44(3):327-335.
doi: 10.1007/s40264-020-01017-z. Epub 2020 Nov 18.

Changes in Erythropoiesis Stimulating Agent Use Under a Risk Evaluation and Mitigation Strategy (REMS) Program

Ameet Sarpatwari  1 , Mengdong He  2 , Frazer A Tessema  2 , Joshua J Gagne  2 , Aaron S Kesselheim  2
Affiliations

Changes in Erythropoiesis Stimulating Agent Use Under a Risk Evaluation and Mitigation Strategy (REMS) Program

Ameet Sarpatwari et al. Drug Saf. 2021 Mar.

Abstract

Introduction: Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal.

Objective: We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL.

Methods: Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods.

Results: In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) -14.98 to 15.05]; slope 1.94 [95% CI -0.22 to 4.10]) and epoetin alfa (level -4.10 [95% CI -16.85 to 8.65]; slope -0.52 [95% CI -2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI -0.58 to 3.74, slope -0.28 [95% CI -15.29 to 14.73]; epoetin alfa level 1.58 (95% CI -0.26 to 3.42], slope 5.74 [95% CI -7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods.

Conclusion: REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety.

PubMed Disclaimer

References

    1. Avorn J, Kesselheim AS, Sarpatwari A. The FDA Amendments Act of 2007—assessing its effects a decade later. N Engl J Med. 2018;379(12):1097–9. - DOI
    1. 21 USC § 355-1.
    1. Sarpatwari A, Avorn J, Kesselheim AS. Using a drug-safety tool to prevent competition. New Engl J Med. 2014;370:1476–8. - DOI
    1. Thalomid (thalidomide) risk evaluation and mitigation strategy (REMS). U.S. Food and Drug Administration. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/rems/Thalomid_2014.09.12_... . Updated Sep 2014. Accessed 29 May 2020.
    1. Cepeda MS, Coplan PM, Kopper NW, Maziere JY, Wedin GP, Wallace LE. ER/LA opioid analgesics REMS: overview of ongoing assessments of its progress and its impact on health outcomes. Pain Med. 2017;18(1):78–85. - DOI

Publication types

LinkOut - more resources