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Outcomes Associated with Generic Drugs Approved Using Product-Specific Determinations of Therapeutic Equivalence

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A Correction to this article was published on 08 March 2018

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Abstract

Objective

We sought to examine rates of clinical outcomes among patients before and after market introduction of generic versions of five drugs approved using product-specific equivalence determinations.

Methods

We used data from a large national insurer to identify patients who initiated a study (acarbose tablets, salmon calcitonin nasal spray, enoxaparin injection, vancomycin capsules, venlafaxine extended-release tablets) or control drug (nateglinide, glimepiride, alendronate, fondaparinux, metronidazole, sertraline, paroxetine) in each calendar month between 2003 and 2012 and to determine rates of claims-based proxies for lack of effectiveness outcomes following initiation. We used segmented time-series analyses to evaluate level (short-term) and slope (longer-term) changes in outcomes upon introduction of a generic study or control drug.

Results

Among study drugs, we observed three increases (one with p < 0.05) and three decreases (two with p < 0.05) in the level of outcome rates. All changes in slope indicated decreases in outcomes from the brand-only to the generic period; four had p < 0.05. For control drugs, we observed positive level changes for eight of nine drug-outcome pairs; two had p < 0.05. We observed negative slope changes for eight out of nine pairs; six had p < 0.05. We observed a significant increase in level change following the introduction of generic bupropion versions that were later found to be not bioequivalent (p < 0.01).

Conclusions

We did not find evidence that introduction of generic drugs approved using product-specific therapeutic equivalence determinations was associated with worse clinical outcomes than those among initiators of the brand-name versions of the same products. We observed similar patterns for control drugs.

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Change history

  • 08 March 2018

    Page 432, Fig. 2 Plots of model-based outcome incidence rates (per 100 person-years of exposure) before and after introduction of first generic versions of study and control drugs.

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Authors and Affiliations

  1. Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, 1620 Tremont St Suite 3030, Boston, MA, 02120, USA

    Joshua J. Gagne, Jennifer M. Polinski, Jing Xie, Joyce Lii, Lisa A. Fulchino & Aaron S. Kesselheim

  2. Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA

    Wenlei Jiang & Sarah K. Dutcher

Authors
  1. Joshua J. Gagne
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  2. Jennifer M. Polinski
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  3. Wenlei Jiang
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  4. Sarah K. Dutcher
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  5. Jing Xie
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  6. Joyce Lii
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  7. Lisa A. Fulchino
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  8. Aaron S. Kesselheim
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Corresponding author

Correspondence to Joshua J. Gagne.

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Conflict of interest

Dr. Gagne is Principal Investigator on research funding to the Brigham and Women’s Hospital from the US Food and Drug Administration, the Patient-Centered Outcomes Research Institute, the Agency for Healthcare Research & Quality, FDA Office of Generic Drugs, and Novartis Pharmaceuticals Corporation. He is a consultant to Aetion, Inc. and Optum, Inc. Dr. Polinski is a current employee of CVS Health, but was an employee of Brigham and Women’s Hospital at the time that this research was conducted. Drs. Jiang and Dutcher are employees of the US Food and Drug Administration. Dr. Xie is currently an employee of Sanofi US, but was an employee of Brigham and Women’s Hospital at the time that this research was conducted. Dr. Kesselheim also receives research funding from the Greenwall Faculty Scholar in Bioethics, and the Harvard Program in Therapeutic Science.

Funding

This study was funded by the US Food and Drug Administration Office of Generic Drugs (U01FD004856). Views expressed in this publication do not necessarily reflect the official policies of the Department of Health and Human Services, nor does any mention of trade names, commercial practices, or organization imply endorsement of the United States Government.

Additional information

A correction to this article is available online at https://doi.org/10.1007/s40265-018-0890-x.

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Gagne, J.J., Polinski, J.M., Jiang, W. et al. Outcomes Associated with Generic Drugs Approved Using Product-Specific Determinations of Therapeutic Equivalence. Drugs 77, 427–433 (2017). https://doi.org/10.1007/s40265-017-0696-2

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  • DOI: https://doi.org/10.1007/s40265-017-0696-2

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