Switch-backs associated with generic drugs approved using product-specific determinations of therapeutic equivalence.
US Food and Drug Administration approval for generic drugs relies on demonstrating pharmaceutical equivalence and bioequivalence; however, some drug products have unique attributes that necessitate product-specific approval pathways. We evaluated rates of patients' switching back to brand-name versions from generic versions of four drugs approved via such approaches.



We used data from Optum LifeSciences Research Database to identify patients using a brand-name version of a study drug (acarbose tablets, salmon calcitonin nasal spray, enoxaparin sodium injection, and venlafaxine extended release tablets) or a control drug. We followed patients to identify switching to generic versions and then followed those who switched to identify whether they switched back to brand-name versions. We calculated switch and switch-back rates and used Kaplan-Meier and log-rank tests to compare rates between study and control drugs.



Our cohort included 201 959 eligible patients. Brand-to-generic switch rates ranged from 66 to 106 switches per 100 person-years for study drugs and 80 to 110 for control drugs. Rates of switch-back to brand-name versions ranged from 5 to 37 among study drugs and 3 to 53 among control drugs. Switch-back rates were higher for venlafaxine vs. sertraline (p < 0.01) and calcitonin vs. alendronate (p = 0.01). Switch-back rates were lower for venlafaxine vs. paroxetine (p < 0.01) and acarbose vs. nateglinide (p < 0.01). Rates were similar for acarbose vs. glimepiride (p = 0.97) and for enoxaparin vs. fondiparinux (p = 0.11).



As compared to control drugs, patients were not more likely to systematically switch back from generic to brand-name versions of the four study drugs. Copyright © 2016 John Wiley & Sons, Ltd.
Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Joshua J
JJ
Gagne
Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jennifer M
JM
Polinski
Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Wenlei
W
Jiang
Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Sarah K
SK
Dutcher
Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jing
J
Xie
Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Joyce
J
Lii
Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Lisa A
LA
Fulchino
Program on Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Aaron S
AS
Kesselheim
D017277:Drug Approval / Q000331:legislation & jurisprudence*; D057915:Drug Substitution / Q000706:statistics & numerical data*; D016568:Drugs, Generic / Q000008:administration & dosage*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D013810:Therapeutic Equivalency; D014481:United States; D014486:United States Food and Drug Administration
D016568:Drugs, Generic
approval; effectiveness; equivalence; generics; pharmacoepidemiology; safety; switch-backs