Outcomes Associated with Generic Drugs Approved Using Product-Specific Determinations of Therapeutic Equivalence.
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.
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. jgagne1@partners.org.
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, 1620 Tremont St Suite 3030, Boston, MA, 02120, 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, 1620 Tremont St Suite 3030, Boston, MA, 02120, 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, 1620 Tremont St Suite 3030, Boston, MA, 02120, 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, 1620 Tremont St Suite 3030, Boston, MA, 02120, 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, 1620 Tremont St Suite 3030, Boston, MA, 02120, USA.
Aaron S
AS
Kesselheim
D017277:Drug Approval; D016568:Drugs, Generic / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
D016568:Drugs, Generic