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

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.

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.

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).

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.