Switch-backs associated with generic drugs approved using product-specific determinations of therapeutic equivalence

Pharmacoepidemiol Drug Saf. 2016 Aug;25(8):944-52. doi: 10.1002/pds.4009. Epub 2016 Apr 22.


Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: approval; effectiveness; equivalence; generics; pharmacoepidemiology; safety; switch-backs.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Drug Approval / legislation & jurisprudence*
  • Drug Substitution / statistics & numerical data*
  • Drugs, Generic / administration & dosage*
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Longitudinal Studies
  • Male
  • Therapeutic Equivalency
  • United States
  • United States Food and Drug Administration


  • Drugs, Generic