Generic drugs make up about 80% of all drug prescribing, and less costly generic drugs promote medication adherence among patients and reduce wasteful health care spending. The success of the generic drug industry relates to the interchangeability of brand name and generic drugs, which in turn relies on the FDA's certification of generic drugs as bioequivalent. In recent years, the FDA has taken a number of different innovative approaches to determining bioequivalence due to unique characteristics of particular drugs. Since these cases have raised controversy, the goal of this project is to use different empirical approaches to study the clinical implications of the FDA's bioequivalence determination in 6 specific circumstances: the approval of generic venlafaxine ER, calcitonin salmon nasal spray, enoxaparin, acarbose, vancomycin capsules, and sodium ferric gluconate. First, we will conduct a national survey of patients to determine their opinions about generic drug safety and effectiveness, attitudes about bioequivalent generic drugs approved via innovative mechanisms, and knowledge about controversies relating to the six specific model drugs at issue in this application. We will use a base population of nearly 125,000 patients and survey those who have filled prescriptions for one of the 6 drugs of interest or other drugs indicated for the same conditions. Second, we will conduct a national survey of physicians to assess the same outcomes. For this survey, we will identify a random national sample of board certified internists, and use online survey tools previously employed in surveys of this population. Third, using large national claims databases, we will identify """"""""switchback"""""""" rates related to the 6 generic drugs (episodes of patients receiving generic versions of the drug and then switching back to the brand name formulations in subsequent prescriptions), and determine whether these switchback rates differ significantly from switchbacks for other related but non-controversial generic drugs. To determine the reliability of switchback studies, we will compare our results to alternative analyses of generic and brand-name drug use that may better account for confounding. Finally, we will conduct systematic reviews and meta-analyses of studies of the 6 generic drugs to determine if any evidence exists in the literature of differences in their safety or effectiveness compared with the brand-name versions. These data will help the FDA assess the success of the innovative regulatory approaches used for these 6 generic drugs and evaluate whether similar pathways may be used for bioequivalence determinations related to future drugs.

Public Health Relevance

Generic drugs are essential to the US health care system, making up about 80% of all drug prescribing, but recent innovative approaches used by FDA to approve generic drugs have led to controversy. To evaluate the clinical outcomes related to 6 cases of generic drugs approved using innovative methods, we will conduct surveys of patients and physicians who used the drugs, evaluate the use of the drugs in large claims datasets with rigorous observational research tools, and conduct systematic reviews of studies of these products. The goal of collecting these data will be to determine how the FDA's approach to establishing bioequivalence in these cases affected use of the generic drugs by physicians and patients.

National Institute of Health (NIH)
Food and Drug Administration (FDA)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZFD1-SRC (99))
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Brigham and Women's Hospital
United States
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Kesselheim, Aaron S; Gagne, Joshua J; Franklin, Jessica M et al. (2016) Variations in Patients' Perceptions and Use of Generic Drugs: Results of a National Survey. J Gen Intern Med 31:609-14
Kesselheim, Aaron S; Polinski, Jennifer M; Fulchino, Lisa A et al. (2015) Modified Regulatory Pathways to Approve Generic Drugs in the US and a Systematic Review of Their Outcomes. Drugs 75:633-50