Project Abstract
Bioequivalence studies that compare a reference formulation to an investigational generic formulation typically
are conducted in healthy adult volunteers and occasionally are conducted in patients. Some populations have
unique physical, biological, and physiological considerations that are not reflected by healthy volunteers or by
the typical patient for whom a drug is indicated. Mixed evidence of the appropriateness of generic substitution
and adverse events associated with generic substitution calls attention to the safety and efficacy profiles of
generic drugs. Furthermore, there is a paucity of evidence in barriers to and patterns of generic substitution in
special populations whose experiences with a drug are not represented by those in whom bioequivalence
studies are conducted. The purpose of the proposed research is to identify research needs, monitor, and
improve generic drug substitution in special populations. We propose to use a mixed-methods approach
including systematic review of the literature, key informant interviews, focus groups, and secondary data
analysis of Medicare and Medicaid claims data to fully explore the practice patterns of generic drug utilization
and substitution in special populations. To achieve this, we propose the following three specific aims: 1) to
collect information on practice patterns in special populations to assess possible barriers to generic
substitution; 2) to compare clinical practice with labeled drug administration information in selected special
populations to identify factors that raise issues for safety and effectiveness with generic substitution; and 3) to
analyze generic drug utilization and substitution patterns and identify the impact of product-level, patient-level,
and provider-level factors on generic drug substitution among special populations. The six special populations
that we will focus on include pediatric patients, women, older adults with multiple medications, racial/ethnic
minorities, individuals with impaired kidney or liver function, and individuals residing in different geographic
regions or settings. We will conduct a systematic review to understand the evidence documenting differences
in generic substitution patterns among special populations. We will evaluate the relevance of product labeling
and drug reference resources to special populations. Qualitative key informant interviews and focus groups will
contribute to development of profiles of barriers for generic substitution among special populations.
Quantitative data analysis of relevant subgroups will allow comparisons of population-level generic drug
utilization and substitution patterns, as well as identify factors associated with generic drug substitution. The
expected outcomes of this study are provision of information to identify research needs and strategies to
improve monitoring of generic drug substitution in special populations, which can help to overcome barriers to
generic drug use in the U.S.