On safety margin for drug interchangeability.

As more and more generic (or biosimilar) drug products become available in the market place, it is a concern whether the approved generic (or biosimilar) drug products are safe and efficacious and hence can be used interchangeably. According to current regulation, most regulatory agencies such as the United States Food and Drug Administration (FDA) indicate an approved generic (or biosimilar) drug product can serve as a substitute for the innovative drug product. Bioequivalence (biosimilarity) assessment for regulatory approval among generic copies (or biosimilars) of the innovative drug product are not required. In practice, approved generic (or biosimilar) drugs are commonly used interchangeably without any mechanism of safety monitoring. In this article, current bioequivalence (or biosimilarity) limit is adjusted according to the observed geometric mean ratio and corresponding variability for development of safety margins for monitoring of drug interchangeability by minimizing the relative change in response with and without the switching.

Studies on drug switchability showed heterogeneity in methodological approaches: a scoping review.

BACKGROUND AND OBJECTIVE: Several drugs share the same therapeutic indication, including those undergoing patent expiration. Concerns on the interchangeability are frequent in clinical practice, challenging the evaluation of switchability through observational research. The objective of this study was to conduct a scoping review of observational studies on drug switchability to identify methodological strategies adopted to deal with bias and confounding. METHODS: We searched PubMed, EMBASE, and Web of Science (updated January 31, 2017) to identify studies evaluating switchability in terms of effectiveness/safety outcomes or compliance. Three reviewers independently screened studies extracting all characteristics. Strategies to address confounding, particularly previous drug use and switching reasons, were considered. All findings were summarized in descriptive analyses. RESULTS: Thirty-two studies, published in the last 10 years, met the inclusion criteria. Epilepsy, cardiovascular, and rheumatology were the most frequently represented clinical areas. Seventy-five percent of the studies reported data on effectiveness/safety outcomes. The most frequent study design was cohort (65.6%) followed by case-control (21.9%) and self-controlled (12.5%). Case-control and case-crossover studies showed homogeneous methodological strategies to deal with bias and confounding. Among cohort studies, the confounding associated with previous drug use was addressed introducing variables in multivariate model (47.3%) or selecting only adherent patients (14.3%). Around 30% of cohort studies did not report reasons for switching. In the remaining 70%, clinical parameters or previous occurrence of outcomes was measured to identify switching connected with lack of effectiveness or adverse events. CONCLUSION: This study represents a starting point for researchers and administrators who are approaching the investigation and assessment of issues related to interchangeability of drugs.