Use of prescription drug samples in the US and implications for pharmacoepidemiologic research: a systematic search of the literature

ABSTRACT

Introduction

Free drug samples are not captured in the pharmacy claims databases used in many pharmacoepidemiologic studies, which could lead to misclassification of drug exposure status and thus bias study results.

Areas Covered

We systematically searched the literature in PubMed/MEDLINE, Embase, and Scopus from database inception to August 2020 for studies assessing the magnitude of exposure misclassification in pharmacy claims data associated with uncaptured drug sample utilization. Our review identified five US-based studies with substantially different characteristics, contexts, methods, and results. Taken together, these studies suggest that the risk of sample-related bias may be higher for (1) studies of newly approved, patented brand-only drugs in specific classes and contexts; (2) studies of populations where sample use is common and the unexposed cohort is small; and (3) studies where the outcomes of interest are expected to be early-onset or acute, with non-constant hazards.

Expert Opinion

In light of declining overall trends in sample use, future research on sample-related exposure misclassification should focus on delineating bias across those modern contexts where sample use remains high and optimizing bias quantification methods to create a more standardized approach. Additionally, further assessment is warranted for other sources of misclassified exposure status in claims-based pharmacoepidemiology research.

KEYWORDS:

• Bias
• drug samples
• exposure ascertainment
• exposure misclassification
• pharmacoepidemiology
• pharmacy claims data
• review

Article highlights

• While long-term trends demonstrate decreases in the provision of drug samples, their use remains widespread in the US, raising concerns that sample-related misclassification bias may affect findings from US claims-based studies.

• We sought to systematically review and derive from the existing literature an understanding of the scale and effects of exposure misclassification in pharmacy claims data associated with uncaptured drug sample utilization.

• Searching the literature in PubMed/MEDLINE, Embase, and Scopus from database inception to August 2020, we identified five eligible studies (three full-text and two abstracts; all based on US claims data).

• Key themes emerging from this review were that the risk of sample-related bias may be higher for (1) studies of newly approved, patented brand-only drugs in specific classes and contexts; (2) studies of populations where sample use is common and the unexposed cohort is small; and (3) studies where the outcomes of interest are expected to be early-onset or acute, with non-constant hazards.

• Future research is warranted on both sample-related and other causes of exposure misclassification relative to their effects on claims-based pharmacoepidemiology research, with a particular need to optimize bias quantification methods and develop a more standardized approach.

Acknowledgments

We thank Manuel de la Cruz Gutierrez PhD, MLS, Director of Data & Innovation Services at the Biomedical Library, University of Pennsylvania, for assisting with search strategy development.

Declaration of interest

EKA has no conflicts of interest. SH is a co-author of a paper [29] that served as the basis for a simulation study that is reviewed in the current systematic review. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

Additional information

Funding

This work was supported by the United States Department of Health and Human Services, National Institute on Aging under Grant R01AG025152 and R01AG064589; and the National Institute on Drug Abuse under Grant R01DA048001.