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A Comprehensive Review of Methods to Measure Oral Oncolytic Dose Intensity Using Retrospective Data.

BACKGROUND
Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics.


OBJECTIVE
To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs.


METHODS
Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction.


RESULTS
Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data.


CONCLUSIONS
This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures.


DISCLOSURES
Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.