Indirect Costs of Oral Versus Non-Oral Therapies in Hematologic Malignancies: A Systematic Literature Review
Authors: Fazeli Mir Sohail , Pushkarna Divya , Howarth Ana , Hux Margaret , Pourrahmat Mir-Masoud , Chen Clara 
Published: November 2020

Introduction: The treatment landscape for hematologic malignancies is evolving rapidly, and a range of therapeutic options with differing routes of administration is now available. The shifting dynamics of these novel therapies and increasing total treatment costs highlight the importance of value-based healthcare decisions that take patient, payer, and societal perspectives into account. It is therefore increasingly important to consider both direct and indirect costs when evaluating therapeutic options. Reducing healthcare visits for administration of non-oral therapies (injectable and/or mixed therapies) results in indirect cost savings and is of particular relevance during the current coronavirus disease (COVID-19) pandemic where there are distinct challenges with respect to visiting hospital settings. However, the indirect cost savings of utilizing oral versus non-oral treatments have yet to be fully assessed from a patient and societal perspective. The objective of this review was to assess the differences in indirect non-treatment-related costs between oral and non-oral therapies for hematologic malignancies.
Methods: A systematic literature review (SLR) was conducted by searching the Embase®, MEDLINE®, EconLit, and Health Technology Assessment/National Health Service economic evaluation (HTA/NHS EED) databases from inception to June 2020. Additionally, literature searches of proceedings from the 2018-2020 American Society of Clinical Oncology (ASCO), American Society of Hematology (ASH), and The Professional Society for Health Economics and Outcomes Research (ISPOR) conferences were performed to capture recent studies not indexed in the main databases. A manual search of the reference list from all included study publications was also performed. Eligibility criteria for study identification were developed using the Population, Intervention, Comparator, and Outcome (PICO) framework. Eligible studies included cost models and observational studies reporting indirect costs from a patient and/or societal perspective for oral versus non-oral therapies.
Results: A total of 4,012 records were identified by the searches. Following title/abstract screening, the full text of 25 publications was reviewed, and 5 studies conducted in the USA (n = 3), Italy (n = 1), and Finland (n = 1) were identified as eligible and selected for qualitative evidence synthesis (Table). Although the SLR protocol included all hematologic malignancies, only studies including patients with multiple myeloma (MM) were identified. The indirect costs reported across the selected studies varied and included costs such as loss of productivity, transportation, and patient and/or caregiver time. Among all 5 studies, total indirect costs for patients with MM were lower for oral versus non-oral regimens. In the USA-based studies, indirect costs were USD 70-1,202 per month for oral regimens versus USD 432-1,526 per month for non-oral regimens. In Europe-based studies, indirect cost estimates were EUR 1,800 versus EUR 17,000 per year for oral versus non-oral regimens (Italian study), and EUR 114 versus EUR 358 per 28-day cycle for oral versus non-oral regimens (Finnish study; averages calculated from ranges in Table).
Conclusions: This SLR demonstrates a paucity of data on the indirect costs to patients and society of oral versus non-oral therapies for hematologic malignancies. The studies included in this review assessed differing types of indirect costs, including loss of productivity, transportation costs, and patient and/or caregiver time; however, all indicated that the administration of oral regimens is associated with lower indirect costs compared with non-oral regimens. This finding is compelling given the current global health crisis due to COVID-19, where prioritizing the concept of "value" means assessing more complex issues, such as indirect costs that may have a meaningful impact on patients and society.

Disclosures
Fazeli: Evidinno Outcomes Research Inc.: Current Employment. Pushkarna:Evidinno Outcomes Research Inc.: Current Employment. Howarth:Evidinno Outcomes Research Inc.: Current Employment. Hux:Evidinno Outcomes Research Inc.: Consultancy. Pourrahmat:Evidinno Outcomes Research Inc.: Current Employment. Chen:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.