Impact of Drug Shortages on Patient Treatment and Survival: The Case of Cytarabine and AML Leukemia

Introduction Drug shortages of parenteral injectable medications reached an all time high in calendar year 2011. The focus of this research is to understand implications of a shortage of the chemotherapy drug cytarabine, for which there is no therapeutically equivalent substitute, and for which prompt initiation thereof is important, on patient receipt of treatment and all cause survival. Methods The study population is patients presenting with an Acute Myelogenous Leukemia diagnosis (AML) between December 2010 and October 2011, during which the FDA determined the cytarabine drug supply to be compromised. Primary data sources were SEER-18 registry data for years 2008-11 linked to Medicare parts A and B fee-for-service claims for the years 2007-13. Persons age 65 and above diagnosed between January 1 and March 31, 2011 were classified as exposed to major shortage while persons diagnosed April 1-December 31, 2011 were classified as moderate shortage respectively. Time to first treatment, proportion receiving any treatment within 14, 28 and 60 days and survival probability were compared to the same parameters for persons diagnosed during calendar years 2008-2010 (non-shortage period). Results Odds for receipt of treatment within 14 days of diagnosis for persons diagnosed during a period of major shortage was reduced by almost 50% (OR=0.537, p < 0.05). Median days to first qualifying dose inpatient chemotherapy jumped from 7 to11 days. Patients for which AML was a secondary/later cancer waited on average 50% longer for treatment, compared to during a non-shortage baseline (IRR=1.488, p < 0.05). Extended Cox models for patients surviving 30 or more days post diagnosis identified elevated probability of death at 60 (HR=1.668, p <0.05), 90 (HR=1.415, p <0.1), and 120 (HR=1.381,p<0.05) days post diagnosis for persons diagnosed during a period of major shortage. Conclusion Diagnosis during a period of major shortage was associated with reduced probability and prolonged time to treatment and a higher hazard for early death. Further study of imbalance between current market price and pharmaceutical manufacturer profitability of generic medications without a close therapeutic substitute is necessary to guide pricing policy and reduce the likelihood of shortage reoccurrence and compromised patient outcomes.