Comparison of Approaches for Measuring Adherence and Persistence to Oral Oncologic Therapies in Patients Diagnosed with Metastatic Renal Cell Carcinoma

Background: Adherence and persistence studies face several methodologic difficulties, including short-term mortality. We compared approaches to quantify adherence and persistence to first line (1L) oral targeted therapy (TT) in patients diagnosed with metastatic renal cell carcinoma (mRCC). Methods: Patients with mRCC ages 66 years or more who initiated TTs within 4 months of diagnosis were identified in the Surveillance, Epidemiology, and End Results Medicare-linked database (2007–2015). Adherence [proportion of days covered (PDC) >80%] was calculated using (i) PDC with a fixed 6-month denominator including then excluding patients who died within the 6 months and (ii) PDC with a denominator measuring time on treatment. Risk of nonpersistence was obtained by censoring death or treating death as a competing risk using cumulative incidence functions. Results: Among 485 patients with mRCC initiating a 1L oral TT (sunitinib, 64%; pazopanib, 25%; other, 11%), 40% died within 6 months. Adherence was higher after restricting to patients who survived (60%) compared with including those patients and assigning zero days covered after death (47%). Risk of nonpersistence was higher when censoring patients at death, 0.91 [95% confidence interval (CI), 0.88–0.94], compared with treating death as a competing risk, 0.75 (95% CI, 0.71–0.79). Conclusions: Different approaches to handling death resulted in different adherence and persistence estimates in the metastatic setting. Future studies should explicitly report the proportion of patient deaths over time and explore appropriate methods to account for death as competing risk. Impact: Use of several approaches can provide a more comprehensive picture of medication-taking behavior in the metastatic setting where death is a major competing risk.