The study sample consisted of patients aged 65 years and older with a new primary diagnosis of stage IV bladder cancer with TNM staging as either T4b, N0, M0; any T, N1–N3, M0; or any T, any N, M1. Patients were required to have continuous enrollment in Medicare Part A and Part B with no HMO enrollment during the study period. Patients were excluded if they had concomitant or prior history of malignancy other than bladder cancer. Patients who received chemotherapy were identified using Healthcare Common Procedures Coding System or National Drug Code code numbers for specific agents categorized as carboplatin-based regimens, cisplatin-based regimens, and nonplatinum-based regimens. A full list of chemotherapy regimens for patients in the study sample is provided in the Online Supplemental Material (Supplementary Table 1).
The outcomes of interest were chemotherapy treatment patterns, health care visits, costs, and survival. Chemotherapy regimens (1L and 2L) were described according to agent, time of initiation after diagnosis, and duration of treatment.
Adverse events (AEs) of interest were those occurring during the 1L and 2L chemotherapy treatment exposure windows, with a severity grade of 3/4, and with an incidence of greater than or equal to 5% as reported in the United States prescribing information for drugs used in 1L and 2L treatment of bladder cancer. AEs of interest that required resource use, and were not only lab investigations (based on the Common Terminology Criteria for Adverse Events description and clinical input), were chosen for inclusion in this study.
Health care visits and costs occurring during the 1L and 2L treatment exposure windows were determined. Health care visits and costs occurring outside of the treatment exposure windows were not included in this analysis. Health care visits and costs were categorized as bladder cancer-related, AE-related, or other. Bladder cancer–related visits and costs were those with an International Classification of Diseases, Ninth Revision (ICD-9) code indicating bladder cancer (codes 188.x, 189.1-189.3, 233.7, 236.7, and 239.4) as the primary diagnosis. AE–related visits and costs were those with a primary claim for a listed AE. Other visits and costs were those that were neither bladder cancer– nor AE–related. Health care costs were also categorized by payer according to data extracted from the Medicare claims data. The claims data divides payments into three categories: Medicare payments, primary payer payments (referred to as “other payer” in this study), and patient copay/deductible payments (referred to as “patient payment” in this study). The primary payer or “other payer” represents any other insurance company that the patient receives health care insurance from.
Patient demographic characteristics were documented in the baseline period. Patient age and cancer disease status (described by TNM stage) were determined as of the index diagnosis date. Comorbidities were identified by ICD-9 diagnostic codes recorded during the baseline period and summarized with the adjusted Charlson Comorbidity Index (CCI) score, with the CCI score adjusted for cancer.
All analyses were stratified by line of chemotherapy treatment (1L and 2L). A descriptive analysis was conducted, and no statistical comparisons of outcomes for different chemotherapy regimens were undertaken. Patient demographic and clinical characteristics at baseline were described. Where applicable, data has been coarsened in order to conform with the Centers for Medicare & Medicaid Services (CMS) Cell Size Suppression Policy, which sets the minimum threshold for the display of CMS data. The policy specifies that no cell containing a value of 1 to 10 patients can be reported directly, and no cell can be reported that allows a value of 1 to 10 to be derived from other reported cells or information. Health care visits and costs during the 1L and 2L treatment exposure windows were reported as averages as well as per-patient-per-month (PPPM) values, to account for variable durations of treatment. PPPM values were calculated as the total value, divided by the patient-specific days in the treatment exposure window, multiplied by 30. Health care visits and costs were classified by setting of care: outpatient, emergency, inpatient, skilled nursing facility, and hospice. Health care costs were further categorized based upon the total amount of money paid as well as the amount of the claim paid by Medicare, patient, and other payer. Costs are reported in 2016 US dollars (USD). Survival from the index therapy date was expressed as a median and as a survival rate (percent survival) at 1, 2, and 3 years. In addition, the Kaplan-Meier method was utilized to evaluate time-to-event outcomes from the index therapy date.