POLYPHARMACY IN CANCER PATIENTS: HEALTH-RELATED QUALITY OF LIFE, EXPENDITURES, AND ADVERSE EVENTS

Polypharmacy (PP), often defined as the use of five or more medications, is highly prevalent in patients with cancer. As the quantity of medications for treating cancer and comorbid conditions in patients with cancer become more numerous and diverse, it is important to understand the various ways in which patient health and economic outcomes may be adversely affected by prescribed medications. The purpose of this dissertation was to investigate three distinct associations between PP and the lives of patients living with cancer by estimating how PP (1) affects healthrelated quality of life (HRQoL), (2) is associated with healthcare expenditures, and (3) affects health complications (HCs). Approximately 25% of cancer survivors, individuals who were diagnosed with cancer and are still alive, report a decreased quality of life related to physical problems, and 10% report a decreased quality of life related to emotional issues, compared to their noncancer counterparts (10% and 6%, respectively). Specifically, cancer survivors report more mobility issues, inferior health, higher psychological distress, and more mental health needs. There is scant published literature describing PP in contributing to these outcomes. This study was conducted to address this gap to better inform cancer survivors, care providers, and health policy decision makers. Cancer was the sixth most expensive condition to treat in the United States (US) in 2015. Most cancers are estimated to have a decreasing incidence and increasing survival rate for the foreseeable future. A decreasing incidence may cause overall cancer-related expenditures to decline over time, but the prevalence of cancer coupled with the aging of the US population will result in an increase in the number of cancer survivors. Thus, expenditures during treatment through end of life are expected to continue to increase in coming years, as cancer survivors are estimated to increase from 15.5 million in 2016, to 26.1 million by 2040. Common cancer-related ailments such as pain, emesis, depression, venous thrombosis, and seizures can require prescription medications. With additional medications arises the risk for a health complication (HC). A HC, for the purposes of this study, is defined as an adverse health problem related to a drug, including adverse drug reactions, worsening of disease symptoms, falls, or overdoses. Although many HCs are preventable, they represent approximately 125,000 hospitalizations, over 3.5 million physician office visits, and an estimated 1 million emergency department visits each year in the general population. Previously identified risk factors for HCs in people with cancer, depending on the type of cancer, include PP, advanced stage of cancer, higher comorbidity, gender (for colorectal cancer), older age, and prior ER visits or hospitalizations. The purpose of the studies in this dissertation was to advance understanding of the role of PP on health and economic outcomes among people with cancer. We examined two data sources: (1) a large national survey database for manuscripts 1 and 2, and (2) a large, commercial claims database of privately-insured individuals for manuscript 3; both of which included United States (US) populations. Manuscript 1: The intent of this manuscript was to evaluate if an association exists between PP and HRQoL in cancer survivors in the US. The analysis used selfreported answers to questions about various demographic and clinical information captured in the Medical Expenditures Panel Survey (MEPS) database for even years 2008-2014. Respondents, who stated they were told that they had cancer, answered questions from the SF-12v2 about their physical and mental health, which were converted to the HRQoL measures PCS and MCS used for this analysis. This study focused on comparing cancer survivors, defined as having ≥ 5 prescribed medication classes in the year of the interview, with those with less than 5 medication classes. Differences among types of cancer were also explored in both descriptive and regression analyses. This study hypothesized that PP would lead to lower HRQoL as compared to patients not having PP. Of 10.1 million survivors per year included in this study, 45% were defined as having PP. We used ordinary least squares (OLS) regression to estimate that PP was associated with a statistically and clinically significant decrease in PCS scores among cancer survivors by 3.75 points. However, PP was not associated with a significant decrease in MCS scores. As such, PP should be analyzed closely in cancer survivors to ensure the best possible HRQoL. Manuscript 2: Healthcare expenditures are increasing in the US, and that is especially true for patients living with cancer. The objective of this manuscript was to determine if PP was associated with increased direct health care expenditures, and if differences in expenditure exist according to cancer type or setting of care. This aim was accomplished by using the same years and source of data as Manuscript 1, while modeling expenditure as a dependent variable. We hypothesized that PP was associated with increased health expenditures in total, by type of cancer and by setting of care. We used OLS regression with log transformed expenditures to obtain estimates of association between PP and increased health expenditures controlling for various demographic, socioeconomic, and clinical variables. PP was present in 43.9% of the 10.6 million (per year) cancer survivors in the study. PP was associated with a mean annual adjusted healthcare expenditure per cancer survivor of $13,266 (SD $3,766), which was significantly higher than those without PP $8,573 (SD 5,082, pvalue <.0001). Cancer survivors with PP accounted for 70% of total healthcare expenditures, yet only comprised 43.9% of the population. Manuscript 3: This study focused on newly diagnosed patients with breast, prostate, colorectal, or lung cancer and investigated if an association exists between PP and nonfatal health complications (HCs). The data source used was Optum Clinformatics DataMart (Optum, Eden Prairie, MN, USA), years 2010-2015. The database contains de-identified claims information with medical, prescription drug, enrollment, and other data tables. PP was measured as the use of ≥ 5 prescribed medication classes in the quarter (3 months) following incident cancer diagnosis. HCs was the dependent variable in the analysis and included a range of medical conditions known to be caused or worsened by effects of medications including falls, fractures, gastrointestinal bleeding, and delirium. Descriptive and logistic regression analyses were conducted to assess any associations between PP and HCs in a multivariable framework. This study hypothesized that HCs would occur more frequently among patients with PP than those without PP. In the primary analysis using multivariable LR modeling, PP was associated with 31% increased odds (adjusted odds ratio: aOR) of having ≥ 1 HCs, controlling for age, region, type of cancer, comorbidities, radiation and chemotherapy treatments. PP was significantly associated with a higher risk of having ≥ 1 HC in each cancer type (aOR: breast 1.37, 95% CI: 1.31-1.42; prostate 1.27, CI: 1.22-1.32; colorectal 1.26, CI: 1.16-1.36; lung 1.25, CI: 1.11-1.40). Active chemotherapy was associated with significantly increased odds of ≥ 1 HC in colorectal (aOR: 1.35, CI: 1.21-1.50) and lung (aOR: 1.33, CI: 1.15-1.54) cancers, but not significantly associated with breast or prostate cancers. Newly diagnosed patients with breast, prostate, colorectal, or lung cancer were all at a higher risk of having ≥ 1 HCs if defined as having PP compared to those without PP. Active chemotherapy treatment was associated with increased risk of HCs in colorectal and lung cancer patients, but not in breast or prostate cancer patients.