Data gaps and opportunities for modeling cancer health equity.

Population models of cancer reflect the overall US population by drawing on numerous existing data resources for parameter inputs and calibration targets. Models require data inputs that are appropriately representative, collected in a harmonized manner, have minimal missing or inaccurate values, and reflect adequate sample sizes. Data resource priorities for population modeling to support cancer health equity include increasing the availability of data that 1) arise from uninsured and underinsured individuals and those traditionally not included in health-care delivery studies, 2) reflect relevant exposures for groups historically and intentionally excluded across the full cancer control continuum, 3) disaggregate categories (race, ethnicity, socioeconomic status, gender, sexual orientation, etc.) and their intersections that conceal important variation in health outcomes, 4) identify specific populations of interest in clinical databases whose health outcomes have been understudied, 5) enhance health records through expanded data elements and linkage with other data types (eg, patient surveys, provider and/or facility level information, neighborhood data), 6) decrease missing and misclassified data from historically underrecognized populations, and 7) capture potential measures or effects of systemic racism and corresponding intervenable targets for change.

Age-related differences in employment, insurance, and financial hardship among colorectal cancer patients: a report from the ColoCare Study.

PURPOSE: Employment and financial hardships are common issues for working-age colorectal cancer patients. We surveyed colorectal cancer survivors to investigate employment, insurance, and financial outcomes by age at diagnosis. METHODS: Cross-sectional survey of six ColoCare Study sites regarding employment, insurance, and financial hardship outcomes. Eligible participants were 1 to 5 years from colorectal cancer diagnosis. Diagnosis age (18-49, 50-64, 65+ years) with outcomes of interest were compared using chi-square and t-tests. Multivariable logistic and Poisson regressions were fit to examine association of demographic factors with any material/psychological hardship (yes/no) and the count of hardships. RESULTS: N = 202 participants completed the survey (age: 18-49 (n = 42, 20.8%), 50-64 (n = 79, 39.1%), 65+ (n = 81, 40.1%)). Most diagnosed age < 65 worked at diagnosis (18-49: 83%; 50-64: 64%; 65+ : 14%, p < 0.001) and continued working after diagnosis (18-49: 76%; 50-64: 59%; 65+ : 13%; p < 0.001). Participants age 18-49 reported cancer-related difficulties with mental (81.3%) and physical (89%) tasks at work more than those working in the older age groups (45%-61%). In regression models, among those reporting any hardship, the rates of material and psychological hardships were higher among those age 18-64 (Incidence Rate Ratios (IRR) range 1.5-2.3 vs. age 65+) and for those with < college (IRR range 1.3-1.6 vs. college +). CONCLUSIONS: Younger colorectal cancer patients are more likely to work after a cancer diagnosis and during cancer treatment, but report higher levels of financial hardship than older patients. IMPLICATIONS FOR CANCER SURVIVORS: Younger colorectal cancer patients may encounter financial hardship, thus may feel a need to work during and after treatment.

Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

BACKGROUND: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. METHODS: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). RESULTS: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. CONCLUSIONS: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. IMPACT: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

An Evaluation of the Utility of Big Data to Supplement Cancer Treatment Information: Linkage Between IQVIA Pharmacy Database and the Surveillance, Epidemiology, and End Results Program.

Oral anticancer medications (OAMs) are increasingly utilized. We evaluated the representativeness and completeness of IQVIA, a large aggregator of pharmacy data, for breast cancer, colon cancer, chronic myeloid leukemia, and myeloma cases diagnosed in six Surveillance, Epidemiology, and End Results Program (SEER) registries between 2007 and 2011. Patient's SEER and SEER-Medicare data were linked and compared with IQVIA pharmacy data from 2006 to 2012 for specific OAMs. Overall, 67.6% of SEER cases had a pharmacy claim in IQVIA during the treatment assessment window. This varied by location, race and ethnicity, and insurance status. IQVIA consistently identified fewer cases who received an OAM of interest than SEER-Medicare. The difference was least pronounced for breast cancer agents and most pronounced for myeloma agents. The IQVIA pharmacy database included a large portion of persons in the SEER areas. Future studies should assess receipt of OAMs for other cancer sites and in different SEER registries.

Time to Follow-up After Colorectal Cancer Screening by Health Insurance Type.

INTRODUCTION: The purpose of this study was to test the hypothesis that patients with Medicaid insurance or Medicaid-like coverage would have longer times to follow-up and be less likely to complete colonoscopy compared with patients with commercial insurance within the same healthcare systems. METHODS: A total of 35,009 patients aged 50-64years with a positive fecal immunochemical test were evaluated in Northern and Southern California Kaiser Permanente systems and in a North Texas safety-net system between 2011 and 2012. Kaplan-Meier estimation was used between 2016 and 2017 to calculate the probability of having follow-up colonoscopy by coverage type. Among Kaiser Permanente patients, Cox regression was used to estimate hazard ratios and 95% CIs for the association between coverage type and receipt of follow-up, adjusting for sociodemographics and health status. RESULTS: Even within the same integrated system with organized follow-up, patients with Medicaid were 24% less likely to complete follow-up as those with commercial insurance. Percentage receiving colonoscopy within 3 months after a positive fecal immunochemical test was 74.6% for commercial insurance, 63.10% for Medicaid only, and 37.5% for patients served by the integrated safety-net system. CONCLUSIONS: This study found that patients with Medicaid were less likely than those with commercial insurance to complete follow-up colonoscopy after a positive fecal immunochemical test and had longer average times to follow-up. With the future of coverage mechanisms uncertain, it is important and timely to assess influences of health insurance coverage on likelihood of follow-up colonoscopy and identify potential disparities in screening completion.

The Association Between Out-of-Pocket Costs and Adherence to Adjuvant Endocrine Therapy Among Newly Diagnosed Breast Cancer Patients.

OBJECTIVE: To determine how out-of-pocket costs for adjuvant endocrine therapy (AET) medication affects adherence among newly diagnosed breast cancer survivors with private health insurance who initiate therapy. MATERIALS AND METHODS: We examined medical and pharmacy claims for the 1-year period after initiating AET using the Truven Health Analytics MarketScan database. Adherence was defined as ≥80% proportion of days covered. Mean out-of-pocket costs for AET fill were measured as the sum of copayments, coinsurance, and deductibles and adjusted to 30-day amounts. Using a multivariable logistic regression model we calculated adjusted risk ratios controlling for age, comorbidities, type of surgery, use of chemotherapy and/or radiation therapy, average out-of-pocket costs for other services, and pharmacy use characteristics. RESULTS: Of the 6863 women 64 years and younger who were diagnosed with breast cancer and initiated AET, 73.9% were adherent (proportion of days covered≥80%). A total of 19% of patients had <$5 monthly out-of-pocket costs for AET, 30% had $5 to $9.99, 17% had $10 to $14.99, 10% had $15 to $19.99, and 25% had $20 or greater. Patients with out-of-pocket costs for AET between $10 and $14.99, $15 and $19.99, and >$20 were 6% to 8% less likely to be adherent compared with patients paying <$5.00, after controlling for covariates (P<0.05). Out-of-pocket costs for inpatient, outpatient, and other pharmacy services were not associated with adherence. CONCLUSIONS: A substantial proportion of privately insured patients are nonadherent to AET and out-of-pocket costs for AET medication are significantly associated with a greater likelihood of nonadherence.

Diabetes Treatments and Risks of Adverse Breast Cancer Outcomes among Early-Stage Breast Cancer Patients: A SEER-Medicare Analysis.

The widely prescribed diabetes medicine metformin has been reported to lower the risk of incident breast cancer, but it is unclear whether it affects malignant progression after diagnosis. In this study, we conducted a retrospective cohort study using the linked Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Women were included in the study if they were aged 66 to 80 years, newly diagnosed with stage I or II breast cancer, and enrolled in Medicare Parts A, B, and D during 2007 to 2011. Information on dispensed diabetes-related medications was obtained from Medicare Part D claims data. Our primary outcomes were second breast cancer events (SBCE), breast cancer recurrence, and breast cancer death. Time-varying Cox proportional hazard models were used to estimate HRs and their 95% confidence intervals (CI). Among 14,766 women included in the study, 791 experienced SBCE, 627 had a recurrence, and 237 died from breast cancer. Use of metformin (n = 2,558) was associated with 28% (95% CI, 0.57-0.92), 31% (95% CI, 0.53-0.90), and 49% (95% CI, 0.33-0.78) lower risks of an SBCE, breast cancer recurrence, and breast cancer death. Use of sulfonylureas or insulin was associated with 1.49- (95% CI, 1.00-2.23) and 2.58-fold (95% CI, 1.72-3.90) higher risks of breast cancer death. Further research may be warranted to determine whether metformin is a preferred treatment for diabetes among breast cancer survivors and whether it benefits breast cancer patients without diabetes. Cancer Res; 77(21); 6033-41. ©2017 AACR.

Use of Antihypertensive Medications and Risk of Adverse Breast Cancer Outcomes in a SEER-Medicare Population.

Background: It is unclear if use of common antihypertensive medications influences the risk of adverse breast cancer outcomes.Methods: Using the linked Surveillance, Epidemiology and End-Results (SEER)-Medicare database, we identified 14,766 women between ages 66 and 80 years diagnosed with incident stage I/II breast cancer between 2007 and 2011. Medicare Part D data were obtained to characterize women's post-cancer use of various antihypertensive medications. Outcomes included a second breast cancer event (SBCE; a composite outcome defined as the first of a recurrence or a second contralateral primary breast cancer), breast cancer recurrence, and breast cancer-specific mortality. Time-varying Cox proportional hazard models were used to estimate hazard ratios (HR) and their associated 95% confidence intervals (CI).Results: There were 791 SBCEs, 627 breast cancer recurrences, and 237 breast cancer deaths identified over a median follow-up of 3 years. Use of diuretics (n = 8,517) after breast cancer diagnosis was associated with 29% (95% CI, 1.10-1.51), 36% (95% CI, 1.14-1.63) and 51% (95% CI, 1.11-2.04) higher risks of a SBCE, recurrence, and breast cancer death, respectively. Compared with nonusers, ß-blockers users (n = 7,145) had a 41% (95% CI, 1.07-1.84) higher risk of breast cancer death. Use of angiotensin II receptor blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors were not associated with risks of breast cancer outcomes.Conclusions: Use of diuretics and ß-blockers may be associated with increased risk of breast cancer outcomes among older women.Impact: Most antihypertensive medications are safe with respect to breast cancer outcomes, but more research is needed for diuretics and ß-blockers. Cancer Epidemiol Biomarkers Prev; 26(11); 1603-10. ©2017 AACR.

Factors Associated with Adherence to Adjuvant Endocrine Therapy Among Privately Insured and Newly Diagnosed Breast Cancer Patients: A Quantile Regression Analysis.

BACKGROUND: Adherence to adjuvant endocrine therapy (AET) for estrogen receptor-positive breast cancer remains suboptimal, which suggests that women are not getting the full benefit of the treatment to reduce breast cancer recurrence and mortality. The majority of studies on adherence to AET focus on identifying factors among those women at the highest levels of adherence and provide little insight on factors that influence medication use across the distribution of adherence. OBJECTIVE: To understand how factors influence adherence among women across low and high levels of adherence. METHODS: A retrospective evaluation was conducted using the Truven Health MarketScan Commercial Claims and Encounters Database from 2007-2011. Privately insured women aged 18-64 years who were recently diagnosed and treated for breast cancer and who initiated AET within 12 months of primary treatment were assessed. Adherence was measured as the proportion of days covered (PDC) over a 12-month period. Simultaneous multivariable quantile regression was used to assess the association between treatment and demographic factors, use of mail order pharmacies, medication switching, and out-of-pocket costs and adherence. The effect of each variable was examined at the 40th, 60th, 80th, and 95th quantiles. RESULTS: Among the 6,863 women in the cohort, mail order pharmacies had the greatest influence on adherence at the 40th quantile, associated with a 29.6% (95% CI = 22.2-37.0) higher PDC compared with retail pharmacies. Out-of-pocket cost for a 30-day supply of AET greater than $20 was associated with an 8.6% (95% CI = 2.8-14.4) lower PDC versus $0-$9.99. The main factors that influenced adherence at the 95th quantile were mail order pharmacies, associated with a 4.4% higher PDC (95% CI = 3.8-5.0) versus retail pharmacies, and switching AET medication 2 or more times, associated with a 5.6% lower PDC versus not switching (95% CI = 2.3-9.0). CONCLUSIONS: Factors associated with adherence differed across quantiles. Addressing the use of mail order pharmacies and out-of-pocket costs for AET may have the greatest influence on improving adherence among those women with low adherence. DISCLOSURES: This research was supported by a Ruth L. Kirschstein National Research Service Award for Individual Predoctoral Fellowship grant from the National Cancer Institute (grant number F31 CA174338), which was awarded to Farias. Additionally, Farias was funded by a Postdoctoral Fellowship at the University of Texas School of Public Health Cancer Education and Career Development Program through the National Cancer Institute (NIH Grant R25 CA57712). The other authors declare no conflicts of interest. DISCLAIMER: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Farias was primarily responsible for the study concept and design, along with Hansen and Zeliadt and with assistance from the other authors. Farias, Hansen, and Zeliadt took the lead in data interpretation, assisted by the other authors. The manuscript was written by Farias, along with Thompson and assisted by the other authors, and was revised by Ornelas, Li, and Farias, with assistance from the other authors.

Insurance status and risk of cancer mortality among adolescents and young adults.

BACKGROUND: Adolescents and young adults with cancer have inferior survival outcomes compared with younger pediatric patients and older adult patients. Lack of insurance may partly explain this disparity. The objective of this study was to identify associations between insurance status and both advanced-stage cancer and cancer-specific mortality. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) 18 registries, 57,981 patients ages 15 to 39 years were identified who were diagnosed between 2007 and 2010 and had complete insurance and staging information. Multinomial logistic regression models were used to identify associations between insurance type and disease stage, with the models adjusted for sex, age, and race. Cox proportional hazards models were used to estimate cancer-specific mortality. RESULTS: Overall, 84% of patients were aged ≥ 25 years, 64% were women, and 79% were privately insured. Compared with patients who had private insurance, those who had nonprivate insurance tended to present with more advanced-stage disease and to die more quickly and more commonly from their cancer. Patients ages 25 to 39 years who had Medicaid coverage or no insurance had 3.2 times and 2.4 times higher odds of having stage IV disease, respectively, than privately insured patients (95% confidence interval [CI], 3.0-3.5 times higher odds and 2.1-2.6 times higher odds, respectively). Among those with stage I/II and III/IV cancers, the risk of death was 2.9 times greater (95% CI, 2.2-3.9 times greater) and 1.7 times greater (95% CI, 1.5-1.9 times greater), respectively, than the risk for privately insured patients. Patients who died from stage III/IV cancers survived at least 2 months longer if they had private insurance. CONCLUSIONS: Among young adults, insurance status is independently associated with advanced-stage cancer and the risk of death from cancer, even for patients who have low-stage disease. Broader insurance coverage and access to health care may improve some of the disparate outcomes of adolescents and young adults with cancer.

Net risk reclassification p values: valid or misleading?

BACKGROUND: The Net Reclassification Index (NRI) and its P value are used to make conclusions about improvements in prediction performance gained by adding a set of biomarkers to an existing risk prediction model. Although proposed only 5 years ago, the NRI has gained enormous traction in the risk prediction literature. Concerns have recently been raised about the statistical validity of the NRI. METHODS: Using a population dataset of 10000 individuals with an event rate of 10.2%, in which four biomarkers have no predictive ability, we repeatedly simulated studies and calculated the chance that the NRI statistic provides a positive statistically significant result. Subjects for training data (n = 420) and test data (n = 420 or 840) were randomly selected from the population, and corresponding NRI statistics and P values were calculated. For comparison, the change in the area under the receiver operating characteristic curve and likelihood ratio statistics were calculated. RESULTS: We found that rates of false-positive conclusions based on the NRI statistic were unacceptably high, being 63.0% in the training datasets and 18.8% to 34.4% in the test datasets. False-positive conclusions were rare when using the change in the area under the curve and occurred at the expected rate of approximately 5.0% with the likelihood ratio statistic. CONCLUSIONS: Conclusions about biomarker performance that are based primarily on a statistically significant NRI statistic should be treated with skepticism. Use of NRI P values in scientific reporting should be halted.

Disparities in access to lung transplantation for patients with cystic fibrosis by socioeconomic status.

RATIONALE: Although previous studies suggest that access to care for patients with cystic fibrosis (CF) does not vary appreciably by socioeconomic status (SES), disparities with respect to access to lung transplantation for patients with CF are largely unknown. OBJECTIVES: To determine whether access to lung transplantation for patients with CF differs according to SES. METHODS: Observational study involving 2,167 adult patients with CF from the CF Foundation Patient registry who underwent their first lung transplant evaluation between 2001 and 2009. The primary outcome was acceptance for lung transplant after initial evaluation. The main SES indicator was Medicaid status. Alternate SES indicators included race, educational attainment, ZIP code-level median household income, and driving time from residence to closest lung transplant center. MEASUREMENTS AND MAIN RESULTS: The odds that Medicaid recipients were not accepted for lung transplant were 1.56-fold higher (95% confidence interval [CI], 1.27-1.92) than patients without Medicaid, after multivariate adjustment for demographic characteristics, disease severity, and potential contraindications to lung transplant, and before or after use of the lung allocation score. This association was independent of other SES indicators, including race, educational attainment, ZIP code-level median household income, and driving time to closest transplant center (odds ratio [OR] = 1.37; 95% CI, 1.10-1.72). Patients not completing high school (OR = 2.37; 95% CI, 1.49-3.79) and those residing in the lowest (vs. highest) ZIP code median household income category (OR = 1.39; 95% CI, 1.01-1.93) also experienced a higher odds of not being accepted for lung transplant in multivariate analysis. CONCLUSIONS: In this nationally representative study of adult patients with CF, multiple indicators of low SES were associated with higher odds of not being accepted for lung transplant.

Disparities in breast cancer characteristics and outcomes by race/ethnicity.

Disparities in breast cancer stage and mortality by race/ethnicity in the United States are persistent and well known. However, few studies have assessed differences across racial/ethnic subgroups of women broadly defined as Hispanic, Asian, or Pacific Islander, particularly using more recent data. Using data from 17 population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) program, we evaluated the relationships between race/ethnicity and breast cancer stage, hormone receptor status, treatment, and mortality. The cohort consisted of 229,594 women 40-79 years of age diagnosed with invasive breast carcinoma between January 2000 and December 2006, including 176,094 non-Hispanic whites, 20,486 Blacks, 15,835 Hispanic whites, 14,951 Asians, 1,224 Pacific Islanders, and 1,004 American Indians/Alaska Natives. With respect to statistically significant findings, American Indian/Alaska Native, Asian Indian/Pakistani, Black, Filipino, Hawaiian, Mexican, Puerto Rican, and Samoan women had 1.3-7.1-fold higher odds of presenting with stage IV breast cancer compared to non-Hispanic white women. Almost all groups were more likely to be diagnosed with estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) disease with Black and Puerto Rican women having the highest odds ratios (2.4 and 1.9-fold increases, respectively) compared to non-Hispanic whites. Lastly, Black, Hawaiian, Puerto Rican, and Samoan patients had 1.5-1.8-fold elevated risks of breast cancer-specific mortality. Breast cancer disparities persist by race/ethnicity, though there is substantial variation within subgroups of women broadly defined as Hispanic or Asian. Targeted, multi-pronged interventions that are culturally appropriate may be important means of reducing the magnitudes of these disparities.

Neonatal encephalopathy and socioeconomic status: population-based case-control study.

OBJECTIVE: To investigate the association between maternal socioeconomic status and the risk of encephalopathy in full-term newborns. DESIGN: Population-based case-control study. SETTING: Washington State births from 1994 through 2002 recorded in the linked Washington State Birth Registry and Comprehensive Hospital Abstract Reporting System. PARTICIPANTS: Cases (n = 1060) were singleton full-term newborns with Comprehensive Hospital Abstract Reporting System International Classification of Diseases, Ninth Revision diagnoses of seizures, birth asphyxia, central nervous system dysfunction, or cerebral irritability. Control cases (n = 5330) were singleton full-term newborns selected from the same database. Main Exposures Socioeconomic status was defined by median income of the census tract of the mother's residence, number of years of maternal educational achievement, or maternal insurance status. MAIN OUTCOME MEASURES: Odds ratios estimating the risk of encephalopathy associated with disadvantaged socioeconomic status were calculated in 3 separate analyses using multivariate adjusted logistic regression. RESULTS: Newborns of mothers living in neighborhoods in which residents have a low median income were at increased risk of encephalopathy compared with newborns in neighborhoods in which residents have a median income more than 3 times the poverty level (adjusted odds ratio, 1.9; 95% confidence interval, 1.5-2.3). There was also a trend for increasing risk of encephalopathy associated with decreasing neighborhood income (P<.001). Newborns of mothers with less than 12 years of educational achievement had a higher risk of encephalopathy compared with newborns of mothers with more than 16 years of educational achievement (adjusted odds ratio, 1.7; 95% confidence interval, 1.3-2.3). Newborns of mothers receiving public insurance also had a higher risk of encephalopathy compared with newborns of mothers who have commercial insurance (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.7). CONCLUSION: Disadvantaged socioeconomic status was independently associated with an increased risk of encephalopathy in full-term newborns. These findings suggest that a mother's socioeconomic status may influence the risk of encephalopathy for her full-term newborn.

Racial and ethnic disparities in breast cancer stage, treatment, and survival in the United States.

Several studies indicate that African-American, Hispanic White, and Native American women with breast cancer present with more advanced stages and have poorer survival rates than non-Hispanic Whites, while Asians/Pacific Islanders do not. However, Asians/Pacific Islanders and Hispanic Whites are heterogeneous populations, and recent data indicate that certain subgroups of these populations have poorer breast cancer outcomes compared to non-Hispanic Whites, while others have better outcomes. Many of these disparities have persisted for decades, but until recently, detailed studies exploring the reasons behind these disparities have been limited. The results of these studies point to the effect of differences in socioeconomic status, access to health care (including both breast cancer screening and treatment services), lifestyle factors, and tumor characteristics on these disparities. Thus, these studies indicate that these disparities are multifactorial, and therefore strategies aimed at reducing them must involve advocacy, research, education, and healthcare services. A key component to the success of these strategies is not only support for them on the federal and state levels, but also the involvement of local communities in developing programs and policies that are culturally and linguistically appropriate for their communities in order to ensure not only the utility, but also the longevity, of these efforts.