Medication delivery factors and adjuvant endocrine therapy adherence in breast cancer.

PURPOSE: Over 50% of breast cancer patients prescribed a 5-year course of daily oral adjuvant endocrine therapy (ET) are nonadherent. We investigated the role of costs and cancer medication delivery mode and other medication delivery factors on adherence. METHODS: We conducted a retrospective cohort study of commercially insured and Medicare advantage patients with newly diagnosed breast cancer in 2007-2015 who initiated ET. We examined the association between 12-month ET adherence (proportion of days covered by fills ≥ 0.80) and ET copayments, 90-day prescription refill use, mail order pharmacy use, number of pharmacies, and synchronization of medications. We used regression models to estimate nonadherence risk ratios adjusted for demographics (age, income, race, urbanicity), comorbidities, total medications, primary cancer treatments, and generic AI availability. Sensitivity analyses were conducted using alternative specifications for independent variables. RESULTS: Mail order users had higher adherence in both commercial and Medicare-insured cohorts. Commercially insured patients who used mail order were more likely to be adherent if they had low copayments (< $5) and 90-day prescription refills. For commercially insured patients who used local pharmacies, use of one pharmacy and better synchronized refills were also associated with adherence. Among Medicare patients who used mail order pharmacies, only low copayments were associated with adherence, while among Medicare patients using local pharmacies both low copayments and 90-day prescriptions were associated with ET adherence. CONCLUSION: Out-of-pocket costs, medication delivery mode, and other pharmacy-related medication delivery factors are associated with adherence to breast cancer ET. Future work should investigate whether interventions aimed at streamlining medication delivery could improve adherence for breast cancer patients.

Implementation-effectiveness trial of systematic family health history based risk assessment and impact on clinical disease prevention and surveillance activities.

BACKGROUND: Systematically assessing disease risk can improve population health by identifying those eligible for enhanced prevention/screening strategies. This study aims to determine the clinical impact of a systematic risk assessment in diverse primary care populations. METHODS: Hybrid implementation-effectiveness trial of a family health history-based health risk assessment (HRA) tied to risk-based guideline recommendations enrolling from 2014-2017 with 12 months of post-intervention survey data and 24 months of electronic medical record (EMR) data capture. SETTING: 19 primary care clinics at four geographically and culturally diverse U.S. healthcare systems. PARTICIPANTS: any English or Spanish-speaking adult with an upcoming appointment at an enrolling clinic. METHODS: A personal and family health history based HRA with integrated guideline-based clinical decision support (CDS) was completed by each participant prior to their appointment. Risk reports were provided to patients and providers to discuss at their clinical encounter. OUTCOMES: provider and patient discussion and provider uptake (i.e. ordering) and patient uptake (i.e. recommendation completion) of CDS recommendations. MEASURES: patient and provider surveys and EMR data. RESULTS: One thousand eight hundred twenty nine participants (mean age 56.2 [SD13.9], 69.6% female) completed the HRA and had EMR data available for analysis. 762 (41.6%) received a recommendation (29.7% for genetic counseling (GC); 15.2% for enhanced breast/colon cancer screening). Those with recommendations frequently discussed disease risk with their provider (8.7%-38.2% varied by recommendation, p-values ≤ 0.004). In the GC subgroup, provider discussions increased referrals to counseling (44.4% with vs. 5.9% without, P < 0.001). Recommendation uptake was highest for colon cancer screening (provider = 67.9%; patient = 86.8%) and lowest for breast cancer chemoprevention (0%). CONCLUSIONS: Systematic health risk assessment revealed that almost half the population were at increased disease risk based on guidelines. Risk identification resulted in shared discussions between participants and providers but variable clinical action uptake depending upon the recommendation. Understanding the barriers and facilitators to uptake by both patients and providers will be essential for optimizing HRA tools and achieving their promise of improving population health. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01956773 , registered 10/8/2013.

Pharmacy deserts and patients with breast cancer receipt of influenza vaccines.

BACKGROUND: Yearly influenza vaccination is strongly recommended at age 65 and reimbursed by Medicare without copays or deductibles at pharmacies and clinical settings. Uptake is low among patients with a high risk for influenza complications and good access to specialist care, such as recent cancer survivors. We hypothesized that more accessible pharmacies could be associated with higher immunization uptake in such patients. OBJECTIVES: To determine whether pharmacy access is associated with influenza vaccination in subjects recently diagnosed with breast cancer, and whether this association differs by additional risk factors for influenza complications. METHODS: We examined a cohort of patients with stage 0-III breast cancer diagnosed 2011-2015 from the Surveillance, Epidemiology, and End Results-Medicare cancer registry. All retail pharmacies in the United States were identified, and pharmacy access was measured by assessing supply and demand in each census tract using a 2-stage floating catchment area approach that accounted for pharmacy driving distances recommended by the Centers for Medicare and Medicaid Services. We examined the association of pharmacy access with influenza vaccination after breast cancer diagnosis in regression models. RESULTS: More than 11% of 45,722 patients with breast cancer lived in census tracts where no pharmacies were within recommended driving distances from the population-weighted tract center. Vaccination in the year after diagnosis was less likely for patients in these very low-access tracts (adjusted odds ratio 0.92 [95% CI 0.86-0.96]), black (0.55 [0.51-0.60]) and Hispanic (0.76 [0.70-0.83]) women, and Medicaid recipients (0.74 [0.69-0.79]). Vaccination was inversely associated with per capita income in the subject's census tract, but there was no difference in the pharmacy effect by race, ethnicity, or census tract income. CONCLUSION: Very low pharmacy access is associated with modest reductions in vaccination that could be useful for policy and planning regarding vaccinator resources and outreach.

The Role of Physician Professional Networks in Physicians' Receipt of Pharmaceutical and Medical Device Industries' Payments.

BACKGROUND: Financial relationships between physicians and the pharmaceutical and medical device industries are common, but the factors associated with physicians receiving payments are unknown. OBJECTIVE: The objective of this study is to evaluate the influence of physicians' professional networks' characteristics on the receipt of payments among physicians. DESIGN: Network analysis of cross-sectional data PARTICIPANTS: US physicians who shared Medicare patients with other physicians in 2015 (N=357,813). EXPOSURE (INTERVENTION): Proportion of a physician's professional network that received industry payments and other network characteristics including number of physician connections, how central the physician is within the network, and the tightness of the referral network in which a physician is located. MAIN OUTCOME MEASURES: Relative risk of receiving industry payments. We used modified Poisson regression to control for confounding by gender, time since graduation, practice size, and practice setting (teaching hospital vs. not). We included dummy variables for specialty and hospital referral region level. KEY RESULTS: The proportion of a physician's peers in their professional network that received payments was strongly associated with receipt of pharmaceutical or device industry payments by the physician (top vs bottom quartile aRR=1.28, 95%CI=1.25-1.31). Physician's centrality within a network had a small positive effect on receiving payment (top vs bottom quartile aRR=1.02, 95%CI=1.01-1.04). Network density also had a small negative association with receipt of payment (top vs bottom quartile aRR=0.97, 95%CI=0.96-0.98). CONCLUSIONS: Network characteristics, particularly the receipt of payments among physicians one shares patients with, are associated with whether a physician receives payments. This finding has implications for institutional regulation of industry payments to physicians and demonstrates how institutional policy may impact not only the physicians within the institution but also physicians outside of the institution.

The Use and Concurrent Use of Side Effect Controlling Medications Among Women on Aromatase Inhibitors.

Background: Women on aromatase inhibitors (AIs) as part of their breast cancer treatment often experience difficult to control side effects. Although there are several medications to manage the side effects of AI therapy, many of them are associated with their own risk, particularly sedation. The objective of this study was to describe the prescribing practices for side effect managing (SE) medications among women with breast cancer on AI therapy and to assess for combinations of medications that may present a clinical risk to patients. Methods: Retrospective data analysis using Surveillance, Epidemiology and End Results (SEER)-Medicare data of all women aged 66-90 years with stage I-III hormone positive breast cancer diagnosed between 2008 and 2014 who initiated AI therapy within 12 months of their diagnosis. We determined the percentage of patients prescribed an SE medication in the 12 months prior and in the 24 months after the initiation of AI therapy. We calculated the number of prescriptions and the number of days of overlapping (i.e., >1 SE) prescriptions, and examined predictors of overlapping prescriptions. Results: The use of SE medications was pervasive and increased after initiation of AI therapy. The most commonly prescribed medications were opiates (55.1%), selective serotonin reuptake inhibitors (22.6%), benzodiazepines (18.4%), tramadol (17.7%) and gabapentin (14.6%). In total 15.5% of patients had overlapping prescriptions; among those, 36.2% had three overlapping prescriptions. Prior use was the strongest predictor of overlapping prescriptions with an odds ratio of 7.9 (95% confidence interval: 7.17-8.77). Conclusion: Among women on AI therapy, the use of SE medications is common and many have overlapping prescriptions raising concern for potential harm from polypharmacy.

At the intersection of precision medicine and population health: an implementation-effectiveness study of family health history based systematic risk assessment in primary care.

BACKGROUND: Risk assessment is a precision medicine technique that can be used to enhance population health when applied to prevention. Several barriers limit the uptake of risk assessment in health care systems; and little is known about the potential impact that adoption of systematic risk assessment for screening and prevention in the primary care population might have. Here we present results of a first of its kind multi-institutional study of a precision medicine tool for systematic risk assessment. METHODS: We undertook an implementation-effectiveness trial of systematic risk assessment of primary care patients in 19 primary care clinics at four geographically and culturally diverse healthcare systems. All adult English or Spanish speaking patients were invited to enter personal and family health history data into MeTree, a patient-facing family health history driven risk assessment program, for 27 medical conditions. Risk assessment recommendations followed evidence-based guidelines for identifying and managing those at increased disease risk. RESULTS: One thousand eight hundred eighty-nine participants completed MeTree, entering information on N = 25,967 individuals. Mean relatives entered = 13.7 (SD 7.9), range 7-74. N = 1443 (76.4%) participants received increased risk recommendations: 597 (31.6%) for monogenic hereditary conditions, 508 (26.9%) for familial-level risk, and 1056 (56.1%) for risk of a common chronic disease. There were 6617 recommendations given across the 1443 participants. In multivariate analysis, only the total number of relatives entered was significantly associated with receiving a recommendation. CONCLUSIONS: A significant percentage of the general primary care population meet criteria for more intensive risk management. In particular 46% for monogenic hereditary and familial level disease risk. Adopting strategies to facilitate systematic risk assessment in primary care could have a significant impact on populations within the U.S. and even beyond. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01956773 , registered 10/8/2013.

Association of Current Opioid Use With Serious Adverse Events Among Older Adult Survivors of Breast Cancer.

Importance: National efforts to improve safe opioid prescribing focus on preventing misuse, overdose, and opioid use disorder. This approach overlooks opportunities to better prevent other serious opioid-related harms in complex populations, such as older adult survivors of cancer. Little is known about the rates and risk factors for comprehensive opioid-related harms in this population. Objective: To determine rates of multiple opioid-related adverse drug events among older adults who survived breast cancer and estimate the risk of these events associated with opioid use in the year after completing cancer treatment. Design, Setting, and Participants: This retrospective cohort study used 2007 to 2016 Surveillance, Epidemiology and End Results-Medicare data from fee-for-service Medicare beneficiaries with first cancer diagnosis of stage 0 to III breast cancer at age 66 to 90 years from January 1, 2008, through December 31, 2015, who completed active breast cancer treatment. Data were analyzed from October 31, 2019, to June 10, 2020. Exposures: Repeated daily measure indicating possession of any prescription opioid supply in Medicare Part D prescription claims. Main Outcomes and Measures: Adjusted risk ratios (aRRs), estimated using modified Poisson generalized estimating equation models, for adverse drug events related to substance misuse (ie, diagnosed opioid abuse, dependence, or poisoning), other adverse drug events associated with opioid use (ie, gastrointestinal events, infections, falls and fractures, or cardiovascular events), and all-cause hospitalization associated with opioid supply the prior day, controlling for patient characteristics. Results: Among 38 310 women included in the study (mean [SD] age, 74.3 [6.3] years), there were 0.010 (95% CI, 0.008-0.011) adverse drug events related to substance misuse per 1000 person-days, 0.237 (95% CI, 0.229-0.245) other adverse drug events associated with opioid use per 1000 person-days, and 0.675 (95% CI, 0.662-0.689) all-cause hospitalizations per 1000 person-days. Opioid use was associated with increased risk of adverse drug events related to substance misuse (aRR, 14.62; 95% CI, 9.69-22.05; P < .001), other adverse drug events related to opioid use (aRR, 2.50; 95% CI, 2.11-2.96; P < .001), and all-cause hospitalization (aRR, 2.77; 95% CI, 2.55-3.02; P < .001). In a dose-response effect, individuals with high daily opioid doses had consistently higher risks of all study outcomes compared with individuals who had low opioid doses. Compared with days with no opioid exposure, the risk of any adverse drug event related to substance misuse was 3.4-fold higher for individuals with a current opioid supply ≥50 mg morphine equivalent dose per day (aRR, 3.40; 95% CI, 2.47-4.68; P < .001), while the risk was 2.3-fold higher for individuals with 1 to 49 mg morphine equivalent dose per day (aRR, 2.29; 95% CI, 1.89-2.77; P < .001). Conclusions and Relevance: These findings suggest that among older adults who survived breast cancer, continued prescription opioid use in the year after completing active cancer treatment was associated with an immediate increased risk of a broad range of serious adverse drug events related to substance misuse and other adverse drug events associated with opioid use. Clinicians should consider the comprehensive risks of managing cancer pain with long-term opioid therapy.

Health Insurance Coverage Disruptions and Cancer Care and Outcomes: Systematic Review of Published Research.

BACKGROUND: Lack of health insurance coverage is associated with poor access and receipt of cancer care and survival in the United States. Disruptions in coverage are common among low-income populations, but little is known about associations of disruptions with cancer care, including prevention, screening, and treatment, as well as outcomes of stage at diagnosis and survival. METHODS: We conducted a systematic review of studies of health insurance coverage disruptions and cancer care and outcomes published between 1980 and 2019. We used the PubMed, EMBASE, Scopus, and CINAHL databases and identified 29 observational studies. Study characteristics and key findings were abstracted and synthesized qualitatively. RESULTS: Studies evaluated associations between coverage disruptions and prevention or screening (31.0%), treatment (13.8%), end-of-life care (10.3%), stage at diagnosis (44.8%), and survival (20.7%). Coverage disruptions ranged from 4.3% to 32.8% of patients age-eligible for breast, cervical, or colorectal cancer screening. Between 22.1% and 59.5% of patients with Medicaid gained coverage only at or after cancer diagnosis. Coverage disruptions were consistently statistically significantly associated with lower receipt of prevention, screening, and treatment. Among patients with cancer, those with Medicaid disruptions were statistically significantly more likely to have advanced stage (odds ratios = 1.2-3.8) and worse survival (hazard ratios = 1.28-2.43) than patients without disruptions. CONCLUSIONS: Health insurance coverage disruptions are common and adversely associated with receipt of cancer care and survival. Improved data infrastructure and quasi-experimental study designs will be important for evaluating the associations of federal and state policies on coverage disruptions and care and outcomes.

The impact of generic aromatase inhibitors on initiation, adherence, and persistence among women with breast cancer: Applying multi-state models to understand the dynamics of adherence.

PURPOSE: Clinical trials have clearly documented the survival benefit of aromatase inhibitors (AIs); however, many women fail to initiate (primary nonadherence) or remain adherent to AIs (secondary nonadherence). Prior studies have found that costs impact secondary nonadherence to medications but have failed to examine primary nonadherence. The purpose of this study is to examine primary and secondary adherence following the reduction in copays due to the introduction of generic AIs. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified 50 054 women diagnosed with incident breast cancer between 2008 and 2013. We compare women whose copays would change and those whose would not, due to the receipt of cost-sharing subsidies before and after generics were introduced using a difference-in-difference (DinD) analysis. To examine primary and secondary nonadherence, we rely on a multistate model with four states (Not yet initiated, User, Not Using, and Death). We adjusted for baseline factors using inverse probability treatment weights and then simulated adherence for 36 months following diagnosis. RESULTS: The generic introduction of AIs resulted in patients initiating AIs faster (DinD = -4.7%, 95%CI = -7.0, -2.3; patients not yet initiating treatment at 6-months), being more adherent (DinD ranging in absolute increase of 8.1%-10.4%) and being less likely to not be using the therapy (DinD range in absolute decrease of 1.2% at 6 months to 8.8% at 24 months) for women that do not receive a subsidy after generics were available. CONCLUSIONS: Introduction of generic alternatives to AIs significantly reduced primary and secondary nonadherence.

Effects of Previous Medication Regimen Factors and Bipolar and Psychotic Disorders on Breast Cancer Endocrine Therapy Adherence.

BACKGROUND: Endocrine therapy adherence remains a barrier to optimal estrogen receptor-positive breast cancer outcomes. We theorized that experience navigating difficult medication regimen factors, such as route of administration complexity, might improve subsequent adherence after stressful cancer diagnoses but not for patients with bipolar and psychotic disorders at risk of poor access and nonadherence. MATERIALS AND METHODS: We included 21,894 women aged ≥ 68 years at their first surgically treated stage I-IV estrogen receptor-positive breast cancer (2007-2013) from the Surveillance, Epidemiology, and End Results-Medicare data set, of whom 5.8% had bipolar or psychotic disorders. We required continuous fee-for-service Medicare (parts A and B) data for ≥ 36 months before and 18 months after the cancer diagnosis. The medication regimen factors in the part D claims for 4 months before included the number of all medications used, pharmacy visits, and administration complexity (medication regimen complexity index subscale). Cox regression analysis was used to model the time to initiation and discontinuation, with longitudinal linear regression for adherence to endocrine therapy. RESULTS: Women with more frequent previous medication use and pharmacy visits were more likely to initiate, 4+ medications and 2+ visits versus no medication (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.33-1.63), to adhere (6.0%; 95% CI, 4.3-7.6), and to continuously use their endocrine therapy (discontinuation HR, 0.48; 95% CI, 0.39-0.59). Medication administration complexity had modest effects. Difficult medication regimens were more common for patients with bipolar and psychotic disorders but had no statistically significant effects. CONCLUSIONS: Experience with frequent previous medication use and pharmacy visits might increase the likelihood of endocrine therapy use for most patients but not for those with bipolar and psychotic disorders.

The impact of patient-generated contextual data on communication in clinical practice: A qualitative assessment of patient and clinician perspectives.

BACKGROUND: Effective communication is integral to patient-centered care, yet external pressures can impede the ability to discuss important topics. One strategy to facilitate communication is pre-visit collection and sharing of patient contextual data (PCD), including life circumstances such as their beliefs, needs, and concerns. OBJECTIVE: To understand how patients and care team members perceive the electronic collection of PCD and its impact on communication in the context of a large academic health system that implemented PatientWisdom, a new technology that elicits PCD from patients and integrates within the electronic health record (EHR). METHODS: We conducted focus groups with patients (n = 26) and semi-structured interviews with primary care team members (n = 20). Qualitative analysis of focus group/interviews included an iterative and reflexive inductive technique to uncover emergent themes. RESULTS: Four themes were reflected among both patient and care team: (1) the technology enhances the patient's voice; (2) the technology creates a safe space for patients to share sensitive topics; (3) PCD facilitates rapport not only between patient and provider but the entire care team; (4) PCD aligns patient and clinician goals. Two unique themes emerged among patients: (1) PCD provides opportunity for reflection; (2) PCD humanizes patients in the clinical context. One theme was evident in provider comments: collecting PCD may potentially undermine trust if not reviewed by clinical teams. CONCLUSION: PCD collected directly from patients and available within the EHR was seen by patients and care team members as beneficial to communication. PCD collection supports a paradigm shift towards coproduction of health information and a shared responsibility for information gathering but requires investment from patients and care team to ensure the data are effectively utilized. PRACTICE VALUE: PCD may be useful for team-based care, enabling physicians and non-physician staff to more quickly and responsively connect with patients.

New-onset persistent opioid use following breast cancer treatment in older adult women.

BACKGROUND: Patients with cancer-related pain are underrepresented in the opioid literature despite high opioid exposure and numerous risk factors for adverse opioid outcomes, including unnecessary persistent opioid use. The objective of this study was to determine the extent, historical trends, and predictors of new-onset persistent opioid use among older adult women after active breast cancer treatment. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data for opioid-naive women diagnosed with stage 0 to III breast cancer at the age of 66 to 90 years between 2008 and 2013, this study estimated overall and quarterly adjusted probabilities of new-onset persistent opioid use, which was defined as receiving ≥90 days' supply of opioids in the year after active breast cancer treatment. Sensitivity analyses were conducted with an alternative definition of persistent opioid use: any opioid fill 90 to 180 days after active cancer treatment. RESULTS: Nearly two-thirds of the subjects received prescription opioid therapy during cancer treatment. Quarterly probabilities of new-onset persistent opioid use after active treatment ranged from 2% to 4%; in sensitivity analyses, the alternative outcome definition resulted in predicted probabilities ranging from 11.4% to 14.7%. Subjects with more advanced disease, a higher comorbidity burden, a low-income status, and greater opioid exposure during active cancer treatment were more likely to develop persistent opioid use. CONCLUSIONS: Persistent opioid use was an infrequent occurrence among older adult patients with breast cancer completing cancer treatment between 2008 and 2013. This finding was encouraging because of the concerning opioid trends seen in noncancer populations. However, opportunities to further mitigate unsafe opioid use as a complication of cancer care, including standardization of persistent opioid use definitions, should be explored.

Temporal trends and regional variation in the utilization of low-value breast cancer care: has the Choosing Wisely campaign made a difference?

PURPOSE: Since 2012, about 80 specialty societies have released Choosing Wisely (CW) recommendations aimed at reducing the use of low-value, unproven, or ineffective medical services. The extent to which these recommendations have influenced the behavior of physicians and patients remains largely unknown. METHODS: Using MarketScan Commercial Claims and Medicare Supplemental and Coordination of Benefits databases, we identified annual cohorts of women with incident, early-stage breast cancer and estimated the prevalence of four initial treatment and six surveillance metrics deemed as low-value breast cancer care by CW. Multivariable logistic regressions were subsequently used to estimate temporal trends and regional variation in the use of these metrics, with a special focus on the year of CW's publication. RESULTS: There were 122,341 women identified as undergoing treatment for incident breast cancer between 2010 and 2014. Two of the four low-value initial treatment metrics and four of the six low-value surveillance metrics declined significantly over time. The temporal trend of declining use, however, preceded the release of CW's guidelines. Declines ranged from 11.0% for follow-up mammography to 40.6% for receipt of surgical biopsy without an attempted needle biopsy. There were marked regional differences in use of low-value breast cancer care for all metrics, much of which persisted after publication of CW. CONCLUSIONS: With two notable exceptions, use of low-value breast cancer care has declined steadily since 2010. The declines, however, were not accelerated by the publication of CW recommendations.

Effect of Sociodemographic Factors on Uptake of a Patient-Facing Information Technology Family Health History Risk Assessment Platform.

OBJECTIVE: Investigate sociodemographic differences in the use of a patient-facing family health history (FHH)-based risk assessment platform. METHODS: In this large multisite trial with a diverse patient population, we evaluated the relationship between sociodemographic factors and FHH health risk assessment uptake using an information technology (IT) platform. The entire study was administered online, including consent, baseline survey, and risk assessment completion. We used multivariate logistic regression to model effect of sociodemographic factors on study progression. Quality of FHH data entered as defined as relatives: (1) with age of onset reported on relevant conditions; (2) if deceased, with cause of death and (3) age of death reported; and (4) percentage of relatives with medical history marked as unknown was analyzed using grouped logistic fixed effect regression. RESULTS: A total of 2,514 participants consented with a mean age of 57 and 10.4% minority. Multivariate modeling showed that progression through study stages was more likely for younger (p-value = 0.005), more educated (p-value = 0.004), non-Asian (p-value = 0.009), and female (p-value = 0.005) participants. Those with lower health literacy or information-seeking confidence were also less likely to complete the study. Most significant drop-out occurred during the risk assessment completion phase. Overall, quality of FHH data entered was high with condition's age of onset reported 87.85%, relative's cause of death 85.55% and age of death 93.76%, and relative's medical history marked as unknown 19.75% of the time. CONCLUSION: A demographically diverse population was able to complete an IT-based risk assessment but there were differences in attrition by sociodemographic factors. More attention should be given to ensure end-user functionality of health IT and leverage electronic medical records to lessen patient burden.

Implementation, adoption, and utility of family health history risk assessment in diverse care settings: evaluating implementation processes and impact with an implementation framework.

PURPOSE: This paper describes the implementation outcomes associated with integrating a family health history-based risk assessment and clinical decision support platform within primary care clinics at four diverse healthcare systems. METHODS: A type III hybrid implementation-effectiveness trial. Uptake and implementation processes were evaluated using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. RESULTS: One hundred (58%) primary care providers and 2514 (7.8%) adult patients enrolled. Enrolled patients were 69% female, 22% minority, and 32% Medicare/Medicaid. Compared with their respective clinic's population, patient-participants were more likely to be female (69 vs. 59%), older (mean age 57 vs. 49), and Caucasian (88 vs. 69%) (all p values <0.001). Female (81.3% of females vs. 78.5% of males, p value = 0.018) and Caucasian (Caucasians 90.4% vs. minority 84.1%, p value = 0.02) patient-participants were more likely to complete the study once enrolled. Patient-participant survey responses indicated MeTree was easy to use (95%), and patient-participants would recommend it to family/friends (91%). Minorities and those with less education reported greatest benefit. Enrolled providers reflected demographics of underlying provider population. CONCLUSION: Family health history-based risk assessment can be effectively implemented in diverse primary care settings and can effectively engage patients and providers. Future research should focus on finding better ways to engage young adults, males, and minorities in preventive healthcare.

Using Group-based Trajectory Models and Propensity Score Weighting to Detect Heterogeneous Treatment Effects: The Case Study of Generic Hormonal Therapy for Women With Breast Cancer.

BACKGROUND: We extend an interrupted time series study design to identify heterogenous treatment effects using group-based trajectory models (GBTMs) to identify groups before a new policy and then examine if the effects of the policy has consistent impacts across groups using propensity score weighting to balance individuals within trajectory groups who are and are not exposed to the policy change. We explore this by examining how adherence to endocrine therapy (ET) for women with breast cancer was impacted by reducing copayments for medications by the introduction of generic ETs among women who do not receive a subsidy (the "treatment" group) to those that do receive a subsidy and are not exposed to any changes in copayments (the "control" group). METHODS: We examined monthly adherence to ET using the proportion of days covered for women diagnosed with breast cancer between 2008 and 2009 using SEER-Medicare data. To account for baseline trends, we characterize adherence for 1 year before generic approval of ET using GBTMs, within each groups we generate inverse probability treatment weights of not receiving a subsidy. We compared adherence after generic entry within each GBTM using a modified Poisson model. RESULTS: GBTMs for adherence in the 1-year pregeneric identified 6 groups. When comparing patients who did and did not receive a subsidy we found no overall effect of generic introduction. However, 1 of the 6 identified adherence groups postgeneric adherence increased [the "consistently low" (risk ratio=1.91; 95% confidence interval=1.34-2.72)]. CONCLUSIONS: This study describes a new approach to identify heterogenous effects when using an interrupted time series research design.

The association of socioeconomic status with receipt of neoadjuvant chemotherapy.

BACKGROUND: There are advantages to neoadjuvant chemotherapy in operable breast cancer, particularly for those with higher-risk cancers, but little is known about factors that are associated with the use of neoadjuvant chemotherapy outside of clinical trials. We examined whether use of neoadjuvant chemotherapy instead of adjuvant chemotherapy varies by nonclinical factors such as patient socioeconomic status or rural residence. METHODS: Women diagnosed with breast cancer in 2013-2014 at eight medical institutions were surveyed by mail regarding their experiences with breast cancer treatment, and this information was linked to hospital-based cancer registries. We examined the use of neoadjuvant chemotherapy among women with histologically confirmed invasive stage I-III breast cancer and used regression models to examine the association of socioeconomic status with chemotherapy timing. We also explored potential mechanisms for those differences. RESULTS: Over 29% of the chemotherapy sample overall received neoadjuvant chemotherapy. Neoadjuvant receipt was lower for those with income < $100,000 (AOR 0.56, 95% CI 0.2-0.9) even with adjustment for other demographics, stage, and biomarker status, and findings for education and a variable for both lowest education and income < $100,000 were similar. Rural/urban residence was not associated with neoadjuvant receipt. Differences by income in perceptions of the importance of neoadjuvant chemotherapy advantages and disadvantages did not appear to explain the differences in use by income. CONCLUSIONS: In a multicenter sample of breast cancer patients, lower income was strongly associated with less receipt of neoadjuvant chemotherapy. Since patients with lower socioeconomic status are more likely to present with later-stage disease, this pattern has the potential to contribute to breast cancer outcome disparities.

Are aromatase inhibitors associated with higher myocardial infarction risk in breast cancer patients? A Medicare population-based study.

BACKGROUND: Theoretically, the estrogen deprivation induced by aromatase inhibitors (AIs) might cause ischemic heart disease, but empiric studies have shown mixed results. We aimed to compare AIs and tamoxifen with regard to cardiovascular events among older breast cancer patients outside of clinical trials. We hypothesized that AIs increase the risk of myocardial infarction. METHODS: We identified women age ≥67 years diagnosed with breast cancer from June 30, 2006 to June 1, 2008 in the surveillance, epidemiology, and end results (SEER)-Medicare database, treated with either tamoxifen or an AI, and followed through December 31, 2012. To compare myocardial infarction (MI) risk for the treatment groups of AIs vs tamoxifen, we developed and assigned stabilized probability of treatment weights and used the Fine and Gray model for time to MI with death not related to MI as a competing risk. RESULTS: Of the cohort of 5648 women, 4690 were treated with AIs and 958 with tamoxifen; a total of 251 patients developed MI, and 22 patients died of MI during the study period while 476 died of other causes. The hazard for MI was not significantly different between AI vs tamoxifen groups (HR = 1.01, 95% CI 0.72-1.42), after adjusting for the following known MI risk factors at the start of adjuvant therapy: diabetes, ischemic heart disease, congestive heart failure, MI, and peripheral vascular disease. CONCLUSIONS: In this SEER-Medicare-based population study, there were no significant differences in the risk of MI between AI and tamoxifen users after adjustment for known risk factors.

Fractures in a nationwide population-based cohort of users of breast cancer hormonal therapy.

PURPOSE: Although users of aromatase inhibitors have higher total fracture risk in some randomized trials, little is known about their risk outside of clinical trials or in older higher-risk cohorts. METHODS: In a population-based retrospective cohort study, we identified all older US Medicare D prescription drug insurance plan-enrolled women who had initial breast cancer surgery in 2006-2008 and began hormonal therapy (an aromatase inhibitor (AI) or tamoxifen) within the subsequent year. Total nonvertebral and hip fractures through 2012 were identified using a validated algorithm. The association of fracture outcomes with hormonal therapy type was assessed using competing risk regression models that accounted for differences in measured baseline covariates. Treatment assignment bias was reduced using inverse probability of treatment weighting computed from propensity scores. RESULTS: Among 23,378 women taking hormonal therapy (23.2% aged 80 or over), there were 3000 total and 436 hip fractures. Although AI users were younger and had lower comorbidity, after propensity score weighting, these and other covariates were balanced. Total nonvertebral risk was higher for users of AIs compared with tamoxifen, HR 1.11 (1.02-1.21), but the small increase in risk for hip fracture was not statistically significant, HR 1.04 (0.84-1.30). CONCLUSIONS: Although total nonvertebral fracture risk was higher among AI users, differences in hip fractures were not significant in a large population-based cohort of older women. IMPLICATIONS FOR CANCER SURVIVORS: Use of aromatase inhibitors by older women is associated with high risk for nonvertebral fracture that is increased compared with use of tamoxifen. Fracture risk should be assessed among patients taking these medications.