Gene Therapy Versus Common Care for Eligible Individuals With Sickle Cell Disease in the United States : A Cost-Effectiveness Analysis.

BACKGROUND: Sickle cell disease (SCD) and its complications contribute to high rates of morbidity and early mortality and high cost in the United States and African heritage community. OBJECTIVE: To evaluate the cost-effectiveness of gene therapy for SCD and its value-based prices (VBPs). DESIGN: Comparative modeling analysis across 2 independently developed simulation models (University of Washington Model for Economic Analysis of Sickle Cell Cure [UW-MEASURE] and Fred Hutchinson Institute Sickle Cell Disease Outcomes Research and Economics Model [FH-HISCORE]) using the same databases. DATA SOURCES: Centers for Medicare & Medicaid Services claims data, 2008 to 2016; published literature. TARGET POPULATION: Persons eligible for gene therapy. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care sector and societal. INTERVENTION: Gene therapy versus common care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs), equity-informed VBPs, and price acceptability curves. RESULTS OF BASE-CASE ANALYSIS: At an assumed $2 million price for gene therapy, UW-MEASURE and FH-HISCORE estimated ICERs of $193 000 per QALY and $427 000 per QALY, respectively, under the health care sector perspective. Corresponding estimates from the societal perspective were $126 000 per QALY and $281 000 per QALY. The difference in results between models stemmed primarily from considering a slightly different target population and incorporating the quality-of-life (QOL) effects of splenic sequestration, priapism, and acute chest syndrome in the UW model. From a societal perspective, acceptable (>90% confidence) VBPs ranged from $1 million to $2.5 million depending on the use of alternative effective metrics or equity-informed threshold values. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the costs of myeloablative conditioning before gene therapy, effect on caregiver QOL, and effect of gene therapy on long-term survival. LIMITATION: The short-term effects of gene therapy on vaso-occlusive events were extrapolated from 1 study. CONCLUSION: Gene therapy for SCD below a $2 million price tag is likely to be cost-effective when applying a societal perspective at an equity-informed threshold for cost-effectiveness analysis. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

BACKGROUND: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments. MATERIALS AND METHODS: We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights. RESULTS: Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04). CONCLUSIONS: Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.

Developing a urinary incontinence primary care pathway: a mixed methods study.

BACKGROUND: While nearly 50% of adult women report at least one episode of urinary incontinence (UI), most never receive treatment. OBJECTIVE: To better integrate primary and specialty UI care, we conducted (i) an environmental scan to assess the availability of key pathway resources in primary care, (ii) interviews with primary care providers to understand barriers to care, and (iii) a pilot UI care pathway intervention. METHODS: Environmental scan: Clinic managers from all primary care clinics within a Midwestern healthcare system were invited to participate in an interview covering the availability of clinic resources. Provider interviews: Primary care providers were invited to participate in an interview covering current practices and perceived barriers to UI care. Pilot UI care pathway: Patients who screened positive for UI were provided resources for first-line behavioral management. Pilot patients completed questionnaires at baseline, 8 weeks, and 6 months. RESULTS: While many clinics had point-of-care urinalysis (17/21, 81%), most did not have a working bladder ultrasound (14/21, 67%) or on-site pelvic floor physical therapy (18/21, 86%). Providers (n = 5) described barriers to completing almost every step of diagnosis and treatment for UI. The most persistent barrier was lack of time. Patients (n = 15) reported several self-treatment strategies including avoiding bladder irritants (7/15, 47%) and performing Kegel exercises (4/15, 27%). Five patients (33%) requested follow-up care. At 6 months, patients reported small improvements in UI symptoms. CONCLUSION: Promising results from a novel UI care pathway pilot indicate that streamlining UI care may assist primary care providers in the first-line treatment of UI.

Although the majority of women will experience urine leakage at some point during their lives, most will never receive treatment. To better understand this discrepancy, we embarked on a multimodal investigation into the barriers to care and trialed a new treatment pathway in the primary care setting within a large academic medical system in the Midwest. Speaking with the clinic managers from 21 primary care clinics, we determined that many clinics lacked the tools to perform the steps outlined in the professional society guidelines for urinary incontinence diagnosis. Additionally, there was limited access to pelvic floor physical therapy, a proven treatment strategy. Interviews with five primary care providers revealed barriers, most notably lack of time during clinic visits, to almost every step of diagnosis and treatment. Finally, we trialed a care pathway for primary care providers to make it easier to provide patients with self-management education or to refer them to specialist care. Fifteen patients participated in a pilot study, about half reported trying self-management, and about 1/3 requested follow-up care. Streamlining urinary incontinence care at the primary care level may alleviate some of the barriers to patients receiving care.

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.

Racial and Ethnic Differences in Medication Initiation Among Adults Newly Diagnosed with Type 2 Diabetes.

OBJECTIVE: Given persistent racial/ethnic differences in type 2 diabetes outcomes and the lasting benefits conferred by early glycemic control, we examined racial/ethnic differences in diabetes medication initiation during the year following diagnosis. METHODS: Among adults newly diagnosed with type 2 diabetes (2005-2016), we examined how glucose-lowering medication initiation differed by race/ethnicity during the year following diagnosis. We specified modified Poisson regression models to estimate the association between race/ethnicity and medication initiation in the entire cohort and within subpopulations defined by HbA1c, BMI, age at diagnosis, comorbidity, and neighborhood deprivation index (a census tract-level socioeconomic indicator). RESULTS: Among the 77,199 newly diagnosed individuals, 47% started a diabetes medication within 12 months of diagnosis. The prevalence of medication initiation ranged from 32% among Chinese individuals to 58% among individuals of Other/Unknown races/ethnicities. Compared to White individuals, medication initiation was less likely among Chinese (relative risk: 0.78 (95% confidence interval 0.72, 0.84)) and Japanese (0.82 (0.75, 0.90)) individuals, but was more likely among Hispanic/Latinx (1.27 (1.24, 1.30)), African American (1.14 (1.11, 1.17)), other Asian (1.13 (1.08, 1.18)), South Asian (1.10 (1.04, 1.17)), Other/Unknown (1.31 (1.24, 1.39)), American Indian or Alaska Native (1.11 (1.04, 1.18)), and Native Hawaiian/Pacific Islander (1.28 (1.19, 1.37)) individuals. Racial/ethnic differences dissipated among individuals with higher HbA1c values. CONCLUSIONS: Initiation of glucose-lowering treatment during the year following type 2 diabetes diagnosis differed markedly by race/ethnicity, particularly for those with lower HbA1c values. Future research should examine how patient preferences, provider implicit bias, and shared decision-making contribute to these early treatment differences.

First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study.

BACKGROUND: Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo-based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

The Longer-Term Benefits and Harms of Glucagon-Like Peptide-1 Receptor Agonists: a Systematic Review and Meta-Analysis.

BACKGROUND: Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov (inception-July 2019) for randomized controlled trials ≥ 52 weeks' duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80-0.90), macrovascular complications (including stroke, RR 0.86, 0.78-0.95), and mortality (RR 0.89, 0.84-0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons. DISCUSSION: GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.

Longer-term Benefits and Risks of Sodium-Glucose Cotransporter-2 Inhibitors in Type 2 Diabetes: a Systematic Review and Meta-analysis.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) are a recent class of medication approved for the treatment of type 2 diabetes (T2D). Previous meta-analyses have quantified the benefits and harms of SGLT2Is; however, these analyses have been limited to specific outcomes and comparisons and included trials of short duration. We comprehensively reviewed the longer-term benefits and harms of SGLT2Is compared to placebo or other anti-hyperglycemic medications. METHODS: We searched PubMed, Scopus, and clinicaltrials.gov from inception to July 2019 for randomized controlled trials of minimum 52 weeks' duration that enrolled adults with T2D, compared an SGLT2I to either placebo or other anti-hyperglycemic medications, and reported at least one outcome of interest including cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events. We conducted random effects meta-analyses to provide summary estimates using weighted mean differences (MD) and pooled relative risks (RR). The study was registered a priori with PROSPERO (CRD42018090506). RESULTS: Fifty articles describing 39 trials (vs. placebo, n = 28; vs. other anti-hyperglycemic medication, n = 12; vs. both, n = 1) and 112,128 patients were included in our analyses. Compared to placebo, SGLT2Is reduced cardiovascular risk factors (e.g., hemoglobin A1c, MD - 0.55%, 95% CI - 0.62, - 0.49), macrovascular outcomes (e.g., hospitalization for heart failure, RR 0.70, 95% CI 0.62, 0.78), and mortality (RR 0.87, 95% CI 0.80, 0.94). Compared to other anti-hyperglycemic medications, SGLT2Is reduced cardiovascular risk factors, but insufficient data existed for other outcomes. About a fourfold increased risk of genital yeast infections for both genders was observed for comparisons vs. placebo and other anti-hyperglycemic medications. DISCUSSION: We found that SGLT2Is led to durable reductions in cardiovascular risk factors compared to both placebo and other anti-hyperglycemic medications. Reductions in macrovascular complications and mortality were only observed in comparisons with placebo, although trials comparing SGLT2Is vs. other anti-hyperglycemic medications were not designed to assess longer-term outcomes.

Concurrent prescribing of opioids with other sedating medications after cancer diagnosis: a population-level analysis.

PURPOSE: Cancer is a major reason for concurrent prescription of opioids with other sedating medications-particularly benzodiazepines and gabapentinoids-yet population-based assessments of the extent and predictors of concurrent prescribing among clinically and demographically diverse patients with cancer are lacking. METHODS: We conducted a retrospective cohort study of patients with non-metastatic cancer using North Carolina cancer registry data linked with Medicare and private insurance claims (2013-2016). We used modified Poisson regression to assess associations of patient characteristic with adjusted relative risk (aRR) of new concurrent prescribing of opioids with benzodiazepines or gabapentinoids after diagnosis. RESULTS: Overall, 15% of patients were concurrently prescribed opioids with benzodiazepines or gabapentinoids. Characteristics independently associated with an increased risk of concurrent prescribing included cancer type (e.g., aRR cervical vs. colorectal cancer: 1.55, 95% CI: 1.12-2.14); prior use of opioids (aRR: 2.43, 95% CI:2.21-2.67), benzodiazepines (aRR: 4.08, 95% CI: 3.72-4.48), or gabapentinoids (3.82, 95% CI: 3.31-4.39), and premorbid mental health conditions, including substance use disorder (aRR: 1.27, 95% CI: 1.05-1.54). Black and Hispanic patients were less likely to experience concurrent prescribing (aRR, Black vs. White: 0.35, 95% CI: 0.15-0.83; aRR, Hispanic vs. White: 0.75, 95% CI: 0.66-0.85). CONCLUSION: Approximately 1 in 7 patients with cancer was concurrently prescribed opioids with other sedating medications. Associations between patient characteristics and risk of concurrent prescribing highlight predictors of concurrent prescribing and suggest a rationale for systematic assessment of substance use history at diagnosis. Future research could explore inequitable pain and symptom management and investigate risk of adverse medication-related events.

Feasibility of a pharmacist-led symptom monitoring and management intervention to improve breast cancer endocrine therapy adherence.

BACKGROUND: Adjuvant endocrine therapy (AET) for breast cancer reduces mortality, but one-third to one-half of patients discontinue it early or are nonadherent. OBJECTIVE: We developed a pilot single-site study of patients with evidence of early nonadherence to AET to assess the feasibility of a novel, clinical pharmacist-led intervention targeting symptom and medication management. METHODS: Patients with prescription fill records showing nonadherence were enrolled in a single-arm feasibility study. Automated reminders were sent by e-mail or text with a link to symptom monitoring assessments weekly for 1 month and monthly until 6 months. Clinical oncology pharmacists used guideline-based symptom management and other medication management tools to support adherence and ameliorate symptoms reported on the assessments. Patient-reported outcome assessments included physical, mental, and social health domains and self-efficacy to manage symptoms and medications. Feasibility outcomes included completion of symptom reports and pharmacist recommendations. RESULTS: Of 19 participants who were nonadherent who enrolled and completed initial assessments, 18 completed all final study procedures, with 14 completing all assessments and no patient missing more than 3 assessments. All 18 participants reported at least one of 3 symptom types, and the majority reported attempting pharmacist recommendations. Patient-reported measures of physical, mental, and social health and self-efficacy improved, and 44% of the patients became adherent. CONCLUSION: An intervention using pharmacists in an oncology practice to systematically monitor and manage symptoms shows promise to reduce symptoms, enhance support and self-efficacy, and improve adherence to AET.

The costs of treating and not treating patients with chronic myeloid leukemia with tyrosine kinase inhibitors among Medicare patients in the United States.

BACKGROUND: Patients with high cost-sharing of tyrosine kinase inhibitors (TKIs) experience delays in treatment for chronic myeloid leukemia (CML). To the authors' knowledge, the clinical outcomes among and costs for patients not receiving TKIs are not well defined. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors evaluated differences in TKI initiation, health care use, cost, and survival among patients with CML with continuous Medicare Parts A and B and Part D coverage who were diagnosed between 2007 and 2015. RESULTS: A total of 941 patients were included. Approximately 29% of all patients did not initiate treatment with TKIs within 6 months (non-TKI users), and had lower rates of BCR-ABL testing and more hospitalizations compared with TKI users. Approximately 21% were not found to have any TKI claims at any time. TKI initiation rates within 6 months of diagnosis increased for all patients over time (61% to 85%), with greater improvements observed in patients receiving subsidies (55% to 90%). Total Medicare costs were greater in patients treated with TKIs, with approximately 50% because of TKI costs. Non-TKI users had more inpatient costs compared with TKI users. Trends in cost remained significant when adjusting for age and comorbidities. The median overall survival was 40 months (95% confidence interval [95% CI], 34-48 months) compared with 86 months (95% CI, 73 months to not reached), respectively, for non-TKI users versus TKI users, a finding that remained consistent when adjusting for age, comorbidities, and subsidy status (hazard ratio, 2.23; 95% CI, 1.77-2.81). CONCLUSIONS: Approximately 21% of all patients with CML did not receive TKIs at any time. Cost-sharing subsidies consistently are found to be associated with higher initiation rates. Non-TKI users had higher inpatient costs and poorer survival outcomes. Interventions to lower TKI costs for all patients are desirable.

Personal Payments from Pharmaceutical Companies to Authors of Oncology Clinical Practice Guidelines.

BACKGROUND: Oncologists who author clinical practice guidelines frequently have financial relationships with the pharmaceutical industry. It is unknown whether participation on clinical practice guideline committees is associated with differences in the amounts of industry money received. MATERIALS AND METHODS: We conducted a nested case-control study from August 2013 to December 2018. We manually abstracted membership records of National Comprehensive Cancer Network (NCCN) Guidelines committees for the 20 most common cancers and linked to Open Payments. The study sample included medical oncologists selected to join an NCCN Guidelines committee ("joiners") during the study period. Joiners were matched 1:2 to medical oncologists who had no participation on NCCN committees (controls) by gender, NCCN institution, and medical school graduation year. We performed difference-in-differences (DiD) estimation to assess whether selection to an NCCN committee was associated with the dollar value of payments received from industry, using generalized estimating equations to address correlation between matched pairs and between repeated observations of the same pair. RESULTS: During the study period, 54 physicians joined an NCCN Guidelines committee. These physicians received more payments than matched controls in the year prior to joining ($11,259 vs. $3,427; p = .02); this difference did not increase in the year after joining (DiD = $731; p = .45). CONCLUSION: Medical oncologists selected to NCCN Guidelines committees had greater financial ties to industry than their peers. The potential influence of industry in oncology clinical practice guidelines may be reduced through the selection of committee members with fewer ties to industry. IMPLICATIONS FOR PRACTICE: Oncologists who author clinical practice guidelines frequently have financial conflicts of interest with the pharmaceutical industry. This creates concern about the potential for industry influence on guidelines. However, it is unknown whether oncologists who author guidelines have greater industry relationships than their peers. This study compared medical oncologists who were newly selected to join a National Comprehensive Cancer Network (NCCN) Guidelines panel with medical oncologists at the same institutions and at similar career stages. At the time they joined, oncologists joining NCCN Guidelines panels had received more than three times the dollar value of industry payments than their peers. The potential for industry influence may be reduced by the selection of less-conflicted panel members.

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.

Impact of Pre-visit Contextual Data Collection on Patient-Physician Communication and Patient Activation: a Randomized Trial.

BACKGROUND: Patient contextual data (PCD) are often missing from electronic health records, limiting the opportunity to incorporate preferences and life circumstances into care. Engaging patients through tools that collect and summarize such data may improve communication and patient activation. However, differential tool adoption by race might widen health care disparities. OBJECTIVE: Determine if a digital tool designed to collect and present PCD improves communication and patient activation; secondarily, evaluate if use impacts outcomes by race. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic, two-armed, non-blinded, randomized controlled trial conducted during 2019 in a primary care setting. INTERVENTION: The PCD tool (PatientWisdom) invited patients to identify preferences, values, goals, and barriers to care. Patients were randomized to a standard pre-visit email or facilitated enrollment with dedicated outreach to encourage use of the tool. MAIN OUTCOMES AND MEASURES: Outcomes of interest were post-visit patient communication and patient activation measured by the Communication Assessment Tool (CAT) and Patient Activation Measure (PAM), respectively. Outcomes were evaluated using treatment-on-the-treated (TOT) and intention-to-treat (ITT) principles. KEY RESULTS: A total of 301 patients were enrolled. Facilitated enrollment resulted in a five-fold increase in uptake of the PCD tool. TOT analysis indicated that the PCD tool was associated with notable increases in specific CAT items rated as excellent: "treated me with respect" (+ 13 percentage points; p = 0.04), "showed interest in my ideas" (+ 14 percentage points; p = 0.03), "showed care and concern" (+ 16 percentage points; p = 0.02), and "spent about the right amount of time with me" (+ 11 percentage points; p = 0.05). There were no significant pre/post-visit differences in PAM scores between arms (- 4.41 percentage points; p = 0.58). ITT results were similar. We saw no evidence of the treatment effect varying by race in ITT or TOT analyses. CONCLUSIONS AND RELEVANCE: The inclusion of PCD enhanced essential aspects of patient-provider communication but did not affect patient activation. Outcomes did not differ by race. TRIAL REGISTRATION: Clincaltrials.gov identifier: NCT03766841.

Clinician burnout during the COVID-19 pandemic before vaccine administration.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has disrupted pharmacy practice. Little research has been done to assess how COVID-19 has affected pharmacists' employment, workload, and feelings of burnout. OBJECTIVES: The objectives of this study were to characterize the impact of COVID-19 on pharmacists' employment status, workload, and feelings of burnout, as well as to examine emotional health concerns related to COVID-19. METHODS: Wisconsin pharmacists were surveyed using an online instrument between August 25, 2020, and September 22, 2020. The data analysis, performed in December 2020, examined employment status, 3 common burnout risk factors (workload, rewards, and social depersonalization), and emotional health concerns related to COVID-19. RESULTS: Of the 1300 pharmacists, 439 completed the survey (33.8%). The study analysis included pharmacists in community (n = 127) and hospital or health system (n = 107) settings. With regard to employment changes and workload, hospital pharmacists (36%) were more likely to have their hours reduced than community pharmacists (13%) (P < 0.01), and, conversely, community pharmacists (19%) were more likely to have their hours increased than hospital pharmacists (8%) (P = 0.01). For the burnout domain of workload, 45% of the pharmacists reported increased feelings of physical exhaustion at work, and 53% reported increased feelings of emotional exhaustion at work, with no difference between settings. Regarding the burnout domain of rewards, 6% of the hospital pharmacists and 1% of the community pharmacists experienced a reduction in hourly wages or salaries as a result of COVID-19. For the burnout domain of depersonalization, 25% of the pharmacists reported that their ability to connect with colleagues and patients decreased during the COVID-19 pandemic. Additional emotional health concerns reported by the pharmacists included 40% experiencing more anxiety and 25% experiencing more sadness or depression during the COVID-19 pandemic, with no difference between settings. CONCLUSION: This study found that the burnout domains related to workload, rewards, and depersonalization were negatively affected by COVID-19. Pharmacy managers need to proactively combat burnout as well as be reactive when employees show signs of burnout to maintain their workforce and meet the COVID-19-associated challenges.

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.

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.

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.

Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology.

BACKGROUND: Financial relationships between physicians and the pharmaceutical industry are common, but factors that may determine whether such relationships result in physician practice changes are unknown. MATERIALS AND METHODS: We evaluated physician use of orally administered cancer drugs for four cancers: prostate (abiraterone, enzalutamide), renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (afatinib, erlotinib), and chronic myeloid leukemia (CML; dasatinib, imatinib, nilotinib). Separate physician cohorts were defined for each cancer type by prescribing history. The primary exposure was the number of calendar years during 2013-2015 in which a physician received payments from the manufacturer of one of the studied drugs; the outcome was relative prescribing of that drug in 2015, compared with the other drugs for that cancer. We evaluated whether practice setting at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center, receipt of payments for purposes other than education or research (compensation payments), maximum annual dollar value received, and institutional conflict-of-interest policies were associated with the strength of the payment-prescribing association. We used modified Poisson regression to control confounding by other physician characteristics. RESULTS: Physicians who received payments for a drug in all 3 years had increased prescribing of that drug (compared with 0 years), for renal cell (relative risk [RR] 1.81, 95% confidence interval [CI] 1.58-2.07), CML (RR 1.22, 95% CI 1.08-1.39), and lung (RR 1.69, 95% CI 1.58-1.82), but not prostate (RR 0.97, 95% CI 0.93-1.02). Physicians who received compensation payments or >$100 annually had increased prescribing compared with those who did not, but NCI setting and institutional conflict-of-interest policies were not consistently associated with the direction of prescribing change. CONCLUSION: The association between industry payments and cancer drug prescribing was greatest among physicians who received payments consistently (within each calendar year). Receipt of payments for compensation purposes, such as for consulting or travel, and higher dollar value of payments were also associated with increased prescribing. IMPLICATIONS FOR PRACTICE: Financial payments from pharmaceutical companies are common among oncologists. It is known from prior work that oncologists tend to prescribe more of the drugs made by companies that have given them money. By combining records of industry gifts with prescribing records, this study identifies the consistency of payments over time, the dollar value of payments, and payments for compensation as factors that may strengthen the association between receiving payments and increased prescribing of that company's drug.

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.