A primer on quality measurement and reporting in pharmacy benefit plans.

Pharmacy benefit plans in the United States are evaluated on quality measures and other requirements of the government and accrediting organizations. This primer describes the roles of key organizations involved in measuring and reporting quality in pharmacy benefit plans and explains the methods that pharmacy benefit plans use to promote quality of medication use.

Association between adherence with oral anticancer medications and short-term health care resource utilization: A 2010-2018 claims-based analysis.

BACKGROUND: There is limited evidence on the effect of adherence to oral anticancer medications on health care resource utilization (HRU) among patients with cancer. OBJECTIVE: To determine the association between adherence to oral anticancer medication and subsequent HRU. METHODS: A retrospective cohort study was conducted using Optum Clinformatics® Data Mart commercial claims database. Patients who initiated an oral anticancer medication between 2010 and 2017 were included. Proportion of days covered was used to calculate medication adherence in the first 6 months after oral anticancer medication initiation. All-cause HRU in the following 6 months was assessed. Multivariable negative binomial regressions were used to determine the association between oral anticancer medication adherence and HRU, after controlling for confounders. RESULTS: Of 37,938 patients, 51.9% were adherent to oral anticancer medications. Adherence with oral anticancer medication was significantly associated with more frequent physician office and outpatient visits for several cancer types with the strongest association among those with liver cancer (adjusted incidence rate ratio [aIRR] = 1.34; 95% CI = 1.18-1.52 and aIRR = 1.32; 95% CI = 1.13-1.55, respectively). Oral anticancer medication adherence was associated with more emergency department visits only among patients with lung cancer (aIRR = 1.22; 95% CI = 1.01-1.48). Oral anticancer medication adherence was significantly associated with a higher rate of inpatient hospitalizations and longer stays among patients with liver cancer (aIRRs were 1.45 [95% CI = 1.02-2.05] and 2.15 [95% CI = 1.21-3.81], respectively), whereas hospitalizations were fewer and length of stay was shorter among patients with colorectal cancer who were adherent with oral anticancer medication (aIRRs were 0.77 [95% CI = 0.68-0.86] and 0.77 [95% CI = -0.66 to 0.90], respectively). Other measures did not reveal statistically significant differences in HRU among adherent and nonadherent patients for the cancer types included in the study. CONCLUSIONS: HRU following the initial phase of oral anticancer medication therapy was generally similar among adherent and nonadherent patients. We observed a slightly higher rate of office and outpatient visits among adherent patients, which may reflect ongoing monitoring among patients continuing oral anticancer medication. Further studies are needed to determine how oral anticancer medication adherence may affect HRU over a longer time period.

Tramadol utilization among patients with higher risk of adverse drug events: A claims analysis of commercially insured and Medicare Advantage members.

OBJECTIVE: To assess prescribing of tramadol among patients with contraindications and higher risks of adverse events in a large population of commercially insured and Medicare Advantage members. DESIGN: We performed a cross-sectional analysis evaluating tramadol utilization in patients with higher risk of adverse outcomes. SETTING: This study utilized 2016-2017 data from the Optum Clinformatics Data Mart. PATIENTS AND PARTICIPANTS: Patients with at least one tramadol prescription without a cancer or sickle cell diagnosis during the study period. MAIN OUTCOME MEASURES: We first determined if tramadol was prescribed among patients with contraindications or risk factors for adverse outcomes. We then determined if patient demographic or clinical factors were associated with the use of tramadol in these higher-risk scenarios using multivariable logistic regression models. RESULTS: Among patients with at least one prescription for tramadol, 19.66 percent (99 percent CI: 19.57-19.75) concurrently received an interacting cytochrome P450 isoenzyme medication, 19.24 percent (99 percent CI: 19.15-19.33) concurrently received a serotonergic medication, and 7.93 percent (99 percent CI: 7.88-8.00) concurrently received a benzodiazepine. Additionally, 1.59 percent (99 percent CI: 1.56-1.61) of patients who received tramadol also had a seizure disorder, while 0.55 percent (99 percent CI: 0.53-0.56) of patients were under the age of 18. Overall, nearly one in three patients (31.17 percent) received tramadol in the presence of at least one of these risks (99 percent CI: 31.06-31.27). CONCLUSION: Almost one in three patients prescribed tramadol had a clinically significant drug interaction or contraindication for use, suggesting that prescribers often disregard these concerns. Real-world studies are needed to better understand the likelihood of harms associated with the use of tramadol in these contexts.

Benzodiazepine Dose Intensity among Patients Concurrently Prescribed Buprenorphine in Rhode Island.

Background: The concomitant use of buprenorphine and benzodiazepines has been linked to patient fatalities, with greater risk occurring with higher doses of benzodiazepines. We assessed benzodiazepine dose intensity among patients who were concurrently prescribed buprenorphine, as compared with patients prescribed benzodiazepines who were not receiving buprenorphine. Methods: We conducted a cross-sectional analysis of adult patients who received at least a 30-day supply of benzodiazepines during 2018, using data from the Rhode Island (RI) Prescription Drug Monitoring Program. Mean daily diazepam milligram equivalents (DME) were calculated overall and according to patient sex, age group, payment type, and RI county. Multivariable logistic regression analyses were conducted to assess the odds of higher-dose benzodiazepine utilization among patients with concurrent use of buprenorphine, as compared with patients not prescribed buprenorphine, adjusting for patient demographics. Results: Compared to patients prescribed benzodiazepines who were not receiving buprenorphine, those with concurrent buprenorphine utilization had a significantly higher mean DME/day (19.22, 95% CI: 18.70-19.74; vs 10.94, 95% CI: 10.93-10.95; p < 0.001). Patients who were prescribed benzodiazepines with concurrent utilization of buprenorphine also had a comparatively higher odds of a DME/day ≥15 (aOR: 2.86, 95% CI: 2.63-3.10), ≥20 DME/day (aOR: 2.98, 95% CI: 2.75-3.24), and ≥25 DME/day (aOR: 2.99, 95% CI: 2.65-3.18). Conclusion: Compared to patients prescribed benzodiazepines for at least 30 days who were not receiving buprenorphine, patients concurrently utilizing benzodiazepines and buprenorphine had more than twice the odds of higher dose benzodiazepine utilization. Future studies are needed to assess the relationship between benzodiazepine dose intensity, overdose outcomes, and treatment retention among patients receiving buprenorphine.

Researcher Views of Barriers to Clinical and Translational Research in a Statewide Program.

The Tracking and Evaluation Core of Rhode Island Advance-CTR conducted an online needs assessment survey at the program's inception in 2016 and again in 2021. Now dealing with well-established support systems provided by the grant, we were particularly interested in how the perceived needs of the research community in Rhode Island might have changed over five years. Specifically, what barriers have been reduced or eliminated and which have persisted or increased? How do those barriers vary by demographic status and what implications do those differences have for the CTR? An online survey was completed by 199 researchers, who reported the extent to which they perceived the lack of access to a range of research supports as a barrier to conducting research at their institution. Overall, researchers indicated statistically significant changes from 2016 to 2021 such that a lack of pilot project funding and proposal development support had decreased as barriers, while space for research, and advice on commercial development, had increased. Statistically significant differences in the salience of particular barriers by some demographic variables were also noted and the results of this study suggest Centers for Clinical and Translational Research can have salutary effects on the research paradigm within their partnering institutions in a relatively short time.

Evaluation of the association between health insurance status and healthcare utilization and expenditures among adult cancer survivors in the United States.

BACKGROUND: Health care expenditures for cancer care has increased significantly over the past decade and is further projected to rise. This study examined the associations between health insurance status and total direct health care expenditures and health care utilization among cancer survivors living in the United States. METHODS: A cross-sectional study of cancer survivors aged ≥18 years, identified from the Medical Expenditures Panel Survey (MEPS) during 2017 using International Classification of Diseases, Tenth Revision codes specific for cancer. Health insurance was categorized into Private, Medicare, Medicaid, and uninsured. Multivariable ordinary least squares regression was used to examine the association between log expenditures and health insurance. Negative binomial regression with log link was used to obtain adjusted incident rate ratios (AIRR) for health care utilization. Survey weights were used to produce nationally representative estimates of the US population. RESULTS: A total of 1140 (weighted = 13.9 million) cancer survivors were identified. Compared to the adjusted mean annual health care expenditures for the private group ($14,265; 95% confidence interval (CI): $12,645 to $16,092), the adjusted mean annual health care expenditures for the Medicare group were higher ($15,112; 95%CI: $13,361 to $17,092). As compared to the private group, the average annual expenditures for uninsured cancer survivors ($2315; 95%CI:1038 to $3501) was significantly lower and so was their health care utilization. Adjusted rates of ER visits for Medicaid were twice (AIRR:2.04; SE:0.28; p = 0.001) as compared to privately insured. CONCLUSIONS: A difference in the average total direct expenditures between uninsured and privately insured patients was found. Uninsured had the lowest health care utilization while Medicaid reported significantly higher number of ER visits. Despite differences in program structures, health care expenditures across insurance types were similar. Lower utilization of health care services among uninsured suggests cost maybe a barrier to accessing care.

Rhode Island Has the Highest Rate of Medicare Part D Claims for Benzodiazepines Among New England States.

BACKGROUND: Benzodiazepine use among older adults is discouraged. METHODS: We analyzed the Medicare Part D Prescribers by Provider and Drug dataset to determine the number of benzodiazepine claims per 100 Medicare enrollees for each NE state between 2016-2020, and to determine the percentage of benzodiazepine claims by provider type. RESULTS: Rhode Island led all NE states the with highest annual rates of Part D benzodiazepine claims for all years from 2016 to 2020. Benzodiazepine claims decreased in all NE states over the 5-year period. Internal medicine and family practice providers were associated with the highest percentage of benzodiazepine claims. CONCLUSION: While Part D benzodiazepine claims declined between 2016-2020, the overall volume of dispensings suggests that these medications remain overprescribed among older adults. Our findings underscore the need for intensified efforts to reduce benzo- diazepine use among Medicare beneficiaries in RI.

PHARMACY DEDUCTIBLES CAN COMPLICATE THE RELATIONSHIP BETWEEN MEASURES OF PATIENT COST SHARING AND MEDICATION ADHERENCE.

DISCLOSURES: This letter pertains to our recent publication in JMCP, which describes a study that was jointly funded by the Pharmacy Quality Alliance and the National Pharmaceutical Council.

The Influence of US Drug Price Dynamics on Cost-Effectiveness Analyses of Biologics.

OBJECTIVES: This study aimed to evaluate the influence of drug price dynamics in cost-effectiveness analyses. METHODS: We evaluated scenarios involving typical US drug price increases during the exclusivity period and price decreases after the loss of exclusivity (LOE). Worked examples are presented using the Institute for Clinical and Economic Review's assessments of tezepelumab for the treatment of severe asthma and targeted immune modulators for rheumatoid arthritis. RESULTS: Tezepelumab case: yearly 2% price increases during the period of exclusivity and a post-LOE price decrease of 25% yielded an incremental cost per quality-adjusted life-year (QALY) gained that increased over the base case from $430 300 to $444 600 (+3.2%). Yearly 2% price increases followed by a steeper post-LOE price reduction of 40% resulted in a cost per QALY gained of $401 400 (6.8% reduction vs the base case). Rheumatoid arthritis case: incorporating post-LOE price reductions for etanercept (intervention) and adalimumab (comparator) ranging from 25% to 40% yielded an incremental cost per QALY of $121 000 and $122 300, respectively (< 3% increase from the base case of $119 200/QALY). Including a 2% yearly price increase during the projected exclusivity periods of both intervention and comparator increased the cost per QALY gained by > 60%. CONCLUSION: Two biologic treatment cases incorporating price dynamics in cost-effectiveness analyses had varied impacts on the cost-effectiveness ratio depending on the magnitude of pre-LOE price increase and post-LOE price decrease and whether the LOE also affected the comparator. Yearly price increase magnitude during the period of exclusivity, among other factors, may counterbalance the effects of lower post-LOE intervention prices.

Network-based Analysis of Prescription Opioids Dispensing Using Exponential Random Graph Models (ERGMs).

The United States has been experiencing an unprecedented level of opioid overdose-related mortality due in part to excessive use of prescription opioids. Peer-driven network interventions may be beneficial. A key assumption of social network interventions is that of some members of the network act as key players and can influence the behavior of others in the network. We used opioid prescription records to create a social network of patients who use prescription opioid in the state of Rhode Island. The study population was restricted to patients on stable opioid regimens who used one source of payment and received the same opioid medication from ≥ 3 prescribers and pharmacies. An exponential random graph model (ERGM) was employed to examine the relationship between patient attributes and the likelihood of tie formation and modularity was used to assess for homophily (the tendency of individuals to associate with similar people). We used multivariable logistic regression to assess predictors of high betweenness centrality, a measure of influence within the network. 372 patients were included in the analysis; average age was 51 years; 53% were female; 57% were prescribed oxycodone, 34% were prescribed hydrocodone and 9% were prescribed buprenorphine/naloxone. After controlling for the main effects in the ERGM model, homophily was associated with age group, method of payment, number and type of opioid prescriptions filled, mean daily dose, and number of providers seen. Type of opioid and number of prescribers were identified as significant predictors of high betweenness centrality. We conclude that patients who use multiple prescribers or have a diagnosis of opioid use disorder may help promote positive health behaviors or disrupt harmful behaviors in an opioid prescription network.

Evaluating systemic changes to support clinical and translational health research.

In evaluation research, "programs" are often conceptualized as clearly bounded, narrow in scope, focused on specific outcomes, using a well-defined linear causal model, and hence, suitable for standard evaluation methods. The evaluation work reported here was carried out in a more challenging context, where large, complex, interwoven systems were targets for change as a means to influence a diffuse array of outcomes. Our evaluation of an NIH-funded program to improve statewide infrastructure for clinical and translational health research ("Advance-CTR") used qualitative data provided by investigators who used the program's services, were funded awardees, or were members of an internal advisory committee (leadership representatives from partnering institutions). We examined perceived barriers to systemic changes to enhance research, as well as how systems have changed due to the Rhode Island Advance-CTR program's efforts, to what degree, and with what effects. Using the causal logic of our program to connect these more distal systemic outcomes to the services and components of Advance-CTR, we discuss the effects this program has had on researchers and their environments, contributing to the development of sustainable programs of research that ultimately improve the health and well-being of our state's residents.

Predictors of adherence to oral anticancer medications: An analysis of 2010-2018 US nationwide claims.

BACKGROUND: Various factors, including patient demographic and socioeconomic characteristics, patient out-of-pocket (OOP) costs, therapy-related factors, clinical characteristics, and health-system factors, can affect patient adherence to oral anticancer medications (OAMs). OBJECTIVE: To determine the proportion of patients initiating oral anticancer therapy who were adherent to OAMs and to identify significant predictors of adherence to OAMs, including patient OOP costs and patient demographics. METHODS: A retrospective cohort study was conducted using data from Optum Clinformatics Data Mart commercial claims database for 2010-2018. Patients with a new pharmacy claim for an OAM between July 1, 2010, and December 31, 2017, were followed for 6 months to ascertain their medication adherence, which was defined as a proportion of days covered value of at least 0.8. Average monthly patient OOP costs for OAM prescriptions were categorized as lower OOP costs (quartiles 1-3) and higher OOP costs (quartile 4). Separate multivariable logistic regressions were conducted to identify predictors of OAM nonadherence for each cancer type. RESULTS: Out of 37,938 patients with cancer, 51.9% were adherent to OAMs, with adherence ranging from 32.8% among those with liver cancer to 70.4% among those with brain tumor. The average monthly OOP costs of OAMs also differed by cancer type, ranging from $749 (SD = $1,014) among patients with blood cancer to $106 (SD = $439) among those with prostate cancer. Higher patient OOP costs were associated with higher odds of OAM nonadherence for many cancer types, including renal cancer (adjusted odds ratio [AOR] = 3.91; 95% CI = 2.80-5.47) and breast cancer (AOR = 1.26; 95% CI = 1.13-1.41). Additionally, patients with inpatient hospitalizations during the 6 months following OAM initiation had significantly higher odds of OAM nonadherence for all cancer types except for stomach cancer. Among patients with stomach cancer, male sex was associated with lower odds of OAM nonadherence (AOR = 0.60; 95% CI = 0.37-0.97). Among patients with renal or stomach cancer, those who had Medicare low-income subsidy had higher odds of OAM nonadherence compared with those with commercial insurance coverage. Among patients with blood cancers, Black and Hispanic patients had higher odds of OAM nonadherence compared with White patients (AOR = 1.48; 95% CI = 1.25-1.75 and AOR = 1.38; 95% CI = 1.13-1.68, respectively). CONCLUSIONS: Overall adherence to OAMs was suboptimal, and for several cancer types, adherence was worse among patients with higher OOP costs, those who were hospitalized, and those who received Medicare low-income subsidy. Policies addressing cost and access to OAMs and health-system strategies to address barriers to the effective use of OAMs are needed to improve patient access to these vital medications. DISCLOSURES: This study was funded by joint funding from the Pharmacy Quality Alliance and the National Pharmaceutical Council (NPC). Drs Vyas and Kogut were partially supported by this joint funding. Mr Descoteaux was supported by this joint funding for performing data analysis. The content is solely the responsibility of the authors and does not necessarily represent the official views of PQA or NPC. Dr Campbell completed this work during his employment at Pharmacy Quality Alliance; he is now an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ.

Real-world utilization of top-down and step-up therapy and initial costs in Crohn disease.

BACKGROUND: Medication treatment strategies for Crohn disease (CD) include step-up (SU) therapy, beginning with oral anti-inflammatory agents, and top-down (TD) therapy, beginning with biologics or immunomodulators. The real-world utilization and short-term medical costs associated with these treatment strategies are not well described. OBJECTIVE: To examine the prevalence of TD therapy use over time and compare the first-year direct medical expenditures among patients initiating CD medication treatment with SU and TD therapy in a real-world setting. METHODS: We conducted a retrospective cohort study of Optum Clinformatics Data Mart examining adult patients with CD newly initiated on medication therapy from 2010 to 2018. Included patients had a CD-indicated medication dispensed within 60 days after their initial CD diagnosis, were continuously enrolled in the health plan throughout the study period, and did not have comorbidities treated with a biologic also indicated for CD. A generalized linear model was used to quantify the differences in adjusted mean first-year CD-specific, direct nonpharmacy medical costs between users of TD and SU therapy. RESULTS: We identified 3,157 patients newly initiating medication therapy for CD (2,392 [75.8%] patients treated with SU therapy and 765 [24.2%] treated with TD therapy). The use of TD therapy over the study period increased from 17% in 2011 to 31% in 2017. TD therapy was also associated with a 149.8% ($1,230) higher adjusted average per-patient first-year CD-direct nonpharmacy medical cost compared with SU therapy (adjusted ratio of cost for TD compared with SU [2.498, 95% CI = 2.12-2.95]). CONCLUSIONS: In patients newly initiating medication therapy for CD, TD therapy use increased between 2010 and 2017 and was associated with higher first-year nonpharmacy medical expenditure. These findings align with the strategy of initiating TD therapy in patients with a higher disease burden. Further research is needed to determine long-term overall health care costs and clinical outcomes associated with SU and TD strategies in a real-world setting. DISCLOSURES: Dr Caffrey received research funding from Gilead, Merck, Pfizer, and Shionogi and is a speaker for Merck. The views expressed are those of the author and do not necessarily reflect the position or policy of the US Department of Veterans Affairs. Material is based on work supported, in part, by the Office of Research and Development.

Toward evaluation of disseminated effects of medications for opioid use disorder within provider-based clusters using routinely-collected health data.

Routinely-collected health data can be employed to emulate a target trial when randomized trial data are not available. Patients within provider-based clusters likely exert and share influence on each other's treatment preferences and subsequent health outcomes and this is known as dissemination or spillover. Extending a framework to replicate an idealized two-stage randomized trial using routinely-collected health data, an evaluation of disseminated effects within provider-based clusters is possible. In this article, we propose a novel application of causal inference methods for dissemination to retrospective cohort studies in administrative claims data and evaluate the impact of the normality of the random effects distribution for the cluster-level propensity score on estimation of the causal parameters. An extensive simulation study was conducted to study the robustness of the methods under different distributions of the random effects. We applied these methods to evaluate baseline prescription for medications for opioid use disorder among a cohort of patients diagnosed with opioid use disorder and adjust for baseline confounders using information obtained from an administrative claims database. We discuss future research directions in this setting to better address unmeasured confounding in the presence of disseminated effects.

Early buprenorphine-naloxone initiation for opioid use disorder reduces opioid overdose, emergency room visits, and healthcare cost compared to late initiation.

Background: Although the effectiveness of buprenorphine-naloxone (BUP-NX) has been established, real-world evidence on the benefits of early treatment initiation is limited.Objective: To evaluate the association between early BUP-NX initiation and health-related outcomes among insured adults with opioid use disorder (OUD).Methods: We conducted a cross-sectional analysis using the Optum's de-identified Clinformatics® Data Mart Database from 2010 to 2018. Patients who initiated BUP-NX within 30 days of OUD diagnosis were classified as early initiators. Patients who initiated BUP-NX later, but within the one-year follow-up, were defined as late initiators. Outcomes included opioid overdose, opioid overdose-related emergency department (ED) visits, and all-cause healthcare cost during the year after OUD diagnosis. We employed generalized linear models to compare outcomes between early and late initiators, adjusting for baseline covariates and accounting for missing information for covariates using multiple imputation.Results: A total of 8,388 patients with OUD were identified; mean age was 39.9 years; 36% were female; and 67.6% were early initiators. Early initiators had an estimated 42% lower rate of opioid overdose (adjusted rate ratio (aRR) = 0.58; 95% confidence interval (CI): 0.52, 0.64); 51% lower rate of opioid overdose-related ED visits (aRR = 0.49; 95% CI: 0.44, 0.55); and 31% lower total healthcare cost (adjusted cost ratio = 0.69; 95% CI: 0.66, 0.72), compared to late initiators.Conclusion: Compared to late BUP-NX initiation, early initiation was associated with a lower risk of opioid overdose and opioid overdose-related ED visits, and reduced total healthcare cost among insured adult patients with OUD.

Addressing Posttreatment Selection Bias in Comparative Effectiveness Research, Using Real-World Data and Simulation.

To examine methodologies that address imbalanced treatment switching and censoring, 6 different analytical approaches were evaluated under a comparative effectiveness framework: intention-to-treat, as-treated, intention-to-treat with censor-weighting, as-treated with censor-weighting, time-varying exposure, and time-varying exposure with censor-weighting. Marginal structural models were employed to address time-varying exposure, confounding, and possibly informative censoring in an administrative data set of adult patients who were hospitalized with acute coronary syndrome and treated with either clopidogrel or ticagrelor. The effectiveness endpoint included first occurrence of death, myocardial infarction, or stroke. These methodologies were then applied across simulated data sets with varying frequencies of treatment switching and censoring to compare the effect estimate of each analysis. The findings suggest that implementing different analytical approaches has an impact on the point estimate and interpretation of analyses, especially when censoring is highly unbalanced.

Application of a diazepam milligram equivalency algorithm to assess benzodiazepine dose intensity in Rhode Island in 2018.

BACKGROUND: Benzodiazepines are indicated for the treatment of many conditions, such as anxiety disorders, muscle spasms, alcohol withdrawal, agitation, movement disorders, and epilepsy, and are one of the most frequently prescribed medication classes. This class of medication has important safety considerations, including an increased risk of dependence and addiction, falls, and death from opioid overdose. Although benzodiazepine safety and prescribing encompasses a rich and important research area, there is a lack of pharmacoepidemiologic literature addressing benzodiazepine dosing intensity in real-world settings. OBJECTIVE: To develop and apply a standardized benzodiazepine milligram equivalency conversion algorithm and assess the dose intensity of benzodiazepine use in Rhode Island (RI) in 2018. METHODS: A systematic literature review was conducted to identify the most commonly used benzodiazepine equivalency values. We then conducted a cross-sectional analysis of 2018 data from the RI Prescription Drug Monitoring Program (PDMP) to calculate the mean daily diazepam milligram equivalency (DME) based on a patient's most recent dispensing. A multivariable logistic regression analysis was conducted to determine the association between higher benzodiazepine doses (≥ 15 DME/day) and recipient characteristics, including concurrent use of opioids or stimulants. RESULTS: We identified 143,026 patients who received at least 1 prescription for a benzodiazepine in RI in 2018. The mean (SD) daily DME was 10.60 (9.05), and 26.2% of individuals had a mean DME per day of at least 15. Approximately 14% (n = 20,168) of patients prescribed a benzodiazepine had concurrent use with a prescription opioid, and 6.7% (n = 9,547) had concurrent use with a prescription stimulant. Females had a 28% lower adjusted odds of receiving a benzodiazepine dose of at least 15 DME per day compared with males (adjusted odds ratio [aOR] = 0.72, 95% CI = 0.70-0.73). The adjusted odds of receiving a benzodiazepine prescription of at least 15 DME per day was lower among the younger (aged 18-34 years) and older age groups (aged 65 years and older) compared with patients aged 35-64 years. Compared with commercial insurance, all other forms of payment had significantly higher adjusted odds of a daily benzodiazepine dose of at least 15 DME per day. The adjusted odds receiving a daily DME of at least 15 was 67% higher among those who also received a concurrent pharmacy dispensing for an opioid and 84% higher among those who also received a concurrent dispensing for a stimulant drug (aOR = 1.67, 95% CI = 1.61-1.72; aOR = 1.84, 95% CI = 1.76-1.93, respectively). CONCLUSIONS: Individuals aged 35-64 years with Medicaid insurance and those aged under 65 years with Medicare were more likely to be prescribed a benzodiazepine of at least 15 DME per day. Higher benzodiazepine DMEs were also dispensed to patients who concurrently used prescription opioids or stimulants who may be at increased risk of medication-related harm. We advocate for routine measurement of benzodiazepine dose intensity as a risk reduction strategy. DISCLOSURES: No funding supported this study. The authors have no conflicts of interest to disclose. The content and results of this study are solely the responsibility of the authors and do not necessarily represent the official views of the Rhode Island Department of Health. Kogut is partially supported by Institutional Development Award Numbers U54GM115677 and P20GM125507 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds Advance Clinical and Translational Research (Advance-CTR) and the RI Lifespan Center of Biomedical Research Excellence (COBRE) on Opioids and Overdose, respectively. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Contents of this study were presented as a poster presentation at AMCP 2019 Nexus; October 29-November 1, 2019; National Harbor, MD.

Evaluation of the Effectiveness of Buprenorphine-Naloxone on Opioid Overdose and Death among Insured Patients with Opioid Use Disorder in the United States.

Opioid use disorder (OUD) is a chronic disease requiring long-term treatment and is associated with opioid overdose and increased risk of mortality. However, existing randomized clinical trials focused on short-term treatment engagement and detoxification rather than overdose or mortality risk due to limited follow-up time and ethical considerations. We used a hypothetical trial framework to conduct a retrospective cohort study to assess the effectiveness of time-varying buprenorphine-naloxone on opioid overdose and death. We identified 58,835 insured adult patients with OUD diagnosis in the US, 2010-2017. We fit a marginal structural model using inverse probability weighting methods to account for measured baseline and time-varying confounders, as well as selection bias due to possibly differential loss-to-follow-up. We found that receipt of buprenorphine-naloxone was associated with reduced risk of opioid overdose (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.91), death (HR = 0.24, 95% CI: 0.08, 0.75), and overdose or death (HR = 0.58, 95% CI: 0.40, 0.84). The E-value for death was 7.8, which was larger than the upper 95% CI of the association between each measured baseline variable and all-cause death, which implies that the unmeasured confounding itself may not explain away the estimated effect of treatment on the endpoint of all-cause mortality.

Association of guideline-concordant initial systemic treatment with clinical and economic outcomes among older women with metastatic breast cancer in the United States.

PURPOSE: We examined guideline-concordant initial systemic treatment among women with metastatic breast cancer, its predictors, and if guideline-concordant treatment was associated with mortality, healthcare utilization and Medicare expenditures. METHODS: This retrospective observational cohort study was conducted using the Surveillance, Epidemiology, End Results-Medicare linked database. Women aged 66-90 years diagnosed with metastatic breast cancer during 2010-2013 (N = 1282) were included. The National Comprehensive Cancer Network treatment guidelines were used to determine the guideline-concordant initial systemic treatment following cancer diagnosis. A logistic regression analysis was conducted to examine significant predictors of guideline-concordant treatment. Generalized linear regressions were used to examine the association between guideline-concordant treatment and healthcare utilization and average monthly Medicare expenditures. RESULTS: About 74% of the study cohort received guideline-concordant initial systemic treatment. Women who received guideline-concordant treatment were significantly more likely to be comparatively younger (p < 0.05), were married/partnered (p = 0.0038), had HER2 positive tumors, and had good performance status. Adjusted hazards ratios for all-cause (2.364, p < 0.0001) and breast-cancer specific mortality (2.179, p < 0.0001) were higher for women who did not receive guideline-concordant treatment. Rates of healthcare utilization were also higher for women not receiving guideline-concordant treatment. Average monthly Medicare expenditures were 100.4% higher (95% confidence interval: $77.3%-126.5%) for women who did not receive guideline-concordant treatment compared to those who received guideline-concordant treatment (p < 0.0001). CONCLUSION: One fourth of the study cohort did not receive guideline-concordant initial systemic treatment. Guideline-concordant initial treatment was associated with reduced mortality, and lower healthcare utilization and Medicare expenditures in women with metastatic breast cancer.