Adjusting starting points for initial price offers: the example of ibrutinib.

The Inflation Reduction Act of 2022 (IRA) allows the Medicare program to negotiate drug prices beginning in 2024. Based on the guidance in the statute, CMS has selected specific data items to use to adjust initial price offers for 10 drugs in the decision-making process. Although much of the data are publicly available, some of these data items will need to be collected directly from drug companies. A 2019 US House of Representatives Committee on Oversight and Accountability investigative report collected a wide range of data from manufacturers of 12 high-revenue drugs that show what is available from the drug companies, including development costs, marketing, pricing, competition, and patent status. This article focuses on the data obtained for ibrutinib, an oral medication for treating hematologic malignancies, which is one of the only drugs reviewed by the committee that also has been selected for Medicare price negotiation. We examine data that can be obtained only from the drug manufacturer that the IRA has explicitly identified as being used to determine the price and suggest potential negotiation strategies for CMS in response.

Simulated impact of mobile opioid treatment program units on increasing access to methadone for opioid use disorder.

OBJECTIVE: To model the potential impact of mobile methadone unit implementation in Louisiana on net medication for opioid use disorder (MOUD) treatment rates. DATA SOURCES/STUDY SETTING: We use secondary Louisiana Medicaid claims data between 2020 and 2021. STUDY DESIGN: We simulate the impact of mobile methadone units in Louisiana using two approaches: (1) a "Poisson regression approach," which predicts the number of opioid use disorder (OUD) patients that might use methadone at mobile locations based on the underlying association between methadone use and proximity to a brick-and-mortar methadone clinic; (2) a "policy approach," which leverages local treatment uptake rates following the expansion of methadone coverage to Louisiana Medicaid beneficiaries in 2020 to estimate methadone use following mobile unit implementation. Models were run in cases where mobile methadone operators could choose their operation locations freely and in a separate instance where they were restricted to serving rural locations. DATA COLLECTION: Our analytic sample includes 43,341 Louisiana Medicaid beneficiaries with one or more primary or secondary diagnoses for opioid dependence. PRINCIPAL FINDINGS: We predict that 10 new mobile methadone units in Louisiana would increase the net MOUD treatment rate in the state by 0.54-2.39 percentage points. If these mobile units delivered Methadone exclusively to rural areas, they could increase rural MOUD treatment by 8.54-13.67 percentage points. Further, roughly 20% of all beneficiaries residing in rural areas being treated with methadone would be an average of 24 miles closer to a methadone treatment provider following mobile unit implementation. CONCLUSIONS: Mobile methadone units represent a promising innovation in the delivery of methadone that is likely to increase methadone use, especially in underserved rural locations. However, we find significant variation in their impact conditional on where they choose to operate, and so careful location planning will be required to maximize their benefit.

Accountable Care Organization Attribution and Post-Acute Skilled Nursing Facility Outcomes for People Living With Dementia.

OBJECTIVES: Under the Accountable Care Organization (ACO) model, reductions in healthcare spending have been achieved by targeting post-acute care, particularly in skilled nursing facilities (SNFs). People with Alzheimer disease and related dementias (ADRD) are frequently discharged to SNF for post-acute care and may be at particular risk for unintended consequences of SNF cost reduction efforts. We examined SNF length of stay (LOS) and outcomes among ACO-attributed and non-ACO-attributed ADRD patients. DESIGN: Observational serial cross-sectional study. SETTING AND PARTICIPANTS: Twenty percent national random sample of fee-for-service Medicare beneficiaries (2013-2017) to identify beneficiaries with a diagnosis of ADRD and with a hospitalization followed by SNF admission (n = 263,676). METHODS: Our primary covariate of interest was ACO (n = 66,842) and non-ACO (n = 196,834) attribution. Hospital readmission and death were measured for 3 time periods (<30, 31-90, and 91-180 days) following hospital discharge. We used 2-stage least squares regression to predict LOS as a function of ACO attribution, and patient and facility characteristics. RESULTS: ACO-attributed ADRD patients have shorter SNF LOS than their non-ACO counterparts (31.7 vs 32.8 days; P < .001). Hospital readmission rates for ACO vs non-ACO differed at ≤30 days (13.9% vs 14.6%; P < .001) but were similar at 31-90 days and 91-180 days. No significant difference was observed in mortality post-hospital discharge for ACO vs non-ACO at ≤30 days; however, slightly higher mortality was observed at 31-90 days (8.4% vs 8.8%; P = .002) and 91-180 days (7.6% vs 7.9%; P = .011). No significant association was found between LOS and readmission, with small effects on mortality favoring ACOs in fully adjusted models. CONCLUSIONS AND IMPLICATIONS: Being an ACO-attributed patient is associated with shorter SNF LOS but is not associated with changes in readmission or mortality after controlling for other factors. Policies that shorten LOS may not have adverse effects on outcomes for people living with dementia.

Racial and ethnic disparities in medication for opioid use disorder access, use, and treatment outcomes in Medicare.

INTRODUCTION: Overdose deaths are increasing disproportionately for minoritized populations in the United States. Disparities in substance use disorder treatment access and use have been a key contributor to this phenomenon. However, little is known about the magnitude of these disparities and the role of social determinants of health (SDOH) and provider characteristics in driving them. Our study measures the association between race and ethnicity and visits with Medication for Opioid Use Disorder (MOUD) providers, MOUD treatment conditional on a provider visit, and opioid overdose following MOUD treatment in Medicare. We also evaluate the role of social determinants of health and provider characteristics in modifying disparities. METHODS: Using a population of 230,198 US Medicare fee-for-service beneficiaries diagnosed with opioid use disorder (OUD), we estimate logistic regression models to quantify the association between belonging to a racial or ethnic group and the probability of visiting a buprenorphine or naltrexone provider, receiving a prescription or medication administration during or after a visit, and experiencing an opioid overdose after treatment with MOUD. Data included Medicare claims data and the Agency for Health Research and Quality Social Determinants of Health Database files between 2013 and 2017. RESULTS: Compared to Non-Hispanic White Medicare beneficiaries, Asian/Pacific Islander, American Indian/Alaska Native, Black, Hispanic, and Other/Unknown Race beneficiaries were between 3.0 and 9.3 percentage points less likely to have a visit with a buprenorphine or naltrexone provider. Conditional on having a buprenorphine or naltrexone provider visit, Asian/Pacific Islander, American Indian/Alaska Native, Black, Hispanic, and Other/Unknown Race were between 2.6 and 8.1 percentage points less likely to receive buprenorphine or naltrexone than white beneficiaries. Controlling for provider characteristics and SDOH increased disparities in visits and MOUD treatment for all groups besides American Indians/Alaska Natives. Conditional on treatment, only Black Medicare beneficiaries were at greater associated risk of overdose than non-Hispanic white beneficiaries, although differences became statistically insignificant after controlling for SDOH and including provider fixed effects. CONCLUSION: Ongoing equity programming and measurement efforts by CMS should include explicit consideration for disparities in access and use of MOUD. This may help ensure greater MOUD utilization by minoritized Medicare beneficiaries and reduce rising disparities in overdose deaths.

Associations between insomnia medications and risk of death by suicide.

PURPOSE: Insomnia is a modifiable risk factor for suicide often treated with medications. However, little is known about the associations between insomnia medications and risk of death by suicide. The purpose of this study is to model the comparative risk of suicide by each insomnia medication compared to zolpidem, a sedative-hypnotic approved for insomnia. METHODS: First prescription fills of medications commonly used to treat insomnia were identified in electronic medical records. Date and cause of death were identified in death certificates. Cox proportional hazards models were used to analyze time from insomnia prescription to suicide. RESULTS: More than 2 million patients filled a new insomnia prescription between 2005 and 2015, and 518 of them died by suicide within 12 months. Compared to zolpidem, the tricyclic antidepressants (amitriptyline, doxepin) were associated with a 64% lower risk of suicide (HR 0.36 (95% CI 0.22-0.66) and the sedating antihistamines (hydroxyzine, diphenhydramine) a 40% lower risk of suicide (HR 0.60 (0.41-0.89)). In contrast, the tetracyclic antidepressant (mirtazapine) was associated with a 62% higher risk of suicide (HR 1.62 (95% CI 1.10-2.38) compared to zolpidem. CONCLUSION: Insomnia is a modifiable risk factor for suicide, yet many medications used to treat insomnia have never been tested for the indication in clinical trials. To define efficacy in the prevention of suicide, trials are warranted.

Increasing overdose deaths among Black Americans: a review of the literature.

In 2020, opioid overdose fatalities among Black Americans surpassed those among White Americans for the first time in US history. This Review analyses the academic literature on disparities in overdose deaths to highlight potential factors that could explain these increases in overdose deaths among Black Americans. Overall, we find that differences in structural and social determinants of health; inequality in the access, use, and continuity of substance use disorder and harm reduction services; variability in fentanyl exposure and risk; and changes in social and economic circumstances since the onset of the COVID-19 pandemic are central to explaining this trend. We conclude with a discussion of opportunities for US policy reform and opportunities for future research.

The Impact of Nurse Practitioner Care and Accountable Care Organization Assignment on Skilled Nursing Services and Hospital Readmissions.

BACKGROUND: Accountable care organizations (ACOs) and the employment of nurse practitioners (NP) in place of physicians are strategies that aim to reduce the cost and improve the quality of routine care delivered in skilled nursing facilities (SNF). The recent expansion of ACOs and nurse practitioners into SNF settings in the United States may be associated with improved health outcomes for patients. OBJECTIVES: To determine the relationship between ACO attribution and NP care delivery during SNF visits and the relationship between NP care delivery during SNF visits and unplanned hospital readmissions. METHODS: We obtained a sample of 527,329 fee-for-service Medicare beneficiaries with 1 or more SNF stays between 2012 and 2017. We used logistic regression to measure the association between patient ACO attribution and evaluation and management care delivered by NPs in addition to the relationship between evaluation and management services delivered by NPs and hospital readmissions. RESULTS: ACO beneficiaries were 1.26% points more likely to receive 1 or more E&M services delivered by an NP during their SNF visits [Marginal Effect (ME): 0.0126; 95% CI: (0.009, 0.0160)]. ACO-attributed beneficiaries receiving most of their E&M services from NPs during their SNF visits were at a lower risk of readmission than ACO-attributed beneficiaries receiving no NP E&M care (5.9% vs. 7.1%; P <0.001). CONCLUSIONS: Greater participation by the NPs in care delivery in SNFs was associated with a reduced risk of patient readmission to hospitals. ACOs attributed beneficiaries were more likely to obtain the benefits of greater nurse practitioner involvement in their care.

Association Between Hospital Adoption of an Emergency Department Treatment Pathway for Opioid Use Disorder and Patient Initiation of Buprenorphine After Discharge.

Importance: Emergency department (ED)-based initiation of buprenorphine has been shown to increase engagement in outpatient treatment and reduce the risk of subsequent opioid overdose; however, rates of buprenorphine treatment in the ED and follow-up care for opioid use disorder (OUD) remain low in the US. The Opioid Hospital Quality Improvement Program (O-HQIP), a statewide financial incentive program designed to increase engagement in OUD treatment for Medicaid-enrolled patients who have ED encounters, has the potential to increase ED-initiated buprenorphine treatment. Objective: To evaluate the association between hospitals attesting to an ED buprenorphine treatment O-HQIP pathway and patients' subsequent initiation of buprenorphine treatment. Design, Setting, and Participants: This cohort study included Pennsylvania patients aged 18 to 64 years with continuous Medicaid enrollment 6 months before their OUD ED encounter and at least 30 days after discharge between January 1, 2016, and December 31, 2020. Patients with a claim for medication for OUD 6 months before their index encounter were excluded. Exposures: Hospital implementation of an ED buprenorphine treatment O-HQIP pathway. Main Outcomes and Measures: The main outcome was patients' receipt of buprenorphine within 30 days of their index OUD ED visit. Between August 2021 and January 2023, data were analyzed using a difference-in-differences method to evaluate the association between hospitals' O-HQIP attestation status and patients' treatment with buprenorphine after ED discharge. Results: The analysis included 17 428 Medicaid-enrolled patients (female, 43.4%; male, 56.6%; mean [SD] age, 37.4 [10.8] years; Black, 17.5%; Hispanic, 7.9%; White, 71.6%; other race or ethnicity, 3.0%) with OUD seen at O-HQIP-attesting or non-O-HQIP-attesting hospital EDs. The rate of prescription fills for buprenorphine within 30 days of an OUD ED discharge in the O-HQIP attestation hospitals before the O-HQIP intervention was 5%. The O-HQIP attestation was associated with a statistically significant increase (2.6 percentage points) in prescription fills for buprenorphine within 30 days of an OUD ED discharge (ß, 0.026; 95% CI, 0.005-0.047). Conclusions and Relevance: In this cohort study, the O-HQIP was associated with an increased initiation of buprenorphine in patients with OUD presenting to the ED. These findings suggest that statewide incentive programs may effectively improve outcomes for patients with OUD.

The association between vitamin D serum levels, supplementation, and suicide attempts and intentional self-harm.

OBJECTIVES: The purpose of this study is to determine the associations between Vitamin D supplementation, 25(OH) blood serum levels, suicide attempts, and intentional self-harm in a population of veterans in the Department of Veterans Affairs (VA). METHODS: A retrospective cohort study of US Veterans supplemented with Vitamin D. Veterans with any Vitamin D3 (cholecalciferol) or Vitamin D2 (ergocalciferol) fill between 2010 and 2018 were matched 1:1 to untreated control veterans having similar demographics and medical histories. Cox proportional hazards regression was used to estimate the time from the first Vitamin D3 (cholecalciferol) or Vitamin D2 (ergocalciferol) prescription fill to the first suicide attempt or intentional self-harm. Analyses were repeated in stratified samples to measure associations by race (Black or White), gender (male or female), blood levels (0-19 ng/ml, 20-39 ng/ml, and 40+ ng/ml), and average daily dosage. RESULTS: Vitamin D3 and D2 supplementation were associated with a 45% and 48% lower risk of suicide attempt and self-harm ((D2 Hazard Ratio (HR) = 0.512, [95% CI, 0.457, 0.574]; D3 HR = 0.552, [95% CI, 0.511, 0.597])). Supplemented black veterans and veterans with 0-19 ng/ml vitamin D serum levels were at ~64% lower risk relative to controls (Black Veteran HR: 0.362 [95% CI: 0.298,0.440]; 0-19 ng/ml HR: 0.359 [95% CI: 0.215,0.598]). Supplementation with higher vitamin D dosages was associated with greater risk reductions than lower dosages (Log Average Dosage HR: 0.837 [95% CI: 0.779,0.900]). CONCLUSIONS: Vitamin D supplementation was associated with a reduced risk of suicide attempt and self-harm in Veterans, especially in veterans with low blood serum levels and Black veterans.

Humira: the first $20 billion drug.

AbbVie's adalimumab (Humira) is the top-selling pharmaceutical in the world. Due to concerns about government health program spending on Humira, the US House Committee on Oversight and Accountability opened an investigation in 2019 to investigate AbbVie's pricing and marketing practices. We review these reports and describe policy debates surrounding the highest-grossing drug to highlight how the legal landscape enables incumbent manufacturers to block competition in the pharmaceutical market. Tactics include patent thickets, evergreening, Paragraph IV settlement agreements, product hopping, and linking executive compensation to sales growth. These strategies are not unique to AbbVie and shed light on pharmaceutical market dynamics that may be hindering a competitive market. Policy reform and legal initiatives may help reduce anticompetitive behaviors by pharmaceutical manufacturers and increase access to competitive therapeutic options such as biosimilars.

The social vulnerability metric (SVM) as a new tool for public health.

OBJECTIVE: To derive and validate a new ecological measure of the social determinants of health (SDoH), calculable at the zip code or county level. DATA SOURCES AND STUDY SETTING: The most recent releases of secondary, publicly available data were collected from national U.S. health agencies as well as state and city public health departments. STUDY DESIGN: The Social Vulnerability Metric (SVM) was constructed from U.S. zip-code level measures (2018) from survey data using multidimensional Item Response Theory and validated using outcomes including all-cause mortality (2016), COVID-19 vaccination (2021), and emergency department visits for asthma (2018). The SVM was also compared with the existing Centers for Disease Control and Prevention's Social Vulnerability Index (SVI) to determine convergent validity and differential predictive validity. DATA COLLECTION/EXTRACTION METHODS: The data were collected directly from published files available to the public online from national U.S. health agencies as well as state and city public health departments. PRINCIPAL FINDINGS: The correlation between SVM scores and national age-adjusted county all-cause mortality was r = 0.68. This correlation demonstrated the SVM's robust validity and outperformed the SVI with an almost four-fold increase in explained variance (46% vs. 12%). The SVM was also highly correlated (r ≥ 0.60) to zip-code level health outcomes for the state of California and city of Chicago. CONCLUSIONS: The SVM offers a measurement tool improving upon the performance of existing SDoH composite measures and has broad applicability to public health that may help in directing future policies and interventions. The SVM provides a single measure of SDoH that better quantifies associations with health outcomes.

Association between vitamin D supplementation and COVID-19 infection and mortality.

Vitamin D deficiency has long been associated with reduced immune function that can lead to viral infection. Several studies have shown that Vitamin D deficiency is associated with increases the risk of infection with COVID-19. However, it is unknown if treatment with Vitamin D can reduce the associated risk of COVID-19 infection, which is the focus of this study. In the population of US veterans, we show that Vitamin D2 and D3 fills were associated with reductions in COVID-19 infection of 28% and 20%, respectively [(D3 Hazard Ratio (HR) = 0.80, [95% CI 0.77, 0.83]), D2 HR = 0.72, [95% CI 0.65, 0.79]]. Mortality within 30-days of COVID-19 infection was similarly 33% lower with Vitamin D3 and 25% lower with D2 (D3 HR = 0.67, [95% CI 0.59, 0.75]; D2 HR = 0.75, [95% CI 0.55, 1.04]). We also find that after controlling for vitamin D blood levels, veterans receiving higher dosages of Vitamin D obtained greater benefits from supplementation than veterans receiving lower dosages. Veterans with Vitamin D blood levels between 0 and 19 ng/ml exhibited the largest decrease in COVID-19 infection following supplementation. Black veterans received greater associated COVID-19 risk reductions with supplementation than White veterans. As a safe, widely available, and affordable treatment, Vitamin D may help to reduce the severity of the COVID-19 pandemic.

Association Between Buprenorphine Treatment Gaps, Opioid Overdose, and Health Care Spending in US Medicare Beneficiaries With Opioid Use Disorder.

Importance: Nonadherence to buprenorphine may increase patient risk of opioid overdose and increase health care spending. Quantifying the impacts of nonadherence can help inform clinician practice and policy. Objective: To estimate the association between buprenorphine treatment gaps, opioid overdose, and health care spending. Design, Setting, and Participants: This longitudinal case-control study compared patient opioid overdose and health care spending in buprenorphine-treated months with treatment gap months. Individuals who were US Medicare fee-for-service beneficiaries diagnosed with opioid use disorder who received at least 1 two-week period of continuous buprenorphine treatment between 2010 and 2017 were included. Analysis took place between January 2010 and December 2017. Interventions: A gap in buprenorphine treatment in a month lasting more than 15 consecutive days. Main Outcomes and Measures: Opioid overdose and total, medical, and drug spending (combined patient out-of-pocket and Medicare spending). Results: Of 34 505 Medicare beneficiaries (17 927 [520%] male; 16 578 [48.1%] female; mean [SD] age, 49.5 [12.7] years; 168 [0.5%] Asian; 2949 [8.5%] Black; 2089 [6.0%] Hispanic; 266 [0.8%] Native American; 28 525 [82.7%] White; 508 [1.5%] other race), 11 524 beneficiaries (33.4%) experienced 1 or more buprenorphine treatment gaps. Treatment gap beneficiaries, compared with nontreatment gap beneficiaries, were more likely to be younger, be male, have a disability, and be Medicaid dual-eligible while less likely to be White, close to a buprenorphine prescriber, and treated with buprenorphine monotherapy (ie, buprenorphine hydrochloride). Beneficiaries were 2.89 (95% CI, 2.20-3.79) times more likely to experience an opioid overdose during buprenorphine treatment gap months compared with treated months. During treatment gap months, spending was $196.41 (95% CI, $110.53-$282.30) more than in treated months. Patients who continued to take buprenorphine dosages of greater than 8 mg/d and 16 mg/d were 2.61 and 2.84 times more likely to overdose in a treatment gap month, respectively, while patients taking buprenorphine dosages of 8 mg/d or less were 3.62 times more likely to overdose in a treatment gap month (maintenance of >16 mg/d: hazard ratio (HR), 2.64 [95% CI, 1.80-3.87]; maintenance of >8 mg/d: HR, 2.84 [95% CI, 2.13-3.78]; maintenance of ≤8 mg/d: HR, 3.62 [95% CI, 1.54-8.50]). Buprenorphine monotherapy was associated with greater risk of overdose and higher spending during treatment gaps months than buprenorphine/naloxone. Conclusions and Relevance: Medicare patients treated with buprenorphine between 2010 and 2017 had a lower associated opioid overdose risk and spending during treatment months than treatment gap months.

Small practice participation and performance in Medicare accountable care organizations.

OBJECTIVES: Alternative payment models (APMs) encouraging provider collaboration may help small practices overcome the participation challenges that they face in APMs. We aimed to determine whether small practices in accountable care organizations (ACOs) reduced their beneficiaries' spending more than large practices in ACOs. STUDY DESIGN: Retrospective cohort study of Medicare patients attributed to ACOs and non-ACOs. METHODS: We conducted a modified difference-in-differences analysis that allowed us to compare large vs small practices before and after the Medicare Shared Savings Program (MSSP) ACO started, between 2010 and 2016. Our sample included Medicare fee-for-service beneficiaries with 12 months of Medicare Part A and Part B (unless death) who were attributed to small (≤ 15 providers) and large (> 15 providers) practices participating in ACOs and non-ACOs. The outcome was patient annual spending based on CMS' total per capita costs. RESULTS: Patients attributed to small practices in ACOs had annual Medicare spending decreases of $269 (95% CI, $213-$325; P < .001) more than patients attributed to large practices in ACOs. Small ACO practices reduced spending more than large practices by $165 for physician services (95% CI, $140-$190; P < .001), $113 for hospital/acute care (95% CI, $65-162; P < .001), and $52 for other services (95% CI, $27-$77; P < .001). Small practices in ACOs spent $253 more on average at baseline than small practices in non-ACOs. ACOs with a higher proportion of small practices were more likely to receive shared savings payments. CONCLUSIONS: Small practices in ACOs controlled costs more so than large practices. Small practice participation may generate higher savings for ACOs.