Naloxone Availability and Cost After Transition to an Over-the-Counter Product.

Importance: The US Food and Drug Administration approved Narcan, a nasal spray formulation of naloxone, for sale as an over-the-counter (OTC) medication in March 2023. The purpose of OTC approval was to improve naloxone accessibility to reduce opioid overdoses; however, research has not yet evaluated whether naloxone's availability and cost changed since this policy was implemented. Objective: To evaluate whether the accessibility and cost of naloxone at North Carolina community pharmacies changed after OTC naloxone became available and whether cost and availability varied by pharmacy type and urbanicity. Design, Setting, and Participants: This longitudinal telephone-based secret shopper survey study included a stratified sample of 202 North Carolina community pharmacies, including health department, independent, and chain pharmacies. There were 2 separate data collection efforts from March to April 2023 (before OTC naloxone could be sold at pharmacies) and November 2023 to January 2024 (after OTC naloxone was sold at pharmacies). Exposure: OTC naloxone first became available for sale at community pharmacies in September 2023. Main Outcomes and Measures: The main outcomes were same-day availability of naloxone without a clinician-issued prescription and the quoted out-of-pocket cost for cash-paying patients. Results: Data were collected from 192 pharmacies. Same-day naloxone availability increased from 42.2% (81 of 192) before OTC naloxone availability to 57.8% (111 of 192) after (P < .001). The mean (SD) quoted out-of-pocket cost decreased from $90.93 ($42.6) pre-OTC availability to $62.67 ($41.0) post-OTC availability (P < .001). Independent pharmacies had higher mean (SD) costs than chain pharmacies in both the pre-OTC phase ($109.47 [$37.90] vs $86.40 [$35.70]; P < .001) and post-OTC phase ($77.59 [$38.90] vs $57.74 [$35.90]; P = .004). Out-of-pocket costs did not differ by urbanicity in the pre-OTC phase; however, mean (SD) costs were higher at suburban ($88.67 [$66.80]) and rural ($65.43 [$35.00]) pharmacies compared with urban pharmacies ($53.58 [$29.00]) in the post-OTC phase (P = .003). Conclusions and Relevance: The Food and Drug Administration's approval of OTC naloxone nasal spray contributed to an increase in pharmacy-based availability of naloxone and a reduction of its cost for cash-paying patients. Cost was higher at independent pharmacies compared with chain pharmacies and lower in urban pharmacies compared with suburban and rural pharmacies.

Association Between Cost-Sharing and Buprenorphine Prescription Abandonment.

BACKGROUND: Prior studies suggest cost-sharing decreases buprenorphine dispensing. However, these studies used databases that only report prescriptions filled by patients, not those that were "abandoned." Consequently, the studies could not calculate the probability of buprenorphine prescription abandonment or evaluate whether cost-sharing is associated with abandonment. OBJECTIVE: To evaluate the association between cost-sharing and buprenorphine prescription abandonment. DESIGN: Cross-sectional analysis of the IQVIA Formulary Impact Analyzer, a pharmacy transaction database representing 63% of U.S. retail pharmacies. The database includes transaction records ("claims") for prescriptions even if they are not filled. PARTICIPANTS: Buprenorphine claims in 2022 among commercially insured and Medicare patients. MAIN MEASURES: We evaluated the association between cost-sharing per 30-day supply and abandonment using logistic regression, controlling for patient characteristics, product type, and buprenorphine use in the prior 180 days. We assessed for effect modification by prior buprenorphine use. KEY RESULTS: Analyses included 2,346,994 and 1,242,596 buprenorphine prescription claims for commercially insured and Medicare patients, respectively. Among these claims, mean (SD) cost-sharing per 30-day supply was $28.1 (46.4) and $8.4 (20.2), and 1.5% and 1.2% were abandoned. Each $10 increase in cost-sharing per 30-day supply was associated with a 0.09 (95% CI: 0.09, 0.10) and 0.09 (95% CI: 0.08, 0.10) percentage-point increase in abandonment among commercially insured and Medicare patients. Among commercially insured and Medicare patients without prior buprenorphine use, respectively, a $10 increase in cost-sharing per 30-day supply was associated with a 0.12 (95% CI: 0.11, 0.14) and 0.13 (95% CI: 0.07, 0.18) percentage-point higher increase in the probability of abandonment compared with patients with > 90 days of prior buprenorphine use. CONCLUSIONS: Among commercially insured and Medicare patients, buprenorphine prescription abandonment is rare and only minimally associated with cost-sharing. Findings suggest elimination of buprenorphine cost-sharing should only be one component of a larger, multi-faceted campaign to increase buprenorphine dispensing.

Association Between Cost Sharing and Naloxone Prescription Dispensing.

Importance: Increasing access to naloxone (an opioid antagonist that can reverse overdose) could slow the US opioid epidemic. Prior studies suggest cost sharing may be a barrier to dispensing of naloxone prescriptions, but these studies were limited by their cross-sectional designs and use of databases that do not capture prescriptions that are not filled (abandoned). Objective: To evaluate the association between cost sharing and naloxone prescription abandonment (nondispensing of naloxone prescriptions). Design, Setting, and Participants: This cross-sectional, regression discontinuity analysis exploited the fact that deductibles typically reset at the beginning of the year in commercial and Medicare plans. The included data were derived from the 2020-2021 IQVIA Formulary Impact Analyzer (a pharmacy transactions database that represents 63% of prescriptions at US pharmacies). The analysis included claims for naloxone nasal spray among commercially insured patients and Medicare patients that occurred during the 60 days before January 1, 2021, through 59 days after January 1, 2021. Exposure: Cost sharing, which is defined as the amount patients would have to pay to fill prescriptions. Main Outcomes and Measures: Local linear regression models were used to assess for abrupt changes in cost sharing and the probability of prescription abandonment on January 1, 2021. To estimate the association between cost sharing and prescription abandonment, a fuzzy regression discontinuity analysis was conducted. Results: These analyses included naloxone claims for 71 306 commercially insured patients and 101 706 Medicare patients (40 019 [56.1%] and 61 410 [60.4%], respectively, were female). The commercially insured patients and Medicare patients accounted for 73 311 and 106 076 naloxone claims, respectively. On January 1, 2021, the mean cost sharing per claim increased by $15.0 (95% CI, $13.8-$16.2) for commercially insured patients and increased by $12.3 (95% CI, $10.9-$13.6) for Medicare patients and the probability of abandonment increased by 4.7 (95% CI, 3.2-6.2) percentage points and 2.8 (95% CI, 1.6-4.1) percentage points, respectively. The results from the fuzzy regression discontinuity analysis suggest a decision by commercial and Medicare plans to increase naloxone cost sharing by $10 would be associated with percentage-point increases of 3.1 (95% CI, 2.2-4.1) and 2.3 (95% CI, 1.4-3.2), respectively, in the probability of abandonment. Conclusions: The elimination of cost sharing might be associated with increased naloxone dispensing to commercially insured and Medicare patients.

Retrospective study investigating naloxone prescribing and cost in US Medicaid and Medicare patients.

BACKGROUND: Opioid overdoses in the USA have increased to unprecedented levels. Administration of the opioid antagonist naloxone can prevent overdoses. OBJECTIVE: This study was conducted to reveal the pharmacoepidemiologic patterns in naloxone prescribing to Medicaid patients from 2018 to 2021 as well as Medicare in 2019. DESIGN: Observational pharmacoepidemiologic study SETTING: US Medicare and Medicaid naloxone claims INTERVENTION: The Medicaid State Drug Utilisation Data File was utilised to extract information on the number of prescriptions and the amount prescribed of naloxone at a national and state level. The Medicare Provider Utilisation and Payment was also utilised to analyse prescription data from 2019. OUTCOME MEASURES: States with naloxone prescription rates that were outliers of quartile analysis were noted. RESULTS: The number of generic naloxone prescriptions per 100 000 Medicaid enrollees decreased by 5.3%, whereas brand naloxone prescriptions increased by 245.1% from 2018 to 2021. There was a 33.1-fold difference in prescriptions between the highest (New Mexico=1809.5) and lowest (South Dakota=54.6) states in 2019. Medicare saw a 30.4-fold difference in prescriptions between the highest (New Mexico) and lowest states (also South Dakota) after correcting per 100 000 enrollees. CONCLUSIONS: This pronounced increase in the number of naloxone prescriptions to Medicaid patients from 2018 to 2021 indicates a national response to this widespread public health emergency. Further research into the origins of the pronounced state-level disparities is warranted.

Patients' willingness to pay for naloxone: A national cross-sectional survey of prescription opioid users with chronic pain in the United States.

BACKGROUND: Millions of U.S. people have been heavily affected by opioids. In March 2023, the Food and Drug Administration approved naloxone as an over-the-counter medication. This has allowed more access to patients at high risk of opioid overdose. However, the patient's willingness to pay for naloxone at the pharmacy counter has not been assessed. OBJECTIVES: This study aimed to characterize factors associated with the willingness to pay for naloxone among the patient group. METHODS: A cross-sectional Qualtrics online panel survey instrument was developed. This survey was distributed to patients in the United States, aged ≥ 18 years, with any chronic pain and taking opioids. The survey included demographics, and clinical characteristics (pain assessment, opioid use, and knowledge of naloxone). In addition, willingness to pay was assessed using a 7-point Likert scale ranging from strongly disagree to strongly agree. An ordinal logistic regression model was used to examine demographic and clinical characteristics. RESULTS: A total of 549 subjects completed the survey (women [53.01%], white or Caucasian (83.61%), age mean [SD] 44 [13]). Women were associated with less willingness to pay (adjusted odds ratio [aOR] 0.685 [95% CI 0.478-0.983], P = 0.0403). Compared with the high household income group (≥ $150,000), low household income ≤ $25,000 (aOR 0.326 [95% CI 0.160-0.662], P = 0.0020) or income between $25,000 and 74,999 (aOR 0.369 [95% CI 0.207-0.657], P = 0.0007) was associated with less likelihood of willing to pay. Patients with a previous diagnosis of obstructive sleep apnea were associated with a higher likelihood of willingness to pay (aOR 1.685 [95% CI 1.138-2.496], P = 0.0092). Each unit increase in pain was also associated with a higher likelihood of willingness to pay (aOR 1.247 [95% CI 1.139-1.365], P < 0.0001). CONCLUSIONS: Demographics and clinical factors were associated with willingness to pay for naloxone. This study's findings are useful in the development of interventions to address pharmacy-based naloxone distribution programs.

Naloxone Accessibility by Standing Order in North Carolina Community Pharmacies.

BACKGROUND: According to a standing order in North Carolina (NC), naloxone can be purchased without a provider prescription. OBJECTIVE: The objective of this study is to examine whether same-day naloxone accessibility and cost vary by pharmacy type and rurality in NC. METHODS: A cross-sectional telephone audit of 202 NC community pharmacies stratified by pharmacy type and county of origin was conducted in March and April 2023. Trained "secret shoppers" enacted a standardized script and recorded whether naloxone was available and its cost. We examined the relationship between out-of-pocket naloxone cost, pharmacy type, and rurality. RESULTS: Naloxone could be purchased in 53% of the pharmacies contacted; 26% incorrectly noting that naloxone could be filled only with a provider prescription and 21% did not sell naloxone. Naloxone availability by standing order was statistically different by pharmacy type (chain/independent) (χ2 = 20.58, df = 4, P value < 0.001), with a higher frequency of willingness to dispense according to the standing order by chain pharmacies in comparison to independent pharmacies. The average quoted cost for naloxone nasal spray at chain pharmacies was $84.69; the cost was significantly more ($113.54; P < 0.001) at independent pharmacies. Naloxone cost did not significantly differ by pharmacy rurality (F2,136 = 2.38, P = 0.10). CONCLUSION: Approximately half of NC community pharmacies audited dispense naloxone according to the statewide standing order, limiting same-day access to this life-saving medication. Costs were higher at independent pharmacies, which could be due to store-level policies. Future studies should further investigate these cost differences, especially as intranasal naloxone transitions from a prescription only to over-the-counter product.

Trends in Out-of-Pocket Costs for and Characteristics of Pharmacy-Dispensed Naloxone by Payer Type.

This study examines mean yearly out-of-pocket cost for naloxone dispensed from retail pharmacies by payer between 2018 and 2022 and by prescription characteristics and payer in 2022.

Real-world changes in US health system hospital-based services following treatment with a prescription digital therapeutic for opioid use disorder.

Outcomes associated with buprenorphine therapy for the treatment of opioid use disorder (OUD) are suboptimal. reSET-O is an FDA-authorized prescription digital therapeutic (PDT) delivering neurobehavioral therapy via mobile devices to patients with OUD treated with buprenorphine. This analysis evaluated the net impact of reSET-O on medical costs among actively-engaged reSET-O patients using real-world observations. This real-world retrospective analysis of health care claims between October 2018 and October 2019 evaluated health care resource utilization up to 6 months before and 6 months after the initiation of a reSET-O prescription after accounting for the subset of patients not continuing on therapy after week 1 (non-engaged patients). Repeated-measures negative binomial models compared incidences of hospital-based encounters/procedures adjusted for days in each period as well as associated costs. The number needed to treat (NNT) to avoid an inpatient visit was calculated. Of the 351 patients who were prescribed reSET-O, 321 met the criteria of active engagement. Treatment with reSET-O was associated with a substantial reduction in medical costs of -$765,450 (-$2,385/patient, $235/patient greater than a previous analysis in which non-engaged patients were included) in the 6-month period after initiation. The gross reSET-O prescription cost of $584,415 ($1,665/patient) was substantially offset by $49,950 ($142.31/patient) in refunds to payers. The medical cost reduction in engaged patients offset the cost of the therapeutic resulting in an overall cost reduction of -$230,985 in this cohort (net savings of -$720 per patient). The number needed to treat to avoid an inpatient visit was 4.8. Engagement and continued treatment with reSET-O in patients with OUD treated with buprenorphine is associated with substantial real-world reductions in medical costs in the 6-month period following the initiation of the reSET-O prescription.

Naloxone's role in the national opioid crisis-past struggles, current efforts, and future opportunities.

Over the past 25 years, naloxone has emerged as a critical lifesaving overdose antidote. Public health advocates and community activists established early methods for naloxone distribution to people who inject drugs, but a legacy of stigmatization and opposition to universal naloxone access continues to limit the drug's full potential to reduce opioid-related mortality. The establishment of naloxone distribution programs under the umbrella of syringe exchange programs faces the same practical, ideological and financial barriers to expansion similar to those faced by syringe exchange programs themselves. The expansion of naloxone from the confines of a few syringe exchange programs to what we see today represents an enormous triumph for the grass-roots activists, service providers, and public health professionals who have fought to guarantee lay access to naloxone. Despite the extensive efforts to expand access to naloxone, naloxone continues to remains a scarce resource in many US localities. Considerable naloxone "deserts" remain and even where there is naloxone access, it does not always reach those at risk. Promising areas for expansion include the development of more robust telehealth methods for naloxone distribution, including subsidized mail delivery programs; lowering barriers to pharmacy access; working with hospitals, ambulances, and law enforcement to expand naloxone "leave behind" programs; providing naloxone co-prescription with medications for opioid use disorder; and working with prisons, shelters, and networks of people who use drugs to increase access to the lifesaving medication. Efforts to ensure over-the-counter and low- or no-cost naloxone are ongoing and stand alongside medication-assisted treatments as efficacious, readily-actionable, and cost-efficient population-level interventions available for combatting opioid-related overdose in the United States.

Factors Affecting Buprenorphine Utilization and Spending in Medicaid, 2002-2018.

OBJECTIVE: Buprenorphine is an essential medication for the treatment of opioid use disorder (OUD), but studies show it has been underused over the last 2 decades. We sought to evaluate utilization of and spending on buprenorphine formulations in Medicaid and to evaluate the impact of key market and regulatory factors affecting availability of different formulations and generic versions. METHODS: We first identified all buprenorphine formulations approved by the Food and Drug Administration for OUD using Drugs@FDA. We then used National Drug Codes to identify each drug in the Medicaid State Drug Utilization Data and extracted annual utilization rates and spending between 2002 and 2018 by drug and according to whether a brand-name or generic version was dispensed. We compared these trends to market and regulatory factors that affected competition, which we identified through searching the Federal Register, Westlaw, PubMed, and Google News. RESULTS: Brand-name buprenorphine-naloxone sublingual tablet and film formulations (Suboxone) were dispensed 2.7 times more (n = 634 213 140) and reimbursed 4.4 times more (n = $4 440 556 473) than all other formulations combined (n = 237 769 689; $1 018 988 133). We identified numerous market and regulatory factors that contributed to an estimated 9-year delay in generic versions of the tablet formulation and 6-year delay for generic versions of the film formulation. CONCLUSIONS: Brand-name buprenorphine formulations have been widely used in Medicaid, leading to substantial costs, in part because generic versions were delayed by multiple years owing to market and regulatory factors. Timely availability of low-cost generics could have helped encourage OUD treatment with buprenorphine during the height of the opioid crisis.

Economic Evaluation of Interventions to Address Opioid Misuse: A Systematic Review of Methods Used in Simulation Modeling Studies.

OBJECTIVES: Several evidence-based interventions exist for people who misuse opioids, but there is limited guidance on optimal intervention selection. Economic evaluations using simulation modeling can guide the allocation of resources and help tackle the opioid crisis. This study reviews methods employed by economic evaluations using computer simulations to investigate the health and economic effects of interventions meant to address opioid misuse. METHODS: We conducted a systematic mapping review of studies that used simulation modeling to support the economic evaluation of interventions targeting prevention, treatment, or management of opioid misuse or its direct consequences (ie, overdose). We searched 6 databases and extracted information on study population, interventions, costs, outcomes, and economic analysis and modeling approaches. RESULTS: Eighteen studies met the inclusion criteria. All of the studies considered only one segment of the continuum of care. Of the studies, 13 evaluated medications for opioid use disorder, and 5 evaluated naloxone distribution programs to reduce overdose deaths. Most studies estimated incremental cost per quality-adjusted life-years and used health system and/or societal perspectives. Models were decision trees (n = 4), Markov (n = 10) or semi-Markov models (n = 3), and microsimulations (n = 1). All of the studies assessed parameter uncertainty though deterministic and/or probabilistic sensitivity analysis, 4 conducted formal calibration, only 2 assessed structural uncertainty, and only 1 conducted expected value of information analyses. Only 10 studies conducted validation. CONCLUSIONS: Future economic evaluations should consider synergies between interventions and examine combinations of interventions to inform optimal policy response. They should also more consistently conduct model validation and assess the value of further research.

Health and economic outcomes of treatment with extended-release naltrexone among pre-release prisoners with opioid use disorder (HOPPER): protocol for an evaluation of two randomized effectiveness trials.

BACKGROUND: Persons with an opioid use disorder (OUD) who were incarcerated face many challenges to remaining abstinent; concomitantly, opioid-overdose is the leading cause of death among this population, with the initial weeks following release proving especially fatal. Extended-release naltrexone (XR-NTX) is the most widely-accepted, evidence-based OUD pharmacotherapy in criminal justice settings, and ensures approximately 30 days of protection from opioid overdose. The high cost of XR-NTX serves as a barrier to uptake by many prison/jail systems; however, the cost of the medication should not be viewed in isolation. Prison/jail healthcare budgets are ultimately determined by policymakers, and the benefits/cost-offsets associated with effective OUD treatment will directly and indirectly affect their overall budgets, and society as a whole. METHODS: This protocol describes a study funded by the National Institute of Drug Abuse (NIDA) to: evaluate changes in healthcare utilization, health-related quality-of-life, and other resources associated with different strategies of XR-NTX delivery to persons with OUD being released from incarceration; and estimate the relative "value" of each strategy. Data from two ongoing, publicly-funded, randomized-controlled trials will be used to evaluate these questions. In Study A, (XR-NTX Before vs. After Reentry), participants are randomized to receive their first XR-NTX dose before release, or at a nearby program post-release. In Study B, (enhanced XR-NTX vs. XR-NTX), both arms receive XR-NTX prior to release; the enhanced arm receives mobile medical (place of residence) XR-NTX treatment post-release, and the XR-NTX arm receives referral to a community treatment program post-release. The economic data collection instruments required to evaluate outcomes of interest were incorporated into both studies from baseline. Moreover, because the same instruments are being used in both trials on comparable populations, we have the opportunity to not only assess differences in outcomes between study arms within each trial, but also to merge the data sets and test for differences across trials. DISCUSSION: Initiating XR-NTX for OUD prior to release from incarceration may improve patient health and well-being, while also producing downstream cost-offsets. This study offers the unique opportunity to assess the effectiveness and cost-effectiveness of multiple strategies, according to different stakeholder perspectives.

Cost-Effectiveness of Intranasal Naloxone Distribution to High-Risk Prescription Opioid Users.

OBJECTIVES: To determine the cost-effectiveness of pharmacy-based intranasal naloxone distribution to high-risk prescription opioid (RxO) users. METHODS: We developed a Markov model with an attached tree for pharmacy-based naloxone distribution to high-risk RxO users using 2 approaches: one-time and biannual follow-up distribution. The Markov structure had 6 health states: high-risk RxO use, low-risk RxO use, no RxO use, illicit opioid use, no illicit opioid use, and death. The tree modeled the probability of an overdose happening, the overdose being witnessed, naloxone being available, and the overdose resulting in death. High-risk RxO users were defined as individuals with prescription opioid doses greater than or equal to 90 morphine milligram equivalents (MME) per day. We used a monthly cycle length, lifetime horizon, and US healthcare perspective. Costs (2018) and quality-adjusted life-years (QALYs) were discounted 3% annually. Microsimulation was performed with 100 000 individual trials. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: One-time distribution of naloxone prevented 14 additional overdose deaths per 100 000 persons, with an incremental cost-effectiveness ratio (ICER) of $56 699 per QALY. Biannual follow-up distribution led to 107 additional lives being saved with an ICER of $84 799 per QALY compared with one-time distribution. Probabilistic sensitivity analyses showed that a biannual follow-up approach would be cost-effective 50% of the time at a willingness-to-pay (WTP) threshold of $100 000 per QALY. Naloxone effectiveness and proportion of overdoses witnessed were the 2 most influential parameters for biannual distribution. CONCLUSION: Both one-time and biannual follow-up naloxone distribution in community pharmacies would modestly reduce opioid overdose deaths and be cost-effective at a WTP of $100 000 per QALY.

Responses among substance abuse treatment providers to the opioid epidemic in the USA: Variations in buprenorphine and methadone treatment by geography, operational, and payment characteristics, 2007-16.

OBJECTIVE: To identify the geographic, organisational, and payment correlates of buprenorphine and methadone treatment among substance abuse treatment (SAT) providers. METHODS: Secondary analyses of the National Survey of Substance Abuse Treatment Services (NSSATS) from 2007-16 were conducted. We provide bivariate descriptive statistics regarding substance abuse treatment services which offered buprenorphine and methadone treatment from 2007-16. Using multiple logistic regression, we regressed geographic, organisational, and payment correlates on buprenorphine and methadone treatment. RESULTS: Buprenorphine is increasingly offered at SAT facilities though uptake remains comparatively low outside of the northeast. SAT facilities run by tribal governments or Indian Health Service which offer buprenorphine remain low compared to privately operated SAT facilities (AOR = 0.528). The odds of offering buprenorphine among facilities offering free or no charge treatment (AOR = 0.838) or a sliding fee scale (AOR = 0.464) was lower. SAT facilities accepting Medicaid payments showed higher odds of offering methadone treatment (AOR = 2.035). CONCLUSIONS: Greater attention towards the disparities in provision of opioid agonist therapies is warranted, especially towards the reasons why uptake has been moderate among civilian providers. Additionally, the care needs of Native Americans facing opioid-related use disorders bears further scrutiny.

Rates and Costs of Dispensing Naloxone to Patients at High Risk for Opioid Overdose in the United States, 2014-2018.

INTRODUCTION: Clinical practice guidelines recommend co-prescribing naloxone to patients at high risk of opioid overdose, but few such patients receive naloxone. High costs of naloxone may contribute to limited dispensing. OBJECTIVE: The aim of this study was to evaluate rates and costs of dispensing naloxone to patients receiving opioid prescriptions and at high risk for opioid overdose. METHODS: Using claims data from a large US commercial insurance company, we conducted a retrospective cohort study of new opioid initiators between January 2014 and December 2018. We identified patients at high risk for overdose defined as a diagnosis of opioid use disorder, prior overdose, an opioid prescription of ≥ 50 mg morphine equivalents/day for ≥ 90 days, and/or concurrent benzodiazepine prescriptions. RESULTS: Among 5,292,098 new opioid initiators, 616,444 (12%) met criteria for high risk of overdose during follow-up, and, of those, 3096 (0.5%) were dispensed naloxone. The average copayment was US$24.83 for naloxone (standard deviation [SD] 67.66) versus US$9.74 for the index opioid (SD 19.75). The average deductible was US$6.18 for naloxone (SD 27.32) versus US$3.74 for the index opioid (SD 25.56), with 94% and 88% having deductibles of US$0 for their naloxone and opioid prescriptions, respectively. The average out-of-pocket cost was US$31.01 for naloxone (SD 73.64) versus US$13.48 for the index opioid (SD 34.95). CONCLUSIONS: Rates of dispensing naloxone to high risk patients were extremely low, and prescription costs varied greatly. Since improving naloxone's affordability may increase access, whether naloxone's high cost is associated with low dispensing rates should be evaluated.

Cost-effectiveness analysis of alternative naloxone distribution strategies: First responder and lay distribution in the United States.

BACKGROUND: The U.S. is facing an unprecedented number of opioid-related overdose deaths, and an array of other countries have experienced increases in opioid-related fatalities. In the U.S., naloxone is increasingly distributed to first responders to improve early administration to overdose victims, but its cost-effectiveness has not been studied. Lay distribution, in contrast, has been found to be cost-effective, but rising naloxone prices and increased mortality due to synthetic opioids may reduce cost-effectiveness. We evaluate the cost-effectiveness of increased naloxone distribution to (a) people likely to witness or experience overdose ("laypeople"); (b) police and firefighters; (c) emergency medical services (EMS) personnel; and (d) combinations of these groups. METHODS: We use a decision-analytic model to analyze the cost-effectiveness of eight naloxone distribution strategies. We use a lifetime horizon and conduct both a societal analysis (accounting for productivity and criminal justice system costs) and a health sector analysis. We calculate: the ranking of strategies by net monetary benefit; incremental cost-effectiveness ratios; and number of fatal overdoses. RESULTS: High distribution to all three groups maximized net monetary benefit and minimized fatal overdoses; it averted 21% of overdose deaths compared to minimum distribution. High distribution to laypeople and one of the other groups comprised the second and third best strategies. The majority of health gains resulted from increased lay distribution. In the societal analysis, every strategy was cost-saving compared to its next-best alternative; cost savings were greatest in the maximum distribution strategy. In the health sector analysis, all undominated strategies were cost-effective. Results were highly robust to deterministic and probabilistic sensitivity analysis. CONCLUSIONS: Increasing naloxone distribution to laypeople and first responder groups would maximize health gains and be cost-effective. If feasible, communities should distribute naloxone to all groups; otherwise, distribution to laypeople and one of the first responder groups should be emphasized.

Methadone, Buprenorphine, or Detoxification for Management of Perinatal Opioid Use Disorder: A Cost-Effectiveness Analysis.

OBJECTIVE: To estimate whether methadone, buprenorphine, or detoxification treatment is the most cost-effective approach to the management of opioid use disorder (OUD) during pregnancy. METHODS: We created a decision analytic model that compared the cost effectiveness (eg, the marginal cost of the strategy in U.S. dollars divided by the marginal effectiveness of the strategy, measured in quality-adjusted life-years [QALYs]) of initiation of methadone, buprenorphine, or detoxification in treatment of OUD during pregnancy. Probabilities, costs, and utilities were estimated from the existing literature. Incremental cost-effective ratios for each strategy were calculated, and a ratio of $100,000 per QALY was used to define cost effectiveness. One-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed. RESULTS: Under base assumptions, initiation of buprenorphine was more effective at a lower cost than either methadone or detoxification and thus was the dominant strategy. Buprenorphine was no longer cost effective if the cost of methadone was 8% less than the base-case estimate ($1,646/month) or if the overall costs of detoxification were 121% less than the base-case estimate for the detoxification cost multiplier, which was used to increase the values of both inpatient and outpatient management of detoxification by a factor of 2. Monte Carlo analyses revealed that buprenorphine was the cost-effective strategy in 70.5% of the simulations. Direct comparison of buprenorphine with methadone demonstrated that buprenorphine was below the incremental cost-effective ratio in 95.1% of simulations; direct comparison between buprenorphine and detoxification demonstrated that buprenorphine was below the incremental cost-effective ratio in 45% of simulations. CONCLUSION: Under most circumstances, we estimate that buprenorphine is the cost-effective strategy when compared with either methadone or detoxification as treatment for OUD during pregnancy. Nonetheless, the fact that buprenorphine was not the cost-effective strategy in almost one out of three of simulations suggests that the robustness of our model may be limited and that further evaluation of the cost-effective approach to the management of OUD during pregnancy is needed.

Impact of a community-based naloxone distribution program on opioid overdose death rates.

BACKGROUND: In August 2013, a naloxone distribution program was implemented in North Carolina (NC). This study evaluated that program by quantifying the association between the program and county-level opioid overdose death (OOD) rates and conducting a cost-benefit analysis. METHODS: One-group pre-post design. Data included annual county-level counts of naloxone kits distributed from 2013 to 2016 and mortality data from 2000-2016. We used generalized estimating equations to estimate the association between cumulative rates of naloxone kits distributed and annual OOD rates. Costs included naloxone kit purchases and distribution costs; benefits were quantified as OODs avoided and monetized using a conservative value of a life. RESULTS: The rate of OOD in counties with 1-100 cumulative naloxone kits distributed per 100,000 population was 0.90 times (95% CI: 0.78, 1.04) that of counties that had not received kits. In counties that received >100 cumulative kits per 100,000 population, the OOD rate was 0.88 times (95% CI: 0.76, 1.02) that of counties that had not received kits. By December 2016, an estimated 352 NC deaths were avoided by naloxone distribution (95% CI: 189, 580). On average, for every dollar spent on the program, there was $2742 of benefit due to OODs avoided (95% CI: $1,237, $4882). CONCLUSIONS: Our estimates suggest that community-based naloxone distribution is associated with lower OOD rates. The program generated substantial societal benefits due to averted OODs. States and communities should continue to support efforts to increase naloxone access, which may include reducing legal, financial, and normative barriers.