Identifying opioid dose reductions and discontinuation among patients with chronic opioid therapy.

PURPOSE: To identify and systematically categorize opioid dose reductions and discontinuations in large administrative datasets. METHODS: Using a dataset of Oregon Medicaid beneficiaries linked with prescription drug monitoring program (PDMP) data between 2014 and 2017, we identified patients with high-dose chronic opioid therapy (COT), ≥84 consecutive days with an average daily MME of ≥50 on each of those days. We categorized patients into four mutually exclusive groups based on the trajectory of opioid use in the year after COT: abrupt discontinuation, dose reduction and discontinuation, dose reduction without discontinuation, and stable or increasing dose. Finally, we examined prescription patterns in each category. RESULTS: Among individuals with high-dose COT, 7636 (37.1%) had an abrupt discontinuation, 2577 (12.5%) had a dose reduction and discontinuation, 7739 (37.6%) had a dose reduction without discontinuation, and 2623 (12.8%) had a stable or increasing dose in the year following the COT episode. Among those who discontinued opioid use (n = 10 213, 49.6%), three in four (74.8%) did so without evidence of tapering. Patients who discontinued opioid use were younger, had higher daily MME during COT, and were more likely to have filled a benzodiazepine or had a multiple provider or multiple pharmacy episode compared to patients who did not discontinue opioid use. CONCLUSIONS: Dose reductions and discontinuations after a COT episode can be identified in large administrative datasets. Those with a discontinuation were more likely to have riskier prescription profiles during their COT episode.

Prescription Opioid Dispensing Patterns Prior to Heroin Overdose in a State Medicaid Program: a Case-Control Study.

BACKGROUND: A large proportion of individuals who use heroin report initiating opioid use with prescription opioids. However, patterns of prescription opioid use preceding heroin-related overdose have not been described. OBJECTIVE: To describe prescription opioid use in the year preceding heroin overdose. DESIGN: Case-control study comparing prescription opioid use with a heroin-involved overdose, non-heroin-involved opioid overdose, and non-overdose controls from 2015 to 2017. PARTICIPANTS: Oregon Medicaid beneficiaries with linked administrative claims, vital statistics, and prescription drug monitoring program data. MAIN MEASURES: Opioid, benzodiazepine, and other central nervous system depressant prescriptions preceding overdose; among individuals with one or more opioid prescription, we assessed morphine milligram equivalents per day, overlapping prescriptions, prescriptions from multiple prescribers, long-term use, and discontinuation of long-term use. KEY RESULTS: We identified 1458 heroin-involved overdoses (191 fatal) and 2050 non-heroin-involved opioid overdoses (266 fatal). In the 365 days prior to their overdose, 45% of individuals with a heroin-involved overdose received at least one prescribed opioid compared with 78% of individuals who experienced a non-heroin-involved opioid overdose (p < 0.001). For both heroin- and non-heroin-involved overdose cases, the likelihood of receiving an opioid increased with age. Among heroin overdose cases with an opioid dispensed, the rate of multiple pharmacy use was the only high-risk opioid pattern that was greater than non-overdose controls (adjusted odds ratio 3.2; 95% confidence interval 1.48 to 6.95). Discontinuation of long-term opioid use was not common prior to heroin overdose and not higher than discontinuation rates among non-overdose controls. CONCLUSIONS: Although individuals with a heroin-involved overdose were less likely to receive prescribed opioids in the year preceding their overdose relative to non-heroin opioid overdose cases, prescription opioid use was relatively common and increased with age. Discontinuation of long-term prescription opioid use was not associated with heroin-involved overdose.

A comparison of trends in opioid dispensing patterns between Medicaid pharmacy claims and prescription drug monitoring program data.

PURPOSE: Public and private payers have implemented benefit limitations to reduce high-risk opioid prescriptions. The effect of these policies on the increase of out-pocket payment is unclear. To understand this gap, we compared the discrepancies in trends between opioid prescription fills vs claims among Medicaid beneficiaries. METHODS: Data from the Oregon Prescription Drug Monitoring Program (PDMP) and Oregon Medicaid administrative claims were used to identify Medicaid beneficiaries 18 years and older enrolled at least one full month from 2015 to 2017. Generalized linear models assessed the trends in the monthly rates of opioid PDMP prescription fills and pharmacy claims per 1000 eligible members. Rates by morphine equivalent dose (MED) tier (<50, 50-89, 90-120, >120 MED) and co-prescribed opioid and benzodiazepine were also assessed. RESULTS: During the study period, an average of 495 355 Medicaid members had 2 797 054 opioid PDMP fills and 2 472 155 opioid Medicaid pharmacy claims. Study participants had 15.4 (95% confidence interval [CI] 13.6 to 17.0; P < .001) more prescriptions per 1000 member per month in the PDMP data (114.1 [SD 7.4]) compared with the Medicaid claims data (98.7 [SD 7.9]). Similarly, there were 1.9 more co-occurring opioid/benzodiazepine prescriptions per 1000 members per month observed in the PDMP data than the Medicaid claims data (95% CI 1.7 to 2.1; P < .001). At each MED tier, the PDMP fills were consistently higher than the claims (P < .001). CONCLUSIONS: Higher rate of fills in the PDMP compared to pharmacy claims suggests that there may be an increasing trend of out-of-pocket payment among Medicaid beneficiaries.

Impact of the RESPOND Toolkit on community pharmacists' opioid safety attitudes, self-efficacy, and knowledge.

OBJECTIVE: Pharmacists are well positioned to reduce risks from opioid-prescribing but often lack resources and training to effectively support these activities. The Resources Encouraging Safe Prescription Opioid and Naloxone Dispensing (RESPOND) Toolkit is an educational package developed to provide community pharmacists with a comprehensive education program and practice resources on prescription drug misuse, prescription drug monitoring programs (PDMPs), and naloxone dispensing. Our objective was to evaluate the effectiveness of the RESPOND Toolkit to improve pharmacists' knowledge and assess changes in pharmacists' attitudes and beliefs toward opioid use disorder (OUD) and PDMPs across a diverse pool of Oregon community pharmacists. METHODS: Pharmacists were recruited using an electronic mailing list of Oregon-licensed pharmacists. Pharmacists were asked to complete a preintervention survey, 3 online educational modules with pre- and post-module quizzes (optional), and a postintervention survey. Data were analyzed using paired t tests, chi-square analyses, and effect size calculations (Cohen's d). RESULTS: A total of 131 pharmacists completed the 3 educational modules and postintervention survey. Respondents were aged 37.6 ± 11.0 (mean ± SD) years and mostly frontline pharmacy staff (n = 86; 65.6%) with 10.5 ± 11.6 years of pharmacy experience. Pharmacists' knowledge and attitudes toward OUD, perceived behavioral control to address OUD, resources to address OUD, and perceptions regarding PDMP-associated difficulties improved significantly as a result of the intervention (all P < 0.001). In addition, 120 pharmacists completed the optional module quizzes, and aggregate knowledge assessment scores improved significantly (P < 0.001). CONCLUSION: The RESPOND Toolkit is an effective and scalable training resource for community pharmacists, with the potential to promote behavioral shifts that support opioid safety among patients. The results demonstrated improved attitudes, knowledge, and perceived behavioral control. Future work on the RESPOND Toolkit should evaluate the effect of implementation on pharmacist clinical activities and dispensing outcomes.

Repository Corticotropin Versus Glucocorticoid for Nephrotic Syndrome: When Will We See the Evidence?

Despite little evidence supporting its superiority to glucocorticoid therapy, use and expenditures for repository corticotropin (rACTH) injection (H.P. Acthar Gel; Mallinckrodt) have increased dramatically in the last 5 years, particularly among a small number of nephrologists, rheumatologists, and neurologists. Recently, the manufacturer justified the extremely high and rapidly increasing cost of rACTH by citing the ongoing need to generate clinical data to support its use. We test this assertion by investigating the quality and provenance of the evidence likely to emerge in the foreseeable future. We identified all completed, in-progress, and proposed studies of rACTH registered at ClinicalTrials.gov. 75 studies representing 2,953 participants met inclusion criteria. Studies addressed primarily nephrologic (n = 23), rheumatologic (n = 28), and neurologic (n =22) indications. Of the 23 studies proposed for renal indications (enrollment, 33 ± 49 [mean ± SD]), 11 were not randomized, 8 compared only different rACTH treatment regimens, and 4 compared rACTH to placebo. No studies of rACTH proposed for renal indications included an rACTH-free arm receiving active treatment (ie, another form of immunosuppression). We conclude that evidence emerging in the foreseeable future is unlikely to broadly support rACTH use over lower-cost glucocorticoid-based alternatives for renal indications.

Pharmacists' attitudes, knowledge, utilization, and outcomes involving prescription drug monitoring programs: A brief scoping review.

OBJECTIVE: While literature on pharmacists' engagement with prescription drug monitoring programs (PDMPs) is growing, no formal synthesis of findings has been conducted to provide overarching recommendations for research or practice. The objective of this study was to identify and synthesize findings from current literature on community pharmacists' attitudes toward, knowledge of, and registration and utilization behaviors regarding PDMPs. DATA SOURCES: Electronic databases (MEDLINE, PsychINFO, Cochrane Database of Systematic Reviews, Google Scholar, and the Brandeis University PDMP Center of Excellence) and reference lists from relevant manuscripts were searched for relevant English-language manuscripts. Key words used in searches included pharmacist, prescription drug monitoring program, opioid safety, attitudes, knowledge, and utilization. STUDY SELECTION: Papers were included from January 1, 2008 up to October 6, 2017. Three authors independently screened articles for full text review; 2 authors independently conducted full text review for final study selection. Discrepancies were resolved through consensus. DATA EXTRACTION: Data were extracted to an evidence table, coded by topic category, and checked for accuracy. RESULTS: Fifteen manuscripts met inclusion criteria. The studies varied greatly in methodological approach. In general, pharmacists' attitudes and knowledge of PDMPs positively influenced likelihood to register and use their state's program. Targeted training had a substantial impact on knowledge, registration, and utilization. CONCLUSION: Pharmacist-targeted PDMPs and opioid safety training is highly recommended to increase knowledge of and insight into behavioral change.

Using prescription monitoring program data to characterize out-of-pocket payments for opioid prescriptions in a state Medicaid program.

BACKGROUND: Out-of-pocket payment for prescription opioids is believed to be an indicator of abuse or diversion, but few studies describe its epidemiology. Prescription drug monitoring programs (PDMPs) collect controlled substance prescription fill data regardless of payment source and thus can be used to study this phenomenon. OBJECTIVE: To estimate the frequency and characteristics of prescription fills for opioids that are likely paid out-of-pocket by individuals in the Oregon Medicaid program. RESEARCH DESIGN: Cross-sectional analysis using Oregon Medicaid administrative claims and PDMP data (2012 to 2013). SUBJECTS: Continuously enrolled nondually eligible Medicaid beneficiaries who could be linked to the PDMP with two opioid fills covered by Oregon Medicaid. MEASURES: Patient characteristics and fill characteristics for opioid fills that lacked a Medicaid pharmacy claim. Fill characteristics included opioid name, type, and association with indicators of high-risk opioid use. RESULTS: A total of 33 592 Medicaid beneficiaries filled a total of 555 103 opioid prescriptions. Of these opioid fills, 74 953 (13.5%) could not be matched to a Medicaid claim. Hydromorphone (30%), fentanyl (18%), and methadone (15%) were the most likely to lack a matching claim. The 3 largest predictors for missing claims were opioid fills that overlapped with other opioids (adjusted odds ratio [aOR] 1.37; 95% confidence interval [CI], 1.34-1.4), long-acting opioids (aOR 1.52; 95% CI, 1.47-1.57), and fills at multiple pharmacies (aOR 1.45; 95% CI, 1.39-1.52). CONCLUSIONS: Prescription opioid fills that were likely paid out-of-pocket were common and associated with several known indicators of high-risk opioid use.

Pharmacists' Knowledge and Perceptions of FDA Approval Standards and the Breakthrough Therapy Designation.

The "breakthrough therapy" designation (BTD) is a recent mechanism implemented by the United States Food and Drug Administration (FDA) to expedite access to drugs that address unmet needs. The purpose of this study is to describe pharmacists' knowledge of FDA drug-approval standards and knowledge and perceptions of the BTD. Pharmacists engaged in advanced clinical practice were identified through membership profiles of a professional pharmacy organization. Eligible participants were then sent a questionnaire to assess knowledge of FDA approval standards and the BTD. A total of 226 pharmacists responded. The majority of respondents were women (70.2%) and had completed post-graduate training (85.8%). Over half correctly answered at least two of three questions on FDA approval standards (58.1%) and the BTD (78.1%). Only 24.1% of respondents identified as being familiar with the BTD. The majority of pharmacists (62.8%) were certain that FDA-approved "breakthrough" drugs represented a major advance over currently approved therapies and most (88.5%) preferred the drug designated as "breakthrough" in a hypothetical scenario. In conclusion, pharmacists were able to correctly answer questions about FDA approval standards and the BTD. However, they were unfamiliar with the implications of a BTD and may overestimate the benefit demonstrated by these drugs. Future research should identify knowledge gaps in pharmacist understanding of regulatory mechanisms designed to expedite drug approval.

Characteristics of Prescription Drug Use Among Individuals With Multiple Sclerosis in the US Medicare Population.

Background: Few studies have characterized the full spectrum of prescription drug use for individuals with multiple sclerosis (MS). The objective of this study was to describe patterns and expenditures for disease-modifying therapies (DMTs) and other prescription drugs among Medicare beneficiaries with MS. Methods: Using Medicare claims data in 2014, we identified a cohort of Medicare beneficiaries with 12 months of continuous eligibility and 3 or more MS-related inpatient, outpatient, or prescription claims. We quantified the number, type, and costs of prescribed DMTs and other medications for MS-related symptoms. Medication costs were calculated according to whether beneficiaries received additional subsidies, which eliminate most out-of-pocket costs. Results: Of 43,283 Medicare beneficiaries identified with MS, 70% were DMT users. Most used self-administered DMTs (67%), and 3% used natalizumab; 93% received a supportive care medication. Among the 82% of individuals without subsidies, the annual median total and out-of-pocket DMT costs were $56,794 (interquartile range [IQR], $44,837-$62,038) and $4566 (IQR, $849-$5270), respectively. The most commonly used supportive care drugs were antidepressants (62%), opioid analgesics (50%), antispasticity drugs (47%), and anticonvulsants (46%). Annual median total and out-of-pocket costs for these drugs were $15,134 (IQR, $6571-$19,620) and $255 (IQR, $56-$877), respectively. Conclusions: Most Medicare beneficiaries with MS using DMTs face considerable out-of-pocket costs. Beneficiaries also used a significant number of medications potentially used for MS-related symptoms, although total and out-of-pocket costs were modest.

Association Between Pharmacy Benefit Restrictions and Disease-Modifying Therapy Use in the Medicare Part D Program.

Background and Objectives: To determine the association between Medicare Part D plan disease-modifying therapy (DMT) restrictiveness and adherence and outcomes among people with multiple sclerosis (MS). Methods: We used Medicare claims data from 2010 to 2014 to identify individuals with a full year enrollment (Parts A, B, and D), an MS diagnosis, and 1 or more self-administered DMT prescription. Plans were considered restrictive if all available DMTs required a prior authorization or step therapy restriction; otherwise they were considered permissive. We compared DMT adherence, defined as a medication possession ratio ≥80%, MS-related emergency department or inpatient admissions, and outpatient visits by Part D plan restrictiveness. We used multivariate regression models to control for patient demographics and comorbidities. Results: There were 37,713 Medicare beneficiaries with MS who were enrolled in either restrictive (n = 29,901) or permissive (n = 7812) Part D plans during the study period. Patients enrolled in restrictive plans were older (60 vs 58 years; p < 0.001), more likely to live in the south (38% vs 23%; p < 0.001), eligible through disability (67% vs 60%; p < 0.001), and more likely to have several chronic comorbid conditions. Patients enrolled in restrictive plans were less likely to be adherent to their DMT (54% vs 57%; p < 0.001; adjusted odds ratio [aOR] 0.92, 95% confidence interval [CI] 0.88-0.98) and had a higher rate of MS-related outpatient visits (1.7 vs 1.4 per year; p < 0.001; aRR 1.27, 95% CI 1.23-1.31). Discussion: Medicare beneficiaries with MS enrolled in restrictive Part D plans were less adherent to their DMT and had higher rates of MS-related outpatient visits.

Characteristics and health care events of patients admitted to treatment for both heroin and methamphetamine compared to patients admitted for heroin only.

INTRODUCTION: Co-occurring heroin and methamphetamine use is a growing public health problem. This study assessed the characteristics of Medicaid patients admitted to substance use disorder (SUD) treatment programs for heroin and methamphetamine use compared with patients admitted for heroin only. METHODS: The study identified patients who entered treatment for heroin and methamphetamine and those admitted for heroin only between 2014 and 2017 from the Oregon Treatment Episode Data Set linked with Medicaid enrollment, and medical and pharmacy claims. We used a cross-sectional design to compare demographics, type of treatment, and substance use characteristics between the two groups. We used logistic regression models to assess differences in the odds of opioid-related and all-cause adverse events. RESULTS: Among the 3802 study sample, 2004 (53%) were admitted for both heroin and methamphetamine use. The heroin and methamphetamine group were more likely to be younger, female, White or American Indian/Alaska Native; and had more comorbidities than patients admitted for heroin only. Patients admitted for heroin and methamphetamine treatment were less likely to receive any medication for opioid use disorder (MOUD) (56% vs 75%, p < 0.001) and received fewer days of MOUD treatment (mean 188 vs. 265 days, p < 0.001) compared to the heroin only group. The heroin and methamphetamine group were more likely to receive buprenorphine (28.1% vs 24.2%) and less likely to receive methadone (39.9% vs 62.5%). The heroin and methamphetamine group began use at a younger age, used and injected more frequently than those admitted for heroin only. Patients treated for heroin and methamphetamine had 17% lower odds of OUD-related adverse events (aOR 0.83; 95% CI 0.70-0.99) and 52% higher odds of all-cause adverse events (aOR 1.52; 95% CI 1.14-2.03) relative to the heroin only group. CONCLUSION: Patients admitted for both heroin and methamphetamine reported greater addiction severity (more frequent use, earlier onset of use, and injection use), yet less commonly received MOUD compared to those who were admitted for heroin only. These findings indicate substantial missed opportunities for MOUD treatment even among people who successfully engage with the SUD treatment system.

Patient outcomes after opioid dose reduction among patients with chronic opioid therapy.

ABSTRACT: The net effects of prescribing initiatives that encourage dose reductions are uncertain. We examined whether rapid dose reduction after high-dose chronic opioid therapy (COT) associates with suicide, overdose, or other opioid-related adverse events. This retrospective cohort study included Oregon Medicaid recipients with high-dose COT. Claims were linked with prescription data from the prescription drug monitoring program and death data from vital statistics, 2014 to 2017. Participants were placed into 4 mutually exclusive dose trajectory groups after the high-dose COT period, and Cox proportional hazard models were used to examine the effect of dose changes on patient outcomes in the following year. Of the 14,596 high-dose COT patients, 4191 (28.7%) abruptly discontinued opioid prescriptions, 1648 (11.3%) reduced opioid dose before discontinuing, 6480 (44.4%) had a dose reduction but never discontinued, and 2277 (15.6%) had a stable or increasing dose. Discontinuation, whether abrupt (adjusted hazard ratio [aHR] 3.63; 95% confidence interval [CI] 1.42-9.25) or with dose reduction (aHR 4.47, 95% CI 1.68-11.88) significantly increased risk of suicide compared with those with stable or increasing dose. By contrast, discontinuation or dose reduction reduced the risk of overdose compared with those with a stable or increasing dose (aHR 0.36-0.62, 95% CI 0.20-0.94). Patients with an abrupt discontinuation were more likely to overdose on heroin (vs. prescription opioids) than patients in other groups (P < 0.0001). Our study suggests that patients on COT require careful risk assessment and supportive interventions when considering opioid discontinuation or continuation at a high dose.

Association between treatment setting and outcomes among oregon medicaid patients with opioid use disorder: a retrospective cohort study.

BACKGROUND: Residential treatment is a common approach for treating opioid use disorder (OUD), however, few studies have directly compared it to outpatient treatment. The objective of this study was to compare OUD outcomes among individuals receiving residential and outpatient treatment. METHODS: A retrospective cohort study used linked data from a state Medicaid program, vital statistics, and the Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episodes Dataset (TEDS) to compare OUD-related health outcomes among individuals treated in a residential or outpatient setting between 2014 and 2017. Multivariable Cox proportional hazards and logistic regression models examined the association between treatment setting and outcomes (i.e., opioid overdose, non-overdose opioid-related and all-cause emergency department (ED) visits, hospital admissions, and treatment retention) controlling for patient characteristics, co-morbidities, and use of medications for opioid use disorders (MOUD). Interaction models evaluated how MOUD use modified associations between treatment setting and outcomes. RESULTS: Of 3293 individuals treated for OUD, 957 (29%) received treatment in a residential facility. MOUD use was higher among those treated as an outpatient (43%) compared to residential (19%). The risk of opioid overdose (aHR 1.39; 95% CI 0.73-2.64) or an opioid-related emergency department encounter or admission (aHR 1.02; 95% CI 0.80-1.29) did not differ between treatment settings. Independent of setting, MOUD use was associated with a significant reduction in overdose risk (aHR 0.45; 95% CI 0.23-0.89). Residential care was associated with greater odds of retention at 6-months (aOR 1.71; 95% CI 1.32-2.21) but not 1-year. Residential treatment was only associated with improved retention for individuals not receiving MOUD (6-month aOR 2.05; 95% CI 1.56-2.71) with no benefit observed in those who received MOUD (aOR 0.75; 95% CI 0.46-1.29; interaction p = 0.001). CONCLUSIONS: Relative to outpatient treatment, residential treatment was not associated with reductions in opioid overdose or opioid-related ED encounters/hospitalizations. Regardless of setting, MOUD use was associated with a significant reduction in opioid overdose risk.

Closing the Part D Coverage Gap and Out-of-Pocket Costs for Multiple Sclerosis Drugs.

OBJECTIVE: To determine whether closing the Part D coverage gap (donut hole) between 2010 and 2019 lowered patients' out-of-pocket costs for disease-modifying therapies (DMTs) for multiple sclerosis (MS). METHODS: Using nationwide Medicare Formulary and Drug Pricing Files, we analyzed Part D drug benefit design and DMT prices in 2010, 2016, and 2019. We calculated average monthly list prices for DMTs available in each year (4 DMTs in 2010, 11 DMTs in 2016, and 14 DMTs in 2019). We projected patients' annual out-of-pocket cost for each DMT alone under a standard Part D plan in that year. We estimated potential savings attributable to closing the coverage gap between 2010 and 2019 (beneficiaries' cost sharing dropped from 100% to 25%) under 3 scenarios: no increase in price, an inflation-indexed price increase (3% annually), and the observed price increase. RESULTS: Median monthly DMT prices rose from $2,804 to $5,987 to $7,009 over the years 2010, 2016, and 2019, respectively. Median projected annual out-of-pocket costs rose from $5,916 to $6,229 to $6,618. With unchanged or inflation-indexed DMT price changes, closing the coverage gap would have reduced annual out-of-pocket costs by $2,260 (38% reduction) and $1,744 (29% reduction), respectively. Despite having the lowest monthly price, generic glatiramer acetate had among the highest out-of-pocket costs ($6,731 to $6,939 a year) in 2019. CONCLUSIONS: Medicare Part D beneficiaries can pay thousands of dollars yearly out of pocket for DMTs. Closing the Part D coverage gap did not reduce out-of-pocket costs for patients because of simultaneous increases in DMT prices.

Patterns of Prescription Opioid Use Prior to Self-reported Heroin Initiation.

OBJECTIVES: To determine the association between self-reported heroin initiation and patterns of prescription opioid use. METHODS: Using linked Oregon Medicaid, prescription drug monitoring program, and Treatment Episodes Data Set data, we conducted a case-control study of individuals reporting heroin initiation between 2015 and 2017 during treatment intake. Prescription drug monitoring program data provided prescription opioid use patterns, including long-term prescription opioid therapy, in the year before self-reported heroin initiation. Four controls were matched to each case on aggregate prescription opioid use and demographics. RESULTS: About half (49%) of individuals who reported heroin initiation filled an opioid in the year before initiation. Individuals who initiated heroin (n = 306) were more likely to receive prescriptions from multiple prescribers (24% vs 18%, P = 0.007) and pharmacies (12% vs 5%, P < 0.001) compared with matched controls (n = 1224). Long-term opioid therapy (13% vs 14%, P = 0.74) was uncommon and did not differ between groups. CONCLUSIONS: Although prescription opioid use commonly preceded self-reported heroin initiation, long-term opioid therapy was not common. Although this study did not find an association between opioid discontinuation and heroin initiation, sample size and follow-up limitations preclude definitive conclusions. Efforts to limit prescription opioids should continue to evaluate for unintended harms.

Pharmacy-related buprenorphine access barriers: An audit of pharmacies in counties with a high opioid overdose burden.

BACKGROUND: Pharmacies sometimes restrict access to buprenorphine-naloxone (buprenorphine) for individuals with opioid use disorder. The objective of this study was to quantify the frequency of barriers encountered by patients seeking to fill buprenorphine prescriptions from pharmacies in United States (US) counties with high opioid-related mortality. METHODS: To characterize buprenorphine availability, we conducted a telephone audit ("secret shopper") study using a standardized script in two randomly selected pharmacies (one chain, one independent) in US counties reporting higher than average opioid overdose rates. Availability across pharmacy type (chain versus independent), county characteristics (rurality, region, overdose rate), and day of week were analyzed using univariate tests of categorical data. Independent predictors of buprenorphine availability were then identified using a multivariable binomial regression model. RESULTS: Among 921 pharmacies contacted (467 chain, 454 independent), 73 % were in urban counties and 42 % were in Southern states. Of these pharmacies, 675 (73 %) reported being able to dispense buprenorphine. There were 183 (20 %) pharmacies that indicated they would not dispense buprenorphine. Independent pharmacies (adjusted prevalence ratio [aPR], 1.59; 95 % CI 1.21-2.08) and pharmacies in Southern states (aPR 2.06; 95 % CI 1.43-2.97) were significantly more likely to restrict buprenorphine. CONCLUSIONS: In US counties with high overdose mortality rates, one in five pharmacies indicated they would not dispense buprenorphine. Buprenorphine access limitations were more common among independent pharmacies and those in Southern states. Pharmacy-directed interventions may be necessary to ensure timely buprenorphine access for patients with opioid use disorder.

Qualitative study on the price of drugs for multiple sclerosis: Gaming the system.

OBJECTIVE: To describe pricing decisions, justifications, and attitudes among current and former biotech industry executives for companies that manufacture multiple sclerosis disease-modifying therapies. METHODS: Four leaders in biotech who have been directly involved in multiple sclerosis disease-modifying therapy pricing or marketing volunteered to participate in 30-minute semistructured interviews conducted via telephone. An expert in qualitative methods moderated and analyzed the interviews alongside the principal investigator. Brief, preinterview online surveys were also administered to provide additional context and insight for discussion. Interviews were audio-recorded and professionally transcribed. RESULTS: Participants consistently stated that initial price decisions were dictated by the price of existing competitors in the market. Revenue maximization and corporate growth were drivers of price escalations in the absence of continued market penetration. Lower revenue predictions outside the United States also informed pricing strategies. The growing complexity and clout of drug distribution and supply channels were also cited as contributing factors. Although decisions to raise prices were motivated by the need to attract investment for future innovation, recouping drug-specific research and development costs as a justification was not strongly endorsed as having a significant influence on pricing decisions. CONCLUSIONS: Contrary to prevailing narratives that underscore drug development costs, findings from our interviews suggest that the existing price ecosystem, overall corporate growth, international pricing disparities, and supply chain-related distortions may play a more central role in drug pricing decision.

The effect of out-of-pocket costs on initiation of disease-modifying therapies among medicare beneficiaries with multiple sclerosis.

BACKGROUND: Medicare beneficiaries with multiple sclerosis (MS) often face high out-of-pocket (OOP) costs for disease-modifying therapies (DMTs). It is unclear how cost-sharing affects therapy initiation. OBJECTIVES: To estimate the effects of patient cost-sharing on initiation of a DMT among Medicare beneficiaries with a new diagnosis code for MS. METHODS: Using Medicare claims data from 2010 to 2014, we identified a cohort of individuals with at least one inpatient or two outpatient diagnostic claims for MS. We restricted this group to beneficiaries with continuous Part A, B, and D coverage in the year before and after their initial diagnosis. To estimate the effect of cost-sharing on time to self-administered DMT initiation, we compared beneficiaries with a Low-Income Subsidy (LIS), who are shielded from cost-sharing, to those without LIS using multivariate Cox Proportional Hazards models adjusting for potential demographic and health-related confounders. RESULTS: There were 39,661 Medicare beneficiaries who met inclusion criteria; 3827 had full LIS benefits throughout the study period. Beneficiaries were predominately White (36,447, 91.9%) and female (29,406, 74.1%). LIS recipients were generally younger (55 vs 67 years, p<0.001) and more likely to be enrolled through disability eligibility (79% vs 36%, p<0.001). In the year after their index diagnosis, 434 LIS recipients initiated DMT versus 1682 non-LIS (11% vs 5%; p<0.001). Among those who started a DMT, the average time to initiation was 115 days in those with LIS and 137 days for non-LIS (p<0.001). After adjustment for covariates, individuals with LIS benefits were significantly more likely to initiate a DMT in the year following their diagnosis (adjusted hazard ratio 1.4, 95% CI 1.25 to 1.57). The effect of OOP costs on initiation did not differ by demographic subgroups. CONCLUSIONS: Medicare beneficiaries with MS who are shielded from traditional cost-sharing are more likely to initiate a DMT in the year following receipt of their first diagnosis code. Future work should examine the effect of cost-related treatment delays on relapse rates and disability progression.