Safer opioid supply and health outcomes

The ongoing opioid overdose crisis, which has killed over 30,000 people in Canada since 2016, is driven by the volatility of an unregulated opioid drug supply comprised primarily of fentanyl. The Canadian government has recently funded safer opioid supply (SOS) programs, which include off-label prescriptions of pharmaceutical-grade opioids to high risk individuals with the goal of reducing overdose deaths. In 2021, we examined the implementation and adaption of four SOS programs in Ontario. These programs use a primary care model and serve communities experiencing marginalisation. We conducted semi-structured interviews with program clients. We present the results of a thematic analysis with the aim of describing clients' self-reported impact of these programs on their health and well-being. We interviewed 52 clients between June and October 2021 (mean age 47 years, 56% men, 17% self-identified Indigenous, 14% living with HIV). Our results indicate multifaceted pathways to improved self-reported health and well-being among clients including changes to drug use practices, fewer overdoses, reduced criminalised activity, improved trust and engagement in health care, and increased social stability (e.g., housing). Most clients reported that the intervention saved their life because of the reduced frequency of overdoses. Findings suggest that SOS programs improved clients' health outcomes and increase opportunities for engagement in health services. Our results provide insight into the mechanisms behind some of the emergent evidence on the impact of safer supply prescribing.

Safer opioid supply and health outcomes – Authors' reply

The Ontario Integrated Supervised Injection Services cohort in Toronto, Canada (OiSIS-Toronto) is an open prospective cohort of people who inject drugs (PWID). OiSIS-Toronto was established to evaluate the impacts of supervised consumption services (SCS) integrated within three community health agencies on health status and service use. The cohort includes PWID who do and do not use SCS, recruited via self-referral, snowball sampling, and community/street outreach. From 5 November 2018 to 19 March 2020, we enrolled 701 eligible PWID aged 18+ who lived in Toronto. Participants complete interviewer-administered questionnaires at baseline and semi-annually thereafter and are asked to consent to linkages with provincial healthcare administrative databases (90.2% consented; of whom 82.4% were successfully linked) and SCS client databases. At baseline, 86.5% of participants (64.0% cisgender men, median ([IQR] age= 39 [33–49]) had used SCS in the previous 6 months, of whom most (69.7%) used SCS for <75% of their injections. A majority (56.8%) injected daily, and approximately half (48.0%) reported fentanyl as their most frequently injected drug. As of 23 April 2021, 291 (41.5%) participants had returned for follow-up. Administrative and self-report data are being used to (1) evaluate the impact of integrated SCS on healthcare use, uptake of community health agency services, and health outcomes; (2) identify barriers and facilitators to SCS use; and (3) identify potential enhancements to SCS delivery. Nested sub-studies include evaluation of “safer opioid supply” programs and impacts of COVID-19.

Prior opioid discontinuation studies have focused on one of two characteristics of opioid prescribing, its duration (long term vs not) or dosage (high vs low). Questions remain about the experience of patients with high-dose, long-term opioid therapy (HLOT) prescriptions who are likely to be at the highest risk for adverse events. We address the following questions among the Veterans Health Administration (VHA) patients receiving HLOT: 1),How has the prevalence of discontinuation of opioids changed over time?2),How do patient characteristics vary between those who do and do not discontinue? And3), how does the prevalence of discontinuation vary geographically? A retrospective observational study of VHA patients with HLOT between fiscal year (FY) 2014 and FY2018. We identified 1,281,330 patients from VHA outpatient opioid prescription data with at least a 1-day opioid supply between FY2014 and FY2018. We identified and excluded those receiving palliative care or diagnosed with metastatic cancer. For a given patient and month, a patient having a 3-month moving average of ≥ 90 daily morphine milligram equivalent (MME) was defined as having HLOT. Similarly, we used a three-month average MME of zero as discontinuation. The prevalence of discontinuation among patients with HLOT increased from 6.3% in FY2014 to 7.8% in FY2018. Across the years, patients who discontinued were younger, less likely to be married, and more likely to have comorbidities related to substance use disorders compared with patients who continued to receive HLOT. Incidence of discontinuation among those with HLOT increased in more than half (64%) of the 129 VHA medical centers. Prevalence of patients receiving HLOT in the VHA decreased as the incidence of discontinuation increased. Further research is needed to understand the process by which patients are discontinued and to assess the relationship between discontinuation and health outcomes.

Prescribed safer opioid supply (SOS) programmes are novel harm reduction interventions. We examined health outcomes among people receiving SOS over time and relative to a similar group of people receiving methadone. We conducted a population-based cohort study among new SOS and methadone recipients in Ontario, Canada, who commenced treatment between Jan 1, 2016 and Dec 31, 2021. People receiving SOS were matched (1:1) to new methadone recipients based on age (within 3 years), sex, location of residence (public health unit), and propensity score (within 0·2 SDs). Primary outcomes were hospital-treated opioid-related toxicities, emergency department visits and inpatient hospitalisations, incident infections, and health-care costs (in CA$, excluding costs related to primary care services and medications) over 1 year of follow-up. Outcome rates were calculated over the follow-up period, with censoring on death, discontinuation of SOS or methadone, or end of follow-up (360 days). Within-group changes in outcomes were assessed using interrupted time-series analysis, and Prentice-Williams-Peterson regression was used to assess between-group differences in recurrent events. Of the 991 new recipients prescribed SOS and 25 116 new methadone recipients who met the eligibility criteria, 856 (86·4%) people receiving SOS were matched to 856 people receiving methadone. In the within-group analysis, matched SOS recipients had significant improvements in the monthly rate of opioid toxicities (step change -1·09 events per 100 individuals [95% CI -2·12 to -0·07]; p=0·037), all-cause emergency department visits (-8·85 per person-year [-13·5 to -4·20]; p=0·0002), all-cause inpatient hospitalisations (-2·08 per person-year [-3·41 to -0·75]; p=0·0022), incident infections (-0·68 per person-year [-1·22 to -0·14]; p=0·013), and non-primary-care-related health-care costs (-$91 699 per person-year [-112 749 to -70 650]; p<0·0001). Results were consistent for methadone recipients. In the between-group analysis, individuals commencing SOS had significantly higher hazards of opioid toxicity (hazard ratio 2·83 [95% CI 1·97 to 4·06]), emergency department visits (1·16 [1·05 to 1·29]), and inpatient admissions (1·50 [1·13 to 1·99]), no significant difference in the rate of incident infection (1·51 [0·87 to 2·61]), and were less likely to discontinue treatment than those commencing methadone (0·62 [0·55 to 0·70]). When treatment discontinuation was removed as a censoring criterion, we found no difference between groups in the hazard of any of the primary outcomes except opioid toxicity (1·65 [1·38 to 1·97]). SOS and methadone were associated with improvements in health outcomes, including reduced opioid toxicities and health-care use, in the year after treatment initiation. The findings suggest SOS programmes play an important, complementary role to traditional opioid agonist treatment in expanding the options available to support people who use drugs. Canadian Institutes of Health Research and Ontario SPOR Support Unit.

ObjectiveTo test associations between several opioid prescribing policy interventions and changes in early (acute/subacute) high‐risk opioid prescribing practices.Data SourcesPopulation‐based workers' compensation pharmacy billing and claims data, Washington State Department of Labor and Industries (January 2008‐June 2015).Study DesignWe used interrupted time series analysis to test associations between three policy intervention timepoints and monthly proportions of population‐based measures of high‐risk, low‐risk, and any workers’ compensation‐related opioid prescribing. We also tested associations between the policy intervention timepoints and five high‐risk opioid prescribing indicators among workers prescribed any opioids within 3 months after injury: (a) >7 cumulative (not necessarily consecutive) days‘ supply of opioids during the acute phase, (b) high‐dose opioids, (c) concurrent sedatives, (d) chronic opioids, and (e) a composite high‐risk opioid prescribing indicator.Principal FindingsWithin 3 months after injury, 9 percent of workers were exposed to high‐risk and 12 percent to low‐risk workers’ compensation‐related opioid prescribing; 79 percent filled no workers’ compensation‐related opioid prescription. Among workers prescribed any early (acute/subacute) opioids, the indicator for >7 days' supply of opioids during the acute phase was present for 30 percent, high‐dose opioids for 18 percent, concurrent sedatives for 3 percent, and chronic opioids for 2 percent. Beyond a general shift toward more infrequent and lower‐risk workers’ compensation‐related opioid prescribing, each policy intervention timepoint was significantly associated with reductions in specific acute/subacute high‐risk opioid prescribing indicators; each of the four specific high‐risk opioid prescribing indicators had significant reductions associated with at least one policy.ConclusionsSeveral state‐level opioid prescribing policies were significantly associated with safer workers’ compensation‐related opioid prescribing practices during the first 3 months after injury (acute/subacute phase), which should in turn reduce transition to chronic opioids and associated negative health outcomes.

Substance abuse disorders among chronic noncancer pain (CNCP) patients add to the clinical challenges and economic burden of caring for such patients. Despite potential risks, some CNCP patients with a history of alcohol abuse or dependence (AAD) and pain that is refractory to nonopioid treatment options may still need opioids for pain management. However, there is a lack of data on adverse outcomes in long-term opioid users with CNCP and a history of substance abuse or AAD disorders. To compare adverse outcomes and all-cause health care costs among CNCP patients on long-term opioid treatment with and without a previous diagnosis of AAD. Using MarketScan claims databases (2006-2012), CNCP patients with ≥ 90 days of opioid supply after CNCP diagnosis and continuous enrollment 12 months before CNCP diagnosis (baseline period) and 12 months after opioid start (post-index period) were identified. AAD was defined by diagnosis codes at any time before opioid initiation. Outcomes included opioid overdose, accident, and injury episodes identified by ICD-9-CM diagnoses codes. T-tests and Mann-Whitney tests compared continuous measures, and chi-square and Fisher's exact tests compared categorical measures between those with and without AAD. Multivariable analyses for outcomes were conducted, adjusting for baseline differences between cohorts. Of 21,203 CNCP patients with long-term opioid treatment, 750 (3.5%) had an AAD diagnosis before opioid initiation. AAD patients were significantly younger (48.4 [SD ± 11.4] years vs. 52.8 [SD ± 14.8] years), less likely to be enrolled in Medicare (17% commercial vs. 4% Medicare), and more likely to be male (67% vs. 48%; all P < 0.001). There were no differences in type or number of CNCP diagnoses or Charlson Comorbidity Index (CCI) scores. Patients with AAD had significantly higher rates of depression and anxiety diagnoses, antidepressant and benzodiazepine use, and drug abuse/dependence diagnoses in the baseline period. Twelvemonth post-index rates of opioid overdose (1.2% vs. 0.2%), accident (7.3% vs. 2.8%), and injury (46.1% vs. 36.8%) were greater in the AAD cohort (all P < 0.001). The differences were nonsignificant for accidents in multivariable analyses. While mean prescription costs were similar ($3,562 vs. $3,312; P = 0.212), AAD patients had significantly higher mean all-cause medical costs ($28,429 vs. $22,082; P < 0.001) and significantly higher all-cause total health care costs ($31,991 vs. $25,395; P < 0.001). The cost differences remained significant in multivariable analyses. In the first year after long-term opioid initiation, CNCP patients with a previous AAD diagnosis had 5 times the rate of opioid overdose, 2.3 times the rate of accidents, 1.2 times the rate of injury, and higher all-cause health care costs compared with those not diagnosed with AAD. Funding for this research study and resultant publication was provided by Teva Global Health Economics and Outcomes Research, which fully reviewed the manuscript. Gajria and Yeung are employees of Teva Pharmaceuticals. White was an employee of Teva Pharmaceuticals at the time this research was conducted. Blumberg and Coutinho are employees of Xcenda, which received research funding from Teva Pharmaceuticals for the conduct of this study and for the preparation of this manuscript. Katz has received research funding and consulting fees from Teva Pharmaceuticals unrelated to this study. Study concept and design were contributed by Katz, White, and Blumberg, along with Coutinho and Yeung. Coutinho took the lead in data collection, assisted by the other authors. Data interpretation was performed by Blumberg, Katz, and Gajria, along with the other authors. The manuscript was written by Gajria, Yeung, Coutinho, and Blumberg, along with Katz and White, and revised by Gajria, Blumberg, Katz, and Coutinho, along with Yeung and White.

SettingThis paper describes the Safer Opioid Supply (SOS) program, a public health intervention in London, Ontario, in response to the toxic unregulated drug supply which is driving the overdose crisis in Canada.InterventionThe London InterCommunity Health Centre (LIHC) SOS program provides comprehensive harm reduction and primary health care services to individuals at risk of overdose from the toxic drug supply. Clients are prescribed high-dose pharmaceutical opioids as replacement for unregulated toxic substances within a low-barrier primary care clinic, with wraparound interdisciplinary social services, embedded in the Ontario Community Health Centre model of care. The program serves people dependent on street-acquired fentanyl who are experiencing medical issues due to their substance use, and who are experiencing challenges accessing other forms of healthcare.OutcomesA qualitative analysis of interviews and focus groups conducted in 2022–2023 with staff (n=5) and clients (n=20) was used to explore impacts of the SOS program. Four outcomes are discussed: safer supply as crucial to engage clients in primary care; safer supply as one component of comprehensive care; the use of a harm reduction approach; and challenges with limited medication options and program capacity.ImplicationsPositive health and social outcomes demonstrate the utility of embedding comprehensive substance use services within a primary health care model to address health and social complexity among people who use drugs amid the continuing toxic drug crisis. Responding to an increasingly volatile unregulated supply of drugs, having limited medication options, and providing comprehensive care without long-term funding remain ongoing challenges.

There has been a dramatic rise in the number of opioid prescriptions and opioid overdose deaths in the United States over the past 15 years. Misuse and abuse of opioids is also a growing public health concern in the United States. Medicaid enrollees are more likely to be prescribed opioids and are at higher risk of prescription drug overdose compared with non-Medicaid populations. Despite rising opioid drug overdose deaths in Georgia, prevalence of indicators for potential inappropriate prescribing practices has not been examined to date. To examine trends in the general use of opioids and the prevalence of indicators for potential inappropriate opioid prescribing among the Georgia Medicaid population across various demographic characteristics over time. This study used data from the Georgia individual Medicaid pharmacy claims database from 2009 to 2014. Data sample included 3,562,227 observations (patient prescriptions) representing 401,488 individuals. Outcome measures assessed the trends in the general use of opioids and the indicators of potential inappropriate prescribing practices by providers. These outcome measures were taken from previous expert panels and clinical guidelines (e.g., overlapping prescriptions of opioids, opioids and benzodiazepines, and opioids and buprenorphine/naloxone, as well as high daily doses of opioids). Analyses were stratified by gender, type of insurance (fee-for-service and managed care), age, and race/ethnicity. The average number of opioid prescriptions, average days supply of opioids per patient, and average daily dose of opioids per patient increased over time across all demographic categories with older, fee-for-service, male, and missing race groups experiencing higher use across all 6 years compared with their counterparts. A similar pattern was observed for average number of incidences of potential inappropriate prescribing of opioids in this population from 2009 to 2014. The percentage of Medicaid enrollees with at least 1 or more indicators of potential inappropriate prescriptions slightly increased from 17.17% to 18.21% during the study time frame. Moreover, the incidence rate of indicators for potential inappropriate prescribing of opioids also increased over time across all demographic groups, with the oldest age group (55-64 years) experiencing the largest increment. The incidence rate of potential inappropriate prescribing practices per patient increased more than 58% over the 6 years. The results of this study show that potentially inappropriate prescribing practices are common and are increasing over time in the Georgia Medicaid population across all demographic categories, with individuals who are listed in the missing race category, have fee-for-service plans, and are older experiencing the largest increments. These findings indicate that patients in certain demographic groups could be at higher risk for experiencing adverse health outcomes related to inappropriate prescribing of opioids. Further research is needed to explore which policy tools or interventions might be more effective in reducing inappropriate prescribing practices in this population. This research was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA039930 and the Georgia Department of Community Health, contract number 2015012. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Georgia Department of Community Health. The authors have nothing to disclose. A previous version of this paper was presented at the following conferences: International Health Economics Association 12th World Congress; July 8-11, 2017; Boston, MA, and Addiction Health Services Research Conference; October 18-20, 2017; Madison, WI.

To estimate health outcomes of policies to mitigate the opioid epidemic. We used dynamic compartmental modeling of US adults, in various pain, opioid use, and opioid addiction health states, to project addiction-related deaths, life years, and quality-adjusted life years from 2016 to 2025 for 11 policy responses to the opioid epidemic. Over 5 years, increasing naloxone availability, promoting needle exchange, expanding medication-assisted addiction treatment, and increasing psychosocial treatment increased life years and quality-adjusted life years and reduced deaths. Other policies reduced opioid prescription supply and related deaths but led some addicted prescription users to switch to heroin use, which increased heroin-related deaths. Over a longer horizon, some such policies may avert enough new addiction to outweigh the harms. No single policy is likely to substantially reduce deaths over 5 to 10 years. Policies focused on services for addicted people improve population health without harming any groups. Policies that reduce the prescription opioid supply may increase heroin use and reduce quality of life in the short term, but in the long term could generate positive health benefits. A portfolio of interventions will be needed for eventual mitigation.

Characteristics and correlates of fentanyl preferences among people with opioid use disorder

ObjectiveIn recent years, Canada’s unregulated drug supply has become permeated by novel adulterants (e.g., fentanyl analogues, benzodiazepines, xylazine). While fentanyl has been shown to be associated with overdose mortality and other non-fatal health outcomes, adverse events (AE) associated with these adulterants remain poorly described. This study seeks to identify whether common adulterants identified through drug checking services are associated with increased prevalence of specific adverse events reportedly experienced by people who use drugs.MethodsDrug checking samples were analyzed using Fourier-transform infrared spectroscopy and immunoassay strips at harm reduction sites in British Columbia. Self-reported AE (e.g., non-fatal overdose, prolonged sedation, seizures) were recorded from individuals who checked opioids post-consumption. Adjusted prevalence ratios (aPR) and 95% confidence intervals (95% CI) of AE among common adulterants were calculated using generalized linear models with a Poisson distribution, controlled for presence of other adulterants, expected drug, geographic location, and month.ResultsBetween February 2022 and May 2024, 80,415 samples were analyzed at community sites. Among eligible samples, 36.1% were expected opioids, 42.2% of which were checked post-consumption. AE were noted among 10.7% of post-consumption opioid drug checks. After adjustment, the presence of benzodiazepines in opioid samples was associated with increased prevalence of any AE (aPR 1.97; 95% CI 1.70–2.27), as was the presence of xylazine (aPR 1.50; 95% CI 1.09–2.07). Considering specific AE, benzodiazepines were associated with increased prevalence of overdose (aPR 2.05; 95% CI 1.68–2.51) and prolonged sedation (aPR 3.35; 95% CI 2.54–4.43).ConclusionNon-fatal AE associated with unregulated opioids have been largely undescribed. Our findings report specific AE associated with different adulterants in the unregulated opioid supply. With this information, tailored public health interventions and services focused on these adulterants can be developed.

Consumption of prescription opioid analgesics (POAs) in Australia has increased steadily in recent years, raising concerns of increasing harms including overdose and dependence, as has occurred in the USA. Exposition of the Royal Australasian College of Physicians Prescription Opioid Policy with reference to the published literature, drawing out principles for harm reduction for psychoactive pharmaceutical drugs. Complex professional, patient, regulatory and market factors influence health professionals balancing the benefits and harms of POAs. Owing to the potential for diversion, overlapping markets probably exist for pharmaceutical opioids used for populations with cancer pain, chronic non-cancer pain, and people dependent on pharmaceutical and illicit opioids (including those needing opioid substitution treatment). Attempts to reduce or restrict supply in one area may increase demand in others. There is a need to consider new harm reduction strategies for people with problematic pharmaceutical opioid use. These people are demographically not well characterised, and may be distinct from the more familiar population of injection drug users. Harm reduction is a valid approach for POAs. However, the role of health professionals as gatekeepers of opioid supply, the need to optimise health benefits of POAs, and the likely interplay of complex market forces among populations consuming opioids have no close parallel in harm reduction for other substances. This poses fundamentally different challenges. Reducing inappropriate supply and demand for POAs while maximising their benefits and minimising their harms may improve health outcomes.

Opioid medication doses among safer supply clients: Current safer supply doses and previous OAT experience.

In March 2020, British Columbia, Canada, became the first jurisdiction globally to launch a large-scale provincewide safer supply policy. The policy allowed individuals with opioid use disorder at high risk of overdose or poisoning to receive pharmaceutical-grade opioids prescribed by a physician or nurse practitioner, but to date, opioid-related outcomes after policy implementation have not been explored. To investigate the association of British Columbia's Safer Opioid Supply policy with opioid prescribing and opioid-related health outcomes. This cohort study used quarterly province-level data from quarter 1 of 2016 (January 1, 2016) to quarter 1 of 2022 (March 31, 2022), from British Columbia, where the Safer Opioid Supply policy was implemented, and Manitoba and Saskatchewan, where the policy was not implemented (comparison provinces). Safer Opioid Supply policy implemented in British Columbia in March 2020. The main outcomes were rates of prescriptions, claimants, and prescribers of opioids targeted by the Safer Opioid Supply policy (hydromorphone, morphine, oxycodone, and fentanyl); opioid-related poisoning hospitalizations; and deaths from apparent opioid toxicity. Difference-in-differences analysis was used to compare changes in outcomes before and after policy implementation in British Columbia with those in the comparison provinces. The Safer Opioid Supply policy was associated with statistically significant increases in rates of opioid prescriptions (2619.6 per 100 000 population; 95% CI, 1322.1-3917.0 per 100 000 population; P < .001) and claimants (176.4 per 100 000 population; 95% CI, 33.5-319.4 per 100 000 population; P = .02). There was no significant change in prescribers (15.7 per 100 000 population; 95% CI, -0.2 to 31.6 per 100 000 population; P = .053). However, the opioid-related poisoning hospitalization rate increased by 3.2 per 100 000 population (95% CI, 0.9-5.6 per 100 000 population; P = .01) after policy implementation. There were no statistically significant changes in deaths from apparent opioid toxicity (1.6 per 100 000 population; 95% CI, -1.3 to 4.5 per 100 000 population; P = .26). Two years after its launch, the Safer Opioid Supply policy in British Columbia was associated with higher rates of safer supply opioid prescribing but also with a significant increase in opioid-related poisoning hospitalizations. These findings will help inform ongoing debates about this policy not only in British Columbia but also in other jurisdictions that are contemplating it.