Evaluating the effectiveness and cost-effectiveness of a digital, app-based intervention for depression (VMood) in community-based settings in Vietnam: Protocol for a stepped-wedge randomized controlled trial.

The COVID-19 pandemic has amplified mental health problems and highlighted inequitable gaps in care worldwide. In response there has been an explosion of digital interventions such as smartphone applications ("apps") to extend care. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of a digital depression intervention (VMood), delivered via a smartphone app. VMood is adapted from an in-person intervention that was delivered by non-specialist providers and shown to be effective in the Vietnamese context in our previous trial (2016-2019). A stepped-wedge, randomized controlled trial will be conducted across eight provinces in Vietnam. Adults aged 18 years and over will be recruited through community-based primary care centres and screened for depression using the embedded Patient Health Questionnaire-9 (primary outcome measure). Participants scoring 10-19, indicating depression caseness, will be randomly allocated to the intervention or control group until the target of 336 is reached. Secondary outcome measures will examine the effect of the intervention on commonly co-occuring anxiety, quality of life and work productivity, along with use of alcohol and tobacco products. Assessments will be administered through an online survey platform (REDCap) at baseline, and at every 3 months until 3 months post-intervention. Intervention-group participants will receive VMood for a 3-month period, with online support provided by social workers. Control-group participants will receive a limited version of the app until they cross into the intervention group. Generalized Linear Mixed-effect Models for clustered measures will be used for all outcomes data. We will conduct a cost-effectiveness analysis alongside the trial to capture VMood's costs and benefits. This trial will provide evidence on the effectiveness and cost-effectiveness of a digital mental health intervention adapted from an in-person intervention. This trial will also contribute important information to the growing and promising field of digital mental health. Trail regulation. Registered at ClinicalTrials.gov, identifier [NCT05783531].

Toward Best Practices for Economic Evaluations of Tumor-Agnostic Therapies: A Review of Current Barriers and Solutions.

OBJECTIVES: Cancer therapies targeting tumor-agnostic biomarkers are challenging traditional health technology assessment (HTA) frameworks. The high prevalence of nonrandomized single-arm trials, heterogeneity, and small benefiting populations are driving outcomes uncertainty, challenging healthcare decision making. We conducted a structured literature review to identify barriers and prioritize solutions to generating economic evidence for tumor-agnostic therapies. METHODS: We searched MEDLINE and Embase for English-language studies conducting economic evaluations of tumor-agnostic treatments or exploring related challenges and solutions. We included studies published by December 2022 and supplemented our review with Canadian Agency for Drugs and Technologies in Health and National Institute for Health and Care Excellence technical reports for approved tumor-agnostic therapies. Three reviewers abstracted and summarized key methodological and empirical study characteristics. Challenges and solutions were identified through authors' statements and categorized using directed content analysis. RESULTS: Twenty-six studies met our inclusion criteria. Studies spanned economic evaluations (n = 5), reimbursement reviews (n = 4), qualitative research (n = 1), methods validations (n = 3), and commentaries or literature reviews (n = 13). Challenges encountered related to (1) the treatment setting and clinical trial designs, (2) a lack of data or low-quality data on clinical and cost parameters, and (3) an inability to produce evidence that meets HTA guidelines. Although attempted solutions centered on analytic approaches for managing missing data, proposed solutions highlighted the need for real-world evidence combined with life-cycle HTA to reduce future evidentiary uncertainty. CONCLUSIONS: Therapeutic innovation outpaces HTA evidence generation and the methods that support it. Existing HTA frameworks must be adapted for tumor-agnostic treatments to support future economic evaluations enabling timely patient access.

Sensitivity to change of generic preference-based instruments (EQ-5D-3L, EQ-5D-5L, and HUI3) in the context of treatment for people with prescription-type opioid use disorder in Canada.

PURPOSE: Using data from a randomized controlled trial for treatment of prescription-type opioid use disorder in Canada, this study examines sensitivity to change in three preference-based instruments [EQ-5D-3L, EQ-5D-5L, and the Health Utilities Index Mark 3 (HUI3)] and explores an oft-overlooked consideration when working with contemporaneous responses for similar questions-data quality. METHODS: Analyses focused on the relative abilities of three instruments to capture change in health status. Distributional methods were used to categorize individuals as 'improved' or 'not improved' for eight anchors (seven clinical, one generic). Sensitivity to change was assessed using area under the ROC (receiver operating characteristics) curve (AUC) analysis and comparisons of mean change scores for three time periods. A 'strict' data quality criteria, defined a priori, was applied. Analyses were replicated using 'soft' and 'no' criteria. RESULTS: Data from 160 individuals were used in the analysis; 30% had at least one data quality violation at baseline. Despite mean index scores being significantly lower for the HUI3 compared with EQ-5D instruments at each time point, the magnitudes of change scores were similar. No instrument demonstrated superior sensitivity to change. While six of the 10 highest AUC estimates were for the HUI3, 'moderate' classifications of discriminative ability were identified in 12 (of 22) analyses for each EQ-5D instrument, compared with eight for the HUI3. CONCLUSION: Negligible differences were observed between the EQ-5D-3L, EQ-5D-5L, and HUI3 regarding the ability to measure change. The prevalence of data quality violations-which differed by ethnicity-requires further investigation.

Cost-effectiveness of flexible take-home buprenorphine-naloxone versus methadone for treatment of prescription-type opioid use disorder.

BACKGROUND: Our objective was to examine the cost-effectiveness of flexible take-home buprenorphine-naloxone (BNX) versus methadone alongside the OPTIMA trial in Canada. METHODS: The OPTIMA study was a pragmatic, open-label, noninferiority, two-arm randomized controlled trial, to assess the comparative effectiveness of flexible take-home BNX vs. methadone in routine clinical care for individuals with prescription-type opioid use disorder. We evaluated cost-effectiveness using a semi-Markov cohort model. Probabilities of overdose were calibrated, accounting for fentanyl prevalence and other overdose risk factors such as naloxone availability. We considered health sector and societal cost perspectives, including costs (2020 CAD) for treatment, health resource use, criminal activity, and health state-specific preference weights as outcomes to calculate incremental cost-effectiveness ratios. Six-month and lifetime (3% annual discount rate) time-horizons were explored. RESULTS: Over a lifetime time horizon, individuals accumulated -0.144 [CI: -0.302, -0.025] incremental quality-adjusted life years (QALYs) in BNX compared with methadone. Incremental costs were -$2047 [CI: -$39,197, $24,250] from a societal perspective, and -$4549 [CI: -$6332, -$3001] from a health sector perspective. Over a six-month time-horizon, individuals accumulated 0.002 [credible interval (CI): -0.011, 0.016] incremental QALYs in BNX compared with methadone. Incremental costs were -$307 [CI: -$10,385, $8466] from a societal perspective and -$1111 [CI: -$1517, -$631] from a health sector perspective. BNX was dominated (costlier, less effective) in 49.7% of simulations when adopting a societal perspective over a lifetime time horizon. CONCLUSIONS: Flexible take-home BNX was not cost-effective versus methadone over a lifetime time horizon, resulting from better treatment retention in methadone compared to BNX.

Translating and disseminating a localised economic model to support implementation of the 'Ending the HIV Epidemic' initiative to public health policymakers.

Background: Despite significant progress in HIV treatment and prevention, the US remains far from its goal of 'Ending the HIV Epidemic' by 2030. Economic models using local data can synthesise the evidence to help policymakers allocate HIV resources efficiently, but persistent research-to-practice gaps remain. Little is known about how to facilitate the use of economic modelling data among local public health policymakers in real-world settings. Aims and objectives: To explore the dissemination of results from a locally-calibrated economic model for HIV prevention and treatment and identify the factors influencing potential uptake of the model for public health decision making at the local level. Methods: Four virtual focus groups with 26 local health department policymakers in Baltimore, Miami, Seattle, and New York City were held between July 2020 and May 2021. Qualitative content analysis of transcripts identified key themes around using the localised economic model in policy decisions. Results: Participants were interested in using local data in their decisions to allocate resources for HIV prevention/treatment. Six themes emerged: 1) importance of understanding local policy context; 2) health equity considerations; 3) using evidence to support current priorities; 4) difficulty of changing strategies, even incrementally; 5) bang for the incremental buck (efficiency) vs. previous impact; and 6) community values. Conclusion and relevance: To optimise acceptance and use of results from economic models, researchers should engage with local community members and public health decision makers early to understand budgetary and community priorities. Participants prioritised evidence that supports their existing strategies, considers budgets and funding streams, and improves health equity; however, real-world budget constraints and conflicting interests serve as barriers to implementing model recommendations and reaching national goals.

The effect of a methadone reformulation on opioid agonist treatment outcomes: A population-based study in British Columbia, Canada, 2013-14.

INTRODUCTION: The province of British Columbia, Canada, changed the existing oral anhydrous methadone solution to a 10-times more concentrated pre-mixed solution, Methadose®, on February 1, 2014. We aimed to assess the immediate effects of the methadone reformulation on missed doses, days off methadone, changes in medication dosing and dispensations of opioids for pain, and hospitalizations and mortality among all people receiving treatment at or near the time of the change. METHODS: We conducted a population-based retrospective cohort study including all individuals receiving at least one methadone dispensation in the 12 months prior to the study period. We executed a difference-in-differences analysis by estimating a multivariate regression model to compare outcomes in the three months before and after the reformulation (November 1, 2013 to April 30, 2014) versus a time-lagged control cohort with similar characteristics observed during an equivalent nonoverlapping interval. We used daily individual-level linked health administrative data capturing missed doses, days off methadone, changes in methadone dosing, concurrent dispensations of opioids for pain, hospitalizations, and mortality. We stratified the cohorts into three subgroups: (i) those receiving OAT for ≥12 months; (ii) those receiving OAT for <12 months; and (iii) those not receiving OAT at the start of the study period. We conducted sensitivity analyses and placebo tests to assess the robustness of our results. RESULTS: Among the 16,339 individuals receiving methadone during the study period, the reformulation was associated with more instances of methadone dose increases (34.5% [95% Confidence Interval (CI): 27.4%, 41.5%]). For those retained in treatment ≥12 months prior to the study period (n = 7449), the reformulation was associated with more instances of methadone dose increases (50.2% [39.5%, 60.8%]) and dispensations of opioids for pain (62.2% [40.8%, 83.5%]), as well as an increase in missed doses (41.9% [29.1%, 54.7%]) and days off methadone (62.6% [39.7%, 85.4%]). We found no statistically significant change in risk of hospitalization or mortality. Sensitivity analyses supported our results. CONCLUSION: Our results reinforce the need expressed by people receiving methadone for greater client involvement in the planning and implementation of regulatory changes that may impact client care, especially those patients with a relatively long treatment history.

Human Immunodeficiency Virus transmission by HIV Risk Group and Along the HIV Care Continuum: A Contrast of 6 US Cities.

BACKGROUND: Understanding the sources of HIV transmission provides a basis for prioritizing HIV prevention resources in specific geographic regions and populations. This study estimated the number, proportion, and rate of HIV transmissions attributable to individuals along the HIV care continuum within different HIV transmission risk groups in 6 US cities. METHODS: We used a dynamic, compartmental HIV transmission model that draws on racial behavior-specific or ethnic behavior-specific and risk behavior-specific linkage to HIV care and use of HIV prevention services from local, state, and national surveillance sources. We estimated the rate and number of HIV transmissions attributable to individuals in the stage of acute undiagnosed HIV, nonacute undiagnosed HIV, HIV diagnosed but antiretroviral therapy (ART) naïve, off ART, and on ART, stratified by HIV transmission group for the 2019 calendar year. RESULTS: Individuals with undiagnosed nonacute HIV infection accounted for the highest proportion of total transmissions in every city, ranging from 36.8% (26.7%-44.9%) in New York City to 64.9% (47.0%-71.6%) in Baltimore. Individuals who had discontinued ART contributed to the second highest percentage of total infections in 4 of 6 cities. Individuals with acute HIV had the highest transmission rate per 100 person-years, ranging from 76.4 (58.9-135.9) in Miami to 160.2 (85.7-302.8) in Baltimore. CONCLUSION: These findings underline the importance of both early diagnosis and improved ART retention for ending the HIV epidemic in the United States. Differences in the sources of transmission across cities indicate that localized priority setting to effectively address diverse microepidemics at different stages of epidemic control is necessary.

Improving health equity and ending the HIV epidemic in the USA: a distributional cost-effectiveness analysis in six cities.

BACKGROUND: In the USA, Black and Hispanic or Latinx individuals continue to be disproportionately affected by HIV. Applying a distributional cost-effectiveness framework, we estimated the cost-effectiveness and epidemiological impact of two combination implementation approaches to identify the approach that best meets the dual objectives of improving population health and reducing racial or ethnic health disparities. METHODS: We adapted a dynamic, compartmental HIV transmission model to characterise HIV micro-epidemics in six US cities: Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle. We considered combinations of 16 evidence-based interventions to diagnose, treat, and prevent HIV transmission according to previously documented levels of scale-up. We then identified optimal combination strategies for each city, with the distribution of each intervention implemented according to existing service levels (proportional services approach) and the racial or ethnic distribution of new diagnoses (between Black, Hispanic or Latinx, and White or other ethnicity individuals; equity approach). We estimated total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios of strategies implemented from 2020 to 2030 (health-care perspective; 20-year time horizon; 3% annual discount rate). We estimated three measures of health inequality (between-group variance, index of disparity, Theil index), incidence rate ratios, and rate differences for the selected strategies under each approach. FINDINGS: In all cities, optimal combination strategies under the equity approach generated more QALYs than those with proportional services, ranging from a 3·1% increase (95% credible interval [CrI] 1·4-5·3) in New York to more than double (101·9% [75·4-134·6]) in Atlanta. Compared with proportional services, the equity approach delivered lower costs over 20 years in all cities except Los Angeles; cost reductions ranged from $22·9 million (95% CrI 5·3-55·7 million) in Seattle to $579·8 million (255·4-940·5 million) in Atlanta. The equity approach also reduced incidence disparities and health inequality measures in all cities except Los Angeles. INTERPRETATION: Equity-focused HIV combination implementation strategies that reduce disparities for Black and Hispanic or Latinx individuals can significantly improve population health, reduce costs, and drive progress towards Ending the HIV Epidemic goals in the USA. FUNDING: National Institute on Drug Abuse.

Characterizing opioid agonist treatment discontinuation trends in British Columbia, Canada, 2012-2018.

BACKGROUND: Given the elevated risk of mortality immediately following opioid agonist treatment (OAT) discontinuation, determining the frequency and timing of OAT discontinuation can help guide the planning of services to facilitate uninterrupted OAT. We sought to describe weekly and monthly trends in OAT episode discontinuations in British Columbia to determine the potential resource needs for implementing support services. METHODS: This population-based retrospective study utilized a provincial-level linkage of health administrative databases to identify all people with opioid use disorder (PWOUD) who received OAT between 01/2012-08/2018. We defined OAT episodes as continuous medication dispensations without interruptions in prescribed doses lasting ≥5 days for methadone and ≥6 days for buprenorphine/naloxone. We derived the percentage of PWOUD discontinuing OAT every month and we considered weekly discontinuations between 09/2017-08/2018, accounting for weeks during which monthly income assistance payments from social service programs occurred. RESULTS: Our study included 37,207 PWOUD discontinuing 158,027 OAT episodes. Discontinuations were relatively stable month-to-month, increasing from 10.6 % to 14.9 % (2012-2018). The monthly percentage of discontinuations was 21.2 % for buprenorphine/naloxone and 10.0 % for methadone. Weekly discontinuations were greater in income disbursement weeks (816; IQR: 752, 901) compared to other weeks (655; IQR: 615, 683; p < 0.01). CONCLUSIONS: We identified a high, and stable rate of monthly OAT discontinuations and a consistently higher rate of discontinuing treatment among PWOUD accessing buprenorphine/naloxone. There is an urgent need to develop the evidence base for interventions to support OAT engagement and to improve clinical management of OUD to address the opioid-related overdose crisis.

The cascade of care for opioid use disorder among youth in British Columbia, 2018.

BACKGROUND: Medication for opioid use disorder (MOUD) is associated with substantial reductions in the risk of mortality, and American and Canadian guidelines recommend it as part of the full range of available treatments for youth with opioid use disorder (OUD). We estimated the OUD cascade of care for all adolescents (ages 12-18) and young adults (19-24) with OUD in British Columbia, Canada (BC) in 2018. METHODS: Using a provincial-level linkage of six health administrative databases, we classified youth with OUD as adolescents (ages 12-18) or young adults (19-24) to compare with older adults (≥25) and described key factors known to influence engagement in health care. The eight-stage cascade of care included diagnosed with OUD, ever engaged in MOUD, recently in MOUD, currently in MOUD, and retained in MOUD for ≥1 month, ≥3 months, ≥12 months, ≥24 months. RESULTS: We identified 4048 youth diagnosed with OUD as of September 30, 2018 (6.3% of all people with OUD). Most were young adults, aged 19-24 (n = 3602; 89.0% of all youth), a majority of whom were males (n = 1984; 55.1%). In contrast, adolescents diagnosed with OUD (n = 446; 11.0% of all youth) were mostly females (n = 287; 64.4%). Compared to adolescents, there were more young adults diagnosed with OUD ever engaged in MOUD (71.4% v. 36.5%), currently on MOUD (29.3% v. 16.8%), and retained in care for ≥1 year (8.6% v. 2.0%). CONCLUSIONS: A high proportion of youth aged 12-24 diagnosed with OUD in a health care setting in British Columbia received MOUD yet continued engagement is infrequent, particularly for adolescents. Long-term treatment plans for youth need to consider including MOUD when appropriate as part of tailored, youth-friendly services.

Attributing health benefits to preventing HIV infections versus improving health outcomes among people living with HIV: an analysis in six US cities.

OBJECTIVE: Combination strategies generate health benefits through improved health outcomes among people living with HIV (PLHIV) and prevention of new infections. We aimed to determine health benefits attributable to improved health among PLHIV versus HIV prevention for a set of combination strategies in six US cities. DESIGN: A dynamic HIV transmission model. METHODS: Using a model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City (NYC) and Seattle, we assessed the health benefits of city-specific optimal combinations of evidence-based interventions implemented at publicly documented levels and at ideal (90% coverage) scale-up (2020-2030 implementation, 20-year study period). We calculated the proportion of health benefit gains (measured as quality-adjusted life-years) resulting from averted and delayed HIV infections; improved health outcomes among PLHIV; and improved health outcomes due to medication for opioid use disorder (MOUD). RESULTS: The HIV-specific proportion of total benefits ranged from 68.3% (95% credible interval: 55.3-80.0) in Seattle to 98.5% (97.5-99.3) in Miami, with the rest attributable to MOUD. The majority of HIV-specific health benefits in five of six cities were attributable HIV prevention, and ranged from 33.1% (26.1-41.1) in NYC to 83.1% (79.6-86.6) in Atlanta. Scaling up to ideal service levels resulted in three to seven-fold increases in additional health benefits, mostly from MOUD, with HIV-specific health gains primarily driven by HIV prevention. CONCLUSION: Optimal combination strategies generated a larger proportion of health benefits attributable to HIV prevention in five of six cities, underlining the substantial benefits of antiretroviral therapy engagement for the prevention of HIV transmission through viral suppression. Understanding to whom benefits accrue may be important in assessing the equity and impact of HIV investments.

Opioid analgesic prescribing for opioid-naïve individuals prior to identification of opioid use disorder in British Columbia, Canada.

BACKGROUND AND AIMS: Prescription opioid analgesics have contributed to the development of opioid use disorder (OUD) in many individuals. We aimed to characterize non-cancer opioid prescribing for opioid-naive individuals prior to OUD identification. DESIGN: Population-based retrospective cohort study using six linked health administrative databases. SETTING: British Columbia (BC), Canada. PARTICIPANTS: People with OUD between 1 January 2001 and 30 September 2018 who initiated opioid analgesic therapy for non-cancer pain prior to OUD identification. MEASUREMENTS: Dose (morphine milligram equivalent per day), days prescribed and clinical guideline non-concordance for initial opioid prescriptions (dose ≥ 90 morphine milligram equivalent per day; ≥ 7 days prescribed; concomitant sedative prescription). We estimated the probability of non-concordant initial prescriptions by source (inpatient post-discharge, non-inpatient acute, non-acute) using logistic regression, adjusting for individual characteristics and comorbidities. FINDINGS: Among 66 372 individuals identified with OUD from 2001 to 2018, 21 331 (32.1%) received opioid analgesics prior to OUD identification. This proportion increased from 3.0% in 2001 to 41.0% in 2011, before decreasing to 34.2% in 2017. Roughly half of opioid prescriptions were attributed to non-acute care visits, peaking at 56.8% in 2007, while the proportion from inpatient visits increased from 19.7% in 2001 to 28.5% in 2017. The predicted probability of receiving non-guideline concordant prescriptions declined over time-periods across all three measures for inpatient and non-inpatient acute care, while remaining stable for non-acute care. In particular, the predicted probability of receiving ≥ 7-day prescriptions following inpatient visits decreased from 53.3% [95% confidence interval (CI) = 50.9, 55.8%] in 2001-06 to 37.2% (95% CI = 33.9, 40.5%) in 2013-18. CONCLUSIONS: Among the 66 372 individuals in British Columbia, Canada diagnosed with opioid use disorder between 2001 and 2018, more than 32% were earlier prescribed non-cancer opioid analgesics. The proportion who had received an opioid analgesic prescription prior to OUD identification peaked at more than 40% in 2011, before stabilizing between 2011 and 2016 and declining thereafter. Guideline concordance improved over time for high-dose and concomitant sedative prescribing.

The effect of British Columbia's Pharmacare coverage expansion for opioid agonist treatment.

Opioid agonist treatment (OAT) is the evidence-based standard of care for people with opioid use disorder. In British Columbia, Canada, only social assistance registrants received full coverage for OAT prior to the introduction of the Pharmacare Plan G coverage expansion on February 1st, 2017. We aimed to determine the effect of the coverage expansion on OAT initiation, re-initiation, and retention. Using linked population-level data, we executed a difference-in-differences analysis to compare outcomes of individuals eligible for the additional coverage and social assistance registrants already receiving the most generous coverage for OAT prior to the policy change, adjusting for individual and prescriber characteristics. We found Plan G coverage expansion significantly increased OAT retention. Specifically, coverage expansion decreased the number of OAT episode discontinuations by 12.8% (95% CI: 8.4%, 17.2%).

Cost-Effectiveness Analysis in Implementation Science: a Research Agenda and Call for Wider Application.

PURPOSE OF REVIEW: Cost-effectiveness analysis (CEA) can help identify the trade-offs decision makers face when confronted with alternative courses of action for the implementation of public health strategies. Application of CEA alongside implementation scientific studies remains limited. We aimed to identify areas for future development in order to enhance the uptake and impact of model-based CEA in implementation scientific research. RECENT FINDINGS: Important questions remain about how to broadly implement evidence-based public health interventions in routine practice. Establishing population-level implementation strategy components and distinct implementation phases, including planning for implementation, the time required to scale-up programs, and sustainment efforts required to maintain them, can help determine the data needed to quantify each of these elements. Model-based CEA can use these data to determine the added value associated with each of these elements across systems, settings, population subgroups, and levels of implementation to provide tailored guidance for evidence-based public health action. There is a need to integrate implementation science explicitly into CEA to adequately capture diverse real-world delivery contexts and make detailed, informed recommendations on the aspects of the implementation process that provide good value. We describe examples of how model-based CEA can integrate implementation scientific concepts and evidence to help tailor evaluations to local context. We also propose six distinct domains for methodological advancement in order to enhance the uptake and impact of model-based cost-effectiveness analysis in implementation scientific research.

Diagnosis of Opioid Use Disorder by Youths Assessed in Acute Care Settings in British Columbia, Canada.

OBJECTIVES: To describe trends in the number of youths diagnosed with opioid use disorder (OUD) and to identify factors associated with OUD diagnosis in acute care settings. STUDY DESIGN: Data from a population-based retrospective cohort study with linkage of 6 health administrative databases for 13 009 youth age 12-24 years identified with OUD between 2001 and 2018 in British Columbia, Canada were used to describe annual diagnoses. Using a multiple logistic regression model, we estimated the association between past-year health care utilization and OUD diagnosis in acute settings, controlling for sociodemographic and OUD-related comorbid conditions. RESULTS: Annual OUD diagnoses quadrupled between 2003 and 2017 (from 326 to 1473). Among the 6579 youth diagnosed with OUD between April 1, 2013 and September 30, 2018, 88.1% had past-year health system contacts. Youth age 12-18 had higher odds of OUD diagnosis in acute care (aOR 2.04; 95% CI 1.78, 2.34). Compared with no health care contact, youth receiving outpatient care only were less likely to be diagnosed with OUD in acute care (aOR 0.69; 95% CI 0.56, 0.84) and those with >1 urgent hospitalization were more likely to be diagnosed with OUD in acute care (aOR 1.87; 95% CI 1.40,2.49). CONCLUSIONS: More than 88% of youth had past-year health system contacts prior to diagnosis. Those age 12-18 years and with urgent hospitalizations in the year prior to diagnosis were more likely to have OUD diagnosed in acute care settings. Establishing an effective evidence-based system for early detection and intervention among youth with OUD must be a priority.

The Potential Epidemiological Impact of Coronavirus Disease 2019 (COVID-19) on the Human Immunodeficiency Virus (HIV) Epidemic and the Cost-effectiveness of Linked, Opt-out HIV Testing: A Modeling Study in 6 US Cities.

BACKGROUND: Widespread viral and serological testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present a unique opportunity to also test for human immunodeficiency virus (HIV) infection. We estimated the potential impact of adding linked, opt-out HIV testing alongside SARS-CoV-2 testing on the HIV incidence and the cost-effectiveness of this strategy in 6 US cities. METHODS: Using a previously calibrated dynamic HIV transmission model, we constructed 3 sets of scenarios for each city: (1) sustained current levels of HIV-related treatment and prevention services (status quo); (2) temporary disruptions in health services and changes in sexual and injection risk behaviors at discrete levels between 0%-50%; and (3) linked HIV and SARS-CoV-2 testing offered to 10%-90% of the adult population in addition to Scenario 2. We estimated the cumulative number of HIV infections between 2020-2025 and the incremental cost-effectiveness ratios of linked HIV testing over 20 years. RESULTS: In the absence of linked, opt-out HIV testing, we estimated a total of a 16.5% decrease in HIV infections between 2020-2025 in the best-case scenario (50% reduction in risk behaviors and no service disruptions), and a 9.0% increase in the worst-case scenario (no behavioral change and 50% reduction in service access). We estimated that HIV testing (offered at 10%-90% levels) could avert a total of 576-7225 (1.6%-17.2%) new infections. The intervention would require an initial investment of $20.6M-$220.7M across cities; however, the intervention would ultimately result in savings in health-care costs in each city. CONCLUSIONS: A campaign in which HIV testing is linked with SARS-CoV-2 testing could substantially reduce the HIV incidence and reduce direct and indirect health care costs attributable to HIV.

Prioritizing Additional Data Collection to Reduce Decision Uncertainty in the HIV/AIDS Response in 6 US Cities: A Value of Information Analysis.

OBJECTIVES: The ambitious goals of the US Ending the HIV Epidemic initiative will require a targeted, context-specific public health response. Model-based economic evaluation provides useful guidance for decision making while characterizing decision uncertainty. We aim to quantify the value of eliminating uncertainty about different parameters in selecting combination implementation strategies to reduce the public health burden of HIV/AIDS in 6 US cities and identify future data collection priorities. METHODS: We used a dynamic compartmental HIV transmission model developed for 6 US cities to evaluate the cost-effectiveness of a range of combination implementation strategies. Using a metamodeling approach with nonparametric and deep learning methods, we calculated the expected value of perfect information, representing the maximum value of further research to eliminate decision uncertainty, and the expected value of partial perfect information for key groups of parameters that would be collected together in practice. RESULTS: The population expected value of perfect information ranged from $59 683 (Miami) to $54 108 679 (Los Angeles). The rank ordering of expected value of partial perfect information on key groups of parameters were largely consistent across cities and highest for parameters pertaining to HIV risk behaviors, probability of HIV transmission, health service engagement, HIV-related mortality, health utility weights, and healthcare costs. Los Angeles was an exception, where parameters on retention in pre-exposure prophylaxis ranked highest in contributing to decision uncertainty. CONCLUSIONS: Funding additional data collection on HIV/AIDS may be warranted in Baltimore, Los Angeles, and New York City. Value of information analysis should be embedded into decision-making processes on funding future research and public health intervention.

Ending the HIV Epidemic Among Persons Who Inject Drugs: A Cost-Effectiveness Analysis in Six US Cities.

BACKGROUND: Persons who inject drugs (PWID) are at a disproportionately high risk of HIV infection. We aimed to determine the highest-valued combination implementation strategies to reduce the burden of HIV among PWID in 6 US cities. METHODS: Using a dynamic HIV transmission model calibrated for Atlanta, Baltimore, Los Angeles, Miami, New York City, and Seattle, we assessed the value of implementing combinations of evidence-based interventions at optimistic (drawn from best available evidence) or ideal (90% coverage) scale-up. We estimated reduction in HIV incidence among PWID, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) for each city (10-year implementation; 20-year horizon; 2018 $ US). RESULTS: Combinations that maximized health benefits contained between 6 (Atlanta and Seattle) and 12 (Miami) interventions with ICER values ranging from $94 069/QALY in Los Angeles to $146 256/QALY in Miami. These strategies reduced HIV incidence by 8.1% (credible interval [CI], 2.8%-13.2%) in Seattle and 54.4% (CI, 37.6%-73.9%) in Miami. Incidence reduction reached 16.1%-75.5% at ideal scale. CONCLUSIONS: Evidence-based interventions targeted to PWID can deliver considerable value; however, ending the HIV epidemic among PWID will require innovative implementation strategies and supporting programs to reduce social and structural barriers to care.

Comparative effectiveness of buprenorphine-naloxone versus methadone for treatment of opioid use disorder: a population-based observational study protocol in British Columbia, Canada.

INTRODUCTION: Despite a recent meta-analysis including 31 randomised controlled trials comparing methadone and buprenorphine for the treatment of opioid use disorder, important knowledge gaps remain regarding the long-term effectiveness of different treatment modalities across individuals, including rigorously collected data on retention rates and other treatment outcomes. Evidence from real-world data represents a valuable opportunity to improve personalised treatment and patient-centred guidelines for vulnerable populations and inform strategies to reduce opioid-related mortality. Our objective is to determine the comparative effectiveness of methadone versus buprenorphine/naloxone, both overall and within key populations, in a setting where both medications are simultaneously available in office-based practices and specialised clinics. METHODS AND ANALYSIS: We propose a retrospective cohort study of all adults living in British Columbia receiving opioid agonist treatment (OAT) with methadone or buprenorphine/naloxone between 1 January 2008 and 30 September 2018. The study will draw on seven linked population-level administrative databases. The primary outcomes include retention in OAT and all-cause mortality. We will determine the effectiveness of buprenorphine/naloxone vs methadone using intention-to-treat and per-protocol analyses-the former emulating flexible-dose trials and the latter focusing on the comparison of the two medication regimens offered at the optimal dose. Sensitivity analyses will be used to assess the robustness of results to heterogeneity in the patient population and threats to internal validity. ETHICS AND DISSEMINATION: The protocol, cohort creation and analysis plan have been approved and classified as a quality improvement initiative exempt from ethical review (Providence Health Care Research Institute and the Simon Fraser University Office of Research Ethics). Dissemination is planned via conferences and publications, and through direct engagement and collaboration with entities that issue clinical guidelines, such as professional medical societies and public health organisations.