Superiority and cost-effectiveness of Individual Placement and Support versus standard employment support for people with alcohol and drug dependence: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial.

Background: Individual Placement and Support (IPS) is a specialist intervention to help people attain employment in the open competitive labour market. IPS has been developed in severe mental illness and other disabilities, but it is of unknown effectiveness for people with alcohol and drug dependence. The Individual Placement and Support-Alcohol and Drug (IPS-AD) is the first superiority trial to evaluate effectiveness and cost-effectiveness. Methods: IPS-AD was a pragmatic, parallel-group, multi-centre, randomised, controlled, phase 3 trial of standard employment support (treatment-as-usual [TAU]) versus IPS. IPS was offered as a single episode for up to 13 months. The study was done at seven community treatment centres for alcohol and drug dependence in England. Study participants were adults (18-65 years), who had been enrolled for at least 14 days in treatment for alcohol use disorder (AUD), opioid use disorder (OUD), or another drug use disorder (DUD; mostly cannabis and stimulants); were unemployed or economically inactive for at least six months; and wished to attain employment in the open competitive labour market. After random allocation to study interventions, the primary outcome was employment during 18-months of follow-up, analysed by mixed-effects logistic regression, using multiple imputation for the management of missing outcome data. There were two cost-effectiveness outcomes: a health outcome expressed as a quality adjusted life year (QALY) using £30,000 and £70,000 willingness-to-pay [WTP] thresholds; and additional days of employment, with a WTP threshold of £200 per day worked. The study was registered with ISRCTN (ISRCTN24159790) and is completed. Findings: Between 8 May 2018 and 30 September 2019, 2781 potentially eligible patients were identified. 812 were excluded before screening, and 1720 participants were randomly allocated to TAU or IPS. In error, nine participants were randomised to study interventions on two occasions-so data for their first randomisation was analysed (modified intention-to-treat). A further 24 participants withdrew consent for all data to be used (full-analysis set therefore 1687 participants [70.1% male; mean age 40.8 years]; TAU, n = 844; IPS, n = 843 [AUD, n = 610; OUD, n = 837; DUD, n = 240]). Standard employment support was received by 559 [66.2%] of 844 participants in the TAU group. IPS was received by 804 [95.37%] of 843 participants in the IPS group. IPS was associated with an increase in attainment of employment compared with TAU (adjusted odds ratio [OR] 1.29; 95% CI 1.02-1.64; p-value 0.036). IPS was effective for the AUD and DUD groups (OR 1.48; 95% CI 1.14-1.92; p-value 0.004; OR 1.45, 95% CI 1.03-2.04, p-value 0.031, respectively), but not the OUD group. IPS returned an incremental QALY outcome gain of 0.01 (range 0.003-0.02) per participant with no evidence of cost-effectiveness at either WTP threshold-but QALY gains were cost-effective for the AUD and DUD groups at the £70,000 WTP threshold (probability 0.52 and 0.97, respectively). IPS was cost-effective for additional days of employment (probability 0.61), with effectiveness relating to the AUD group only (probability >0.99). Serious Adverse Events were reported by 39 participants (13 [1.5%] of 844 participants in the TAU group and 23 [2.7%] of 43 participants in the IPS group). There was a total of 25 deaths (1.5%; 9 in the TAU group and 16 in the IPS group)-none judged related to study interventions. Interpretation: In this first superiority randomised controlled trial of IPS in alcohol and drug dependence, IPS helped more people attain employment in the open competitive labour market than standard employment support. IPS was cost-effective for a QALY health outcome (£70,000 WTP threshold) for the AUD and DUD groups, and for additional days of employment for the AUD group (£200 per day worked WTP threshold). Funding: UK government Work and Health Unit.

Superiority and cost-effectiveness of monthly extended-release buprenorphine versus daily standard of care medication: a pragmatic, parallel-group, open-label, multicentre, randomised, controlled, phase 3 trial.

Background: Daily methadone maintenance or buprenorphine treatment is the standard-of-care (SoC) medication for opioid use disorder (OUD). Subcutaneously injected, extended-release buprenorphine (BUP-XR) may be more effective-but there has been no superiority evaluation. Methods: This pragmatic, parallel-group, open-label, multi-centre, effectiveness superiority randomised, controlled, phase 3 trial was conducted at five National Health Service community-based treatment clinics in England and Scotland. Participants (adults aged ≥ 18 years; all meeting DSM-5 diagnostic criteria for moderate or severe OUD at admission to their current maintenance treatment episode) were randomly assigned (1:1) to receive continued daily SoC (liquid methadone (usual dose range: 60-120 mg) or sublingual/transmucosal buprenorphine (usual dose range: 8-24 mg) for 24 weeks; or monthly BUP-XR (Sublocade;® two injections of 300 mg, then four maintenance injections of 100 mg or 300 mg, with maintenance dose selected by response and preference) for 24 weeks. In the intent-to-treat population (senior statistician blinded to blinded to treatment group allocation), and with a seven-day grace period after randomisation, the primary endpoint was the count of days abstinent from non-medical opioids between days 8-168 (i.e., weeks 2-24; range: 0-161 days). Safety was reported for the intention-to- treat population. Adopting a broad societal perspective inclusive of criminal justice, NHS and personal social service costs, a trial-based cost-utility analysis estimated the Incremental Cost-effectiveness Ratio (ICER) per quality-adjusted life year (QALY) of BUP-XR versus SoC at the National Institute for Health and Care Excellence threshold. The study was registered EudraCT (2018-004460-63) and ClinicalTrials.gov (NCT05164549), and is completed. Findings: Between Aug 9, 2019 and Nov 2, 2021, 314 participants were randomly allocated to receive SoC (n = 156) or BUP-XR (n = 158). Participants were abstinent from opioids for an adjusted mean of 104.37 days (standard error [SE] 9.89; range: 0-161 days) in the SoC group and an adjusted mean of 123.43 days (SE 4.76; range: 24-161 days) in the BUP-XR group (adjusted incident rate ratio [IRR] 1.18, 95% confidence interval [CI] 1.05-1.33; p-value 0.004). The incidence of any adverse event was higher in the BUP-XR group than the SoC group (128 [81.0%] of 158 participants versus 67 [42.9%] of 156 participants, respectively-most commonly rapidly-resolving (mild-moderate range) pain from drug administration in the BUP-XR group (121 [26.9%] of 450 adverse events). There were 11 serious adverse events (7.0%) in the 158 participants in the BUP-XR group, and 18 serious adverse events (11.5%) in the 156 participants in the SoC group-none judged to be related to study treatment. The BUP-XR treatment group had a mean incremental cost of £1033 (95% central range [CR] -1189 to 3225) and was associated with a mean incremental QALY of 0.02 (95% CR 0.00-0.05), and an ICER of £47,540 (0.37 probability of being cost-effective at the £30,000/QALY gained willingness-to-pay threshold). However, BUP-XR dominated the SoC among participants who were rated more severe at study baseline, and among participants in maintenance treatment for more that 28 days at study enrolment. Interpretation: Evaluated against the daily oral SoC, monthly BUP-XR is clinically superior, delivering greater abstinence from opioids, and with a comparable safety profile. BUP-XR was not cost-effective in a base case cost-utility analysis using the societal perspective, but it was more effective and less costly (dominant) among participants with more severe OUD, or those whose current treatment episode was longer than 28 days. Further trials are needed to evaluate if BUP-XR is associated with better clinical and health economic outcomes over the longer term. Funding: Indivior.

Adjunctive Medication Management and Contingency Management to enhance adherence to acamprosate for alcohol dependence: the ADAM trial RCT.

Background: Acamprosate is an effective and cost-effective medication for alcohol relapse prevention but poor adherence can limit its full benefit. Effective interventions to support adherence to acamprosate are therefore needed. Objectives: To determine the effectiveness of Medication Management, with and without Contingency Management, compared to Standard Support alone in enhancing adherence to acamprosate and the impact of adherence to acamprosate on abstinence and reduced alcohol consumption. Design: Multicentre, three-arm, parallel-group, randomised controlled clinical trial. Setting: Specialist alcohol treatment services in five regions of England (South East London, Central and North West London, Wessex, Yorkshire and Humber and West Midlands). Participants: Adults (aged 18 years or more), an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of alcohol dependence, abstinent from alcohol at baseline assessment, in receipt of a prescription for acamprosate. Interventions: (1) Standard Support, (2) Standard Support with adjunctive Medication Management provided by pharmacists via a clinical contact centre (12 sessions over 6 months), (3) Standard Support with adjunctive Medication Management plus Contingency Management that consisted of vouchers (up to £120) to reinforce participation in Medication Management. Consenting participants were randomised in a 2 : 1 : 1 ratio to one of the three groups using a stratified random permuted block method using a remote system. Participants and researchers were not blind to treatment allocation. Main outcome measures: Primary outcome: self-reported percentage of medication taken in the previous 28 days at 6 months post randomisation. Economic outcome: EuroQol-5 Dimensions, a five-level version, used to calculate quality-adjusted life-years, with costs estimated using the Adult Service Use Schedule. Results: Of the 1459 potential participants approached, 1019 (70%) were assessed and 739 (73 consented to participate in the study, 372 (50%) were allocated to Standard Support, 182 (25%) to Standard Support with Medication Management and 185 (25%) to Standard Support and Medication Management with Contingency Management. Data were available for 518 (70%) of participants at 6-month follow-up, 255 (68.5%) allocated to Standard Support, 122 (67.0%) to Standard Support and Medication Management and 141 (76.2%) to Standard Support and Medication Management with Contingency Management. The mean difference of per cent adherence to acamprosate was higher for those who received Standard Support and Medication Management with Contingency Management (10.6%, 95% confidence interval 19.6% to 1.6%) compared to Standard Support alone, at the primary end point (6-month follow-up). There was no significant difference in per cent days adherent when comparing Standard Support and Medication Management with Standard Support alone 3.1% (95% confidence interval 12.8% to -6.5%) or comparing Standard Support and Medication Management with Standard Support and Medication Management with Contingency Management 7.9% (95% confidence interval 18.7% to -2.8%). The primary economic analysis at 6 months found that Standard Support and Medication Management with Contingency Management was cost-effective compared to Standard Support alone, achieving small gains in quality-adjusted life-years at a lower cost per participant. Cost-effectiveness was not observed for adjunctive Medication Management compared to Standard Support alone. There were no serious adverse events related to the trial interventions reported. Limitations: The trial's primary outcome measure changed substantially due to data collection difficulties and therefore relied on a measure of self-reported adherence. A lower than anticipated follow-up rate at 12 months may have lowered the statistical power to detect differences in the secondary analyses, although the primary analysis was not impacted. Conclusions: Medication Management enhanced with Contingency Management is beneficial to patients for supporting them to take acamprosate. Future work: Given our findings in relation to Contingency Management enhancing Medication Management adherence, future trials should be developed to explore its effectiveness and cost-effectiveness with other alcohol interventions where there is evidence of poor adherence. Trial registration: This trial is registered as ISRCTN17083622 https://doi.org/10.1186/ISRCTN17083622. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 22. See the NIHR Journals Library website for further project information.

Many people who are trying to stop drinking alcohol can find it difficult to remain alcohol free. There is a medication called acamprosate (Campral) that can reduce cravings thereby increasing the likelihood of abstinence. However, some people have trouble taking the right amount of acamprosate tablets needed every day at the right time, preferably at mealtimes. This means the medication is not as effective. We have tested some new ways to help support people taking acamprosate. We tested three different strategies to find the best way to support people taking acamprosate. We recruited 739 people aged 18 and over who were receiving alcohol treatment to stop drinking and were taking acamprosate. We randomly allocated these people to three groups. The first was Standard Support, the usual support people receive when taking acamprosate. The second group received Standard Support plus Medication Management. This consisted of 12 telephone calls over 6 months with a trained pharmacist to discuss the importance of taking the right amount of the medication, how the medication works and strategies to help people take the medication correctly. The third group received Standard Support, Medication Management and Contingency Management. This involved giving people shopping vouchers for participating with Medication Management calls. The maximum value of vouchers per person was £120. People who were in the group receiving Medication Management and Contingency Management took a greater number of acamprosate tablets. We also found that Medication Management plus Contingency Management was more cost-effective; there were greater gains in health with a smaller cost per person compared to Standard Support alone. This shows that there is likely to be a benefit to patients of Medication Management plus Contingency Management for supporting people taking acamprosate.

Patients' perceptions of self-administered dosing to opioid agonist treatment and other changes during the COVID-19 pandemic: a qualitative study.

OBJECTIVES: During the COVID-19 pandemic, addiction treatment services received official guidance asking them to limit face-to-face contact with patients and to prescribe opioid agonist treatment (OAT) medication flexibly. With the aim for most patients to receive take-home supplies for self-administration rather than attendance for observed daily dosing. DESIGN: This was a theory-driven, clinically applied qualitative study, with data for thematic analysis collected by semi-structured, audio-recorded, telephone interviews. PARTICIPANTS: Twenty-seven adults (aged ≥18 years) enrolled in sublingual (tablet) buprenorphine and oral (liquid) methadone OAT. SETTING: Community addictions centre in the London Borough of Lambeth operated by South London and Maudsley NHS Trust. RESULTS: Three major themes were identified: (1) dissatisfaction and perceived stigma with OAT medication dispensing arrangements before the pandemic; (2) positive adaptations in response to COVID-19 by services; (3) participants recommended that, according to preference and evidence of adherence, OAT should be personalised to offer increasing medication supplies for self-administration from as early as 7 days after commencement of maintenance prescribing. CONCLUSIONS: In an applied qualitative study of patients enrolled in OAT during the COVID-19 pandemic, participants endorsed their opportunity to take medication themselves at home and with virtual addiction support. Most patients described a preference for self-administration with increased dispensing supplies, from as early as 7 days into maintenance treatment, if they could demonstrate adherence to their prescription.

Polysubstance Use in Adults With Opioid Use Disorder Receiving Buprenorphine Maintenance.

INTRODUCTION: Studying polysubstance use is a public health recommendation. In the United Arab Emirates, more than 80% of adults with opioid use disorder (OUD) use 2 or more nonopioid substances. This secondary analysis contrasts the characteristics of polysubstance users (OUD + ≥1 nonopioid) with OUD, explores the correlates and predictors of nonfatal overdose, and examines the impact of polysubstance use on OUD treatment outcomes using buprenorphine (BUP). METHODS: This analysis uses data from a 16-week outpatient randomized controlled trial of 141 adults with OUD allocated to BUP + incentivized adherence and abstinence monitoring (n = 70) and BUP in usual care (control, n = 71). Outcomes were nonfatal overdose events over the preceding 12 months, positive drug screens, and treatment retention. Participant characteristics were contrasted, and bivariate statistical tests were conducted for simple associations followed by logistic regression. RESULTS: Polysubstance use was reported by 117 participants (82.9%), the majority of whom used pregabalin 72.1% (n = 75). Compared with OUD, polysubstance users observed higher arrests (median, 1.0 [interquartile range, 0.0-3.0] vs 0.5 [interquartile range, 0.0-2.0]; P = 0.04]) and nonfatal overdose events (n = 33 [31.8%] vs 2 [10.8%], P = 0.003). Carisoprodol and injecting drug use independently predicted nonfatal overdose (adjusted odds ratio, 4.519 [95% confidence interval, 1.81-11.22] and 2.74 [95% confidence interval, 1.15-6.51], respectively). No significant difference was observed in opioid use and retention in treatment outcomes between groups. CONCLUSION: Carisoprodol and injecting drug use increase the likelihood of nonfatal overdose in adults with OUD. Polysubstance use does not impact response to BUP treatment compared with OUD.

Experience and response to a randomised controlled trial of extended-release injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone for opioid use disorder: protocol for a mixed-methods evaluation.

INTRODUCTION: Opioid use disorder (OUD) is a debilitating and persistent disorder. The standard-of-care treatment is daily maintenance dosing of sublingual buprenorphine (BUP-SL) or oral methadone (MET). Monthly, extended-release, subcutaneous injectable buprenorphine (BUP-XR) has been developed to enhance treatment effectiveness. This study aims to investigate the experiences of participants who have been offered BUP-XR (evaluation 1), health-related quality-of-life among participants who have opted to receive BUP-XR longer term (evaluation 2) and the experiences of participants allocated to receive BUP-XR or BUP-SL or MET with the offer of adjunctive personalised psychosocial intervention (evaluation 3). METHODS AND ANALYSIS: Three qualitative-quantitative (mixed-methods) evaluations embedded in a five-centre, head-to-head, randomised controlled trial of BUP-XR versus BUP-SL and MET in the UK. Evaluation 1 is a four-centre interview anchored on an OUD-related topic guide and conducted after the 24-week trial endpoint. Evaluation 2 is a two-centre interview anchored on medications for opioid use disorder-specific quality-of-life topic guide conducted among participants after 12-24 months. Evaluation 3: single-centre interview after the 24-week trial endpoint. All evaluations include selected trial clinical measures, with evaluation 2 incorporating additional questionnaires. Target participant recruitment for evaluations 1 and 2 is 15 participants per centre (n=60 and n=30, respectively). Recruitment for evaluation 3 is 15 participants per treatment arm (n=30). Each evaluation will be underpinned by theory, drawing on constructs from the behavioural model for health service use or the health-related quality-of-life model. Qualitative data analysis will be by iterative categorisation. ETHICS AND DISSEMINATION: Study protocol, consent materials and questionnaires were approved by the London-Brighton and Sussex research ethics committee (reference: 19/LO/0483) and the Health Research Authority (IRAS project number 255522). Participants will be provided with information sheets and informed written consent will be obtained for each evaluation. Study findings will be disseminated through peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: 2018-004460-63.

Lower buprenorphine elimination rate constant is associated with lower opioid use.

BACKGROUND: Opioid craving is suggested to correlate with the rate of reduction in buprenorphine (BUP) plasma levels. No studies explored Buprenorphine elimination rate constant (BUP EL.R) as a predictor of opioid use or retention in BUP treatment. METHODS: Analysis was performed using data from a randomized controlled trial of 141 adults with opioid use disorder (OUD) randomized to Incentivized Adherence and Abstinence monitoring (I-AAM; experimental (n = 70) and treatment-as-usual; control (n = 71). In the I-AAM, structured access to unsupervised BUP doses was provided up to 28 days contingent of adherence measured by Therapeutic Drug Monitoring and abstinence by Urinary Drug Screens (UDS). In contrast, the treatment-as-usual (control) provided unstructured access to unsupervised doses was provided for up to 14 days considering UDS results. The primary outcome was percentage negative UDS. The secondary outcome, retention in treatment, was continuous enrollment in the study and analysis was via intention-to-treat. Significant bivariate correlations with the outcomes were adjusted for group allocation. RESULTS: A significant negative correlation between BUP EL.R and percentage negative opioid screens (Pearson correlation coefficient - 0.57, p < 0.01) was found. After adjusting for trial group, BUP EL.R was shown to be an independent predictor of percentage negative opioid screens (Standardized Beta Coefficient - 0.57, 95% CI - 221.57 to - 97.44, R2 0.322). CONCLUSION: BUP EL.R predicted 32.2% of the variation in percentage negative opioid UDS and may serve as a potential promising tool in precision medicine of BUP treatment. Higher buprenorphine elimination is associated with higher positive opioid urine screens during treatment. TRIAL REGISTRATION: ISRCTN41645723 retrospectively registered on 15/11/2015.

Extended-release pharmacotherapy for opioid use disorder (EXPO): protocol for an open-label randomised controlled trial of the effectiveness and cost-effectiveness of injectable buprenorphine versus sublingual tablet buprenorphine and oral liquid methadone.

BACKGROUND: Sublingual tablet buprenorphine (BUP-SL) and oral liquid methadone (MET) are the daily, standard-of-care (SOC) opioid agonist treatment medications for opioid use disorder (OUD). A sizable proportion of the OUD treatment population is not exposed to sufficient treatment to attain the desired clinical benefit. Two promising therapeutic technologies address this deficit: long-acting injectable buprenorphine and personalised psychosocial interventions (PSI). This study will determine (A) the effectiveness and cost-effectiveness - monthly injectable, extended-release (BUP-XR) in a head-to-head comparison with BUP-SL and MET, and (B) the effectiveness of BUP-XR with adjunctive PSI versus BUP-SL and MET with PSI. Safety, retention, craving, substance use, quality-adjusted life years, social functioning, and subjective recovery from OUD will be also evaluated. METHODS: This is a pragmatic, multi-centre, open-label, parallel-group, superiority RCT, with a qualitative (mixed-methods) evaluation. The study population is adults. The setting is five National Health Service community treatment centres in England and Scotland. At each centre, participants will be randomly allocated (1:1) to BUP-XR or SOC. At the London study co-ordinating centre, there will also be allocation of participants to BUP-XR with PSI or SOC with PSI. With 24 weeks of study treatment, the primary outcome is days of abstinence from non-medical opioids during study weeks 2-24 combined with up to 12 urine drug screen tests for opioids. For 90% power (alpha, 5%; 15% inflation for attrition), 304 participants are needed for the BUP-XR versus SOC comparison. With the same planning parameters, 300 participants are needed for the BUP-XR and PSI versus SOC and PSI comparison. Statistical and health economic analysis plans will be published before data-lock on the Open Science Framework. Findings will be reported in accordance with the Consolidated Standards of Reporting Trials and Consolidated Health Economic Evaluation Reporting Standards. DISCUSSION: This pragmatic randomised controlled trial is the first evaluation of injectable BUP-XR versus the SOC medications BUP-SL and MET, with personalised PSI. If there is evidence for the superiority of BUP-XR over SOC medication, study findings will have substantial implications for OUD clinical practice and treatment policy in the UK and elsewhere. TRIAL REGISTRATION: EU Clinical Trials register 2018-004460-63.

Policies and interventions to reduce harmful gambling: an international Delphi consensus and implementation rating study.

There is increasing public health concern about harmful gambling, but no consensus on effective policies and interventions to reduce risk and prevent harm has been reached. Focusing on policies and interventions (ie, measures), the aim of this study was to determine if expert consensus could be reached on measures perceived to be effective that could be implemented successfully. Our work involved a pre-registered, three-round, independent Delphi panel consensus study and an implementation rating exercise. A starting set of 103 universal and targeted measures, which were sourced from several key resources and inputs from public health stakeholders, were grouped into seven domains: price and taxation; availability; accessibility; marketing, advertising, promotion, and sponsorship; environment and technology; information and education; and treatment and support. Across three rounds, an independent panel of 35 experts individually completed online questionnaires to rank each measure for known or potential effectiveness. A consensus was reached if at least 70% of the panel judged a measure to be either not effective, moderately effective, or highly effective. Then, each measure that reached a consensus for effectiveness was evaluated on four implementation dimensions: practicability, affordability, side-effects, and equity. A summative threshold criterion was used to select a final optimal set of measures for England. The panel reached consensus on 83 (81%) of 103 measures. Two measures were judged as ineffective by the panel. The remaining 81 effective measures were drawn from all domains (14 of 15 measures in the the marketing, advertising, promotion, and sponsorship domain were judged as effective, whereas five of ten measures in the information and education domain were judged as effective). During the evaluation exercise, the 81 measures were assessed for likelihood of implementation success. This assessment considered the practicality, affordability, ability to generate unanticipated side-effects, and ability to decrease differences between advantaged and disadvantaged groups in society of each measure. We identified 40 universal and targeted measures to tackle harmful gambling (three measures from the price and taxation domain; ten from the availability domain; five from the accessibility domain; six from the marketing, advertising, promotion, and sponsorship domain; eight from the environment and technology domain; three from the information and education domain; and five from the treatment and support domain). Implementation of these measures in England could substantially strengthen regulatory controls while providing new resources. The findings of our work offer a blueprint for a public health approach to preventing harms related to gambling.

Service Users' Views and Experiences of Alcohol Relapse Prevention Treatment and Adherence: New Role for Pharmacists?

AIMS: To understand service users' views and experiences of alcohol relapse prevention medication, views of a telephone behavioural modification intervention delivered by pharmacists and the use of Contingency Management (CM) to support acamprosate adherence following assisted alcohol withdrawal. METHODS: Four focus groups were conducted within four alcohol treatment and recovery groups across England (UK), with service users with lived experience of alcohol dependence (26 participants). Semi-structured topic guide was used to explore participants' views and experiences of alcohol relapse prevention medication, a telephone behavioural modification medication intervention delivered by pharmacists, and the use of CM to support acamprosate adherence. These were audio-recorded, transcribed verbatim and thematically analysed inductively and deductively. RESULTS: Four themes were identified: concerns about support and availability of alcohol relapse prevention medication; lack of knowledge and understanding about acamprosate treatment; positive perceptions of acamprosate adherence telephone support from pharmacists; and negative perceptions of CM to support acamprosate adherence. There were misunderstandings about acamprosate's mode of action and strong negative beliefs about CM. However, most were positive about pharmacists' new role to support acamprosate adherence. CONCLUSION: This study highlighted challenges service users face to commence alcohol relapse prevention medication. It appears service users could benefit from a pharmacist-led telephone intervention to improve understanding about acamprosate medication, particularly, if delivered in an engaging and motivating way.

The opioid use disorder core outcomes set (OUD-COS) for treatment research: findings from a Delphi consensus study.

BACKGROUND AND AIM: There is no gold-standard and considerable heterogeneity in outcome measures used to evaluate treatments for opioid use disorder (OUD) along the opioid treatment cascade. The aim of this study was to develop the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) opioid use disorder core outcomes set (OUD-COS). DESIGN: Four-round, e-Delphi expert panel consensus study and plenary research group discussion and targeted consultation. SETTING: United States. PARTICIPANTS: A panel of 25 members including clinical practitioners, clinical researchers and administrative staff from the CTN, the network's affiliated clinical and community sites and the NIDA Centre for the CTN. MEASUREMENTS: From a pool of 24 candidate items in four domains (biomedical/disease status; behaviors, symptoms and functioning; opioid treatment cascade; and morbidity and mortality), the panel completed an on-line questionnaire to rank items with defined specification on a 9-point scale for importance, with a standard 70% consensus criterion. FINDINGS: After the fourth round of the questionnaire and subsequent discussion, consensus was reached for five outcomes: two patient-reported (global impression of improvement and incident non-fatal overdose); one clinician-reported (illicit/non-medical drug toxicology); and two from administrative records (duration of treatment and fatal opioid poisoning). CONCLUSIONS: An e-Delphi consensus study has produced the US National Institute on Drug Abuse (NIDA) National Drug Abuse Treatment Clinical Trials Network opioid use disorder core outcomes set (version 1) for opioid use disorder treatment efficacy and effectiveness research.

The effect evaluation of Individual Placement and Support (IPS) for patients with substance use disorders: study protocol for a randomized controlled trial of IPS versus enhanced self-help.

BACKGROUND: Employment is associated with better outcomes of substance use treatment and protects against relapse after treatment completion. Unemployment rates are high for people with substance use disorders (SUD) who undergo treatment, with Norwegian estimates ranging from 81 to 91%. Evidence-based vocational models are lacking for patients in SUD treatment but exist for patients with psychosis in terms of Individual Placement and Support (IPS). The aim of the IPS for substance use disorders (IPS-SUD) trial is to investigate the effect of IPS in a SUD population. METHODS/DESIGN: The IPS-SUD trial is a randomized controlled trial (RCT) comparing IPS to an enhanced control intervention. The study is a seven-site, two-arm, pragmatic, parallel-group, superiority RCT. Participants are randomly assigned (1:1) to receive either IPS plus treatment as usual (TAU) or to receive a self-help guide book and 12-h workshop plus 1-h individual vocational guidance plus TAU. Aiming to recruit 200 participants, we will be able to detect a 20% difference in the main outcome of employment with 90% power. We will make assessments at inclusion and at 6- and 12-month follow-ups and obtain outcome data on employment from national mandatory registries. The primary outcome will be at least 1 day of competitive employment during the 18-month follow-up period. Secondary employment outcomes will capture the pattern and extent of employment in terms of total time worked (days/hours), time to first employment, number of different jobs, duration of the longest employment, and sustained employment. Secondary non-employment outcomes will be substance use, mental distress, and quality of life measured by validated instruments at 6, 12, and 18 months follow-up assessments. To be eligible, participants must be between 18 and 65 years, currently unemployed and in treatment for SUD. DISCUSSION: The IPS-SUD trial will provide evidence for the use of IPS in a SUD population. Findings from the study will have implications for service delivery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04289415 . Registered on February 28, 2020.

Exploratory Economic Evaluation of Buprenorphine Treatment in Opioid Use Disorder.

BACKGROUND: Burden of opioid use disorder (OUD) is expressed in economic values or health metrics like Disability Adjusted Life Years (DALYs). Disability Weight (DW), a component of DALYs is estimated using economic methods or psychometric tools. Estimating DW at patient level using psychometric tools is an alternative to non-population specific DW overestimated by economic methods. Providing Medication Assisted Treatment (MAT) using buprenorphine/naloxone film (BUP/NX-F) for OUD is limited by financial constraints. AIM: To estimate the burden of OUD at patient level and explore the cost-benefit of two buprenorphine treatment interventions. METHODS: The present study was conducted alongside a randomized controlled trial of 141 adults with OUD stabilized on BUP/NX-F and randomized to BUP/NX-F with Incentivized Abstinence and Adherence Monitoring (experimental, n=70) and BUP/NX-F in usual care (control, n=71). The cost of illness was estimated applying a societal perspective. The Impairment Weight (IW) was estimated over a '0' to '1' scale, where '0' represents no impairment and '1' full impairment using the Work and Social Adjustment Scale (WSAS). RESULTS: Median (interquartile range) annual cost of OUD per participant was AED 498,171.1 (413,499.0 -635,725.3) and AED 538,694.4 (4,211,398.0 - 659,949.0) in the experimental and control groups, respectively (p=0.33). Illicit drug purchase represented 60 % of the annual cost of illness. At baseline, the mean Impairment Weight (IW) was 0.55 (SD 0.26) and 0.62 (SD 0.24) in the experimental and control groups, respectively. At end of the study, the IW was 0.26 (SD 0.28) representing 51% reduction in the experimental group compared to 0.42 (SD 0.33) in the control group representing a 27% reduction. Excluding imprisonment, the cost-benefit of treatment was not realized. In contrast, accounting for imprisonment, cost benefit expressed as a return-on-investment was established at 1.55 and 1.29 in the experimental and control groups, respectively. IMPLICATIONS FOR MENTAL HEALTH POLICY: Cost benefit analysis can serve as a simple and practical tool to evaluate the cost benefit of treatment interventions. Demonstrating the cost benefit of buprenorphine treatment has the potential to facilitate public funding and accessibility to opioid assisted treatment.