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Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study



Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD.


The project adopts a multidisciplinary approach, where the primary cohort for analysis will consist of approximately 250 patients in Norway, observed during the period of 2022–2026. Cohorts for comparative analysis will include all HAT-patients in Denmark from 2010 to 2022 (N = 500) and all Norwegian patients in conventional OAT (N = 8300). Data comes from individual in-depth and semi-structured interviews, self-report questionnaires, clinical records, and national registries, collected at several time points throughout patients’ courses of treatment. Qualitative analyses will use a flexible inductive thematic approach. Quantitative analyses will employ a wide array of methods including bi-variate parametric and non-parametric tests, and various forms of multivariate modeling.


The project’s primary strength lies in its comprehensive and longitudinal approach. It has the potential to reveal new insights on whether pharmaceutical heroin should be an integral part of integrated conventional OAT services to individually tailor treatments for patients with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some do not succeed with conventional OAT will strengthen the knowledge base for drug treatment in general. Results will be disseminated to the scientific community, clinicians, and policy makers.

Trial registration

The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK),

Peer Review reports


Opioid use disorder (OUD) is a major global health concern with an estimated caseload of 31.5 million in 2022 [1]. It is frequently related to infectious diseases from injection-based drug use, psychiatric disorders, deterioration of social relations, reduced workforce participation, and a tenfold increase in crude all-cause rate of mortality [2]. The treatment and care for patients with OUD has gradually developed from an initial emphasis on abstinence and withdrawal management, to regular prescriptions of opioid agonists for maintenance treatment (OAT) [3].

Half a century after the first initiatives of prescribing methadone for OUD in a regular manner [4, 5] OAT now has a strong evidence-base [6]. Overall, it contributes to a substantial reduction in mortality, general health benefits, and reduced use of illicit drugs and criminal activity [6,7,8,9]. Still, not all individuals find conventional OAT sufficiently attractive over time, and cycles of dropout and re-entering are ongoing challenges in these programs [10,11,12]. A variable retention rate of 20–84% has been observed [13]. Among the efforts to improve the inclusion of patients in OAT is the introduction of more diverse medication options, such as rapid-onset, short-acting injectable pharmaceutical opioids such as heroin [14].

The use of medical grade heroin (diacetylmorphine) in treating OUD has been applied in England since the 1920s, originally as hand-out prescriptions to take home [15, 16]. Initiatives to incorporate it into more regular OAT started in Switzerland in 1994, with promising results [17, 18]. Now, three decades later and after clinical trials from several European countries and Canada, the body of research suggests that heroin-assisted treatment (HAT) is beneficial for a sub-selection of patients in regard to health outcomes and reductions in use of illicit drugs and criminal behavior [19,20,21]. The results are less clear for longer-term outcomes such as mortality [6, 19].

Still, HAT remains politically controversial [22], and reduced illicit heroin use and criminal behavior may not be compelling arguments for its efficacy. Rather, as for any other medical treatment its impact may better be assessed by patients’ improvement in quality of life, everyday level of function, and mortality [23].

Although newer studies suggests that take home doses are a feasible and safe alternative for patients deemed suitable [24, 25], medical heroin is typically administered under rigorous and comprehensive medical supervision due to the risk of serious adverse events and diversion [26]. Studies on cost effectiveness suggest both excessive expenses and inconclusive results when compared with methadone treatment, which are possibly dependent on methodological issues and poor consideration of the mechanisms involved [20, 27, 28].

Additionally, most of the research on the effectiveness of HAT originates from randomized clinical trials which may have limitations concerning the understanding of long-term outcomes and the mechanisms behind [23]. Thus, the main contribution of HAT may lie in the engagement of a high-risk population in utilization of health- and social services over time, like the more conventional options of OAT [23, 29]. A more comprehensive view of outcomes beyond the mere quantity and frequency of drug use and criminal behaviour can provide crucial information about the mechanisms responsible for treatment effectiveness, and its possible impact on other clinically and socially relevant parameters [30].

The current Norwegian HAT study is presented in this context. The study is part of a clinical project by the Norwegian Directorate of Health, with the aim to evaluate the implementation of HAT into the national OAT services. It is based on a model from Denmark where the use of medical heroin was introduced in 2010, following the British “RIOTT” line of test trials from 2005 [31]. Denmark currently has five clinics as permanent parts of the national healthcare system, although a limited amount of research has been published from this model [32].

The Norwegian HAT-project

OAT programs based on prescription of methadone and buprenorphine has in various forms been integrated into the Norwegian health and social services-system since 1997 [33]. In the spring of 2020, the Norwegian Directorate of Health introduced a time-limited, clinically based project on the use of pharmaceutical heroin in the specialist healthcare services. Based on a day-center model, treatment is offered at two designated clinics in the largest Norwegian cities of Oslo and Bergen. The clinics consist of injection sites and medical personnel for the administration of pharmaceutical heroin twice a day, in combination with a take-home oral overnight dose of slow-releasing opioid-agonist such as methadone or morphine. Take-home doses of heroin are not granted, and patients must attend daily all year around. Psychosocial services and support are also offered [34]. Patients are referred from other services of substance use disorder treatment, specialist healthcare services or general practitioners. Criteria for admission are ongoing OUD with at least one former attempt of conventional OAT, being over 18 years of age and with general competency of consent. Exclusion criteria are severe mental disorders with reduced competency of consent, pregnancy, or repeated violent behavior.

The Norwegian Centre for Addiction Research (SERAF) at the University of Oslo was granted the research-based evaluation of the HAT project in 2021. The study will be conducted together with Section for Clinical Addiction Research (RusForsk) at Oslo University Hospital, Bergen Addiction Research Group (BAR) at Haukeland University Hospital in Bergen, Centre for Alcohol and Drug Research (CRF) at Aarhus University in Denmark, and the Norwegian user organization proLARNett.

Study aims

The primary aim of the research project is to examine the effects from implementing HAT in Norway for individual patients and for the health services organization. A secondary aim is to compare these findings with the Danish HAT program.

Based on the Norwegian Directorate of Health’s specifications in the project proposal, the study will cover the following thematic areas:

  1. 1.

    Explore the attitudes, experiences and challenges of HAT as perceived by patients, their relatives, and clinical staff.

  2. 2.

    Describe changes in mental and physical health among patients receiving HAT, and in what way it is associated with outcomes such as quality of life, utilization of health- and social services, social reintegration, criminal behavior and use of illicit drugs.

  3. 3.

    Report any serious adverse events and incidents at treatment initiation, during treatment, and after discharge from HAT.

  4. 4.

    Perform an economic evaluation of the program with associated clinical benefits and societal costs.

  5. 5.

    Evaluate the organizational processes involved in the implementation of HAT in Norwegian specialist healthcare services, and the eventual impact from HAT on OUD patients’ utilization of conventional OAT.

  6. 6.

    Additional research relevant to HAT that is not explicitly outlined in the proposal (may require additional approvals from the Norwegian Regional Committee for Medical and Health Research Ethics.)

The themes were operationalized into six work packages, with corresponding research questions and data sources (shown in Table 1).

Table 1 Overview of work packages

Methods and design

The project is a multi-dimensional study, involving an array of methodological approaches and data sources. The main part is a prospective cohort study of all Norwegian HAT patients, compared with the cohorts of all Danish HAT patients and Norwegian patients in conventional OAT.

Study populations and size

The primary target group is all patients enrolled in the two HAT clinics in Oslo and Bergen during the period 2022–2026, with an expected total sample size of N = 250. Based on earlier findings, the ratio of men to women is expected to be 4:1, with an age distribution of 27–60, presenting multiple substance use disorders. As the study is based on the total clinical population, representation will be determined by its demographics, with no exclusion of genders or ethnic minorities. The patients who have applied to but have not been accepted for HAT will be used for comparison, with an expected sample size of 100.

Comparative data from the Danish cohort will be drawn from the comprehensive dataset at Aarhus University from 2010 and onwards, with a sample size of approximately 500 [35]. Likewise, the comprehensive dataset at SERAF on the cohort of Norwegian patients in conventional OAT from 2003 has an approximate sample size of 8300.

Data sources

Data on the primary cohort of Norwegian HAT patients will be based on a prospective collection of both qualitative and quantitative variables from treatment inclusion and throughout the project period. For the cohorts of Danish patients, of Norwegian patients that have been referred to but not granted HAT, and of Norwegian patients in conventional OAT, data are mainly based on national registries.

In-depth and semi-structured interviews and observation

The qualitative part of the project includes individual in-depth and semi-structured interviews with patients and relatives on their views and experiences with HAT, and focus group interviews with staff concerning implementation, clinical and legal aspects of the project. Semi-structured interview protocols have been developed by the project group and user representatives. Interviews will include 25–35 patients and 10–20 family members, conducted by a team of researchers and user representatives at 1, 6, 18 months after patients enter treatment, and with relatives after 4 and 12 months. Focus group interviews with staff will be conducted at 3, 9 and 18 months. Further, the clinic managers are being interviewed at several timepoints from the planning of the clinics and throughout the duration of the project.

For insights into clinic aspects not identified through interviews, researchers will conduct participant observation in the clinics over several periods of 1–2 weeks throughout the study.


The quantitative part of the project will use similar questionnaires to preceding projects involving patients in conventional OAT. These will evaluate changes in physical and mental health, personal economy, utilization of social services, criminal behavior and illegal drug use by repeated measures administered at inclusion, by 3, 6 and 12 months of treatment, and thereafter yearly (24, 36 and 48 months). Staff are asked to complete a separate questionnaire if a patient leaves treatment.

Clinical records

Information will also be obtained from the individual patient’s routine clinical records on variables such as main vital signs, nutritional status, cognitive function and mental health, medication, and comorbidities, as well as more HAT-specific variables such as adverse events, dosage, and administration routes of the pharmaceutical heroin.

Central register databases

Nordic national registers are an important and useful source for epidemiological and healthcare services research, including the study of substance use disorders [36,37,38,39,40,41,42,43]. The project will utilize databases from national registries in both Norway and Denmark to describe the cohorts and to monitor the changes and outcomes in a wider context. Currently, one study has explored the use of the Short Form (SF-36) Health Survey in patients enrolled in the Danish HAT database, finding support for the structural and external validity for its use in HAT [44].

Table 2 gives an overview of the relevant Norwegian and Danish register databases along with their relevant variables.

Table 2 Central register databases, Norway and Denmark

Additional studies

Currently, the only planned sub-study is on the pharmacokinetics of heroin and its metabolites, and its subjective effects on patients. Despite its widespread use, the pharmacology of heroin remains poorly understood [45,46,47]. A subsample of patients will therefore be invited to participate in this observational study with post-administration blood samples collected at different time points, with analysis of the concentration of heroin and its metabolites together with scales of subjective experience. The study has been granted separate approvals from Norwegian Regional Committee for Medical and Health Research Ethics.

Analysis strategy

Exploration and analysis of data will be both by qualitative and quantitative strategies, for individual patients and at the organizational level.


Treatment satisfaction of patients is particularly significant to the project and is often dependent on the context of factors such as staff, management, and clinical environment [48, 49]. Qualitative analyses are widely considered valuable for description of phenomena and hypothesis generation, taking into consideration the natural context in which people and organizations function [50]. Transcribed interviews will be coded following the principles of a flexible inductive thematic analysis and multidimensional approach [51].


Given the large amount and comprehensive nature of the data, variables of interest will vary in levels of measurement and distribution, so parametric and non-parametric tests will be used accordingly.

Presentation of cohorts will include descriptive statistics by basic parameters such as mean or medians, standard deviations and ratios, and bivariate analyses by ANOVA and Chi-Square tests. Various advanced methods such as survival analysis and logistic and linear regression modeling will be applied based on the type and distribution of dependent variables and co-variates. To avoid ecological fallacy and nested dimensions, multi-level methods will be applied for analyses of patients in relation to services’ organization [52]. Given the longitudinal design and to address the repeated measurements and correlated data, linear mixed models (LMM) (random intercepts or random slope models) will be used for person-specific effects, and marginal models like Generalized Estimating Equations (GEE) for population effects.

A theoretical sample size for statistical power will not be calculated because the study is based on the total clinical population available. For analyses of discrete and possible repeated events such as the number of criminal acts or medical prescriptions, statistical power will most likely be sufficient even with a restricted number of individuals. For analyses where the proportion of patients to number of variables may imply low statistical power, stratification of the study-population and restrictions to the number of covariates in the multivariate models will be applied.

Economic evaluations

Health economics and methods of cost-effectiveness analysis can guide decision makers, but at the same time they intrinsically rely on sets of politically and administratively determined rules and contexts [53]. In general, the cost-effectiveness of a treatment is intended to reflect the difference between the recourse’s opportunity costs (medical heroin) and those of the foregone or conventional alternative, to capture a broader set of values beyond the scope of mere financial costs [54].

Initially, for operating costs a three-step, top-down methodology used and refined by a former healthcare services project will be applied, where total costs are distributed on service units and units of treatment for individual patients [55].

For cost-effectiveness analyses of healthcare interventions, outcome is often measured in quality-adjusted life years (QALYs) for individual patients, in number of accidents or fatal incidents, or as societal costs associated with patients’ level of functioning and societal (criminal) behavior [56]. This will readily apply to the project and is in line with the national Norwegian recommendations for evaluation of new health interventions [57, 58]. The relationships between HAT and various forms of criminal behavior (both property crime and illegal drug offences), labor market attachment, income and drug expenditures are also unclear and possible subjects for investigation during the project [20].

The data for all analyses will come from key account figures and relevant variables already obtained in the project.


The main strength of the study comes from its clinical and longitudinal approaches. The use of patient-interviews combined with clinical records, self-report data and register-based information will enhance the analyses and may uncover important associations between the individual patients, treatment, and the organizational level of healthcare services. The results are therefore expected to address aspects of HAT that may contribute to the development of clinical services and individually tailored treatments for OUD.

Study limitations are mainly related to the designs’ limitation for isolation of the effects from HAT on the outcome variables. Although valuable associations often have been suggested by longitudinal ecological studies, this limited possibility of unbiased causal inference remains a major weakness of both epidemiological and cohort designs [59]. Consequently, analyses will be cautiously interpreted within the context of previous findings, as well as patient and staff experiences. The triangulation of different types of data sources and cohorts, with the use of multivariate analysis and modeling might nevertheless provide more nuanced insights than currently exist.

Also, socially desirable bias concerning self-report questionnaires may be inherent in all self-reported outcomes [60]. This will apply to the study, as patients in the Norwegian cohort are possibly aware that the prospects of HAT may depend on the results from the study.

The sample of patients in the main cohort might also not be representative of individuals with OUD who do not seek the HAT option for reasons related to the study outcomes, such as social deprivation and isolation, behavioral misconduct, and incarceration [61, 62]. Comparison with patients not granted access to the HAT-treatment may partly address this, although not to a full extent.

Lastly, the results will emerge in the context of a Nordic cultural and political system with healthcare reimbursements, insurance models and legal aspects that may limit their generalizability to other countries and societies. Given a cautious interpretation, the project may nonetheless be considered relevant to populations where OAT is used, and a wide range of medications are potentially provided.

Results from this project have the potential to identify new insights of value to patients, healthcare personnel, service administrators and policy makers as to whether an option for pharmaceutical heroin could be implemented as a conventional part of OAT services. We believe that the results will suggest future themes for research within the field of HAT with a potential for individually tailored treatment and care for individuals with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some patients do not succeed with conventional OAT or specific OAT medications will strengthen the knowledge base for drug treatment in general.

Data availability

Data sharing is not applicable to this article as no datasets are currently completed or analyzed. The data that support the eventual findings of this study are available from both national registries, individual health journals and the project-specific database, but restrictions apply to the availability which are under license for the current study. Data may be available from the authors upon reasonable request and dependent on permissions from the Norwegian Regional Committee for Medical and Health Research Ethics. All information on subjects will be stored in the University of Oslo's secure services for sensitive data (TSD). Files for analysis will not contain directly identifying information of patients. Data will be stored in a non-identifiable way for 15 years after the end of the project.



Opioid agonist treatment


Opioid use disorder


Heroin assisted treatment


Generalized Estimating Equations


Linear mixed models


Quality-Adjusted Life Years


Norwegian Regional Committee for Medical and Health Research Ethics


Norwegian Centre for Addiction Research, Oslo


Section for Clinical Addiction Research, Oslo


Bergen Addiction Research Group, Bergen


Centre for Alcohol and Drug Research, Aarhus


Norwegian User-union


  1. United Nations Office on Drugs and Crime (UNODC). World Drug Report 2023. 2023.

  2. Degenhardt L, Grebely J, Stone J, Hickman M, Vickerman P, Marshall BDL, et al. Global patterns of opioid use and dependence: harms to populations, interventions, and future action. Lancet. 2019;394(10208):1560–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Babor TF, Caulkins J, Fischer B, Foxcroft D, Medina-Mora ME, Obot I, et al. Drug Policy and the Public Good: a summary of the second edition. Addiction. 2019;114(11):1941–50.

    Article  Google Scholar 

  4. Dole VP, Nyswander M. A Medical treatment for Diacetylmorphine (Heroin) addiction. A clinical trial with Methadone Hydrochloride. JAMA. 1965;193:646–50.

    Article  CAS  PubMed  Google Scholar 

  5. Isbell H, Vogel VH. The addiction liability of methadon (amidone, dolophine, 10820) and its use in the treatment of the morphine abstinence syndrome. Am J Psychiatry. 1949;105(12):909–14.

    Article  CAS  PubMed  Google Scholar 

  6. Strang J, Volkow ND, Degenhardt L, Hickman M, Johnson K, Koob GF et al. Opioid use disorder. Nat Rev Dis Primers. 2020;6(1).

  7. Chaillon A, Bharat C, Stone J, Jones N, Degenhardt L, Larney S, et al. Modeling the population-level impact of opioid agonist treatment on mortality among people accessing treatment between 2001 and 2020 in New South Wales, Australia. Addiction. 2022;117(5):1338–52.

    Article  PubMed  Google Scholar 

  8. Havnes I, Bukten A, Gossop M, Waal H, Stangeland P, Clausen T. Reductions in convictions for violent crime during opioid maintenance treatment: a longitudinal national cohort study. Drug Alcohol Depend. 2012;124(3):307–10.

    Article  PubMed  Google Scholar 

  9. Clausen T, Anchersen K, Waal H. Mortality prior to, during and after opioid maintenance treatment (OMT): a national prospective cross-registry study. Drug Alcohol Depend. 2008;94(1–3):151–7.

    Article  PubMed  Google Scholar 

  10. Sordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bukten A, Skurtveit S, Waal H, Clausen T. Factors associated with dropout among patients in opioid maintenance treatment (OMT) and predictors of re-entry. A national registry-based study. Addict Behav. 2014;39(10):1504–9.

    Article  PubMed  Google Scholar 

  12. Bukten A, Roislien J, Skurtveit S, Waal H, Gossop M, Clausen T. A day-by-day investigation of changes in criminal convictions before and after entering and leaving opioid maintenance treatment: a national cohort study. BMC Psychiatry. 2013;13:262.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Klimas J, Hamilton MA, Gorfinkel L, Adam A, Cullen W, Wood E. Retention in opioid agonist treatment: a rapid review and meta-analysis comparing observational studies and randomized controlled trials. Syst Rev. 2021;10(1):216.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Timko C, Schultz NR, Cucciare MA, Vittorio L, Garrison-Diehn C. Retention in medication-assisted treatment for opiate dependence: a systematic review. J Addict Dis. 2016;35(1):22–35.

    Article  PubMed  Google Scholar 

  15. Strang J, Sheridan J. Heroin prescribing in the British system of the mid 1990s: data from the 1995 national survey of community pharmacies in England and Wales. Drug Alcohol Rev. 1997;16(1):7–16.

    Article  CAS  PubMed  Google Scholar 

  16. Berridge V. Heroin prescription and history. N Engl J Med. 2009;361(8):820–1.

    Article  CAS  PubMed  Google Scholar 

  17. van den Brink W, Hendriks VM, Blanken P, Koeter MW, van Zwieten BJ, van Ree JM. Medical prescription of heroin to treatment resistant heroin addicts: two randomised controlled trials. BMJ. 2003;327(7410):310.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rehm J, Gschwend P, Steffen T, Gutzwiller F, Dobler-Mikola A, Uchtenhagen A. Feasibility, safety, and efficacy of injectable heroin prescription for refractory opioid addicts: a follow-up study. Lancet. 2001;358(9291):1417–23.

    Article  CAS  PubMed  Google Scholar 

  19. Strang J, Groshkova T, Uchtenhagen A, van den Brink W, Haasen C, Schechter MT, et al. Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addictiondagger. Br J Psychiatry. 2015;207(1):5–14.

    Article  PubMed  Google Scholar 

  20. Smart R, Reuter P. Does heroin-assisted treatment reduce crime? A review of randomized-controlled trials. Addiction. 2022;117(3):518–31.

    Article  PubMed  Google Scholar 

  21. Oviedo-Joekes E, Brissette S, Marsh DC, Lauzon P, Guh D, Anis A, et al. Diacetylmorphine versus methadone for the treatment of opioid addiction. N Engl J Med. 2009;361(8):777–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Farrell M, Hall W. Heroin-assisted treatment: has a controversial treatment come of age? Br J Psychiatry. 2015;207(1):3–4.

    Article  PubMed  Google Scholar 

  23. Bell J, van der Waal R, Strang J. Supervised Injectable Heroin: a clinical perspective. Can J Psychiat. 2017;62(7):451–6.

    Article  Google Scholar 

  24. Meyer M, Strasser J, Kock P, Walter M, Vogel M, Dursteler KM. Experiences with take-home dosing in heroin-assisted treatment in Switzerland during the COVID-19 pandemic-Is an update of legal restrictions warranted? Int J Drug Policy. 2022;101:103548.

    Article  PubMed  Google Scholar 

  25. Oviedo-Joekes E, Dobischok S, Carvajal J, MacDonald S, McDermid C, Klakowicz P, et al. Clients’ experiences on North America’s first take-home injectable opioid agonist treatment (iOAT) program: a qualitative study. BMC Health Serv Res. 2023;23(1):553.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ferri M, Davoli M, Perucci CA. Heroin maintenance for chronic heroin-dependent individuals. Cochrane Database Syst Rev. 2011;2011(12):CD003410.

    PubMed  PubMed Central  Google Scholar 

  27. Dijkgraaf MG, van der Zanden BP, de Borgie CA, Blanken P, van Ree JM, van den Brink W. Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials. BMJ. 2005;330(7503):1297.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Byford S, Barrett B, Metrebian N, Groshkova T, Cary M, Charles V, et al. Cost-effectiveness of injectable opioid treatment v. oral methadone for chronic heroin addiction. Br J Psychiatry. 2013;203(5):341–9.

    Article  PubMed  Google Scholar 

  29. Poulter HL, Walker T, Ahmed D, Moore HJ, Riley F, Towl G, et al. More than just ‘free heroin’: caring whilst navigating constraint in the delivery of diamorphine assisted treatment. Int J Drug Policy. 2023;116:104025.

    Article  PubMed  Google Scholar 

  30. Tiffany ST, Friedman L, Greenfield SF, Hasin DS, Jackson R. Beyond drug use: a systematic consideration of other outcomes in evaluations of treatments for substance use disorders. Addiction. 2012;107(4):709–18.

    Article  PubMed  Google Scholar 

  31. Groshkova T, Metrebian N, Hallam C, Charles V, Martin A, Forzisi L, et al. Treatment expectations and satisfaction of treatment-refractory opioid-dependent patients in RIOTT, the Randomised Injectable Opiate Treatment Trial, the UK’s first supervised injectable maintenance clinics. Drug Alcohol Rev. 2013;32(6):566–73.

    Article  PubMed  Google Scholar 

  32. Sundhetsstyrelsen. Evaluering af ordningen med lægeordineret heroin til opioidafhængige patienter. Opgørelse over årene 2013–2020. København; 2021.

  33. Waal H. Merits and problems in high-threshold methadone maintenance treatment. Evaluation of medication-assisted rehabilitation in Norway 1998–2004. Eur Addict Res. 2007;13(2):66–73.

    Article  PubMed  Google Scholar 

  34. Ellefsen R, Wusthoff LEC, Arnevik EA. Patients’ satisfaction with heroin-assisted treatment: a qualitative study. Harm Reduct J. 2023;20(1):73.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Gabrhelik R, Handal M, Mravcik V, Nechanska B, Tjagvad C, Thylstrup B et al. Opioid maintenance treatment in the Czech Republic, Norway and Denmark: a study protocol of a comparative registry linkage study. Bmj Open. 2021;11(5).

  36. Arendt M, Munk-Jorgensen P, Sher L, Jensen SO. Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up study of Danish substance users in treatment. Drug Alcohol Depend. 2011;114(2–3):134–9.

    PubMed  Google Scholar 

  37. Bukten A, Lokdam NT, Skjaervo I, Ugelvik T, Skurtveit S, Gabrhelik R et al. PriSUD-Nordic-diagnosing and treating Substance Use disorders in the Prison Population: protocol for a mixed methods study. Jmir Res Protoc. 2022;11(3).

  38. Bukten A, Stavseth MR, Clasuen T. From restrictive to more liberal: variations in moratlity among patients in opioid maintenance treament over a 12-year period. BMC Health Serv Res. 2019;19(1):553.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Mortensen LH, Rehnberg J, Dahl E, Diderichsen F, Elstad JI, Martikainen P, et al. Shape of the association between income and mortality: a cohort study of Denmark, Finland, Norway and Sweden in 1995 and 2003. Bmj Open. 2016;6(12):e010974.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Munk-Jorgensen P, Ostergaard SD. Register-based studies of mental disorders. Scand J Public Health. 2011;39(7 Suppl):170–4.

    Article  PubMed  Google Scholar 

  41. Lassemo E, Myklebust LH. Changes in patterns of coercion during a nine-year period in a Norwegian psychiatric service area. Int J Methods Psychiatr Res. 2021;30(4):e1889.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Myklebust LH, Sorgaard KW, Bjorbekkmo S, Eisemann MR, Olstad R. Time-trends in the utilization of decentralized mental health services in Norway - A natural experiment: the VELO-project. Int J Ment Health Syst. 2010;4:5.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Myklebust LH, Lassemo E. The role of local inpatient psychiatric units and general practitioner on continuity of care in Northern Norway: a case-register study. Int J Methods Psychiatr Res. 2021;30(2):e1866.

    Article  PubMed  Google Scholar 

  44. Kvamme T, Thylstrup B, Hesse M. Quality of life assessment in Danish Heroin Assisted Treatment Patients: Validity of the SF-36 Survey. submitted.

  45. De Pirro S, Galati G, Pizzamiglio L, Badiani A. The affective and neural correlates of Heroin versus Cocaine Use in Addiction are influenced by environmental setting but in Opposite directions. J Neurosci. 2018;38(22):5182–95.

    Article  PubMed  PubMed Central  Google Scholar 

  46. De Pirro S, Lush P, Parkinson J, Duka T, Critchley HD, Badiani A. Effect of alcohol on the sense of agency in healthy humans. Addict Biol. 2020;25(4):e12796.

    Article  PubMed  Google Scholar 

  47. Milella MS, D’Ottavio G, De Pirro S, Barra M, Caprioli D, Badiani A. Heroin and its metabolites: relevance to heroin use disorder. Translational Psychiatry. 2023;13(1):120.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Kelly SM, O’Grady KE, Brown BS, Mitchell SG, Schwartz RP. The role of patient satisfaction in methadone treatment. Am J Drug Alcohol Abuse. 2010;36(3):150–4.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Barbosa CD, Balp MM, Kulich K, Germain N, Rofail D. A literature review to explore the link between treatment satisfaction and adherence, compliance, and persistence. Patient Prefer Adherence. 2012;6:39–48.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Korstjens I, Moser A, Series. Practical guidance to qualitative research. Part 2: context, research questions and designs. Eur J Gen Pract. 2017;23(1):274–9.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Braun V, Clarke V. One size fits all? What counts as quality practice in (reflexive) thematic analysis? Qual Res Psychol. 2021;18(3):328–52.

    Article  Google Scholar 

  52. Dyjack D. Ecological fallacies. J Environ Health. 2019;81(9):50–.

    Google Scholar 

  53. Gold MR, Russell JES, Weinstein LB. MC. Cost-Effectiveness in Health and Medicine: Oxford University Press; 1996 1996.

  54. Turner HC, Sandmann FG, Downey LE, Orangi S, Teerawattananon Y, Vassall A, et al. What are economic costs and when should they be used in health economic studies? Cost Eff Resour Alloc. 2023;21(1):31.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lassemo E, Myklebust L, Sorgaard K. Patient cost and treatment unit cost comparison in the VELO-Study. Psychiat Prax. 2011;38.

  56. Yates BT. Cost-inclusive evaluation: a banquet of approaches for including costs, benefits, and cost-effectiveness and cost-benefit analyses in your next evaluation. Eval Program Plann. 2009;32(1):52–4.

    Article  PubMed  Google Scholar 

  57. The Directorate of Health. Recommendations for the economic evaluation of new interventions in the Norwegian health sector. Oslo2012.

  58. Meld. St. 34. Principles for priority settings in health care. Summary of a white paper on priority setting in the Norwegian health care sector. In: Servces NMoHaC, editor. Oslo2017.

  59. Jekel JF, Katz DL, Elmpre JG. Epideimology, biostatisticvcs and preventive medicine. Pennsylvania, USA: B.W.Saunders; 2001.

    Google Scholar 

  60. Latkin CA, Edwards C, Davey-Rothwell MA, Tobin KE. The relationship between social desirability bias and self-reports of health, substance use, and social network factors among urban substance users in Baltimore, Maryland. Addict Behav. 2017;73:133–6.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Hosseinbor M, Yassini Ardekani SM, Bakhshani S, Bakhshani S. Emotional and social loneliness in individuals with and without substance dependence disorder. Int J High Risk Behav Addict. 2014;3(3):e22688.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Chandler RK, Fletcher BW, Volkow ND. Treating drug abuse and addiction in the criminal justice system: improving public health and safety. JAMA. 2009;301(2):183–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cho HL, Danis M, Grady C. Post-trial responsibilities beyond post-trial access. Lancet. 2018;391(10129):1478–9.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Cook K, Snyder J, Calvert J. Attitudes toward Post-trial Access to Medical interventions: a review of academic literature, legislation, and International guidelines. Dev World Bioeth. 2016;16(2):70–9.

    Article  PubMed  Google Scholar 

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We would like to thank the representatives from proLARNett for inputs on the design and aims of the study. Also thanks to associate professor Eva Lassemo at SINTEF-Helse, Norway for inputs on economical analysis.


The project is funded by the Norwegian Directorate of Health for the duration of 4.5 years with an annual limit of 5 million NOK (assignment No.20/00546). No remuneration is planned for the subjects’ participation in the project.

Open access funding provided by University of Oslo (incl Oslo University Hospital)

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LHM wrote and drafted the manuscript with critical input from all the authors. The study was planned and designed by TC, DE, LTF and LECW. The statistical section had essential inputs from FM and LHM, the section on economic evaluation had substantial inputs from OD, FM and LHM. The litterature search was conducted LHM, with inputs from TC and LECW. Authors OD, SDP, RE, MH, BT, TLK, EAA and AO read the manuscript and had substantial contributions on data-aquisition and corresponding background material.

Corresponding author

Correspondence to Lars Henrik Myklebust.

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The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK 195733). Informed consent was obtained from all participants. A particular revision of the Helsinki declaration on eventual continued post-trial provisions of clinical care and treatment [63, 64] does not apply as the project solely observes the outcomes from already provided treatment and does not initiate any research interventions. No specific insurances for subjects are taken out for the study. In case of injury or complications despite all precautions, patients have the right to apply for compensation through the Norwegian System of Patient Injury Compensation (NPE).

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Not applicable.

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The authors declare no competing interests.

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Myklebust, L.H., Eide, D., Arnevik, E.A. et al. Evaluation of heroin-assisted treatment in Norway: protocol for a mixed methods study. BMC Health Serv Res 24, 398 (2024).

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