• National Institute for Health and Clinical Excellence (NICE). Methadone and buprenorphine for the management of opioid dependence. London (UK): National Institute for Health and Clinical Excellence (NICE); 2007 Jan. 37 p. (Technology appraisal guidance; no. 114).

This is the current release of the guideline.

Opioid dependence

Assessment of Therapeutic Effectiveness
Management
Treatment

Family Practice
Internal Medicine
Pharmacology
Psychiatry
Psychology

Advanced Practice Nurses
Nurses
Physician Assistants
Physicians
Psychologists/Non-physician Behavioral Health Clinicians
Substance Use Disorders Treatment Providers

• To assess the clinical and cost effectiveness of buprenorphine maintenance therapy (BMT) and methadone maintenance therapy (MMT) for the management of opioid dependent individuals from the perspective of the National Health Service and Personal Social Services

  Three specific questions were addressed:

  • Is MMT effective and cost effective compared to no drug therapy?
  • Is BMT effective and cost effective compared to no drug therapy?
  • Is MMT or BMT more effective and cost effective?
• To explore the potential variation in effectiveness of BMT and MMT across drug dose, patient subgroups and treatment settings; assess the cost-effectiveness of BMT and MMT from a wider societal perspective; and compare the effectiveness of BMT compared to buprenorphine detoxification (BDT) and MMT compared to methadone detoxification (MDT)

Opioid dependent adults (18 years and over)

1. Methadone
2. Buprenorphine

• Clinical effectiveness
  • Changes in illicit drug use (frequency of use, type of use, dosage)
  • Proportion of patients remaining illicit-drug free
  • Retention in treatment
  • Compliance with recommended dose
  • Quality of life
  • Side effects and adverse effects of treatment drugs
  • Illicit-drug related morbidity (e.g., blood borne virus infection)
  • Mortality
  • Non-health outcomes of criminal activity and employment
• Cost-effectiveness of treatment

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Searches of Unpublished Data

Clinical Effectiveness

31 systematic reviews were included in this report. In addition, 27 RCTs were included.

Cost-Effectiveness

Previous Economic Evaluations

Eleven published economic evaluations met the inclusion criteria.

Industry Economic Evidence

Two industry submissions were received – Schering Plough for buprenorphine and Cardinal Health for methadone. Only Schering-Plough submitted cost effectiveness evidence.

Expert Consensus

Not applicable

Review of Published Meta-Analyses
Systematic Review with Evidence Tables

Note from the National Guideline Clearinghouse (NGC): The National Institute for Health and Clinical Excellence (NICE) commissioned an independent academic centre to perform a systematic literature review on the technology considered in this appraisal and prepare an assessment report. The assessment report for this technology appraisal was prepared by the West Midlands Health Technology Assessment Collaboration (see the "Companion Documents" field.)

Clinical Effectiveness

Critical Appraisal Strategy

Review of Systematic Reviews

The methodological quality and quality of reporting of the included systematic reviews and meta-analyses was assessed using the validated Overview Quality Assessment Questionnaire (OQAC) instrument developed by Oxman et al 1991*.

Review of Recent Randomised Controlled Trials (RCTs)

The methodological quality of included RCTs was assessed on the basis of randomisation, adequate concealment of randomisation, level of blinding, use of intention-to-treat-analysis, and description of loss to follow up. An overall quality score (Jadad) was assigned to each RCT using a modified Jadad instrument (see Appendix 5 in the Assessment Report [see "Availability of Companion Documents" field] for details on quality assessment instruments).

* Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol 1991; 44(11):1271-1278.

Data Extraction

One reviewer extracted data from systematic reviews and RCTs into pre-designed data forms. Extracted data was checked by at least one other reviewer and disagreement resolved by discussion. Data from studies with multiple publications were reported as a single study, but the source of publications noted.

For both included systematic reviews and RCTs, the following outcomes were sought:

• Drug use, i.e., changes in illicit drug use; concordance with, and retention in treatment
• Health of drug user, i.e., drug-related mortality; drug-related morbidity (e.g., blood-borne virus infection rates); health-related quality of life; use of health care system; major adverse effects of treatment (i.e., drug interactions, liver disease, cardiac abnormality, exacerbation of comorbidity)
• Social effects, i.e., effects on employment; effects on family
• Effects on criminal justice system i.e., rates of crime; recidivism

Economic Analyses

Data Extraction and Quality Assessment Strategy

Data were extracted by one reviewer using a pre-designed data extraction form and were independently check by a second reviewer. Data on the following were sought:

• Study characteristics, such as study question, form of economic analysis, population, interventions, comparators, perspective, time horizon, and modelling used.
• Clinical effectiveness and cost parameters, such as effectiveness data, health state valuations (utilities), resource use data, unit cost data, price year, discounting, and key assumptions.
• Results and sensitivity analyses.

These characteristics and the main results of included economic evaluations are summarized in Tables 8 to 11 of the Technology Assessment Report (see "Availability of Companion Documents" field). The quality of included studies and industry submissions was assessed using an adapted version of the Drummond and Jefferson BMJ criteria for economic evaluations was used to assess non-model studies and the Phillips (2004) Consensus on Health Economic Criteria quality criteria was used to assess economic model reports. The use of the predetermined quality criteria was agreed at the outset of the review. In the first instance the quality of economic aspects of the studies was assessed. Papers failing more than two quality criteria were excluded. Papers failing two items were reviewed to identify key messages contained in the papers and marked with a query. Papers that failed just one or none of the items were reviewed in full and marked with a pass.

The final data on incremental cost effectiveness ratios (ICERs) extracted from the relevant papers were converted from their respective currencies to sterling using purchasing power parities from the Organization for Economic Cooperation and development. Once converted to sterling the cost data were inflated to 2004 prices using the National Health Services (NHS) Executive Hospital and Community Health Services Pay and Prices inflation index.

Expert Consensus

Considerations

Technology appraisal recommendations are based on a review of clinical and economic evidence.

Technology Appraisal Process

The National Institute for Health and Clinical Excellence (NICE) invites 'consultee' and 'commentator' organisations to take part in the appraisal process. Consultee organisations include national groups representing patients and carers, the bodies representing health professionals, and the manufacturers of the technology under review. Consultees are invited to submit evidence during the appraisal and to comment on the appraisal documents.

Commentator organisations include manufacturers of the products with which the technology is being compared, the National Health Service (NHS) Quality Improvement Scotland and research groups working in the area. They can comment on the evidence and other documents but are not asked to submit evidence themselves.

NICE then commissions an independent academic centre to review published evidence on the technology and prepare an 'assessment report'. Consultees and commentators are invited to comment on the report. The assessment report and the comments on it are then drawn together in a document called the evaluation report.

An independent Appraisal Committee then considers the evaluation report. It holds a meeting where it hears direct, spoken evidence from nominated clinical experts, patients and carers. The Committee uses all the evidence to make its first recommendations, in a document called the 'appraisal consultation document' (ACD). NICE sends all the consultees and commentators a copy of this document and posts it on the NICE website. Further comments are invited from everyone taking part.

When the Committee meets again it considers any comments submitted on the ACD; then it prepares its final recommendations in a document called the 'final appraisal determination' (FAD). This is submitted to NICE for approval.

Consultees have a chance to appeal against the final recommendations in the FAD. If there are no appeals, the final recommendations become the basis of the guidance that NICE issues.

Who is on the Appraisal Committee?

NICE technology appraisal recommendations are prepared by an independent committee. This includes health professionals working in the NHS and people who are familiar with the issues affecting patients and carers. Although the Appraisal Committee seeks the views of organisations representing health professionals, patients, carers, manufacturers and government, its advice is independent of any vested interests.

Not applicable

Eight studies assessed the cost effectiveness of methadone maintenance therapy (MMT), one assessed the cost effectiveness of buprenorphine maintenance therapy (BMT), and two compared the cost effectiveness of BMT directly with that of MMT. The studies reported results using a range of outcome measures. The Assessment Group reported that direct comparison of the incremental cost-effectiveness rations (ICERS) between the studies was not possible because of differences in the approaches to modelling, time horizons, comparators and perspective, country of origin, source of preference weights, and effectiveness data used.

Although most of the included papers were considered to be of high quality, none used all of the appropriate parameters, effectiveness data, perspectives, and comparators required to make their results generalisable to the National Health Service (NHS) and personal social services (PSS).

Manufacturers' Models

No economic evaluations were submitted by the manufacturers of methadone oral solution.

The manufacturer of buprenorphine (Schering-Plough) submitted a cost-effectiveness analysis of BMT compared with MMT for opioid-dependent people over a 1-year time horizon. Cost effectiveness was assessed as the incremental cost per quality-adjusted life year (QALY) using a decision-tree-based model. Costs were calculated from an NHS and PSS perspective. Both simple one-way and probabilistic sensitivity analyses were undertaken.

The model was designed to estimate the cost effectiveness of BMT in three scenarios: BMT compared with no treatment for the 20% of opioid-dependent people seeking maintenance treatment who are unable to take methadone for "clinical reasons" (as stated by the manufacturer); BMT compared with MMT for the remaining 80% of opioid-dependent people; and maintenance therapy (methadone and buprenorphine) compared with drug-free treatment for all opioid-dependent people.

Assessment Group's Model

The Assessment Group developed a decision tree with Monte Carlo simulation to assess the cost effectiveness of BMT and MMT compared with drug-free therapy, and of BMT compared with MMT. The model estimated costs and outcomes from an NHS and PSS perspective for a 12-month period for the three strategies. Maintenance therapy was assumed to be a flexible dosing regimen, and the mean daily dose was assumed to be constant from week 13 onwards. The average cost of dispensing drugs was based on assumptions of supervised self-administration 6 days a week for the first 3 months, then unsupervised self-administration 6 days a week from 3 to 6 months, and unsupervised self-administration three times a week from 6 to 12 months. In addition to drug costs, estimates of resource use included counselling sessions, monitoring of treatment, general practitioner (GP) visits, emergency department visits, inpatient hospital stays, outpatient mental health appointments and inpatient mental health admissions.

See section 4.2 in the original guideline document for a complete summary of the evidence of cost effectiveness from the manufacturer and the economic evaluation undertaken by the Assessment Group.

External Peer Review

Consultee organizations from the following groups were invited to comment on the draft scope, Assessment Report and the Appraisal Consultation Document (ACD) and were provided with the opportunity to appeal against the Final Appraisal Determination.

• Manufacturer/sponsors
• Professional/specialist and patient/carer groups
• Commentator organisations (without the right of appeal)

In addition, individuals selected from clinical expert and patient advocate nominations from the professional/specialist and patient/carer groups were also invited to comment on the ACD.

• Methadone and buprenorphine (oral formulations), using flexible dosing regimens, are recommended as options for maintenance therapy in the management of opioid dependence.
• The decision about which drug to use should be made on a case-by-case basis, taking into account a number of factors, including the person's history of opioid dependence, their commitment to a particular long-term management strategy, and an estimate of the risks and benefits of each treatment made by the responsible clinician in consultation with the person. If both drugs are equally suitable, methadone should be prescribed as the first choice.
• Methadone and buprenorphine should be administered daily, under supervision, for a least the first 3 months. Supervision should be relaxed only when the patient's compliance is assured. Both drugs should be given as part of a programme of supportive care.

None provided

The type of evidence supporting the recommendations is not specifically stated.

Appropriate use of methadone and buprenorphine for the management of opioid dependence

This guidance represents the view of the Institute, which was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. The guidance does not, however, override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.

Living with Illness

Effectiveness
Patient-centeredness

• National Institute for Health and Clinical Excellence (NICE). Methadone and buprenorphine for the management of opioid dependence. London (UK): National Institute for Health and Clinical Excellence (NICE); 2007 Jan. 37 p. (Technology appraisal guidance; no. 114).

Not applicable: The guideline was not adapted from another source.

2007 Jan

National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]

National Institute for Health and Clinical Excellence (NICE)

Appraisal Committee

Committee Members: Dr Darren Ashcroft, Senior Clinical Lecturer, School of Pharmacy and Pharmaceutical Sciences, University of Manchester; Professor David Barnett (Chair) Professor of Clinical Pharmacology, University of Leicester; Dr Peter Barry, Consultant in Paediatric Intensive Care, Leicester Royal Infirmary; Mr Brian Buckley, Lay Member; Professor John Cairns, Public Health and Policy, London School of Hygiene and Tropical Medicine; Professor Mike Campbell, Statistician, University of Sheffield; Professor David Chadwick, Professor of Neurology, Walton Centre for Neurology and Neurosurgery, Liverpool; Dr Mark Chakravarty, Industry Member; Dr Peter I Clark, Consultant Medical Oncologist, Clatterbridge Centre for Oncology, Merseyside; Dr Mike Davies, Consultant Physician, University Department of Medicine and Metabolism, Manchester Royal Infirmary; Mr Richard Devereaux-Phillips, Industry Member; Professor Jack Dowie, Health Economist, London School of Hygiene; Dr Fergus Gleeson, Consultant Radiologist, The Churchill Hospital, Oxford; Ms Sally Gooch, Independent Healthcare Consultant; Mr Sanjay Gupta, Stroke Services Manager, Basildon and Thurrock University Hospitals NHS Trust; Professor Philip Home, Professor of Diabetes Medicine, University of Newcastle upon Tyne; Dr Peter Jackson, Clinical Pharmacologist, University of Sheffield; Professor Peter Jones, Professor of Statistics and Dean, Faculty of Natural Sciences, Keele University; Dr Mike Laker, Medical Director, Newcastle Hospitals NHS Trust; Dr George Levvy, Chief Executive, Motor Neurone Disease Association, Northampton; Ms Rachel Lewis, Nurse Advisor to the Department of Health; Mr Terence Lewis, Lay Member; Professor Jonathan Michaels, Professor of Vascular Surgery, University of Sheffield; Dr Neil Milner, General Practitioner, Sheffield; Dr Ruairidh Milne, Senior Lecturer in Health Technology Assessment, National Coordinating Centre for Health Technology; Dr Rubin Minhas, General Practitioner and CHD Clinical Lead, Medway PCT; Dr Rosalind Ramsay, Consultant Psychiatrist, Adult Mental Health Services, Maudsley Hospital; Mr Miles Scott, Chief Executive, Bradford Teaching Hospitals NHS Foundation Trust; Dr Lindsay Smith, General Practitioner, East Somerset Research Consortium; Mr Roderick Smith, Director of Finance, Adur, Arun and Worthing PCT; Dr Ken Stein, Senior Lecturer, Peninsula Technology Assessment Group (PenTAG), University of Exeter; Professor Andrew Stevens, Professor of Public Health, University of Birmingham

Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal.

This is the current release of the guideline.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.