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 "Availability of Companion Documents" field.)
Clinical Effectiveness
Identification of Studies
Review of Systematic Reviews
Searches for existing systematic reviews (that included randomised controlled trials [RCTs] or non-RCTs) were undertaken using the Aggressive Research Intelligence Facility (ARIF) search protocol which includes sources such as Cochrane Library, internet sites of health technology assessment organisations, and MEDLINE (see Appendix 1 in the Assessment Report [see "Availability of Companion Documents" field]). In addition the Cochrane Drugs and Alcohol Group were contacted to seek any recent updates of current Cochrane reviews. The searches were not restricted by date or language.
Review of Recent Randomised Controlled Trials
The following sources were searched for RCTs:
- Bibliographic databases: Cochrane Library (CENTRAL)(Wiley internet interface) 2005 Issue 3, MEDLINE (Ovid) 2001–Aug 2005, MEDLINE In-Process & Other Non-Indexed Citations (Ovid) 12 Aug 2005, EMBASE (Ovid) 2001–Aug 2005, PsycINFO (Ovid) 2001–Aug 2005, International Bibliography of the Social Sciences(BIDS) 2001–Aug 2005, Sociological Abstracts (CSA Illumina) 2001–2005. Searches were based on text words and index terms, where available, which encompassed methadone, buprenorphine; opioid misuse, dependence, and withdrawal. No language restrictions were applied. (see Appendix 1 in the Assessment Report for full search strategies [see "Availability of Companion Documents" field.])
- Citations of relevant studies
- Further information was sought from contact with author reports where necessary
- Research registers of ongoing studies were searched as follows: National Research Register 2005 Issue 3, Current Controlled Trials and ClinicalTrials.gov.
- Invited industry submissions to NICE for this appraisal
Inclusion and Exclusion Criteria
Review of Systematic Reviews
A systematic review was defined for the purposes of this report as a review that stated that at least one substantial database (e.g., EMBASE) had been scrutinised in conjunction with appropriate search terms. Meta-analyses were also included if they satisfied this criterion. In addition reviews were included if their inclusion criteria encompassed:
- Studies of opioid dependent individuals
- Studies (RCTs or non RCTs) of methadone and/or buprenorphine as maintenance therapy or detoxification strategies
Foreign language reviews were excluded, but those of potential relevance were identified and commented upon. Two reviewers independently undertook the selection of reviews with a third reviewer resolving any disagreement.
Review of Recent Randomised Controlled Trials
RCTs were included if they had not already been analysed and considered within included systematic reviews. Further inclusion criteria for RCTs were that they encompassed:
- A population of opioid dependent individuals
- Study of methadone and or buprenorphine as maintenance therapy or detoxification strategies
RCTs were excluded if the population was a mixture of cocaine abusers and opioid abusers, or if the population were in methadone or buprenorphine maintenance, temporarily switched prior to randomisation to an alternative, and subsequently randomly allocated back to methadone or buprenorphine maintenance (with or without supplementary pharmacotherapy or other therapy). Two reviewers undertook selection of RCTs and a third reviewer resolved disagreement.
Cost-Effectiveness
Search Strategy
A comprehensive search for literature on the cost and cost effectiveness of methadone and buprenorphine as substitute opiates for opioid dependent drug misusers was conducted. The searches identified existing economic models and information on costs, cost effectiveness, and quality of life from the following sources:
- Bibliographic databases: MEDLINE (Ovid) 1966–week 1 2005, EMBASE (Ovid) 1980–Aug 2005, Cochrane Library (NHS EED and DARE) (Wiley internet interface) 2005 Issue 3, HEED database Aug 2005.
- Industry submissions.
- Internet sites of national economic units.
Full details of search strategies are contained in Appendix 1 of the Assessment Report (see "Availability of Companion Documents" field).
Inclusion and Exclusion Criteria
The following inclusion criteria were used:
Study Design: Cost-consequence analysis, cost-benefit analysis, cost-effectiveness analysis, cost-utility analysis, cost studies (UK only), and quality of life studies.
Population: People who are dependent on opioids
Interventions: Buprenorphine or methadone employed in maintenance therapy irrespective of dose. The following operational definition was employed: any trial that calls itself "maintenance" or any trial that does not include a reducing or cessation of methadone/buprenorphine dose as part of its intervention.
Comparator: Any comparator regime used in maintenance therapy (including no therapy or placebo) or the intervention drug used in withdrawal/detoxification therapy.
Outcome: Quality of life estimates, cost estimates, cost-effectiveness
Study Selection
An experienced health economist applied the inclusion and exclusion criteria – checked by a second health economist.