Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers.
Nalmefene has been approved in Europe for the treatment of alcohol dependence and subsequently recommended by the UK National Institute for Health and Care Excellence (NICE). This study examines critically the evidence base underpinning both decisions and the issues arising.



Published studies of nalmefene were identified through a systematic search, with documents from the European Medicines Agency, the NICE appraisal and public clinical trial registries also examined to identify methodological issues.



Efficacy data used to support the licensing of nalmefene suffer from risk of bias due to lack of specification of a priori outcome measures and sensitivity analyses, use of post-hoc sample refinement and the use of inappropriate comparators. Despite this, evidence for the efficacy of nalmefene in reducing alcohol consumption in those with alcohol dependence is, at best, modest, and of uncertain significance to individual patients. The relevance of existing trial data to routine primary care practice is doubtful.



Problems with the registration, design, analysis and reporting of clinical trials of nalmefene did not prevent it being licensed and recommended for treating alcohol dependence. This creates dilemmas for primary care clinicians and commissioning organisations where nalmefene has been heavily promoted, and poses wider questions about the effectiveness of the medicines regulation system and how to develop the alcohol treatment evidence base.
Institute for Social Marketing, UK Centre for Tobacco Alcohol Studies, University of Stirling, Scotland, UK.
Niamh
N
Fitzgerald
Institute for Social Marketing, UK Centre for Tobacco Alcohol Studies, University of Stirling, Scotland, UK.
Kathryn
0000-0002-3643-8165
K
Angus
Glasgow Caledonian University, Glasgow, Scotland, UK.
Andrew
A
Elders
School of Health in Social Science, University of Edinburgh, Edinburgh, Scotland, UK.
Marisa
M
de Andrade
Leeds Addiction Unit, Leeds, UK.
Duncan
D
Raistrick
Department of Psychology, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
Nick
N
Heather
Department of Health Sciences, University of York, York, UK.
Jim
J
McCambridge
D000437:Alcoholism / Q000188:drug therapy*; D017277:Drug Approval; D005060:Europe; D019317:Evidence-Based Medicine; D006801:Humans; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D017410:Practice Guidelines as Topic; D006113:United Kingdom
D009292:Narcotic Antagonists; D009271:Naltrexone; C038981:nalmefene
Addiction; alcohol; brief intervention; nalmefene; trial regulation; vested interests