The Department of Health and the Welsh Assembly Government have asked the National Institute for Health and Clinical Excellence (NICE or the Institute) to conduct an appraisal of naltrexone and provide guidance on its use to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the use of naltrexone.

This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website, www.nice.org.uk).

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in section 1 are preliminary and may change after consultation.

The process the Institute will follow after the consultation period is summarised below. For further details, see the ‘ Guide to the technology appraisal process’ (this document is available on the Institute’s website, www.nice.org.uk).

The Appraisal Committee will meet again to consider the original evidence and this Appraisal Consultation Document in the light of the views of the formal consultees.

At that meeting, the Committee will also consider comments made on the document by people who are not formal consultees in the appraisal process.

After considering feedback from the consultation process, the Committee will prepare the Final Appraisal Determination (FAD) and submit it to the Institute.

Subject to any appeal by consultees, the FAD may be used as the basis for the Institute’s guidance on the use of the appraised technology in the NHS in England and Wales.

The key dates for this appraisal are:
Closing date for comments: 21 July 2006
Second Appraisal Committee meeting: 6 September 2006

Details of membership of the Appraisal Committee are given in appendix A and a list of the sources of evidence used in the preparation of this document is given in appendix B.

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in section 1 are preliminary and may change after consultation.

Naltrexone is recommended as a treatment option in detoxified formerly opioid-dependent people who are highly motivated to remain on treatment.

Naltrexone should only be administered under adequate supervision to patients who have been fully informed of the potential adverse effects of treatment. It should be given as part of a care programme that includes access to psychosocial therapy.

The effectiveness of naltrexone in preventing opioid misuse in individuals should be reviewed regularly. Discontinuation of naltrexone treatment should be considered if there is evidence of such misuse.

The term ‘opioids’ refers to opiates and other semi-synthetic and synthetic compounds with similar properties. Opiates are a group of psychoactive substances derived from the poppy plant that includes opium, morphine, codeine and others. The term ‘opiate’ is also used for the semi-synthetic drug diamorphine (heroin), which is produced from poppy compounds. Opioid dependence can cause a wide range of health problems and is often associated with misuse of other drugs (including alcohol). Diamorphine is the most widely misused opiate, and dependence on illicit diamorphine can cause physical problems as a result of the spread of blood-borne viruses when it is injected (for example, HIV and hepatitis B or C) and the risk of an accidental overdose. The mortality risk of people dependent on illicit diamorphine is estimated to be around 12 times that of the general population. Psychiatric comorbidity – particularly anxiety but also affective, antisocial and other personality disorders – is common among opioid-dependent people.

A ssociated social problems include marital and relationship breakdown, unemployment, homelessness and child neglect, often resulting in children being taken into the care system. There is also a clear association between illicit drug use and crime. Many opioid-dependent people become involved in crime to support their drug use. It is estimated that half of all recorded crime is drug related, with associated costs to the criminal justice system in the UK estimated as £1 billion per annum in 1996.

Biological, psychological, social and economic factors influence when and why a person starts taking illicit opioids. Opioid use quickly escalates to misuse (repeated use despite adverse consequences) and then dependence (opioid tolerance, withdrawal symptoms, compulsive drug-taking). Dependence has been defined in the ‘Diagnostic and statistical manual’ (‘DSM’) as a maladaptive pattern of substance use, leading to clinically significant impairment or distress. Physical and psychological dependence can develop within a relatively short period of continuous use (2–10 days), and is characterised by an overwhelming need to continue taking the drug in order to avoid withdrawal symptoms (such as sweating, anxiety, muscle tremor, disturbed sleep, loss of appetite, and raised heart rate, respiratory rate and blood pressure). The body also becomes tolerant to the effects of opioids and the dose needs to be increased to maintain the effect. Getting the next dose can become an important part of each day and may take over people’s lives. It is difficult to stop using these drugs and remain abstinent because of a combination of craving, unpleasant withdrawal symptoms, and the continued or worsening personal circumstances that led to drug use in the first place.

When an opioid-dependent person manages to become abstinent, there are usually repeated cycles of cessation and relapse, with extensive treatment histories spanning decades. Nevertheless, some dependent people may make dramatic changes in their drug use without formal treatment. The histories of people using illicit diamorphine who attend treatment services suggest that most people develop dependence in their late teens and early twenties, several years after their first use of heroin, and continue use over the next 10–20 years. Treatment can alter the natural history of opioid dependence, most commonly by prolonging periods of abstinence from illicit opioid misuse.

National estimates, which combine local prevalence data and routinely available indicator data, suggest that in the UK the prevalence of problem drug use is 9.35 per 1000 of the population aged 15–64 years (360,811 people), and that 3.2 per 1000 (123,498 people) are injecting. The National Drug Treatment Monitoring System (NDTMS) estimates that in 2004–05 there were 160,450 people in contact with treatment services in England. Because of the lack of substitute medications for other drugs (such as crack cocaine and alcohol), most people in treatment were dependent on opioids. About 70% of people newly presenting for treatment were male. There are about 40,000 people who misuse drugs in prison in England and Wales at any time. In one UK survey, 21% of prisoners had used opiates at some point during their sentence, and 10% of prisoners had used it during the previous week.

The UK has a range of treatment services for opioid dependency. Medical and psychosocial interventions are provided in the community and the criminal justice system and include inpatient, residential, day-patient and outpatient services.

The interventions used for opioid-dependent people range from needle exchange to maintenance therapy and abstinence. Pharmacological treatments are broadly categorised as maintenance (also known as harm reduction and a substitution regimen), or abstinence (also known as detoxification and withdrawal). In a bstinence strategies, a person who is physically dependent on a drug stops taking it. Some people can achieve abstinence from opioids rapidly; others require the support of prescribed medication for longer than a few months. The opioid antagonist naltrexone can be used to help maintain abstinence. In maintenance strategies, people initially receive a long-acting opioid (methadone or buprenorphine) as a substitute for the illicit drug of unknown purity and quality. They may then progress to abstinence therapy.

Currently, the decision about which drug treatment to offer is based on local availability and on the individual’s previous history, current situation, social support network and expressed wishes. Treatment decisions are taken together with the person and based on the clinician’s judgement of the required degree of structure, monitoring and support.

Psychosocial and behavioural therapies play an important role in the treatment of drug misuse; the therapies aim to give people the ability to resist substance use and cope with problems related to drug use. For opioid users they are often an important adjunct to pharmacological treatments.

The government’s ‘Drug strategy’ (2004) aims to reduce the harm caused by illegal drugs (for example, by treatment through the criminal justice system), increase enrolment in drug treatment programmes and reduce the use of Class A and illicit drugs.

In England , naltrexone tr eatment accounts for 11,000–14,000 prescriptions per annum and a total annual drug cost of less than £500,000.

Naltrexone (Bristol-Myers Squibb Pharmaceutical Ltd) is an opioid antagonist with a high affinity for opioid receptors. It competitively displaces opioid agonists (for example, diamorphine or methadone), blocking the euphoric and other effects of opioids and thereby minimising the positive rewards associated with their use. The ‘Summary of product characteristics’ states that naltrexone is licensed for use as an adjunctive prophylactic therapy for use in detoxified formerly opioid-dependent patients (who have remained opioid-free for at least 7–10 days). There are unlicensed long-lasting formulations of naltrexone in development (depot preparations and implants), but these do not fall within the scope of this appraisal.

Naltrexone is rapidly absorbed, metabolised by the liver and excreted in urine with an elimination half-life of 4 hours. Liver function tests are recommended before and during naltrexone treatment to check for liver impairment. The ‘Summary of product characteristics’ states that ‘caution should be observed in administering the drug to patients with impaired hepatic or renal function’.

Naltrexone is associated with opioid withdrawal symptoms if patients are opioid dependent. Challenge testing with naloxone hydrochloride (a shorter-acting injectable opioid antagonist) is recommended to screen for the presence of opioids if it is not certain that a patient is detoxified. Patients may be at risk of fatal overdose if they relapse while taking naltrexone (because a larger dose of diamorphine is required to achieve euphoria) and if they return to diamorphine use after naltrexone treatment (because of loss of tolerance to diamorphine). For full details of side effects and contraindications, see the ‘Summary of product characteristics’.

The cost of naltrexone is £1.52 per 50-mg tablet excluding VAT (‘British National Formulary’ [BNF], edition 51). Patients should receive 25 mg naltrexone on day 1 followed by 50 mg daily thereafter for an initial period of 3 months. However, extended treatment may be necessary because time to full recovery from opioid dependence is variable. A three-times-a-week dosing schedule may be considered if it is thought likely to improve compliance with treatment. Costs may vary in different settings because of negotiated procurement discounts.

The Appraisal Committee considered evidence from a number of sources (see appendix B).

The review identified 17 studies of the clinical effectiveness of naltrexone treatment: 1 systematic review (Cochrane review), 13 randomised controlled trials (RCTs) and 3 non-randomised comparative studies. None of the studies were conducted in the UK. The length of follow-up varied in the RCTs from 20 days to 1 year. The RCTs and comparative studies evaluated the effectiveness of naltrexone treatment in a total of 1269 individuals and reporting was of poor quality (for example, randomisation was not adequately reported in most RCTs). Two of the RCTs were conducted in a prison setting (parolees or probationers), and seven included various psychosocial treatments in both arms of the trials (for example, twice-weekly drug counselling, psychotherapy and behavioural therapy).

In addition to the 17 studies of the clinical effectiveness of naltrexone treatment, 9 RCTs studied the effectiveness of different strategies to improve retention on naltrexone treatment. Three of these studies assessed reward with vouchers for treatment compliance (one study also included relationship counselling), four studies evaluated psychosocial therapies and two trials examined the effectiveness of pharmaceutical agents. These studies were of poor to moderate quality (the methods of randomisation were not adequately described and intention-to-treat analyses were not performed in most of the trials).

The main effectiveness outcomes reported in the RCTs were retention, relapse rates (opioid use) and re-incarceration of parolees or probationers.

Retention on treatment was reported in the Cochrane review and seven RCTs. The Cochrane review showed no significant difference in retention for patients treated with naltrexone and adjunctive psychosocial therapy compared with psychosocial therapy alone (risk ratio [RR] 1.08; 95% confidence interval [CI], 0.74 to 1.57). Six of the seven RCTS (three of which included adjunctive psychosocial therapy in each arm) reported no significant difference in retention with naltrexone treatment. One trial reported a significant improvement in retention on naltrexone treatment compared with psychosocial therapy (RR 0.66; 95% CI, 0.43 to 0.93). A fixed-effect meta-analysis of all seven RCTs conducted by the Assessment Group showed no difference in retention on treatment with naltrexone, with a RR of stopping treatment of 0.94 (95% CI, 0.84 to 1.06) and a hazard ratio (HR) from five RCTs of 0.90 (95% CI, 0.69 to 1.17). However, a fixed effects model for performing meta analysis was not the most appropriate analysis because heterogeneity between trials was found. A random-effects meta-analysis gave a RR of stopping treatment of 0.90 (95% CI, 0.55 to 1.48).

Relapse rates (assessed by the presence of opioids in urine samples) were reported in the Cochrane review and six RCTs. The Cochrane review showed a significant reduction in illicit diamorphine use (RR 0.72; 95% CI, 0.58 to 0.90). Of the six RCTs that reported relapse rates, three included adjunctive psychosocial therapy in each arm. Five of the six RCTs reported no statistically significant differences in relapse rates with naltrexone treatment. One RCT reported a statistically significant improvement in relapse rates with naltrexone treatment (RR 0.41; 95% CI, 0.21 to 0.74). Pooled analysis of relapse rates of the six RCTs showed a statistically significant reduction in the risk of opioid use with naltrexone compared with placebo; the RR of relapse was 0.72 (95% CI, 0.58 to 0.90), with a HR of 0.53 (95% CI, 0.34 to 0.82) and a number needed to treat (NNT) of eight patients to prevent one opioid relapse. One trial reported the number of patients that were opioid free as a proportion of patients retained in treatment. This trial showed no difference in the number of opioid-free patients treated with naltrexone compared with psychosocial therapy over 26 weeks (statistical significance was not reported).

Two small RCTs reported re-incarceration rates of parolees or probationers having naltrexone treatment compared with placebo, with adjunctive psychosocial treatment in each arm. Pooled analysis showed a significant reduction in re-incarceration rate in favour of naltrexone (RR 0.50; 95% CI, 0.27 to 0.91).

Mortality was not reported in any of the trials. A retrospective study in the USA examined the number of deaths in people who had received naltrexone treatment over a period of 2 years (n = 1196) and in people who had not received naltrexone treatment (total number not reported). Diamorphine overdose resulted in 21 out of 33 (64%) deaths in the naltrexone group and 71 out of 96 (74%) deaths in people not being treated with naltrexone.

The National Coronial Information Service reported 32 naltrexone-related deaths in the period from 2000–2003 in Australia. The mortality rate was estimated at 1 per 100 person years during naltrexone treatment and 22.1 per 100 person years during the first 2 weeks post treatment.

Nine RCTs evaluated the effectiveness of different strategies to increase retention on naltrexone treatment (incentive vouchers, behavioural therapy and pharmaceutical agents). The length of follow-up in these trials ranged from 12 to 52 weeks. Pooled analysis of the effect of adjunctive psychosocial therapies on compliance with naltrexone treatment in six trials reported a significant improvement of 19% with adjunctive psychosocial therapy compared with naltrexone treatment alone.

In summary, the small evidence base reported conflicting results. The quality of the studies was poor and randomisation was not adequately reported in RCTs. One trial reported a significant improvement in retention and relapse rates with naltrexone treatment, but the majority of RCTs reported no significant difference between naltrexone and control treatment. When the results from these trials were pooled, naltrexone was associated with a significant reduction in relapse, but not a difference in treatment retention compared with control treatment. Adverse events reported in two trials showed no difference in mortality between naltrexone and control treatment. Although useful data for the comparison of adverse events were not reported in the majority of the RCTs, mortality data from the USA showed no difference in mortality rates with naltrexone compared with non-naltrexone treatment.

No published economic evaluations of the cost effectiveness of naltrexone treatment were identified. The manufacturer did not submit evidence for this appraisal.

The Assessment Group developed a decision analytical model to assess the cost effectiveness of naltrexone plus psychosocial support compared with placebo plus psychosocial support (psychosocial support alone). The model estimated costs and outcomes from a National Health Service (NHS) perspective. Costs were based on estimates of resource use including a daily dose of 50 mg naltrexone, counselling sessions, monitoring of treatment, GP visits, emergency department visits, inpatient hospital stays, outpatient mental health visits and inpatient mental health visits. The time horizon of the model was limited to 12 months. This was because of the length of follow-up in the trials, and clinical advice that patients are not retained on naltrexone treatment in the long term.

Data on retention on treatment at 2, 6, 13 and 25 weeks and 12 months were included in the model. Data on this endpoint for naltrexone (with or without psychosocial therapy) compared with placebo treatment (with or without psychosocial therapy) was based on the meta-analysis of five RCTs (pooled HR 0.90; 95% CI, 0.69 to 1.17). This HR was applied to the survival curve for naltrexone treatment to generate an estimate of retention on psychosocial treatment alone. Data on the proportion of opioid-free patients retained on treatment was based on a single RCT, which reported little difference between the naltrexone arm (84% opioid-free patients) and the control arm (86% opioid-free patients). Data from the ‘National treatment outcome research study’ (NTORS) were used to inform the proportion of drug-taking patients who were injecting and not injecting.

Health outcomes were expressed as quality adjusted life years (QALYs). In the absence of published data on quality of life associated with drug misuse, the Assessment Group obtained health-related utility data from a panel of members of the public. Average QALYs were calculated for patients retained on naltrexone treatment and psychosocial therapy, patients retained on psychosocial therapy alone and patients not retained on treatment. Patients retained on naltrexone treatment gain fewer QALYs than those retained on control treatment, based on evidence from one RCT which showed a higher number of patients relapsing on naltrexone. The total QALYs associated with each treatment arm were then determined by different retention rates.

The base-case analysis demonstrated that naltrexone plus psychosocial therapy is associated with an incremental cost effectiveness ratio (ICER) of £42,500 per QALY gained. This is based on the assumption of a slightly higher (non-significant) proportion of patients relapsing with naltrexone plus psychosocial therapy compared with psychosocial therapy alone.

Data on the proportions of patients that are opioid free in each arm of the model was based on one trial. A one-way sensitivity analysis that assumed the same proportion of patients taking opioids in both arms reduced the ICER to £34,600 per QALY gained.

A probabilistic sensitivity analysis around the base case analysis was also undertaken. The probability of naltrexone being cost effective does not rise much above 50%, regardless of the acceptable amount to pay for an additional QALY. This is because of the uncertainty in the estimates of clinical effectiveness reported in the RCTs.

An analysis that included the costs of the criminal justice system/victims of crime was also performed. Costs to victims of crime included the costs of increased security measures and the direct costs of material or physical damage. The results of this analysis found that naltrexone plus psychosocial support dominates (is less costly and more effective) psychotherapy alone. The dominance of naltrexone therapy is driven by the reduction in costs to the victims in the naltrexone arm, owing to the increased retention on treatment and the associated reduction in crime. A one-way sensitivity analysis in which the costs to the victim were excluded resulted in an ICER of approximately £51,000 per QALY.

The Committee reviewed the data available on the clinical and cost effectiveness of naltrexone, having considered evidence on the nature of the condition and the value placed on the benefits of naltrexone by people who are dependent on opioids, those who represent them, and clinical experts. It was also mindful of the need to take account of the effective use of NHS resources.

The Committee was persuaded of the likely clinical effectiveness of naltrexone as a disincentive for opioid use in individuals following detoxification because of their understanding of the pharmacological basis of its action; that is, naltrexone blocks the receptors responsible for the euphoric effects of opioids.

The Committee considered the quality and outcomes of the RCTs. The Committee noted that the RCTs showed that naltrexone therapy resulted in no significant difference in retention on treatment, but did result in a lower rate of relapse to illicit opioid use compared with control treatment. The Committee was persuaded by the experts’ testimony that, in clinical practice, naltrexone therapy was often associated with dramatic improvements in abstinence from opioid use, which is the principal goal of treatment. The Committee considered that mortality in individuals retained on naltrexone treatment was likely to be reduced specifically because of the lower relapse rate to illicit opioid use. The Committee additionally concluded that the reduction in opioid use could lead to substantial improvements in overall quality of life for those individuals retained on naltrexone treatment.

The Assessment Group and experts raised concerns regarding the external generalisability of the RCTs, none of which were conducted in the UK and recruited a general population of people with differing patterns of opioid misuse. The Committee heard from experts that naltrexone is normally only prescribed for people highly motivated to remain on naltrexone treatment who are fully informed of the risks and benefits of treatment, and for whom an abstinence regimen is judged to be appropriate based on initial clinical assessment. Experts also noted that none of the RCTs were conducted in the UK, and the degree of supervision of naltrexone administration was likely to be variable, whereas it is currently recommended best clinical practice in the UK. The Committee was persuaded that close monitoring is particularly important when naltrexone treatment is initiated because of the higher risk of fatal overdose at this time. In addition, the Committee understood that discontinuation of naltrexone may be associated with an increase in inadvertent overdose from illicit opioids. The Committee therefore considered that supervision of naltrexone administration is important for continued compliance with medication, in order to maximise retention on treatment and abstinence from illicit opioid use, and to minimise the adverse effects of treatment. The Committee was also aware of two uncontrolled studies that reported higher effectiveness of naltrexone in highly motivated people. The Committee was convinced that effectiveness outcomes for retention on treatment and abstinence from opioid use are likely to be higher in clinical practice than reported in the RCTs, because treatment is targeted to motivated individuals who have expressed a preference for an abstinence regimen. The Committee concluded that close monitoring of treatment is likely to lead to further improvements in the effectiveness of naltrexone treatment over and above that seen in the RCTs.

The Committee considered the personal statements and testimonies of patient experts on the adverse effects of naltrexone treatment. The Committee heard that people taking naltrexone often experience adverse effects of unease (dysphoria), depression and insomnia, which can lead to relapse to illicit opioid use while on naltrexone treatment, or failure to continue on treatment. Experts therefore stressed the importance of prescribing naltrexone as part of a care programme that includes psychosocial therapy and general support. The Committee noted the importance of patients and carers being fully informed of the risks and benefits associated with naltrexone treatment and considered psychosocial therapy to be instrumental in some patients remaining on naltrexone treatment.

The Committee considered the uncertainties relating to the external generalisability of the effectiveness evidence used in the economic model and the consequent uncertainties in interpreting the ICERs. The Assessment Group advised that for the purpose of economic modelling, the rate of relapse to illicit opioids, used in their assessment was based on a small study that reported no significant difference in relapse rates between naltrexone and control treatment. The Committee noted that this was contrary to the pooled estimate of relapse rates reported in the systematic review (HR 0.53; 95% CI, 0.34 to 0.82), which showed a significant reduction in relapse with naltrexone compared with control treatment. The Committee concluded that the model may have underestimated the reduction in relapse to opioid use, and therefore also underestimated the cost effectiveness of naltrexone treatment on the basis of potential improvements in both quality of life and mortality.

The Committee further considered the base (reference) case ICER of £42,500 per QALY for adjunctive naltrexone treatment plus psychosocial therapy compared with psychosocial therapy alone. The Committee considered that this ICER was based on data on the effectiveness of adjunctive naltrexone treatment compared with psychosocial therapy alone in a general population of drug misusers. The Committee was persuaded that this ICER was a conservative figure that underestimated the cost effectiveness of naltrexone in individuals selected on the basis of high motivation and who were enrolled in a supervised treatment programme. The Committee was persuaded that in these individuals, the ICER for naltrexone treatment would be substantially lower than the base case, principally because of the factors outlined in section 4.3.6

In summary, the Committee was convinced of the clinical effectiveness of naltrexone treatment in a selected, highly motivated group of people. The Committee concluded that in patients who preferred an abstinence regimen, were fully informed of the risks and benefits of treatment, and were highly motivated to remain on treatment, naltrexone treatment would fall within acceptable cost effectiveness limits.

The Healthcare Commission assesses the performance of NHS organisations in meeting core and developmental standards set by the Department of Health in ‘Standards for better health’ issued in July 2004. The Secretary of State has directed that the NHS provides funding and resources for medicines and treatments that have been recommended by NICE technology appraisals normally within 3 months from the date that NICE publishes the guidance. Core standard C5 states that healthcare organisations should ensure they conform to NICE technology appraisals.

'Healthcare Standards for Wales’ was issued by the Welsh Assembly Government in May 2005 and provides a framework both for self-assessment by healthcare organisations and for external review and investigation by Healthcare Inspectorate Wales. Standard 12a requires healthcare organisations to ensure that patients and service users are provided with effective treatment and care that conforms to NICE technology appraisal guidance. The Assembly Minister for Health and Social Services issued a Direction in October 2003 which requires Local Health Boards and NHS Trusts to make funding available to enable the implementation of NICE technology appraisal guidance, normally within 3 months.

NICE has developed tools to help organisations implement this guidance (listed below). These are available on our website (www.nice.org.uk/TAXXX). [Note: tools will be available when the final guidance is issued]

Proposed recommendations for further research

NICE is in the process of producing the following technology appraisal and clinical guidelines.

Methadone and buprenorphine for the management of opioid dependence. NICE technology appraisal (publication expected March 2007).

Drug misuse: psychosocial management of drug misusers in the community and prison settings. NICE clinical guideline (publication expected July 2007).

Drug misuse: opiate detoxification management of,drug misusers in the community and prison settings. NICE clinical guideline (publication expected July 2007)

The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider whether the technology should be reviewed. This decision will be taken in the light of information gathered by the Institute, and in consultation with consultees and commentators.

It is proposed that the guidance on this technology is considered for review in March 2013. The Institute would particularly welcome comment on this proposed date.

David Barnett

Chair, Appraisal Committee

June 2006

Appendix A. Appraisal Committee members and NICE project team

A. Appraisal Committee members

The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets twice a month except in December, when there are no meetings. The Committee membership is split into two branches, with the chair, vice-chair and a number of other members attending meetings of both branches. Each branch considers its own list of technologies and ongoing topics are not moved between the branches.

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.

The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website.

Dr Darren Ashcroft
Senior Clinical Lecturer, School of Pharmacy and Pharmaceutical Sciences, University of Manchester

Professor David Barnett
Professor of Clinical Pharmacology, University of Leicester

Dr Peter Barry
Consultant in Paediatric Intensive Care, Leicester Royal Infirmary

Mr Brian Buckley
Lay Representative

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

Dr Mark Chakravarty
Industry Representative

Dr Peter I Clark
Consultant Medical Oncologist, Clatterbridge Centre for Oncology, Merseyside

Dr Mike Davies
Consultant Physician, University Department of Medicine & Metabolism, Manchester Royal Infirmary

Mr Richard Devereaux-Phillips
Industry Representative

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 & 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 Representative

Professor Jonathan Michaels
Professor of Vascular Surgery, University of Sheffield

Dr Neil Milner
General Medical Practitioner, Sheffield

Dr Ruairidh Milne
Senior Lecturer in Health Technology Assessment, National Coordinating Centre for Health Technology

Dr Rubin Minhas
General Practitioner, 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

Each appraisal of a technology is assigned to a Health Technology Analyst and a Technology Appraisal Project Manager within the Institute.

Eleanor Donegan
Technical Lead, NICE project team

Louise Longworth
Technical Advisor, NICE project team

Emily Marschke
Project Manager, NICE project team

The assessment report for this appraisal was prepared by West Midlands Health Technology Assessment Collaboration.

Burls A, Yaser A, Juarez-Garcia A et al. ( West Midlands Health Technology Assessment Collaboration). Oral naltrexone as a treatment for relapse prevention in formerly opioid dependent drug users – a systematic review and economic evaluation , February 2006

The following organisations accepted the invitation to participate in this appraisal. They were invited to make submissions and comment on the draft scope and assessment report. They are also invited to comment on the ACD and consultee organisations are provided with the opportunity to appeal against the FAD.

I Manufacturers/sponsors:

• Bristol-Myers Squibb Pharmaceuticals Ltd (naltrexone)

II Professional/specialist and patient/carer groups:

• Addiction
• Addiction Recovery Foundation
• ADFAM
• Alliance (formerly the Methadone Alliance)
• Association of Nurses in Substance Abuse (ANSA)
• British Association for Psychopharmacology
• Families Anonymous
• Federation of Drug and Alcohol Professionals
• Lifeline
• National Drug Prevention Alliance
• National Pharmaceutical Association
• Pharmaceutical Services Negotiating Committee
• Rehabilitation for Addicted Prisoners Trust (RAPt)
• Release
• Royal College of General Practitioners
• Royal College of Nursing
• Royal College of Physicians
• Royal College of Physicians of Edinburgh
• Royal College of Psychiatrists
• Royal Pharmaceutical Society
• Specialist Clinical Addiction Network (SCAN)
• Substance Misuse Management in General Practice (SMMGP)
• UK Harm Reduction Alliance
• Turning Point

III Consultee (others)

• Department of Health
• East Leeds PCT
• Great Yarmouth PCT
• Welsh Assembly Government

IV Commentator organisations (without the right of appeal):

• Action on Addiction
• British National Formulary
• Centre for Research on Drugs and Health Behaviour ( Imperial College)
• Department of Addictive Behaviour ( St George’s Hospital Medical School)
• DrugScope
• Drugs Misuse – Psychosocial Guidelines Development Group
• Drugs Misuse – Detoxification Guidelines Development Group
• HM Prison Service
• Independent Drug Monitoring Unit (IDMU)
• National Addiction Centre ( Institute of Psychiatry)
• National Coordinating Centre for Health Technology Assessment
• National programme on substance abuse deaths, St George’s Hospital Medical School
• National Treatment Agency for Substance Misuse (NTA)
• NHS Confederation
• NHS Purchasing and Supplies Agency
• NHS Quality Improvement Scotland
• Society for the Study of Addiction
• West Midlands Health Technology Assessment Collaboration

The following individuals were selected from clinical expert and patient advocate nominations from the professional/specialist and patient/carer groups. They participated in the Appraisal Committee discussions and provided evidence to inform the Appraisal Committee’s deliberations. They gave their expert personal view on Naltrexone for the management of opioid dependence by attending the initial Committee discussion and/or providing written evidence to the Committee. They are invited to comment on the ACD.

• Dr Ed Day – Senior Lecturer in Addiction Psychiatry, Queen Elizabeth Psychiatric Hospital – clinical specialist
• Dr Chris Ford – GP Clinical Lead, Substance Misuse Management in General Practice (SMMGP) – clinical specialist
• Dr Judith Myles – Consultant Psychiatrist, Royal College of Psychiatrist – clinical specialist
• Dr Duncan S Raistrick– Consultant in Addiction Psychiatry, Specialist Clinical Addiction Network (SCAN) – clinical specialist
• Mr Peter McDermott – Patient Advocate, The Alliance – patient expert
• Ms Moya Pinson – Volunteer at Release, Release – patient expert
• Mr Gary Sutton – Head, Drug Advice Team, Release – patient expert

The following individual(s) representing the National Collaborating Centre for Mental Health, which is responsible for developing the Institute’s clinical guidelines on detoxification and psychosocial interventions for drugs misuse, were invited to attend the ACD meeting as observers and to contribute as advisers to the Committee.

• Dr Clare Gerada – Royal Collage of General Practitioners, Chair, Drug Misuse Detoxification Guideline Development Group
• Professor John Strang – Professor of Psychiatry of Addictions, National Addiction Centre ( Institute of Psychiatry), Chair, Drug Misuse Psychosocial Interventions Guideline Development Group
• Mr Steve Pilling – Director, National Collaborating Centre for Mental Health