Nalmefene for Reducing Alcohol Consumption in People with Alcohol Dependence: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company (Lundbeck) marketing nalmefene (Selincro) to submit evidence of its clinical and cost effectiveness for reducing alcohol consumption in people with alcohol dependence. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG) and to produce a critical review of the company's submission to NICE. The clinical evidence was derived from three phase III, company-sponsored, randomised, double-blind, placebo-controlled trials in adults with a diagnosis of alcohol dependence comparing nalmefene, taken on an as-needed basis, in conjunction with psychosocial support with placebo in conjunction with psychosocial support. Psychosocial support was provided in the form of BRENDA, an intervention of lower intensity than that recommended in NICE Clinical Guideline 115 (NICE CG115). Post-hoc subgroup analyses were conducted in people who were drinking at high or very high risk levels at baseline and maintained this level of drinking during the screening phase prior to randomisation. This subgroup forms the licensed population. There were a number of limitations and uncertainties in the clinical evidence base which warrant caution in its interpretation. In particular, the post-hoc subgroup analyses and high dropout rates in the three nalmefene studies meant that the inference of treatment effects might be confounded. The company's economic evaluation showed that use of nalmefene in conjunction with psychosocial support in the form of BRENDA dominated the use of BRENDA in conjunction with placebo, providing more quality-adjusted life-years (QALYs) at a reduced cost. However, this evaluation did not meet the final scope issued by NICE, which specified that the comparator should be psychological intervention as defined in NICE CG115. The ERG produced alternative cost per QALY values for the comparison undertaken by the company and suggested three further comparisons deemed relevant: (1) nalmefene with psychological intervention as defined in NICE CG115; (2) delayed use of nalmefene in those who did not respond to psychological intervention as recommended in NICE CG115 alone; and (3) use of naltrexone outside of its marketing authorisation. The ERG thought it probable that using nalmefene in only those people who do not respond to psychological intervention alone was likely to be more cost effective compared with its immediate use in the entire licensed population. The Appraisal Committee accepted the comparison with psychosocial support in the form of BRENDA and believed that the most plausible cost per QALY was likely to be below £5100. Therefore, the Appraisal Committee concluded that nalmefene in conjunction with psychosocial support was a cost effective use of NHS resources compared with psychosocial support alone for treating people with alcohol dependence drinking at a high risk level, without physical withdrawal symptoms and not requiring immediate assisted withdrawal from alcohol.