Evolution of the evidence on the effectiveness and cost-effectiveness of acetylcholinesterase inhibitors and memantine for Alzheimer’s disease: systematic review and economic model

Introduction: in 2007 the National Institute of Health and Clinical Excellence (NICE) restricted the use of acetylcholinesterase inhibitors and memantine.

Methods: we conducted a health technology assessment (HTA) of the effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of AD to re-consider and up-date the evidence base used to inform the 2007 NICE decision. The systematic review of effectiveness targeted randomised controlled trials. A comprehensive search, including MEDLINE, Embase and the Cochrane Library, was conducted from January 2004 to March 2010. All key review steps were done by two reviewers. Random effects meta-analysis was conducted. The cost-effectiveness was assessed using a cohort-based model with three health states: pre-institutionalised, institutionalised and dead. The perspective was NHS and Personal Social Services and the cost year 2009.

Results: confidence about the size and statistical significance of the estimates of effect of galantamine, rivastigmine and memantine improved on function and global impact in particular. Cost-effectiveness also changed. For donepezil, galantamine and rivastigmine, the incremental cost per quality-adjusted life year (QALY) in 2004 was above £50,000; in 2010 the same drugs ‘dominated’ best supportive care (improved clinical outcome at reduced cost). This was primarily because of changes in the modelled costs of introducing the drugs. For memantine, the cost-effectiveness also improved from a range of £37–53,000 per QALY gained to a base-case of £32,000.

Conclusion: there has been a change in the evidence base between 2004 and 2010 consistent with the change in NICE guidance. Further evolution in cost-effectiveness estimates is possible particularly if there are changes in drug prices.