Cost effectiveness of donepezil in the treatment of mild to moderate Alzheimer's disease: a UK evaluation using discrete-event simulation.
Recommendations in the UK suggest restricting treatment of Alzheimer's disease with cholinesterase inhibitors, on cost-effectiveness grounds, to patients with moderate cognitive decline. As the economic analyses that informed these recommendations have been the subject of debate, we sought to address the potential limitations of existing models and produce estimates of donepezil treatment cost effectiveness in the UK using the most recent available data and simulation techniques. A discrete-event simulation was developed that predicts progression of Alzheimer's disease through correlated changes in cognition, behavioural disturbance and function. Patient-level data from seven randomized, placebo-controlled donepezil trials and a 7-year follow-up registry provided the basis for modeling longitudinal outcomes. Individuals in the simulation were assigned unique demographic and clinical characteristics and then followed for 10 years, with severity of disease tracked on continuous scales. Patient mix and costs were developed from UK-specific literature. Analyses were run for severity subgroups to evaluate outcomes for sub-populations with disease of mild versus moderate severity from both a healthcare payer and societal perspective. All costs are reported in pound, year 2007 values, and all outcomes are discounted at 3.5% per annum. Over 10 years, treatment of all patients with mild to moderate disease reduces overall direct medical costs by an average of over pound2300 per patient. When unpaid caregiver time is also taken into consideration, savings increase to over pound4700 per patient. Compared with untreated patients, patients receiving donepezil experience a discounted gain in QALYs averaging 0.11, with their caregivers gaining, on average, 0.01 QALYs. For the subset of patients starting treatment with more severe disease, savings are more modest, averaging about pound1600 and pound3750 from healthcare and societal perspectives, respectively. In probabilistic sensitivity analyses, donepezil dominated no treatment between 57% and 62% of replications when only medical costs were considered, and between 74% and 79% of replications when indirect costs were included, with results more favourable for treatment initiation in the mild versus moderate severity stages of the disease. Although the simulation results are not definitive, they suggest that donepezil leads to health benefits and cost savings when used to treat mild to moderately severe Alzheimer's disease in the UK. They also indicate that both benefits and savings may be greatest when treatment is started while patients are still in the mild stages of Alzheimer's disease.
Getsios
Denis
D
United BioSource Corporation, Lexington, MA02420, USA. denis.getsios@unitedbiosource.com
Blume
Steve
S
Ishak
K Jack
KJ
Maclaine
Grant D H
GD
D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics* / Q000401:mortality; D017028:Caregivers / Q000191:economics; D003198:Computer Simulation; D017281:Cost of Illness; D003362:Cost-Benefit Analysis; D016208:Databases, Factual; D000077265:Donepezil; D016527:Drug Costs / Q000706:statistics & numerical data; D005260:Female; D017048:Health Care Costs / Q000706:statistics & numerical data; D006801:Humans; D007189:Indans / Q000191:economics* / Q000627:therapeutic use*; D008297:Male; D018803:Models, Economic; D018697:Nootropic Agents / Q000191:economics / Q000627:therapeutic use; D010880:Piperidines / Q000191:economics* / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D016896:Treatment Outcome; D006113:United Kingdom
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil
BMJ. 2008 Feb 2;336(7638):258-62
18187696
Dement Geriatr Cogn Disord. 2006;21(5-6):353-63
16508298
Stat Med. 2000 Jun 15-30;19(11-12):1607-16
10844722
Stat Med. 2000 Jun 15-30;19(11-12):1401-9
10844705
Int J Geriatr Psychiatry. 2003 Aug;18(8):740-7
12891643
Pharmacoeconomics. 2006;24(6):623-5; author reply 625-6
16761908
CNS Drugs. 2007;21(3):177-84
17338591
Neurology. 2007 Jul 31;69(5):459-69
17664405
Neurology. 2001 Aug 28;57(4):613-20
11524468
Neurology. 2001 Aug 14;57(3):489-95
11502918
Neurology. 2001 Aug 14;57(3):481-8
11502917
Neurology. 2001 Sep 25;57(6):964-71
11571318
BMJ. 2006 Sep 2;333(7566):491-3
16946340
Pharmacoeconomics. 2007;25(12):997-1006
18047386
Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593
16437532
Dement Geriatr Cogn Disord. 2008;25(3):226-31
18230972
BMJ. 2008 May 10;336(7652):1035
18467392
Arch Neurol. 2001 Mar;58(3):427-33
11255446
Alzheimers Dement. 2008 May;4(3):212-22
18631970
Alzheimer Dis Assoc Disord. 2006 Jan-Mar;20(1):49-55
16493236
Am J Geriatr Psychiatry. 2007 Apr;15(4):314-27
17384314
Expert Rev Pharmacoecon Outcomes Res. 2008 Jun;8(3):273-89
20528379
Arch Intern Med. 1998 May 11;158(9):1021-31
9588436
Clin Interv Aging. 2008;3(2):211-25
18686744
Pharmacoeconomics. 2007;25(9):735-50
17803333
J Health Econ. 2002 Mar;21(2):271-92
11939242
Am J Psychiatry. 1994 Mar;151(3):390-6
8109647
Age Ageing. 2007 Jan;36(1):16-22
17175565
Lancet. 2006 Apr 1;367(9516):1057-1065
16581404
Neurology. 1998 Jan;50(1):136-45
9443470