Cost-effectiveness of cerebrospinal biomarkers for the diagnosis of Alzheimer’s disease

Lee, Spencer A. W.; Sposato, Luciano A.; Hachinski, Vladimir; Cipriano, Lauren E.

doi:10.1186/s13195-017-0243-0

Alzheimer's Research & Therapy

Table 1 Base case inputs, ranges for sensitivity analysis, and sources

From: Cost-effectiveness of cerebrospinal biomarkers for the diagnosis of Alzheimer’s disease

Parameter	Base case	Low value	High value	Source [reference]
Patient population
Start age, years	65	55	75	[4]
Initial AD severity distribution (%)
Mild	70	0.5400	0.783	[67]
Moderate	28	0.1850	0.427	[67]
Severe	2	0.0170	0.033	[67]
Diagnosis
Diagnostic test accuracy
Status quo: clinical assessment plus MR neuroimaging (CA + MR)
Sensitivity (SN_MR)	0.54	0.46	0.62	[13]
Specificity (SP_MR)	0.84	0.79	0.89	[13]
Revised criteria: clinical assessment plus MR neuroimaging and/or biomarker analysis
Sensitivity (SN_MR+BM)	0.86	0.80	0.92	[13]
Specificity (SP_MR+BM)	0.79	0.74	0.84	[13]
Diagnostic accuracy of CSF biomarkers in patients with no medial temporal lobe atrophy on MRI
Sensitivity (SN_BM\|MR−)	0.698	0.54	0.86	Calculated^a
Specificity (SP_BM\|MR−)	0.941	0.89	0.98	Calculated^a
Biomarker analysis				(see Methods)
Cost	463	250	600	[50]
QALY toll	−0.008	0	−0.02	[19, 57]
AD natural history model
Mortality
Age-specific mortality due to causes other than AD	Annual mortality rate = 3.53e^0.0909×Age			Estimated^b [53, 68]
HRs for AD-specific mortality
Mild	2.92	2.34	3.52	[29]
Moderate	3.85	2.94	5.05	[29]
Severe	9.52	6.60	13.4	[29]
Disease progression without AD treatment (annual rate per 100,000)
From mild
To moderate	27,710	24,939	30,481	[25, 31]
To severe	1385	1247	1524	[25, 31]
From moderate
To mild	4478	4030	4925	[25, 31]
To severe	31,829	28,647	35,012	[25, 31]
From severe
To mild	385	347	424	[25, 31]
To moderate	5332	4799	5865	[25, 31]
Transition to long-term care facility (annual rate per 100,000)
From mild	2110	500	4000	[31, 43, 44]
From moderate	6957	1500	8000	[31, 43, 44]
From severe	11,747	2500	15,000	[31, 43, 44]
AD treatment
Treatment uptake and adherence
Treatment initiation
Donepezil, at diagnosis	0.45	0.27	0.56	[37, 39, 41]
Memantine, at transition to severe AD	0.36	0.22	0.45	[38]
Treatment discontinuation (annual rate per 100,000)
Donepezil, community dwelling	28,768	10,536	35,667	[36]
Donepezil, long-term care facility dwelling	62,362	51,083	69,315	[42]
Memantine	30,111	12,783	44,629	[6]
Treatment reinitiation after quitting (annual rate per 100,000)
Donepezil	33,142	23,105	40,132	[38]
Memantine	22,314	17,834	25,541	[6]
Treatment effectiveness
Donepezil HRs
Transition from mild to moderate	0.5	0.253	0.989	[25]
Transition from moderate to mild	2.36	0.802	6.95	[25]
Transition from community to long-term care facility	0.37	0.2	0.5	[43]
Memantine
Incremental utility (annualized)	0.051	0	0.1	[7]
HR, transition from community to long-term care facility	0.37	0.2	0.5	Assumed same as donepezil
Costs (US$)
Age-specific baseline costs	Annual costs = 893e^0.0404×Age			Estimated (see Methods)
45–64 years	5499	4000	8000	[51]
65–84 years	12,336	11,000	16,000	[51]
>84 years	27,674	25,000	34,000	[51]
Annual incremental costs by disease severity (including costs of informal caregiving)
Community dwelling
Patients without AD	24,128	17,369	30,369	Assumed the same as Mild AD
Mild AD	24,128	17,369	30,369	(see Additional file 1)
Moderate AD	33,845	25,000	40,000	(see Additional file 1)
Severe AD	60,160	50,000	69,000	(see Additional file 1)
Long-term care facility dwelling
Facility cost	83,950	70,000	95,000	[52]
Patients without AD	9872	7000	12,000	Assumed the same as Mild AD
Mild AD	9872	7000	12,000	(see Additional file 1)
Moderate AD	9872	7000	12,000	(see Additional file 1)
Severe AD	9847	7000	12,000	(see Additional file 1)
Medication (annual)
Donepezil, 10 mg/day	2473	2000	4288	[69]
Memantine, 10 mg/day	3192	2500	5957	[69]
Age-specific annual health care costs in the year of death
<90 years	35,158	32,000	39,500	[70]
>90 years	25,455	22,000	28,000	[70]
Utilities
Age-specific weights				[54, 55]
60–64 years	0.83	0.822	0.835
65–69 years	0.82	0.820	0.826
70–74 years	0.81	0.803	0.818
75–79 years	0.79	0.786	0.794
>79 years	0.74	0.730	0.742
Health state-specific weights
Community dwelling
Patients without AD	0.68	0.52	0.80	Assumed same as mild AD
Mild AD	0.68	0.52	0.80	[25]
Moderate AD	0.54	0.30	0.70	[25]
Severe AD	0.37	0.25	0.50	[25]
Long-term care facility dwelling
Patients without AD	0.71	0.55	0.80	Assumed same as mild AD
Mild AD	0.71	0.55	0.80	[25]
Moderate AD	0.48	0.30	0.60	[25]
Severe AD	0.31	0.20	0.45	[25]

Abbreviations: AD Alzheimer’s disease, BM Biomarker, CA Clinical assessment, CSF Cerebrospinal fluid, MR Magnetic resonance, MRI Magnetic resonance imaging, QALY Quality-adjusted life-year, SN Sensitivity, SP Specificity
^aThe sensitivity of biomarker analysis in patients without abnormal medial temporal lobe atrophy on MRI (SN_BM|MR-) was calculated using the sensitivity of the revised criteria (in which patients are diagnosed with AD if they have abnormal findings on MRI or abnormal biomarkers, denoted SN_MR+BM) and the sensitivity of clinical assessment and MRI alone (SN_MR) using the formula: SN_MR+BM = SN_MR + (1 − SN_MR) × SN_BM|MR−.The specificity of biomarker analysis in patients without abnormal medial temporal lobe atrophy on MRI (SP_BM|MR−) was calculated using the specificity of the revised criteria (SP_MR+BM) and the specificity of clinical assessment and MRI alone (SP_MR) using the formula: SP_MR+BM = SP_MR × SP_BM|MR−
^bTo avoid double-counting the deaths caused by AD, the age-specific mortality rate due to AD was subtracted from the all-cause mortality rate using an excess mortality model. The resulting “other-cause” age-specific mortality rate was smoothed using an exponential fit

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