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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 (SNMR) 0.54 0.46 0.62 [13]
   Specificity (SPMR) 0.84 0.79 0.89 [13]
  Revised criteria: clinical assessment plus MR neuroimaging and/or biomarker analysis
   Sensitivity (SNMR+BM) 0.86 0.80 0.92 [13]
   Specificity (SPMR+BM) 0.79 0.74 0.84 [13]
  Diagnostic accuracy of CSF biomarkers in patients with no medial temporal lobe atrophy on MRI
   Sensitivity (SNBM|MR−) 0.698 0.54 0.86 Calculateda
   Specificity (SPBM|MR−) 0.941 0.89 0.98 Calculateda
 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 = 3.53e0.0909×Age Estimatedb [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 = 893e0.0404×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]
  1. 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
  2. aThe sensitivity of biomarker analysis in patients without abnormal medial temporal lobe atrophy on MRI (SNBM|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 SNMR+BM) and the sensitivity of clinical assessment and MRI alone (SNMR) using the formula: SNMR+BM = SNMR + (1 − SNMR) × SNBM|MR−.The specificity of biomarker analysis in patients without abnormal medial temporal lobe atrophy on MRI (SPBM|MR−) was calculated using the specificity of the revised criteria (SPMR+BM) and the specificity of clinical assessment and MRI alone (SPMR) using the formula: SPMR+BM = SPMR × SPBM|MR−
  3. 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