Treating MCI patients at low risk generated greater benefits, although it may be counterintuitive. |
With a high degree of uncertainty, the decision of whether to treatment MCI patients or not based on their risk levels may benefit from gathering more information on the treatment effectiveness for MCI. |
1 Introduction
2 Methods
2.1 Model Structure
2.2 Treatment Strategies
2.3 Model Parameters
Parameter | Mean | 95% CI | Distribution | Source |
---|---|---|---|---|
Annual probability of progression from MCI to AD by CSF biomarker scorea
| [19] | |||
Low-risk group | 0.064 | 0.01–0.16 | Beta (2.46, 35.93) | |
Intermediate-risk group | 0.108 | 0.03–0.22 | Beta (4.05, 33.48) | |
High-risk group | 0.244 | 0.17–0.33 | Beta (27.89, 86.40) | |
Prevalence of MCI patients by risk levels | [19] | |||
Low-risk group | 0.6 | |||
Intermediate-risk group | 0.2 | |||
High-risk group | 0.2 | |||
Annual transition probability | ||||
Stage to stage (AD) | ||||
Mild to moderate | 0.167 | 0.156–0.178 | Beta (690.43, 3443.86) | |
Mild to severe | 0.014 | 0.010–0.018 | Beta (59.63, 4199.86) | |
Moderate to severe | 0.299 | 0.286–0.312 | Beta (1355.02, 3176.83) | |
Community to nursing home | ||||
Mild AD | 0.012 | 0–0.028 | Beta (2.27, 186.70) | |
Moderate AD | 0.034 | 0–0.069 | Beta (3.57, 101.46) | |
Severe AD | 0.066 | 0.005–0.128 | Beta (3.74, 52.91) | |
Excess mortality due to AD (additive effect)b
| 0.11 | 0.055–0.165 | ||
Treatment effectiveness (RR) | ||||
MCI patients | 0.84 | 0.70–1.02 | Lognormal (−0.17, 0.096) | [36] |
AD patients | ||||
Mild to moderate | 0.58 | 0.35–0.76 | Lognormal (−0.55, 0.198) | Estimated by authors |
Moderate to severe | 0.95 | 0.64–1.41 | Lognormal (−0.05, 0.114) | [42] |
Treatment harm | ||||
Annual prob. of AE (control) | 0.23 | 0.2–0.26 | Beta (173.78, 581.77) | [43] |
AEs in MCI (RR) | 1.09 | 1.02–1.16 | Lognormal (0.086, 0.033) | [36] |
AEs in AD (RR) | 2.09 | 1.81–2.40 | Lognormal (0.736, 0.073) | [44] |
Withdrawal due to AEc
| 0.18 | 0.13–0.22 | Beta (41.67, 181.76) | [44] |
Withdrawal due to non-AE in MCI | 0.046 | 0.035–0.058 | Beta (52.94, 1201.7) | Assumed |
Withdrawal due to non-AE in AD | 0.11 | 0.10–0.12 | Beta (190.03, 1543.9) | Assumed |
Health utility | ||||
MCI | 0.73 | 0.58–0.88 | Beta (23.86, 8.82) | |
AD | [49] | |||
Mild | ||||
Community | 0.68 | 0.54–0.82 | Beta (28.34, 13.34) | |
Nursing home | 0.71 | 0.57–0.85 | Beta (27.97, 11.42) | |
Moderate | ||||
Community | 0.54 | 0.43–0.65 | Beta (42.08, 35.85) | |
Nursing home | 0.48 | 0.37–0.59 | Beta (37.59, 40.72) | |
Severe | ||||
Community | 0.37 | 0.29–0.45 | Beta (67.3, 114.6) | |
Nursing home | 0.31 | 0.24–0.38 | Beta (51.72, 115.11) | |
AEd
| 0.95 | 0.916–0.976 | Beta (190, 10) | [29] |
Lumbar punctured
| 0.01 | 0.009–0.012 | Beta (9800, 99) | Assumed, [52] |
Cost (US$, per person-year) | ||||
MCI | 7467 | 3733–11,200 | Gamma (15.36, 0.0021) | [56] |
Formal | [55] | |||
Mild AD | ||||
Community | 9380 | 4690–14,070 | Gamma (15.37, 0.0017) | |
Nursing home | 50,865 | 25,432–76,297 | Gamma (15.37, 3.06) | |
Moderate AD | ||||
Community | 13,859 | 6929–20,788 | Gamma (15.37, 0.0011) | |
Nursing home | 55,362 | 27,681–83,043 | Gamma (15.37, 2.81) | |
Severe AD | ||||
Community | 20,889 | 10,445–31,334 | Gamma (15.37, 7.46) | |
Nursing home | 59,327 | 29,664–88,991 | Gamma (15.37, 2.63) | |
Informal | [55] | |||
Mild AD | ||||
Community | 11,876 | 5938–17,815 | Gamma (15.37, 0.0013) | |
Nursing home | 1267 | 633–1900 | Gamma (15.33, 0.0127) | |
Moderate AD | ||||
Community | 20,559 | 10,279–30,838 | Gamma (15.37, 7.58) | |
Nursing home | 973 | 486–1459 | Gamma (15.35, 0.016) | |
Severe AD | ||||
Community | 20,724 | 10,362–31,086 | Gamma (15.37, 7.52) | |
Nursing home | 1028 | 514–1542 | Gamma (15.33, 0.0151) | |
Drug (donepezil) | 2884 | 1442–4325 | Gamma (15.35, 0.0054)) | AWP, [57] |
Office visit due to treatment (per time) | 83 | 42–125 | Gamma (14.88, 0.1837) | [49] |
CSF biomarker testing (per person) | 324 | 162–487 | Gamma (15.50, 0.0492) | [25] |
2.3.1 Disease Progression
2.3.2 Treatment Effectiveness
2.3.3 Adverse Events (AEs) Associated with Treatment
2.3.4 Withdrawal of Cholinesterase Inhibitor (ChEI) Treatment
2.3.5 Health Utilities
2.3.6 Excess Mortality
2.3.7 Costs
2.4 Analyses
2.4.1 Base-Case Analysis
2.4.2 Sensitivity Analysis
2.4.3 Scenario Analysis
3 Results
3.1 Base-Case Analysis
Strategy | Cost (US$) | QALYs | ICER (US$/QALY)a
|
---|---|---|---|
Test and treat high or intermediate risk | 270,593 | 7.471 | |
Test and treat high risk | 270,735 | 7.475 | Weakly dominated |
No testing and treat all MCI patients | 271,083 | 7.509 | 12,800 |
No testing and no MCI treatment | 275,302 | 7.627 | Weakly dominated |
Test and treat low or intermediate risk | 276,286 | 7.647 | Weakly dominated |
Test and treat low risk | 276,428 | 7.651 | 37,700 |
3.2 Deterministic Sensitivity Analysis
Analysisa
| Test-and-treat strategy | |||||
---|---|---|---|---|---|---|
Test and treat low risk | Test and treat low or intermediate risk | No test and no MCI treatment | No test and treat all MCI | Test and treat high risk | Test and treat high or intermediate risk | |
Base-case | 37,700b
| Weakly DOM | Weakly DOM | 12,800c
| Weakly DOM | – |
Annual probability of progression from MCI to AD | ||||||
At low risk, 1% | 38,500b
| Weakly DOM | Weakly DOM | 19,000c
| Weakly DOM | – |
At low risk, 16% | Weakly DOM | Weakly DOM | 35,600b
| – | Weakly DOM | Weakly DOM |
At intermediate risk, 3% | Weakly DOM | 40,700b
| Weakly DOM | 20,400c
| – | Weakly DOM |
At intermediate risk, 22% | 38,100b
| Weakly DOM | Weakly DOM | 9400c
| Weakly DOM | – |
At high risk, 17% | 64,400d
| Weakly DOM | 36,200b
| 9500c
| Strongly DOM | – |
At high risk, 33% | 64,400d
| Weakly DOM | 38,000b
| 9500c
| Strongly DOM | – |
Treatment effectiveness (RR) | ||||||
Mild AD, 0.35 | Strongly DOM | Strongly DOM | 16,400e
| Strongly DOM | 7500c
| – |
Mild AD, 0.76 | Strongly DOM | 438,000b
| Strongly DOM | 5800c
| Strongly DOM | – |
Moderate AD, 0.64 | 199,000d
| Strongly DOM | 27,800b
| 8800c
| Weakly DOM | – |
Moderate AD, 1.41 | 64,400d
| Weakly DOM | 37,300b
| 9500c
| Strongly DOM | – |
MCI patients, 0.70 | Strongly DOM | 131,800b
| Strongly DOM | – | Strongly DOM | Strongly DOM |
MCI patients, 1.02 | Strongly DOM | Strongly DOM | 10,300e
| Strongly DOM | – | Strongly DOM |
Treatment harm | ||||||
Annual prob. of AE (control), 20% | 75,300d
| Strongly DOM | 34,400b
| 9300c
| Strongly DOM | – |
Annual prob. of AE (control), 26% | 65,200d
| Weakly DOM | 36,600b
| 9600c
| Strongly DOM | – |
AEs in MCI (RR), 1.02 | 69,600d
| Weakly DOM | 37,500b
| 8600c
| Strongly DOM | – |
AEs in MCI (RR), 1.16 | 64,700d
| Weakly DOM | 33,300b
| 10,200c
| Strongly DOM | – |
AEs in AD (RR), 1.81 | 79,200d
| Strongly DOM | 33,400b
| 9400c
| Strongly DOM | – |
AEs in AD (RR), 2.40 | Strongly DOM | Strongly DOM | 10,200b
| Strongly DOM | – | Strongly DOM |
Withdrawal due to AE, 13% | 78,700d
| Strongly DOM | 44,500b
| 7500c
| Strongly DOM | – |
Withdrawal due to AE, 22% | 64,800d
| Weakly DOM | 35,600b
| 10,700c
| Weakly DOM | – |
Health utility | ||||||
MCI patients, 0.58 | 995,200d
| Strongly DOM | 26,500e
| Weakly DOM | 15,400c
| – |
MCI patients, 0.88 | Strongly DOM | 52,800b
| Weakly DOM | 6200c
| Strongly DOM | – |
Health utility | ||||||
AE, 0.916 | 53,500f
| 53,000d
| 44,900b
| 8600c
| Strongly DOM | – |
AE, 0.976 | 84,900d
| Strongly DOM | 31,700b
| 10,300c
| Strongly DOM | – |
Lumbar puncture, 0.009 | 78,600d
| Strongly DOM | 35,500b
| 9000c
| Strongly DOM | – |
Lumbar puncture, 0.012 | 61,300d
| Weakly DOM | 37,300b
| 9700c
| Strongly DOM | – |
Annual costs | ||||||
MCI, US$3733 | 72,100d
| Strongly DOM | 35,500b
| 8600c
| Strongly DOM | – |
MCI, US$11,200 | 67,800d
| Weakly DOM | 35,500b
| 10,200c
| Strongly DOM | – |
Formal costs for patients dwelling in the community | ||||||
Mild AD, US$4690 | 96,600d
| Strongly DOM | 14,300e
| Weakly DOM | – | Strongly DOM |
Mild AD, US$14,070 | 95,400f
| 60,400b
| Strongly DOM | – | Strongly DOM | Strongly DOM |
Moderate AD, US$6929 | 59,100d
| Weakly DOM | 42,100b
| 4400c
| Strongly DOM | – |
Moderate AD, US$20,788 | 80,400d
| Weakly DOM | 28,900b
| 14,500c
| Weakly DOM | – |
Severe AD, US$10,445 | 53,900f
| 47,000b
| Weakly DOM | 1300c
| Strongly DOM | – |
Severe AD, US$31,334 | 78,600d
| Weakly DOM | 36,100b
| 21,500e
| 7400c
| – |
Formal costs for patients dwelling in a nursing home | ||||||
Mild AD, US$25,432 | 75,900d
| Weakly DOM | 26,800b
| 17,600e
| 10,700c
| – |
Mild AD, US$76,297 | 57,000d
| Weakly DOM | 45,300b
| 3400c
| Strongly DOM | – |
Moderate AD, US$27,681 | 62,800d
| Weakly DOM | 38,200b
| 8700c
| Strongly DOM | – |
Moderate AD, US$83,043 | 70,800d
| Weakly DOM | 35,200b
| 9900c
| Strongly DOM | – |
Severe AD, US$29,664 | 62,500f
| 49,700b
| Weakly DOM | 1600c
| Strongly DOM | – |
Severe AD, US$88,991 | 88,700d
| Weakly DOM | 22,700e
| Weakly DOM | 2400c
| – |
Excess mortality in moderate AD | ||||||
Multiplier, 10% | 74,700d
| Weakly DOM | 26,200b
| 20,800e
| 6200c
| – |
Multiplier, 90% | 57,800d
| Strongly DOM | 44,600b
| 2200c
| Strongly DOM | – |