Table 3.
Outcome metrics for simulation scenarios evaluated
| Neutropenia duration (d) [median, 95% PI] | Efficacy (days) [median, 95% PI] | Ci (CU) [median, 95% PI] | Compared to the No Treatment Scenario [median, 95% PI] | Comparison to the Base Scenario [median, 95% PI] | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Scenarios | Dose intensity (%) [median, 5th–95th percentiles] | Neutropenia incidence (grade 3, 4) | Grade 3 | Grade 4 | Survival | Dose | AEs | Total | Life years gained (days) | ICER (CU) | QALY (CU/QOL) | |
| B | Base | 0.77 (0.39 – 1) | (63.4, 34.9) | 4 (0 – 28) | 0 (0 – 19) | 517 (100 – 2081) | 1418.9 (400.15 – 4024.58) | 299 (0 – 2300.45) | 1985.5 (501.95 – 4856.3) | 29 (0 – 401) | – | – |
| S2 | Dose regimen – 1.0 mg/m2 at t=[1,8] days | 0.96 (0.44 – 1) | (45.4, 17.7) | 0 (0 – 25) | 0 (0 – 10) | 512 (99 – 2069) | 1161.8 (325.89 – 2971.67) | 189 (0 – 1256.3) | 1469 (374.95 – 3520.45) | 25 (0 – 391) | 18.9 (–12.93 – 140.91) | 0 (–45 – 37.1) |
| S3 | Dose regimen – 1.4 mg/m2 at t=1 days | 0.96 (0.75 – 1) | (40.8, 17.8) | 0 (0 – 19) | 0 (0 – 8) | 491 (97 – 2033) | 747.94 (294.25 – 2053.36) | 180.5 (0 – 1037.35) | 1042 (303.8 – 2752.4) | 3 (0 – 377) | 32.71 (6.91 – 858.51) | –2.51 (–120.7 – 0) |
| S4 | Progression after 50% increase from nadir (instead of 25%) | 0.77 (0.38 – 1) | (65.9, 38.8) | 6 (0 – 29) | 0 (0 – 21) | 517 (100 – 2081) | 1918 (513.99 – 4063.7) | 390.5 (10 – 2395.6) | 2735.5 (734.7 – 4964.95) | 30 (0 – 401) | 19.05 (–22.66 – 243.59) | 0 (0 – 0) |
| S5 | Dose reductions – No dose reductions | 1 (1 – 1) | (66.8, 45.4) | 6 (0 – 39) | 0 (0 – 53) | 539 (103 – 2123) | 2806.26 (597.39 – 4478.2) | 511.5 (0 – 5687.05) | 3770 (618.55 – 9847.2) | 69 (1 – 420) | 59.37 (12.28 – 403.31) | 0 (0 – 112.15) |
| S6 | Dose reductions – Permanent dose reduction (instead of single) | 0.69 (0.36 – 1) | (63.2, 32.8) | 3.5 (0 – 27) | 0 (0 – 9) | 514 (100 – 2073) | 1285.92 (400.15 – 3870.67) | 280 (0 – 1259.05) | 1760.5 (501.95 – 4349.9) | 25 (0 – 395) | 24.43 (–23.51 – 161.33) | 0 (–18.57 – 0) |
| S7 | Changed dose reduction for grade 3 (50%) and 4 (65%) toxicity | 0.75 (0.39 – 1) | (63.2, 34.5) | 4 (0 – 26) | 0 (0 – 17) | 515 (100 – 2077) | 1364.21 (361.82 – 3986.15) | 322.5 (0 – 2007.8) | 1927.5 (472.8 – 4716.65) | 26 (0 – 399) | 13.14 (–71.73 – 203.26) | 0 (–5.07 – 0) |
| S8 | Patient population – Lower PSA baseline (5 ng/mL) | 0.78 (0.39 – 1) | (63.8, 35) | 4 (0 – 30) | 0 (0 – 22) | 644.5 (125 – 2594) | 1685.45 (400.15 – 4074.53) | 344 (0 – 2408.65) | 2366.5 (503.9 – 5060.85) | 165 (27 – 902) | 0.23 (–2 – 8.26) | 127.68 (47 – 397) |
| S9 | Patient population – Taxane pre–treated (200 days) patients | 0.78 (0.39 – 1) | (63.3, 34.7) | 4 (0 – 27) | 0 (0 – 19) | 433 (84 – 1750) | 1366.2 (398.76 – 3986.74) | 274 (0 – 2212.05) | 1884 (503.9 – 4914.1) | –22 (–130 – 96) | 0 (–2.99 – 6.1) | –84 (–253.5 – 30) |
| S10 | Comparators – Increased drug effect (3*KD0), and equal toxicity | 0.79 (0.39 – 1) | (64.1, 35.9) | 5 (0 – 30) | 0 (0 – 22) | 555 (106 – 2131) | 2037.97 (408.65 – 4157.49) | 355.5 (1 – 2689.25) | 2949.5 (545.4 – 5123) | 86 (1 – 430) | 7.94 (–9.58 – 56.11) | 21.75 (0 – 118.07) |
| S11 | Comparators – Increased drug effect (3*KD0), higher toxicity | 0.59 (0.34 – 1) | (84.3, 60.7) | 8.5 (0 – 31) | 4 (0 – 34) | 547 (104 – 2127) | 1554.39 (391.65 – 3807.68) | 682.5 (3 – 3712.65) | 2793 (499.7 – 5831.45) | 79 (1 – 427) | 13.25 (–28.47 – 89.21) | 13.35 (0 – 113.58) |
| S12 | Comparators – Decreased drug effect (0.5*KD0), and lower toxicity | 1 (0.5 – 1) | (24.9, 6.2) | 0 (0 – 15) | 0 (0 – 3) | 503 (99 – 2053) | 1588.91 (495.7 – 4236.81) | 145 (0 – 877.45) | 1804.5 (530 – 4716.35) | 5 (0 – 380) | 9.54 (–26.05 – 107.82) | 0 (–69.37 – 23.34) |
| S13 | Uncertainty – Increased neutropenia (1.5*ANCSLOPE) | 0.71 (0.45 – 1) | (86.4, 68.8) | 6 (0 – 26) | 4 (0 – 36) | 524 (101 – 2090) | 1312.78 (497.43 – 3626.11) | 890 (1 – 3966.8) | 2398.5 (587.85 – 6219.9) | 52 (1 – 398) | 21.04 (–124.28 – 261) | 0 (–35.07 – 66) |
| S14 | Uncertainty – Increased peripheral neuropathy (3*kn+1) | 0.78 (0.39 – 1) | (63.4, 34.9) | 4 (0 – 27) | 0 (0 – 19) | 517 (100 – 2081) | 1418.9 (400.15 – 4027.44) | 400 (0 – 2445.55) | 2103 (512.8 – 4981.35) | 30 (0 – 401) | –9.48 (–23.85 – 45.28) | 0 (0 – 0) |
NDLT = non dose–limiting toxicity (grade 1 or 2); DLT = Dose–limiting toxicity (grade 3 or 4); LYG = Life–years gained; QALY = Quality adjusted life years gained; ICER = Incremental cost–effectiveness ratio.
*
Other adverse events (pooled): U = Cost unit; TTN = Time to PSA nadir; QOL = Quality of life metric; Ci = Total costs per individual i.