Table 1.
Input parameters used in deterministic and probabilistic sensitivity analysis. Parameter adjustments for scenario analyses are indicated per scenario
| Variable | Mean value TDM (SE) | Mean value tamoxifen SC (SE) | Distribution | References |
|---|---|---|---|---|
| Age, years | 57 | 57 | Fixed | [10] |
| Discount rates | ||||
| Costs (%) | 4 | 4 | n.a. | [29] |
| Effects (%) | 1.5 | 1.5 | n.a. | |
| Transition state | ||||
| RFS | Weibull | [1] | ||
| AIC | 11,055.72 | 11,729.69 | ||
| Intercept | 3.4116 | 3.3832 | ||
| Log (scale) | − 0.0449 | − 0.0039 | ||
| OS | Weibull | |||
| AIC | 10,885.48 | 11,344.88 | ||
| Intercept | 3.1694 | 3.1392 | ||
| Log (scale) | − 0.3305 | − 0.3295 | ||
| Utility | ||||
| RFS state | 0.88 (0.22) | 0.87 (0.20) | Beta | [10, 24] |
| RD state | 0.74 (0.26) | 0.74 (0.26) | Beta | |
| Endoxifen concentration | ||||
| < 16 nM (%) | 10 | 20 | Fixed | [10] |
| ≥ 16 nM (%) | 90 | 80 | Fixed | |
| Costs per cycle—RFS | ||||
| Drug acquisition costs | €33 | €27 | [13, 26, 27] | |
| Resources hospital | ||||
| Year 0–1 | €383 | €261 | Gamma | [10, 29] |
| Year 1–5 | €90 | €90 | Gamma | |
| Resources GP | €38 | €38 | Gamma | [28, 29] |
| Costs per cycle—RD | €10,153 | €10,153 | Gamma | [32] |
| Productivity loss | ||||
| RFS | €0 | €0 | Gamma | |
| RD | €0 | €0 | Gamma | |
| Death | €0 | €0 | Gamma | |
| Alternative parameters scenario analysis | ||||
| S1a. Endoxifen concentration (100% on threshold) | ||||
| < 16 nM (%) | 0 | 20 | Fixed | |
| ≥ 16 nM (%) | 100 | 80 | Fixed | |
| RFS | Weibull | [1] | ||
| AIC | 10,526.35 | 11,729.69 | ||
| Intercept | 3.4355 | 3.3832 | ||
| Log (scale) | − 0.0885 | − 0.0039 | ||
| OS | Weibull | |||
| AIC | 11,154.34 | 11,344.88 | ||
| Intercept | 3.2161 | 3.1392 | ||
| Log (scale) | − 0.3234 | − 0.3295 | ||
| S1b. Endoxifen concentration (95% on threshold) | ||||
| < 16 nM (%) | 5 | 20 | Fixed | |
| ≥ 16 nM (%) | 95 | 80 | Fixed | |
| RFS | Weibull | [1] | ||
| AIC | 10,783.76 | 11,729.69 | ||
| Intercept | 3.42592 | 3.3832 | ||
| Log (scale) | − 0.0663 | − 0.0039 | ||
| OS | Weibull | |||
| AIC | 10,746.67 | 11,344.88 | ||
| Intercept | 3.18265 | 3.1392 | ||
| Log (scale) | − 0.3309 | − 0.3295 | ||
| S1c. Endoxifen concentration (85% on threshold) | ||||
| < 16 nM (%) | 15 | 20 | Fixed | |
| ≥ 16 nM (%) | 85 | 80 | Fixed | |
| RFS | Weibull | |||
| AIC | 11,325.18 | 11,729.69 | ||
| Intercept | 3.39738 | 3.3832 | ||
| Log (scale) | − 0.0245 | − 0.0039 | ||
| OS | Weibull | |||
| AIC | 10,651.92 | 11,344.88 | ||
| Intercept | 3.18965 | 3.1392 | ||
| Log (scale) | − 0.3282 | − 0.3295 | ||
| S1d. Correction factor recurrence rate assumption | ||||
| < 16 nM (%) | – | 20 | Fixed | |
| ≥ 16 nM (%) | – | 80 | Fixed | |
| RFS | Weibull | [1] | ||
| AIC | 10,526.35 | 11,729.69 | ||
| Intercept | 3.4355 | 3.3832 | ||
| Log (scale) | − 0.0885 | − 0.0039 | ||
| OS | Weibull | |||
| AIC | 11,154.34 | 11,344.88 | ||
| Intercept | 3.2161 | 3.1392 | ||
| Log (scale) | − 0.3234 | − 0.3295 | ||
| S2. RD costs | ||||
| A. RD-high | €11,990 | €11,990 | Gamma | [32] |
| B. RD-low | €3194 | €3194 | Gamma | |
| S3. Productivity loss | ||||
| RFS | €397 | €397 | NA | [10, 34] |
| RD | €4477 | €4477 | NA | |
| Death | €4477 | €4477 | NA | |
| S4a. Alternative curve fit: Loglogistic | ||||
| RFS | Loglogistic | [1] | ||
| AIC | 11,060.01 | 11,732.21 | ||
| Intercept | 3.1388 | 3.0864 | ||
| Log (scale) | − 0.1572 | − 0.1249 | ||
| OS | Loglogistic | |||
| AIC | 10,895.21 | 11,354.41 | ||
| Intercept | 2.9835 | 2.9484 | ||
| Log (scale) | − 0.4212 | − 0.4238 | ||
| S4b. Alternative curve fit: lognormal | ||||
| RFS | Lognormal | [1] | ||
| AIC | 11,055.81 | 11,720.28 | ||
| Intercept | 3.2897 | 3.2222 | ||
| Log (scale) | 0.4914 | 0.5116 | ||
| OS | Lognormal | |||
| AIC | 10937.21 | 11397.70 | ||
| Intercept | 3.1116 | 3.0674 | ||
| Log (scale) | 0.2460 | 0.2378 | ||
| S4c. Alternative curve fit: exponential | ||||
| RFS | Exponential | [1] | ||
| AIC | 11,056.43 | 11,727.71 | ||
| Intercept | 3.4648 | 3.3875 | ||
| Log (scale) | 0 | 0 | ||
| OS | Exponential | |||
| AIC | 11,022.10 | 11,488.17 | ||
| Intercept | 3.5119 | 3.4704 | ||
| Log (scale) | 0 | 0 | ||
AIC Akaike Information Criteria, GP general practitioner, nM nmol/L, OS overall survival, RD recurrent disease, RFS recurrence-free survival, SC tamoxifen standard care (without therapeutic drug monitoring), SE standard error, TDM therapeutic drug monitoring-guided adjuvant tamoxifen dosing