Table 2 Adapted input parameters for cost-effectiveness model per scenario
Adapted parameter | Initial deterministic value | Deterministic value | SE | Distribution | Source / Assumption |
|---|---|---|---|---|---|
Scenario: “TIL more effective” | |||||
PFS TIL | 0.234 | 0.257 | 0.068 | Beta | Assumption: 10% increase of survival rates as described in the scenario |
OS TIL | 0.412 | 0.453 | 0.046 | Beta | |
Scenario: “Combination therapy” | |||||
PFS TIL | 0.234 | 0.264 | 0.089 | Beta | 12mo PFS 4/13 patients [19] SE was kept the same as the initial model |
OS TIL | 0.412 | 0.499 | 0.098 | Beta | 12mo OS 9/13 patients [19] SE was kept the same as the initial model |
Costs TIL | € 62.000 | € 107.744 | €13.743 | Gamma | On average 2 times ipilimumab and administration costs and costs to anticipate on the side effects (€693.75 + €45,050) [19, 20]. |
Failure rate | 0.10 | 0.10 | 0.015 | Beta | 1/13 received no TIL due to progression during TIL growth; 1 patient did not receive ipilimumab after TIL due to dose-limiting colitis [19]. Assumed to be similar as basecase model. |
Scenario: “Low cost competition” | |||||
Drug costs Ipilimumab | € 90.100 | € 71.184 | €9080 | Gamma | Reduced price for ipilimumab in such a way that TIL is not cost-effective anymore with a willingness to pay threshold of 30.000. A reduction of 21%. |
Scenario: “Less IL2 treatment” | |||||
Total TIL costs | € 62.000 | € 61.450 | € 7838 | Gamma | Assuming the decrescendo regimen described by Andersen et al. 2016 6 vials of Aldesleukin (Novartis) [20] 550 euros reduced compared to the initial costs. |
Utility decrements for side effects in providing TIL therapy due to toxicity | 0.145 | 0.145 | 0.020 | Beta | It was assumed to be the same as in the initial model because the availability of data on toxicity after a high or decrescendo dose scheme is limited. |
PFS TIL | 0.234 | 0.234 | 0.089 | Beta | Assumed to be the same as no data shows that efficacy of TIL therapy decreased with a lowered dose IL2. |
OS TIL | 0.412 | 0.412 | 0.098 | Beta | |
Scenario: “TIL production outsourced” | |||||
TIL production costs | € 35.500 | € 106.500 | €11.990 | Gamma | Since no commercial price is available, we made an assumption based on expert opinion (WvH and JvB) that commercial costs of TIL are at least 3 times higher. Taking into account the necessary logistical arrangements and general costs when starting a biotech company |
Scenario: “Automatic TIL production” | |||||
TIL production costs | € 35.500 | € 24.850 | 1268 | Gamma | Assumption: 30% decrease of production costs as described in the scenario. |