Table 2 Simulation conditions, assumptions, and trial design parameter space

Maximum patients

100 per arm

400 per arm

100 per arm

400 per arm

Recruitment rate

10 patients/week

10 patients/week

Culture and data lag time

6 weeks

6 weeks

Proportion of easy/moderate/hard to treat sub-populations

0.33 | 0.33 | 0.33

0.33 | 0.33 | 0.33

Intermediate and surrogate endpoints evaluated

TCC HR

TCC HR

TS-52

TS-8

TS-24

TS-8

TS-24

TS-52

Number of interim analyses

1–2*

2–3*

–

–

Timing of interim analysis

10–100 patients*

100–400 patients*

–

–

Interim criteria

TCC HR threshold: 1.1–2.3*

Relapse % threshold: 4–20%*

–

–

Equal recruitment period (before adaptive algorithm is initiated)

–

–

10 patients per arm

10–50 patients per arm*

Bayesian adaptive randomization tuning parameters

–

–

Nonaggressive–Aggressive

ɣ = 1–25*

η = 0.1–2.0*

Trial stopping rules

–

–

4 Arms reach max N

3 Arms reach max N

Priors

–

–

–

Optimistic*

Skeptical*