This program generates Simon's admissible two-stage designs (Simon, 1989; Jung et al., 2004) for Phase II single arm clinical trials with relaxed probability of stopping for futility (Ivanova and Deal, 2013).
The primary outcome is the probability of treatment response (TR), where treatment response is defined as complete response (CR) or partial response (PR), TR = CR + PR.
The null hypothesis is that the TR rate is p_{0T} and
the alternative is that the TR rate is p_{AT}.
However, the trial is stopped for futility only if the number of patients with disease control (DC) is less than or equal to stage 1 futility boundary, where disease control is defined as DC = TR + SD, with SD denoting stable disease.
The trial is also stopped for futility if the number of TRs in stage 1 is such that it is impossible to reject H_{0} after stage 2, that is, if the number of TRs is less than r_{2} - (n - n_{1}).
The user needs to input lower and upper bounds for the probability of stable disease,
p_{S}^{L} and p_{S}^{U} , 0 ≤
p_{S}^{L} ≤ p_{S}^{U} ≤ 1 -
p_{AT}.
We assume that p_{S} ~ Uniform(p_{S}^{L}, p_{S}^{U}).
The optimal design minimizes the expected sample size under H_{0}, that is, given
p_{0T} and over the distribution of p_{0S}.
The design guarantees the type I error rate not exceeding α for given p_{0T} and p_{S}^{U}, and required power for given p_{AT} and p_{S}^{L}.
When p_{S}^{L}=p_{S}^{U}=0 the design is equivalent to the Simon's two-stage design.
1. Simon R (1989). Controlled Clinical Trials 10: 1-10.
Click here to download Simon's (1989) article.
2. Jung SH, Lee TY, Kim KM, George S (2004). Admissible two-stage designs for phase II cancer clinical trials, Statistics in Medicine 23: 561-569.
3. Ivanova, A and Deal, A. (2013). Two-stage design for phase II oncology trials with relaxed futility stopping.