ss_tte

Depending on the results of phase II and our strategy ,i.e. whether we proceed only with the best promising treatment (l = 1) or with all promising treatments (l = 2), this program calculates the number of participants in phase III.
l=1: according to Schoenfeld to guarantee power for the log rank test to detect treatment effect of phase II;
l=2: according to Dunnett to guarantee y any-pair power (Horn &amp; Vollandt)

internal

Plan optimal sample size allocation and go/no-go decision rules
for phase II/III drug development programs with time-to-event, binary or
normally distributed endpoints when assuming fixed treatment effects or a
prior distribution for the treatment effect, using methods from Kirchner et al.
(2016) <doi:10.1002/sim.6624> and Preussler (2020). Optimal is in the sense of
maximal expected utility, where the utility is a function taking into account
the expected cost and benefit of the program. It is possible to extend to more
complex settings with bias correction (Preussler S et al. (2020)
<doi:10.1186/s12874-020-01093-w>), multiple phase III trials (Preussler et
al. (2019) <doi:10.1002/bimj.201700241>), multi-arm trials (Preussler et al.
(2019) <doi:10.1080/19466315.2019.1702092>), and multiple endpoints
(Kieser et al. (2018) <doi:10.1002/pst.1861>).

Lukas D. Sauer

drugdevelopR

Utility-Based Optimal Phase II/III Drug Development Planning

Stella Erdmann

Johannes Cepicka

Marietta Kirchner

Meinhard Kieser

ss_tte function

<dl><dt>alpha</dt>
<dd>significance level</dd>
<dt>beta</dt>
<dd>1-beta power for calculation of sample size for phase III</dd>
<dt>ec</dt>
<dd>control arm event rate for phase II and III</dd>
<dt>ek</dt>
<dd>event rate of arm k (either arm 1 or arm 2)</dd>
<dt>y</dt>
<dd>hat_theta_2; estimator in phase II</dd>
<dt>l</dt>
<dd>number of treatments in phase III:<ul>
<li>l=1: according to Schoenfeld to guarantee power for the log rank test to detect treatment effect of phase II;</li>
<li>l=2: according to Dunnett to guarantee y any-pair power (Horn &amp; Vollandt)</li>
</ul></dd></dl>

Arguments

Total sample size for phase III trial with l treatments and equal allocation ratio for time-to-event outcomes — ss_tte

<dl>

<dt>alpha</dt>
<dd>significance level</dd>


<dt>beta</dt>
<dd>1-beta power for calculation of sample size for phase III</dd>


<dt>ec</dt>
<dd>control arm event rate for phase II and III</dd>


<dt>ek</dt>
<dd>event rate of arm k (either arm 1 or arm 2)</dd>


<dt>y</dt>
<dd>hat_theta_2; estimator in phase II</dd>


<dt>l</dt>
<dd>number of treatments in phase III:<ul>
<li>l=1: according to Schoenfeld to guarantee power for the log rank test to detect treatment effect of phase II;</li>
<li>l=2: according to Dunnett to guarantee y any-pair power (Horn &amp; Vollandt)</li>
</ul></dd>

</dl>

ss_tte: Total sample size for phase III trial with l treatments and equal allocation ratio for time-to-event outcomes

Description

Usage

Value

Arguments

Examples