An efficient multiple-stage procedure for phase II clinical trials that have high response rate objectives

Chen, Shande; Soong, Seng‐Jaw; Wheeler, Richard

doi:10.1016/0197-2456(94)90043-4

Cited by 12 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Note that in order to attempt to address aforementioned issues around the interim stopping rule in Gehan’s design being too relaxed, an extension to Gehan’s framework to make it more applicable to trials with high response rates has been presented [21]. We might hope a modification of this form may improve how the operating characteristics of Gehan’s design fair in comparison to Simon’s designs.…”

Section: Discussionmentioning

confidence: 99%

Re-formulating Gehan’s design as a flexible two-stage single-arm trial

Grayling

Mander

2019

BMC Med Res Methodol

View full text Add to dashboard Cite

BackgroundGehan’s two-stage design was historically the design of choice for phase II oncology trials. One of the reasons it is less frequently used today is that it does not allow for a formal test of treatment efficacy, and therefore does not control conventional type-I and type-II error-rates.MethodsWe describe how recently developed methodology for flexible two-stage single-arm trials can be used to incorporate the hypothesis test commonly associated with phase II trials in to Gehan’s design. We additionally detail how this hypothesis test can be optimised in order to maximise its power, and describe how the second stage sample sizes can be chosen to more readily provide the operating characteristics that were originally envisioned by Gehan. Finally, we contrast our modified Gehan designs to Simon’s designs, based on two examples motivated by real clinical trials.ResultsGehan’s original designs are often greatly under- or over-powered when compared to type-II error-rates typically used in phase II. However, we demonstrate that the control parameters of his design can be chosen to resolve this problem. With this, though, the modified Gehan designs have operating characteristics similar to the more familiar Simon designs.ConclusionsThe trial design settings in which Gehan’s design will be preferable over Simon’s designs are likely limited. Provided the second stage sample sizes are chosen carefully, however, one scenario of potential utility is when the trial’s primary goal is to ascertain the treatment response rate to a certain precision.Electronic supplementary materialThe online version of this article (10.1186/s12874-019-0659-2) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Re-formulating Gehan’s design as a flexible two-stage single-arm trial

Grayling

Mander

2019

BMC Med Res Methodol

View full text Add to dashboard Cite

show abstract

“…The optimal combination of m , n and r S is chosen by minimizing the average sample number (ASN), which is the average of the expected sample size under the null and alternative hypotheses. ASN is a widely used criterion in designing phase II clinical trials 9,16–18 . The rationale behind using the ASN is to consider both the null and alternative hypotheses when choosing the optimal design parameters.…”

Section: Methodsmentioning

confidence: 99%

“…ASN is a widely used criterion in designing phase II clinical trials. 9,[16][17][18] The rationale behind using the ASN is to consider both the null and alternative hypotheses when choosing the optimal design parameters. The ASN is given by…”

Section: Optimizing Design Parametersmentioning

confidence: 99%

Bayesian single‐to‐double arm transition design using both short‐term and long‐term endpoints

Shi

Lin

2023

Pharmaceutical Statistics

View full text Add to dashboard Cite

The choice between single-arm designs versus randomized double-arm designs has been contentiously debated in the literature of phase II oncology trials.Recently, as a compromise, the single-to-double arm transition design was proposed, combining the two designs into one trial over two stages. Successful implementation of the two-stage transition design requires a suspension period at the end of the first stage to collect the response data of the already enrolled patients. When the evaluation of the primary efficacy endpoint is overly long, the between-stage suspension period may unfavorably prolong the trial duration and cause a delay in treating future eligible patients. To accelerate the trial, we propose a Bayesian single-to-double arm design with short-term endpoints (BSDS), where an intermediate short-term endpoint is used for making early termination decisions at the end of the single-arm stage, followed by an evaluation of the long-term endpoint at the end of the subsequent double-arm stage. Bayesian posterior probabilities are used as the primary decision-making tool at the end of the trial. Design calibration steps are proposed for this Bayesian monitoring process to control the frequentist operating characteristics and minimize the expected sample size. Extensive simulation studies have demonstrated that our design has comparable power and average sample size but a much shorter trial duration than conventional single-to-double arm design.Applications of the design are illustrated using two phase II oncology trials with binary endpoints.

show abstract

References

2014

A Practical Guide to Designing Phase II Trials in Oncology

View full text Add to dashboard Cite

An efficient multiple-stage procedure for phase II clinical trials that have high response rate objectives

Cited by 12 publications

References 11 publications

Re-formulating Gehan’s design as a flexible two-stage single-arm trial

Re-formulating Gehan’s design as a flexible two-stage single-arm trial

Bayesian single‐to‐double arm transition design using both short‐term and long‐term endpoints

References

Contact Info

Product

Resources

About