1 / 15

Phase II Design Strategies

Phase II Design Strategies. Sally Hunsberger Ovarian Cancer Clinical Trials Planning Meeting May 29, 2009. Single arm Phase II study. Fact or fiction: Using single arm phase II study designs reduces the number of patients needed in drug development.

miya
Download Presentation

Phase II Design Strategies

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Phase II Design Strategies Sally Hunsberger Ovarian Cancer Clinical Trials Planning Meeting May 29, 2009

  2. Single arm Phase II study • Fact or fiction: • Using single arm phase II study designs reduces the number of patients needed in drug development

  3. True: If the specified null rate is correct • How bad can things get if the null rate is specified incorrectly? • Need to consider the drug development cost (in terms of patients) • End of phase II if don’t go to phase III • End of phase II if go to phase III

  4. Evaluation of designs • Look at expected sample size E[N] • E[N]=NII+NIII(P{continuing to phase III})

  5. Phase II Design parameters • PFS as primary endpoint • Type I error and II error of .1 • Median null PFS = 3 months • Interesting activity would result in a median PFS of 4.5 (hazard ratio=1.5) • Minimum follow up=3 months • Sample size = 69

  6. Phase III design parameters • OS as primary endpoint • Type I error 1-sided .025 • Median null OS = 6 months • Interesting activity would result in a median OS of 7.8 (hazard ratio=1.3) • Minimum follow up = 6 months • Sample size = 692

  7. Under the null of no treatment benefit • What happens if we set the null bar too low • Go to phase III too often and this will increase the Expected sample size,E[N].

  8. Under null hypothesis of no Treatment effect Null assumption is 3 months *Truth agrees with assumption. E[N] for a randomized phase II study is 271 with α=β=.1

  9. Under the alternative of a treatment benefit • What happens if we set the null bar too high • Do not go to phase III often enough • This will decrease power of finding a treatment benefit at the end of drug development

  10. Under Alternative hypothesis of a Treatment effect Null assumption is 3 months Treatment benefit of a hazard ratio of 1.5 *Truth agrees with assumption. Probability of concluding a benefit when a randomized phase II study is used .81

  11. If we need a randomized phase II how can we speed up drug development • Phase II/III design • Futility analysis based on PFS • Study power for a conclusion on OS

  12. Simulation study results • Performed simulation study so I could have correlated PFS and OS • Comparison designs: • Sequence of a randomized phase II study and then a randomized phase III • Skip phase II go right to a phase III with a futility analysis based on OS (appropriate if you don’t expect an effect on PFS)

  13. Over all probability of concluding a benefit when it exists is .81

  14. Conclusions • Single arm studies may appear to use less patients but if the null bar is set incorrectly this could have a major impact on E[N] and the probability of identifying a beneficial treatment • When there is no true treatment effect setting the bar two low increases the E[N] • When there is a true treatment effect and the bar is set too high the probability of identifying a beneficial treatment is reduced

  15. Conclusions • integrated phase II/III design works well under the global null. • E[N] and E[T] were no larger than that of a randomized phase II study • E[N] and E[T] smaller than skipping the phase II study • integrated II/III better than the separate randomized phase II study under the global alternative • did not increase E[T] and E[N] when compared to skipping the phase II component.

More Related