Enrichment design with patient population augmentation

Contemporary Clinical Trials
Bo YangLu Cui

Abstract

Clinical trials can be enriched on subpopulations that may be more responsive to treatments to improve the chance of trial success. In 2012 FDA issued a draft guidance to facilitate enrichment design, where it pointed out the uncertainty on the subpopulation classification and on the treatment effect outside of the identified subpopulation. We consider a novel design strategy where the identified subpopulation (biomarker-positive) is augmented by some biomarker-negative patients. Specifically, after sufficiently powering biomarker-positive subpopulation we propose to enroll biomarker-negative patients, enough to assess the overall treatment benefit. We derive a weighted statistic for this assessment, correcting for the disproportionality of biomarker-positive and biomarker-negative subpopulations under enriched trial setting. Screening information is utilized for weight determination. This statistic is an unbiased estimate of the overall treatment effect as that in all-comer trials, and is the basis to power for the overall treatment effect. For analysis, testing will be first performed on biomarker-positive subpopulation; only if treatment benefit is established in this subpopulation will overall treatment effect be tested usi...Continue Reading

References

Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard Simon, Aboubakar Maitournam
Nov 20, 2004·Statistics in Medicine·A Maitournam, R Simon
Oct 21, 2005·The New England Journal of Medicine·Martine J Piccart-GebhartUNKNOWN Herceptin Adjuvant (HERA) Trial Study Team
Feb 24, 2006·The New England Journal of Medicine·Heikki JoensuuUNKNOWN FinHer Study Investigators
Aug 11, 2007·Pharmaceutical Statistics·Sue-Jane WangH M James Hung
Nov 6, 2007·The New England Journal of Medicine·Stephen D WiviottUNKNOWN TRITON-TIMI 38 Investigators
Mar 28, 2008·The New England Journal of Medicine·Soonmyung PaikNorman Wolmark
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard Simon
Apr 10, 2009·Biometrical Journal. Biometrische Zeitschrift·Sue-Jane WangRobert T O'Neill
Jan 16, 2010·Journal of the National Cancer Institute·Boris FreidlinEdward L Korn
Aug 11, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Edith A PerezRobert B Jenkins
Mar 26, 2013·Biostatistics·Noah Simon, Richard Simon
Jun 7, 2013·Cancer Research·Hasan Korkaya, Max S Wicha
Sep 26, 2013·Contemporary Clinical Trials·Howard M Mackey, Thomas Bengtsson
Oct 8, 2013·Journal of the National Cancer Institute·Fangxin Hong, Richard Simon

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Citations

Sep 18, 2018·Statistics in Medicine·Ting WangStephen L George
Sep 22, 2017·Journal of Biopharmaceutical Statistics·Xiaofei WangStephen L George
Nov 28, 2017·Journal of Biopharmaceutical Statistics·Weidong ZhangSandeep Menon

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