Impact of Biomarker-based Design Strategies on the Risk of False-Positive Findings in Targeted Therapy Evaluation

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Tat-Thang VoRaphaël Porcher

Abstract

When there is more than one potentially predictive biomarker for a new drug, the drug is often evaluated in different subpopulations defined by different biomarkers. We aim to (i) estimate the risk of false-positive findings with this approach and (ii) evaluate the cross-validated adaptive signature design (CVASD) as a potential alternative. By using numerically simulated data, we compare the current approach and the CVASD across different settings and scenarios. We consider three strategies for CVASD. The first two CVASD strategies are different in terms of the partitioning of the overall significance level (between the population test and the subgroup test). In the third CVASD strategy, the order of the two tests is reversed, that is, the population test is realized when the prioritized subgroup test is not statistically significant. The current approach results in a high risk of false-positive findings, whereas this risk is close to the nominal level of 5% once applying the CVASD, regardless of the strategy. When the treatment is equally effective to all patients, only the CVASD strategies could specify correctly the absence of a sensitive subgroup. When the treatment is only effective for some sensitive responders, the thir...Continue Reading

References

Nov 10, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Boris Freidlin, Richard Simon
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard Simon
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Boris FreidlinRichard Simon
Jan 16, 2010·Journal of the National Cancer Institute·Boris FreidlinEdward L Korn
Oct 15, 2010·Clinical Pharmacology and Therapeutics·R Temple
Jun 7, 2011·JAMA : the Journal of the American Medical Association·Aaron S KesselheimJerry Avorn
Aug 5, 2011·Statistics in Medicine·Jared C FosterStephen J Ruberg
May 4, 2012·Biometrics·Baqun ZhangMarie Davidian
Jun 22, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Parvin TajikPatrick M Bossuyt
Aug 10, 2013·Genetics in Medicine : Official Journal of the American College of Medical Genetics
Nov 28, 2013·Nature Reviews. Clinical Oncology·Boris Freidlin, Edward L Korn
Jan 8, 2014·Journal of Biopharmaceutical Statistics·Nigel StallardTim Friede
Sep 2, 2014·European Respiratory Review : an Official Journal of the European Respiratory Society·Jessica MenisBenjamin Besse
Dec 19, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Alexandre VivotRaphaël Porcher
May 21, 2015·American Society of Clinical Oncology Educational Book·Sumithra J MandrekarRichard Simon
Aug 1, 2015·Nature Reviews. Drug Discovery·Asher Mullard
Oct 6, 2015·Nature Reviews. Drug Discovery·Nicholas S DowningNilay D Shah
Dec 4, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Patricia DeverkaSean R Tunis
Dec 19, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Alexandre VivotRaphaël Porcher
May 24, 2016·Annals of Internal Medicine·Richard Simon
Dec 9, 2016·JAMA Oncology·Howard Jack West
Feb 14, 2017·JAMA Internal Medicine·Mark J Pletcher, Charles E McCulloch
Apr 6, 2017·The New England Journal of Medicine·Nicholas S DowningJoseph S Ross
Sep 26, 2017·Journal of the American Statistical Association·Xin ZhouMichael R Kosorok

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Citations

Jul 11, 2019·Contemporary Clinical Trials Communications·Arinjita Bhattacharyya, Shesh N Rai

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