Some drop-the-loser designs for monitoring multiple doses

Statistics in Medicine
Y H Joshua ChenK K Gordon Lan

Abstract

A scenario not uncommon at the end of a Phase II clinical development is that although choices are narrowed down to two to three doses, the project team cannot make a recommendation of one single dose for the Phase III confirmatory study based upon the available data. Several 'drop-the-loser' designs to monitor multiple doses of an experimental treatment compared with a control in a pivotal Phase III study are considered. Ineffective and/or toxic doses compared with the control may be dropped at the interim analyses as the study continues, and when the accumulated data have demonstrated convincing efficacy and an acceptable safety profile for one dose, the corresponding dose or the study may be stopped to make the experimental treatment available to patients. A decision to drop a toxic dose is usually based upon a comprehensive review of all the available safety data and also a risk/benefit assessment. For dropping ineffective doses, a non-binding futility boundary may be used as guidance. The desired futility boundary can be derived by using an appropriate combination of risk level (i.e. error rate for accepting null hypothesis when the dose is truly efficacious) and spending strategy (dropping a dose aggressively in early ana...Continue Reading

References

Mar 1, 1990·Statistics in Medicine·B E Storer
May 30, 1993·Statistics in Medicine·M D Hughes
Jun 1, 1993·Controlled Clinical Trials·T R Fleming, D L DeMets
Aug 15, 1998·The New England Journal of Medicine·UNKNOWN Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigato
May 24, 2000·Controlled Clinical Trials·D M ReboussinK K Lan
Sep 12, 2001·Biometrics·M Hellmich
Feb 15, 2003·Statistics in Medicine·Nigel Stallard, Susan Todd
Dec 16, 2006·Clinical Trials : Journal of the Society for Clinical Trials·David L Demets
Sep 19, 2007·Statistics in Medicine·Franz KoenigMartin Posch
Nov 7, 2007·The New England Journal of Medicine·Philip J BarterUNKNOWN ILLUMINATE Investigators
Sep 16, 2008·Statistics in Medicine·Nigel Stallard, Tim Friede

❮ Previous
Next ❯

Citations

Nov 16, 2013·BMC Medical Research Methodology·Daniel J BrattonMahesh K B Parmar
Feb 5, 2013·Expert Opinion on Drug Discovery·Lucas Moreno, Andrew D J Pearson
May 16, 2014·Statistics in Medicine·D MagirrT Jaki
Jun 7, 2014·Journal of Biopharmaceutical Statistics·Joseph WuMark Chang
Jun 14, 2014·Journal of Biopharmaceutical Statistics·Ping GaoCyrus Mehta
Mar 28, 2017·Biometrics·Pranab GhoshCyrus Mehta
May 1, 2014·Therapeutic Innovation & Regulatory Science·Matilde Sanchez-KamThomas Laage

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anxiety Disorders

Discover the latest research on anxiety disorders including agoraphobia, panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder here.