title: Challenging Issues in Clinical Trial Design: Part 4 of a 4-Part Series on Statistics for Clinical Trials.
abstract: As a sequel to last week's paper on the fundamentals of clinical trial design, this paper tackles related controversial issues: noninferiority trials, the value of factorial designs, the importance and challenges of strategy trials, Data Monitoring Committees (including when to stop a trial early), and the role of adaptive designs. All topics are illustrated by relevant examples from cardiology trials.
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address: stuart.pocock@lshtm.ac.uk.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Pocock
authors.affiliation: Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Tim C
authors.initials: TC
authors.lastname: Clayton
authors.affiliation: Columbia University Medical Center, New York-Presbyterian Hospital, and the Cardiovascular Research Foundation, New York, New York.
authors.forename: Gregg W
authors.initials: GW
authors.lastname: Stone
mesh_terms: D002309:Cardiology / Q000379:methods*; D026661:Clinical Trials Data Monitoring Committees; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003627:Data Interpretation, Statistical; D017408:Guidelines as Topic; D006801:Humans
keywords: Data Monitoring Committees; adaptive designs; factorial designs; noninferiority trials; randomized controlled trials as topic; statistical stopping guidelines; strategy trials