title: Challenges of clinical trial design when there is lack of clinical equipoise: use of a response-conditional crossover design.
abstract: Clinical equipoise is widely accepted as the basis of ethics in clinical research and requires investigators to be uncertain of the relative therapeutic merits of trial comparators. When clinical equipoise is in question, innovative trial designs are needed to reduce ethical tension while satisfying regulators' requirements. We report a novel response-conditional crossover study design used in a Phase 3, randomized, double-blind, placebo-controlled clinical trial of intravenous 10% caprylate-chromatography purified immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. During the initial 24-week period, patients crossed over to the alternative treatment at the first sign of deterioration or if they failed to improve or were unable to maintain improvement at any time after 6 weeks. This trial design addressed concerns about lack of equipoise raised by physicians interested in trial participation and proved acceptable to regulatory authorities. The trial design may be applicable to other studies where clinical equipoise is in question.
authors.affiliation: Grifols Inc. (formerly Talecris Biotherapeutics), 79 TW Alexander Drive, Research Triangle Park, Durham, NC 27709, USA. CQ.Deng@Talecris.com
authors.forename: Chunqin
authors.initials: C
authors.lastname: Deng
authors.forename: Kim
authors.initials: K
authors.lastname: Hanna
authors.forename: Vera
authors.initials: V
authors.lastname: Bril
authors.forename: Marinos C
authors.initials: MC
authors.lastname: Dalakas
authors.forename: Peter
authors.initials: P
authors.lastname: Donofrio
authors.forename: Pieter A
authors.initials: PA
authors.lastname: van Doorn
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Ingemar S J
authors.initials: IS
authors.lastname: Merkies
mesh_terms: D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000188:drug therapy*; D012107:Research Design; D057212:Therapeutic Equipoise
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors