title: A meta-analytic approach to an integrated summary of efficacy: a case study of becaplermin gel.
abstract: This paper presents a case study involving a meta-analytic approach for an integrated summary of efficacy based upon four phase II and III clinical trials that comprised the basis for a Biologics License Application to the U.S. Food and Drug Administration for approval of becaplermin gel. There were substantial variations in observed response rates across the four studies that were of concern to regulatory agencies. Due to these variations and because there were various treatment combinations in the four trials, standard statistical methods for an integrated analysis of efficacy were problematic. A meta-analytic model that focused on the variations of concern was employed to permit a suitable integrated analysis. The resulting integrated analysis clarified response rate variability and provided accurate estimates of treatment effects based upon the four clinical trials. While this meta-analysis was viewed by neither regulators nor the sponsor as a confirmatory analysis, it was seen by both regulators and sponsor as strongly supportive of the efficacy of becaplermin gel.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, NJ 08869, USA. bperry@prdus.jnj.com
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Perry
authors.forename: Allan R
authors.initials: AR
authors.lastname: Sampson
authors.forename: Barry H
authors.initials: BH
authors.lastname: Schwab
authors.forename: M Rezaul
authors.initials: MR
authors.lastname: Karim
authors.forename: Janice M
authors.initials: JM
authors.lastname: Smiell
mesh_terms: D000925:Anticoagulants; D000077214:Becaplermin; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval / Q000379:methods*; D005782:Gels; D006801:Humans; D016015:Logistic Models; D015201:Meta-Analysis as Topic; D015233:Models, Statistical; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D014456:Ulcer / Q000188:drug therapy; D014481:United States; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000925:Anticoagulants; D005782:Gels; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin