Utilizing Multiple Biomarkers To Assess Myocardial Function in a Dose-Finding Study: Determining the Optimal Dose by 'Scoring' the Outcomes

• Activity Number: 329
• Type: Topic Contributed
• Date/Time: Tuesday, July 31, 2007 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Cynthia L. Green*+ and Kathleen Trollinger and Saling Huang and Matthew Roe
• Companies: Duke Clinical Research Institute and Duke Clinical Research Institute and KAI Pharmaceuticals and Duke Clinical Research Institute
• Keywords: surrogate ; biomarkers

Abstract

Biomarkers are often chosen as primary endpoints in Phase I/II trials. Biomarkers are intended to simulate the effect of the treatment on clinical outcome by providing a surrogate known to have strong effects on measures of the biological process. Multiple biomarkers have been studied which correlate to myocardial function, including TIMI flow, enzymes, sestamibi scans, ejection fraction and ST resolution. The DELTA-MI study evaluated the safety and efficacy of KAI-9803 in 154 patients with acute MI. Subjects were randomized 2:1 to KAI-9803 or placebo into one of four dosing groups (0.05, 0.5, 1.25 and 5.0 mg). Multiple biomarkers of myocardial function were analyzed to determine the optimal dosing level. Our goal was to provide a statistical model to determine the optimal dose by "scoring" the direction and amount of treatment benefit for each biomarker within each dose group.