Longitudinal Assessment of Hearing Toxicity in a Phase III Clinical Trial for Reduction of Sporadic Adenomas

• Activity Number: 134
• Type: Contributed
• Date/Time: Monday, August 4, 2008 : 10:30 AM to 12:20 PM
• Sponsor: Biometrics Section
• Author(s): Christine E. McLaren*+ and Wen-Pin Chen and Sharon Fujikawa-Brooks and Frank L. Meyskens
• Companies: University of California, Irvine and Chao Family Comprehensive Cancer Center and Chao Family Comprehensive Cancer Center and Chao Family Comprehensive Cancer Center
• Keywords: Clinikcal Trials ; Repeated measures ; GEE ; Toxicity ; Data and Safety Monitoring

Abstract

A DSMB recommended early termination of a Phase III trial in favor of efficacy and requested methodology to assess hearing toxicity. By initial criteria, there were 25 of 136 (18.4%) in the treatment group and 12 of 123 (9.8%) taking placebo who experienced hearing loss (RR, 1.88; 95% CI, 0.99 to 3.59). Treatment groups were similar with regard to time between randomization and the outcome audiogram. Lowess-smoothed profiles showed comparable hearing changes over time. GEE methodology was applied with subjects as clusters and pure tone threshold measured at the end of the therapy as the outcome variable, showing an average of < 2 dB difference in thresholds for the two groups, below the limits of testing accuracy. For assessment of longitudinal toxicity in clinical trials, appropriate methods are necessary to estimate and compare the degree of difference between groups.