Compliance as an Explanatory Variable in Hepatitis-C

Abstract

A Hepatitis C clinical trial program for patients infected with Hepatitis C virus of genotype I demonstrated that the sustained virologic response rate is higher with 48 weeks of Ribavirin in combination with Interferon (I/R) than with 48 weeks of interferon and placebo (UP). The intent-to-treat (ITT) response rate for the I/R group is 29%, versus 9% for the UP group. However, since not all patients completed their treatment, it is likely that the benefit would have been greater if all the patients had taken their full dose for 48 weeks. Assessing the impact of taking the full dose is not trivial; clearly the ITT approach underestimates the response, whereas subsetting the patients who took a large majority of their full dose (eg, 80% of the total dose) likely overestimates the response. Using methodology developed by Efron and Feldman (I), we develop a statistical model that incorporates compliance as a covariate, thereby allowing for an estimate of the fully compliant response rate. It is estimated that the treatment benefit as measured by the difference in sustained virologic response rates of I/R versus UP at full compliance ranged from 23% to 26% compared to 20% for the ITT analysis and 27% for the 80% compliant subgroup.