Comparison of absolute benefits of anticancer therapies determined by snapshot and area methods

Abstract

Reporting of relative risk reduction as the measure of treatment effect in randomized clinical trials (RCTs) may be difficult to understand. Here, we compare two methods for assessing absolute benefits of anticancer therapies. We searched PubMed for RCTs comparing therapies for breast and colorectal cancers published 1975-2009 (adjuvant setting) and 2000-2010 (metastatic setting). Eligible trials reported statistically significant differences. Kaplan-Meier curves were assessed for absolute differences in time-to-event end points at a single point (snapshot method) and as the area between curves (area method). Pooled absolute benefits determined by both methods were compared by the Pitman-Morgan test. Eighty-three and 39 paired curves were assessed in the adjuvant and metastatic settings, respectively. In trials of adjuvant therapy, absolute benefits were larger and more variable when assessed at different time points by the snapshot compared with the area method (median and ranges for 60-month difference in overall survival: 7.6% [2.5%-28.4%] and 4.5% [1.8%-13.6%]; P = 0.002, respectively). For metastatic disease, both methods were within 0.5 month of each other in 62% of trials. The area method provides an alternative measure of absolute treatment effect, which uses all of the available data and is less dependent on the shape of survival curves.