Reporting of cause-specific treatment effects in cancer clinical trials with competing risks: a systematic review

Separate analysis of cause-specific treatment effects is important for interpreting results of randomized trials. We sought to determine the extent to which cause-specific effects on primary events are reported in contemporary randomized controlled trials in oncology.

We screened 833 randomized trials published in eight leading medical journals between January 2006 and December 2009. We excluded prevention studies (n=52), secondary reports (n=100), and one retracted study. Analysis was further restricted to 116 trials in non-metastatic/recurrent cancer that used an event-free survival primary endpoint. For each study included in the analysis, we evaluated whether treatment effects on both cancer and non-cancer events comprising the primary endpoint were reported separately and whether statistical analysis was provided.

Of the 116 randomized trials, 47 (40%; 95% confidence interval (CI), 32-50%) reported effects on both cancer and non-cancer events comprising the primary endpoint, with statistical analysis provided in 13 (11%; 95% CI, 7-19%). Twenty-six trials (22%; 95% CI, 15-31%) reported effects on cancer but not non-cancer events, with statistical analysis provided in 11 (9%; 95% CI, 5-17%). In 43 studies (37%; 95% CI, 28-47%), no effects on cancer-specific components of the primary endpoint were given. Of these, 33 studies (28%; 95% CI, 21-38%) did report effects on some cancer-specific event, while ten (9%; 95% CI, 4-16%) did not report effects of treatment on any cancer event.

Many randomized trials in oncology do not report cause-specific effects on primary events. Increased specificity is needed in the design and reporting of cancer clinical trials.