Treatment Success in Cancer.

Background: The evaluation of research output, such as an estimation of the proportion of treatments successes is of ethical, scientific, and public importance. How often experimental cancer treatments that undergo testing in randomized clinical trials (RCTs) result in discovery of successful new interventions has rarely been evaluated systematically.

Methods: We evaluated treatment success in a consecutive cohort of RCTs performed by the National Cancer Institute cooperative groups over the past five decades. We investigated therapeutic success in 3 ways:

• assessing the proportion of statistically significant trials favoring new or standard treatments,

• determining the proportion of the trials in which new treatments were considered to be superior to standard treatments according to the original researchers,

• quantitatively synthesizing data for overall survival and event-free survival.

Results: Data from 624 trials (781 randomized comparisons) involving 216,451 patients were analyzed. 30% of trials had statistically significant results. Among these, new interventions were superior to established treatments in 80% of trials. The original researchers judged that the risk-benefit profile favored new treatments in 41% trials. Hazard ratio for survival and event-free survival was 0.95 (99% CI 0.93–0.98) and 0.90 (99%CI 0.87– 0.93) respectively, slightly favoring the new treatments. Breakthrough interventions were discovered in 15% of trials. The main advances have occurred in the management of gastro-intestinal cancer and hematological malignancies

Conclusions: When cancer treatments have been tested in RCTs by the NCI cooperatives groups, about one third of the trials lead to the discovery of successful new treatments. On average, the death rate in these trials has been reduced by 5% with the new treatments. Grant support: NIH/ORI (No 1R01NS044417–01; 5 R01 NS052956–02).