Stopping a trial early in oncology: for patients or for

F. Trotta1, G. Apolone2, S. Garattini2 & G. Tafuri1,3*
1Italian Medicines Agency (AIFA), Rome; 2Mario Negri Institute for Pharmacological Research, Milan, Italy; 3Utrecht University, Utrecht Institute for Pharmaceutical
Sciences, Utrecht, The Netherlands
Received 18 December 2007; revised 25 January 2008; accepted 28 January 2008
Background: The aim of this study is to assess the use of interim analyses in randomised controlled trials (RCTs)
testing new anticancer drugs, focussing on oncological clinical trials stopped early for benefit.
Materials and methods: All published clinical trials stopped early for benefit and published in the last 11 years,
regarding anticancer drugs and containing an interim analysis, were assessed.
Results: Twenty-five RCTs were analysed. The evaluation of efficacy was protocol planned through time-related
primary end points, >40% of them overall survival. In 95% of studies, at the interim analysis, efficacy was evaluated
using the same end point as planned for the final analysis. As a consequence of early stopping after the interim
analysis, 3300 patients/events across all studies were spared. More than 78% of the RCTs published in the last 3
years were used for registration purposes.
Conclusion: Though criticism of the poor quality of oncological trials seems out of place, unfortunately early
termination raises new concerns. The relation between sparing patients and saving time and trial costs indicates that
there is a market-driven intent. We believe that only untruncated trials can provide a full level of evidence which can be
translated into clinical practice without further confirmative trials.