Abstract P4-17-02: Guidelines for the definitions of time-to-event endpoints in randomized clinical trials: Results of the datecan project for breast group

Abstract

Abstract Background: Surrogate endpoints of overall survival (OS) are increasingly being used in cancer RCTs with the necessity of reducing randomized clinical trial (RCT) duration, cost and number of patients. However, most of these endpoints currently lack of standardized definition enabling a comparison of RCT results. The objective of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) initiative is to provide guidelines to standardize definitions of time-to-event endpoints in RCTs for different cancer sites. Some recommendations have been proposed for specific cancer sites but they do not rely on a formal consensus methodology. Here, we presented results for BREAST cancer. Methods: We relied on a validated formalized consensus process for the development of practice guidelines using a modified Delphi consensus method. International experts with various backgrounds and expertises were involved. First, the coordinating committee, a group of statisticians and epidemiologists involved in the design and conduct of RCTs, led a comprehensive literature review to identify time-to-event endpoints, events of interest and the existence of guidelines in metastatic and non metastatic settings. The steering committee, which included additional medical experts, validated the list and prepared the questionnaire sent for rating to an independent expert committee. Results: The consensus process involved 2 rounds of scoring (31 experts) and finally one in-person meeting. Each expert had to rate on a 1-9 scale if s/he agreed or not for including events (e.g. death from breast cancer) in the definition of time-to-event endpoints (e.g. progression-free survival). 150 events had to be scored for the 11 selected endpoints. Consensus was reached for 57% of the events after the 2 rounds of scoring. After the in-person meeting, consensus was reached for all the remaining events but one. Conclusions: The DATECAN guidelines should help standardizing definitions of commonly used endpoints. This process should (i) facilitate the comparison of RCTs and (ii) improve the quality of future RCTs by providing better estimation of sample size and treatment effect by disseminating the recommendations in major congress. (previously presented to ASCO’13) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-17-02.