Circulating Tumour DNA Analysis Informing Adjuvant Chemotherapy in Stage II Colon Cancer (DYNAMIC Trial): Statistical Analysis Plan

BACKGROUND: Detection of circulating tumour DNA (ctDNA) after curative intent treatment reflects the presence of minimal residual disease and predicts for recurrence. DYNAMIC trial is a randomised phase II investigating the clinical utility of ctDNA-guided adjuvant treatment strategy compared with the standard of care (non-ctDNA based) approach in patients with stage II colon cancer. The primary trial endpoint is recurrence-free survival estimated from Kaplan Meier Method at 2 years. Secondary endpoints include proportion of patients treated with adjuvant chemotherapy, time-to-recurrence, overall survival, ctDNA clearance rate (investigational arm) and quality-adjusted life-years. OBJECTIVE: To outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis. METHODS: The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data. TRIAL REGISTRATION: ANZ Clinical Trials Registry, ACTRN12615000381583. Registered on 27th April 2015.