Statistical analysis
tumour
SECONDARY, RECURRENCE, RECRUITMENT, TUMOUR
The sample size of the study was estimated to achieve sufficient power in the assessment of the effect of mitotane on recurrence-free survival (the primary endpoint). Based on retrospective data available at the time the study was designed,The assumed study duration for patients without recurrence was 2 years. In December, 2018, 10 years after the start of the randomised trial, only 91 patients had been enrolled in the randomised ADIUVO trial (recruitment per year is in the Primary and secondary endpoints were analysed on the intention-to-treat population that included all randomly assigned participants. The per-protocol and safety populations included all participants who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. Recurrence-free survival and overall survival in the two groups were estimated with the Kaplan-Meier method and compared using the log-rank test. The Cox's proportional hazard model was used to estimate the hazard ratios (HRs) with 95% CIs. Exploratory post-hoc intention-to-treat comparisons on the risk of recurrence at 5 years were made between treatment assignment and subgroups of interest defined by demographic characteristics (age and sex) and clinical characteristics (tumour size, stage, preoperative hormone secretion, Ki67 index, and surgical approach) at baseline, using a set of Cox's proportional hazard models that included an interaction term between the treatment assignment and the subgroup variable. Time to recurrence, defined as the time from randomisation to the time of recurrence, was also assessed. Data are restricted mean survival time and 95% CI, since the median survival was not reached.The proportionality of hazards was checked using graphical diagnostics based on the scaled Schoenfeld residuals. Continuous variables are presented as medians and IQRs and were compared between groups using Mann-Whitney In the ADIUVO Observational study, recurrence-free survival and overall survival in the mitotane and surveillance groups were compared using a Cox model, after adjusting for baseline covariate unbalances with an inverse probability weighting (IPW) approach based on propensity score (All group comparisons in both studies were made with the use of a two-sided test at an α level of 5%. An independent data and safety monitoring board supervised the collection of efficacy and safety data. Statistical analyses were done with R (version 4.0.2) and SAS (version 9.4).The ADIUVO trial is registered with 