Impact of tumour size measurement inter‑operator variability on model‑based drug effect evaluation

Purpose
During oncology clinical trials, tumour size (TS) measurements are commonly used to monitor disease progression and to assess drug efficacy. We explored inter-operator variability within a subset of a phase III clinical trial conducted from August 1995 to February 1997 and its impact on drug effect evaluation using a tumour growth inhibition model.

Methods
One hundred twenty lesions were measured twice at each time point; once at the hospital and once at the centralised centre. A visual analysis was performed to identify trends within the profiles over time. Linear regression and relative error
ratios were used to explore the inter-operator variability of raw TS measurements and model-based estimates.

Results While correlation between patient-level estimates of drug effect was poor (r2 = 0.28), variability between the studylevel estimates was much less affected (9%).

Conclusions The global evaluation of drug effect using modelling approaches might not be affected by inter-operator variability. However, the exploration of covariates for drug effect and the characterisation of an exposure–tumour shrinkage relationship seems limited by the high measurement variability that translates to a poor correlation of individual drug effect estimates. This might be addressed by the use of more precise computer-aided measurement methods.