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

Abstract

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 study-level 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.