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Cancer Chemotherapy and Pharmacology

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Open Access 01-04-2020 | Original Article

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

Authors: Aurélie Lombard, Hitesh Mistry, Sonya C. Chapman, Ivelina Gueoguieva, Leon Aarons, Kayode Ogungbenro

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2020

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.

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Title: Impact of tumour size measurement inter-operator variability on model-based drug effect evaluation
Authors: Aurélie Lombard
Hitesh Mistry
Sonya C. Chapman
Ivelina Gueoguieva
Leon Aarons
Kayode Ogungbenro
Publication date: 01-04-2020
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04049-5

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Abstract

Purpose

Methods

Results

Conclusions

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