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Published on: July 25, 2020
On the analysis of count data of birth-and-death process type: with application to molecularly targeted cancer
Hao Liu1, Laurel A Beckett, Gerald L DeNardo
1Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis, CA 95616, USA. ucdliu@ucdavis.edu
Abstract:
For molecularly targeted cancer therapy, potency of a novel monoclonal antibody is typically studied in vitro in order to observe directly the effect of the antibody on a malignant tumour cell population. Numbers of viable cells of the population are counted over time to evaluate how the antibody may change the population growth pattern. Usually, such count data is analysed by a log-linear model to estimate the average antibody effects, but it is based on a Poisson-like process and is not appropriate for modelling the growth pattern of the tumour cells. In this paper, we propose to analyse the count data from the point of view of a birth-and-death process, which is a more natural description of the biological process in these experiments. Assuming a simple birth-and-death process and a naïve regression model for the birth rate and death rate, we show that the log-linear relationship still holds for the average count and the covariates, although the linear predictor needs to satisfy a specific functional form. The estimation can be based on the quasi-likelihood method. The variance is not a simple function of the mean, but can be adequately approximated by a function of mean of either quadratic form or linear form, available in most standard statistical packages. We perform a simulation study to show that the proposed method provides consistent and robust estimations. The utility of the method is demonstrated by the analysis of a data set for experiment for anti-lymphoma monoclonal antibodies.
Insights
This study introduces a birth-and-death process model for analyzing cancer cell count data in monoclonal antibody therapy experiments. The new method offers a more biologically accurate approach than traditional log-linear models.
Area of Science:
- Biostatistics
- Cancer Therapy
- Immunology
Background:
- Monoclonal antibodies are crucial for targeted cancer therapy, with in vitro studies assessing their potency on tumor cell populations.
- Current analysis of cell count data often uses log-linear models, which are biologically inappropriate for tumor growth dynamics.
Purpose of the Study:
- To propose a novel statistical approach for analyzing in vitro cancer cell count data using a birth-and-death process model.
- To provide a more biologically relevant framework for evaluating monoclonal antibody efficacy in cancer research.
Main Methods:
- Utilizing a birth-and-death process model to describe tumor cell population dynamics.
- Applying a naive regression model for birth and death rates, with estimation via quasi-likelihood methods.
- Approximating variance using quadratic or linear functions of the mean for statistical package compatibility.
Main Results:
- The proposed birth-and-death model demonstrates that a log-linear relationship persists for average counts and covariates.
- The method yields consistent and robust estimations, as confirmed by simulation studies.
- The approach effectively analyzes experimental data for anti-lymphoma monoclonal antibodies.
Conclusions:
- A birth-and-death process model offers a superior alternative to log-linear models for analyzing in vitro cancer cell growth data.
- This novel statistical framework enhances the accurate assessment of monoclonal antibody potency in cancer therapy research.
- The proposed method is validated and applicable to real-world experimental datasets in oncology.
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