Early diagnosis of gestational trophoblastic neoplasia based on trajectory classification with compartment modeling

Abstract

Abstract Background In randomized clinical trials or observational studies, it is common to collect biomarker values longitudinally on a cohort of individuals. The investigators may be interested in grouping individuals that share similar changes of biomarker values and use these groups for diagnosis or therapeutic purposes. However, most classical model-based classification methods rely mainly on empirical models such as splines or polynomials and do not reflect the physiological processes. Methods A model-based classification method was developed for longitudinal biomarker measurements through a pharmacokinetic model that describes biomarker changes over time. The method is illustrated using data on human Chorionic Gonadotrophic Hormone measurements after curettage of hydatidiform moles. Results The resulting classification was linked to the evolution toward gestational trophoblastic neoplasia and may be used as a tool for early diagnosis. The diagnostic accuracy of the pharmacokinetic model was more reproducible than the one of a purely mathematical model that did not take into account the biological processes. Conclusion The use of pharmacokinetic models in model-based classification approaches can lead to clinically useful classifications.

Keywords

• Early diagnosis
• Model-based classification
• CEM algorithm
• Compartment model
• Longitudinal study