A two-component nonlinear mixed effects model for longitudinal data, with application to gastric emptying studies.

Area of Science:

• Biomedical research
• Pharmacokinetics and toxicokinetics
• Physiological research

Background:

• Gastric emptying studies are crucial in human and veterinary medicine to assess treatments and side effects.
• Current scintigraphy methods often use the power exponential model, which has limitations in describing localized gastric events.
• Accurate summarization of gastric emptying data is essential for comparing study results and treatment effects.

Purpose of the Study:

• To develop a novel mixture model for gastric emptying studies that improves population and individual inferences.
• To enhance the description of gastric emptying patterns by incorporating both global and local intragastric events.
• To provide a more accurate representation and summary of gastric emptying curves through interpretable model parameters.

Main Methods:

• A two-component nonlinear mixed effects model was developed, combining a power exponential model for global patterns and a locally extended power exponential model for local events.
• Two fitting methods were proposed: a mixture of Expectation Maximization (EM) and a global two-stage method, and a mixture of EM and the Monte Carlo EM algorithm.
• Model performance and fitting approaches were compared using simulation studies.

Main Results:

• The proposed two-component nonlinear mixed effects model accurately captures both global and local gastric emptying patterns.
• Both developed fitting methods demonstrated comparable performance in simulations.
• The Monte Carlo EM-based approach showed improved efficiency and numerical stability for variance-covariance matrix estimation in certain cases.

Conclusions:

• The new model offers a more comprehensive analysis of gastric emptying compared to traditional methods.
• The developed fitting approaches are robust and suitable for complex gastric emptying data.
• This model and methodology are broadly applicable to human and veterinary medical research, including pharmacokinetics, toxicokinetics, and physiological studies.