Part I: *Can we fix it in the mix?* A Practical Introduction to Mixed Models

Mixed models are a powerful statistical tool used to model data that have both fixed and random effects. They are particularly useful when data exhibit grouping or hierarchical structure, as is common in longitudinal studies, clinical trials, and multi-center studies.

Fixed Effects and Random Effects

  • Fixed effects: These are the effects we are specifically interested in estimating. For example, the effect of a treatment in a clinical trial.
  • Random effects: These account for the variability due to random differences in groups or subjects that aren’t of direct interest but must be controlled for.

Mixed Model Equation

A simple linear mixed model can be represented as:

$$ y_{ij} = \beta_0 + \beta_1 X_{ij} + u_j + \epsilon_{ij} $$

Where:

  • $y_{ij}$ is the observed outcome for the $i$-th observation in group $j$,
  • $\beta_0$ and $\beta_1$ are the fixed effect coefficients,
  • $X_{ij}$ is the fixed effect predictor for the $i$-th observation in group $j$,
  • $u_j$ is the random effect for group $j$, assumed to be normally distributed with mean 0 and variance $\sigma_u^2$,
  • $\epsilon_{ij}$ is the residual error, assumed to be normally distributed with mean 0 and variance $\sigma_\epsilon^2$.

Interpreting Mixed Models

In a mixed model, fixed effects are treated as parameters to be estimated, while random effects are treated as draws from a distribution (usually normal). The random effects introduce correlation within groups and allow for the modeling of intra-group variability.

Example Application

Mixed models are commonly applied in longitudinal data analysis, where repeated measurements are taken on subjects over time. They can also be used in multi-level data, such as students nested within schools, patients within hospitals, or animals within treatments.

Animation: Understanding Random Effects

[Insert Animation of Random Effects Here]

This animation shows how random effects vary across groups, explaining the difference between fixed effects (consistent across all groups) and random effects (varying by group).

Model Fitting

Mixed models can be fit using several software tools, such as R’s lme4 package. The typical steps involve:

  1. Specifying the model,
  2. Estimating parameters for fixed and random effects,
  3. Checking assumptions (normality of random effects, etc.),
  4. Interpreting the results.
# R code to fit a mixed model
library(lme4)
model <- lmer(y ~ X + (1|group), data = your_data)
summary(model)
Vishal Sarsani
Vishal Sarsani
Computational Scientist

An applied statistician working in translational omics and biomarker discovery