Using causal frameworks to reduce bias in observational TB research: a comparison of model-building approaches.

BACKGROUND: Observational studies investigating causal (aetiological) questions often address confounding bias using data-driven predictive models where variables are selected regardless of their causal role, challenging interpretation. We compared the estimated effect of HIV co-infection on end-of-treatment outcomes among people with multidrug/rifampicin-resistant TB using a causal framework model and a data-driven predictive model.

METHODS: The causal framework guided confounder adjustment. Results were compared to those from models that applied alternative variable selection strategies (based on values and change-in-estimate), which do not draw on domain knowledge to identify relevant variables.

RESULTS: The model informed by a causal diagram indicated that people living with HIV had a 31% lower probability of achieving a successful outcome compared to those without HIV (adjusted relative risk [aRR] 0.69, 95% confidence interval [CI]: 0.41-0.98). In contrast, data-driven models produced attenuated associations (aRR 0.78, 95% CI: 0.50-1.06 and aRR 0.80, 95% CI: 0.5-1.09 for the value and change-in-estimate strategies, respectively), reflecting omission of key confounders, and inappropriate inclusion of mediators and colliders.

DISCUSSION: When the research question is aetiological, using a causal approach to guide variable selection ensures proper adjustment, improves interpretability, and establishes a stronger foundation for future observational research.

© 2026 The Authors.