Hybrid Study Designs

Summary

Introduces hybrid designs as engineered variants solving specific problems, starting with case-crossover designs that use each person as their own control across time to answer the why-now rather than why-me question, illustrated by Maclure's heart-attack-and-exertion work, Canadian waterborne outbreaks, and a French salmonella outbreak with Mantel-Haenszel matched-pair odds ratios. Develops self-controlled case-series for vaccine safety after Farrington and Whitaker, then case-case, case-case-control, and gene-environment case-only designs for outcome heterogeneity and interaction. Closes with case-cohort designs and two-stage sampling that lets investigators pay for expensive measurement only where it matters most.