Optimal multiwave validation of secondary use data with outcome and exposure misclassification.

Observational databases provide unprecedented opportunities for secondary use in biomedical research. However, these data can be error-prone and must be validated before use. It is usually unrealistic to validate the whole database because of resource constraints. A cost-effective alternative is a two-phase design that validates a subset of records enriched for information about a particular research question. We consider odds ratio estimation under differential outcome and exposure misclassification and propose optimal designs that minimize the variance of the maximum likelihood estimator. Our adaptive grid search algorithm can locate the optimal design in a computationally feasible manner. Because the optimal design relies on unknown parameters, we introduce a multiwave strategy to approximate the optimal design. We demonstrate the proposed design's efficiency gains through simulations and two large observational studies.