The increasing prevalence of rich sources of data and the availability of electronic medical record databases and electronic registries opens tremendous opportunities for enhancing medical research. For example, controlled trials are ubiquitously used to investigate the effect of a medical treatment, perhaps dependent on a set of patient covariates, and traditional approaches have relied primarily on randomized patient sampling and allocation to treatment and control group. However, when covariate data for a large cohort group of patients have already been collected and are available in a database, one can potentially design a treatment/control sample and allocation that provides far better estimates of the covariate-dependent effects of the treatment. In this paper, we develop a new approach that uses optimal design of experiments (DOE) concepts to accomplish this objective. The approach selects the patients for the treatment and control samples upfront, based on their covariate values, in a manner that optimizes the information content in the data. For the optimal sample selection, we develop simple guidelines and an optimization algorithm that provides solutions that are substantially better than random sampling. Moreover, our approach causes no sampling bias in the estimated effects, for the same reason that DOE principles do not bias estimated effects. We test our method with a simulation study based on a testbed data set containing information on the effect of statins on low-density lipoprotein (LDL) cholesterol.
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