Up-front matching: an ongoing recruitment method for prospective observational studies that mimics randomization for selected baseline covariates.

In a prospective observational study (POS) designed to assess the average causal effect of a treatment (e.g. Drug A) compared to a comparator (e.g. Drug B) in the treatment population, enrolling all patients who are assigned to the treatments of interest for follow-up has a potentially large negative impact on the statistical efficiency and bias of the analysis of the outcomes and on the cost of the study. "Up-front matching" is an innovative enrollment method for selecting patients for long-term follow-up among those who have already been assigned to treatment or comparator which uses frequency matching and hence avoids the restrictions of individual matching that other methods have used. To achieve potential statistical and logistical efficiencies in the POS, in up-front matching, a target population is defined based on a retrospective database which then enables selecting populations of patients for follow-up that have desirable statistical properties. In particular, the resulting populations of patients who are enrolled look like the population of treatment patients were randomized to treatment or comparator for the baseline covariates that are used to select patients for follow-up. The method is illustrated in detail for a study designed to assess the effect of injectable antipsychotics versus oral antipsychotics.