Realizing the Full Potential of Registry-Based Randomized Controlled Trials

CONTEXT: Advantages of registry-based randomized controlled trials (RRCTs) include their relatively low-cost and ability to recruit many individuals. Notably, the registry infrastructure captures data on all individuals, which facilitates a direct comparison of the baseline characteristics of enrolled and non-enrolled individuals. IMPORTANCE: Decision-makers can then assess how representative the trial population is of the target population to which the results are intended to be applied. CURRENT CHALLENGES: There are two important factors that must be considered. First, a potentially overlooked issue is the differing proportion of missing baseline data for enrolled and non-enrolled individuals. This discrepancy may be attributable to the individuals' underlying clinical condition, their level of healthcare engagement, or their clinicians' awareness of their enrolment status. The data is therefore likely to be missing not at random, and comparisons of baseline characteristics may not be valid. Second, it is important to consider whether non-enrolled individuals would be eligible for the trial's target population, where only clinically ineligible individuals should be excluded. Individuals who are not enrolled because they do not or cannot consent, or were not asked, should therefore be included. However, many trials, including RRCTS, do not always explicitly report the reasons for non-enrolment. OPPORTUNITIES: To take full advantage of RRCTs, we recommend 1) reporting the proportion of missing data for baseline characteristics of both enrolled and non-enrolled individuals, and 2) reporting the reasons for non-enrolment, and 3) restricting comparisons of baseline characteristics to those enrolled in the trial, and those who would be in the trials' target population.