Routinely collected data for randomized trials: promises, barriers, and implications

Abstract

Background: Routinely collected health data (RCD) are increasingly used for randomized controlled trials (RCTs). This can provide three major benefits: increasing value through better feasibility (reducing costs, time, and resources), expanding the research agenda (performing trials for research questions otherwise not amenable to trials), and offering novel design and data collection options (e.g., point-of-care trials and other designs directly embedded in routine care). However, numerous hurdles and barriers must be considered pertaining to regulatory, ethical, and data aspects, as well as the costs of setting up the RCD infrastructure. Methodological considerations may be different from those in traditional RCTs: RCD are often collected by individuals not involved in the study and who are therefore blinded to the allocation of trial participants. Another consideration is that RCD trials may lead to greater misclassification biases or dilution effects, although these may be offset by randomization and larger sample sizes. Finally, valuable insights into external validity may be provided when using RCD because it allows pragmatic trials to be performed.

Methods: We provide an overview of the promises, challenges, and potential barriers, methodological implications, and research needs regarding RCD for RCTs.

Results: RCD have substantial potential for improving the conduct and reducing the costs of RCTs, but a multidisciplinary approach is essential to address emerging practical barriers and methodological implications.

Conclusions: Future research should be directed toward such issues and specifically focus on data quality validation, alternative research designs and how they affect outcome assessment, and aspects of reporting and transparency.

Keywords: Clinical epidemiology; Electronic health records; Evidence-based medicine; Registries; Routinely collected health data; Trials.

Fig. 1

The role of routinely collected health data (RCD) in randomized controlled trials in various phases of a clinical trial (based on the Consolidated Standards of Reporting Trials [CONSORT] flow diagram [11]). (1) During enrollment, RCD sources can be screened retrospectively for eligible patients, but they can also be used prospectively as targeted screening and recruitment tools. (2) Informed consent could be given both for data use and for trial participation, so that when patients decline to participate in the randomized component of the trial, their usual care can still be followed. (3) Allocation can be facilitated by RCD through point-of-care randomization. Patients who are not allocated to an intervention but select care on the basis of personal and clinical preferences can be observed with RCD. (4) During the follow-up phase, RCD allows patients who would otherwise be lost to follow-up to be tracked, and thus less missing data may be encountered. (5) Long-term follow-up, such as in registries, may be possible with RCD even after formal completion of the primary study phase. (6) RCD allows analysis of both nonrandomized and randomized patients and direct supplementation of information to the randomized part of the trial