Defining key design elements of registry-based randomised controlled trials: a scoping review

Abstract

Background Traditional randomised controlled trials remain the gold standard for improving clinical care but they do have their limitations, including their associated high costs, high failure rate and limited external validity. An alternative methodology is the newly defined, prospective, registry-based randomised controlled trial (RRCT), where treatment and outcome data is collected in an existing registry. This scoping review explores the current literature regarding RRCTs to help identify the key design elements of RRCTs and the characteristics of clinical registries on which they are reliant on. Methods A scoping review methodology conducted in accordance with the Joanna Briggs Institute guidelines was performed. Four databases were searched for articles published from inception to June 2018: Medline; Embase; the Cumulative Index to Nursing and Allied Health Literature and; Scopus. The search strategy included MeSH and text words related to RRCT. Results We identified 2369 articles of which 75 were selected for full-text screening. Of these, only 17 articles satisfied our inclusion criteria. All studies were published between 1996 and 2017 and all were investigator-initiated. Study designs were mainly multi-site comparative/effectiveness studies incorporating the use of disease registries (n = 8), procedure registries (n = 8) and a health services registry (n = 1). The low cost, reduced administrative burden and enhanced external validity of RRCTs make them an attractive research methodology which can be used to address questions of public health importance. We identified that that there are variable definitions of what constituted a RRCT and that issues related to ethical conduct and data integrity, completeness, timeliness, validation and endpoint adjudication need to be carefully addressed. Conclusion RRCTs potentially have an important role to play in informing best clinical practice and health policy. There are a number of issues that need to be addressed to optimise the utility of this approach, including establishing universally accepted criteria for the definition of a RRCT.

Realising the potential: leveraging clinical quality registries for real world clinical research

“…The potential advantages of registry‐based clinical trials to evaluate interventions compared with standard randomised controlled trials (RCTs) have been well documented 5‐9 . A major benefit is that registry‐based trials can represent broader population groups.…”

“…Where registry‐based trials are particularly suited is in comparative studies of real world outcomes of different existing clinical care practices 5 . A 2020 scoping review noted, based on a strict definition of a registry‐based RCT, that there were 17 outcome trials in the literature published between 1996 and 2017, predominantly from European countries or the United States, and one from Australia 5 .…”

“…Where registry‐based trials are particularly suited is in comparative studies of real world outcomes of different existing clinical care practices 5 . A 2020 scoping review noted, based on a strict definition of a registry‐based RCT, that there were 17 outcome trials in the literature published between 1996 and 2017, predominantly from European countries or the United States, and one from Australia 5 . This highlights the extent of the missed opportunity of registry‐based trials, from both a lack of explicit support from research funding bodies until very recently, and challenges with implementation.…”

“…Registry‐based trials have several different characteristics, some of which may pose methodological and other challenges or uncertainty compared with traditional trial methods. Additionally, within this relatively new area of research methodology, no agreed approaches, or standardised methods to undertake registry‐based trials yet exist, and their processes, data and reporting are neither uniform nor standardised 5,7 . This is currently limiting the potential use and uptake of registry‐based trials as a scientifically validated approach to answering research questions.…”

Mapping the Landscape of Surgical Registries in the United Kingdom: A Review According to the SWiM Methodology

“…Well-designed registries have the potential to support high-quality efficient research including registry-based randomised control trials (RCTs) [ 9 10 ] that are increasingly utilised to overcome the traditional barriers to RCTs including high cost and complexity. Hypothesised variation in the design of existing surgical registries may limit this potential.…”