Understanding the Value of Real-World Evidence: Focus on Stroke Prevention in Atrial Fibrillation with Rivaroxaban

Abstract

Real-world data are a well-recognized component within the drug lifecycle, and such data are generated from a range of sources and study designs, including claims databases, electronic health records, non-interventional studies (NIS) and registries. While this information can be of vital clinical importance, there may be challenges in understanding the relevance of the differing study designs, endpoints and populations. Here, we summarize the value of real-world evidence and considerations pertinent to their use in clinical research. Owing to the variety of analyses being conducted using real-world data, it is important for researchers and clinicians to have a clear understanding of the nature and origin of those data, and to ensure they are valid, reliable and robust in terms of extrapolating meaningful findings. There are crucial questions to address when evaluating real-world studies, and we introduce a checklist to meet these objectives. In addition to advice for appraising data quality and study designs, several updates will be covered from real-world studies of rivaroxaban for stroke prevention in patients with atrial fibrillation (AF): the nationwide Danish cohort study, U.S. Department of Defense Military Health System database, retrospective claim database study REAFFIRM and a pooled analysis from the global NIS XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation (XANTUS). Real-world studies consistently show that rivaroxaban is an effective treatment option with acceptable safety when used for stroke prevention in a large number of patients with AF across the globe.

Impact of direct oral anticoagulant off‐label doses on clinical outcomes of atrial fibrillation patients: A systematic review

“…Real-world studies are currently regarded as an essential resource for evaluating the long-term safety and effectiveness of DOACs in routine clinical practice, including those patients who may not be represented in randomized controlled trials. 85 In the real-world studies included in this review, most patients with AF treated with a DOAC in the community were receiving doses according to approved labelling but off-label doses still very common across all DOACs and dose levels. Likewise, in this review, most of the studies had dose adjustment percentages between 50 and 75% ( Figure 2D), which can show the discrepancy between recommended doses by the guidelines and those that are used in clinical practice.…”

Effectiveness and Safety of Oral Anticoagulants in Older Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis

“…The included RCTs have many strengths, such as the use of rigorous methodologies, detailed protocols, pre-specified statistical analyses and well-defined patient cohorts (Beyer-Westendorf et al, 2016). However, RCTs are usually underpowered for subgroups analyses and run too short for (long-term) safety outcomes, do not take into account the complexity of real-world clinical decision-making, and difficult-to-reach populations tend to be underrepresented due to ethical and practical considerations (Beyer-Westendorf et al, 2016;Maetens et al, 2016;Camm et al, 2018). The included observational studies tackle these shortcoming in part, including large vulnerable patient subgroups with long follow-up in a real-world setting.…”

Linking the Paul Coverdell National Acute Stroke Program to commercial claims to establish a framework for real-world longitudinal stroke research

“…5 6 Generated evidence needs to be internally valid and generalisable to an identifiable target population in order to be actionable. [31][32][33] A valid evaluation Open access of patients who had a stroke in routine setting of care requires the joint contribution of data sources that can ensure the access to large populations with complete healthcare longitudinal information and rich clinical descriptors. Our study provides evidence that the creation of such a research framework is feasible and can provide a valid platform in which to address a range of clinical and pharmacoepidemiological research questions.…”