The Open Hand Initiative: Facilitating the Use of Real-World Evidence in Regulatory Submissions Through Collaboration and Transparency.

Real-world data (RWD) collected to generate real-world evidence (RWE) holds promise for expediting patient and healthcare provider access to new in vitro diagnostics (IVDs) by serving as evidence to demonstrate test performance or utility. However, uncertainties remain for IVD developers (device manufacturers), regulators, and other healthcare stakeholders on the specifics of collecting fit-for-purpose RWD and using RWE for regulatory decision-making. We report on a unique approach to medical device regulatory review called the Open Hand Initiative, by which the US Food and Drug Administration (FDA) and device manufacturers collaborate to ensure the appropriate use of RWD/RWE to support regulatory decision-making.

The Current Landscape and Emerging Applications for Real-World Data in Diagnostics and Clinical Decision Support and its Impact on Regulatory Decision Making.

Real-world data (RWD) and real-world evidence (RWE) are becoming essential tools for informing regulatory decision making in health care and offer an opportunity for all stakeholders in the healthcare ecosystem to evaluate medical products throughout their lifecycle. Although considerable interest has been given to regulatory decisions supported by RWE for treatment authorization, especially in rare diseases, less attention has been given to RWD/RWE related to in vitro diagnostic (IVD) products and clinical decision support systems (CDSS). This review examines current regulatory practices in relation to IVD product development and discusses the use of CDSS in assisting clinicians to retrieve, filter, and analyze patient data in support of complex decisions regarding diagnosis and treatment.

Application of Real-World Data to External Control Groups in Oncology Clinical Trial Drug Development.

Randomized controlled trials (RCTs) that assess overall survival are considered the "gold standard" when evaluating the efficacy and safety of a new oncology intervention. However, single-arm trials that use surrogate endpoints (e.g.

Defining Clinically Relevant Target Populations Using Real-World Data to Guide the Design of Representative Antidiabetic Drug Trials.

The US Food and Drug Administration is considering replacing cardiovascular outcome trials of antidiabetic drugs with trials that better represent patients with type 2 diabetes. However, designing such representative trials requires understanding the underlying target populations (i.e.

Use of Real-World Data to Emulate a Clinical Trial and Support Regulatory Decision Making: Assessing the Impact of Temporality, Comparator Choice, and Method of Adjustment.

External controls have been primarily used in the setting of single-arm trials of rare diseases; their use in common diseases has not been readily investigated, nor is there guidance on how to best select comparators. Thus, the objective of this study was to emulate a large cardiovascular outcome trial of type 2 diabetes to compare associations of effectiveness with different comparator groups to those reported in the trial. Using the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, we investigated six comparator groups using three calendar time periods (Early: 1999-2003; Later: 2004-2008, and Contemporaneous: 2009-2013) and two comparators (sulfonylureas and other second-to-third-line antidiabetic drugs).