Category: Fellows Posters
Purpose: Historically, real-world evidence (RWE) was primarily used to confirm efficacy and safety findings of randomized-controlled-trials (RCTs). Lately, RWE gained regulatory prominence as the U.S. Food & Drug Administration (FDA) developed a framework to leverage RWE in support of approvals for new drug indications. However, robustness of RWE in terms of completeness and accuracy of data is crucial to warrant such consideration. This systematic literature review (SLR) examines two key questions: 1) In what instances has FDA considered real-world data in its decision-making? and 2) Are outcomes from RWE similar to RCTs, based on evaluations published in literature?
Methods: Systematic review of Medline, Embase, and grey literature (Google/Google Scholar) between January 1st, 2010 and June 30th, 2019 was conducted. A comprehensive search criterion was developed which included acronyms and variations of the terms “real-world data/evidence”, “FDA decision making”, and “randomized controlled trial”. The inclusion criteria for the first key question comprised of all articles that indicated the use of RWE to support an approval decision made by the FDA. The inclusion criteria for the second key question comprised of studies comparing outcomes in efficacy including patient reported outcomes (PROs) between RWE and RCT. Eligibility of studies for both objectives was determined by two independent reviewers through title, abstract, and full text screening as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The eligible studies were then summarized descriptively for the two objectives independently. Categorization of studies for the first objective was based on the form of consideration (application type, therapeutic areas and outcome type) by the FDA. For the second objective, the literature summarization was based on descriptive congruence of outcome comparisons, indications, and type of outcomes
Results: For the first key question, 25 instances were identified in which RWE was utilized for regulatory decision making. Nearly half (48%) were in support of a new drug application (NDA), and closely 44% were for biological license applications (BLAs). Of these 25 instances, 44% were for rare diseases and 20% within the oncology therapeutic area. RWE was utilized as external control in more than half (14/25) of these instances. The RWE outcomes reported were primarily efficacy focused, accounting for 60% of the instances, safety constituted 20%, and the remaining 20% explored both efficacy and safety. The efficacy outcomes included survival-related (67%), normalization of irregular vital/lab values (20%), and functional assessment tests (13%).
For the second key question, 38 eligible studies were identified in which a comparison between RWE and RCT outcomes was the primary objective. Of these, 79% (30/38) concluded that the real-world outcomes were similar to corresponding clinical trial outcomes. In terms of indications wherein the similarities of RWE with RCT data was assessed, oncology represented 32% and rheumatoid arthritis, psoriasis, and Hepatitis C each represented 11%. A majority (87%) of the studies evaluated standard efficacy-related outcomes and the remaining (13%) studies assessed health-related quality of life using PROs.
Conclusion: This SLR summarizes the utility of RWE by FDA in their decision making over the last decade across multiple therapeutic areas. Additionally, this analysis identified multiple studies demonstrating the concordance of efficacy and PROs between RCT data and RWE. As indicated by the high degree of similarity between RCT and RWE outcomes data, leveraging RWE could potentially help stakeholders better understand the translation of clinical trial efficacy to real-world effectiveness and also help biopharmaceuticals operating across a variety of disease states develop appropriate data submission packages for FDA’s regulatory decision making.