Real-world Evidence—What Does It Really Mean?

Abstract

Much has been written about real-world evidence (RWE) in scientific papers and the lay media. Although some researchers and journalists tout its value, opponents are vocal in challenging its validity, pointing out shortcomings and downplaying any potential benefits. Despite an emphasis on the importance of RWE in the 21st Century Cures Act, a standard definition of the term has not been uniformly embraced. 1 The US Food and Drug Administration defines RWE as "data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than traditional clinical trials." 2,3 In addition, the agency's Real-world Evidence Program framework defines real-world data (RWD) as "data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources." 4(p4) To maximize the potential of RWE and define its role moving forward, limitations must be balanced with merits when considering RWD sources (Table ).Real-world evidence is obtained from RWD, which encompass data collected outside randomized clinical trials (RCTs), ideally in diverse groups such as those representing all Americans, all Europeans, or all global citizens. Real-world evidence can be derived through routine daily clinical practice or through patient interactions in their customary daily living environment. Because greater than 90% of patients with cancer are treated outside RCTs, 5 RWE presents a unique avenue for obtaining data on patients with characteristics outside those typically required for trial eligibility. Randomized clinical trials that lead to Food and Drug Administration approval of drug therapies often enroll younger patients who lack comorbidities, have adequate organ functions, possess proper psychosocial support, are able to travel to study sites, and are white. 2 Generation of RWE allows assessing how therapy affects a heterogeneous population-those who are older and those with concurrent medical problems, impaired organ function, limited social resources, and varied ethnicities/races.Moreover, the Food and Drug Administration uses RWE and RWD to monitor postmarketing safety and adverse events, which may go unnoticed during RCTs. These findings can have regulatory and strategy implications for payers, physicians, and manufacturers. RWD Sources Administrative ClaimsThese administrative data sets contain patient medical and pharmacy claims generated for health care encounters and submitted for reimbursement from government and commercial payers. Medical and pharmacy claims contain coded data that capture patient demographics, diagnosis, procedures, and medications, as well as associated dates, place of ser-vice, and costs for each claim. When these claims are linked to a given patient over time, a longitudinal history that depicts his or her journey through the health care system can be created.

U.S. Food and Drug Administration anticancer drug approval trends from 2016 to 2018 for lung, colorectal, breast, and prostate cancer

“…In order to improve data for drug approval, the FDA recently launched a guideline for real-world evidence submission to generate information on effectiveness (19). However, some authors are concerned about the lack of standardized data collection and the allowance of retrospective studies (20).…”

Emerging opportunities to harness real world data: An introduction to data sources, concepts, and applications

“…RWE has been defined as “information on health care that is derived from multiple sources outside typical clinical research settings, including electronic health records (EHRs), claims and billing data, product and disease registries, and data gathered through personal devices and health applications.” (Figure ) The 21st Century Cures Act, a bill passed by the United States Congress in 2016, defined RWE even more broadly as “data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than randomized clinical trials.” This definition has subsequently and appropriately been broadened, recognizing that RWE encompasses data beyond that related to just drugs and can also be utilized to assess the potential benefits or risks of a medical product . Thus, real world evidence refers to the analysis and assessment of data derived from clinical practice, commonly referred to as real world data (RWD) . RWD may be generated within a variety of clinical contexts (eg, primary care office visit) or outside of clinical contexts (eg, physiologic data obtained through wearable technology) .…”

Real-world evidence of poly ADP-ribose polymerase inhibitors in the treatment of ovarian cancer: A systematic literature review

“…[32][33][34] RWE is generated from data collected outside of RCT such as administrative claims databases, disease or medication registries, electronic health records (EHRs), medical chart reviews, and patient generated data. 29,30,35,36 A targeted search was conducted with the search terms "PARP inhibitor OR olaparib OR rucaparib OR niraparib AND ovarian" (Appendix 1: Table 3). Article type was restricted in the PubMed/Medline search to "clinical study", "clinical trial", "clinical trial, phase I", "clinical trial, phase II", "clinical trial, phase III", "clinical trial, phase IV", "comparative study", "controlled clinical trial", "multicenter study", "observational study", "pragmatic clinical trial", or "randomized controlled trial".…”

“…28,29 RWE has an opportunity to inform clinical decision making by assessing patients in real-world settings who otherwise might have been excluded from RCTs. 30 While more RWE has been published in oncology, additional data may guide practitioners in selecting a PARP inhibitor. 31 With this growing need for RWE and relatively new approval of PARP inhibitors for the treatment of ovarian cancer, our goal was to locate and assess real-world studies measuring the safety and effectiveness of PARP inhibitors and analyze the results.…”