The Case for Real-world Evidence in the Future of Clinical Research on Chronic Myeloid Leukemia

Abstract

Purpose: In light of recently published guidelines from the US Food and Drug Administration (FDA) on the communication of real-world data (RWD) and real-world evidence (RWE) to support regulatory decision making, it is important to understand how such data are developed, the limitations of these data, and how to best use RWD to improve patient care. Historically, the use of RWE has been approached with skepticism because of its often-retrospective nature compared with data from conventional randomized controlled trials (RCTs). This review discusses the role and function of RWE and RWD in clinical research. We summarize the types of RWE used in clinical research, outline the challenges and limitations involved with these data, and suggest how these types of analyses can supplement results from clinical trials to foster a more complete understanding of a drug or disease area of interest. In particular, we focus on the role of RWE in investigating chronic myeloid leukemia (CML) and tyrosine kinase inhibitor therapy for CML. Methods: We reviewed FDA guidance on the use of RWE and conducted a PubMed literature search to evaluate published data from real-world studies in CML. Findings: RWE includes analysis of RWD gathered from nonconventional sources, including patient registries, observational studies, and social media, among others. Importantly, although real-world studies do not adhere to the same degree of controlled conditions and predefined patientmanagement strategies as do conventional clinical trials, analyses resulting from these studies can be held to a high degree of validation and standardization, making them as meaningful as those from RCTs. In CML, RWE has informed early treatment milestones and has provided a window into patient perspectives regarding treatment. These types of analyses have already informed and can continue to inform disease management. These improvements in disease management, in turn, will help clinicians to better forecast treatment challenges and allow for the optimization of future treatment paradigms. Implications: Real-world studies are different from conventional RCTs and therefore provide insight into distinct aspects of treatment and patient outcomes. Together with results from clinical trials, RWE can help to illustrate a more complete picture of the tolerability, effectiveness, and impact of a drug. The recently published guidelines indicate that the FDA expects a growing role for RWE. (Clin Ther.

Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data

“…Such implications also highlight the importance of computationally analyzing real world and big data towards their translation into more informed patient management [22,23,24,25]. For example, the high bone and/or back pain signals observed in radium-223 dichloride AEs may likely be attributed to progression of skeletal disease burden.…”

Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective

“…92 As real-world studies do not adhere to the same degree of controlled conditions and predefined patient-management strategies as clinical studies, RWE is still considered to be of lower quality and less reliable than randomized controlled trial (RCT) data. 93 Issues can depend on whether data are retrospective or prospective, but include selection bias at a patient and treatment center level, 94 missing data on confounders, and low interoperability in general. 86 The recording of drug-related toxicities in clinical practice also differs to the criteria used in clinical trials.…”

“…Despite this, RWE provides data that are not readily available in an RCT, such as long-term outcomes. 93 Thus, some HTA agencies, such as the French Transparency Commission or NICE, will provide reimbursement conditional on further efficacy and safety data being collected. The collected postlaunch data provide clinicians with a greater understanding of the long-term safety of IO therapies, and they are of value to HTA agencies during HTAs of new IO therapies or in reassessments.…”

Identifying the Characteristics of Patients With Cervical Degenerative Disease for Surgical Treatment From 17-Year Real-World Data: Retrospective Study

“…Comparatively, real-world data (RWD), which are health care data that have been collected from different sources, including electronic health records, insurance payment and billing databases, disease registration databases, family monitoring equipment data, and mobile health devices, can be complementary sources of RCT data for establishing a more robust evidence base on the effectiveness of medicines, as well as the relative effectiveness as compared with existing products in clinical practice [2,3]. Recent studies have focused on designing and implementing evidence-based surgical safety information systems, and big data analytics on RWD can yield new and powerful insights into the effectiveness of different medicines and patient care [4][5][6]. RWD enable new opportunities to be explored in clinical studies.…”