Evolving Use of Real-World Evidence in the Regulatory Process: a Focus on Immuno-Oncology Treatment and Outcomes

Abstract

In recent years, regulatory bodies have increasingly recognized the utility of real-world evidence (RWE) for supplementing and supporting clinical trial data in new drug applications. Nevertheless, the integration of RWE into established regulatory processes is complex and generation of ‘regulatory-grade’ real-world data faces operational, methodological, data-related and policy-related challenges. In parallel with this evolving role for RWE, immuno-oncology therapies have emerged as leading cancer treatments and are expected to continue to play a central role in the future. In this article, we review the current literature on the use of RWE for regulatory submissions, with a focus on novel anticancer immunotherapies, and discuss the utility and current limitations of RWE in the context of drug development and regulatory approvals.

Real-world studies: bridging the gap between trial-assessed efficacy and routine care

“…While open-label, single-arm clinical trials were frequently designed to examine chimeric antigen receptor T-cell (CAR-T) therapies against advanced B-cell leukemia/lymphoma [ 37 ] , the comparable RWD of refractory myeloma have been prepared as a historical control for developing anti-myeloma CAR-T medicine [ 52 ] . In parallel, RWE approach has been utilized for the initial approval of a novel immune check point inhibitor Avelumab for treating metastatic Merkel cell carcinoma, which represents a rare aggressive disease with unmet medical need and very small patient population being unpractical to run a large RCT [ 53 ] . Well-managed RWD have been playing an unique role in the clinical evaluation of COVID-19 vaccines regarding extrapolation of population segments, duration of protection and safety monitoring [ 51 ] .…”

Use of Real‐World Evidence to Drive Drug Development Strategy and Inform Clinical Trial Design

“…A companion project by ISPE described the steps needed to provide transparency that is sufficient to enable other researchers to reproduce or replicate RWE study findings, which is considered an important element to increase public trust in RWE. 97 Key recommendations to achieve greater transparency when reporting RWE studies included fully describing the: (1) RWD used (e.g., provider, data type, and dates); (2) data processing (e.g., cleaning or transformation prior to analyses); (3) study design using a diagram (e.g., patient flow); (4) study inclusion/exclusion criteria; providing operational definitions of (5) study exposure (e.g., medication); (6) follow-up period (e.g., time from first exposure); (7) outcomes of interest (e.g., occurrence of events); (8) covariates used (e.g., comorbidity scores); (9) control groups (e.g., matching method); and (10) any statistical software (e.g., name, version, and packages) used. Researchers also encouraged the public sharing of source data and programs but acknowledged the potential barriers to doing so (e.g., prohibitions in data use agreements).…”

“…Although key stakeholders, such as biopharmaceutical companies, regulators, payers, health technology assessment agencies, patient advocates, and policy makers, generally agree on the limitations of RCTs (e.g., insufficient follow-up duration, use of surrogate endpoints, and smaller sample sizes), they have yet to reach consensus on the optimal use of RWE. [4][5][6][7][8][9][10][11] Because much of the recent RWE literature has focused on regulatory aspects (e.g., approval of new products for rare diseases based on single-arm trials with external control arms) 6,11,12 , this paper will instead focus on the value of RWE to guide the research and development (R&D) process within biopharmaceutical companies. 13 The following topics will be discussed: (1) use of RWD to guide pipeline and portfolio strategy; (2) use of novel sources of RWD to inform product development; (3) use of RWD to inform clinical development; (4) advanced analytics and tokenization to harness "big" RWD; and (5) considerations when using RWD to inform internal decisions.…”

Seltene Erkrankungen und Hals-Nasen-Ohren-Heilkunde, Kopf und Halschirurgie

“…Die Analyse von "Real Word"-Daten können die Nutzenbewertung von Arzneimitteln auch im Kontext seltener Erkrankungen unterstützen. Die durch fortschreitende Digitalisierungsprozesse verbesserte Datenverfügbarkeit [18,19] lässt erwarten, dass "Real Word Evidence" zukünftig eine zunehmende Rolle auch bei der Entwicklung, der Nutzenbewertung und bei den regulatorischen Prozessen (Zulassung) von Therapien für seltene Erkrankungen spielen wird [20][21][22][23].…”

“…Analysis of real-world data may support the benefit assessment of drugs used in the context of rare diseases. Data availability has been improved by progressive digitization [18,19], suggesting that in the future real-world evidence will play a major role in the development, benefit assessment, and regulatory processes (approval) of therapies for orphan diseases [20][21][22][23].…”