Real-World Evidence in Support of Oncology Product Registration: A Systematic Review of New Drug Application and Biologics License Application Approvals from 2015–2020

Arondekar, Bhakti; Duh, Mei Sheng; Bhak, Rachel H.; DerSarkissian, Maral; Huynh, Lynn; Wang, Kelsey; Wojciehowski, John; Wu, Melody; Wornson, Bryon; Niyazov, Alexander; Demetri, George D.

doi:10.1158/1078-0432.ccr-21-2639

Cited by 33 publications

(38 citation statements)

References 2 publications

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“…With the recent and rapid adoption of electronic health records (EHR) to document patient information at the point of care, real-world data (RWD) have become a viable source of clinical information (1). Since the passing of the 21st Century Cures Act into law to accelerate medical development and bring innovations faster and more efficiently to patients (2), greater focus has emphasized the use of real-world evidence to help inform treatment effectiveness and regulatory decisions (3,4). In certain instances when randomization to a control arm is either unethical or infeasible, RWD have supported drug approval (3) or label expansion (5) decisions.…”

Section: Introductionmentioning

confidence: 99%

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data

Ton¹,

Pal²,

Trinh³

et al. 2022

Clinical Cancer Research

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Purpose: The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was to replicate control arms from four non-small cell lung cancer (NSCLC) randomized controlled trials (RCTs) to analyze overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) using RWD. Experimental Design: This study used RWD from a nationwide de-identified database and a clinico-genomic database to replicate OS, PFS, and ORR endpoints in the chemotherapy control arms of four first line NSCLC RCTs evaluating atezolizumab (IMpower150-wildtype [WT], IMpower130-WT, IMpower131, and IMpower132). Additional objectives were to develop a definition of real-world PFS (rwPFS) and to evaluate the real-world response rate (rwRR) endpoint. Results: Baseline demographic and clinical characteristics were balanced after application of propensity score weighting methods. For rwPFS and OS, RWD external controls were generally similar to their RCT control counterparts. Across all four trials, the hazard ratio point estimates comparing trial controls with external controls were closer to 1.0 for the PFS endpoint than for the OS endpoint. An exploratory assessment of rwRR in RWD revealed a slight but non-significant overestimation of RCT ORR, which was unconfounded by baseline characteristics. Conclusions: RWD can be used to reasonably replicate the OS and PFS of chemotherapy control arms of first line NSCLC RCTs. Additional studies can provide greater insight into the utility of RWD in drug development.

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Section: Introductionmentioning

confidence: 99%

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data

Ton¹,

Pal²,

Trinh³

et al. 2022

Clinical Cancer Research

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“…A first systematic review evaluated oncological new drug applications and biologics license application between 2015 and 2020 [ 34 ] and found that, among other results, already 11 among 133 oncology new therapy approvals utilized RWE to support the efficacy of the drugs. The review concluded “that real-world studies used as external controls complemented efficacy data from single-arm trials in successful oncology product approvals, and that the key attributes identified include early engagement, a priori protocol development, and robust research design” [ 34 ]. Given the help of RWE research, the utility and application of cancer therapies can be studied, e.g., in second- or third-line treatment where several equivalent options exist.…”

Section: Resultsmentioning

confidence: 99%

Real-World Evidence—Current Developments and Perspectives

Schad

Thronicke

2022

IJERPH

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Real-world evidence (RWE) is increasingly involved in the early benefit assessment of medicinal drugs. It is expected that RWE will help to speed up approval processes comparable to RWE developments in vaccine research during the COVID-19 pandemic. Definitions of RWE are diverse, marking the highly fluid status in this field. So far, RWE comprises information produced from data routinely collected on patient’s health status and/or delivery of health care from various sources other than traditional clinical trials. These sources can include electronic health records, claims, patient-generated data including in home-use settings, data from mobile devices, as well as patient, product, and disease registries. The aim of the present update was to review current RWE developments and guidelines, mainly in the U.S. and Europe over the last decade. RWE has already been included in various approval procedures of regulatory authorities, reflecting its actual acceptance and growing importance in evaluating and accelerating new therapies. However, since RWE research is still in a transition process, and since a number of gaps in this field have been explored, more guidance and a consented definition are necessary to increase the implementation of real-world data.

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“…In fact, the number of applications including RWE as supporting evidence to both the US FDA and the EMA has increased [ 11 , 12 ]. At the same time, the number of approvals where RWE influenced regulatory decision making and was included in product labels has also increased [ 12 , 13 ], highlighting the emerging role of RWE in the regulatory decision-making process. The potential role of RWE on cost-effectiveness analyses has also been highlighted as a valuable aspect that could impact health technology assessment decisions [ 9 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma: A Meta-analysis

et al. 2022

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Background Both randomized controlled trials (RCTs) and real-world evidence (RWE) studies provide results regarding the efficacy and toxicity of checkpoint inhibitors in cancer patients. The results from these two sources are considered complementary but whether they are comparable remains unknown. Objective The aim of this study was to compare the efficacy and toxicity of checkpoint inhibitors between RCTs and RWE studies in patients with advanced non-small cell lung cancer (NSCLC) or melanoma. Patients and Methods Two electronic databases were searched to identify eligible studies, either RCTs or RWE studies, investigating the efficacy or toxicity of checkpoint inhibitors given for indications that were approved by the European Medicines Agency (EMA) at the date of the last search. A meta-analysis was performed and the pooled estimates of objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and toxicity and treatment discontinuation between RCTs and RWE studies were compared. Results In total, 43 RWE studies and 15 RCTs were eligible, with adequate data for pooled estimates for immunotherapy indications regarding NSCLC and melanoma. No statistically significant or clinically meaningful differences in terms of pooled PFS, OS, or rates of treatment discontinuation due to toxicity between RCTs and RWE studies were observed. In some indications, a higher rate of response rates and lower rate of toxicity in favor of RWE was observed. Conclusion In patients with melanoma or NSCLC, the clinical value of checkpoint inhibitors is evident in both RCTs and real-world settings. Some differences in response or toxicity rates in favor of RWE mainly reflects the inherent difficulties in evaluating these outcomes in RWE studies.

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Real-World Evidence in Support of Oncology Product Registration: A Systematic Review of New Drug Application and Biologics License Application Approvals from 2015–2020

Cited by 33 publications

References 2 publications

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data

Real-World Evidence—Current Developments and Perspectives

Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma: A Meta-analysis

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