The Bar Is High: Evaluating Fit-for-Use Oncology Real-World Data for Regulatory Decision Making

Lerro, Catherine C.; Bradley, Marie C.; Forshee, Richard A.; Rivera, Donna R.

doi:10.1200/cci.23.00261

Cited by 4 publications

(2 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some challenging aspects of this study included the use of real-world data to generate real-world evidence, which has limitations when compared to dedicated interventional studies [ 56 ]. While real-world data and evidence have many potential benefits and implications when applied in oncology care, data collection and the reliability of data with issues such as duplication or missingness remain a challenge [ 56 ]. Similarly, given that our study was based on real-world data, accuracy and access to electronic health record data was another demanding aspect of the study.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Incidental Pathogenic Germline Findings Detected via ctDNA among Patients with Non-Small Cell Lung Cancer in a Predominantly Hispanic/Latinx Population

Vallabhaneni,

Kareff,

Barnett

et al. 2024

Cancers

View full text Add to dashboard Cite

Pathogenic germline variants (PGVs) may be under-detected as causative etiologies in patients with non-small cell lung cancer (NSCLC). The prevalence of PGVs has been reported between 1 and 15% of patients, depending on the patient population. The rate within Hispanic/Latinx populations remains unknown. We retrospectively analyzed the genomic results (Guardant360, Redwood City, CA, USA) of 878 patients with advanced or metastatic NSCLC at five centers in South Florida, USA, from 2019 to 2022 to analyze the rate of incidental PGVs (iPGVs) identified via circulating cell-free tumor DNA (ctDNA). We then stratified the results by tumor histology, age, gender, race, ethnicity, genetic pathway, and co-mutations. Twenty-one iPGVs were identified (21/878 = 2.4%). Among the 21 iPGVs identified, 14 patients were female (66.7%) and 7 were male (33.3%), with a median age of 67 years and tobacco history of 2.5 pack-years. In total, 52.4% of patients identified as Hispanic/Latinx (n = 11) of any race; 19.0% as Ashkenazi Jewish (n = 4), 9.5% as non-Hispanic/Latinx black (n = 2), and 19.0% as non-Hispanic/Latinx white (n = 4). iPGVs in the homologous recombination repair pathway were solely expressed in this cohort (10 ATM, 8 BRCA2, and 3 BRCA1). In total, 76% (16/21) of patients with iPGVs co-expressed somatic alterations, with 56% (9/16) demonstrating alterations in targetable genes. Overall, our real-world findings offer a point prevalence of iPGVs in patients with NSCLC of diverse populations, such as patients who report Hispanic/Latinx ethnicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of Incidental Pathogenic Germline Findings Detected via ctDNA among Patients with Non-Small Cell Lung Cancer in a Predominantly Hispanic/Latinx Population

Vallabhaneni,

Kareff,

Barnett

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

“…20 Registries that are designed to generate reusable data for randomized trials and observational studies represent other examples. 21,22 In contrast to the operational focus of reusability, multipurpose is a more technical concept that involves a variety of factors, including data quality (reliability and relevance), 23 to determine the appropriateness for use across a range of studies. For example, although some data collected in routine care settings may not have the level of reliability (eg, completeness, accuracy, known provenance, and traceability) required for use in clinical trials, 23 these data elements may be useful for real-world observational studies intended to inform payer decision-making or practice guidelines.…”

Section: Vision For a Modernized Infrastructure: Integrating Multiple...mentioning

confidence: 99%

Modernizing the Data Infrastructure for Clinical Research to Meet Evolving Demands for Evidence

Franklin,

Marra,

Abebe

et al. 2024

JAMA

View full text Add to dashboard Cite

ImportanceThe ways in which we access, acquire, and use data in clinical trials have evolved very little over time, resulting in a fragmented and inefficient system that limits the amount and quality of evidence that can be generated.ObservationsClinical trial design has advanced steadily over several decades. Yet the infrastructure for clinical trial data collection remains expensive and labor intensive and limits the amount of evidence that can be collected to inform whether and how interventions work for different patient populations. Meanwhile, there is increasing demand for evidence from randomized clinical trials to inform regulatory decisions, payment decisions, and clinical care. Although substantial public and industry investment in advancing electronic health record interoperability, data standardization, and the technology systems used for data capture have resulted in significant progress on various aspects of data generation, there is now a need to combine the results of these efforts and apply them more directly to the clinical trial data infrastructure.Conclusions and RelevanceWe describe a vision for a modernized infrastructure that is centered around 2 related concepts. First, allowing the collection and rigorous evaluation of multiple data sources and types and, second, enabling the possibility to reuse health data for multiple purposes. We address the need for multidisciplinary collaboration and suggest ways to measure progress toward this goal.

show abstract

Important tool in our rare disease toolbox: hybrid retrospective-prospective natural history studies serve well as external comparators for rare disease studies

Ugoji,

Heidt,

Largent

et al. 2024

Front. Drug Saf. Regul.

View full text Add to dashboard Cite

Natural history studies (NHS) can support regulatory decision-making at different stages of the drug product life cycle and are especially important in the context of rare diseases, which are associated with not only delayed or erroneous diagnoses but also a lack of approved treatments. Real-world evidence can fill knowledge gaps and support treatment decision-making, thereby benefiting affected patients. In this context, there are three important options for NHS design: retrospective, prospective, and cross-sectional. Each of these has been successfully used to support regulatory approval as external comparator arms (ECAs) for clinical studies, especially single-arm trials (SATs). While longitudinal data obtained from retrospective or prospective designs have been more commonly used and have been the focus of regulatory guidance documents, hybrid designs that combine retrospective and prospective data collection are particularly powerful for rare disease studies. This is due, in part, to the smaller number of patients impacted by each rare disease. In these settings, retrospective or prospective data collection alone may not be sufficient or fit-for-purpose for an external comparator. Rather, a strategic combination of all available data, regardless of timing, can deliver the right information of the desired quality and completeness to answer these important questions and support regulatory evidentiary needs. For instance, patients included in retrospective studies may differ from recently treated patients in terms of disease severity, disease variants, clinical management, or other important aspects of the disease that may impact patient outcomes. Further, retrospectively collected data may lack specific data elements required to achieve adequate comparison with the treated group in single-arm studies. In the context of prospective designs, the recruitment of sufficient new patients for prospective follow-up may not be feasible or may be prolonged due to the rarity of the disease. Further, the potential for premature truncation of patient follow-up may result in insufficient longitudinal data, or prospectively collected data alone may not provide insights into the disease course for specific groups of patients. In these situations, primary data collection in a prospective study may be supplemented with retrospectively collected data from chart reviews, registries, or electronic medical record databases, either for the same patients, in an ambispective design, or for a different set of patients. These hybrid designs allow for broader and more robust contextual information on the patient journey and the natural course of the disease to be obtained, which can improve the suitability of the data as an external comparator for SATs or studies that lack internal control in situations where a prospective design alone might not be sufficient. Because retrospective and prospective data, or any two data sources that are being combined, may differ in availability and quality, there are unique challenges alongside the strengths of these designs. In this paper, we discuss considerations for the design, analysis, and conduct of hybrid NHS intended as ECAs for single-arm studies in clinical development programs for rare diseases.

show abstract

The Bar Is High: Evaluating Fit-for-Use Oncology Real-World Data for Regulatory Decision Making

Cited by 4 publications

References 6 publications

Characterization of Incidental Pathogenic Germline Findings Detected via ctDNA among Patients with Non-Small Cell Lung Cancer in a Predominantly Hispanic/Latinx Population

Characterization of Incidental Pathogenic Germline Findings Detected via ctDNA among Patients with Non-Small Cell Lung Cancer in a Predominantly Hispanic/Latinx Population

Modernizing the Data Infrastructure for Clinical Research to Meet Evolving Demands for Evidence

Important tool in our rare disease toolbox: hybrid retrospective-prospective natural history studies serve well as external comparators for rare disease studies

Contact Info

Product

Resources

About