scholarly journals FDA Oncology Center of Excellence Review of Real World Data Submissions Supporting Drug Development in Hematologic Malignancies

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5037-5037
Author(s):  
Donna R. Rivera ◽  
Jennifer J Lee ◽  
Melanie Royce ◽  
R. Angelo de Claro ◽  
Nicole J. Gormley ◽  
...  
Keyword(s):  
Decision Making ◽  
Overall Survival ◽  
Real World ◽  
Response Rate ◽  
Hematologic Malignancies ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Real World Evidence ◽  
Regulatory Submissions

Abstract Background Aligning with 21st Century Cures legislation, FDA is exploring methodologies to advance appropriate uses of Real World Data (RWD) to generate Real World Evidence (RWE). RWD to support regulatory decision making has markedly increased in oncology. This review specifically focused on the analysis of RWD containing submissions for medical products in development for the treatment of hematological malignancies and associated treatment related conditions (e.g., Cytokine Release Syndrome (CRS), Graft Versus Host Disease (GVHD). Methods A systematic search was conducted using internal FDA databases to identify RWD submissions from 2010 to 2020. Search terms included: real world evidence, real world data, electronic health record, cancer registry, administrative claims, external control arm, observational cohort, historical control arm, real world Overall Survival (rwOS) , real world Response Rate (rwRR), real world Overall Response Rate rwORR and real world Complete Response (rwCR). Regulatory submissions specific to malignant hematology and associated treatment related conditions were reviewed, and pre-defined common data elements were extracted and validated by independent dual review. Descriptive statistics were calculated. Results A total of 142 regulatory submissions included RWD from 2011-2020. A subset of 94 RWD submissions met the criteria for further evaluation, of which 20 (21%) submissions corresponding with 14 molecular entities were for hematologic malignancies or treatment related conditions (e.g., CRS, GVHD). RWD submissions increased substantially over time, with 14 (70%) of submissions received between 2019-2020. Specific evaluation for pediatric indications was referenced in 15% of submissions. The most commonly referenced RWD source was EHR data (55%), followed by use of multiple sources (20%), and registry data (15%). Approximately 90% of the submissions aimed to support treatment effectiveness. Primary RWD study objectives included supporting approval of a new molecular entity (NME) (40%), expanding an approved indication (25%), conversion from accelerated to regular approval (15%), and providing data to inform postmarketing safety evaluation (20%). Among RWD submissions, response endpoints (e.g., rwORR, rwCR, rwPR, Partial Response) and overall survival (e.g., rwOS) were most frequently selected as primary outcomes for 50% and 20% of proposals respectively; however, these outcomes were included as any endpoint in 65% and 75% of submissions. Conclusion This review demonstrates increasing use of various RWD sources to support evidence generation for drug development in hematologic malignancies and associated treatment related conditions with the primary objective of supporting demonstration of effectiveness using rwOS or real world response measures as primary endpoints. Given the increased inclusion of RWD in regulatory submissions, further methodological development is needed, including in the selection and validation of rwEndpoints. Appropriate study design must be aligned with a clear regulatory objective to ensure that RWD can be adequately evaluated. Additionally, the development of standardized metrics for data characterization and transparency in reporting of RWD are foundational steps to the evaluation of fit for purpose RWD to support regulatory decision making. Disclosures No relevant conflicts of interest to declare.

FDA Oncology Center of Excellence landscape analysis of real-world data submissions for oncology drugs.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18787-e18787
Author(s):  
Donna Rivera ◽  
Jennifer J. Lee ◽  
Melanie E Royce ◽  
Paul Gustav Kluetz
Keyword(s):  
Decision Making ◽  
Real World ◽  
Landscape Analysis ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Real World Evidence ◽  
Regulatory Submissions ◽  
Oncology Center ◽  
Oncology Drug Development

e18787 Background: Aligning with 21st Century Cures legislation, the FDA is exploring trial design modernization and methodology to advance appropriate uses of Real World Data (RWD) to generate Real World Evidence (RWE). The Oncology Center of Excellence RWE Program was established in 2020 to advance RWE efforts specific to oncology drug development. Inclusion of RWD to support regulatory decision making has increased in oncology, and a landscape analysis was conducted to characterize the RWD included in submissions. Methods: A systematic search was conducted using internal FDA databases to identify RWD submissions from 2010 to 2020. Search terms included: real world evidence, real world data, electronic health record, cancer registry, administrative claims, external control arm, observational cohort, historical control arm, rwOS, rwRR, rwCR, and rwORR. Relevant regulatory submissions were reviewed, and pre-defined common data elements were extracted. A team of FDA reviewers assessed agreement through subset validation (20%). Descriptive statistics were calculated. Results: A total of 142 regulatory submissions included RWD from 2011 to 2020. A subset of 94 submissions met the criteria for evaluation, consisting of 78 unique studies evaluating 56 molecular entities. RWD submissions increased substantially over time, with 28 submissions in 2020. Nearly half of the RWD submissions were for solid tumor indications (68%), with lung cancer being the most predominant site. More than one third of the RWD submissions (37%) were for rare indications. The most common primary RWD study objective was effectiveness (62%) and the most commonly referenced RWD source was EHR/clinical data (54%). The most frequently used primary RWD endpoints were survival (rwOS, 35%) and response (rwORR/PR/BTR, 31%) outcomes (Table). Conclusions: Our review demonstrates a dramatic increase in RWD submissions to support FDA oncology drug development programs. Submissions included a variety of study objectives, data sources, and endpoints. While this landscape analysis provides a picture of potential regulatory objectives, the adequacy of each proposal to support regulatory decision making was not evaluated. Establishing a set of clear regulatory objectives can help advance the development of metrics for robust data characterization and outcome validation to ensure that RWD can be appropriately evaluated and provide the rigor necessary to be considered adequate RWE.[Table: see text]

Current Status and Examples of US FDA or EMA’s Regulatory Decision using Real World Data/Real World Evidence

Yakhak Hoeji ◽  
2020 ◽  
Vol 64 (2) ◽  
pp. 136-155
Author(s):  
Hi Gin Sung ◽  
Han-Heui Park ◽  
Gyu-Won Jung ◽  
Ju-Young Shin
Keyword(s):  
Real World ◽  
Current Status ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Real World Evidence ◽  
Us Fda

scholarly journals Health Canada & Canadian Society for Pharmaceutical Sciences - Use of Real World Data/Evidence to Inform Regulatory Decision Making

2020 ◽  
Vol 23 ◽  
pp. 1s-47s
Author(s):  
Real World Data Workshop Group CSPS/Health Canada
Keyword(s):  
Health Care ◽  
Decision Making ◽  
Clinical Trials ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Regulatory Agencies ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Health Canada

Real world data (RWD) and real world evidence (RWE) are playing increasing roles in health-care decisions. Real world data are routinely employed to support reimbursement and coverage decisions for drugs and devices. More recently, clinical trials incorporating pragmatic designs and observational studies are considered to supplement traditional clinical trials (e.g., randomized clinical trials). Regulatory agencies and large co-operative groups including academia and industry are exploring whether leveraging big databases such as electronic medical records and claims databases can be used to garner clinical insights extending beyond those gained from randomized controlled studies. Whether RWE can ultimately replace or improve traditional clinical trials is the big question. The workshop held on December 3, 2019 at Health Canada included presenters from regulatory agencies, industry and academia. Health Canada, US FDA and European Medicine Agency presented current thinking, draft frameworks and guidance available in the public domain. While the three agencies might be at different stages of utilizing RWE for regulatory decision making, the consensus is not whether RWE would be used but when and how it can be incorporated into regulatory decision making while maintaining a high evidentiary bar. The complexity of data sourcing, curating databases, aligning on common data models, illustrated by high-profile work conducted as part of Sentinel, DSEN, OHDSI and Duke-Margolis initiatives, was presented and discussed during the workshop, creating great learning opportunities for the attendees. The design and analysis of RWE studies were compared and contrasted to those of RCTs. While there are gaps, they are closing quickly as novel analytical methods are employed and innovative ways of curating data, including natural language processing and artificial intelligence, are explored.   This proceeding contains summaries of information presented by the speakers, including current highlights about the use of RWE in regulatory decision making. In the world where the uptake of “big data” in everyday life is happening at unprecedented speed, we can expect RWE to be a fast-moving area and with the potential for big impact in health-care decision making in the years to come.

scholarly journals Do existing real-world data sources generate suitable evidence for the HTA of medical devices in Europe? Mapping and critical appraisal

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Benedetta Pongiglione ◽  
Aleksandra Torbica ◽  
Hedwig Blommestein ◽  
Saskia de Groot ◽  
Oriana Ciani ◽  
...  
Keyword(s):  
Decision Making ◽  
Medical Devices ◽  
Real World ◽  
Real World Data ◽  
Data Accessibility ◽  
World Data ◽  
Transcatheter Aortic Valve ◽  
Real World Evidence ◽  
Hip And Knee Arthroplasty ◽  
Valve Implantation

Abstract Aim Technological and computational advancements offer new tools for the collection and analysis of real-world data (RWD). Considering the substantial effort and resources devoted to collecting RWD, a greater return would be achieved if real-world evidence (RWE) was effectively used to support Health Technology Assessment (HTA) and decision making on medical technologies. A useful question is: To what extent are RWD suitable for generating RWE? Methods We mapped existing RWD sources in Europe for three case studies: hip and knee arthroplasty, transcatheter aortic valve implantation (TAVI) and mitral valve repair (TMVR), and robotic surgery procedures. We provided a comprehensive assessment of their content and appropriateness for conducting the HTA of medical devices. The identification of RWD sources was performed combining a systematic search on PubMed with gray literature scoping, covering fifteen European countries. Results We identified seventy-one RWD sources on arthroplasties; ninety-five on TAVI and TMVR; and seventy-seven on robotic procedures. The number, content, and integrity of the sources varied dramatically across countries. Most sources included at least one health outcome (97.5%), with mortality and rehospitalization/reoperation the most common; 80% of sources included resource outcomes, with length of stay the most common, and comparators were available in almost 70% of sources. Conclusions RWD sources bear the potential for the HTA of medical devices. The main challenges are data accessibility, a lack of standardization of health and economic outcomes, and inadequate comparators. These findings are crucial to enabling the incorporation of RWD into decision making and represent a readily available tool for getting acquainted with existing information sources.

Contributions of Real-World Evidence and Real-World Data to Decision-Making in the Management of Soft Tissue Sarcomas

Oncology ◽  
2021 ◽  
Vol 99 (Suppl. 1) ◽  
pp. 3-7
Author(s):  
George D. Demetri ◽  
Silvia Stacchiotti
Keyword(s):  
Decision Making ◽  
Soft Tissue ◽  
Real World ◽  
Soft Tissue Sarcomas ◽  
Clinical Settings ◽  
Disease Entity ◽  
Real World Data ◽  
World Data ◽  
Real World Evidence

Real-world data are defined as data relating to any aspect of a patient’s health status collected in the context of routine health surveillance and medical care delivery. Sources range from insurance billing claims through to electronic surveillance data (e.g., activity trackers). Real-world data derive from large populations in diverse clinical settings and thus can be extrapolated more readily than clinical trial data to patients in different clinical settings or with a variety of comorbidities. Real-world data are used to generate real-world evidence, which might be regarded as a “meta-analysis” of accumulated real-world data. Increasingly, regulatory authorities are recognizing the value of real-world data and real-world evidence, especially for rare diseases where it may be practically unfeasible to conduct randomized controlled trials. However, the quality of real-world evidence depends on the quality of the data collected which, in turn, depends on a correct pathological diagnosis and the homogeneous behaviour of a reliably defined and consistent disease entity. As each of the more than 80 varieties of soft tissue sarcoma (STS) types represents a distinct disease entity, the situation is exceedingly complicated. Discordant diagnoses, which affect data quality, present a major challenge for use of real-world data. As real-world data are difficult to collect, collaboration across sarcoma reference institutions and sophisticated information technology solutions are required before the potential of real-world evidence to inform decision-making in the management of STS can be fully exploited.

scholarly journals Applying real-world data to support regulatory decision — making in the United States

2021 ◽  
Vol 20 (1) ◽  
pp. 64-69
Author(s):  
M. A. Borzova ◽  
А. S. Kolbin
Keyword(s):  
United States ◽  
Decision Making ◽  
Real World ◽  
The United States ◽  
Legal Basis ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Eurasian Economic Union ◽  
Economic Union

The article describes the legal basis for the application of real-world data to support regulatory decision-making in the United States, as well as the possibility of implementing the relevant approaches in the legislation of the Eurasian Economic Union.

scholarly journals Integrating Real-World Evidence in the Regulatory Decision-Making Process: A Systematic Analysis of Experiences in the US, EU, and China Using a Logic Model

2021 ◽  
Vol 8 ◽  
Author(s):  
Meng Li ◽  
Shengqi Chen ◽  
Yunfeng Lai ◽  
Zuanji Liang ◽  
Jiaqi Wang ◽  
...  
Keyword(s):  
Decision Making ◽  
Real World ◽  
Decision Making Process ◽  
Real World Data ◽  
Systematic Analysis ◽  
Regulatory Decision ◽  
Real World Evidence ◽  
The Us ◽  
Post Market ◽  
New Treatment

Real world evidence (RWE) and real-world data (RWD) are drawing ever-increasing attention in the pharmaceutical industry and drug regulatory authorities (DRAs) all over the world due to their paramount role in supporting drug development and regulatory decision making. However, there is little systematic documentary analysis about how RWE was integrated for the use by the DRAs in evaluating new treatment approaches and monitoring post-market safety. This study aimed to analyze and discuss the integration of RWE into regulatory decision-making process from the perspective of DRAs. Different development strategies to develop and adopt RWE by the DRAs in the US, Europe, and China were reviewed and compared, and the challenges encountered were discussed. It was found that different strategies on development of RWE were applied by FDA, EMA, and NMPA. The extent to which RWE was adopted in China was relatively limited compared to that in the US and EU, which was highly related to the national pharmaceutical environment and development stages. A better understanding of the overall goals, inputs, activities, outputs, and outcomes in developing RWE will help inform actions to harness RWD and leverage RWE for better health care decisions.

scholarly journals Validate Real-World Data-based Endpoint Measures of Cancer Treatment Outcomes

2021 ◽  
Author(s):  
Qian Li ◽  
Hansi Zhang ◽  
Zhaoyi Chen ◽  
Yi Guo ◽  
Thomas George ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Data Quality ◽  
Treatment Outcomes ◽  
Real World ◽  
Gold Standard ◽  
Surrogate Marker ◽  
Real World Data ◽  
World Data ◽  
Real World Evidence

Recently, there is a growing interest in using real-world data (RWD) to generate real-world evidence (RWE) that complements clinical trials. Nevertheless, to quantify the treatment effects, it is important to develop meaningful RWD-based endpoints. In cancer trials, two real-world endpoints are particularly of interest: real-world overall survival (rwOS) and real-world time to next treatment (rwTTNT). In this work, we identified ways to calculate these real-world endpoints with structured EHR data, and validated these endpoints against the gold-standard measurements of these endpoints derived from linked EHR and TR data. In addition, we also examined and reported the data quality issues especially the inconsistency between the EHR and TR data. Using survival model, our result showed that patients (1) without subsequent chemotherapy or (2) with subsequent chemotherapy and longer rwTTNT, would have longer rwOS, showing the validity of using rwTTNT as a real-world surrogate marker for measuring cancer endpoints.

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