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 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]

Role of real world data and real world evidence in regulatory decision making

2021 ◽  
Vol 14 (2) ◽  
pp. 1177-1182
Author(s):  
B. C. Bharath ◽  
V. Balamuralidhara ◽  
M. P. Gowrav
Keyword(s):  
Decision Making ◽  
Real World ◽  
Real World Data ◽  
World Data ◽  
Regulatory Decision ◽  
Real World Evidence

scholarly journals Development of an Innovative Real-World Evidence Registry for the Herpes Simplex Virus: Case Study

10.2196/16933 ◽  
2020 ◽  
Vol 3 (1) ◽  
pp. e16933 ◽  
Author(s):  
Michelle Helena van Velthoven ◽  
Ching Lam ◽  
Caroline de Cock ◽  
Terese Stenfors ◽  
Hassan Chaudhury ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Real World ◽  
Physical Symptoms ◽  
Use Cases ◽  
Real World Data ◽  
World Data ◽  
Real World Evidence ◽  
Simplex Virus

Background Infection with the herpes simplex virus (HSV) is common but not well understood. Furthermore, there remains a social stigma surrounding HSV that can have psychosocial implications for those infected. Despite many patients infected with HSV experiencing mild-to-severe physical symptoms, only one subeffective treatment is available. A registry collecting real-world data reported by individuals potentially infected with HSV could help patients to better understand and manage their condition. Objective This study aimed to report on the development of a registry to collect real-world data reported by people who might be infected with HSV. Methods A case study design was selected as it provides a systematic and in-depth approach to investigating the planning phase of the registry. The case study followed seven stages: plan, design, prepare, collect, analyze, create, and share. We carried out semistructured interviews with experts, which were thematically analyzed and used to build use cases for the proposed registry. These use cases will be used to generate detailed models of how a real-world evidence registry might be perceived and used by different users. Results The following key themes were identified in the interviews: (1) stigma and anonymity, (2) selection bias, (3) understanding treatment and outcome gaps, (4) lifestyle factors, (5) individualized versus population-level data, and (6) severe complications of HSV. We developed use cases for different types of users of the registry, including individuals with HSV, members of the public, researchers, and clinicians. Conclusions This case study revealed key considerations and insights for the development of an appropriate registry to collect real-world data reported by people who might be infected with HSV. Further development and testing of the registry with different users is required. The registry must also be evaluated for the feasibility and effectiveness of collecting data to support symptom management. This registry has the potential to contribute to the development of vaccines and treatments and provide insights into the impact of HSV on other conditions.

Real-World Evidence and Real-World Data for Evaluating Drug Safety and Effectiveness

JAMA ◽  
2018 ◽  
Vol 320 (9) ◽  
pp. 867 ◽  
Author(s):  
Jacqueline Corrigan-Curay ◽  
Leonard Sacks ◽  
Janet Woodcock
Keyword(s):  
Drug Safety ◽  
Real World ◽  
Real World Data ◽  
World Data ◽  
Real World Evidence

scholarly journals Real world evidence in cardiovascular medicine: ensuring data validity in electronic health record-based studies

2019 ◽  
Vol 26 (11) ◽  
pp. 1189-1194 ◽  
Author(s):  
Tina Hernandez-Boussard ◽  
Keri L Monda ◽  
Blai Coll Crespo ◽  
Dan Riskin
Keyword(s):  
Real World ◽  
Digital Health ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Cardiovascular Medicine ◽  
Real World Data ◽  
Chi Square ◽  
Regulatory Decision ◽  
Real World Evidence ◽  
Electronic Health

Abstract Objective With growing availability of digital health data and technology, health-related studies are increasingly augmented or implemented using real world data (RWD). Recent federal initiatives promote the use of RWD to make clinical assertions that influence regulatory decision-making. Our objective was to determine whether traditional real world evidence (RWE) techniques in cardiovascular medicine achieve accuracy sufficient for credible clinical assertions, also known as “regulatory-grade” RWE. Design Retrospective observational study using electronic health records (EHR), 2010–2016. Methods A predefined set of clinical concepts was extracted from EHR structured (EHR-S) and unstructured (EHR-U) data using traditional query techniques and artificial intelligence (AI) technologies, respectively. Performance was evaluated against manually annotated cohorts using standard metrics. Accuracy was compared to pre-defined criteria for regulatory-grade. Differences in accuracy were compared using Chi-square test. Results The dataset included 10 840 clinical notes. Individual concept occurrence ranged from 194 for coronary artery bypass graft to 4502 for diabetes mellitus. In EHR-S, average recall and precision were 51.7% and 98.3%, respectively and 95.5% and 95.3% in EHR-U, respectively. For each clinical concept, EHR-S accuracy was below regulatory-grade, while EHR-U met or exceeded criteria, with the exception of medications. Conclusions Identifying an appropriate RWE approach is dependent on cohorts studied and accuracy required. In this study, recall varied greatly between EHR-S and EHR-U. Overall, EHR-S did not meet regulatory grade criteria, while EHR-U did. These results suggest that recall should be routinely measured in EHR-based studes intended for regulatory use. Furthermore, advanced data and technologies may be required to achieve regulatory grade results.

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