The evolving role of data & safety monitoring boards for real-world clinical trials

Bryan J Bunning; Haley Hedlin; Jonathan H Chen; Jody D Ciolino; Johannes Opsahl Ferstad; Emily Fox; Ariadna Garcia; Alan Go; Ramesh Johari; Justin Lee; David M Maahs; Kenneth W Mahaffey; Krista Opsahl-Ong; Marco Perez; Kaylin Rochford; David Scheinker; Heidi Spratt; Mintu P Turakhia; Manisha Desai

doi:10.1017/cts.2023.582

The evolving role of data & safety monitoring boards for real-world clinical trials

J Clin Transl Sci. 2023 Aug 2;7(1):e179. doi: 10.1017/cts.2023.582. eCollection 2023.

Authors

Bryan J Bunning^{1

2}, Haley Hedlin¹, Jonathan H Chen³, Jody D Ciolino⁴, Johannes Opsahl Ferstad⁵, Emily Fox^{6

7}, Ariadna Garcia¹, Alan Go⁸, Ramesh Johari⁵, Justin Lee¹, David M Maahs⁹, Kenneth W Mahaffey¹⁰, Krista Opsahl-Ong⁹, Marco Perez¹¹, Kaylin Rochford⁵, David Scheinker¹², Heidi Spratt¹³, Mintu P Turakhia¹⁰, Manisha Desai¹

Affiliations

¹ Quantitative Sciences Unit, Stanford University, Stanford, CA, USA.
² Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
³ Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA.
⁴ Department of Preventative Medicine - Biostatistics, Northwestern University, Chicago, IL, USA.
⁵ Department of Management Science and Engineering, Stanford University, Stanford, CA, USA.
⁶ Department of Statistics, Stanford University, Stanford, CA, USA.
⁷ Kaiser Permanente Northern California Division of Research, Kaiser Permanente, Oakland, CA, USA.
⁸ Department of Computer Science, Stanford University, Stanford, CA, USA.
⁹ Department of Pediatrics, Stanford Medicine Children's Hospital, Stanford, CA, USA.
¹⁰ Stanford Center for Clinical Research, Stanford University, Stanford, CA, USA.
¹¹ Department of Medicine, Cardiovascular Medicine, Stanford Medicine, Stanford, CA, USA.
¹² Systems Design and Collaborative Research, Stanford Medicine Children's Hospital, Stanford, CA, USA.
¹³ Department of Preventative Medicine & Community Health, University of Texas Medical Branch, Galveston, TX, USA.

Abstract

Introduction: Clinical trials provide the "gold standard" evidence for advancing the practice of medicine, even as they evolve to integrate real-world data sources. Modern clinical trials are increasingly incorporating real-world data sources - data not intended for research and often collected in free-living contexts. We refer to trials that incorporate real-world data sources as real-world trials. Such trials may have the potential to enhance the generalizability of findings, facilitate pragmatic study designs, and evaluate real-world effectiveness. However, key differences in the design, conduct, and implementation of real-world vs traditional trials have ramifications in data management that can threaten their desired rigor.

Methods: Three examples of real-world trials that leverage different types of data sources - wearables, medical devices, and electronic health records are described. Key insights applicable to all three trials in their relationship to Data and Safety Monitoring Boards (DSMBs) are derived.

Results: Insight and recommendations are given on four topic areas: A. Charge of the DSMB; B. Composition of the DSMB; C. Pre-launch Activities; and D. Post-launch Activities. We recommend stronger and additional focus on data integrity.

Conclusions: Clinical trials can benefit from incorporating real-world data sources, potentially increasing the generalizability of findings and overall trial scale and efficiency. The data, however, present a level of informatic complexity that relies heavily on a robust data science infrastructure. The nature of monitoring the data and safety must evolve to adapt to new trial scenarios to protect the rigor of clinical trials.

Keywords: Clinical trials; DSMB; RWD; data and safety monitoring board; data integrity; data quality; decentralized; digital; pragmatic; real world data; real-world data; real-world evidence.

Grants and funding

UL1 TR003142/TR/NCATS NIH HHS/United States