Speakers
Adrian Hernandez, MD
Executive Director, Duke Clinical Research Institute
Vice Dean, Duke University School of Medicine
Christopher J. Lindsell, PhD
Professor and co-Chief of Biostatistics, Department of Biostatistics & Bioinformatics
Director, Data Science and Biostatistics, Duke Clinical Research Institute
Duke University School of Medicine
Editor in Chief, Journal of Clinical and translational Science
Keywords
Decentralized Clinical Trials, Virtual Vigilance, Data and Safety Monitoring
Key Points
- There has been global growth of decentralized clinical trials (DCTs) and with that a growing need to develop best practices and to ensure quality results are generated from trials. The global decentralized clinical trial market is expected to grow at a compound annual growth rate of 30.1% from 2021 to 2026.
- But there are concerns to developing DCTs including lack of standardization and validation, regulatory and ethical uncertainties, engagement vs. coercion, data security and privacy issues, technological literacy and access, resistance to change and adoption, and lack of “safe” sharing.
- There is agreement that trials need to meet the people, at home and covering clinical trial deserts.
- There are 5 guiding principles for defining quality that should inform DCTs: Have we enrolled the right participants according to the protocol with adequate consent? Did participants receive the assigned treatment and did they stay on the treatment? Was there complete ascertainment of primary and secondary efficacy data? Was there complete ascertainment of primary and secondary safety data? Were there any major GCP-related issues?
- Regardless of the trial inclusion and exclusion is routine. What we often do not think about is verifying the identity of the participant. In a remote study, it would be possible for duplicate enrollment, falsified or fabricated eligibility source documents, or data completed by surrogates. Consider secure digital identification, two-fact authentication or virtual/video visits. Balance with not adding barriers for participation.
- Getting study drug and other study materials into the hands of a participant requires distribution via mail or courier, breaking the traditional chain of custody. Under RBM, the process by which study materials get to participants should be considered high risk and monitored accordingly.
- As roles for sites change, it remains critical that participants can be actively managed and that data about patient status can be acted upon, including mechanisms for participants to ask questions and get timely responses, participants to report worrisome events, participants to report healthcare encounters and other events, tracking adherence to study intervention, and tracking adherence to data collection procedures. Solutions include a bi-directional EDC (electronic data capture system), MyChart for research, and active notifications to study personnel based on entered data.
- Baseline state, treatment, outcome, and safety data are critical to understanding treatment benefits and risks. Outcomes including patient reported outcomes, functional assessments including via digital technology, healthcare events or mortality may require identify verification. Supporting documentation may include recordings of functional assessments, EHR data, or other information that can be uploaded for remote review. Note that the release of medical records may be needed for health systems unrelated to sites.
- New issues to consider for DCTs: Geographic distribution of participants; enrollment of two or more participants who share the same digital resource; enrollment of participants who do not have sufficient digital resources; and rogue digital and social media recruitment practices
Discussion Themes
-Do you anticipate that a new set of clinical practices will emerge from this work? I think we must. One of the things we are in the process of sharing in terms of what we are observing is putting new procedures for what we monitor in a study. It is based on good study design and focusing on the key principles we are trying to adhere to. There has to be a range of approaches that could be fit for use.
–Can you comment on how this is perceived at NIH and some of the institutes? I am sure NIH is trying to accelerate our understanding of DCTs. The knowledge base isn’t there yet in terms of what you need to look for that would be missing in terms of monitoring efforts. From my perspective, if one key goal for NIH is to reach people in underserved communities having sound practices for decentralized methods will be important.
–How can we prepare research teams that do not always have the training and compensation to do all of these things? We need to train the workforce for what we need them to do. We are building out what are the core competencies, the technological, legal, ethical, clinical research administration competencies that are needed in addition to data management for a CRC. I hope we see further development of education programs that support the workforce with the skills needed. The skills may also vary between trials and getting participants the care they need.
Tags
#pctGR, @Collaboratory1