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Lindsay Hughes, PhD, principal scientific advisor of Clario, a clinical trial data management company, presented a poster session at the recent DIA Annual Meeting titled “BYOD vs. Provisioned Devices: A Cross-Study Exploration of Factors Influencing Patient Compliance.” Exploring related factors ahead, Hughes discusses the current electronic clinical outcome assessment (eCOA) environment, new technology applications, and how technology implementations should be supported by science.
ACT: Can you share recent research or regulatory guidance in data management or data collection that our audience of clinical operations professionals should be aware of?
Lindsay Hughes: In 2021, the EMA (European Medicines Agency) and FDA released draft guidelines on the use of digital systems and electronic data acquisition in clinical trials, in June and December, respectively. My team has been doing research on these documents and have a white paper forthcoming that compares the two.
But high-level, the good news is that there is no conflicting guidance between the two, only extra topics that are covered on both sides.
The FDA’s focus is more on patient and study environment, as well as reducing patient burden to allow for more diverse study populations. The EMA focuses more on technical recommendations, such as device validation, data collection and governance, the importance of collecting and storing metadata for in-depth audit trails, and information that should be available for review. Basically, if you’re compliant with one—even with a more conservative interpretation of all the categories—then you’ll be compliant with both. Specifically, in the application of eCOA science, these considerations are already covered. For example, the EMA focuses on fit-for-purpose ePROs (electronic patient-reported outcomes), and that instruments have been designed for the intended patient population. That also is in line with what FDA guidance on this topic has been for about a decade, as well as a standard of what Clario has been doing.
ACT: What’s your take on the resurgence of eCOAs as a result of the foothold decentralized trials have gained during the pandemic?
LH: At DIA, my boss Bryan McDowell [VP, eCOA science and consulting, Clario] gave a talk, where he defined decentralized trials very succinctly. If we’re thinking of a decentralized trial, it is just a clinical trial that has one or more endpoints that are collected outside of the clinic. Pretty simple. There are many components that contribute to the success of a clinical trial. Those can vary depending on phase, therapeutic area, indication, a well-designed protocol, and reliable and valid measurements of two types of data—biomedical and health-related outcomes.
To situate where COA falls, those biomarkers are physiologic anatomic pathologic characteristics that are objectively measured as an indicator of biological or pathologic processes or responses to an intervention or clinical outcomes assessments. Clinical outcome assessments are outcomes that describe or reflect how an individual feels, functions, or survives. Within that, there are four types of reported outcomes: clinician-reported outcomes, or ClinROs; observer-reported outcomes, or ObsROs; patient-reported outcomes, or PROs; and performance outcomes, or PerfOs.
If a decentralized trial is one that has one or more endpoint that’s collected outside the clinic, the electronic, or “e”, of the eCOA enhances the hybrid models. Real-time data availability to sites or monitors enhances the ability to get information from patients in diverse environments, to put more weight on the information that’s provided directly by the patient. Because of the increased data quality, the ability for validation or adjudication, and, again, real-time monitoring, all contribute to reduce the potential for error or lost data during the data entry process.
ACT: What are the newer capabilities that sponsors and CRO should be considering for eCOAs?
LH: Two innovations we have at Clario—eCOA Multimedia and eCOA Live—enhance virtual visits. eCOA Live uses an encrypted web portal that allows participants to complete assessments remotely on their home device, meeting the minimum screen requirement—tablet, laptop, or desktop computer. And the screens that are used live exactly match, so both the patient and the clinician are seeing the same screen, which allows them to walk through assessments together much as they would in person. With eCOA Multimedia, a patient can take a photo of whatever the visual problem is; for example, reactogenicity in vaccine trials, the size of a bump, or a skin condition, will improve the ability for those objective measures to be evaluated by the clinician remotely, which would typically have required an in-person visit.
Also, the newer capabilities of connected devices and the addition of mobility endpoints, which are a big factor in quality of life. But it’s important to remember that we tie these into eCOA. Right now, the regulatory space is not accepting many digital-mobility endpoints just on their own for labeling claims, because the gold standard is eCOA.
By choosing a complementary quality of life assessment, a wearable technology that can bring data that improves the science and understanding of the treatment, will help that study, but also help design better future studies.
ACT: What current challenges are your clients and sponsors having with decentralized trials?
LH: At the World Vaccine Congress, discussions around the importance of hybrid models during the height of COVID was a popular topic. But presenters shared that it was challenging because they went to vendors who could stand things up as quickly as possible but then had 10 to 15 different vendors providing the services. So every time there was a protocol amendment, it negatively impacted their timelines because it was very uncoordinated.
This matches with what our experience and recommendations have been in doing more complex hybrid trials. We do recommend an integrated system managed under one roof, which Clario has, but even if the sponsor wants to outsource a piece, we recommend that we do the vendor management so we can benchmark the receiving data through eCOA, or connected devices to make the analysis easier, and the comparison and triangulation of data better. Again, that’s the importance of integration. If it’s not integrated you burden the site staff who need to enter data into different computers or five tablets in a session with one patient.
ACT: Can you talk about science as a service?
LH: eCOAs are only as good as the quality of the information that is coming in—so the science behind the technology. Our team is comprised of behavioral scientists who do patient engagement, patient retention, everything around the human aspect of the trial, and making sure that we get the right information, from the right people, at the right time. We now have the opportunity and the responsibility to look back and make sure that tech companies are providing science as a service as well—that there is good science behind the implementation.