When the condition at the center of a clinical study is a complex disesase like systemic lupus erythematosus (SLE), several unique challenges surface. With outdated data processes, ineffective study design, and lack of understanding, these obstacles can increase.
Outsourcing-Pharma (OSP) recently spoke with Doug Pierce (DP), president of clinical trial data solutions provider Clinical Ink, about the specialized challenges faced in SLE trials and other complex-disease studies, and how sites and sponsors can harness advanced data capture practices to overcome them.
OSP: Could you please talk about some of the reasons why SLE is a difficult therapeutic area to study?
DP: Often, the investigators at the research sites might be experienced in treating lupus, but less experienced in conducting research. They lack sufficient understanding of the disease assessments that are required for lupus research. There are structured diagnostic questionnaires (SDQs) specific to research, not used on treatment; one of the challenges is the lack of sufficient understanding of how to properly complete the SDQ used in research.
Also, lupus research often suffers from insufficient documentation to support scores and grades, and to respond to queries. Documentation requirements for lupus research are extensive--far more than in a typical patient medical chart.
Typically, there’s a very long time lag between when a patient is seen, and when the study team has access to the data. The study team, the sponsor or CRO team, needs to have immediate or near-real-time access, but often they wait weeks or months to see it—at the end of the study, there’s a big lag time between the last patient’s last visit and when they can lock the database.
Finally, there is an extraordinarily high number of queries generated in a lupus trial. That places a burden on the site, and the sponsor.
OSP: You’ve mentioned that when it comes to study planning and protocol design, sites are traditionally left out of the equation. Could you please elaborate on that—how do sites get left out, what the dangers are in that, how does that impact sites and staff administering studies, etc.?
DP: They’re left out deliberately--it’s not an oversight. Sites are not typically part of a protocol design, not part of the technology selection, not part of the tech design; they simply aren’t included in those steps.
The irony is the sites are the sine qua non of clinical trials. If the sites can’t perform well, nothing else works. If there was only one site, they’d be included, but sometimes there’s hundreds.
How do you include their perspective? At the end of the day, protocol design and technology solutions need to fit the needs of the sites. Sometimes there’s technology that’s burdensome or obtrusive. Streamlining documentation and data capture can alleviate the burden, increasing productivity and quality.
OSP: Please share what we mean when we talk about “fit for purpose.”
DP: Clinical Ink has developed a module called eLAS (electronic lupus assessment suite). eLAS is a therapeutic-area specific application of our direct data capture (DDC) platform, not just an e-version of a paper form; it’s purposely built to address these challenges.
eLAS has over 6500 data connections, allowing patient and clinician data to flow between fields, forms and visits. Seeing data in the context of previously reported data is critical to understanding changes in the patient manifestations over time, which is a core component of lupus research.
eLAS enables us to improve execution of the protocol by highlighting information required to be captured. Doing this ensures documentation needed to support investigators’ conclusions is created—it goes back to the problems of insufficient documentation, and insufficient understanding.
It can guide through completion of the necessary documentation. In guiding, we need to be careful—we can’t bias investigators or lead them to any conclusions, but you can let them know what is required of them from a documentation point of view.
OSP: Would you please explain how tools like DDC, eConsent, ePro, eCOA and risk-based management (RBM) can help address trial complexities, especially when relateed to lupus?
DP: Electronic suites that include DDC, eConsent, ePro, eCOA, RBM—all of these address the site’s needs to capture data during the patient visit and highlight data that can be indicative of risk.
Let’s look at an eConsent tool that allows a subject to work through an informed consent form and increases their understanding of the trial. We can use pop-up definitions, illustrations and even video to make the informed consent clear and increase the patient’s understanding.
After you consent a person and they join, ‘technologies like DDC and ePRO can streamline data capture and documentation generation necessary to support the protocol. This ensures compliance with regulations, improves quality of data, and allows the sponsor team to gain access to the data in near real time.
Having real-time access to data eliminates one of the biggest risks: not knowing what’s going on at the sites, not being aware of potential risks because you haven’t seen data. Giving near-real-time to data, and targeting data indicative of a problem, helps deal with risk.
OSP: Could you please talk about the differences between electronic data capture (EDC) and DDC?
DP: If you think about how you document a patient visit and then share data, there are two approaches. The dominant approach is EDC.
However I believe EDC is a misnomer, since you are actually capturing data on paper during the visit and only later transcribing it into the EDC application. EDC should really be called EDT, for electronic data transcription.
DDC, as the abbreviation indicates, allows you to record during a patient visit; the moment that matters is the patient visit. You’re entering data directly into an application, allowing you to run edit checks while the patient is there, cleaning as you go.
When the visit is complete, you upload the chart, and the entire study team has access to it before the patient gets to their car.
DDC and ePRo and eCOA, all share one quality that sets them apart: all are used during the patient visit, and all allow direct data capture. That’s a critical difference--modern studies that take advantage of new technology, and traditional studies that don’t.
An important difference between these two approaches is that monitors don’t have to go to sites or review paper source documents—everything needs to be done remotely. Virtual trials can’t run on systems that require the completion of paper forms during the patient visit. Running virtual trials, being able to remotely monitor—all of this requires a DDC system.
Real-time access to things used to be impossible; now, it’s what we should all demand. In the US, the average time between a patient visit and information upload is 18 days, which may be too late to catch and correct an issue.
If you’re using a DDC solution like ours….say you’ve got a new coordinator at a site, and the first patient visit is Monday at 10 a.m. At 11 a.m., you can log in check data and see immediately that they did a great job, or that you need to correct them. Real-time access to what’s going on makes that possible.