Data Capture in the Age of Decentralized Trials: Why “Electronic” Is Not Enough

By: Ed Seguine – CEO – Clinical Ink

The clinical research industry has made gradual, steady progress toward incorporating remote monitoring and virtual clinic visits as well as virtual enrollment, electronic informed consent (eConsent), and electronic patient-reported outcomes (ePRO), among other digital solutions. The disruptions caused by COVID-19 have shown us that it’s time to pick up the pace.

The pandemic accelerated adoption of decentralized clinical trials, usually combining fewer sites and site visits with remote options. Now that more sponsors and CROs have adjusted to and support this format, the underlying platform used to collect clinical trial data must change.

As technology advances, the amount of data generated and the number of data sources used to collect that data have both grown exponentially. As a frame of reference, International Data Corporation (IDC) predicts that by 2025, the global DataSphere will reach 175 zettabytes — the equivalent of 175 trillion gigabytes.(1) IDC estimates healthcare and life sciences data comprise about seven percent of the enterprise DataSphere.(2)

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Data Demands on Clinical Research

In decentralized trials, remote visits are conducted via telemedicine or by home health clinicians. Data are collected using remote patient monitoring technology (pulse oximeters, blood glucose monitors), or for ePRO, an app on a provisioned mobile device or on participants’ smartphones (BYOD). 

The increasing amount of data generated by clinical research, from an expanding variety of sources, provides enormous opportunity for researchers. With advanced analytics, researchers can use that data to expand eligibility criteria, expand indications for existing therapies, develop precision medicines, and stop disease before it starts. 

At the site level, sponsors and investigators can, with the right technology, observe and analyze data in real time. With digitized data immediately visible, site staff can detect and resolve anomalies before they become trial-derailing issues. Standard practice doesn’t allow that to happen efficiently or effectively.

According to Veeva’s 2020 Clinical Operations Survey Report, most sponsors and CROs surveyed use electronic data capture (EDC) to “automate” clinical trials. However, all respondents (100%) said they needed to improve information-sharing — whether to reduce manual processes (75%), improve visibility and oversight (58%), and/or speed trials (58%).(3)

EDC will not help sponsors and CROs achieve these goals. While EDC does store data electronically, it relies on paper-based source documents transcribed into the system and saved in an electronic case report form (eCRF). Later, monitors must double-check this step in a process called source data verification (SDV).

If researchers plan to collect and integrate all the data captured from in-person and remote site visits, often using multiple devices and methods, EDC is not a feasible, sustainable solution. EDC systems are built to accommodate relatively low-volume, discrete data inputs. They are not well-suited for the complex workflows that most sites encounter when they use technology to capture source data during the patient visit.

eSource direct data capture (DDC) is an efficient alternative suited to complex workflows and decentralized trials. eSource DDC captures data electronically, directly into the eCRF at the moment of data creation, the clinic visit. There’s no need to manually transcribe values into the EDC after the fact, and there’s little to no need for SDV. 

For example, if a clinician needs to record a participant’s blood glucose level, the clinician will take the reading and enter the value into a tablet equipped with the eSource platform’s app. The eSource system produces valid results instantly. If the value falls outside of a preset, acceptable range, the team receives an alert and addresses the issue during the patient visit. Using EDC’s paper-based process, an out-of-range value wouldn’t be caught for weeks, compromising patient safety and the integrity of that patient’s data.

The Move Toward DDC

A holistic eSource DDC system integrates all data sources into a single output, simplifying tracking, evaluation, and reporting for sponsor and CRO teams. eSource DDC systems are designed to handle a range of clinical data: vitals, lab results, ePRO, electronic clinician-reported outcomes (eCOA), lab results, and even audio, video, and handwritten notes. 

eSource DDC has the capacity and functionality to meet the data demands of decentralized trials. It prevails over the current standard, EDC, in the following ways:

1. Reduces duplicate data entry. eSource DDC systems typically have user-friendly interfaces that allow site staff, clinicians, and even patients to enter information directly. This removes the time-consuming step of transferring data from a paper form into the eCRF. By eliminating this extra step, the potential for data-entry error is reduced.
   
2. Promotes study compliance. eSource applications used on mobile devices are designed with patients in mind. They’re intuitive, so patients can easily fill-out ePRO assessments and diaries. Automatic reminders and alerts prompt patients, caregivers, and/or site staff to complete assessments or take some other necessary action at the right time. Patients are less likely to forget to fill out their dairies or take their medication. Patient-friendly interfaces provide the encouragement and reinforcement patients need to stay engaged throughout the study, potentially lowering dropout rates.
3. Improves data accuracy. Completing ePRO assessments at the right time improves data accuracy. Patients aren’t completing a month’s worth of assessments the day of their site visit, struggling to remember how they felt weeks ago. Further, eSource is built around site workflows, optimizing the flow of information between patients, sites, and sponsors, and automating rote tasks for sites. Streamlining workflows improves data accuracy by reducing the number of steps between patient encounter and site audit. A 2016 study compared eSource and non-eSource workflows for OB/GYN research. eSource reduced overall data capture time by 37 percent compared to traditional methods. The study also found eSource reduced transcription error frequency from nine percent to zero.(4)
4. Provides potential for full remote monitoring. Sending monitors to sites to perform SDV is inefficient, expensive, and in the case of infectious disease studies or a pandemic, unsafe. A common alternative among sites is to email scanned paper documents to CRAs or enable direct access to electronic medical records (EMRs). These options raise the potential for human error and potential HIPAA violations. Because SDV is nearly eliminated with eSource, monitors can conduct oversight without administrative burden and without travel, resulting in significant time and cost savings. With real-time review, monitors and other study staff can spot trends and anomalies more quickly and easily, which allows sponsors/CROs to resolve potential issues before they become major problems. With this more efficient review, sites can achieve database lock within 24 hours.
5. Makes data interoperable and accessible. eSource databases update in real-time. The systems typically integrate data points under a common language; instead of employing checkers and reviewers, sponsors/CROs can rely on interoperability to simplify data workflow. With data from nearly every stage of a trial accessible almost instantly, and simultaneously, sponsors/CROs can glean deeper insights about the study. These insights are important when implementing a risk-based monitoring plan an approach recommended by the FDA.
6. Lowers operational costs. On-site monitoring comprises up to 30 percent of a clinical trial’s total costs.(5) On top of that, sites spend, on average, about two weeks per study creating source forms, transcribing data into the EDC, and conducting study visits.(6) For a study with sites around the globe, eliminating CRA travel costs and reducing site staff workload leads to six-figure savings. Add improvements in workflow, productivity, and speed, and eSource becomes a financially attractive solution.

Challenges to Widespread Implementation

TransCelerate BioPharma, an organization dedicated to efficient biopharmaceutical research and development, outlines a few key challenges that have hindered eSource adoption:(7)

• Lack of stakeholder involvement
• Source data access and correction
• Site and participant burden
• Errors due to technology

These perceived challenges aren’t deal-breakers for eSource DDC. In other words, as with most problems, there are solutions.

Lack of Stakeholder Involvement

An agile study build involves multiple stakeholders. These stakeholders come together to acceptance-test the deployment and provide immediate feedback as it’s being deployed. This helps streamline the implementation process.

In addition, TransCelerate recommends including eSource experts in the clinical trial design process to improve efficiency. Specifying eSource DDC in the protocol helps prevent unnecessary amendments. 

Lack of stakeholder buy-in also inhibits adoption of innovative technology such as eSource. Former FDA Commissioner Scott Gottlieb once said efforts to streamline drug development “can be frustrated by legacy business models that discourage collaboration and data sharing, and the adoption of disruptive technologies that can make clinical research more effective.”(8)

It’s no surprise, then, that smaller, more agile biotech companies are more willing and able to adopt advanced data management platforms. It’s no coincidence many new drug approvals stem from emerging drug companies and biotech startups. They’re not encumbered by legacy technology platforms and can move forward efficiently.

Source Data Access and Correction

Sponsors and CROs may be unclear on processes for querying and correcting source data. eSource collects data during the patient visit. Edit checks within the app trigger immediate correction of any abnormally high or low values. In addition, by nearly eliminating SDV, the error rate drops even further.

Other data sources, such as ePRO, can be immediately saved as part of the electronic record. Immediate data capture provides a clear audit trail, which decreases site burden. If a clinician scribbled a blood pressure reading on the back of an envelope, that envelope would need to be saved and recorded, creating a cumbersome process for site staff.

Site and Participant Burden

Some sponsors and CROs believe eSource implementation increases the burden on sites and patients. While moving from EDC to eSource DDC is an adjustment, the technology promotes a positive site and patient experience. Adequate training, including in-app walk-throughs and interactive tutorials, will facilitate this result.

Ultimately eSource DDC reduces site burden due to the time savings from eliminating duplicative data entry. To reduce possible burden on patients, sponsors can seek and incorporate feedback from sites on protocol design to ensure patient and site-centricity.

Errors Due to Technology

Some sponsors are concerned that using new technology could cause “unexpected behaviors” or errors at the point of data capture. Risk assessments by modality can help sponsors understand how eSource behaves under various circumstances. By conducting periodic risk mitigation, sponsors can make sure eSource performs as it should during patient visits. This reduces the possibility of errors during an assessment. 

It’s also worth restating that the simple user interfaces, reduction of manual data entry, and ongoing edit checks lower the potential for errors as compared to EDC.

Conclusion

As researchers collect more data from more sources, paper-based data-collection methods will only hinder clinical research. An effi cient eSource DDC platform has the capability and capacity to handle the industry’s growing data demands. To maintain a competitive advantage, larger pharmaceutical companies and CROs will have to let go of established processes and adopt technology that supports the next generation of clinical research.

References

1.  Data Age 2025: Is Your Business Ready? Seagate.
2. Reinsel, David et al. “Monitoring the Pulse of the Healthcare and Life Sciences DataSphere.” IDC Market Perspective, November 2020.
3. “Veeva 2020 Unified Clinical Operations Survey Report.” September 2020.
4. Nordo AH, Eisenstein EL, Hawley J, Vadakkeveedu S, Pressley M, Pennock J, Sanderson I. A comparative effectiveness study of eSource used for data capture for a clinical research registry. Int J Med Inform. 2017 Jul;103:89-94. doi: 10.1016/j.ijmedinf.2017.04.015. Epub 2017 Apr 29. PMID: 28551007; PMCID: PMC5942198.
5. “Examination of Clinical Trial Costs and Barriers for Drug Development. 4.6.3 Data and Site Monitoring.” Office of the Assistant Secretary for Planning and Evaluation, July 25, 2014.
6. “Why is Clinical Source Data Still Collected on Paper?” Society for Clinical Research Sites, 2017.
7. Parab AA, Mehta P, Vattikola A, et al. Accelerating the Adoption of eSource in Clinical Research: A Transcelerate Point of View. Ther Innov Regul Sci. 2020;54(5):1141-1151.doi:10.1007/s43441-020-00138-y
8. “Statement by FDA Commissioner Scott Gottlieb, MD, on new strategies to modernize clinical trials to advance precision medicine, patient protections and more efficient product development.” FDA Statement, March 14, 2019.

About the Author

Ed Seguine, CEO at Clinical Ink, has more than 20 years of experience as a clinical technology executive at Big Pharma and startup organizations. Before joining Clinical Ink, he served as general manager, trial planning at Medidata Solutions. He also served as CEO of Fast Track Systems, where he oversaw the turnaround process and established early commercial successes for a novel product that became the rationale for acquisition by Medidata Solutions.

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