Human Interaction: Risk-Mitigation Recommendations When Using Technology in Clinical Trials
Bill Barrasso
Clinical Ink
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ecent technological advances have expanded accessibility of clinical studies to larger and more diverse populations. However, technology alone will not ensure successful completion of research studies. The human element—how sites, sponsors, and patients use technology within applicable regulatory guidelines—is still the key to maintaining compliance, minimizing risks, and ensuring patient safety.

This article references recent guidance from the FDA (Decentralized Clinical Trials for Drugs, Biological Products, and Devices, Guidance for Industry, Investigators, and Other Stakeholders, May-2023) and EMA (Guideline on computerised systems and electronic data in clinical trials, March-2023). These publications highlight the importance of human involvement when using technology in clinical trials.

The FDA draft guidance provides a good collection of evolving Decentralized Clinical Trial (DCT) best practices. Newcomers to the space will benefit from reviewing the details included therein. There are also key sections regarding site and sponsor responsibilities that are crucial to ensuring compliant trial completion.

Decentralized Clinical Trial (DCT) Design Considerations for Sponsors
FDA, Section III-C Digital Health Technologies (DHT)

While technology can enable remote participation, it is important to acknowledge that a one-size-fits-all DCT study design approach is not feasible. There are still some therapeutic areas where traditional site-based study design is the best option. For example, Oncology studies may require direct access to physician expertise and in-person procedures and labs, which makes them not suitable for full DCT models.

Recommendation: In such cases, a hybrid DCT model may balance required in-person interactions with technology-enabled remote participation, prioritizing patient care and safety.

Safety Alerts and Monitoring Considerations for Sites
FDA, Section III-H. Safety Monitoring Plan

In some study designs, technology mechanisms have been incorporated to record Adverse Events (AEs) and in some cases, alert study staff about serious AEs. Although covered in Informed Consent agreements, patients must be trained to promptly contact their Healthcare Provider (HCP) or seek emergency medical assistance if their condition worsens, or they experience unexpected side effects.

Direct contact between patients and healthcare professionals is crucial to ensuring patient safety. Technology tools used in a study may not have the necessary cellular/Wi-Fi connectivity at the required moment to provide the intended site notification and timely response. Reliance solely on technology to alert HCPs of serious AEs may lead to delayed intervention and put patients at risk.

Recommendation: Unless specifically designed and validated as a monitored emergency notification system, study design should not recommend technology tools as the sole method for reporting/alerting of serious AEs for required intervention.

Patient Training Considerations for Sites and Sponsors
FDA, Section III-I Software Used in Conducting DCTs

Not all patients have the same level of familiarity or comfort with technology. Sites must train patients during the initial visit to ensure they are comfortable using the technology. Simple and intuitive practices should be emphasized, and biometric security access (for example, fingerprint identification) can help alleviate the frustration of forgotten PIN codes.

Recommendation: Sites should periodically review patient-submitted data compliance and regularly check in with patients throughout their study participation to identify potential needs for retraining.

Timely Data Clarification Request (DCR) Processing
EMA, Section A5.1.1.4 Data changes

Timely management of data clarification requests is crucial to preventing delays in study timelines. Late DCR submissions, close to interim or final database lock milestones, create an urgent need for site approval of DCR data to complete the required processing, which can be a drain on site resources.

Late DCR processing may delay study timelines to the point where site contracts have expired, necessitating process deviations to complete the required work. Attempting to collect site DCR approvals after study contracts have expired is often difficult because site staff may be fully assigned to other contracted work.

Recommendation: Deviations are never a desired asterisk on any study data-processing timeline. These can be avoided with timely management of DCR requests, weekly or monthly throughout the study lifecycle, while sites are fully engaged.

Patient Record Retention
EMA, Section 6.6. Control of data

The referenced guidance highlights the requirement for sites to maintain ready access to their patient records even after the study ends. That is, sites need to receive and maintain copies of their patient records locally before online access is removed from study data servers. Sites may not be able to accept, process, and store these records if they are made available after site contracts have expired.

Recommendation: Include a final payment milestone in site contracts that specifically compensates sites for end-of-study activities such as DCR approval and receipt/acknowledgment of their patient study records. This will compensate sites for required actions if site contracts have expired and ensure sites retain ready access to study records for review any time a patient safety concern arises.

Best Practices: Daily Site Preparation is Important

Trials that require some level of Direct Data Capture (DDC) or electronic Clinical Outcome Assessment (eCOA) completion by site staff and patients often utilize technology tools. While these tools are often reliable and capabilities are evolving, some human oversight is required.

Recommendations: When preparing for daily site visits by patients, site staff should:

  • Perform a cursory check of the technology devices to ensure they have sufficient battery power to enable data transmissions.
  • Regularly confirm there is sufficient Wi-Fi coverage in all areas where patient interaction will occur. Insufficient Wi-Fi coverage may prevent study devices from making required communications with a data portal, which can cause delays during patient visits.
  • While such checks are typically done during Site Initiation Visits, Wi-Fi coverage can change over time due to equipment replacement, new construction at sites, or network latency. For these reasons, it’s beneficial to regularly confirm proper device operation.

Conclusion

While technology plays a valuable role in facilitating clinical research studies, effective planning and human involvement from sites and sponsors is required to achieve compliance. Prioritizing patient well-being and maintaining direct communication between patients and healthcare professionals will help adhere to regulatory guidelines and ensure patient safety.
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