linical trials generate evidence that ultimately defines the safety and efficacy of a new medical product. The evidence is then evaluated and approved by a regulatory agency before it is launched commercially. As stakeholders in the pharmaceutical industry, we recognize that clinical trials have been becoming increasingly costly and time-consuming. Therefore, we need tangible solutions to help trials become quicker, more cost-efficient, and sustainable while supporting inclusivity of all populations.

Decentralized clinical trials (DCTs) offer practical solutions to this field by bringing the trial experience closer to the participants through appropriate trial designs, technology, operational flexibility, and trial services. They offer renewed hope that future clinical trials can enroll more efficiently, retain more participants, and ultimately bring medical advancements to mankind faster. To examine the true advantages of DCTs in clinical research, we believe that an in-depth analysis is needed, which would help bolster adoption of these innovative approaches.

Project SHASTA: Evaluating the True Impact of Decentralized Clinical Trials

It is assumed that trials with decentralized elements are more advantageous to run than traditional brick-and-mortar (B&M) trials, but is this actually true? While DCTs may theoretically present clear advantages, their true impact still needs rigorous evaluation. Project SHASTA—which stands for MeaSuring tHe Added BenefitS of Decentralized TriAl Elements—conducted such an evaluation; some of the findings and recommendations are described here.

SHASTA is one of the industry’s earliest attempts at pooling learnings from a single sponsor. The sponsor is a global pharmaceutical company with broad experience in DCTs. The purpose of SHASTA is to examine the quantitative and qualitative learnings from multiple US-based DCTs, identify operational and regulatory opportunities, and fully capture the value of DCTs for stakeholders.

The clinical team addressed the following research questions:

• What is the improvement in clinical trial enrollment efficiency compared to historical benchmarks, defined as the number of participants enrolled per site per month?
• What is the improvement in enrollment of the demographic minority population compared to historical benchmarks, specifically African American, Asian, and Hispanic participants?
• How do we measure data quality obtained in a DCT versus the brick-and-mortar approach?
• What have been some notable clinical operational learnings that can be applied across DCTs?

The full results of the SHASTA project will be published in the near future, but a summary of identified regulatory opportunities is presented below.

SHASTA Identified Regulatory Opportunities

The regulatory frameworks governing clinical trials have traditionally been designed around B&M trials, where participant oversight and data collection occur within established healthcare facilities. DCTs introduce novel operational elements, such as mobile healthcare delivery and remote data capture, which complicate regulatory oversight.

SHASTA has identified a number of regulatory opportunities to improve the conduct of DCTs:

1. Standardized Training for DCT Personnel: It is observed that vendors involved in DCTs ideally need to have specialized disease state training and a track record of handling the specific data sources, such as electronic medical records. Current FDA guidance documents do not address the specific training required for personnel in decentralized settings. Standardization in this regard could significantly enhance data reliability and regulatory compliance.
2. Enhanced Oversight Mechanisms for Mobile Health Services: Mobile nursing, while advantageous for participant convenience, raises questions about consistent clinical oversight and accountability outside traditional settings. Developing stringent oversight mechanisms is crucial, such as a governance structure and metrics tracking. These would ensure that participant care quality remains consistent with traditional B&M trials, thereby minimizing regulatory risks that affect participant safety, clinical accountability, and general trial management.
3. Adaptability to Demographic and Regional Variations: The deployment of DCTs can be influenced by participant demographics and site-sponsor relationships. The SHASTA project shows that results from certain trials might not be generalizable due to specific participant demographics and site partnerships. For example, some trials in SHASTA are noninterventional and cross-state licensure is not required. Regulators need to tailor guidance documents to account for such variations, ensuring that trial outcomes are widely applicable.
4. Robust Data Quality Assurance Processes: Ensuring that data quality in DCTs matches that of B&M trials is a matter of regulatory and sponsor priority. Insights from SHASTA suggest leveraging continuous feedback and adaptation to enhance data integrity systematically. This can be completed upfront through a mitigation plan. Regulatory frameworks need to incorporate processes for regular quality checks and data validation specific to decentralized settings.

The SHASTA project sheds light on crucial aspects of the regulatory landscape surrounding trials with decentralized elements. While the transition towards DCTs offers promising benefits in terms of speed and diversity, it also presents unique challenges that require vigilant regulatory oversight. By addressing existing gaps, regulatory bodies can foster the successful integration of DCTs into mainstream clinical research.

Given recent changes in the Presidential Administration and the resulting reduction in FDA staff, clinical trialists must present clear plans and mitigation strategies upfront to ensure streamlined conversations with regulators. FDA will experience resource constraints in the next few years. The pharmaceutical industry needs to show ever stronger leadership to identify opportunities for close conversations with health authorities and recommend pragmatic solutions proactively. The SHASTA effort can be seen as one sponsor’s recommendation of novel processes. May this be a call to action for other sponsors to share their voices as well.