Industry groups seek more flexibility for DHTs in clinical trials
Industry groups have asked the US Food and Drug Administration (FDA) to provide more clarity about its regulatory approach to digital health technologies (DHTs), as well as for greater flexibility in their use in clinical trials.
In a March request for information, FDA asked stakeholders what opportunities there are for using DHTs when developing medical products and what challenges they face. The agency said the feedback would be used to develop guidance and to inform its decision-making. It noted that DHTs encompass a wide range of software and connected products that may include sensors in wearable, implantable, and ingestible devices.
FDA published a 2023 framework that includes demonstration projects, public meetings, guidance development, and the creation of a DHT steering committee that can promote the use of DHTs and help bring new drugs and devices to market. The same year, the agency published guidance on using DHT to collect clinical investigation data remotely. However, it noted that over the past three years, DHTs and sensors have advanced significantly, offering new opportunities for their use.
"Many of these sensors are present in smartwatches and mobile phones and may be customized using mobile applications (apps) for clinical investigations," said FDA. "Apps and other DHTs are being designed to perform interactive clinical tests of patient function.
"Besides mechanical tasks, screen-based technologies are being explored to test neuropsychiatric functions such as reaction time, cognition, vision, hearing and to evaluate conditions such as autism or post-traumatic stress disorder," the agency added. "In addition, DHTs are being designed specifically for pediatric use and may play a role in evaluating new drugs and biological products in children."
PhRMA
Among the stakeholders who responded to the FDA's RFI, the Pharmaceutical Research and Manufacturers of America (PhRMA), argued that, despite the agency's efforts, there has been limited progress toward allowing the use of DHTs to inform regulatory decision-making. It noted that DHT-derived endpoints have not been used as primary or secondary endpoints in clinical trials to the extent anticipated.
PhRMA noted that DHTs have the potential to advance clinical investigations by enabling innovative trial designs and data acquisition, and to support decentralized clinical trials that allow patients who otherwise would not be able to participate.
"Technologies, such as wearable, implantable, and ingestible sensors, software, and mobile applications, enrich our understanding of patient experiences and outcomes through continuous monitoring and more frequent, robust data collection," said FDA. "The COVID-19 pandemic highlighted the utility of DHTs by demonstrating how remote data acquisition can maintain trial continuity during public health emergencies.
"PhRMA encourages FDA to advance DHT adoption by building on learnings from demonstration projects, pilot programs, public meetings, and guidance development," the group added. "We also encourage increased engagement through the DHT Steering Committee and the Digital Health Center of Excellence (“DHCoE”), including enhanced opportunities for targeted engagements with sponsors (e.g., through pre-IND meetings)."
PhRMA asked FDA for flexibility to accommodate evolving DHTs. More specifically, the group asked the agency to provide a clear, flexible, and risk-based approach to allow use of fit-for-purpose DHTs; provide practical tools such as templates and decision trees to use DHTs; clarify the agency's expectations for managing DHT changes, such as software updates; and ensure regulatory harmonization on DHTs not only between product centers but also with other drug regulators.
CPC
The Combination Products Coalition (CPC) wrote to FDA and said there is a lack of clarity about differentiation across DHT use cases, timing and placement of DHT information in submissions, and cross-center expectations.
The group asked the agency to promote transparency by clarifying how DHTs will be evaluated and incorporated into regulatory decision-making. It also asked that DHCoE be empowered to serve as a formal cross-center coordination body for DHT matters and that the agency play a leadership role in promoting global harmonization on the topic. It also asked FDA to support least‑burdensome submission mechanisms, such as enabling a master file-type approach for DHTs.
"This would allow third-party providers to maintain centralized, risk-proportionate, documentation on DHT and AI tool performance, validation, and lifecycle management, which sponsors could then reference across multiple programs, especially in cases where a third-party is producing a clinical trial only use product and therefore does not seek FDA clearance/approval," said CPC. "Such an approach is particularly valuable where proprietary information limits the ability of third-party developers to fully disclose underlying methodologies directly to multiple sponsors, creating inefficiencies and potential barriers to adoption. This helps to reduce duplicative submissions, facilitate more efficient review, and appropriately delineate responsibilities between product sponsors and external technology developers.
"This supports scalable adoption of DHTs and AI-enabled tools, while ensuring FDA maintains appropriate oversight of critical information supporting regulatory decision-making," the group added.
BIO
The Biotechnology Innovation Organization (BIO) said that its members agreed the most significant barriers to adopting DHTs include the lack of clarity about evidentiary expectations for DHT-derived endpoints, verification and validation requirements, and selecting the right regulatory pathways for DHT use in drug development. The group also noted that the lack of cross-center consistency, the opaqueness of FDA's internal processes regarding DHT reviews, and the lack of publicly available information have been major challenges for its members.
"BIO recommends timely Agency-stakeholder engagement mechanisms, both formal and informal, including prioritizing in-person meetings, transparent feedback timelines, and coordinated cross-Center alignment," said BIO. "BIO members also highlight the need for practical tools, such as risk‑tiered templates, case studies, decision trees, and examples to support consistent implementation.
"Specifically, BIO considers evidentiary templates to be essential, practical instruments that enable fit-for-purpose development and promote more consistent and predictable integration of DHTs into clinical research," the group added.
BIO also asked for more clarity on how sponsors should handle missing or incomplete data, manage software and firmware updates during clinical trials, establish composite or multimodal endpoints, and determine when evidence can be reused or bridged across contexts of use, populations, and device versions. The group also said it's important for FDA to address equity and accessibility considerations to ensure DHTs reliably perform across diverse populations and don't widen the digital divide.
