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US FDA’s final guidance on Digital Health Technologies for Clinical Investigations

US FDA’s final guidance on Digital Health Technologies for Clinical Investigations

The landscape of clinical investigations is evolving rapidly with the integration of Digital Health Technologies (DHTs). The US FDA has released comprehensive guideline aimed at sponsors, investigators, and stakeholders involved in remote data acquisition during clinical trials. DHT encompasses systems utilizing computing platforms, software, and sensors for healthcare purposes. The guideline covers broad spectrum of DHTs, emphasizing the need for sponsors to ensure compatibility with supporting technologies. 

The DHTs offer opportunities for continuous data collection, enabling remote monitoring and potentially broadening participation in decentralized clinical trials. The guideline addresses regulatory considerations, stating that some DHTs may qualify as devices but may be exempt from certain regulatory requirements. It highlights the importance of early engagement with the FDA for discussions on DHT usage in specific clinical investigations. Additionally, developers can pursue qualification of DHTs as Drug Development Tools (DDTs) or Medical Device Development Tools (MDDTs) through voluntary qualification programs, supporting their use in clinical submissions. 

Regulatory considerations for usage of DHT in Clinical Investigations:

  • Selection of a Digital Health Technology: Sponsors are advised to carefully select DHTs based on the clinical event, technical specifications, and trial population. Considerations include factors such as education, language, age, and technical aptitude of participants. The design, technical specifications, and operation of DHTs are crucial, and sponsors should assess factors like battery life, data storage, and cybersecurity risks.

  • Digital Health Technology Description in a Submission: Detailed descriptions of DHTs should be included in submissions, covering design, technological characteristics, data output, and data flow. Emphasis is placed on ensuring privacy and security and providing options for participants to report additional information.

  • Verification, Validation, and Usability Evaluations: Usability evaluations are crucial to assess participant interactions and potential errors. Considerations include involving DHT manufacturers, patients, caregivers, and technical experts. The guidelines stress the need for interoperability to exchange information securely and efficiently.

  • Evaluation of Endpoints Involving Data Collected Using DHTs: Endpoints involving data from DHTs need precise definition and justification. The guidance discusses the distinction between established and novel endpoints, emphasizing the importance of clinical relevance, predictability of clinical benefit, and relationship to existing endpoints.

  • Statistical Analysis and Trial Design Considerations: The guidelines emphasize the importance of a consistent method for data collection across study arms, appropriate trial designs, and a well-defined statistical analysis plan. Considerations include the estimated framework, handling missing data, and strategies for identifying and addressing events that may affect data collection.

Risk considerations associated with the use of DHTs in Clinical Investigations

The risks usually associated with the use of DHT in clinical investigations can be clinical related or privacy related or centered around informed consent.

Clinical Risks:

  • Physical Features Evaluation: The physical attributes of DHTs, such as wrist bands or skin-contacting components, should undergo thorough evaluation to minimize discomfort and the risk of injury. Safety testing and usability evaluations, conducted by either the DHT manufacturer or the clinical investigation sponsor, play a vital role in ensuring participant safety.

  • Treatment Modification Risks: When DHT measurements influence investigational product administration or participant treatment, the risk of erroneous measurements leading to inappropriate treatment becomes critical. Rigorous evaluation and risk assessment are imperative in such cases.

Privacy-Related Risks:

  • Disclosure of Personally Identifiable Information: The potential disclosure of participant information or locations due to DHT breaches poses a unique privacy risk. Safeguards, including robust security measures, must be implemented to prevent unauthorized access.

  • End-User Licensing Agreements: DHTs may have agreements allowing data sharing with third parties. Sponsors should proactively work with manufacturers to modify these agreements for study purposes, ensuring participant data privacy.

Informed Consent:

Sponsors must consider cybersecurity threats that could impact DHT functionality, potentially leading to clinical risks for participants. Compliance with FDA cybersecurity guidelines is crucial for secure data storage and transmission. The informed consent process must describe foreseeable risks related to DHT use, including discomforts, and outline mitigation strategies. Participants should be informed that DHT use may involve currently unforeseeable risks. Participants must understand the type of information collected by DHTs, its usage, and monitoring protocols. Clear instructions on actions to take in case of abnormal clinical events detected by DHTs, requiring medical attention, should be provided. The informed consent process should specify who may access DHT data during or after the clinical investigation. Participants must be informed of measures to protect their privacy and data limitations associated with DHT use. Participants should be aware of any additional expenses resulting from DHT use during the clinical investigation, such as data use charges. Participants should be made aware if DHTs are covered by end-user license agreements or terms of service, detailing potential sharing of personal information. 

Record Protection and Retention:

All data captured from DHTs, along with relevant metadata, should be securely transferred to and retained in a durable electronic data repository. Sponsors should discuss DHT data types with review divisions for FDA review. The data output supporting clinical investigation endpoints should be transmitted to a durable electronic data repository. FDA considers electronic data in the first repository as source data, available for inspection. The clinical investigators must review source data for participant safety and permit FDA access in accordance with regulations.

Other Considerations When Using Digital Health Technologies (DHT) - 

The Sponsor must plan to train the trial personnel and participants on DHT usage, incorporating feedback from usability evaluations. He must also establish a plan for technical assistance, risk management, and safety monitoring related to DHT use. The sponsor must ensure data transfer to a durable repository, develop end-of-study closeout procedures, and address potential issues proactively.

The investigator must ensure participants understand DHT data collection, usage, security, and privacy. The investigator must provide sponsor-developed training on DHT usage and review data as specified in the safety monitoring plan.

The training must be planned to train trial participants, personnel, and caregivers on DHT usage before data collection. The training must include schedule and also document ongoing training, addressing potential issues during the investigation. The training should also include various aspects of DHT such as DHT setup, data collection intervals, security, and proper usage.

Updates and Other Changes in the DHT: A comprehensive strategy must be in place to plan for unanticipated, unforeseen alterations to DHTs, ensuring flexibility and adaptability during the investigation. Keeping meticulous records of the timing and nature of updates is essential to track the evolution of the technology throughout the trial. To guarantee the continued fitness-for-purpose of DHTs, a rigorous process of verifying and validating measurements after each update is imperative. Addressing any observed differences and promptly specifying mitigation steps in the trial analysis allows for a transparent and accountable approach, assuring data integrity and reliability despite the dynamic nature of the digital tools employed. This proactive stance not only aligns with regulatory expectations but also underscores the commitment to maintaining the highest standards of quality and precision in clinical investigations leveraging DHTs.

DHT Error or Loss: While using the Digital Health Technologies (DHTs) utilized in clinical investigations, the establishment of robust procedures to swiftly identify and address errors or losses in DHTs is imperative. A proactive approach involves implementing comprehensive contingency plans to navigate through downtime, ensuring that alternate data collection mechanisms are seamlessly activated when needed. This strategic preparedness not only mitigates potential disruptions but also upholds the integrity of the trial by maintaining continuous and reliable data flow. Furthermore, should the unfortunate circumstance of malware detection on a DHT arise during a clinical investigation, swift and decisive corrective action is paramount. This involves a meticulous and targeted response to eliminate the threat, safeguarding the security and reliability of the data generated by the DHT. By adhering to these proactive measures, sponsors and investigators can navigate the challenges posed by DHT errors, losses, or security breaches with agility and precision, thereby fortifying the overall robustness of the clinical investigation.

Implementing DHTs in clinical investigations demands meticulous planning and proactive measures to safeguard data integrity and participant safety. By adhering to regulatory guidelines, conducting thorough training, and anticipating potential challenges, sponsors and investigators can harness the full potential of DHTs while ensuring the success and ethical conduct of clinical trials.


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