5.2 Pre-trial: Achieve first participant in (FPI) readiness

Before any sDHT is shipped, the precise logistics of the data acquisition process must be mapped and documented. The adopter is the ultimate owner of the clinical trial, but success relies on leveraging the developer’s technical knowledge here.

Adopters Developers

Adopters: Clinical/trial readiness

You are accountable for integrating the sDHT into the existing trial workflow and ensuring all captured data align with the finalized protocol.

• Finalize protocol language: You must clearly specify sDHT usage in the protocol. This includes non-negotiable details like eligibility requirements (e.g., “bring your own device” (BYOD) compatibility if that applies), clear wear/use time requirements, and explicitly locking down the specific version of the sDHT’s hardware, firmware, and algorithm that will be used for the trial.

• Create a data flow diagram: Produce a single-page visual schematic that clearly illustrates every data “hop” (e.g., sDHT sensor → mobile app → cloud service → EDC/Sponsor database). This diagram is considered standard practice and foundational for demonstrating data integrity and traceability for regulatory review. This diagram must clearly identify the entity responsible for each step, acting as a crucial internal resource that significantly shortens troubleshooting when issues arise.
  
  To learn more and see an example, view this resource:

Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative

Advancing the Use of Mobile Technologies in Clinical Trials: Recommendations from the Clinical Trials Transformation Initiative

2019 Digit Biomark

Recommendations / best practices

Authors

Philip Coran, Jennifer C Goldsack, Cheryl A Grandinetti, Jessie P Bakker, Marisa Bolognese, E Ray Dorsey, Kaveeta Vasisht, Adam Amdur, Christopher Dell, Jonathan Helfgott, Matthew Kirchoff, Christopher J Miller, Ashish Narayan, Dharmesh Patel, Barry Peterson, Ernesto Ramirez, Drew Schiller, Thomas Switzer, Liz Wing, Annemarie Forrest, Aiden Doherty

Recommendations from the Clinical Trials Transformation Initiative (CTTI) on advancing the use of mobile technologies in clinical trials, including in the areas of technology selection, data collection/analysis/interpretation, data management, protocol design/execution, and FDA submission/inspection.

Findings
Widespread use of mobile technologies in clinical trials is impeded by perceived challenges.
Scientific and technical challenges affect decision-making around using mobile technology for data capture.
Concerns include choosing appropriate technology, data collection and analysis, ensuring data authenticity, and designing protocols.

Recommendations
Use CTTI’s framework for mobile technology selection to assist sponsors.
Conduct feasibility studies prior to launching trials.
Engage with regulatory authorities early to discuss endpoint appropriateness and validation processes.
Secure data generated by mobile technologies using recommended practical approaches.
Optimize data quality to minimize variability and ensure robust conclusions.

Regulatory Considerations
Engage with the FDA early in the trial design process.
Ensure data integrity and security throughout the data life cycle.
Maintain open dialogue with regulatory authorities regarding trial-specific strategies for data collection and sharing.

Keywords

Algorithms Clinical trial design Clinical trials Clinical validation Data collection Data management Data privacy and security Data quality Digital health technologies (DHTs) Digital outcome measures Drug development FDA Feasibility studies Metadata Patient centricity Real-world data (RWD) Regulatory framework Technical validation Usability Wearables

Technologies

Sensors (general & ambient) Wearables & activity monitors

Open Resource

Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.

Developers: Technical readiness

You are responsible for supplying the necessary technical specifications and confirming that the technology can reliably execute the data capture plan.

• Supply technical specifications: Provide documented records of the firmware, app, and algorithm versions planned for trial use, ensured through immutable storage or audit trails. This ‘version provenance’ is critical to maintaining the data integrity and reproducibility required for regulatory submission. Immutability means that once a version is recorded, it cannot be changed without detection, preventing tampering and allowing auditors to trace data back to the exact configuration used.

• Define telemetry/adherence data: Clearly define the non-endpoint, operational data available (e.g., battery life, connection status, data loss). This operational data is essential for the adopter to build effective adherence tracking and set timely intervention thresholds.

FDA SPOTLIGHT

“[Decentralized clinical trials] that permit tests to be performed independently by participants at home (e.g., spirometry) may introduce variability compared to tests performed under supervision at traditional clinical trial sites. Training or video supervision (i.e., during a telehealth visit) may reduce such variability. Likewise, allowing participants to choose whether an assessment will be performed at a traditional clinical trial site or remotely may result in bias (e.g., sicker participants may prefer remote visits). The protocol should specify which visits will be conducted at traditional clinical trial sites, which visits will be conducted remotely, and which visits can be left to participants’ choice.”
– Conducting Clinical Trials With Decentralized Elements, Final, 2024 (FDA), Section III.A (DCT Design and Conduct), p. 4.

Conducting Clinical Trials With Decentralized Elements

Conducting Clinical Trials With Decentralized Elements

2024 FDA

FDA guidance – final

Authors

U.S. Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Devices and Radiological Health (CDRH), Oncology Center of Excellence (OCE)

This guidance provides recommendations for implementing decentralized elements in clinical trials to improve participant access and engagement while maintaining compliance with FDA regulations. Decentralized Clinical Trials (DCTs) involve trial activities conducted at non-traditional sites, such as participant homes, local healthcare facilities, or via telehealth. The document outlines responsibilities for sponsors and investigators, considerations for informed consent, investigational product management, safety monitoring, and the use of digital health technologies. It aims to expand trial participation, enhance convenience, and improve data collection and monitoring.

Findings
Coordination challenges with multiple locations in DCTs.
Variability in data collection across decentralized locations and remote tools.
Challenges in implementing certain statistical approaches in DCTs.
Need for DHTs to be accessible and suitable for all trial participants.
Ensuring compliance with local laws and regulations.

Recommendations
Develop clear protocols for integrating decentralized elements into clinical trials, specifying remote and in-person activities.
Use digital health technologies (DHTs) and electronic systems to streamline data acquisition, informed consent, and investigational product tracking.
Provide training for all stakeholders, including trial personnel, local health care providers, and participants, on decentralized processes.
Implement robust safety monitoring plans to address adverse events in decentralized settings.
Ensure compliance with local and international laws governing telehealth, data privacy, and investigational product use.

Regulatory Considerations
Maintain compliance with FDA requirements under 21 CFR parts 312 and 812 for drug and device trials, respectively.
Document all trial activities and data flows in trial protocols and data management plans, ensuring traceability and integrity.
Ensure informed consent processes meet FDA standards and provide clear communication to participants about decentralized trial activities and data handling.
Address investigational product accountability by documenting IP distribution, storage, and return or disposal.
Design electronic systems for decentralized trials to comply with 21 CFR part 11 requirements for data reliability, security, and confidentiality.

Keywords

Clinical trials Data management Decentralized clinical trials (DCTs) Digital health technologies (DHTs) FDA guidance Informed consent Investigational device exemptions (IDE) Investigational new drug application (IND) Patient diversity Recruitment Risk management Safety monitoring Telehealth Validation

Technologies

Clinical decision & monitoring systems Operating systems & platforms Recruitment & trial tools Remote monitoring

Open Resource

Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.

PRO TIP

Conduct a joint mapping session
Developers can walk adopters through the precise technical journey from sensor signal to data repository. This ensures adopters can anticipate infrastructure needs, and developers fully grasp the clinical complexities that might influence data integrity, laying a durable foundation for the trial. 

A live, end-to-end rehearsal is highly recommended to stress-test your system and ensure your theoretical workflow is practically sound before first participant in.

Investing in robust training is vital for preventing data quality issues caused by user error. Clear and correct training ensures reliable data collection and significantly reduces the total burden of participation.

Effective onboarding provides sites and participants with clear, role-appropriate materials and easy access to help. Many teams find that a one-page quick-start guide, a short explainer video (approximately 90 seconds), and a simple FAQ cover the majority of needs when paired with hands-on practice during the site initiation visit. These materials should address pairing, any device permissions required, expected wear and charging patterns, when synchronization occurs, and how to obtain assistance. Consider accessibility from the outset by providing captions, adequate font sizes, plain-language variants, and offline availability where appropriate.

Because remote data collection introduces specific considerations for informed participation, you should include information in the informed consent discussion that explains what is being collected, foreseeable risks related to the sDHT, what participants should do if the application indicates an error, and how quickly support will respond.

Adopters Developers

Adopters: Trial execution

You are the primary owner of site training, participant support logistics, and ensuring all training materials are IRB-approved.

• Site training should be scenario-based and focused on proactive problem-solving using the monitoring dashboards. Training focuses on when and how to intervene, not merely following a checklist.

• You must document who was trained on what, when, and with which version of the materials, filing this completion log in the electronic Trial Master File (eTMF) to maintain a robust audit trail.

Developers: Technical content and usability

You contribute the deep technical and usability knowledge, often providing the Tier 1 help desk and essential troubleshooting guides.

• As participant training materials, provide high-fidelity Quick Start Guides and Instructions for Use that are concise, jargon-free, and incorporate findings directly from usability validation (see section 4.2: Usability validation).

• Ensure there is a clear mechanism for immediate and non-technical assistance to participants. Work with the adopter team to determine which types of support are handled by your organization versus the clinical trial operations team. With a strong partnership and clear delineation of roles, your expertise will keep the sDHT data flow moving while the trial ops team prioritizes clinical/safety issues. 

PRO TIP

Support handoffs
Clearly distinguish between the two types of support and how each will be handled:

• Technical support: (e.g., app won’t sync, battery troubleshooting) 

• Clinical support: (e.g., concerns about symptoms, adverse events) 

Participants must be triaged or directed appropriately, knowing whom to contact for a technical issue versus a clinical safety concern. To learn more, see 5.3: Trial monitoring and 5.4: Risk mitigation

Ambiguity over data ownership or support chains increases trial fragility. A detailed RACI (responsible, accountable, consulted, informed) matrix should be finalized and shared across all parties, clearly defining the owner for every step of the process.

For example:

Adopters Developers

Adopters

You own the operational outcome and ultimate trial conduct.

• Accountable for: Final adherence thresholds, key risk indicator (KRI) escalation plans, site training, and clinical/safety oversight.

• Activities include: Weekly adherence review, maintenance of training records, and incident logging in the electronic Trial Master File (eTMF).

Developers

You own the underlying technical performance of the sDHT and data transfer systems.

• Responsible for: Device interfaces, API stability, version provenance, and Tier 1 technical support.

• Consulted on: Setting realistic technical KRIs and troubleshooting severe data-pipeline issues.

Implement more intensive monitoring during the initial period following first participant in (FPI), such as the first week of trial operations, to set monitoring thresholds and pay close attention to identifying any unanticipated technical issues. This includes establishing key risk indicators (KRIs) for data flow, device performance, connectivity, and participant engagement, with predefined thresholds that trigger alerts or interventions. 

This activity formalizes the link to the broader discussion in Section 5.3: Trial monitoring as you set initial thresholds for key operational and adherence indicators. An example could look like this: