Draft Guidance on Decentralized Clinical Trials: Operational Considerations
Published November 2025 — Comprehensive analysis of the FDA's draft guidance addressing operational expectations for decentralized and hybrid clinical trial designs, including remote consent, telehealth documentation, and quality management for distributed trial models.
The Rise of Decentralized Clinical Trials
Decentralized clinical trials (DCTs) — trials in which some or all trial-related activities occur at locations other than a traditional clinical research site — have evolved from an experimental concept to a significant operational model in clinical research. The COVID-19 pandemic served as an inflection point, forcing the industry to rapidly adopt remote trial elements that had previously been discussed primarily in theoretical terms. Telehealth visits, remote consent processes, direct-to-patient investigational product shipment, and home health nursing visits became operational necessities virtually overnight.
As the pandemic receded, the industry did not revert to pre-pandemic models. Instead, sponsors and sites recognized that decentralized elements — when properly implemented — offer meaningful benefits for patient access, enrollment diversity, retention, and participant experience. Industry surveys indicate that approximately 35% of new clinical trials initiated in 2025 incorporated at least one decentralized element, compared to fewer than 10% in 2019.
However, the regulatory framework for DCTs has not kept pace with their adoption. The FDA issued temporary guidance during the pandemic emergency but did not establish comprehensive, durable guidance for the ongoing conduct of decentralized trials. This draft guidance, issued in November 2025, represents the FDA’s first comprehensive effort to articulate operational expectations for DCT elements across the trial lifecycle. While it is a draft — meaning the final guidance may incorporate changes based on public comment — it provides the clearest signal to date of how the FDA views the operational requirements for decentralized trial models.
Key Provisions
The draft guidance addresses operational considerations across six major areas of decentralized trial conduct. Each area includes specific expectations for documentation, quality management, and regulatory compliance.
The guidance establishes that remote informed consent — whether conducted via video conference, telephone, or electronic consent platforms — is an acceptable modality, provided specific safeguards are in place. Remote consent discussions must be conducted by qualified, delegated study personnel. Video-based consent is preferred over telephone-only consent for trials with higher risk profiles. All remote consent sessions must be documented with at least the same level of detail as in-person consent discussions, including the date, time, duration, personnel involved, questions asked by the participant, and responses provided.
Electronic consent (eConsent) platforms must meet specific technical and usability requirements. The platform must be validated for its intended use, must provide a complete audit trail of all consent interactions (including time spent on each section, comprehension quiz results, and signature timestamps), must be accessible to participants with varying levels of technical literacy, and must provide participants with the ability to download or print a copy of the signed consent document. The guidance also addresses re-consent workflows, requiring that protocol amendments be re-consented through the same platform with full traceability.
For trials utilizing direct-to-patient (DTP) shipment of investigational product, the guidance outlines chain-of-custody requirements, temperature monitoring expectations, and accountability documentation standards. Sponsors must demonstrate that the DTP supply chain maintains product integrity from the depot to the participant’s location. This includes validated shipping containers, continuous temperature monitoring with alerting capabilities, proof of delivery documentation, and a defined process for participants to report receipt issues or suspected product damage.
Telehealth visits conducted as part of clinical trial procedures must be documented in the source record with the same rigor as in-person visits. The guidance specifies that source documentation for telehealth visits must include the platform used, confirmation of participant identity verification, clinical assessments performed (with notation of any limitations due to the remote modality), adverse event assessment, and concomitant medication review. The investigator must document whether the telehealth visit was adequate for the intended clinical assessment or whether an in-person follow-up is needed.
The guidance addresses the use of remote monitoring technologies — including wearable devices, connected health sensors, and patient-reported outcome (PRO) applications — for clinical trial data collection. All remote monitoring technologies must be validated for their specific use case in the clinical trial context, not merely cleared or approved for general clinical use. Data transmitted from remote monitoring devices must flow through validated data pathways that maintain integrity, security, and audit trail requirements. The guidance recommends that sponsors define acceptable data quality thresholds for remotely collected data and establish procedures for handling missing, implausible, or corrupted data points.
For trials that include home health nursing visits for sample collection, drug administration, or clinical assessments, the guidance requires that home health personnel be appropriately trained, delegated, and supervised by the principal investigator. Training documentation must be maintained in the site’s regulatory files. Home health personnel must follow site-specific SOPs for the procedures they perform, and the investigator must maintain adequate oversight of their activities — including review of completed visit documentation within a defined timeframe.
Technology Requirements
Decentralized trial elements are inherently technology-dependent. The draft guidance establishes a framework for technology validation, data integrity, and patient privacy that applies across all DCT technology platforms.
Platform Validation
All technology platforms used for clinical trial data collection, consent, or communication must be validated for their intended use in the trial context. The guidance distinguishes between “fit-for-purpose” validation (which may rely on vendor-provided validation documentation supplemented by user acceptance testing) and “full validation” (which requires independent verification of all critical functions). The level of validation required should be proportionate to the risk associated with the data being collected. Platforms collecting primary efficacy endpoints require more rigorous validation than those used for administrative communications.
Data Integrity for Remote Data Collection
Data collected remotely must meet the same ALCOA+ (Attributable, Legible, Contemporaneous, Original, Accurate, plus Complete, Consistent, Enduring, and Available) standards as data collected at physical research sites. The guidance provides specific considerations for each ALCOA+ element in the remote context. For example, “Attributable” requires that the identity of the person generating the data (whether participant or healthcare professional) be verifiable through the technology platform. “Contemporaneous” requires that timestamps on remotely collected data accurately reflect the time of data generation, not the time of data transmission or upload.
Patient Privacy Considerations
Decentralized trial elements introduce unique privacy challenges. Video consent sessions, telehealth visits, and in-home health visits all create situations where clinical trial data is generated, transmitted, or discussed outside the controlled environment of a research site. The guidance emphasizes that sponsors and sites must implement privacy safeguards that address these unique risks, including encrypted communication channels for all telehealth and video consent interactions, secure data transmission protocols for wearable and sensor data, privacy notices and consent for any recording of remote interactions, and clear policies for data storage and retention on participant-owned devices.
Site Implications
Clinical research sites are at the operational center of decentralized trial execution. The draft guidance creates specific expectations for site readiness, technology infrastructure, and staff capabilities.
Most decentralized trials are actually hybrid models — combining traditional in-person visits with remote elements. Sites must develop the operational flexibility to manage both modalities simultaneously, including scheduling systems that accommodate mixed visit types, documentation workflows that maintain consistency across modalities, and staff who are trained to deliver care and collect data effectively in both settings.
Sites must have reliable, secure technology infrastructure to support DCT elements. This includes high-bandwidth internet connectivity for telehealth visits, validated eConsent platforms, secure messaging systems for participant communication, and integration capabilities with sponsor-provided remote monitoring platforms. Sites should conduct technology readiness assessments and develop contingency plans for technology failures during remote visits.
Conducting clinical assessments via telehealth requires specific skills beyond traditional clinical research competencies. Staff must be trained in telehealth communication techniques, remote clinical assessment methodology, technology platform operation, troubleshooting procedures for common technical issues, and documentation requirements specific to remote visits. Training must be documented and refreshed periodically.
The guidance emphasizes that investigator oversight responsibilities are not diminished by the decentralized model. In fact, oversight may need to be more structured in DCT settings because activities occur outside the investigator's direct line of sight. Investigators must have defined processes for reviewing remote visit documentation, overseeing home health personnel, monitoring data quality from remote collection platforms, and ensuring participant safety across all trial modalities.
Regulatory Expectations
The draft guidance establishes several regulatory expectations that will shape how decentralized trial elements are inspected, audited, and evaluated during regulatory review.
Documentation Standards
The FDA expects that all decentralized trial activities will be documented to the same standard as traditional site-based activities. This means source documentation for telehealth visits must be as complete and detailed as for in-person visits. Consent documentation must include the same elements regardless of whether consent was obtained in person or remotely. Safety assessments conducted remotely must be documented with the same rigor as those conducted in clinic. Any limitations inherent to the remote modality must be explicitly acknowledged in the source record.
Source Data Verification for Remote Visits
Monitors must be able to verify source data for all trial activities, including those conducted remotely. The guidance recommends that sponsors define in advance how source data verification will be accomplished for each type of remote activity. For telehealth visits, source records in the electronic health record or EDC system serve as the source document. For wearable device data, the raw data files from the device platform serve as the source, with the data flowing into the EDC through a validated interface. Sponsors must ensure that monitors have appropriate access to all source data repositories, including remote technology platforms.
Safety Reporting in Decentralized Settings
Safety reporting obligations remain fully applicable in decentralized trial models. The guidance emphasizes that the decentralized modality does not alter the investigator’s responsibility to identify, assess, and report adverse events and serious adverse events within the required timelines. Sites must have procedures for capturing adverse events reported through remote channels (telehealth visits, patient portals, telephone calls) with the same urgency and thoroughness as events identified during in-person visits. The guidance recommends that protocols specify clear procedures for participants to report urgent safety concerns outside of scheduled remote visits.
Quality Considerations
Maintaining data quality in hybrid and decentralized trial models requires intentional planning and ongoing monitoring. The draft guidance highlights several quality domains that require specific attention.
When a trial combines in-person and remote data collection, sponsors must ensure that data quality is consistent across both modalities. This requires calibration between site-based measurements and remote measurements, standardized training for all data collectors regardless of location, and statistical analysis plans that account for any systematic differences between data collection modalities. Quality tolerance limits should be established separately for remote and site-based data to enable early detection of modality-specific quality issues.
The guidance recommends that sponsors conduct specific risk assessments for each decentralized element in the trial. These risk assessments should identify potential failure modes (such as technology failures, participant non-compliance with remote procedures, or data transmission errors), evaluate the likelihood and impact of each failure mode, and define mitigation strategies. Risk assessments should be reviewed and updated throughout the trial as operational experience with the decentralized elements accumulates.
Decentralized elements shift some data collection responsibilities to participants (such as wearing devices, completing ePRO diaries, or attending telehealth visits on schedule). The guidance acknowledges that participant compliance with remote procedures may differ from compliance with site-based activities and recommends that sponsors build compliance monitoring and support strategies into the study design. This may include automated reminders, participant helpdesk support, and defined procedures for managing non-compliance with remote data collection requirements.
Implementation Recommendations for Sites
Sites seeking to build or strengthen their decentralized trial capabilities should consider the following phased approach to implementation.
Assess Current Capabilities
Conduct an honest assessment of your site's current readiness for decentralized trial elements. Evaluate your technology infrastructure (internet reliability, available platforms, device compatibility), staff capabilities (telehealth experience, remote assessment skills, technology proficiency), operational processes (documentation workflows, scheduling systems, communication protocols), and regulatory readiness (SOPs covering remote activities, consent templates, delegation logs for remote personnel).
Build Technology Foundation
Invest in the technology infrastructure needed to support DCT elements reliably. This includes secure, high-bandwidth internet with redundancy, validated telehealth platforms that meet clinical trial documentation requirements, eConsent platform access (either sponsor-provided or site-owned), secure messaging and communication systems for participant interaction, and integration capabilities with remote monitoring platforms and wearable device data systems.
Develop DCT-Specific SOPs
Create standard operating procedures that specifically address decentralized trial activities. These should cover remote consent procedures (video and telephone), telehealth visit conduct and documentation, home health visit oversight and documentation, remote monitoring device management and troubleshooting, direct-to-patient investigational product accountability, and procedures for handling technology failures during remote activities.
Train Staff Comprehensively
Develop and deliver training programs that prepare site staff for decentralized trial operations. Training should include telehealth communication skills and virtual assessment techniques, platform-specific training for all DCT technology tools, documentation requirements specific to remote activities, participant technology support and troubleshooting, and privacy and security protocols for remote interactions.
Pilot with Lower-Risk Elements
Rather than attempting to implement all DCT elements simultaneously, begin with lower-risk elements such as remote follow-up visits for safety assessments, ePRO data collection through validated patient apps, or eConsent for protocol amendments and re-consent. Use pilot experiences to refine workflows, identify operational challenges, and build staff confidence before progressing to more complex DCT elements such as remote primary endpoint assessments or direct-to-patient drug shipment.
Establish Quality Monitoring
Implement quality monitoring processes specific to decentralized trial activities. Track metrics such as telehealth visit completion rates, remote data quality indicators, participant technology support request frequency, and any protocol deviations related to decentralized elements. Use these metrics to continuously improve DCT operations and demonstrate quality to sponsors during feasibility assessments.
Looking Ahead
This draft guidance is open for public comment for 90 days following publication. Based on historical patterns, the final guidance is expected within 12 to 18 months after the comment period closes. Organizations should not wait for the final guidance to begin building DCT capabilities — the draft provides a clear directional signal of the FDA’s expectations, and early movers will be better positioned to participate in decentralized trials as sponsor adoption continues to accelerate.
The broader trajectory is clear: decentralized trial elements are becoming a permanent feature of clinical research. The question for sites is not whether to develop DCT capabilities, but how quickly and comprehensively to do so. Sites that invest in technology, training, and operational processes now will have a significant competitive advantage as sponsors increasingly seek sites with demonstrated hybrid trial readiness.
The Clinitiative network is actively building decentralized trial capabilities across our site portfolio, with a goal of having 80% of network sites hybrid-trial-ready by Q3 2026. This investment positions our network to support sponsors who are leading the adoption of patient-centric trial designs that reduce burden, improve access, and ultimately accelerate the delivery of new therapies to the patients who need them.
Ready to Build DCT Capabilities?
Contact our team to learn how the Clinitiative network supports decentralized and hybrid clinical trial designs with site-level operational readiness.