FDA Guidance on Clinical Trials with Decentralized Elements: Technologies and Responsibilities

Table of content

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to conducting clinical trials with decentralized elements. The document provides an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by the parties responsible for clinical investigations (study sponsors) in order to ensure the accuracy and reliability of the results, as well as the safety of study participants. 

At the same time, provisions of the guidance are non-binding in their legal nature, nor are they intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the relevant legislation and has been agreed with the authority in advance.

Overview of Remote Clinical Trial Visits and Related Activities

By virtue of the present document, the FDA provides detailed guidance on incorporating remote clinical trial visits and related activities in decentralized clinical trials (DCTs). The goal of these recommendations is to enhance the accessibility and convenience of clinical trials for participants, thus facilitating broader patient inclusion and improving engagement. 

Remote visits can encompass telehealth consultations, in-person visits by trial personnel at participants’ homes, or visits to local healthcare providers (HCPs). Each option comes with unique considerations regarding feasibility, regulatory compliance, and participant safety.

As explained by the authority, sponsors and investigators must carefully evaluate the appropriate type of remote visit based on the investigational product (IP), the participant population, and the nature of the clinical assessments. The guidance emphasizes the importance of ensuring participant privacy, minimizing data variability, and adhering to local regulations when implementing remote clinical trial components.

Planning and Implementing Remote Visits

When designing a DCT, sponsors can consider telehealth visits as a substitute for in-person visits when physical interaction is not essential. 

Key factors to consider include:

1. Suitability of Telehealth Visits: Telehealth visits are suitable when the IP and the participant’s medical condition do not necessitate direct in-person examination. The trial protocol should clearly specify when a telehealth visit is appropriate and under what circumstances an in-person consultation is needed.
2. In-Home Visits and Local HCP Involvement: In-home visits can be conducted by trial personnel sent to participants’ homes or by local HCPs who are situated near participants. The local HCPs’ role should be confined to activities within their clinical qualifications, such as physical examinations or obtaining vital signs. Any trial-specific activities that require in-depth protocol knowledge should be handled by appropriately trained trial personnel.
3. Training and Protocol Compliance: Trial personnel, local HCPs, and participants should receive comprehensive training on remote procedures and telehealth platforms. Study records should meticulously document whether a visit was conducted via telehealth, noting the date, time, and personnel involved in the visit.
4. Handling Adverse Events: The trial protocol should detail how adverse events identified during remote visits will be managed. For serious adverse events that require urgent attention, the protocol should outline the appropriate steps for ensuring immediate care.
5. Legal and Regulatory Compliance: Sponsors and investigators must ensure that remote visits comply with telehealth laws and regulations in the U.S. states or territories and other relevant countries where participants are located. Compliance with local medical practice laws is essential to maintaining trial integrity and participant safety.

Use of Digital Health Technologies (DHTs)

According to the guidance, Digital Health Technologies (DHTs) play a crucial role in enabling the remote collection of clinical data in DCTs. DHTs allow secure, real-time transmission of participant data, supporting decentralized trial designs. 

The FDA’s guidance on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations provides recommendations on the selection, verification, validation, and usability of DHTs in remote clinical settings. 

In particular, the document emphasizes the importance of the following aspects:

1. Selecting DHTs: The chosen DHTs should be user-friendly, validated for the specific clinical measures they are intended to collect, and accessible to all trial participants. When permitting the use of participant-owned devices, sponsors should offer equivalent DHTs to ensure that participants without access to the required technology are not excluded.
2. Ensuring Equitable Participation: To prevent socioeconomic disparities from affecting trial participation, sponsors should provide necessary telecommunication services to participants who lack the resources to acquire them independently. This approach ensures that participants from various demographic backgrounds can engage in the trial.
3. Risk Management and Data Security: Sponsors should proactively assess and manage risks associated with using DHTs, including data privacy and security concerns. DHTs must be capable of transmitting data reliably and securely to preserve data integrity throughout the study.

Roles and Responsibilities in DCTs

Under the general rule, the responsibilities of sponsors and investigators in DCTs are similar to those in traditional trials but require additional considerations for managing decentralized elements.

Sponsors are ultimately accountable for ensuring the proper coordination and oversight of all decentralized activities, which may involve numerous contracted service providers, such as networks of local HCPs, pharmacies, or mobile clinical units. 

Key sponsor responsibilities include:

• Coordination of Remote Activities: Sponsors should document the roles and activities of contracted service providers and establish clear communication channels. Maintaining records of service providers and their assigned roles is critical to managing complex DCT operations.
• Data Management Plan: A comprehensive data management plan should outline data flow from all sources, including trial personnel, local HCPs, and clinical laboratories. The plan should describe the data origin, flow, and methods for secure data transmission.
• Participant Diversity: Sponsors should aim for a trial population reflective of the intended treatment demographic. This includes targeting diverse participant groups in terms of race, ethnicity, and geography. Leveraging local HCPs and community health centers can help reach underrepresented populations.
• Compliance with Local Regulations: Given the complex regulatory landscape, sponsors must ensure compliance with local laws and licensing requirements across multiple jurisdictions. A robust monitoring plan should be in place to address any local variations in regulations and practices.

Investigators are responsible for the direct oversight of all trial activities and ensuring participant safety and data integrity. 

Key responsibilities include:

• Oversight of Remote and In-Person Activities: Investigators must ensure that any remote or in-person activities conducted by local HCPs are performed according to protocol standards. Although local HCPs do not need to be listed as trial personnel, the investigator must monitor their activities closely and review data regularly.
• Supervision of Telehealth Visits and Training: Investigators should supervise remote visits through telehealth or videoconferencing, particularly for activities that require visual verification (e.g., assessing a lesion or conducting a clinical outcome assessment). Investigators should ensure that training is adequate for both trial personnel and participants.
• Documentation and Data Management: Investigators should maintain accurate records of each subject’s case history, including observations, assessments, and any relevant interactions with local HCPs. This documentation must be comprehensive, capturing the type of visit, location, and personnel involved.

Conclusion

In summary, decentralized clinical trials provide a flexible and patient-centric approach to research, allowing greater accessibility and convenience for participants. Implementing DCTs requires careful planning and coordination, especially in managing multiple remote locations and personnel. The present guidance emphasizes the need for meticulous oversight, training, and risk management to ensure trial quality and compliance with the applicable standards as well as regulatory requirements set forth under the existing legal framework.

Source

https://www.fda.gov/media/167696/download

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