FDA Guidance on Clinical Trials with Decentralized Elements: Administration and Oversight

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.

FDA Oversight

Under the general rule, the FDA maintains oversight of decentralized clinical trials (DCTs) through a range of tools, including on-site inspections and, when necessary, remote regulatory assessments. These inspections ensure that sponsors, investigators, and other entities comply with regulatory requirements. 

FDA inspections are conducted under sections 704(a)(1) or 704(a)(5) of the Federal Food, Drug, and Cosmetic (FD&C) Act and are designed to evaluate the integrity of clinical trial operations and data collection. During an FDA inspection, clinical investigators should designate a physical location where a responsible individual can facilitate access to trial-related records, whether they are in paper or electronic form. 

This designated location should also allow for interviews with trial personnel, which may be conducted in-person or remotely. The typical inspection location for clinical investigators is the address provided in the investigational new drug (IND) application, listed on Form FDA 1572, or in the investigational device exemption (IDE) application. 

However, other physical locations can be designated for these purposes. FDA inspections aim to verify compliance, confirm data validity, and ensure that trial participants’ rights and safety are upheld throughout the DCT process.

Informed Consent and Institutional Review Board (IRB) Oversight

As explained by the authority, the process of obtaining informed consent is a fundamental ethical requirement in any clinical trial, including DCTs. In a decentralized setting, obtaining informed consent remotely – either electronically or in paper format – is permissible as long as it meets all applicable regulatory requirements. 

The FDA emphasizes that informed consent should be obtained by the clinical investigator or appropriately trained and credentialed personnel capable of addressing any participant concerns regarding the trial.

Key considerations for informed consent in DCTs include:

1. Ensuring Participant Understanding: The informed consent process must be structured to provide participants with clear information about the trial, including how remote or local HCPs will be involved, what trial activities will take place at their homes, and who will have access to their protected health information.
2. Designating Responsibility: Obtaining informed consent is the investigator’s responsibility and should not be delegated to local HCPs who lack detailed protocol knowledge or the ability to address participant inquiries comprehensively. Only individuals with a thorough understanding of the protocol and investigational product (IP) should be involved in this process.
3. Use of Central IRBs: In DCTs, FDA recommends using a central IRB to facilitate the efficient review of informed consent documents and ensure consistent oversight across all decentralized sites.
4. Compliance with Regulations: The informed consent process must comply with 21 CFR part 50, ensuring that participants (or their legally authorized representatives) are informed of whom to contact for questions about their rights, research-related issues, or in the event of injury.

Investigational Products in a DCT

The administration and management of investigational products (IPs) in DCTs depend on the nature of the product, its safety profile, and the required level of supervision. The FDA provides guidance for both drugs and biological products, as well as medical devices, to ensure that trial participants are appropriately monitored and that safety concerns are adequately addressed.

Drugs and Biological Products

In accordance with the applicable regulatory requirements, the administration of investigational drugs and biological products should be performed under the supervision of the investigator or a sub-investigator. 

Sponsors should consider the following factors when determining the suitability of a DCT for drug administration:

• Safety Profile and Complexity: Drugs with a well-established safety profile and that do not require intensive post-administration monitoring may be suitable for administration at home or in a local healthcare facility. In contrast, drugs with high-risk safety profiles, complex preparation requirements, or those in early development stages may necessitate administration at a traditional clinical site.
• Administration by Local HCPs: For lower-risk products, local HCPs or remote trial personnel may be involved in drug administration, provided they are trained and equipped to manage any immediate safety concerns.
• Direct Shipment to Participants: Drugs that are stable and do not require specialized handling can be shipped directly to participants’ homes. However, drugs with stringent storage or handling requirements should remain within the control of traditional clinical sites.
• Risk Management: Sponsors must evaluate the urgency and complexity of care that may be needed based on the IP’s safety profile and the underlying condition of the study population. Investigators should ensure that participants have access to appropriate levels of local care for adverse events.

Medical Devices

For investigational medical devices, the decision to use or administer a device remotely should consider the device’s complexity, intended use, and potential risks to participants. 

Devices used in DCTs can be categorized as follows:

• Devices for Home Use: Devices intended for self-use by participants may not require direct oversight if the risks are minimal and the participants can use them independently. Such devices are generally suitable for decentralized trials if appropriate training is provided.
• Devices Requiring Professional Use: Devices typically used in clinical or hospital settings should only be handled by qualified trial personnel under the investigator’s oversight. For example, surgical implantation devices or devices with significant risk should remain under strict supervision.
• Remote Follow-Up Assessments: For devices requiring follow-up after implantation or use, remote assessments via telehealth or local HCPs can be utilized if the nature of the follow-up does not pose significant risk to the participant. These assessments should be carefully planned, with protocols in place for managing any adverse events identified during remote visits.

Special Considerations for Investigational Product Administration

The FDA recommends that sponsors and investigators take the following steps to ensure the proper administration and monitoring of IPs in a DCT:

1. Selection of Administration Location: The decision on whether an IP should be administered at home, in a local healthcare facility, or at a traditional clinical site should be based on a risk-benefit analysis considering the IP’s safety profile and administration complexity.
2. Oversight and Supervision: Investigators should ensure that IP administration, whether by trial personnel or local HCPs, is conducted in line with the investigational plan and applicable regulations. Continuous oversight is essential to safeguard participant safety.
3. Documentation and Compliance: All activities related to IP administration, including direct shipment, handling, and storage, should be meticulously documented to maintain compliance and accountability throughout the trial.

Conclusion

In summary, the present guidance dedicated to oversight, informed consent, and investigational product administration in DCTs emphasizes the need for detailed planning, clear communication, and strict adherence to regulatory requirements. As explained in the document, proper implementation of these guidelines will enable the safe and effective conduct of DCTs, benefiting both trial participants and the broader research community.

Source

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

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