Key takeaways from the FDA’s draft guidance for Decentralized Clinical Trials

A new Draft Guidance has been released by the FDA, which provides recommendations for sponsors, investigators, and other stakeholders on the implementation of decentralized clinical trials (DCTs) for drugs, biological products, and devices.

In this guidance, a DCT refers to a clinical trial where some or all of the trial-related activities occur at locations other than traditional clinical trial sites. In fully decentralized clinical trials, all activities take place at locations other than traditional trial sites. These trial-related activities may take place at the homes of trial participants or in local health care facilities that are convenient for trial participants. In hybrid DCTs, some trial activities involve in-person visits by trial participants to traditional clinical trial sites, and other activities are conducted at locations other than traditional clinical trial sites, such as participants’ homes.

OVERVIEW

• Decentralized clinical trials (DCTs) reduce or eliminate the need for patients to access hospital-based trial sites.
• DCTs use digital technologies to enable access to clinical research, remote data collection and monitoring, and communication between investigators and participants.
• Direct delivery of IMPs, laboratory examinations and/or instrumental tests, and home visits by healthcare professionals can be used to assess the effectiveness of an investigational medicinal product.
• Remote data collection in DCTs can be active or passive. Active data collection requires the patient to enter data, while passive data is logged by the device/s without active intervention.
• DCTs are most applicable to therapeutic areas where telemedicine is advanced, such as diabetes, neurorehabilitation, cardiovascular diseases, pulmonary diseases, and COVID-19.
• Pfizer conducted the first fully-decentralized randomized study in 2011, using the Internet for subject enrolment, online screening questionnaires, and electronic outcomes diaries. The investigational medicinal product was delivered to the patient’s homes.

The guidance provides recommendations on the following topics:

• Design considerations for a DCT include having a physical location where all clinical trial data is accessible and where personnel can be interviewed. FDA review divisions should be consulted when planning a trial in a DCT setting due to the high variability and precision of data obtained from DCT.
• Conduct of remote clinical trial visits and clinical trial-related activities: The protocol should specify when a telehealth visit with a trial participant is appropriate and when a participant should be seen in person. Local HCPs can also conduct in-person visits and trial-related activities. Case report forms and other documentation should be completed for telehealth visits, including the date and time of the visit. The trial protocol should specify how adverse events identified remotely will be evaluated and managed.
• Use of digital health technologies to remotely acquire data: Sponsors should ensure that digital health technologies (DHTs) used in a DCT are available and suitable for use by all trial participants. Sponsor-provided DHTs should be available as an option to ensure participants who do not have a protocol-specified DHT are not excluded from the DCT.
• The roles and responsibilities of the sponsor and investigators in a DCT are the same as in traditional site-based clinical trials.
• Obtaining informed consent (IC) and institutional review board oversight of the IC process: Trial participants may offer electronic informed consent, which should include contact information in case of questions.
• Determination of the appropriateness of investigational products for use: When deciding whether administration outside of a clinical study site is appropriate, the nature of the IP should be taken into account. In-person monitoring by the investigator at a trial site may be required for IPs that entail complicated administration methods, have a high-risk safety profile, or are in the early phases of research. It may be suitable for nearby HCPs or trial workers working remotely to administer the IP at local health facilities for IPs for which the safety profile is well-characterized and does not require specialized monitoring during the immediate subsequent administration.
• Packaging and shipping of investigational products: The protocol for packaging and shipping investigational products in a DCT should describe how the physical integrity and stability of the IP will be maintained during shipment. A central distribution service could be used to ship the IP directly to trial participants. Investigators should track and document that, trial participants receive IPs, and procedures should be documented for returning or disposing of unused IPs.
• Safety monitoring of trial participants: The sponsor is responsible for making sure that studies are properly monitored and carried out in line with the overall investigative strategy and methods specified in the IND or IDE applications. The sort of data that will be gathered by a DHT should be described in the safety monitoring strategy. Sponsors must stop using or administering medications remotely, inform the FDA, the IRB, and all researchers, and decide whether to continue the experiment if there are any major safety hazards.

To download the Draft Guidance document, visit

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