DCTDecentralized Clinical Trial

A Decentralized Clinical Trial (DCT) is a clinical trial in which some or all of the trial-related activities take place at locations other than a traditional clinical investigator site. Those activities can include informed consent, IMP shipment and administration, biospecimen collection, source-data capture, safety assessments, and the final close-out visit. The location can be the participant's home, a local pharmacy, a local non-investigator healthcare provider, a mobile nurse, or a telehealth platform.

A trial is rarely fully decentralized in practice. The dominant model is hybrid — a traditional investigator site is still responsible for medical oversight and protocol-defined assessments that require specialised equipment, but routine visits move to telehealth or to the participant's home. FDA's September 2024 final guidance, 'Conducting Clinical Trials With Decentralized Elements', deliberately covers both fully decentralized trials and the much more common hybrid model.

The most important regulatory point in FDA's 2024 guidance and the EMA/HRA/MHRA 2022 Recommendation Paper is unchanged from traditional GCP: the sponsor is responsible for the overall conduct of the trial, and the investigator listed on the FDA Form 1572 (or its EU equivalent) is responsible for medical decisions and overall conduct at their site, even when 'their site' is now a network of telehealth visits and home-health nurses.

Sponsor responsibilities

• Selecting and qualifying any local healthcare providers (LHCPs) used to perform protocol-defined activities.
• Ensuring DCT software (eConsent, ePRO, telehealth platform) is fit for purpose and validated.
• Ensuring IMP is shipped, stored and dispensed under conditions that maintain integrity — including any direct-to-participant shipment.
• Ensuring the trial protocol and informed consent document accurately describe the decentralized elements and the participant's role.

Investigator responsibilities

The investigator remains responsible for medical decisions regarding study participants, regardless of where the participant is physically located. The investigator is also responsible for the conduct of LHCPs performing protocol-specified activities for their participants, even when those LHCPs are arranged by the sponsor. FDA's 2024 guidance was explicit that LHCPs do not become co-investigators by performing routine activities (drawing blood, taking vitals) but the investigator remains the responsible physician.

Direct-to-participant (DtP) shipment of investigational medicinal product is allowed by FDA and EMA when the protocol describes it, the IMP is appropriate for it (stability, dosing, route of administration), and the shipping conditions are controlled and documented. Cold-chain products require validated shippers and temperature loggers. Controlled substances are subject to DEA registration constraints in the US and equivalent national controls in the EU.

Self-administration by the participant is acceptable for IMPs already considered safe for self-administration in clinical practice (oral tablets, subcutaneous injectables with appropriate training). IV infusions, complex devices and any product where dose-related adverse events require immediate medical intervention are typically administered by an LHCP or in a hybrid site visit.

Electronic informed consent is acceptable when it meets the requirements of 21 CFR 50.27 (signed, dated, copy provided to participant) and the FDA/OHRP guidance 'Use of Electronic Informed Consent' (December 2016). eConsent can be administered via telehealth with a remote investigator present, or in two stages where the participant reviews the document at home and the investigator subsequently confirms understanding by telehealth.

ePRO data captured on a sponsor-provisioned device or a BYOD app is source data when no paper version exists, and must meet Part 11 / Annex 11 requirements. The data must be attributable to the participant (not a family member), contemporaneous (captured at the time of the experience, not reconstructed later), original (the electronic record is the source), and accurate (validated instrument). Audit-trail records must reconstruct who entered what and when.

Any software used to capture trial data, document consent, schedule visits, ship IMP or interact with participants in a regulated way is a GxP computerised system. It must be validated under GAMP 5 (or the sponsor's equivalent CSV / CSA framework), the data it produces must be Part 11 compliant, and the sponsor remains accountable for that validation even when the software is a SaaS product from a vendor. FDA's 2024 guidance was explicit on this — sponsors cannot delegate validation responsibility to a vendor by SLA.

ICH E6(R3), finalised in January 2025, formalises this as part of GCP. Section 4 (Computerised Systems) requires sponsors to maintain a documented assessment of every computerised system used in the trial, scaled to the system's risk to participant rights, safety and data reliability.

DCTs are not a fit for every trial. Indications that require specialised equipment for primary endpoint assessment (imaging, lung function, specialised cardiology), early-phase trials with intensive safety monitoring, IMPs with severe acute toxicity profiles, and trials in populations who cannot reliably self-administer or self-report all favour traditional or only-lightly-decentralized models.

FDA's guidance is also clear that DCTs do not automatically improve access or diversity. Without deliberate planning, BYOD and telehealth models can exclude participants without high-quality internet, without a smartphone, or with limited digital literacy. Sponsors should plan for and document how they will reach the intended trial population.