Decentralized Clinical Trials: Key Sponsor Considerations Under FDA And EMA Guidance

Introduction

The FDA and the European Medicines Agency (EMA) (jointly with the European Commission and Heads of Medicines Agencies) each have issued or updated their respective guidance addressing decentralized clinical trials (DCT), i.e., clinical trials that include trial-related activities conducted at locations other than the traditional investigative site.

These publications reinforce a broader regulatory trend: post-Covid decentralized trial elements are increasingly accepted by regulators in both the United States and Europe, but they require careful planning, documentation, oversight, and allocation of responsibility. Although DCT models may offer important operational and participant-facing benefits, they may not operate to lessen any sponsor responsibility for participant safety, data quality, regulatory compliance, or trial integrity.

This alert highlights key themes from the FDA and EMA guidance, identifies notable differences between the U.S. and EU approaches, and outlines practical steps sponsors should consider when designing or updating trials to include decentralized elements.

What the FDA Guidance Means for Sponsors

The FDA’s final guidance confirms that decentralized elements can be incorporated into appropriate clinical trials but emphasizes that decentralization does not change the sponsor’s core obligations.

From a practical standpoint, the FDA expects sponsors to be able to show that decentralized activities are thoughtfully built into the trial design, clearly described in the protocol and associated materials, and supported by appropriate oversight mechanisms. That includes clearly assigning responsibilities among investigators, vendors, home health providers, telehealth providers, participants, and other third parties; ensuring that off-site activities and data collection are appropriately monitored; and putting in place workable processes for safety reporting, investigational product handling, and participant support outside the traditional site setting.

In short, the FDA supports decentralization, but only where the operational model is well controlled, adequately documented, and consistent with applicable legal and regulatory requirements.

How the EMA Guidance Differs

The EMA’s guidance is broadly aligned with the FDA’s approach — echoing that a sponsor’s regulatory obligations may not diminish because of off-site trial activities. However, the EMA guidance places greater emphasis on GDPR and Member State law, both of which are important considerations for sponsors conducting trials in Europe.

GDPR and Data Protection

Generally, sponsors should, on an activity-by-activity basis, treat privacy and data protection as a core workstream when designing a DCT, particularly where remote technologies, wearables, telemedicine, or direct-to-participant interactions are involved.

Member State-Specific Legal Requirements

Many DCT-related issues are not fully harmonized across Europe. This means a sponsor must additionally determine the national requirements of each applicable EU Member State. To illustrate, whether a sponsor may lawfully use direct-to-participant drug shipment, electronic consent tools, home nursing, or other decentralized features may vary by country.

For multinational EU studies, this means a DCT model may need to be tailored jurisdiction by jurisdiction.

Practical Steps for Sponsors

Sponsors conducting or considering DCTs should take a structured approach early in trial planning, including:

Review Contracts and ICFs

DCTs often require a more detailed contractual framework than traditional site-based trials because more parties may be involved in trial conduct, including home health providers, telemedicine vendors, local laboratories, device suppliers, platform providers, couriers, and other service providers. In addition, informed consent forms (ICFs) may need to reflect these various parties and unique aspects of off-site trial activities, both in terms of what participants will need to do as well as additional risks they may face. 

Contracts, and to the extent applicable, ICFs, should be reviewed to ensure they appropriately address, among other issues:

• Scope of decentralized services.
• Training and qualification responsibilities.
• Safety event escalation and reporting.
• Data ownership, access, transfer, and security.
• Investigational product handling and accountability.
• Audit and inspection support.
• Subcontracting controls.
• Jurisdiction-specific legal compliance.
• Allocation of responsibility among sponsors, CROs, sites, and vendors.

Map DCT Activities Early

Identify which activities will occur away from the site, who will perform them, the technologies and processes that will be used, and how they will be supervised and documented.

Conduct a Targeted Risk Assessment

Evaluate participant safety, data integrity, privacy, product accountability, and regulatory compliance risks for each decentralized element and implement appropriate responsive measures. Ensure trial activities are appropriately documented and monitored.

Assess Data Flows and Privacy Controls

Understand who collects, accesses, transfers, and stores trial data, and confirm that privacy and security protections are appropriate.

Confirm Vendor and Personnel Qualifications

Verify training, licensure, and oversight for remote personnel and third-party providers.

Build in EU Country Review

For multinational European trials, sponsors should include country-level analysis in the initial timeline — not as a late-stage add-on.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.