Decentralized Clinical Trials: What Patients Should Ask

In September 2024 the U.S. Food and Drug Administration (FDA) finalized guidance called Conducting Clinical Trials With Decentralized Elements. Its definition is short. A decentralized clinical trial is one "that includes decentralized elements where trial-related activities occur at locations other than traditional clinical trial sites."

The elements FDA names are "telehealth visits with trial personnel, in-home visits with remote trial personnel, or visits with local health care providers."

FDA's stated reason is access. Announcing the draft guidance in May 2023, the agency said these trials should "increase the breadth and diversity of participants in clinical trials and improve accessibility for those with rare diseases or mobility challenges."

That is a real gain if you live two hours from a cancer center. It also raises questions a normal trial does not.

FDA says trials "where all activities are decentralized may be appropriate for investigational products (IPs) that have well-characterized safety profiles."

Most cancer trials do not fit that. The drug being tested is exactly the thing whose safety is not yet known. So cancer trials with remote elements are usually hybrid. FDA describes the pattern: sometimes "the administration of an IP or a complex medical assessment needs to be performed at a traditional clinical trial site and some follow-up assessments could be performed remotely."

So ask which visits are remote and which still need travel. Get that split in writing, visit by visit, before you agree.

A remote trial may send you to a clinic near home. FDA draws a clear line around what that clinic may do.

FDA says the trial-related activities local providers perform "should not differ from those that they are qualified to perform in clinical practice." These "should not require a detailed knowledge of the protocol." FDA's examples are "performing physical examinations or obtaining vital signs."

Anything research-specific goes back to the study team. FDA says activities "unique to a research study" should be done "by qualified trial personnel." Local providers "would not be considered trial personnel, nor would they be considered subinvestigators in a drug trial."

One boundary is worth memorizing. FDA "does not consider obtaining informed consent to be an appropriate activity for a local HCP to perform." If a local clinic that is not part of the study hands you a consent form, stop and call the study coordinator.

FDA also tells sponsors and investigators to make sure telehealth visits "comply with laws governing telehealth in the relevant U.S. States or territories." Ask whether your investigator is licensed to see you in the state where you actually live.

If the study drug is shipped rather than given at a site, some rules still hold. The investigator, not the courier, "must authorize the release of the IP by the distributor." Giving the drug "must be performed under the supervision of the investigator or subinvestigator responsible to the investigator." Local staff may give it at a local facility, a mobile research unit, or your home only "if the safety profile of the IP is well characterized." FDA also notes that drugs "best suited for direct shipment to the participant's home include those with good stability profiles."

Ask what temperature it ships at and what to do if it arrives warm. Ask who signs for it, and whether a missed dose takes you off the study.

Many remote trials use digital health technologies: apps, wearables, and connected devices. FDA notes these "may allow transmission of data remotely and securely from trial participants wherever they are located."

Here is the protection to know about. FDA says sponsors "should ensure that DHTs used in a DCT are available and suitable for use by all trial participants." Where a trial lets people use their own devices, "sponsor-provided DHTs should be available as an option," so that people who cannot afford a device are not shut out. FDA says the same about telecommunications access.

In plain terms: you should not have to buy a phone, a watch, or a data plan to take part.

Nail this down before your first dose.

FDA requires the safety monitoring plan to describe how participants "respond to and report adverse events, including where to seek medical assistance locally when necessary and where to receive follow-up care." The protocol must also say "how care will be provided for adverse events that require urgent or in-person attention."

FDA is equally plain about emergencies. Anyone with "any health emergency" should "seek medical attention at local health care facilities (such as an emergency room), as appropriate."

Get these in writing and keep them where a family member can find them:

• The 24-hour phone number for the study team, and who answers it at 2 a.m.
• The name of the emergency department they want you to use.
• A wallet card naming the study drug, the protocol number, and the investigator.
• The exact temperature at which they want you to call. NCI advises contacting the care team for a "fever of 100.4 °F (38 °C) or higher" during cancer treatment, but your protocol may set its own number, so use theirs.

An app that logs a symptom is research data collection. It is not a person deciding whether you need to be seen.

Remote consent is allowed. FDA says investigators "may obtain informed consent (either electronically or on paper) from trial participants at their remote locations." The process "can include a remote visit."

The person walking you through it must "have a detailed knowledge of the protocol" and the right training and credentials. It must also tell you whom to contact about the research, whom to contact about your rights, and whom to contact if the research injures you.

Signing on a screen removes the waiting room, not your right to take time. Ask for the document in advance and read it away from the call.

• Which visits are remote and which need travel, listed one by one?
• Is my investigator licensed to treat me by telehealth in my state?
• What will the local clinic do, and what must go back to the study team?
• Who ships the drug, how is it stored, and what do I do if delivery fails?
• Does the sponsor supply the device and the data connection if I need them?
• Which emergency department should I use, and what do I hand them at the desk?
• Who reads my remote symptom reports, and how quickly?

• U.S. Food and Drug Administration — Conducting Clinical Trials With Decentralized Elements (final guidance).
• U.S. Food and Drug Administration — Conducting Clinical Trials With Decentralized Elements, full guidance text.
• U.S. Food and Drug Administration — Guidance Snapshot: Conducting Clinical Trials With Decentralized Elements.
• U.S. Food and Drug Administration — FDA Takes Additional Steps to Advance Decentralized Clinical Trials.
• National Cancer Institute — Infection and Neutropenia during Cancer Treatment.

Helpful next pages include Joining a Clinical Trial: Risks and Questions, Clinical Trial Screening Visit: What to Expect, Reporting Side Effects in a Clinical Trial, Clinical Trial Results: What They Mean.