What “decentralized” means in the FDA’s final playbook (and what it doesn’t)

12-Nov-2025

When we talk about a clinical trial being “decentralized,” it may conjure images of patients doing everything from their couch: telehealth calls, wearables, perhaps even delivery of investigational medicine to the door. But the truth is more nuanced.
The Food and Drug Administration (FDA) final guidance — titled “Conducting Clinical Trials With Decentralized Elements” — makes clear that a trial may include decentralised elements, rather than needing to be entirely remote.

In plain language: “decentralized” doesn’t mean the site disappears, the oversight vanishes, or the need for rigorous Protocol adherence goes away. On the contrary, this new era accentuates the importance of drug compliance. Trial participants, sponsors, local care providers, technology vendors — all must remain aligned and diligent.

What “decentralized” means:

Activities take place away from the traditional clinical site — e.g., at the participant’s home, via telehealth, or at a local HC
The use of digital health tools to capture participant data remotely.
A participant-centric approach: fewer burdens, more convenience, more inclusive access.

What it doesn’t mean:

It doesn’t mean “no oversight” or no regulatory checks. The Food and Drug Administration explicitly states that the regulatory requirements are the same whether or not decentralised elements are used.
It doesn’t mean drug compliance is optional. Remote or hybrid trial elements make the challenge of maintaining compliance even greater: ensuring correct dosing, tracking adverse events, monitoring how the investigational product is handled.
It doesn’t mean every trial should be fully decentralized. The guidance emphasises that appropriateness depends on the investigational product’s risk profile, population, complexity.

A story to bring this home: imagine Sarah, a patient in rural Nevada, living two hours from the nearest research hospital. Under a decentralised model, her weekly follow-ups might happen via telehealth, a local nurse (doing home-visits) collects a blood sample, and a wearable sends activity data. But Sarah still receives investigational medicine, the study team still monitors her, a local Home Health Nursing partner checks in, and the trial sponsor remains legally and ethically accountable for regulatory compliance. The remote model doesn’t mean we “let go” of compliance — it means we re‐engineer it for this new setting.

The big 2025 update: Final FDA guidance vs. earlier draft

It’s been a journey to this point. The Food and Drug Administration had published a draft titled “Decentralized Clinical Trials for Drugs, Biological Products, and Devices” in May 2023. Then, on September 18, 2024, the final guidance became available.

What changed: big picture

Title shift: The change from “Decentralized Clinical Trials (DCTs)…” to “Conducting Clinical Trials With Decentralized Elements” signals a shift from “all or nothing” to “some elements”.
Removal of the local HCP “task log” requirement: In the draft, there was more emphasis on having local healthcare personnel formally tracked via “task logs.” The final guidance removed that specific requirement, simplifying the burden
Clarified data variability concerns: The final version contains more nuance on how to limit variability when remote elements are used (training, video supervision, standardised instructions) to maintain high levels of data integrity.

Why that matters for drug compliance

Because when trial visits, monitoring, and dosing happen partly in remote settings, the stakes for drug compliance go up. Think of:

A patient self-administering at home instead of under direct site supervision → how do you ensure they took the investigational product properly
A local HCP or home-visit nurse administers it instead of the main site staff → the sponsor must ensure training and oversight, maintain logs, check storage/handling.
Data flowing in from devices, wearable sensors, telehealth visits → the sponsor must ensure that the remote Data Acquisition pipeline is robust, secure, and that systems capture correct dosing, adverse events, deviations.

In short: the new guidance is an endorsement of decentralisation, yes—but also a reminder: you still need rock-solid compliance. The new frontier requires you to evolve your compliance model.

Roles & oversight: Who does what in a DCT

With decentralised elements in the fold, it becomes more important than ever to nail down roles, responsibilities, and oversight — because drug compliance doesn’t happen by itself.

Sponsor

The sponsor remains ultimately responsible. According to the guidance, the sponsor must ensure that trial design, conduct, and monitoring are adequate even if many activities happen remotely.
In the context of drug compliance: the sponsor must ensure that drug shipments arrive intact, are stored properly, administered correctly (even at home), deviations are documented, participant adherence is captured. The sponsor also must build a Compliance Framework that spans remote visits and ensures monitoring, auditability, and traceability.

Investigator & Delegation

The investigator retains responsibility for participant safety and safeguarding the integrity of the trial. But in a decentralised model, they may delegate visits, local measurements, remote monitoring, home-visits via local HCPs or home health nursing. The guidance clarifies who can do what, under what supervision.
For drug compliance: the investigator must ensure that every person administering the investigational product (IP) at home or via a local HCP is trained, aware of the protocol, and that dosing is appropriately monitored.

Local HCPs / Home-Visits

This is a big shift. The guidance explicitly allows visits with local health-care providers (HCPs) or home-health visitors.
That means, for Regulatory compliance, if a home-visit nurse administers the IP, the sponsor and investigator must ensure that nurse is qualified, the chain-of-custody of the drug is maintained, the IP is stored and chilled if needed, dosing is recorded accurately, any deviations are flagged.

Oversight & Monitoring

Even though participants may not set foot in a traditional trial site, protocols must include oversight of remote activities, monitoring plans, risk-based processes, audit trails, and readiness for inspection.
In practice, this means remote dashboards tracking dosing adherence, remote query resolution, flagging missed doses, tracking participant-reported outcomes. It also means the sponsor must incorporate remote drug compliance checks and handle deviation management.

In short: the web of responsibility expands. That’s why having a strong Compliance Framework is also key—not just at the site, but across decentralised operations.

Inspection readiness for remote trials

A big emotional moment for many trial-teams: how do you prepare for an inspection when parts of your trial are happening out in people’s homes, via telemedicine, or via local clinics scattered across geographies?

The Food aDA guidance emphasises: even if parts of the trial are remote, the regulatory requirements do not change.
Here are some practical tips (with a nod to ensuring Regulatory compliance):

Ensure there is a physical location (or designated records location): The agency expects there to be a physical location where the trial records are accessible, including for remote or decentralised visits.
Audit trails for remote events: If a participant receives the IP at home, a home-visit nurse or the local HCP must generate records: who administered the dose, when, how, with timestamp. The audit trail must include remote interactions.
Remote Data Acquisition systems must be compliant: Wearables, apps, telehealth systems need to support data integrity, timestamping, traceability. Sponsors must ensure that dosing, adherence, and participant-generated data are captured reliably.
Drug storage, shipping and handling documentation: Especially when IP is shipped to homes or local clinics. Inspectors will want to see how temperature control, chain-of-custody, participant receipt of medication was handled — all part of ensuring compliance.
Deviation management: With remote or home-visits, the risk of missed visits or deviations may increase. Systems must have logs of missed doses, late visits, remote visits versus site visits, and corrective action plans.
Training documentation: All personnel, including remote/home personnel, must have training records. If a home-health nurse administers an IP, sponsor/IG must ensure training records exist. That ensures compliance and readiness

Emotionally speaking: there’s a moment in many trials where you realise “Yes — we are on the journey of decentralisation, but we still carry the weight of regulatory expectations.” The home-visit, the telehealth video call, the wearable sending data — they are enablers but also triggers the need for stronger vigilance. Ensuring Investigational product compliance in this environment becomes not just a checkbox but a core trust element: trust of the participant, trust of the regulator, trust of the public.

Investigational product (IP) use outside the site

Let’s talk about the medicine, the heart of many clinical trials: the investigational product (IP). When you move parts of a trial outside the traditional site, you are moving risk—so the way you manage IP becomes even more critical for Investigational product compliance.

The FDA guidance spells out recommendations for packaging, shipping, handling, and administration of IP when decentralised elements are used.

Key considerations

Appropriateness for decentralised use: Not every investigational product is suitable for remote/home use. If it requires complex preparation, in-hospital monitoring, or intensive safety checks, decentralisation might not be appropriate. The guidance calls this out
Packaging & Shipping: IP may need cold-chain, temperature monitoring, tracking of delivery to a participant’s home or local clinic. A wrong temperature, a damaged package, or a missed delivery can jeopardise compliance and participant safety.
Receipt and Administration at Home or Local Clinic: How do you know the participant actually took the dose? How is that recorded? Is a local HCP involved? The sponsor must define it in the protocol.
Storage & Handling: If the dose sits in a home refrigerator, how do you verify conditions? If a home-health nurse administers, is there an audit trail of the administration, time, lot number?
Participant Adherence: When the participant self-administers at home, you must build mechanisms to track whether they took it, missed it, or had side-effects. That’s Investigational product compliance in action.

Real-world example

Let’s imagine a trial of a novel oral therapy in heart failure. The sponsor decides to allow participants to take the dose at home, with a local nurse visiting every other week and a telehealth check weekly. The nurse delivers the blister pack, checks the participant has taken the previous month’s dose (via a smart blister-pack sensor), documents timing, lot, batch, and instructs the participant how to record dosing in an app (remote Data Acquisition). If the participant misses a dose, the nurse records the reason, triggers a protocol deviation, alerts the site physician. The sponsor overlays this data in a compliance dashboard. When an FDA inspector comes by, the sponsor can show: participant ID #2343, home-visit on June 10, lot AB-123, blister pack, logged app timestamp, remote video confirmation, deviation logged June 11, corrective action initiated. That’s decentralised elements + drug compliance done right.

Packaging & shipping details

Packaging and shipping might sound like logistics-boring. But in decentralised trials they become compliance-critical. If your investigational product arrives late, at the wrong temperature, unsealed, or goes missing, you risk non-compliance, participant harm, data integrity issues, regulatory headwinds.

In the final guidance, the FDA emphasises that sponsors must evaluate whether participants may safely receive IP outside the site, how shipping/storage will be handled, who will administer, and how records will be maintained.

What you should pay attention to in your planning

Shipment tracking: Ensure end-to-end visibility from warehouse → courier → participant or local clinic.
Temperature/Condition monitoring: If the IP is temperature sensitive, ensure cold-chain or validated ambient shipping; record temperature logs.
Participant Receipt: At home or local clinic, there should be documented confirmation that the dose arrived intact and stored appropriately.
Administration documentation: If local HCP or home-health nurses administer, they must document dose, lot, time, any deviations.
Return or disposal of unused product: Sponsors must plan for what happens if a participant drops out, misses doses, or trial ends – how the IP is retrieved, how accountability is maintained.
Protocol definition: The trial protocol must clearly outline shipping, storage, administration, monitoring processes for remote product use.

Emotional angle

Think of a grandmother in a remote area: she receives the package at her home, opens it, takes the medicine, but day-to-day she wonders, “Is this really safe? Did I get the right dose?” The sponsor and trial team have to ensure that she is assured, supported, and that behind the scenes the chain (shipment–receipt–administration–documentation) is watertight. That’s where Medication adherence meets human experience.

Digital health tech (DHT) used for remote data capture

One of the most transformative enablers of decentralised trials is digital health technology (DHT) — wearables, remote monitoring apps, telehealth platforms, mobile sensors. The FDA final guidance explicitly addresses these tools under remote Data Acquisition.

Why DHT matters for drug compliance

When a participant takes investigational medicine at home, how do you verify dosing, adherence, side-effects, vitals? DHT can be the bridge.
Remote Patient Monitoring: If you’re monitoring heart rate, ECG, oxygenation at home, you can detect adverse events, deviations, missed doses faster.
The data flows back into the sponsor’s system; you can build dashboards, queries, alerts — enabling a proactive approach to Medication adherence rather than reactive.
DHT design must include training, support, alternative options for participants without tech, and must ensure data integrity, security, and usability. The guidance flags this.

Example in practice

Let’s say the investigational product is for managing diabetes. Participants are given a wearable continuous glucose monitor linked to the trial app, plus a smart pill-bottle cap that logs when doses are taken. The data feeds into the remote monitoring dashboard. If a participant misses a dose, or their glucose patterns deviate, the system flags an alert: remote nurse calls the participant, discusses barriers, reinforces dosing, documents the intervention. The sponsor sees real-time compliance metrics: percent of participants with ≥95 % dosing adherence, average time to follow-up on missed doses, number of remote interventions. That operationalises regulatory compliance in real-time.

But remember the caution

DHT doesn’t replace human oversight. The guidance reminds sponsors that while remote tools are helpful, risks of variability, data integrity, participant usability and training still apply.
In fact, for therapeutic compliance: many of the failure points emerge when technology is used but the human train-up is weak, connectivity fails, or participant literacy is low. So the emotional connection: treat every wearable, every app, every remote visit as part of the patient experience — not just as a tech project. Because when participants feel seen and supported, they’re more likely to stay adherent, report issues, and engage. That’s drug compliance and it’s deeply human.

Local HCPs and home-health personnel

Lastly, one of the most practical shifts in the field: embracing local healthcare providers (HCPs) and home-health nursing as part of the trial ecosystem. The guidance opens the door for local HCPs to perform trial-related activities (as long as they’re within their scope of practice) and for home visits to be part of the protocol.

Why this matters for Therapeutic compliance

A dedicated home-visit nurse or local HCP means dosing can be supervised or supported in the participant’s environment, rather than expecting them to travel. That reduces missed doses, improves adherence.Z
That local support builds trust: participants feel less like remote subjects and more like valued partners. When participants feel cared for, therapeutic compliance often improves.
The sponsor must ensure training, oversight, documentation, and inclusion of those local partners in the broader Compliance Framework. Local HCPs must know the protocol, know the IP handling, know dosing, know when to escalate.
In many decentralised trials, the home-health nurse becomes the face of the trial for the participant. That relationship matters deeply — it helps adherence, helps capture adverse events, helps motivate participants to follow the regimen.

Real-life nuance

Consider Mark, a 68-year-old participant living in a suburban area. Instead of traveling to a research centre every two weeks, a home-health nurse visits him every week, refills his investigational drug, checks his vitals, and asks how he is feeling. They chit-chat. Mark feels supported. Because he feels someone cares, he makes sure he takes the dose on time. If he forgets one morning, the nurse gently reminds him when she exists. That in turn feeds back into the sponsor’s monitoring dashboard: dosing adherence is logged, blurbs of patient experience being collected, home-visit outcome documented. That’s a powerful illustration of how local HCP/home-health personnel and decentralised trial design can uplift therapeutic compliance.

Ethical Oversight Across States: IRB Strategy in Multi-State DCTs

In multi-state decentralized trials, a clear IRB strategy is key to keeping everything compliant and ethical. Even though the FDA’s final guidance doesn’t have a separate section for IRBs, it makes one thing clear — participant safety and oversight don’t change just because a trial goes remote. A central IRB is often the best choice for multi-state DCTs since it ensures consistent review, faster approvals, and stronger drug compliance across all locations.

The IRB must confirm that all investigators and home-health providers are licensed in the participant’s state and that electronic informed consent tools meet privacy and security standards. It should also review how data, remote monitoring, and safety events are managed across different regions. In short, the IRB acts as the ethical compass of a DCT — ensuring every home visit, telehealth check-in, and remote data capture stays within safe and compliant boundaries.