Direct-to-Patient Clinical Trials: DtP Shipping

“Direct-to-patient” (DtP) refers to a specific logistics model within clinical trial supply management: shipping investigational product (IP), also called investigational medicinal product (IMP), directly to a trial participant’s home instead of requiring the participant to travel to the investigator site to receive it. See CASRAI’s Investigational Medicinal Product (IMP) entry for the formal definition. DtP is a supply-chain and logistics arrangement, not a trial design in itself — it is one operational component that a sponsor can layer onto an otherwise conventional or decentralized protocol.

DtP is easy to conflate with the broader term decentralized clinical trial (DCT), but the two are not synonyms. A DCT can include remote consent, telehealth visits, electronic patient-reported outcomes, and home health nursing without ever shipping product directly to a participant; conversely, a conventional, fully site-based trial can still use DtP shipping for a single visit a participant cannot make in person. This guide covers the DtP shipping model specifically: what it is, how the physical and documentary chain of custody works when the “last mile” ends at a private residence instead of a pharmacy or investigator site, and the regulatory and operational considerations that come with moving IMP outside institutional walls.

Why Sponsors Use Direct-to-Patient Shipping

DtP shipping is used to reduce the burden a trial places on participants, which in turn supports enrollment and retention. It is particularly common in:

Rare disease trials, where the eligible population is small and geographically dispersed relative to the number of qualified investigator sites, making frequent site visits impractical for many participants.
Long-duration or maintenance-phase trials, where routine dosing visits after an initial in-clinic period add little clinical value but a meaningful travel burden.
Trials enrolling populations with mobility, immunocompromised status, or geographic access limitations, where an in-person visit carries its own risk or cost.
Trials that lost visit continuity to a disruption — DtP shipping saw large-scale adoption during the COVID-19 pandemic as sponsors needed a way to keep participants dosed without in-clinic visits, and much of that infrastructure and vendor capability has remained in routine use since.

How Direct-to-Patient IMP Shipping Actually Works

DtP shipping extends the standard IMP supply chain by one additional link. In a conventional trial, IMP moves from the manufacturing site through a central or regional depot to the investigator site’s pharmacy, where it is dispensed under the oversight of the investigator or a delegated site pharmacist. In a DtP model, the same upstream chain applies, but the final leg is re-routed around the site. Three operational patterns are in common use, often in combination within a single program:

Specialty pharmacy or clinical courier shipment. A specialty pharmacy (or the site pharmacy, depending on the protocol and jurisdiction) dispenses the IMP and a specialty logistics provider ships it directly to the participant’s address, typically in temperature-controlled, tamper-evident packaging with an embedded temperature data logger. This is the model most associated with the specialist clinical-trial logistics vendors (courier and depot networks, and the randomization/trial-supply-management, or RTSM, platforms that trigger and track each shipment) that this sub-vertical of the industry has built out.
Home health nursing administration. Product is shipped to a mobile or home health nurse, or to the participant with a nurse visit scheduled to coincide with delivery, and the nurse administers the dose and documents the visit. See CASRAI’s guide to mobile and home health nursing vendors in decentralized trials for how delegation and credentialing work for that model.
Local pharmacy network with last-mile courier. Some programs route through a network of local retail or specialty pharmacies near each participant rather than a single central specialty pharmacy, shortening the last-mile leg and reducing in-transit time and temperature risk.

Whichever pattern is used, the underlying accountability does not change: under Good Clinical Practice, the investigator remains responsible for the accountability, storage, and proper handling of IMP at the site, and for ensuring that any function delegated to a third party (a courier, a specialty pharmacy, a home health nurse) is performed to the same standard the investigator would be held to directly. Shipping the “last mile” to a residence delegates a task; it does not delegate the responsibility for it.

Regulatory Considerations

DtP shipping sits inside the same regulatory framework that governs IMP handling generally, with a few considerations that become more pronounced once product leaves institutional custody:

ICH E6(R3), the current core Good Clinical Practice guideline, was written with decentralized and hybrid trial designs explicitly in view, and treats trial-related activities that occur at locations other than the traditional investigator site — including a participant’s home — as activities the sponsor and investigator must still control and document to the same evidentiary standard as anything happening on-site. It does not create a separate, lighter standard for off-site activity.
FDA and EMA have each published guidance addressing decentralized elements of clinical trials, including the use of local health care providers, telehealth visits, and shipment of investigational product to a trial participant’s location. Sponsors running DtP shipments into a given jurisdiction should confirm the current version of that jurisdiction’s guidance directly with the regulator rather than relying on a secondary summary, since this is an area of guidance that has continued to be refined as the practice matures.
State and cross-border pharmacy licensure is one of the most concrete legal constraints on DtP shipping in the United States. Pharmacy practice, including dispensing, is licensed at the state level, and shipping a dispensed prescription product across a state line can trigger a requirement that the dispensing pharmacy also hold a non-resident (out-of-state) pharmacy license in the participant’s state, in addition to its home-state license. This is a real, program-level constraint on which participants a DtP arm can enroll or continue to serve if they relocate mid-trial, not a paperwork formality.
Controlled substances add a further layer: an IMP that is a Schedule I–V controlled substance under the Controlled Substances Act is subject to DEA registration and handling requirements that are considerably more restrictive than those for a non-controlled IMP, and direct-to-residence shipment of a controlled investigational product requires specific attention to those requirements rather than assuming a standard DtP courier arrangement automatically satisfies them.

Chain of Custody and Cold Chain Documentation for Home Delivery

A site pharmacy dispensing IMP has controlled storage, a pharmacist verifying identity and appropriateness at the point of dispensing, and immediate documentation. None of that infrastructure exists by default at a participant’s home, so DtP programs have to build it into the shipment itself:

Temperature monitoring in transit. Shipments typically include a calibrated data logger that records temperature continuously from dispatch to delivery, so any excursion outside the product’s approved storage range can be identified and assessed against the product’s stability data before the dose is used, rather than assumed acceptable.
Proof of delivery and identity confirmation. Because there is no pharmacist or site staff member present to confirm the right participant is receiving the right product, DtP programs rely on signature-required delivery, ID verification protocols, or a scheduled nurse visit to close that gap.
Participant-facing handling instructions. The participant (or a caregiver) becomes a link in the chain of custody the moment the package is accepted, so clear, simple instructions for storage (e.g., “refrigerate immediately”) and what to do in the event of a damaged package or missed delivery window need to travel with the shipment, not just live in the protocol.
Return, reconciliation, and destruction. Accountability records — what was shipped, what was used, what is unused and needs to be returned or destroyed — still have to reconcile at the end of the trial or a participant’s participation, which typically means arranging a return shipment or a documented in-home destruction/collection process rather than relying on the participant to dispose of unused product themselves.

See CASRAI’s broader guide to clinical trial supply management for how DtP shipping fits into IMP forecasting, depot strategy, and accountability more generally, and the Investigational Medicinal Product Dossier (IMPD) entry for how a product’s approved storage and stability parameters — the reference point against which any in-transit temperature excursion gets assessed — are documented in the first place.

Operational Risks and How Programs Mitigate Them

Blinding integrity. A courier or delivery label that inadvertently reveals dosage strength, formulation differences between arms, or a visibly distinct package between investigational and comparator product can unblind a participant or an unblinded household member. DtP packaging design has to account for this in a way site-dispensing, where a pharmacist controls what the participant sees, does not have to.
Missed or refused deliveries. A courier attempting delivery to an empty residence, or a package requiring a signature from someone unavailable, creates both a temperature-excursion risk (the package sitting in a vehicle or on a doorstep) and a protocol-deviation risk (a missed or delayed dose). Programs mitigate this with delivery-window scheduling and confirmed appointment windows rather than unscheduled shipment.
Adverse event response at a distance. Without site staff present, a participant experiencing an adverse reaction after a DtP-delivered dose is relying on a phone-based safety contact rather than in-person clinical staff, which shapes how DtP arms are usually reserved for products and populations where that risk profile is acceptable.
Vendor and vendor-of-vendor oversight. A DtP arrangement typically adds at least one, and often two, delegated third parties (a specialty pharmacy and a courier, or a courier and a home health staffing vendor) to the trial’s oversight burden. Sponsors and sites need vendor qualification, monitoring, and audit processes that reach those parties, not just the investigator site itself.

Direct-to-Patient vs. Decentralized Clinical Trials: Keeping the Terms Straight

Because DtP shipping is so closely associated with the rise of decentralized trials, the two terms are frequently used loosely as if interchangeable. They are not:

Decentralized clinical trial (DCT) is the broader design concept: some or all trial-related activities — consent, visits, assessments, data collection — happen away from a traditional investigator site, using any combination of telehealth, remote monitoring, local labs, home health visits, and electronic data capture. See the Decentralized Clinical Trials (DCTs) and Decentralized Clinical Trial (DCT) Platform dictionary entries for the fuller definition and the technology layer that supports it.
Direct-to-patient (DtP) is specifically the IMP supply-chain arrangement described in this guide: shipping investigational product to a participant’s home rather than dispensing it at a site.

A trial can be decentralized without using DtP shipping (e.g., a fully telehealth-and-remote-monitoring trial where the participant still visits a local infusion center for dosing), and a trial can use DtP shipping for one visit without being decentralized in any other respect. Treating them as the same thing risks scoping a program’s vendor and regulatory review too narrowly — a DtP arrangement needs its own supply-chain, pharmacy-licensure, and chain-of-custody review even inside a trial that is otherwise fully site-based.

Frequently Asked Questions

Is direct-to-patient shipping the same as a decentralized clinical trial?

No. DtP shipping is one specific supply-chain arrangement — shipping investigational product to a participant’s home instead of dispensing it at the investigator site. A decentralized clinical trial (DCT) is a broader design concept that can include DtP shipping alongside other remote elements such as telehealth visits and remote monitoring, or none of them.

Who is responsible for investigational product once it is shipped to a participant’s home?

The investigator retains overall accountability for the investigational product under Good Clinical Practice, even when a specialty pharmacy, courier, or home health vendor performs the physical dispensing, shipping, or administration on the investigator’s behalf. Delegating the task does not delegate the responsibility for it, which is why DtP programs need documented oversight of every vendor in that chain.

Can any investigational product be shipped direct-to-patient?

Not always. Products requiring specialized administration (e.g., infusions that must be given by trained clinical staff), controlled substances subject to DEA handling requirements, and products with narrow stability windows that make in-transit temperature control difficult are all cases where DtP shipping may be limited, modified (e.g., paired with a home health nurse visit), or excluded from the protocol’s supply strategy entirely.

Does DtP shipping require the participant’s local pharmacy to be involved?

It depends on the model. Some programs use a single specialty pharmacy licensed to ship into every state a trial enrolls participants from; others route through a network of local pharmacies near each participant. In the United States, a pharmacy dispensing and shipping across a state line typically needs a non-resident pharmacy license in the participant’s state in addition to its home-state license, which shapes which model a given program uses.

What happens to unused investigational product after a DtP shipment?

It still has to be accounted for under the trial’s drug accountability records, the same as product dispensed at a site. In practice this usually means arranging a scheduled return shipment back to the pharmacy or depot, or a documented in-home collection or destruction process, rather than leaving disposal to the participant.

For the surrounding supply-chain, quality, and manufacturing context this guide sits inside, see CASRAI’s clinical research administration hub.