Consider Patients First in Direct-to-Patient Trial Designs

Randomization & Trial Supply Management (RTSM) solutions have existed for over 20 years and have evolved to include more functionality based on the changing needs of the studies they support. However, since their inception, one thing has remained constant: the flow of inventory always goes from depot-to-site-to-patient, and then the system’s job is done.

Historically, there was nothing wrong with this situation. A patient in a trial would go to the nearest investigational site, go through all the patient-related processes and procedures, and then receive medication as appropriate based on their assigned treatment arm and associated medication requirements. But multiple site visits for subsequent processes over the course of a study can complicate the trial experience.

When pivoting to trials that leverage decentralized elements like direct-to-patient (DtP) provision models, such changes must consider patient burdens. Along with data integrity in the study, the patient should be our primary focus and the right solution should offer them flexibility. Ideally, the solution should also ensure the required medication is available at the site, which is not always the case.

What needs to change?

If we want to be more empathetic to patients’ requirements and circumstances, the industry needs to update our thinking and best practices to simplify things for all patients without negatively impacting sites. So, can we change the packaging designs and reduce the number of site visits while maintaining high standards of patient care?

Is direct-to-patient medication provision the answer?

When talking about DtP medication provision, we are specifically referring to the mechanisms by which patient supplies are sent directly to the patient or caregiver, reducing the need to bring the patient into the site to collect them. It is one element of decentralization that can simplify participation.

Now, let’s consider DtP specifically. DtP involves securely getting trial materials to the patient’s home or other location while demonstrating a complete study inventory chain of custody to ensure regulatory compliance. We should not simply send inventory from depot-to-site and then let the site arrange last mile delivery to the patient outside of the RTSM system. Aside from transferring burdens to the site, this approach fails to always ensure the full visibility of trial medications. Systems should be in place to track shipments and allow tracking data to be consolidated with all the other trial shipment and inventory data. This is especially important when considering the increasingly complicated and necessary storage conditions of trial supplies.

The destination address for inventory is also very important. It can be exceptionally damaging if patient identifiable information (PII) were to leak, and privacy regulations must be considered. Name and address information must be stored securely and kept up to date in a system rather than a manual spreadsheet, but remain accessible enough to ensure supplies are shipped to the right location.

Of course, what works for one country or site will not work for all. Some countries allow DtP shipments while others don’t. Some sites can support DtP activities and others can’t. The recent EMA recommendation paper on decentralized elements in clinical trials is a good illustration of the variance in member state regulations across the EU/EEC [REF]. Further, when it comes to applying decentralized elements post-pandemic, the regulatory position is evolving. What was set up today may not work tomorrow, so any solution we create must be flexible.

The final thing to consider is the trial design itself – we cannot assume that all visits will be home-based or at-site. Any RTSM solution should be configurable at the study, country, then site levels, and needs the ability be able to react to unplanned changes in patients’ circumstances.

What does an effective DtP solution look like?

The previous section draws attention to key considerations for RTSM-DtP solutions. Let’s explore each in more detail.

PII and the Patient

In terms of supplies, PII needs to be managed correctly as part of the solution. RTSM should hold this data, assuming proper controls are in place, since the systems raises the shipments, and fully formed shipment requests require a destination. If PII is securely stored, encrypted, and managed in a compliant way, then everything else becomes much simpler and involves far less risk than with manual methods.

Finally, any RTSM solution must keep the patient informed through shipment tracking data to ensure that they or their caregiver are available to receive the shipment and allow for patient override of the visit location as needed. As a standard, flexibility must be baked in by design through configuration rather than customization.

Chain of Custody

Where any DtP shipment is required for a specific patient or visit assignment, RTSM reporting must reflect this and inform the source & destination of the shipment. This means that any RTSM solution must be able to integrate with the myriad of patient-facing mobile apps, or a courier’s existing solution to send shipment requests and receive updates. It’s important to note that shipment requests must use encryption to ensure patient addresses are only used by the intended recipient. In the absence of another centralized inventory management system, RTSM should act as the central hub for the study where supplies are concerned.

Once the patient has confirmed receipt, controls should be in place to allow the investigator or study nurse to make the ultimate decision on what the patient should or should not consume, especially for temperature-controlled medications.

Study and Inventory Design

Direct-to-patient provision must be able to scale with the study and inventory designs, since we cannot assume that all visits will be the same type within one study or country. However, there will be some visits that cannot be overridden at a lower level, so the RTSM solution must allow configuration for what can and cannot be changed. As best practice, the visit design needs to be tied to the inventory design – a site visit does not necessarily mean the patient will pick up all assigned inventory and take it home. Separate from the visit design, we must configure the pathway that inventory will take per item type and allow time for inventory to travel to the right location. Any RTSM solution must predict for hybrid visits carefully, and more site stock may be required.

Changes per Country or Site

Studies change, regulations change, and site capabilities change. Any DtP solution must be able to adapt to those changes with little to no downtime for the study. So, the ability to configure and then re-configure country and site aspects through self-service is key.

In Summary

There are many industry buzzwords and a lot of material about how those buzzwords are supported. However, let’s forget that jargon and concentrate on the important things. For any decentralized or DtP solution to be successful, the patient must be the most important consideration after the trial’s data reliability. Therefore, any RTSM solution must be flexible enough to ensure that the patient receives the highest standard of care and system functionality along with a simplified participation experience.