Where Does Direct-to-Patient Fit in a Post-COVID World?

As we look forward, questions exist about how the use of direct-to-patient model will evolve—and what is needed to ensure the success of these trials in a rapidly evolving healthcare and clinical trial landscape. In the following Q&A, Andrea Zobel, PhD, Senior Director of Personalized Supply Chain at AmerisourceBergen’s World Courier, a global specialty logistics provider, and Graham Wylie, MBBS, Executive Chairman & Founder of the Medical Research Network (MRN), discuss the demand for decentralized clinical trials (DCTs), the unique challenges and considerations for implementing the model around the world, and how the emergence of technology and data solutions will affect DCT moving forward.

ACT: How will the demand for decentralized clinical trials change?

Andrea Zobel

Andrea Zobel: We saw a tremendous spike in DCTs and direct-to-patient shipments in the early months of the pandemic. Given the success seen across the industry over the last couple of years, coupled with the recruitment, retention, and economic benefits of this approach, we anticipate decentralized clinical trials will be a feature of more clinical trial designs in the future.

Research continues to suggest patients prefer this approach, too. In fact, patients would be more likely to enroll in clinical trials if burdens on their time and travel were reduced, according to recent research. By bringing products and customized care directly into patients’ homes, sponsors can reduce barriers and expand access to a broader and more diverse range of patients, including those who otherwise wouldn’t have been able to participate due to location, lack of transport or mobility issues. That’s particularly important as about 70% of potential trial participants live more than two hours away from study centers.

Graham Wylie

Graham Wylie: The pandemic provided a proof-of-concept moment for DCTs and pushed it into the mainstream as an option for all trials. However, the ROI during the pandemic was totally different—studies were in a ‘fail or survive’ situation with essentially black and white outcomes, and in that scenario, it was simple to use the services to keep trials going. What it did not do was test the post pandemic ROI where the cost had to be justified against a more nuanced financial benefit that is still, in the minds of pharma at least, untested. We also know that the pandemic put severe financial stresses on trial specialist sites, many of whom folded as trials failed. These resources are a priority to be rebuilt by Pharma as they try to put trials back on a pre-pandemic footing.

What we can see so far is that the overall market for DCT continues to grow, so we expect to see many more studies include the services, probably reaching 7% of all new trials this year using these tools and methods. Pre-pandemic growth rates would see this continue to rise a percent or so per annum, a rate we expect to be surpassed as familiarity is so much higher and the ROI is better understood, speeding up recruitment and retention of patients.

ACT: Is the DCT model suitable for countries worldwide? What are some of the unique challenges of operating a DCT in various countries?

AZ: There are a number of factors—such as varying levels of infrastructure and unreliable access to electricity and Internet—that can make it more difficult to run DCTs in certain countries or regions. From a logistics standpoint, proper planning is essential to ensure the integrity of the investigational medicinal product remains protected throughout transport and reaches patients on-time and in the right condition. It’s also imperative to have a deep understanding of the regulatory requirements, as they vary across the world. Countries, for the first time, issued DCT guidance in the emergency guidelines for conducting clinical trials amid the pandemic.

The relevant guidances in the medicinal product laws, pharmacy guidances and clinical trials regulations simply do not foresee the concept of a visit conducted at the patient’s home. For example, some markets allow clinical trial drugs to be dispensed by local pharmacies or a storage depot with a licensed pharmacist, while others only permit distribution from trial sites. Denmark is the first country which had issued a guidance for decentralized clinical trials including detailed instructions for home visits. Given the variations in current regulations and the fact that some regulators are evaluating DCT on a case-by-case basis, it’s increasingly important for sponsors to work with an experienced partner that can help them navigate local regulations and restrictions and execute direct-to-patient services on a global level.

GW: Clinical services within theDCT sector will work in any country with a nursing commercial infrastructure and a courier infrastructure, as long as the regulations allow. Very few countries have any legislative hurdles to DCT services, and those that do tend to be quite specific to certain patient populations and IMP types. Nearly all digital tools for DCT will work wherever there is an appropriate technology infrastructure—not just for data flow in the cloud, but also for data privacy and application support, which needs to be in local language. Finally, there are some cultural barriers to adoption in some countries. Although some of these are medical infrastructure related, either due to how PIs are paid or how sites collaborate with commercial service providers, the vast majority of resistance is in pharma and CRO company affiliates, who do not want to deviate from their comfort zone or disturb the status quo.

ACT: As the use of DCT expands globally, what are some of the primary logistics and home healthcare considerations?

AZ: Clinical trial material can be too heavy, fragile, or temperature-sensitive for patients to transport from the clinical site to their home, requiring direct-to-patient delivery. During the clinical supply chain, the materials must be transported from the manufacturing site to local depots to clinical site pharmacies quickly and safely, using shipment solutions which protect them from temperature excursions and any damage. For global trials, the product, support materials and samples must all be packaged, stored, and transported in a manner that complies with the regulations in each of the countries the shipment passes through. As products are shipped over longer distances, across several countries, it’s critical to deploy tracking solutions that record the temperature data and packaging solutions that protect the product integrity throughout transport—even if unforeseen factors arise.

Direct-to-patient shipments can extend these controlled conditions through to the patient’s home, instead of patients having to assume the responsibility of bringing the products back home in the right condition. And the products need to be delivered within a predetermined, extremely narrow timeframe—often timed to the arrival of a home healthcare provider. The precise timing underscores the importance of collaboration among stakeholders across the supply chain, including logistics and technology partners and home healthcare providers, to ensure the medication is delivered on time, in the right condition and with the right support.

GW: Many activities need to happen at the same time to get a Home Trial Support (HTS) visit to work, ranging from getting the nurse, IMP, equipment, and supplies all in the same place at the same time, in top quality condition, through to ensuring the nurse builds a relationship with the site, is well trained, has the confidence of the patient and can operate alone, in the field.

Home healthcare has to be available as widely as possible around each country, covering all of the core trial operational countries and at least 50% of all patients in the trial. Nurses need to be appropriately qualified and trained, not just in the trial activities and GXP, but also in looking after a patient in the home. For digital solutions, a process for patient and nurse support to use the application, in local language is important, and an open architecture that allows data transfer between systems easily. Technology must be simple to use and robust and conform to data privacy requirements.

ACT: How will the emergence of technology and data solutions affect DCT moving forward?

GW: DCT has both clinical and digital components, each with its own place in a trial design. They can and should be used synergistically. We classify our trials across a spectrum of “ultra-low and low touch,” which is ideal for digital solutions through to “medium and high touch,” which require a mix of nursing and digital solutions. Phase I to III research will almost always be using IMP about which little is known, and which have to be treated as ‘unsafe’ until proven otherwise. This means visits of a patient to a site and by a nurse to a patient will always be needed at regular intervals to ensure that level of medical care is maintained to allow more holistic and ‘human judgement’ on the state of a patient’s health. This means the future is mostly hybrid designs of trials, using site visits, nurse visits to the patient, eCOA and telemedicine, as well as e consent and other tools such as digital biomarkers and even digital therapeutics. The correct use of these tools in well-designed protocols will eventually lead to hybrid designs being the norm, with tools designed data item by data item to maximize the efficiency of collection of all data types.

AZ: Advances in technology can create more efficient processes and improve the patient experience, while also increasing connectivity among all stakeholders—from the logistics partners and home healthcare providers to the sponsors and patients themselves. For example, mobile technology can be used for eConsent, integration of data with EHRs, standardized reporting from nurse’s home visits, and robust distribution of trial protocols—all of which ensures data collection is consistent and compliant with ethical and privacy requirements. Technology also plays a key role in providing real-time visibility throughout the shipment and protecting patients’ information. Sponsors and their partners should deploy digital solutions that can anonymize patient information while also ensuring data can be attributed to a consistent ‘patient ID,’ so it remains comprehensible to centralized trial sites.