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What are the key characteristics of hybrid direct-to-patient studies and supply chain structures that can make them a standard consideration for clinical trial adoption?
The Covid-19 pandemic was a major catalyst for the pharmaceutical industry to finally embrace the benefits of decentralized clinical trials (DCTs), specifically the various types of direct-to-patient (DtP) trial models associated with the framework. Prior to Covid, adoption of the DtP design was slow. Pharma sponsors only stood up DtP studies when circumstances dictated their need, but the fallout of the virus changed everything. Vulnerable patient populations demanded the flexibility of access afforded to them by DtP trials to maintain safety and convenience. And as preferences for clinical trial participation changed, sponsors and contract research organizations (CROs) had to adapt. They recognized that DtP trials can improve enrollment, ease patient burden and create greater transparency in the investigational medicinal product (IMP) journey from the clinical site to patients’ homes. Hybrid DtP trial models combine the support and reliability of on-site clinics with more patient-centric comforts afforded by DCTs.
Digging deeper, what are the key characteristics of hybrid studies and supply chain structures that will make them a standard consideration for clinical trials?
DtP’s orchestration across diverse therapeutic areas
Hybrid DtP clinical trials address common challenges associated with decentralized trials: not all types of therapeutic trials can be executed completely through telemedicine or remote healthcare. In some areas, such as oncology, investigators have limited options because of the nature of the treatment, which very rarely allow patients the option to participate in DCTs.
The hybrid trial model recognizes the sensitive nature of these therapeutic areas and provides a solution. Where fully DtP trials can produce uncertainty, the hybrid model expands sponsor control over data outcomes as patients participate in the clinic on-site under direct supervision of investigators. The benefits are twofold. The hybrid trial model reduces the strain on patients and sponsors by saving time, energy, and effort.1 It also allows for recruitment and retention of a more diverse trial population in sensitive therapeutic areas. Giving patients the ability to choose to continue trial participation on-site or having the drug sent to their home offers greater freedom to patients who can't be present at all appointments or who may be immunocompromised, resulting in better retention and faster recruitment across a larger variety of populations compared to relying solely on traditional on-site trials or pure DtP.
Hybrid DtP’s configuration with compliance and regulations
The hybrid model creates a unique challenge when it comes to configuration to compliance protocols pertaining to patient privacy, safety and drug handling. With the right technology and preparation, however, the design can easily become more flexible. Since there are no set regulations to guide DtP/DCTs, sponsors must follow best practices as they exist today when submitting a trial protocol. Guidelines will differ based on geographic region, and adhering to them can be a complex, amorphous process. This is especially important to consider when a clinical trial is deployed globally. Regulatory teams must apply in-depth knowledge to determine how to optimize shipping, storage and supply processes2 while staying compliant. Equally important is that the same level of care is extended to patient data handling. Practices should always follow regional privacy rules(e.g., GDPR),3 which can change in nuance from country to country. However, coupling an iterative randomization and trial supply management (RTSM) system to deploy hybrid studies alongside Internet of Things (IoT) tech can make adapting study designs to various regulations much easier on a larger scale. It can also mitigate supply chain and shipment coordination risks to ensure timely and accurate distribution.
Hybrid DtP models are much more complex and must support two processes in parallel. The first is to ship from the site/depot to the patient while providing remote support. The second is managing inventory at the sites, treating patients at the clinic and maintaining a list of who is part of the DtP trial and who isn’t. Other challenges involve shipping costs, courier-patient coordination and pharmacist involvement at the depot/central pharmacy. An effective hybrid supply chain is by nature more agile, more consistent when it comes to quality and versatile enough to better ensure the timely delivery of drugs and therapies to patients while reducing the potential for drug waste.
Hybrid DtP = better patient autonomy, safety and participation
Patient autonomy is a critical benefit of the hybrid model. In this case, patient choice leads to patient centricity and safety;4 a major advantage in a post-pandemic world. Patients can decide how they want to participate in the study while having the convenience of receiving medications at their home to minimize clinical site visits. The hybrid model also addresses patient health concerns and travel, cost and time burdens often associated with on-site studies. The flexibility, accessibility and patient autonomy afforded to patients in hybrid trials will continue to be a driver for trial recruitment rates long after the pandemic subsides. Equally important, however, are the ways that hybrid DtP designs and supply chains are contributing to the evolution of the trial experience, changing patient roles and benefitting sponsors.
In a hybrid DtP trial, the supply chain is a critical link between the manufacturer and the patient. Once a protocol has been approved, these models can streamline the shipment of trial materials to patients’ homes and make it easier to retrieve samples for lab analysis. A hybrid supply chain model can also mitigate the drug excursion risks, a safer option because it includes temperature controlled delivery during the “last mile” to the patient. In a consolidated hybrid supply chain, transport, management, data gathering and home healthcare services alleviate these issues.
Hybrid studies also allow patients to become more active participants in the trial, resulting in more freedom and deeper understanding of the significance of their role in it. Patients are required to use various apps and tools to authorize receipt of drugs at home; to learn how to store and administer medicines; better understand how to receive remote guidance and go through exams virtually; and, in some cases, log into multiple telehealth systems to report physical changes and communicate with their physician. This is a far cry from the traditionally passive on-site trial experience and likely contributes to better retention. Promoting greater patient participation can also, in turn, reduce dropout rates because participants feel like they’re having a tangible impact on the clinical trial’s outcome.5
In the last few years, the number of clinical trials adopting the hybrid DtP model has significantly increased. The challenges that have impacted the global clinical trial space spurred greater interest by sponsors and CROs because it marries patient benefits associated with on-site and pure DtP trial frameworks, while offering a compliant, flexible, safe and accessible study option that can be applied across therapeutic needs. It isn’t difficult to understand why the industry has embraced the model despite its complexities.
Since these studies don’t come without risk, it will be important to continue to understand how to design and execute them in ways that protect patient privacy and supply chain integrity. If done correctly, hybrid DtP models illustrate a future for the clinical trial space that can help streamline studies and contribute to getting medicines to those in need with greater speed and better results.
About the Author
Neta Bendelac is Director of Strategy at 4G Clinical.