DEK: Decentralized clinical trials (DCTs) utilizing direct-to-patient (DTP) services, including the provision of drug products, ancillary supplies, and home healthcare visits, have demonstrated significant benefits in patient recruitment and enrollment and reducing burdens on patients. Additionally, they have facilitated trials investigating rare diseases with geographically dispersed populations and other challenges that were previously impossible. The risks and challenges incurred on clinical trials logistics by the COVID-19 pandemic have made traditional, site-based trials challenging during the pandemic and thus have significantly accelerated the adoption of DCT and DTP trials models to keep site investigators and potentially vulnerable and immunocompromised patients safe from infection. Pandemic impacts have also added new roadblocks to the provision of DTP services that require agility, flexibility, and comprehensive global capabilities to avoid.
Evolution of Decentralized Trials and DTP Services
In the United States, clinical trials are performed to demonstrate safety and efficacy to gain U.S. Food and Drug Administration (FDA) approval, and the situation is analogous with regulatory agencies in different countries. While the FDA provides guidance, the pandemic has forced improved drug development processes with more emphasis on safety, efficacy, and speed. The global impact of the pandemic has affected other countries as well, particularly those with active participation in clinical trials. The outreach of decentralized clinical trials had already begun its expansion to offer patients with chronic and rare diseases hope with new experimental medicines in places where there was previously no chance of participation. Direct-to-patient (DTP) clinical study protocols have become a welcome solution to both patients and to the industry itself. There had previously been hesitation among some sponsors to implement DTP models, but these fears are gradually dissipating, driven by the need for solutions due to the pandemic, as well as the benefits these approaches offer in terms of patient recruitment and retention, the speed of data transfer, and overall trial compliance.
Clinical sites have had to rework their strategies to maintain patient engagement even in the most critical situations in distant countries with limited access. Novel technologies had to be either created or reconfigured to enable the crucial DTP home healthcare visits. The key was often a decentralized approach that met both regulatory and patient privacy criteria. In some cases, the clinical study protocol was modified for reformulation so that the drug could be self-administered by the patient or the patient's family, which either limited or eliminated the need for home visits. Administration of the drug itself had to be flexible, and protocols had to become more creative.
Accelerated Adoption of DTP During the Pandemic
The rate of organizations adopting decentralized clinical trials has been accelerated due to global issues stemming from the COVID-19 pandemic. The main benefits of DTP trials are improved enrollment and patient convenience and safety, since much of the trial can be undertaken outside of the investigator site, such as the patient home, workplace, or even a travel destination. Other advantages have included reduced patient drop-out rates and the increased attractiveness of the clinical trial at the outset. In many instances, particularly for oncology patients, the idea of an experimental trial, which may involve randomization and receiving a placebo, has severely hampered patient enrollment. By offering DTP and remote decentralized monitoring, clinical study sponsors have been able to garner patient interest when previously there was little or none.
Patient centricity has become the focus. A clear way ahead to achieve more patient-dedicated clinical logistic solutions for some of the most sensitive medications is to move toward decentralization of the clinical trials, creating a virtual hospital experience.
There are three models for how clinical supplies are provisioned directly to patients. In depot-to-patient protocols, the investigational medicinal product (IMP) is shipped from a main depot or central pharmacy and to the patient. In the second model (site to patient), the IMP is shipped from the depot to the clinical site, and then from the study site to the patient's home. The third model is a hybrid of these two models and has often been employed on a global scale during the pandemic.
To conduct successful and efficient clinical trials under these challenging circumstances, sponsor companies benefit from partnering with clinical trials logistics partners who possess the malleability and agility to implement decentralized platforms and a myriad of DTP models, including the creation of hybrid solutions in certain circumstances, such as orchestrating multiple methods of travel to provide a customized approach to meet deadlines for specific studies. Global travel has been either shut down or severely hampered; at some points over the last year, travel restrictions spanned entire swaths of the world due to the risk of COVID-19 spread. Commercial flight schedules that are disrupted or canceled can potentially disrupt trials completely unless the provider is capable of developing sound contingency plans.
The challenges of the global pandemic created immediate needs for in-home healthcare and specialized logistics, which included both DTP and direct-from-patient (DFP) services. Many clinical studies required not just delivery of the IMP to patients at their homes, but also the collection of biological samples from their homes to be sent to multiple labs. Effective and compliant provision of DTP and DFP services requires significant resources, particularly when protocols involve complex drug administration, multiple blood or body fluid sampling, or complex temperature-controlled logistics for these delicate samples, which may even be headed to different clinical laboratory sites under different temperature requirements.
Regulations and restrictions for clinical trials on a global level have evolved rapidly. The pandemic hastened the need for continual monitoring by regulatory professionals and clinical teams to maintain study integrity. Since many studies have expanded their reach to several countries, the volume of data and the subsequent data analysis coupled with dealing with every changing global regulatory authority have created enormous questions. There has been a need for improved evolution of technologies to facilitate clinical trials across a multitude of global arenas; to make matters more difficult, the information must fit into a viable universal platform. Healthcare interoperability remains a global challenge, but effective clinical logistics partners are proving solutions with rapid deployment, secure cloud storage, and approaches to simplify risk management. Regulatory compliance on top of that intricacy has driven more patient centricity, which is where clinical studies need to be in the long run, with DTP and decentralization at their core.
Advantages of an Integrated Provider with a Global Network
Yourway has a proven, comprehensive global network of 21 GMP depots spanning six continents with the bandwidth to handle any project of any size, in multiple countries, and across multiple jurisdictions within that country, despite the regulatory complexity and the evolving healthcare crisis. The company ensures that all clinical trial components (e.g., IND, comparator drugs, ancillary supplies, and kits) are consistently procured, produced, managed, and controlled according to required quality standards. Each facility has all the GMP processes in place and the necessary controls to make sure that what is being released meets all the necessary protocols, goes to the correct patient, and is delivered at the precise dosage. Risk is minimized or eliminated through all aspects of production, including starting materials, premises, equipment, training, COVID-19 personal protective equipment (PPE), and personal hygiene of the staff. The availability of PPE supplies has been an ongoing challenge as well. The company has tailored to the formulations of various global requirements and made sure the sponsors and patients had what they needed, demonstrating its superior agility in a difficult healthcare crisis.
Yourway presents clients with choices from a menu of services geared toward DTP/decentralized solutions. If a client needs storage and distribution, Yourway can deliver. If the client needs competitor drug products and ancillary supplies, Yourway can procure on their behalf; if they need clinical packaging, drug product randomization, kit design and distribution, or specific transportation services, Yourway can customize a solution for their needs with our expert team, providing a white glove level of attention to every detail. Yourway's stellar performance model opens the door to a multitude of projects by offering the assurance tackling just about any situation, whether a trial was impacted by local government regulations, travel bans due to the pandemic, Brexit, or the complexity of patient safety and privacy. These proved to be remarkable resolutions on a global level for many clients in many locations. Clients found themselves in scenarios where they were able to choose what was best for their specific situation while Yourway provided expert assistance in that decision-making process, a welcome relief to many who were struggling. DTP and decentralization salvaged some clinical studies that otherwise faced almost total disruption.
Yourway excels at the delicate logistics needed to effectively and compliantly manage biological sample collection and distribution. Given the clinical significance (and often irreplaceable nature) of biological samples obtained from the patient by nurses during DTP/DFP visits and the stringent temperature-control conditions necessary for the transport and storage of these samples, DFP sample management requires careful coordination to ensure that Yourway has a courier ready immediately upon collection of samples by nurses and that validated and calibrated temperature control is assured through distribution and storage, whether the collected samples are bound for a central lab, multiple individual labs, or a biorepository. This complicated coordination is an area in which Yourway excels and takes pride, which underscores the added value in a partner with both the nuanced understanding of clinical trial needs and a robust and dynamic courier network.
The regulatory landscape can vary widely within the United States alone, but the company can navigate throughout the world. DTP and decentralization have opened the possibilities for global outreach on a massive scale, which has been a welcome advance for both patients and the industry. Yourway has been an integral part of this transition.
Yourway has fielded multiple requests to take charge of projects that had started with another provider. Some of these rescue projects involved short "crisis" time frames, as short as one or two weeks, or the projects faced shutdowns. Yourway was able to answer questions and provide solutions when the problems appeared insurmountable on a global scale. In addition, the company helped several organizations quickly transition from a centralized to a decentralized model to avoid catastrophe. The crux of many of the solutions was transitioning the clinical trials to a DTP model, but there were regulatory issues to deal with, in some cases involving the need for Qualified Person (QP) releases in relevant countries. In Europe, all drug products need to be certified for release in line with the requirements of EU Good Manufacturing Practices (GMP) and Good Clinical Practices (GCP) and that must be done by a QP. The QP must personally acknowledge that the operational responsibilities have been fulfilled, and the IMP can be used in the EU. Yourway is well-positioned with QPs in the United Kingdom and Slovakia to provide QP services in all European countries in which they are required.
As the only truly integrated premium courier and clinical packager in the global biopharmaceutical industry, Yourway has weathered diverse challenges during the COVID-19 pandemic, solidifying its position as a standard-setter in the industry. Despite the obstacles, the company has been able to increase its capacity to compensate for supply chain gaps due to various factors, such as travel restrictions, specific country regulations, and an ongoing need for adaptability to protect IMP integrity, intellectual property, ancillary products, and patient safety and privacy.
Note: This article was originally published on PharmasAlmanac.com in April 2021.