September 29, 2020 PAP-Q3-20-CL-009
The days of blockbuster drugs that treat millions of patients via a systemic delivery approach is over. The focus has shifted to customized medicine, developed for patients with specific biomarkers and disease characteristics, resulting in highly targeted therapies. Traditional trials — in which sick patients are expected to visit investigator sites according to the doctor’s schedule, often waiting long periods — are outdated and cumbersome. Finding enough patients with a rare disease that live near a trial site can be challenging. Retaining recruited patients also remains an issue: the average patient in a clinical trial lives 50 miles from the nearest site, 48% of trials fail to complete enrollment, and the average dropout rate is nearly 49%.1 In addition, less than 5% of the U.S. population currently participates in clinical trials.
Decentralized trials address many of these difficulties for both patients and sponsors because they are conducted remotely, with patient subjects remaining at home during a significant portion — or all — of the study. They are executed using telemedicine, mobile/local healthcare providers, and other processes and technologies that differ from the traditional clinical trial model.
For patients that are infirm or immunocompromised or simply live in remote areas, study participation becomes possible with decentralized trials, helping them, and enabling sponsors to boost enrollment and participant diversity. All patients benefit from reduced travel and scheduling burdens. The less invasive nature of participation results in a more positive experience, leading to greater compliance and retention, which also benefits sponsors. Data capture is also more efficient, centralized, and continuously updated. As a result, some of the issues and costs of traditional methods are mitigated while preserving clinical trial oversight.
The benefits of decentralized trials are realized through the use of a number of tools and technologies. For example, virtual site visits for study start-up, as well as site monitoring and closeout, can be conducted using a smartphone and video recording glasses. Trained clinical research associates (CRAs) would be connected via video conference ensuring that the site meets all requirements. This approach provides an efficient and cost-effective solution.
Patient benefits include doctor appointments conducted via video conference or over the phone (telemedicine), supported by home-health nurse visits, during which bloodwork can be collected and specialty medications administered (e.g., infusions), ensuring patient safety. Where appropriate, continuous monitoring can be achieved through the use of wearable devices. Self-administered drugs can be shipped directly to the home, with patients self-reporting their experiences through mobile devices and through patient-interactive portals.
Of course, decentralization creates a new set of challenges, such as investigational product distribution to more remote locations, as well as oversight of compliance and study procedures in the patient’s home. New tools and technologies also make it possible to overcome these hurdles.
Remote solutions include digital technologies and online workstations for managing patient recruitment, scheduling of visits, sample collection, and standardizing/validating trial data from multiple sources with real-time visibility. These trial monitoring solutions are designed to ensure patient adherence to treatment, coordination of technology, and communication among all stakeholders.
When considering decentralized trials, sponsors have two clear options. In a hybrid case, some interactions with patients occur in the home, but occasional visits take place at the investigational site. In a completely remote trial, all patient interactions occur within the home. There are also gradations of these main options that comprise the full spectrum from traditional to completely virtual clinical trials. Each clinical trial is unique, with a unique set of requirements. Customization across the decentralized spectrum enables the development of optimized trial designs.
The choice of which decentralized approach — and whether or not decentralization is appropriate at all — will depend on the study protocol, the nature of the disease being treated (e.g., stage/severity of the illness), the medication format/administration requirements, the comfort level of the sponsor, and the experience and capabilities of the organization managing the trial. Best practice involves the use of a risk-based approach when making this determination.
The potential benefits of a specific decentralized trial and how patients will be impacted by it should be identified. The virtual and technological capabilities of vendors and clinical teams must be evaluated, as well as solutions for data collection and security. Global regulations that will impact the trial must be taken into account, as should a means for ensuring patient and nurse safety, risk mitigation, and trial goals, with milestones clearly outlined.
Nursing considerations are primary for decentralized trials because nurses interact directly with patients in the home and make them feel supported. Nurses are also a significant driver of patient satisfaction, which translates to retention.
The pharmacies used in decentralized trials are also important and should not only be accredited and adhere to USP guidelines, but have strong policies and procedures in place to support appropriate drug storage and handling. The pharmacy must also be accountable for drug distribution and maintain a dedicated team for clinical trial work.
Other important considerations relate to project management and business-related activities. Examples include scheduling and logistics coordination; onboarding of nursing, pharmacy, and investigational sites; the use of cross-functional teams in strategic planning; the development of realistic timelines given the complexity of decentralized trials; and the choice of strategic, collaborative partners that understand home health and the requirements for implementing successful decentralized trials.
Regulatory agencies are focused on two important aspects of clinical trials: patient safety and data validity. With decentralized trials, these agencies expect to be provided with detailed information regarding how patient safety will be ensured and how the sponsor will know that the data collected is coming from actual, treated human patients.
The U.S. Food and Drug Administration and other regulatory agencies around the world have issued guidance regarding decentralized trials, but those guidances continue to evolve through more experience with hybrid and virtual trials.
The best approach to addressing regulatory agency concerns is to schedule a meeting before filing an application for a decentralized clinical trial to discuss the trial design. In this meeting, the specific steps that will be taken to ensure patient safety and data validity can be outlined and the agency’s concerns identified and addressed. With this approach, sponsors have a much higher likelihood of receiving approval, even for fully virtual trials.
Implementing all of the elements needed to ensure compliant and seamless decentralized trials requires a technology platform that integrates all aspects of trial operations and execution, from site selection and monitoring to patient interactions and study closeout. The technology solution must also provide the tools needed to track the status of site activities; support patient identification, engagement, and communication; and enable comprehensive data capture, cleansing, and inquiry, all in accordance with regulatory requirements.
The COVID-19 pandemic has created two critical challenges for traditional clinical trials that were underway when the SARS-CoV-2 virus became a serious global threat. Patient interaction with clinical sites has been limited due to lockdowns and travel restrictions. Similarly, CRO interactions with sponsors, sites, and staff have been negatively impacted at all phases, from introductory visits to monitoring and study completion, endangering the viability of many trials.
Decentralized trials bring to bear patient-centric solutions that are independent of site geography and physical interactions. The key to success in switching to a decentralized solution is a seamless transition. This requires a CRO experienced in conducting hybrid and virtual trials along the entire decentralized trial spectrum; the CRO must also possess a comprehensive technology platform, a set of digitalized tools, and access to home-health nurses, pharmacies, and logistics providers with appropriate expertise. Such CROs have an understanding of timelines and goals and can streamline logistics, apply international strategies, and amend protocols so they are suitable for the new decentralized approach.
With respect to data management, functional sites may have the ability to directly link to the data capture system; however, in many cases, documents must be physically scanned via a secure portal. Telemedicine, home healthcare, wearables, remote monitoring, and even social media (e.g., for patient recruitment) are all important means of communicating with, treating, and monitoring patients.
While the COVID-19 pandemic has been a health and economic tragedy on a massive scale, some good may come of it. Regulatory agencies — the FDA included — have become more open to the decentralized approach to clinical trials, as it has been critical to enabling important clinical studies to proceed, including those for therapeutics and vaccines against the novel coronavirus. The experience has demonstrated the value of digital solutions, which should lead to greater engagement in technology from more conservative pharmaceutical companies and regulatory authorities alike.
In the current competitive environment, sponsor companies must be first-to-market or risk losing significant business opportunities. Time and speed matter, and CROs must facilitate accelerated development timelines.
Doing so requires the agility to quickly adapt and change trial designs while remaining compliant. CROs must also be sufficiently flexible in working with each sponsor’s quality system. Access to decision-makers is also essential; CRO representatives that come to the discussion table should be able to make decisions or quickly get an answer with one phone call.
CROs such as Biorasi that focus on nimbleness, transparency, and collaboration are therefore better positioned than larger, more encumbered organizations to support clinical trials now and into the future.
Biorasi understands that clinical development is never static. It continually enhances its services to best support clients at all times, including in crisis situations. Biorasi has expertise in implementing the full spectrum of clinical trials from traditional to fully virtual and the ability to change direction as needed throughout the clinical trial.
As an experienced CRO, Biorasi knows that each clinical trial is unique. That’s why it offers a wide spectrum of decentralized solutions with remote components that can be customized to fit all trial parameters.
Biorasi has developed strategic relationships that ensure clinical trial expertise and capabilities, patient accessibility, and the completion of studies according to sponsor timelines and goals. These relationships are supported by advanced technologies related to home healthcare, data capture, and other aspects of trial execution, all of which are coordinated and managed through our proprietary TALOS™ system. In addition, operations are optimized through the use of adaptive designs and streamlined logistics.
The use of a centralized system for capturing data from multiple platforms alleviates security concerns. The ability to combine site-based requirements with telemedicine and home-based visits helps to ensure consistent assessments and reliable results. In addition, with extensive experience in both starting new virtual trials and switching traditional to decentralized studies, Biorasi has the knowledge needed to appropriately adapt clinical protocols while maintaining regulatory compliance.
Mamta joined Biorasi as the new Vice President of Quality Assurance and Pharmacovigilance in November 2019. Mamta comes to us with an extensive background in pharma and QA, including time with Quintiles, Spectrum, Regeneron, Amgen and others. Her experience extends beyond QA and includes leadership roles in supply chain, quality control, and data management.