Conducting a successful clinical trial is by no means an easy endeavor; it requires extensive planning to ensure that multiple resource- and time-intensive activities are completed seamlessly. In a post-Covid-19 world that is heavily reliant on virtual tools, the healthcare industry is leveraging digital health technologies to optimize clinical trials.\r\n\r\n\r\n\r\nClinical trial planning starts off with approving an optimized protocol and is soon followed by a host of steps that include pursuing and obtaining approvals from authorities; recruiting participants; procuring and administering treatments; collecting and analyzing data; and finally reporting.\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\u201cToday, all major tasks in clinical trial planning -- barring one important exception -- can theoretically be done digitally,\u201d said Gunnar Danielsson, Senior Regulatory Advisor at LINK Medical, a European early-stage development to post-market CRO.\u00a0\r\n\r\n\r\n\r\n\r\n\r\nThis task is patient examination and assessment by a physician, which requires a clinic visit. However, this in-person task can be conducted digitally as well.\u00a0\r\n\r\n\r\n\r\nWhen almost all aspects of a trial are performed digitally, it is considered a decentralized trial. \u201cIn a decentralized trial, activities like patient consent, assessment, and data collection are not conducted in a traditional setting such as clinics or hospitals. Instead, digital health technologies such as sensors, online patient-reported outcome surveys, or video assessments can be used,\u201d clarified Danielsson.\r\n\r\n\r\n\r\nThe advantages of decentralized trials\u00a0\r\n\r\n\r\n\r\nDecentralized trials are aimed at reducing patient burden and optimizing trial operations. A recent McKinsey survey found that roughly 70% of all trial participants live more than two hours away from the trial site, which can make trial participation a burden.\u00a0\r\n\r\n\r\n\r\n\r\n\r\n\u201cWith decentralized trials, we can conduct clinical assessments where the patient is situated, for example in their homes, and at times suited to them. This can significantly reduce patient burden, positively impacting patient recruitment and retention in a study,\u201d said Jo Anders R\u00f8nneberg, Biometrics Director at LINK Medical.\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\nDecentralized trials can reduce the required travel time, costs, and logistical arrangements, offering a practical option compared with on-site trials. This is especially relevant in the context of restrictions imposed by the Covid-19 pandemic.\u00a0\r\n\r\n\r\n\r\nMoreover, conducting decentralized trials digitally allows information to be exchanged and clarified rapidly between the patient and trial staff through multiple mediums, such as texts, presentations, emails, or video calls. Danielsson added that this typically increases data flow and enhances patient engagement in the studies.\u00a0\r\n\r\n\r\n\r\nBy increasing patient convenience and involvement, decentralized trials allow access to a broader and more engaged patient population versus on-site trials, effectively eliminating time zone and geographical restrictions.\u00a0\r\n\r\n\r\n\r\nThe benefits of this trial type also extend to the trial staff. In on-site trials, data is first documented in hospital records and then transferred to electronic databases. Decentralized trials have fewer data transfer steps, as the data gets directly captured in an electronic format at patients\u2019 homes. This reduces data collection and management arrangements, cutting staff workload and limiting the introduction of errors or discrepancies in the data.\u00a0\r\n\r\n\r\n\r\n\u201cBy reducing the site involvement and resource use, decentralized trials not only result in time- and money-savings, but they also multiply the chances of finding sites ready to participate in a study,\u201d said R\u00f8nneberg.\r\n\r\n\r\n\r\nLastly, depending on the study requirement and the digital health technology involved, decentralized studies can also offer higher quality, real-time data, with potentially more extensive datasets compared with that from on-site trials. This can provide important context, enabling the examination of different trends and the application of risk-based approaches in downstream data analysis, ultimately improving the rigor of outcome reporting.\r\n\r\n\r\n\r\nDefining where a decentralized trial is appropriate\r\n\r\n\r\n\r\nThe feasibility of a decentralized study is determined by the availability of a suitable digital health technology -- which has been validated for verifiable and secure data collection and monitoring -- within the therapy area in question.\u00a0\r\n\r\n\r\n\r\nFor instance, an Apple watch collecting blood pressure data in real-time can enable a decentralized trial for a hypertension treatment. However, tumor size can only be measured via physical examination and diagnostic imaging tools. As no technological aid to replace the latter currently exists, such an assessment must be conducted in-person.\u00a0\r\n\r\n\r\n\r\nDecentralized trials are also more suited to simpler studies, where extensive assessments may not be needed. These include \u201cstudies that are based on subjective ideas, centered on patient perceptions captured using patient diaries or questionnaires,\u201d explained Danielsson. \u201cAn ideal contender would be neuroscience studies, where questionnaires can be filled by the patient at home instead of in a clinic waiting room.\u201d\r\n\r\n\r\n\r\nConversely, early-stage trials during the drug discovery and development process are not suited to the decentralized format. For example, in a phase II chemotherapy study, outcomes can be unpredictable due to adverse events or unknown effects. Considering the complexity in administering and monitoring treatments in such studies, the trials need to be conducted almost fully on-site.\r\n\r\n\r\n\r\n\u201cDefining where a decentralized trial is appropriate boils down to complexity, which can vary based on parameters like the indication, knowledge of the drug, trial phase, prior experience, and what sort of assessments can be done electronically,\u201d said Danielsson.\r\n\r\n\r\n\r\n\r\n\r\n\r\n\r\nChallenges to overcome\r\n\r\n\r\n\r\nEnsuring the availability of and access to a suitable digital health technology for all participants is a main challenge associated with decentralized trials. Participants should also be comfortable using the digital tools intrinsic to the study. This creates the need for patient training and support, which can be time and resource consuming.\r\n\r\n\r\n\r\n\u201cRegulatory requirements on data capture can also vary between countries, which can complicate the tailoring of data management to local requirements in a global decentralized study,\u201d added R\u00f8nneberg.\r\n\r\n\r\n\r\nWhile these challenges may present significant hurdles today, such issues can soon be overcome with the increased use and evolution of the tools involved.\r\n\r\n\r\n\r\nLooking to a decentralized future\u00a0\r\n\r\n\r\n\r\n\u201cAlthough a majority of trial protocols may not be fully decentralized today, the tools to run decentralized trials are already widely in use,\u201d emphasized R\u00f8nneberg. Leading CROs like LINK Medical are well versed in employing tools like electronic data capture systems to integrate data from different sources; telemedicine platforms to interact with patients in real-time; and patient diary applications to track patient reported outcomes across trials.\u00a0\r\n\r\n\r\n\r\nInitial pilots have received an overwhelmingly positive response from patients, advocacy groups, regulatory agencies, health authorities, pharmaceutical industry, and CROs alike.\r\n\r\n\r\n\r\nAnd this enthusiasm is likely to sustain, especially as the Covid-19 pandemic has accelerated the adoption of decentralized solutions. In a recent Global Data survey conducted with 150 healthcare stakeholders, 83% of respondents stated they believed that decentralized studies will be more frequently used in the next one to four years.\u00a0\r\n\r\n\r\n\r\nIn therapy areas where a fully decentralized study may not be feasible, Danielsson suggested the use of hybrid trials as a viable alternative instead. \u201cIn the short term, the way forward is to use the technology of decentralized visits in combination with on-site visits. This will enable advantages in times of resource saving and patient retention, without compromising on safety and efficacy assessments.\u201d\u00a0\r\n\r\n\r\n\r\nAlthough decentralized trials may never fully replace on-site trials, \u201cDecentralized trials will become increasingly common, as the healthcare industry starts to fully leverage the possibilities we have today,\u201d Danielsson concluded.\r\n\r\n\r\n\r\nTo learn how you can partner with LINK Medical and access the latest technologies to optimize your clinical trial, please visit the company\u2019s website.\r\n\r\n\r\n\r\nAny questions? Contact the LINK Medical team or join them on the upcoming webinar on decentralized trials happening April 28. Learn more.\r\n\r\n\r\n\r\n\r\nImages via Shutterstock.com. Headshots courtesy of LINK Medical.