By Steve Jones, Chief Data Officer
Traditionally, clinical trials have relied heavily on centralized sites and face-to-face interactions between researchers and participants. However, the limitations of this model have become increasingly apparent, especially during the COVID-19 pandemic, which prompted an unprecedented emergence of decentralized clinical trials (DCTs), whose characteristics of remote patient engagement, virtual assessments, and mobile health technologies allowed the healthcare industry to continue drug development (albeit at a slower pace). As the healthcare landscape continues to evolve, DCTs are emerging as a vital component of the clinical research ecosystem. By leveraging technology and data to streamline processes and the need to enroll a greater diverse patient population, DCTs promise enhanced patient engagement, improved data quality, and accelerated study timelines. As with everything in life, nothing is always that simple. In this blog, we will explore the future of decentralized clinical trials and look at the challenges faced by sponsors, sites, and patients when planning, implementing, and running a DCT. We will also discuss how Medable is continuously adapting its platform and software capabilities to reduce risks and provide solutions that allow the benefits of DCTs listed above to be fully realized.
Sponsor perspective: Data management, variability, and clinical trial diversity
The addition of participants, who are allowed to participate in a clinical trial with minimal interaction with a site and investigator, requires technology that will ensure that the participant can fully participate in the trial without adding noise or unwanted variability to the data collected; protocols must specify the planned sample size, which should be based, where possible on referenceable literature. Now, the issue is that the literature is only just beginning to include results from DCTs (of various proportions), and so the impact of potential increased variability will, if considered at all, most likely be based on a number that is big enough to keep the statistician appeased that their concerns have been heard, but tempered by the clinical development department to keep the trial on budget and on time. Am I being pessimistic about the risk of increased variability and the consequences of ending up with a borderline statistical significance? As a statistician, I believe that worrying about data variability is an important contribution that needs to be discussed at all protocol development meetings; I feel that I am right to be concerned for the following reasons:
- The FDA has mandated the need for diversity in pivotal trials to mirror the demographic and economic profile of the US population. This indicates to me that they don’t consider current trials as being representative (otherwise, why mandate an increase in trial management complexity.)
- It is physically impossible to reduce variability by adding something different to anything (the most one can hope for is no increase!)
- There is complexity in modeling out the increased variability—if a patient has no site, then how do you include them in a covariate (as they don’t have the site influences, and potentially all remote participants could be considered their own site)?
Choosing the right platform that allows variability to be managed in a way that maintains the benefits of being remote while remaining in control of remote patient engagement, data collection, and communications can be daunting due to the plethora of available technologies. At Medable, we recognize the challenge that new technology can bring and the potential inefficiency of outsourcing the implementation that can arise when a protocol, developed based on past protocols, is passed over for implementation. Late changes to protocol design place pressure on achieving recruitment timelines. Medable recognizes that protocol design is an art and a science and takes time. Trial objectives from all teams (e.g., clinical operations, IT, regulatory affairs) must be properly aligned, that technology integrations work seamlessly, and organizations spend time identifying and evaluating risks (both general and those unique to decentralized trials, including technology failures, recruitment hurdles, and data loss). It is also critical that appropriate budgets and resources are allocated. While DCTs can reduce some costs, sponsors must also invest in technology, training, and support. Balancing these financial commitments can strain budgets. Organizing resources efficiently across clinical sites and ensuring all trial components are adequately funded can be difficult.
Medable must navigate the requirements of sponsors, sites, and patients to ensure that all three groups remain at least satisfied with the technology solution.
Medable Studio is designed to be a self-service platform, adopting no-code solutions wherever possible to allow faster adoption (in-house support is available, too). The value of self-service is that it allows for draft protocol designs that can be generated from the outset and minimizes the chance of last-minute challenges. Maintaining regulatory compliance is paramount, and with the framework constantly evolving, Medable employs individuals who monitor the changing guidelines to ensure compliance across different jurisdictions and that all remote processes meet regulatory requirements for documentation, audit trails, and data integrity.
In my opinion, sponsors will get the most out of Studio if combined with all of their other sources of trial data and define which components are best suited for which role. An example of this is monitoring participants' adherence to the trial. Adherence calculations require the following data inputs:
- Actual data completed by the participant
- An expectation of what data should be available when producing the report.
The determination of expectedness often requires information that needs to be integrated with Studio as it is not captured automatically; integration rather than duplication of data entry is best in the long term as it avoids the manual reconciliation that often occurs where two or more sources contain the same information.
Take, for example, a straightforward oncology trial set up to assess the response to treatment in terms of tumor response, progression-free survival, and overall survival. In order for Studio to be able to measure adherence accurately, knowledge of when each dosing cycle started and ended is critical. Unlike for other more straightforward therapeutic areas, where the randomization date (and early withdrawal date where applicable) can be used as the milestone to set up an expectation of data flow, it is critical to know if a participant has had a dose-limiting toxicity which has impacted the timing of the next cycle or when disease progression means that the cadence and type of follow-up changes. Without this information, no data for a task could represent the scenario that the participant has missed a task (for whatever reason and not just because they forgot); equally, it could represent that the participant has had to delay the next cycle or their disease has progressed.
Medable Studio's strengths lie in its capture of eCOA information and the underlying metadata, which provides unique insight into completion patterns.
Site perspective: Evolving technology and regulations
The reliance on advanced technology platforms can be overwhelming. Ensuring site staff and investigators receive adequate training on DCT procedures and technology is crucial but can strain resources, especially for smaller sites. DCTs often require integration with various digital tools and electronic health records (EHRs), which can create compatibility issues or data silos. Maintaining participant motivation and protocol adherence can be difficult when interactions are primarily remote. Investigators must implement strategies to keep participants engaged throughout the trial. The transition to decentralized methodologies may require reallocating resources or increasing staff capacity, which can be challenging for sites with limited budgets.
The evolving regulatory landscape for DCTs means that sites must stay informed about regulation changes and ensure compliance, which can be a resource-intensive endeavor. Maintaining thorough documentation of remote interactions and data collection processes can be more complex, necessitating robust systems and protocols. These are often different for different countries and/or states, meaning Studio often has to balance being generic, which is needed for global trials, with specificity, which is important for optimizing data quality and achieved through making the Site interaction straightforward.
Medable is developing a site portal, including a library of training modules, that will be intuitive for the Site, making it easy for data to be generated, reviewed, and transferred. By facilitating access to data, either by download or review using a dashboard of simple visualizations (as an alternative to pages of data listing that are difficult to review), the positive experience of using Studio will not only facilitate compliance to regulatory guidelines, but should also translate to an increase in recruitment.
Participant perspective: Patient access and flexibility
It’s fair to say that not all participants are naturally suited to clinical trials. The population that benefits the most are those living in remote locations or who find it difficult due to either scheduling, disability, or availability of transportation to travel to the site and prefer to participate from home or who have no access to healthcare due to unaffordable insurance costs. Wearable devices and apps facilitate real-time data collection and communication, which can enhance patient engagement and adherence to study protocols. DCTs may empower patients to take a more active role in their health management through self-monitoring and remote assessments. It is important to recognize that there is still a limit on how remotely located a patient can be; a stable internet connection and/or a sufficiently strong cell phone signal is a requirement for DCT participation. While offline mode exists, it is my view that this should not be encouraged for long periods of time; the lack of visibility to the data means that it is impossible to provide health support to the participant or carers, as well as any retraining identifiable through data review which may make the participant ineligible to continue participation and increase trial costs!
Some patients might feel less confident if there are delays in addressing concerns due to remote connectivity or less trusting of the trial process without in-person interactions and oversight. In case of adverse events or complications, patients might feel less secure without immediate access to healthcare providers. Depending on the setup of the DCT, patients might have limited access to support services that are typically provided in traditional trials and/or care settings. With increased reliance on technology, there will also be a small proportion of patients who will be concerned about the security of their personal health information and data privacy and may be hesitant to share sensitive data used in the trial due to fears surrounding data breaches or mishandling.
The Medable platform has capabilities for both face-to-face and remote consultations as well as informed consent, which allows the patient time to fully understand and ask questions as part of the consent process. Ensuring that participants understand the trial process and procedures may require additional outreach efforts. Despite these efforts, it is important to recognize that there will be participants who are enrolling in a DCT for the first time and who thought that remote participation would be okay but discovered that they missed the personal connection and support from healthcare professionals. I would suggest the following two solutions:
- If possible, the trial should be set up with flexibility as to whether assessments can be performed remotely or at the site, but as mentioned above, it should consider the impact of flexibility on potential increases in measurement variability and the risk of loss of study power. From a statistical analysis perspective, it is better if a participant is enrolled/randomized as an on-site participant OR a remote participant and is NOT allowed to chop and change; this facilitates the ability for any additional variability to be accounted for at the data analysis stage (and this should be described as part of the protocol and/or statistical analysis plan).
- During the early trial period and certainly prior to randomization/enrolment that some form of conversation is held with each Participant as well as a review of data including the metadata for signs of incompatibility with DCT participation eg. missed or incomplete diary entries or signs that entries are being rushed (disengagement) or taking longer than expected (internet connectivity). The sooner any data issues can be identified, the less impactful they will be on the overall trial results (even if that means the early termination of participants.
As a data company, Medable recognizes both the benefits and challenges associated with remote data capture and is fully engaged in minimizing the risks of data loss, data breach and the need to protect and uphold patient confidentiality and privacy. Whilst wearables can enhance data insights, Medable recognizes the additional training that sites and patients may need in their use. Data monitoring is also of paramount importance. Whereas with Site-based trials, the occurrence of data fraud is rare and often detected through differences between sites in the observed inter- and intra-participant variability, with DCTs, there is less impact from the Site in terms of collected data. Data fraud ranges from the participant fabricating data either by making up answers and/or attaching their pedometer to the pet dog to providing answers that they anticipate will produce a desired response from the Investigator. The use of other metadata available on the wearable, such as its gyroscope, may be useful in identifying changes of the wearer.
Future Medable plans: AI, ML, automation and more
Medable remains committed to enhancing remote monitoring and data collection, with plans for 2025 to further integrate artificial intelligence (AI) and machine learning (ML) functionality into its platform. The use of AI is strictly limited to using technology in a way that makes development easier and/or faster, such as the implementation of the no-code study-build functionality in the Studio platform. In 2025 the reporting capabilities are scheduled for a major overhaul and I expect that AI capabilities will be front-and-center in this redesign. Medable has no intention of using the data collected during trials to develop new products but remains focused on the ultimate goal of reducing the time required from the first phase I trial to the regulatory submission of new medicines.
Medable has developed a culture that promotes innovation, encouraging teams to explore new ideas and solutions. Personally, I feel that there needs to be a balance between innovation and development. Innovation takes resources away from development, and at the end of the day, successful development and sales bring in revenue. However, without innovation, advancement is lost, and Medable loses its shine. In order to maintain its position as a key player, I believe that we should foster partnerships with other startups, universities as well as Pharmaceutical Companies that can be catalysts for even greater innovation.
Medable will continue to perform pulse checks to ensure that products are relevant and will continue to form relationships with hospitals, clinics, and patient advocacy groups to ensure a more comprehensive approach to trial design that is both fully compliant with the current regulatory landscape, but also makes data capture robust to remoteness and understandable by a diverse patient population.
Conclusion: A foundation for better DCTs
The future of decentralized clinical trials holds immense promise, paving the way for a more efficient, inclusive, and patient-centered research landscape. The transformation of the Medable Platform over the past four years since I joined the Company has been amazing. Medable Studio represents a giant step forward and provides a secure foundation upon which to develop tools that can significantly impact the clinical trial process, ultimately driving better health outcomes for us all.
As we look forward to a new era of clinical trials, the adaptability and vision of companies like Medable working in data-sharing partnerships with the pharmaceutical industry will shape the future of healthcare research and influence future regulatory policy!
