This piece is an extract of the upcoming ADAMAS white paper “Making the Model: Solving the Data Integrity Challenge of Decentralized Clinical Trials”.
It may be easy to think that Decentralized Clinical Trials (DCCTs) have emerged because of the necessity to fit processes and procedures around social distancing and lockdowns. However, with the advancement of available technologies, decentralization has been on the rise for a number of years. Discussion and development of remote elements and facilitators for reduced travel have steadily increased, with 76% of researchers now reportedly running DCCTs and it is clear to see why.
A Solution to the Patient Recruitment Struggle
Clinical trials have long struggled with patient recruitment, with the main challenge always being ensuring enough patients are recruited to guarantee a viable trial that provides sufficient data to certify the efficacy of the results. Finding those committed to a study and setting up sites to aid their involvement is not only complex but costly – particularly in trials that require widespread or even global locations.
On average, it costs $6,533 to recruit one patient to a clinical study, approximately 30% of patients drop out of clinical trials and the cost of replacing patients rises even higher. In fact, reportedly 85% of clinical trials fail to retain enough patients to be completed. However, the ability for DCCTs to reduce or eliminate the need to travel to specific sites makes trials easier on patients and has been shown to reduce drop-out rates, increase study effectiveness, reduce costs and get drugs and products to market faster.
Nonetheless, with 70% of patients living more than two hours from a research site and 50% of participants finding it difficult to stay enrolled due to poor health, it is understandable why dropout rates can be high. Further to this, subjects will also be managing their day-to-day lives with businesses, full-time jobs, where families and site visits involving hours of travel and numerous costs are just not viable.
By introducing technology and other novel solutions, sponsors and CROs can better fit the usually inflexible systems of a trial around the lives of a patient, ensuring a “patient-centric” approach. By reducing the required time and cost it takes to participate in a clinical trial, DCCTs ease the pressures placed on participants and secure higher retention rates and efficiencies.
The Digital Revolution
It is unlikely that data collection at the traditional clinical site will be fully replaced, trials will still require information that can only be collected using equipment that healthcare facilities can provide, such as MRI scans. However, new remote monitoring technologies and devices have been revolutionizing new and inventive points of data collection. Devices such as wearables, whether they be wrist straps or adhesive patches are now measuring patient heart rates, stride cadence, and metabolism remotely. Linked to the Clinical Database through secure networks, they allow data to be collected, received, and processed in real-time.
Electronic diaries (ePRO) where patients note down reactions, emotions, and attitudes has captured the quality of life during the Trial which provides patients a sense of autonomy. Evidence has even suggested that this makes participants even more informed and engaged with individuals completing tasks, with more accuracy and honesty than previous engagements. These records can then be automatically time-stamped and verified, ensuring a more accurate and broader coverage of subject data. This capability has evolved into a clear measure of Clinical Trial subject ‘Quality of Life’ while in treatment.
Through digital technology it is now possible to discover a better assessment over the lifetime of a trial, capturing more continuous data in a better context of lifestyle and habits. Through utilizing varied technologies DCCTs can collect even more data from patients than traditional site-based studies, without further disruption to subjects’ lives. Ultimately it is through the development of digital technologies that patients’ morale can be improved, more accurate data can be collected and medicines can be developed to effectively find cures while improving the quality of life of Clinical Subjects.
The Shift in Risk
However, while DCCTs have numerous benefits, it is important to consider the shift in risk to Subject Safety and Data Integrity. Efforts that move away from Clinical Site based data collection to Remote data collection using mobile technologies require the data to be transferred, stored, and transferred again.
Throughout a DCCT, data may be transferred to and stored among several different parties, locations and systems, multiple times. Most organizations are missing the key fact that the greatest risk for a DCCT is the multiple points of Data Transfer, Storage, and Data Transfer again. The greatest risk is the compilation and reconciliation of multiple Data Streams from a great number of Data collection points. The proper alignment of Data from: Medical Devices, EDC, Wearables, Imaging Applications, and Mobile Tablets into one Clinical Data Base presents an incredible risk. This risk presents itself in the potential misalignment, corruption, and/or disorganization of the Clinical Data set. It is also a Regulatory imperative to be able to evidence a Disaster Recovery solution for the DCCT Clinical Data Base.
Through all those transfers sponsors must therefore have the confidence that data can be properly compiled and reconciled at each stage, with the assurance that no corruption, loss or disorganization has occurred.
With so many benefits to this new format of Clinical Trials, a system or model must therefore be put in place that mitigates this new risk to Subject Safety and Data Integrity. With challenge comes great opportunity to put in place a process that ensures trials exceed Regulatory Compliance and are Inspection Ready.
In order to reduce this associated Data Integrity Risk, a new Validation Process has been developed. This Validation Process will evidence the accuracy and reliability of the complete (compiled) Clinical Data Base and its Back-up solution. When automated, this Validation Process exceeds Regulatory Compliance and ensures the DCCT is Inspection Ready. This new model of Validation Methodology will be presented in the upcoming ADAMAS white paper “Making the Model: Solving the Data Integrity Challenge of Decentralized Clinical Trials”.
Sources:
Palmer J, Oien P. Survey: COVID-19 the Tipping Point for Decentralized Clinical Trials. Oracle.com. https://www.oracle.com/news/announcement/covid-19-the-tipping-point-decentralized-clinical-trials-111820.html. Published 2021. Last Accessed September 7, 2021.
Moore TJ, Zhang H, Anderson G, Alexander GC. Estimated Costs of Pivotal Trials for Novel Therapeutic Agents Approved by the US Food and Drug Administration, 2015-2016. JAMA Intern Med. 2018;178(11):1451-1457. doi:10.1001/jamainternmed.2018.3931.
Alexander W. The uphill path to successful clinical trials: keeping patients enrolled. P T. 2013;38(4):225-227.
Charlton, L. The Rise of Decentralized Trials | Medrio. Medrio. https://medrio.com/blog/10-key-takeaways-on-the-rise-of-decentralized-trials/. Undated. Last Accessed September 7, 2021.
