By Mohammed Ali, Chief Domain Expert & Kevin Potgieter, Vice President of Regulatory Affairs at Medable
As clinical trials rapidly modernize, government regulators work to evolve even as the same core principles apply. Still, decentralized clinical trials are – simply – clinical trials, as all research today is decentralized in some way, yet we lack global harmonization of regulations. Is it time for agencies to catch up to the technology evolution and drive faster medical scientific progress?
Guiding Principles Remain the Same
The steady drumbeat of growth of digital technologies to enable a decentralized approach to clinical trials continues into 2023. The decentralized model adopted by some pre-pandemic and most post-pandemic has proven to achieve a return on investment. The Tufts Center for the Study of Drug Development found net financial benefits ranging from 5x for Phase II and 13x for Phase III trials, equating to roughly $10 million ROI and $39 million ROI, respectively and some large pharmaceutical companies like GSK and CROs like Syneos are signing enterprise deals with DCT technology providers.
These are all positive signs for the widespread modernization of clinical trials, yet uncertainties remain – particularly in the uncharted areas of global regulations.
The good news is steps are being taken around the world to evolve. Most recently, the European Medicines Agency (EMA), European Commission (EC), and Heads of Medicines Agencies (HMA) acknowledged the growing role of decentralized elements in clinical trials and published a series of recommendations with a focus on data integrity, participant safety and inclusion. The recommendation paper was published on December 13, 2022 but is not yet part of a harmonized approach with the national provisions of the individual EU member states, or with the United States. However, it is expected that the U.S. FDA will make similar recommendations later this year.
The EMA paper emphasized that trial participants' rights, safety, dignity, and well-being should come first, and decentralization in clinical trials should not increase these risks. None of this is earth-shattering, and does little to impact how trials are run using new technologies. However, the paper did emphasize that early participant and investigator involvement in clinical trial design increases the scientific value and boosts trial trust, recruitment, and adherence – core values of a successful clinical trial – decentralized or not.
Bottom line? The inclusion of decentralized elements in clinical research does not change the guiding principles of clinical trial conduct. Regardless of where trial activities take place, the same principles apply to trial conduct: participant rights, safety, dignity, and well-being should prevail as well as data integrity and robustness for regulatory decision-making should be guaranteed. Further, it does not change the guiding principles from the ICH GCP, GDPR, EU CTR and sunsetting EU CTD framework whereby patient safety and trial integrity are assessed against a thorough risk assessment and risk management plan.
In addition to the EMA paper, various U.S. industry associations are forming committees to develop recommendations for DCT implementation, including the Association of Clinical Research Professionals (ACRP). On a global scale, the World Health Organization (WHO) just formed the “Technical Advisory Group on Development of Guidance on Best Practices for Clinical Trials” to develop guidance to help the official implementation of scientifically and ethically sound trials at national and regional levels. But it extends beyond government bodies to also provide advice on the “design and conduct of clinical trials” for non-state actors ranging from scientists and clinicians to industry and non-profit organizations.
Decentralized clinical trials have proven their merits – so much so, that they are becoming synonymous with clinical trials, and as such, require new, updated regulatory guidelines that can be harmonized globally. Are regulators moving fast enough? Taking bold enough action? While there is valuable progress being made, and regulators are actively collaborating with the industry, the historically cautious pace of change may become the biggest roadblock to modernizing clinical research. After all, the technology is here, proven, and being widely used already.
Yet, a recent ACRP survey of 291 investigators found that lack of clarity around regulation – not technology – is the leading barrier to the widespread adoption of DCTs. A follow-up ACRP Think Tank revealed a need for “harmonized global expectations and clarity about who accepts oversight liability for remote elements, how data should flow, and where new methods and technologies fit.”
Appropriateness should be a key decision driver for the inclusion of decentralized elements in any clinical trial. And, the appropriateness depends on the specific trial population, the condition under study, the assessment types in the trial, along with the nature of the investigational medical product(s). Patient and investigator engagement early in the development process of the trial design is key and offers the opportunity to increase recruitment and adherence, as these stakeholders are in the best position to provide valid perspectives on the likely success of the decentralized elements. Additionally, the EMA paper emphasizes that roles and responsibilities for all stakeholders (sponsor, site investigators, technology solutions providers, etc.) must be clearly defined during study planning stages. Read more about Medable’s perspectives on how to evaluate the appropriateness of DCT elements in a trial.
The life sciences industry is at the very nascent stages of absorbing emerging regulatory frameworks for DCT that will inspire the full confidence of trial sponsors and sites, and Medable is at the forefront of influencing these changes. We’ve been focused on decentralized trials at scale since 2015, and we have the experience and depth of teams who work with these regulations every day.
This year, we are excited to take this knowledge and experience and share it with the market. Medable is working closely with ACRP on new FDA guideline recommendations (to be announced at ACRP 2023 Annual Meeting, April 28-May 1) while collaborating with other industry associations, leaders, academia, investigators, and government officials to help design a new regulatory path forward that makes it clearer, easier, and faster to safely implement a decentralized approach to clinical research.
Let's work together towards this common goal because, let’s face it, a decentralized trial is still a clinical trial, and its delivery should not be distinctive, but rather take into consideration how we have run clinical trials up until now, and how we expect to run them in the future. Technology enables broader participant access, reduces patient burden, improves data integrity, and increases patient safety. And this benefits every stakeholder.
Read an in-depth analysis from Medable's Senior Director, eCOA Science & Solutions, Dr Florence Mowlem here: https://www.medable.com/resource-center/what-does-the-new-european-medicine-regulatory-network-recommendation-paper-on-decentralized-elements-in-clinical-trials-tell-us