Proof-of-Concept Study Uses AI-Based ‘Digital Twins’ to Replace Control Arms in Clinical Trials
Digital twin technology could address key challenges in clinical trial development, including reducing patient burden
Boston, USA — June 20, 2024: New research published in the journal Bone Marrow Transplantation (BMT-Nature) demonstrates that AI-powered digital twin solutions can potentially replace the standard-of-care control arm of a clinical trial. The new method was used as a way to evaluate novel therapies in chronic graft-versus-host disease (cGvHD), a rare and serious complication that can develop in patients who undergo allogeneic hematopoietic cell transplantation (HCT).
The study was funded by Phesi and co-authored by Dr. Yi-Bin Chen, director for the blood and marrow transplant program at Massachusetts General Hospital.
What is digital twin technology?
Digital twin (DT) technology uses real-world data and evidence from clinical trials conducted across the globe to create digital cohorts that can used for the placebo/standard-of-care control arms of studies. “The strength of DT technology lies in the volume, diversity, and dynamic nature of the data used for DT construction,” wrote the authors. “However, obtaining high-quality source data is a challenge.”
Creating a digital twin for chronic graft versus host disease
In the study, researchers created a digital twin for cGvHD in the primary treatment setting using Phesi’s Trial Accelerator™ DT platform, which contains data from more than 108 million patients in almost 367,000 cohorts.
The digital twin was developed to replicate patients receiving prednisone, the first-line treatment currently used as the standard-of-care for cGvHD and commonly used in control arms of prospective clinical trials. While 2,042 patients (32 cohorts) with cGvHD were selected and used to construct the (first-line therapy) flGvHD digital twin cohort, 438 patients from 8 cohorts were used to construct the flGvHD digital twin standard-of-care cohort.
Gen Li, PhD, MBA, is the president and founder of Phesi Inc., a global provider of patient-centric data software and analytics. Li has extensive experience in clinical development. His work inspired him to create Phesi—ensuring the insights held from historical data, or data collected from planned and current clinical trials, were not lost.
“Digital twins can support the industry to overcome longstanding challenges faced in patient recruitment, the ethical issues associated with placebo arms, and the impact these constraints have on cycle and approval times,” said Dr. Gen Li, president, Phesi. “We have demonstrated that digital twins offer real potential to replace standard-of-care comparator arms to streamline the implementation of clinical trials and dramatically reduce patient burden.
“This study shows the use of digital twins for clinical trials could benefit many other disease indications as well as cGvHD. Our hope is this approach will gain regulatory approval in the future and find its place in the design and implementation of clinical trials. We look forward to working with regulatory bodies such as the FDA to explore the use of digital twin solutions in clinical development.”
Potential benefits of digital twin solutions
More than 50,000 cancer patients receive HCT each year worldwide; cGvHD occurs in 30–50 percent of these patients as a complication that can significantly impair long-term quality of life. Corticosteroids are the front-line treatment for this condition, but the long-term effects of corticosteroids combined with the chronic nature of cGvHD has highlighted the urgent need for alternative treatments.
“With a significant number of patients [affected by] cGvHD in a given year, recruiting patients for clinical trials into this condition is challenging. When half of trial participants must be assigned to a control arm, clinical trial accrual is oftentimes difficult,” explained Dr. Yi-Bin Chen, co-author and director for the blood and marrow transplant program at Massachusetts General Hospital. “This digital twin would allow clinical researchers to accelerate clinical trials into this challenging condition by automating an external control arm and allowing sponsors to test new therapies faster.”
The Phesi Digital Twin solution aims to replace control arms in clinical trials. Phesi’s Trial Accelerator platform yields additional significant incremental benefits for trial sponsors in several areas.
Phesi’s digital patient profiles (DPP) optimize trial and protocol design and enable sponsors to generate a patient access score (PAS) to identify leading investigator sites with highest enrollment potential. The DPP and PAS empower patient-centered analysis and serve as the precursor to digital twin implementation.
The integrated and contextualized analysis addresses the three evergreen challenges in clinical development—to reduce protocol amendments, identify the best enrolling investigator sites, and reduce patient burden.