Researchers have demonstrated the potential of digital twin (DT) technology to replicate standard-of-care (SOC) treatment outcomes in a clinical trial setting for graft-vs-host disease (GVHD). By creating a DT arm based on a real-world clinical trial database, they were able to mirror the efficacy of prednisone, the SOC treatment for GVHD, offering a novel approach to clinical trial design and execution.
The study, utilizing the Phesi Trial Accelerator platform, enrolled patients with chronic GVHD undergoing first-line treatment into a DT cohort. The findings revealed a 52.7% overall response rate at 6 months, aligning with existing literature. This suggests that DTs can provide reliable data and support the utility of DT SOC arms in real-world clinical trials.
Digital Twin Construction and Validation
To construct the DT arm, investigators selected patients from a database of over 61 million individuals, focusing on those with chronic GVHD receiving first-line treatment. Inclusion and exclusion criteria were applied to create a cohort of 2,042 patients from 32 cohorts across 16 countries, spanning from 1997 to 2021. This DT arm was then evaluated in the same manner as a comparator arm in a traditional clinical trial.
"These findings demonstrate that reliable and robust data can be obtained from diverse sources to construct DT arms and support the potential utility of DT SOC arms in real-world clinical trials," study investigators noted.
Evolution and Applications of Digital Twins
The development of DTs has been two decades in the making, with recent technological advancements in IoT, big data analytics, cloud computing, and AI enabling their widespread adoption. Researchers are now evaluating clinical developments to identify areas where clinical data science can reduce the time and economic resources required for clinical trials, facilitate patient participation, and enhance clinician engagement.
Other trials have explored DTs for KRAS G12C non-small cell lung cancer, assessing SOC treatment and measuring progression-free survival, and for CAR-T cell therapy in cytokine release syndrome (CRS), evaluating outcomes based on CRS severity grades.
Advantages and Regulatory Perspective
DTs offer several advantages, including improved understanding of patient needs, better-aligned trial designs, and identification of design issues before trial commencement, minimizing protocol amendments. They can also reduce the sample size of the control arm, leading to reduced cycle times, lower costs, and decreased burdens on patients.
From a regulatory perspective, using historical controls is seen as an enhancement to trial designs. While replacing traditional control arms in phase 3 trials with digital alternatives requires careful consideration and regulatory engagement, DTs can provide valuable insights in scenarios such as rare diseases or specific cancer strains.
Vulnerabilities and Ethical Considerations
The use of DTs necessitates extensive patient data collection and storage, raising ethical concerns regarding data confidentiality and security. Cybersecurity of DT databases is a significant concern, and regulations such as the GDPR enforce legal requirements to protect patient data. Gathering comprehensive and high-quality data is also challenging due to fragmentation across healthcare institutions and inherent biases.
Despite these concerns, DTs offer the potential to gain new insights and understanding of diseases, potentially leading to new treatment opportunities and revealing previously unknown nuances.
