Cancer clinical trials have long been the cornerstone of advancements in oncology, guiding the development of new therapies and improving patient outcomes. However, traditional clinical trials often face challenges such as lengthy durations, high costs, and difficulty in patient recruitment as well as ethics committee requirements and other regulatory approvals.
One innovative approach that has emerged to address these challenges is the use of external control arms (ECAs). By leveraging historical data and real-world evidence (RWE), ECAs offer a promising alternative to traditional control groups (i.e., placebo arm, where patients do not receive the experimental drug), potentially transforming the landscape of cancer clinical trials.
Understanding ECAs
An ECA refers to a group of patients whose data is derived from sources outside the current clinical trial. These sources can include real-world data (RWD) repositories such as historical clinical trial data, electronic health records (EHRs), patient registries, and data generated by chart reviews.
Unlike traditional randomized controlled trials (RCTs), where patients are randomly assigned to either the experimental group or the control group receiving standard treatment, ECAs use pre-existing data to create a comparator group.
Benefiting From ECAs: Clinical Affairs and Medical Affairs
ECAs offer the life sciences industry several key advantages.
Benefits to clinical affairs teams include:
- Accelerated Clinical Trial Timelines: One of the most significant advantages of ECAs is the potential to speed up clinical trials. By using existing data, clinical affairs teams can bypass the often lengthy and complex process of recruiting and enrolling patients for the control group. This acceleration can be particularly beneficial in oncology, where the urgency to bring effective treatments to patients is paramount.
- Cost Efficiencies: Traditional RCTs are expensive, partly due to the costs associated with recruiting, monitoring, and maintaining control groups. ECAs can reduce these expenses by eliminating the need for a separate control group, thereby reallocating resources towards other critical aspects of the trial.
- Reduction in Ethical Concerns: In cases where the experimental treatment shows early signs of significant benefit, it may be ethically challenging to continue enrolling patients in a control group receiving standard or less effective treatment. ECAs mitigate this issue by allowing all participants in the trial to potentially receive the new therapy, thereby addressing ethical considerations.
- Improved Patient Recruitment: Recruiting patients for clinical trials, particularly for control groups, can be challenging. Potential participants are often reluctant to enroll if there is a chance they might not receive the experimental treatment. ECAs can make trials more appealing to patients by ensuring that all participants have access to the new therapy. They can also make it easier to find a representative sample that meets participant diversity requirements.
Benefits of ECAs to medical affairs teams include:
- Regulatory Flexibility: Regulatory bodies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), are increasingly accepting ECAs as valid control arms, particularly for rare diseases and oncology trials. This allows for exploration of innovative trial designs and engagement in more flexible discussions with regulators.
- Shortened Time to Approval: Streamlining the clinical trial process with ECAs helps to reduce the number of patients needed in the control arm and potentially shortens the time required for data collection. This can accelerate the submission and approval process.
- Enhanced Data Robustness: ECAs, built from large, diverse datasets, provide comprehensive insights into the treatment landscape. This strengthens the data package submitted for regulatory approval, increasing the likelihood of a positive outcome from agencies.
- Support for Health Outcomes Research: ECAs provide robust data that medical affairs teams can use in health outcomes and economic studies, such as cost-effectiveness analyses, to support value propositions for therapies.
TriNetX: Shaping the Future of Oncology Research with ECAs
TriNetX ECAs provide a proven methodology to create comparison cohorts, enabling the generation of control data that is representative and fit-for-purpose. By employing a fit-for-purpose ECA followed by a TriNetX comparative analysis of clinical trial data and ECA data, life sciences organizations can:
- Improve the integrity and reliability of data analysis,
- Have more successful Health Technology Assessment (HTA) and European Medicines Agency (EMA) submissions, and
- Better understand treatment impacts in trials to inform assumptions for later phase trials.
ECA Success: The TriNetX Oncology team has delivered two very large ECAs for an oncology study in Europe, resulting in greater efficiencies, including saved time and expense, in recruiting patients for the trial’s comparator group. The team has been able to collect regulatory grade data from a representative and diverse group of patients across several European countries and the results of the ECA will be published soon. Meanwhile, the team has started another large, pan-European ECA.
Looking Ahead
The use of ECAs in cancer clinical trials is still in its early stages, but at TriNetX, we are leading this new approach and see substantial potential for growth. Advances in data science, artificial intelligence, and machine learning are expected to further enhance the ability to generate high-quality ECAs. These technologies can help identify relevant patient cohorts, address biases, and ensure data accuracy, thereby strengthening the validity of trial results.
As the regulatory landscape evolves and technological advancements continue, the use of ECAs is poised to become an integral part of the future of oncology research, ultimately improving the speed and efficiency with which new cancer therapies reach patients in need.
Additional Insights:
- Watch our on-demand webinar, Unlocking the Power of Real-World Evidence for Success in Europe’s Evolving HTA and Regulatory Landscape.
- Read our blog, The Future of Oncology Research in Europe: Integrating Real-World Evidence into Joint Clinical Assessments.
- Discover how TriNetX’s non-U.S. oncology data can enhance your clinical studies and regulatory submissions.
About Andreas Weber
As a senior executive with a proven track record in management and leadership, Andreas is known for his deep understanding of life sciences, spanning the entire industry continuum. His expertise encompasses pharmacovigilance, drug safety, regulatory affairs, and end-to-end eClinical processes, with a strong focus on business process optimization, outsourcing, and information technology
