External Control Arms
Advancing clinical development with real-world comparator data
Randomized controlled trials (RCTs) are the accepted gold standard for medical product clinical development programs. However, there are times when an RCT with a traditional control arm is not feasible; for example, when there’s a high unmet medical need, the potential for a large benefit-to-risk ratio, or when conducting an RCT becomes impractical or unethical due to factors like limited patient populations or safety concerns.
Advances such as gene and mRNA therapies, in addition to the increasing focus on rare disease and new cancer treatments, have led to trials in indications for which there is a high unmet medical need and corresponding questions about the suitability of a traditional RCT control arm. In these cases, a single-arm study is considered, and ECAs are an important and viable option to generate comparator data.
Benefits of ECAs
An external control arm uses existing patient-level data, either clinical trial or real-world data (RWD), to create a cohort of patients that can be used as a comparator arm – or can supplement an existing randomly allocated control arm – that mimics the characteristics of an RCT control arm. ECAs provide several benefits, including:
- Strengthening regulatory submissions to facilitate product approval
- Eliminating or reducing the need to enroll control participants
- Enhancing trial efficiency and product development time
- Increasing patient access to the experimental treatment arm
- Informing development and treatment decisions
- Enabling quicker patient access, benefiting the larger affected population
When to consider an ECA
Reduce recruitment demands and increase trial efficiencies where RCTs are insufficient or unethical with real-world data. External control arms support a variety of applications, including regulatory approvals, label expansion or changes, medical affairs, and market access and reimbursement. There are several scenarios ECAs bring value to your trial in::
- Rare indications with high need, urgency or poor outcomes
- Therapies with large benefit versus risk
- Unethical or unfeasible RCTs, resulting in significant delays to patient access
- Scientific concerns about treatment switching/cross-over or other barriers to RCTs
Benefit from proven experience
Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), acknowledge the value of ECA use in specialized trials. There is, however, still much scrutiny given potential bias within the data.
Navigate the use and implementation of ECAs with our real-world studies team to ensure the highest quality results for optimal outcomes and decisions by stakeholders. Advance your product development with a knowledgeable and experienced team providing:
- Strategic guidance on appropriate use of an ECA
- Support for your regulatory strategy and interactions, as well as broader product strategy
- Insights into prioritizing key criteria for data selection
- Validation of real-world outcomes
- Identification of RWD sources that are fit-for-purpose to meet the study’s needs
- Design and validation of state-of-the-art ECA methods
- Full implementation and operationalization of the ECA
