MHRA Opens Consultation on External Control Arms Using Real World Data

**MHRA Opens Consultation on External Control Arms Using Real World Data**

The Medicines and Healthcare products Regulatory Agency (MHRA), the UK’s regulatory body for medicines and medical devices, has initiated a public consultation on the use of external control arms (ECAs) in clinical trials, leveraging real-world data (RWD). This move is part of a broader effort to modernize clinical trial methodologies and enhance the regulatory framework to support innovative approaches in drug development.

**Background and Rationale**

Traditional randomized controlled trials (RCTs) have long been the gold standard for evaluating the efficacy and safety of new medical interventions. However, they can be resource-intensive, time-consuming, and sometimes ethically challenging, especially in cases where withholding treatment is not feasible. To address these challenges, the MHRA is exploring the use of ECAs, which utilize data from sources outside the traditional clinical trial setting, such as electronic health records, patient registries, and other real-world evidence (RWE).

**What Are External Control Arms?**

External control arms are groups of patients used for comparison in a clinical trial, but unlike traditional control groups, they are not randomized within the trial. Instead, they are constructed using RWD from patients who have received standard care outside the trial. This approach can potentially reduce the number of participants needed in the experimental arm and expedite the trial process.

**Consultation Objectives**

The consultation aims to gather insights from stakeholders, including researchers, healthcare professionals, industry representatives, and patient groups, on the following key areas:

1. **Methodological Considerations**: Understanding the best practices for selecting and validating RWD sources to ensure that ECAs are scientifically robust and reliable.

2. **Regulatory Standards**: Determining the criteria and standards that should be applied to ECAs to ensure they meet the regulatory requirements for evidence generation.

3. **Ethical Implications**: Addressing ethical concerns related to patient consent, data privacy, and the use of historical data in lieu of prospective data collection.

4. **Operational Challenges**: Identifying potential challenges in implementing ECAs, such as data integration, quality control, and harmonization across different data sources.

**Potential Benefits**

The use of ECAs can offer several advantages, including:

– **Accelerated Drug Development**: By reducing the need for large control groups, ECAs can shorten the time required to conduct trials and bring new therapies to market faster.
– **Cost Efficiency**: Utilizing existing data can lower the costs associated with recruiting and maintaining control groups.
– **Enhanced Patient Access**: Patients may gain quicker access to potentially life-saving treatments, particularly in areas with high unmet medical needs.

**Challenges and Considerations**

While promising, the use of ECAs also presents challenges. Ensuring the quality and relevance of RWD is crucial, as is addressing potential biases and confounding factors inherent in non-randomized data. The MHRA’s consultation seeks to address these issues by developing clear guidelines and standards for the use of ECAs.

**Conclusion**

The MHRA’s consultation represents a significant step towards integrating RWD into the regulatory framework for clinical trials. By engaging with stakeholders, the agency aims to develop a robust, flexible, and ethical approach to using ECAs, ultimately fostering innovation in drug development and improving patient outcomes. Stakeholders are encouraged to participate in the consultation process to shape the future of clinical trial methodologies in the UK.