ISSUE:

The growing implementation of Single Arm Trials (SAT) with External-Control Arms (ECA) has been the subject of heated debate with some advocating its use when traditional RCTs are unfeasible, while others fear that it is a means to accelerate timelines and limit costs at the expense of robust quality of evidence. Contrasting perspectives on the different uses and applications of ECA will be discussed.

OVERVIEW:

While RCTs remain the gold standard to demonstrate the efficacy and safety of technologies, with the growing number of targeted therapies and innovative technologies (e.g., cell and gene therapies), SAT are becoming increasingly common, especially in rare diseases where it may be unethical or unfeasible to implement a traditional control arm. Leveraging RWE with carefully designed ECA, can address evidence gaps of SATs and inform decision-making for regulators (EMA, FDA), and Health Technology Assessment (HTAs) bodies. However, criteria evaluating ECAs vary and several technologies receiving EMA/FDA approval with SATs supported by ECAs, face different outcomes when undergoing country-level HTA.

Additionally, ECA extracted from RWD can also enrich RCTs by extending the results of a controlled environment to a broader real-world population, which can bring additional value for HTAs.

Dr. Proenca will provide an overview (approximately 15 min) on the regulatory and HTA use of ECA, supported by case studies and inputs from patient-representatives about their perspective on usage of ECA. Dr. Olsen brings an industry perspective discussing the rationale and engagement process with Regulatory agencies and HTAs and some of the strategies considered when designing RCTs with ECA. Dr. Dietrich, will draws on her HTA/payer perspective to challenge the uses and design of ECA with SAT, reinforcing the benefits of RCTs. Finally, Dr. Mukherjee leverages his background in biostatistics and EMA submissions, proposing high-level methodological considerations that should be respected for the successful design of ECA.