Making a Difference for Cancer Patients with Hybrid and External Control Arms in Clinical Trials

Clinical trials bring hope to millions of patients every year, including cancer patients who have tried numerous therapies in the past with mixed success. 

While the traditional approach of studying control and intervention arms concurrently is an effective way to bring new treatment options to patients, the growing availability of high-quality real-world data (RWD) is changing the way we can accelerate results.

What are Hybrid and External Control Arms?

Hybrid and External Control Arms (ECAs), also known as synthetic control arms, are a key part of the future of drug development.  ECAs allow investigators to simulate control populations using historical records from patients with the targeted condition.  These patients meet the same clinical criteria as other participants in the trial, and the treatments they received align with the care protocols under scrutiny. 

 Why are Hybrid and External Control Arms Important?

For Investigators:

  • Less time finding and screening hard-to-find participants quickly to ensure emergent care (especially in highly specialized trials)
  • More time focusing on patient care and ensuring the best possible patient outcomes


For Trial Sponsors:

  • Diminished ethical quandary of assigning a proportion of patients currently in need to standard care
  • Faster clinical trials
  • Fewer enrollment delays and drop-outs concerns

What are some challenges clinical trial sponsors have seen with Hybrid and External Control Arms?

  • Real-world data quantity, quality and format- Up until very recently, clinical trial sponsors have struggled to access enough detailed, accurate, diverse data with the right mix of patients to make ECAs a viable strategy for supplementing clinical trials.
  • Regulatory concerns- Low participation rates and regulatory hurdles ,some of which are getting easier to tackle as stakeholders become more familiar with and accepting of RWD as an integral part of the research process. Some trial sponsors would prefer to not use RWD until it is fully mature with regulatory bodies, but this can result in longer time to adoption.

How is COTA leading the way?

At COTA, we are excited to be leading the way toward these changes.

In partnership with our life science customers, we are making clinical trials with ECAs a reality. Our pipeline for regulatory submissions with ECAs is extensive with ten active submissions and, most recently, COTA’s data has been used to support FDA approval for a multiple myeloma treatment.

We make it our mission to work closely with regulatory bodies and trial sponsors to ensure the best possible data for control and comparator arms, and ensure that we evolve our processes to feedback we receive from the FDA and others.

As some of the first uses of ECAs to support the development of a life-changing treatment option, this is a critical milestone in the use of RWD for next-generation research and patient care.

COTA has been steadily working toward this goal by curating rich, meaningful data with laser focus on patient privacy. We are excited to see that ECAs are starting to make a real difference for real patients with complex cancers and are committed to making them a reality at scale. ECAs are poised to become an important part of the therapeutic development process, and we are looking forward to continuing to leverage our expertise in RWD to help more people with cancer live longer, healthier lives.