United States–Japanese Clinical and Regulatory Harmonization Opportunities for Cardiovascular Devices Discussed at CRT 2021

March 11, 2021—Regulators, academicians, and members of the cardiovascular device industry representing the United States and Japan held a Harmonization By Doing (HBD) Think Tank to discuss emerging clinical and regulatory topics of interest to all stakeholders.

Formed in 2003, the HBD initiative’s goal is the promotion of timely access to innovative cardiovascular devices in the United States and Japan through greater collaboration and communication across all stages of product development and by developing practical solutions to shared real-world challenges. This year’s Think Tank took place on February 19 and 26 as part of CRT 2021, the Cardiovascular Research Therapeutics annual scientific conference, which is being held virtually on Saturdays from February 13 to April 24.

The Think Tank discussions focused on several key topics impacting device evaluation and availability in both countries, as listed and summarized below.

• Pediatric device development: Development of these devices offers unique challenges that can be mitigated by greater availability of funding sources, manufacturer incentives, and academic or governmental coordination of development efforts. Greater utilization of real-world clinical evidence, shifting data collection to the postmarket space, and leveraging adult data would be especially valuable approaches in this area. Guidance or case studies describing successful examples would be beneficial.
• Evaluation of heart failure therapies: Regional differences in patient populations, treatment patterns, and other key clinical factors can affect study endpoints and should be taken into account. Additional cooperative efforts, including multistakeholder collaborations and the use of registries for postmarket surveillance, offer the potential to reduce the burden for clinical evidence collection, especially when these efforts involve United States and Japanese participation.
• Conduct of global clinical trials: Clinical studies involving the United States and Japan are viable, particularly when these studies are designed with such a focus in mind from the beginning and when regulators have the opportunity to provide input early in development. It is important to understand the expected impact of differences in key clinical factors in each country, including patient demographics and clinical practices. In addition, opportunities for postmarket global surveillance in addition to premarket studies should not be overlooked.
• Regulatory pathways for early device access: United States and Japanese regulators have made concerted efforts in recent years to facilitate access to promising device-based therapies, particularly to advance the use of patient-reported data and real-world clinical evidence and to accommodate the appropriate regulation of digital health technologies. Incorporating other geographies in harmonization projects may offer additional benefits in accelerating novel device evaluation and access.
• Impact of COVID-19 on clinical studies: During the past year, many clinical studies were disrupted because of challenges in patient recruitment and follow-up, monitoring, and site support. Strategies to overcome these challenges have included improved remote connections with sites and proactive planning of appropriate changes to the statistical analysis plan while preserving study integrity. Some approaches to virtual site management may endure beyond the pandemic. Both United States and Japanese regulators have been available to discuss these strategies.

The Think Tank discussions will guide the next steps for HBD members, including publications, new and ongoing collaborative projects, and outreach at future scientific symposia. More information about HBD can be found here or by contacting the HBD Secretariat at hbd.contact@pmda.go.jp.