Global Medical Device Clinical Trials Involving Both the United States and Japan: Key Considerations for Development, Regulatory Approval, and Conduct.

As medical device development becomes increasingly global, the opportunities and potential advantages offered by international clinical trial and regulatory approval strategies are also growing. In particular, medical device clinical trials involving sites in both the United States and Japan and intended to support marketing in both countries may warrant particular consideration, given the similarities in their regulatory systems, patients and clinical practice patterns, and market sizes. Since 2003, the US-Japan Harmonization By Doing (HBD) initiative has been focused on identifying and addressing clinical and regulatory barriers to medical devices access in both countries via collaboration between governmental, academic, and industry stakeholders.

The associations of the national health and productivity management program with corporate profits in Japan.

Objectives: Using a dataset from a survey on national health and productivity management, we identified health and productivity factors associated with organizational profitability.

Methods: The Ministry of Economy, Trade and Industry conducted an annual survey on Health and Productivity Management between 2014 and 2021. We assessed the associations of organizational health and productivity management using survey questions collected in 2017 and 2018, with the rate of change in profits from 2017 and 2018 to 2020.

Japan-USA Orbital Atherectomy for Calcific Coronary Lesions: COAST Study, Harmonization by Doing Proof-of-Concept.

Effective treatment strategies and medical devices continue to be needed in Japan and the United States of America (US) to mitigate the growing burden of cardiovascular disease and coronary heart disease. Unfortunately, there can be a delay in gaining cardiovascular device approval in Japan after a device has already been approved and is in use in the US. The Harmonization by Doing (HBD) program; however, can eliminate this delay and reduce the cost of completing a clinical trial in Japan.

In Vivo Translation of the CIRPI System: Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques.

Thin-cap fibroatheroma (TCFA) are the unstable lesions in coronary artery disease that are prone to rupture, resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphologic and biologic features make early detection and risk assessment difficult. We tested our newly developed catheter-based ircumferential-ntravascular-adioluminescence-hotoacoustic-maging (CIRPI) system in vivo to enable detection and characterization of vulnerable plaque structure and biology in rabbit abdominal aorta.

The East-West late lumen loss study: Comparison of angiographic late lumen loss between Eastern and Western drug-eluting stent study cohorts.

Background: Regulatory decisions approving new coronary drug-eluting stent (DES) require mechanistic observations of angiographic late lumen loss (LLL). Patient safety and device approval times could be enhanced if angiographic follow-up data were found to be generalizable across jurisdictions and geographies. The objectives were to assess the comparability of in-segment LLL in Eastern and Western DES populations using the world's largest compilation of follow-up quantitative coronary angiography data.

Design Strategies for Global Clinical Trials of Endovascular Devices for Critical Limb Ischemia (CLI) - A Joint USA-Japanese Perspective.

For more than 10 years, the Harmonization by Doing (HBD) program, a joint effort by members from academia, industry and regulators from the United States of America (USA) and Japan, has been working to increase timely regulatory approval for cardiovascular devices through the development of practical global clinical trial paradigms. Consistent with this mission and in recognition of the increasing global public health effects of critical limb ischemia (CLI), academic and government experts from the USA and Japan have developed a basic framework of global clinical trials for endovascular devices for CLI. Despite differences in medical and regulatory environments and complex patient populations in both countries, we developed a pathway for the effective design and conduct of global CLI device studies by utilizing common study design elements such as patients' characteristics and study endpoints, and minimizing the effect of important clinical differences.

Dose-Dependent Cardioprotection of Moderate (32°C) Versus Mild (35°C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction.

Objectives: The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia.

Background: Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage.

Correction to: Cost-effectiveness of orbital atherectomy compared to rotational atherectomy in treating patients with severely calcified coronary artery lesions in Japan.

In the original publication of this article, in Abstract the 1-year mortality of OAS should be stated as 4.7 and not 5.5%.

Cost-effectiveness of orbital atherectomy compared to rotational atherectomy in treating patients with severely calcified coronary artery lesions in Japan.

Compared to rotational atherectomy (RA), orbital atherectomy (OA) has been shown to decrease procedure failure and reintervention rates in the treatment of severely calcified coronary artery lesions. Our objective was to explore the cost-effectiveness of OA compared to RA in the Japanese healthcare system. A decision-analytic model calculated reintervention rates and consequent total 1-year costs.

Differences in Vascular Response between Balloon Overstretch and Stent Overexpansion in Nonatherosclerotic Porcine Coronary Arteries.

Which preclinical models are best suited for restenosis research remains uncertain. Here we compared the restenotic responses after balloon or stent overstretch injury in a porcine coronary artery. A total of 30 coronary lesions in 5 pigs were treated by balloon overdilatation or oversized stent implantation at various balloon-to-artery (B:A) ratios.

Assessment of bioresorbable scaffold with a novel high-definition 60 MHz IVUS imaging system: Comparison with 40-MHz IVUS referenced to optical coherence tomography.

Background: In vivo assessment of bioresorbable scaffold (BRS) is of growing clinical interest. The novel 60MHz high-definition intravascular ultrasound (HD-IVUS) has been developed to overcome the limitations of conventional 40 MHz IVUS. This study aimed to evaluate the performance and limitations of 60 MHz HD-IVUS compared with 40 MHz IVUS with respect to polymeric-strut visualization, quantitative and qualitative analysis, and feasibility of high-speed pullback in the assessment of BRS.

Improvement of Local Cell Delivery Using Helix Transendocardial Delivery Catheter in a Porcine Heart.

Cardiac regeneration strategies using stem cells have shown variable and inconsistent results with respect to patient cardiac function and clinical outcomes. There has been increasing consensus that improving the efficiency of delivery may improve results. The Helix transendocardial delivery system (BioCardia Inc.

SYNTAX Score and Long-Term Outcomes: The BARI-2D Trial.

Background: The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease.

Objectives: This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial.

Clinical value of post-percutaneous coronary intervention fractional flow reserve value: A systematic review and meta-analysis.

Background: Fractional flow reserve (FFR) prior to percutaneous coronary intervention (PCI) is useful to guide treatment. Whether post-PCI FFR assessment might have clinical impact is controversial. The aim of this study is to evaluate the range of post-PCI FFR values and analyze the relationship between post-PCI FFR and clinical outcomes.

Rationale and design of the East-West late lumen loss study: Comparison of late lumen loss between Eastern and Western drug-eluting stent study cohorts.

Background: The contemporary evaluation of novel drug-eluting stents (DES) includes mechanistic observations that characterize postdeployment stent behavior. Quantification of late lumen loss due to neointimal hyperplasia 8-13 months after stent implantation, via quantitative coronary angiography (QCA), constitutes such an observation and is required by most regulatory authorities. Late lumen loss, as determined by QCA, has been validated as a surrogate for clinical endpoints such as target vessel revascularization.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene.

Acute stent recoil and optimal balloon inflation strategy: an experimental study using real-time optical coherence tomography.

Aims: Our aim was to evaluate stent expansion and acute recoil at deployment and post-dilatation, and the impact of post-dilatation strategies on final stent dimensions.

Methods And Results: Optical coherence tomography (OCT) was performed on eight bare metal platforms of drug-eluting stents (3.0 mm diameter, n=6 for each) during and after balloon inflation in a silicone mock vessel.

Transcatheter Alcohol-Mediated Perivascular Renal Denervation With the Peregrine System: First-in-Human Experience.

Objectives: This study evaluated the first clinical use of a new endovascular approach to renal denervation, using chemical neurolysis, via periadventitial infusion of dehydrated alcohol (ethanol) to perform "perivascular" renal artery sympathetic denervation.

Background: Renal denervation remains a promising technology for the treatment of hypertension and other disorders.

Methods: A novel 3-needle delivery device (Peregrine System Infusion Catheter, Ablative Solutions, Inc.

Therapeutic Hypothermia for Cardioprotection in Acute Myocardial Infarction.

Mild therapeutic hypothermia of 32-35°C improved neurologic outcomes in outside hospital cardiac arrest survivor. Furthermore, in experimental studies on infarcted model and pilot studies on conscious patients with acute myocardial infarction, therapeutic hypothermia successfully reduced infarct size and microvascular resistance. Therefore, mild therapeutic hypothermia has received an attention as a promising solution for reduction of infarction size after acute myocardial infarction which are not completely solved despite of optimal reperfusion therapy.

Quantitative precision of optical frequency domain imaging: direct comparison with frequency domain optical coherence tomography and intravascular ultrasound.

No systematic validation study is available with optical frequency domain imaging (OFDI), directly compared with frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS). Controversy also remains about the impact of different stent contour tracing methods by OFDI/FD-OCT. In vitro: coronary phantom models (1.

Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model.

Background: The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts.

Optical Coherence Tomography of Pulmonary Arterial Walls in Humans and Pigs (Sus scrofa domesticus).

Pulmonary arterial hypertension (PAH) is a devastating disorder characterized by progressive elevation of the pulmonary pressures that, in the absence of therapy, results in chronic right-heart failure and premature death. The vascular pathology of PAH is characterized by progressive loss of small (diameter, less than 50 μm) peripheral pulmonary arteries along with abnormal medial thickening, neointimal formation, and intraluminal narrowing of the remaining pulmonary arteries. Vascular pathology correlates with disease severity, given that hemodynamic effects and disease outcomes are worse in patients with advanced compared with lower-grade lesions.

Serial changes of coronary endothelial function and arterial healing after paclitaxel-eluting stent implantation.

Several studies have shown coronary endothelial dysfunction and delayed arterial healing associated with first-generation drug-eluting stents. However, it remains unclear whether those issues persist for a longer term. We thus evaluated serial changes in endothelial function and intra-stent condition after paclitaxel-eluting stents (PES) implantation.