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.

Empirical Evaluation of the Possible Contribution of Group Practice of the Transcendental Meditation and TM-Sidhi Program to Reduction in Drug-Related Mortality.

CDC data indicate that the U.S. is experiencing a sustained epidemic of drug-related mortality, with such deaths exceeding a record 100,000 in 2021, up 47% from 2019.

Editor's Choice - Real World Study of Mortality After the Use of Paclitaxel Coated Devices in Peripheral Vascular Intervention.

Objective: This observational cohort study examined outcomes after peripheral vascular intervention (PVI) with paclitaxel coated devices (PCD) and non-PCD, and evaluated heterogeneity of treatment effect in populations of interest.

Methods: The study included patients undergoing percutaneous transluminal angioplasty and or stent placement between 1 October 2015 and 31 December 2018 in the Vascular Quality Initiative Registry linked to Medicare claims. It determined differences in patient mortality and ipsilateral major amputation after PVI with PCD and non-PCD using Kaplan-Meier analyses and Cox regressions with inverse probability weighting in three cohorts: (A) patients treated for femoropopliteal or infrapopliteal occlusive disease with or without any other concurrent treatment (n = 11 452); (B) those treated for isolated superficial femoral or popliteal artery disease (n = 5 519); and (C) patients with inclusion criteria designed to approximate RCT populations (n = 2 278).

Navigating the Regulatory Pathway for Medical Devices-a Conversation with the FDA, Clinicians, Researchers, and Industry Experts.

Successful translation of new and innovative medical products from concept to clinical use is a complex endeavor that requires understanding and overcoming a variety of challenges. In particular, regulatory pathways and processes are often unfamiliar to academic researchers and start-ups, and even larger companies. Growing evidence suggests that the successful translation of ideas to products requires collaboration and cooperation between clinicians, researchers, industry, and regulators.

Japan-USA Orbital Atherectomy for Calcific Coronary Lesions: COAST Study, a Harmonization by Doing Proof-of-Concept: The Japanese and US Regulatory Perspective.

Regulatory approval processes for medical devices in Japan and the United States of America (US) often require similar clinical trials to establish safety and effectiveness. The Harmonization by Doing (HBD) program provides a collaborative environment for communication between regulators, academics and industry, facilitating the design and conduct of US/Japanese clinical trials supporting approval in both countries.

Electrophysiology devices and the regulatory approval process within the U.S. FDA and abroad.

Almost all electrophysiology (EP) devices need to obtain premarket approval before they can be commercially sold and available for use in the community. The US Food and Drug Administration (FDA) has different paths to market approval depending on the intended use and the associated risks of the device. The European Union and Japan have device approval processes that have many similarities as well as differences to the US regulatory system.

Decision analysis of retrievable inferior vena cava filters in patients without pulmonary embolism.

Background: Retrievable filters are increasingly implanted for prophylaxis in patients without pulmonary embolism (PE) but who may be at transient risk. These devices are often not removed after the risk of PE has diminished. This study employs decision analysis to weigh the risks and benefits of retrievable filter use as a function of the filter's time in situ.

FDA perspective on objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia.

The article by Conte et al.(1) on behalf of the Society for Vascular Surgery (SVS) in this issue of the Journal of Vascular Surgery provides guidelines for improving the consistency and interpretability of clinical trials intended to evaluate treatment options for patients with critical limb ischemia (CLI). This article identifies a number of key challenges with conducting and comparing CLI trials, including the wide spectrum of clinical presentations that CLI encompasses, the use of disparate eligibility criteria and endpoint measurements, and logistical and economic considerations that can limit study initiation and completion.

How dysregulated colonic crypt dynamics cause stem cell overpopulation and initiate colon cancer.

Based on investigation of the earliest colonic tissue alteration in familial adenomatous polyposis (FAP) patients, we present the hypothesis that initiation of colorectal cancer by adenomatous polyposis coli (APC) mutation is mediated by dysregulation of two cellular mechanisms. One involves differentiation, which normally decreases the proportion (proliferative fraction) of colonic crypt cells that can proliferate; the other is a cell cycle mechanism that simultaneously increases the probability that proliferative cells are in S phase. In normal crypts, stem cells (SC) at the crypt bottom generate rapidly proliferating cells, which undergo differentiation while migrating up the crypt.

Stretch increases alveolar epithelial permeability to uncharged micromolecules.

We measured stretch-induced changes in transepithelial permeability in vitro to uncharged tracers 1.5-5.5 A in radius to identify a critical stretch threshold associated with failure of the alveolar epithelial transport barrier.

Measurement of stretch-induced loss of alveolar epithelial barrier integrity with a novel in vitro method.

Mechanical ventilation with high tidal volumes has been shown to contribute to the formation or worsening of interstitial and alveolar edema. Previously we showed that application of large biaxial deformations in vitro perturbs the concentration and distribution of functional tight junction proteins in alveolar epithelial cells. Using a novel method, we determined that applied epithelial strain increases paracellular permeability in a dose- and rate-dependent manner.