Pediatric Medical Devices Research Articles

Lessons learned from the RE(ACT) conference on medical devices for rare diseases

The field of rare disease therapeutics has witnessed significant growth in recent years, highlighting the need for diverse therapeutic approaches to cater to the unique needs of individuals with rare diseases. Rare disease therapies encompass a broad spectrum of interventions, including orphan medicinal products, orphan medical devices, rehabilitative therapies, and digital therapeutics, with the lines between these categories blurring. This paper covers the session of the RE (ACT)-IRDiRC Conference 2023 and delves into the landscape of orphan medical device research and development, shedding light on the challenges and opportunities in this burgeoning field. It provides a short overview of the different international legislations in the field. In addition, it highlights several exemplary orphan medical devices. The first example is an exoskeleton for boys with Duchenne Muscular Dystrophy, enabling them to maintain arm functionality and independence. Another example presented was an EEG device linked to an app detecting seizures in rare epilepsy conditions, which alerts caregivers to seizures in real-time but also facilitates objective seizure reporting for clinicians, aiding in diagnosis and treatment optimization. It also showcases the role of gamification and enabling technologies in addressing rare diseases, by showing a game designed for children with cystic fibrosis, and a telemedicine system for rehabilitation therapy. Both solutions aim to improve patients' understanding of their conditions and enhance their self-management. In conclusion, this paper underscores the critical need for patient-centric orphan and pediatric medical devices to provide therapeutic options for individuals with rare diseases. It highlights the impact of existing devices on enhancing the quality of life for rare disease patients and emphasizes the necessity for greater incentives and support for research and development in this field.

A Comparative Analysis of the Regulatory Framework and Collaborative Environment for Pediatric Medical Device Development in Japan and the United States: Identifying Challenges, Support Mechanisms, and Emerging Opportunities.

There are specific obstacles to designing medical devices for children, such as commercial distortions and regulatory hurdles. This study compares the regulatory frameworks and collaborative ecosystems of the United States (US) and Japan, enabling the development of pediatric medical devices. The study illustrates the differences as well as parallels between the two countries by outlining their primary obstacles, channels of assistance, and prospects. The regulatory regimes of the US and Japan pose substantial challenges due to their intricate approval procedures and the dearth of pediatric-specific guidelines. However, while Japan's ecosystem is more dispersed, the US offers more well-established support mechanisms, such as funding initiatives and research alliances. Despite these difficulties, there are still prospects for innovative thinking and collaborative work. The article demonstrates successful partnerships between business, academia, and government in both countries, which have helped propel the advancement of pediatric devices. For stakeholders endeavoring to maneuver through thecomplex terrain of pediatric medical device development, this study offers valuable insights. With a comprehensive understanding of the regulatory and collaborative frameworks in Japan and the US, developers can more effectively leverage resources, overcome obstacles, and bring vital technology to market. The study's findings have implications for researchers, industry leaders, and policy regulators, providing recommendations for strategies aimed at stimulating innovation and enhancing children's healthcare outcomes internationally.

Pediatric Device Clinical Trials Activity: 1999-2022.

This study assessed the state of pediatric medical device (PMD) development by comparing PMD clinical trials to pediatric trials evaluating drugs and biologics, from 1999 to 2022. The site www.clinicaltrials.gov was used to identify and quantify both PMD clinical trials and pediatric trials for drugs and biologics. Clinical specialty was also assessed. The institutions included were the 7 children's hospitals primarily affiliated with the Food and Drug Administration (FDA) Pediatric Device Consortia (PDC) grant program between 2018 and 2023. For a national comparison, an additional search assessed PMD trials across all US medical institutions. A total of 243 PMD clinical trials were identified at the FDA-PDC institutions on the basis of the year of initiation; the average number of PMD trials initiated per year per institution was 1.5 from 1999 to 2022. However, PMD trials significantly increased during the period 2014 to 2022 compared with 1999 to 2013 (P < .001); the rate of initiation of drug and biologic pediatric trials demonstrated no significant differences between these time periods. A national survey of all institutions initiating PMD trials, and drugs and biologics trials, identified 1885 PMD trials out of a total 12 943. A comparable trend was noted in the national survey with initiation of PMD trials increasing significantly from 2014 to 2022 (P < .001), compared with 1999 to 2013, whereas the rate of initiation of drug and biologic trials during these periods did not demonstrate a significant change. Although pediatric clinical trial initiation for drugs and biologics remained stable from 1999 to 2022, the rate of new PMD trials significantly increased during the period 2014 to 2022 at FDA-PDC institutions and nationally.

A prospective multicenter feasibility study of a miniaturized implantable continuous flow ventricular assist device in smaller children with heart failure

There is no FDA-approved left ventricular assist device (LVAD) for smaller children permitting routine hospital discharge. Smaller children supported with LVADs typically remain hospitalized for months awaiting heart transplant-a major burden for families and a challenge for hospitals. We describe the initial outcomes of the Jarvik 2015, a miniaturized implantable continuous flow LVAD, in the NHLBI-funded Pumps for Kids, Infants, and Neonates (PumpKIN) study, for bridge-to-heart transplant. Children weighing 8 to 30 kg with severe systolic heart failure and failing optimal medical therapy were recruited at 7 centers in the United States. Patients with severe right heart failure and single-ventricle congenital heart disease were excluded. The primary feasibility endpoint was survival to 30 days without severe stroke or non-operational device failure. Of 7 children implanted, the median age was 2.2 (range 0.7, 7.1) years, median weight 10 (8.2 to 20.7) kilograms; 86% had dilated cardiomyopathy; 29% were INTERMACS profile 1. The median duration of Jarvik 2015 support was 149 (range 5 to 188) days where all 7 children survived including 5 to heart transplant, 1 to recovery, and 1 to conversion to a paracorporeal device. One patient experienced an ischemic stroke on day 53 of device support in the setting of myocardial recovery. One patient required ECMO support for intractable ventricular arrhythmias and was eventually transplanted from paracorporeal biventricular VAD support. The median pump speed was 1600 RPM with power ranging from 1-4 Watts. The median plasma free hemoglobin was 19, 30, 19 and 30 mg/dL at 7, 30, 90 and 180 days or time of explant, respectively. All patients reached the primary feasibility endpoint. Patient-reported outcomes with the device were favorable with respect to participation in a full range of activities. Due to financial issues with the manufacturer, the study was suspended after consent of the eighth patient. The Jarvik 2015 LVAD appears to hold important promise as an implantable continuous flow device for smaller children that may support hospital discharge. The FDA has approved the device to proceed to a 22-subject pivotal trial. Whether this device will survive to commercialization remains unclear because of the financial challenges faced by industry seeking to develop pediatric medical devices. (Supported by NIH/NHLBI HHS Contract N268201200001I, clinicaltrials.gov 02954497).

Balancing pediatric device utility and harm: navigating the challenges for safer healthcare.

This article discusses the challenges in balancing the utility and harm associated with pediatric medical devices. Takashima et al. explored the prevalence and complications of invasive devices across three Australian pediatric tertiary hospitals and reported a high prevalence of complications, particularly with vascular access devices. We also highlight the need to pay attention to the use of these devices, particularly intravenous catheters, and the importance of a culture of patient safety in healthcare systems. We emphasize the need for a nuanced approach that carefully weighs the benefits against potential risks and encourages collaboration among stakeholders to establish robust regulatory frameworks and prioritize the safety and well-being of pediatric patients. Finally, we conclude by advocating the involvement of parents and families in gathering information about hospital safety incidents and fostering a culture of safety that supports reporting, flexibility, and learning. IMPACT: Reporting adverse events and their consequences is essential in the strategy to prevent them, allowing comparison with national or international standards, and identifying indicators to optimize and harbor the possibility of determining improvement measures that pursue a multifactorial approach and are cost-effective. Our comment advocates limiting the prevalence of medical invasive devices and their consequences by reviewing their epidemiology. Although advancements in medical technology have undoubtedly improved the diagnostic and therapeutic possibilities, the delicate balance between device utility and potential harm necessitates careful consideration.

Gaps and priorities in innovation for children's surgery

Lack of access to pediatric medical devices and innovative technology contributes to global disparities in children's surgical care. There are currently many barriers that prevent access to these technologies in low- and middle-income countries (LMICs). Technologies that were designed for the needs of high-income countries (HICs) may not fit the resources available in LMICs. Likewise, obtaining these devices are costly and require supply chain infrastructure. Once these technologies have reached the LMIC, there are many issues with sustainability and maintenance of the devices. Ideally, devices would be created for the needs and resources of LMICs, but there are many obstacles to innovation that are imposed by institutions in both HICs and LMICs. Fortunately, there is a growing interest for development of this space, and there are many examples of current technologies that are paving the way for future innovations. Innovations in simulation-based training with incorporated learner self-assessment are needed to fast-track skills acquisition for both specialist trainees and non-specialist children's surgery providers, to scale up access for the larger population of children. Pediatric laparoscopy and imaging are some of the innovations that could make a major impact in children's surgery worldwide.

Shortages of Care and Medical Devices Affecting the Pediatric Patient Population

What Is the Issue? Shortage events, the phenomena when demand exceeds supply, can affect both medical care and medical devices. The COVID-19 pandemic caused a global shortage event, the consequences of which are still being experienced beyond the peak of the pandemic (e.g., the lack of pediatric pain medication available in fall 2022). Children are vulnerable to shortage events as they represent a small proportion of the overall population, have distinct needs, and the pediatric medical device market has historically offered a lack of options. What Are the Technologies? Technologies such as artificial intelligence (AI)-enabled devices, point of care testing, and virtual care options could contribute to alleviating shortages in pediatric care. Technologies such as 3D printing, alternative interventions such as tracheostomy during shortages of mechanical ventilators, and the reprocessing of single use devices such as ventilator tubes have been suggested in times of pediatric medical device shortages. Solutions to shortage events can take the form of novel devices, interventions, or policies; however, due to the complexity of this problem, a multipronged approach is likely needed. What Is the Potential Impact? Shortages can cause delayed intervention, which has health and financial costs. When cancer diagnoses and treatments are delayed, overall survival rates decrease. High-quality early intervention can change a child’s developmental trajectory and improve outcomes for children, families, and communities. Finding solutions to shortages, particularly for children as they are already at risk for health inequities, is crucial to ensure good health care outcomes in the long-term. What Else Should We Know? During a shortage event, alternative interventions may have different safety profiles or require different training than default practices. Equity should be a consideration when implementing technologies, interventions, and policies to address shortage events so that these solutions do not end up replicating or exacerbating existing inequities.

Characteristics and Results of Pediatric Medical Device Studies: 2017-2022.

The development of medical devices for children faces unique challenges that have contributed to a paucity of devices specifically designed and tested for children. Increased knowledge on research activities for pediatric devices can guide optimal study design and ensure timely dissemination of clinical findings. We performed a cross-sectional analysis of interventional studies registered on ClinicalTrials.gov, initiated January 1, 2017, through December 12, 2022, evaluating a Food and Drug Administration-regulated class II or III device, and enrolling any pediatric patients (aged ≤17 years). Data were extracted from ClinicalTrials.gov on study characteristics and from Devices@FDA on device features. For completed studies, we determined whether results were reported in a peer-reviewed publication as of December 27, 2022. Among 482 studies, 406 (84.2%) examined a class II device and 76 (15.8%) a class III device. The most common device types were diabetes-related devices (N = 57, 11.8%) and monitors and measurement devices (N = 39, 8.1%). Most studies were single-center (N = 326, 67.6%), used a nonrandomized (N = 255, 52.9%), open label (N = 350, 72.6%) design, and were funded by academic institutions (N = 278, 57.7%) or industry (N = 142, 29.5%). A total of 291 (60.4%) studies included a primary outcome of only efficacy without safety endpoints. Among completed studies, more than half (N = 64, 51.6%) enrolled <50 participants and 71.0% (N = 88) <100. After median follow-up of 3.0 years, results were available in publications for 27 (21.8%) completed studies. Our findings serve to inform programs and initiatives seeking to increase pediatric-specific device development. In addition to considerations on ensuring rigorous trial design, greater focus is needed on timely dissemination of results generated in pediatric device studies.

Advancing Equity in Medical Device Development for Children

This Viewpoint reviews activities to increase pediatric medical device development, assesses ongoing challenges, and recommends strategies to strengthen pediatric programs.

PMDedu: Assessing the educational needs of startups and academic investigators focused on pediatric medical device development.

The pediatric medical device development (PMDD) process is highly complex, beset by a variety of financial, technical, medical, and regulatory barriers. Startup company innovators and academic investigators often struggle with accessing specialized knowledge relating to regulatory requirements, product development, research, and marketing strategies. The West Coast Consortium for Technology & Innovation in Pediatrics (CTIP) conducted an educational needs assessment to understand knowledge gaps and inform our educational strategy. We surveyed a total of 49 medical device startups and 52 academic investigators. Electronic surveys were developed for each group on Qualtrics and focused on manufacturing, regulatory, research, commercialization, and funding. Descriptive statistics were used. A larger proportion of academic investigator respondents had a clinical background compared to the startup respondents (45% vs. 22%). The biggest barriers for academic investigators were understanding regulatory and safety requirements testing (52%) and finding and obtaining non-dilutive funding was the most difficult (54%). Among startups, understanding clinical research methods and requirements was the biggest barrier (79%). Startup companies and academic investigators have similar, but not identical, educational needs to better understand the PMD development process. Investigators need more support in identifying funding sources, while startup companies identified an increased need for education on research regulatory topics. These findings can help guide curriculum development as well as opportunities for partnerships between academia and startups.

Pediatric Medical Device Development and Regulation: Current State, Barriers, and Opportunities.

Few medical devices are designed and marketed specifically for children. Instead, adult devices are often repurposed and used off-label in pediatrics. The innovation gap between pediatric and adult devices is complex and multifactorial. This review aims to summarize the medical device landscape, describe barriers to pediatric device development, and provide an update on current strategies to help overcome these limitations. Medical devices are regulated by the Food and Drug Administration. They are registered, cleared, or approved on the basis of a 3-tier risk classification system and a differentiated set of regulatory pathways. This includes some for products that receive special designations on the basis of specific aspects that warrant more rapid review and approval. Pediatric devices number only one-quarter of those developed for adults for multiple reasons. Clinically, innovators must adjust their products to address the smaller sizes, growth, and longer duration of use in children. Smaller sample sizes and population heterogeneity also challenge the ability to obtain sufficient safety data for regulatory submissions. Financial concerns stem from lower pediatric reimbursement rates coupled with a lack of nationally standardized coverage. There are a number of promising initiatives, including the Pediatric Device Consortia Program, Early Feasibility Studies, and the new System of Hospitals for Innovation in Pediatrics - Medical Devices. However, the gap will likely not be narrowed without broad cooperation across stakeholders from industry, academia, patient advocacy groups, health care providers, investors, payors, regulators, and Congress.

A novel maturity index for assessing medical device startups.

Startup companies in the healthcare sector often fail because they lack sufficient entrepreneurial, regulatory, and business development expertise. Maturity models provide useful frameworks to assess the state of business elements more systematically than heuristic assessments. However, previous models were developed primarily to characterize the business state of larger nonmedical companies. A maturity index designed specifically for startup companies in the medical product sector could help to identify areas in which targeted interventions could assist business development. A novel MedTech Startup Maturity Index (SMI) was developed by a collaborative team of academic and industry experts and refined through feedback from external stakeholders. Pediatric medical device startups associated with the West Coast Consortium for Technology & Innovation in Pediatrics (CTIP) were scored and ranked according to the SMI following semi-structured interviews. The CTIP executive team independently ranked the maturity of each company based on their extensive experiences with the same companies. SMI scores for 16 companies ranged from 1.2 to 3.8 out of 4. These scores were well aligned with heuristic CTIP rankings for 14 out of 16 companies, reflected by strong correlations between the two datasets (Spearman's rho = 0.721, P = 0.002, and Kendall's tau-b = 0.526, P = 0.006). The SMI yields maturity scores that correlate well with expert rankings but can be assessed without prior company knowledge and can identify specific areas of concern more systematically. Further research is required to generalize and validate the SMI as a pre-/post-evaluation tool.

Medical Device Development for Children and Young People-Reviewing the Challenges and Opportunities.

Development of specific medical devices (MDs) is required to meet the healthcare needs of children and young people (CYP). In this context, MD development should address changes in growth and psychosocial maturation, physiology, and pathophysiology, and avoid inappropriate repurposing of adult technologies. Underpinning the development of MD for CYP is the need to ensure MD safety and effectiveness through pediatric MD-specific regulations. Contrary to current perceptions of limited market potential, the global pediatric healthcare market is expected to generate around USD 15,984 million by 2025. There are 1.8 billion young people in the world today; 40% of the global population is under 24, creating significant future healthcare market opportunities. This review highlights a number of technology areas that have led to successful pediatric MD, including 3D printing, advanced materials, drug delivery, and diagnostic imaging. To ensure the targeted development of MD for CYP, collaboration across multiple professional disciplines is required, facilitated by a platform to foster collaboration and drive innovation. The European Pediatric Translational Research Infrastructure (EPTRI) will be established as the European platform to support collaboration, including the life sciences industrial sector, to identify unmet needs in child health and support the development, adoption, and commercialization of pediatric MDs.

The Scarcity of Approved Pediatric High-Risk Medical Devices

Samuel J. Lee, BSPH; Lauren Cho; Eyal Klang, MD; James Wall, MD; Stefano Rensi, PhD; Benjamin S. Glicksberg, PhD

Pediatric Medical Devices - Survey of Pediatric Cardiologists and Cardiovascular Surgeons in Japan.

Background: In Japan, the choice of pediatric medical devices is limited because of 2 “device lag” problems: Japan lags behind the USA and Europe in device development, and development of pediatric devices lags behind that of adult devices. We aimed to identify the problems with and impediments to pediatric medical device development as recognized by pediatric physicians in Japan.Methods and Results: A voluntary survey of pediatric medical devices for all council members of the Japanese Society of Pediatric Cardiology and Cardiac Surgery was conducted in 2019. The response rate was 47.1% (154/327). The respondents were 115 pediatric cardiologists (74.7%) and 39 cardiovascular surgeons (25.3%). Approximately 90% believed that difficulties in development existed. Approximately 70% were dissatisfied with the pediatric medical devices currently available in Japan, which was a result of the unavailability of medical devices approved overseas, few types and sizes, and off-label use. Factors that hindered the development of pediatric medical devices included anatomical issues specific to children with congenital heart disease, as well as system issues such as lack of corporate profitability, development cost, and amount of time for development.Conclusions: Pediatric cardiologists and cardiovascular surgeons regard “device lag” and “off-label use” in Japan as important hindrances to the delivery of better medical care for pediatric patients with congenital heart disease.

Advancing pediatric medical device development via non-dilutive NIH SBIR/STTR grant funding

IntroductionA shortage of medical devices designed for children persists due to the smaller pediatric population and market factors. Furthermore, pediatric device development is challenging due to the limited available funding sources. We describe our experience with pediatric device projects that successfully received federal grant support towards commercializing the devices that can serve as a guide for future innovators. MethodsThe developmental pathways of pediatric device projects at a tertiary-care children's hospital that received NIH SBIR/STTR funding between 2016–2019 were reviewed. The clinical problems, designs, specific aims, and development phase were delineated. ResultsPediatric faculty successfully secured NIH SBIR/STTR funding for five pediatric devices via qualified small business concerns (SBC's). Three projects were initiated in the capstone engineering design programs and developed further at two affiliated engineering schools, while the other two projects were developed in the faculty members’ labs. Four projects received funding via established SBC's, while one was awarded funding via a newly established SBC. ConclusionNIH SBIR/STTR grants are an essential source of external non-dilutive funding for pediatric device innovation and especially for academic-initiated projects. This funding can provide needed early-stage support to facilitate commercialization. In addition, these grants can serve as achievable accomplishments for pediatric faculty portfolios toward academic promotion. Our experience shows that it is possible to build a robust innovation ecosystem comprised of academic faculty (clinical/engineering) collaborating with local device development companies while jointly implementing a product development strategy leveraging NIH SBIR/STTR funding for critical translational research phases of pediatric device development.

Challenges and our efforts in the development of pediatric medical device

Challenges and our efforts in the development of pediatric medical device

Solving Unmet Needs With Innovative Pediatric Medical Devices.

In the last decade, only 24% of class III life-saving devices approved by the U.S. Food and Drug Administration (FDA) were for pediatric use-and most of those were for children over 12. Of these, less than 4% were labeled for pediatric patients ages 0-2 years old and the number of approved devices is even lower for neonatal patients. For these young patients, adult medical devices are often manipulated by pediatric specialists in order to provide stop-gap solutions. However, these repurposed devices are not always able to fulfill the unique needs of children's biology and growth patterns.

Comparison of supportive regulatory measures for pediatric medical device development in Japan and the United States

Further development of medical devices for children is required in Japan, but the development of such devices is delayed compared to that of medical devices for adults. Herein, we investigated policies for advancing the development of pediatric medical devices in Japan and the United States. Considering the achievements of each policy, we proposed a strategy to promote further development of pediatric medical devices in Japan. We investigated policies for supporting the development of pediatric medical devices and approved cases in Japan and the United States by searching contents of websites of regulatory bodies and other related administrations, and scientific papers. We found the main six policies in Japan and nine main policies in the United States for the development of pediatric medical devices. In the United States, various measures have initiated mainly in the 2000s, while in Japan, the main measures have been in place since 2013. Similarities were found in both countries, such as subsidies for application fees and research and development expenses, exemption of requirements for regulatory approval, and priority review and consultation by the regulatory body. Our study revealed that there are similarities in initiatives by both countries. To promote further development of pediatric medical devices in the future, improvements to expediting the review process to approval by the regulatory body, global development, and implementation of alternative measures to ensure the efficacy and safety of the device instead of large-scale clinical trials should be anticipated through cooperation among industry, government, and academia.

Innovation in Pediatric Medical Devices: Proceedings From The West Coast Consortium for Technology &amp; Innovation in Pediatrics 2019 Annual Stakeholder Summit

Pediatric medical devices cover a broad array of indications and risk profiles, and have helped to reduce disease burden and improve quality of life for numerous children. However, many of the devices used in pediatrics are not intended for or tested on children. Several barriers have been identified that pose difficulties in bringing pediatric medical devices to the market. These include a small market and small sample size; unique design considerations; regulatory complexities; lack of infrastructure for research, development, and evaluation; and low return on investment. In 2007, the Food and Drug Administration (FDA) created the Pediatric Device Consortia (PDC) Grants Program under the administration of the Office of Orphan Products Development. In 2018, the FDA awarded over US $30 million to five new PDCs. The West Coast Consortium for Technology &amp; Innovation in Pediatrics (CTIP) is one of these PDCs and is centered at the Children’s Hospital Los Angeles. In February 2019, CTIP convened its primary stakeholders to discuss its priorities and activities for the new grant cycle. In this paper, we have presented a report of the summit proceedings to raise awareness and advocate for patients and pediatric medical device innovators as well as to inform the activities and priorities of other organizations and agencies engaged in pediatric medical device development.