Digital Health Technology (DHT) in European Clinical Trials, How to Improve the Status-Quo of the Regulatory Landscape?

Digital health technology (DHT) is increasingly used to facilitate the conduct of clinical drug trials. The European regulatory environment would benefit from some adjustments to realize the full potential of DHTs. Considering current discussions such as the European Accelerating Clinical Trial Initiative (ACT EU), we propose four concrete adjustments to this regulatory landscape to introduce risk-based qualification approaches for DHTs. In our view, these changes would have the potential to facilitate the use of DHT in clinical research and thus provide access to innovative therapies in Europe.

Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients.

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4-10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium. Term control neonates (n = 21, 1 sample per patient) were included from the maternity ward. Phthalate and alternative plasticizers' metabolites were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Phthalate metabolites were detected in almost all urine samples. Metabolites of alternative plasticizers, di-(2-ethylhexyl)-adipate (DEHA), di-(2-ethylhexyl)-terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic-di-isononyl-ester (DINCH), had detection frequencies ranging 30-95 %. Urinary phthalate metabolite concentrations were significantly higher in premature compared to control neonates (p = 0.023). NICU exposure to respiratory support devices and blood products showed increased phthalate metabolite concentrations (p < 0.001). Phthalate exposure increased from birth until four weeks postnatally. The estimated phthalate intake exceeded animal-derived no-effect-levels (DNEL) in 10 % of samples, with maximum values reaching 24 times the DNEL. 29 % of premature neonates had at least once an estimated phthalate intake above the DNEL. Preterm neonates are still exposed to phthalates during NICU stay, despite the EU Medical Devices Regulation. NICU exposure to alternative plasticizers is increasing, though currently not regulated, with insufficient knowledge on their hazard profile.

Post-trial access to implantable neural devices: an exploratory international survey.

Objectives: Clinical trials of innovative neural implants are rapidly increasing and diversifying, but little is known about participants' post-trial access to the device and ongoing clinical care. This exploratory study examines common practices in the planning and coordination of post-trial access to neurosurgical devices. We also explore the perspectives of trial investigators on the barriers to post-trial access and ongoing care, as well as ethical questions related to the responsibilities of key stakeholder groups. Design setting and participants: Trial investigators (n=66) completed a survey on post-trial access in the most recent investigational trial of a surgically implanted neural device they had conducted. Survey respondents predominantly specialized in neurosurgery, neurology and psychiatry, with a mean of 14.8 years of experience working with implantable neural devices. Main outcome measures: Outcomes of interest included rates of device explantation during or at the conclusion of the trial (pre-follow-up) and whether plans for post-trial access were described in the study protocol. Outcomes also included investigators' greatest 'barrier' and 'facilitator' to providing research participants with post-trial access to functional implants and perspectives on current arrangements for the sharing of post-trial responsibilities among key stakeholders. Results: Trial investigators reported either 'all' (64%) or 'most' (33%) trial participants had remained implanted after the end of the trial, with 'infection' and 'non-response' the most common reasons for explantation. When asked to describe the main barriers to facilitating post-trial access, investigators described limited funding, scarcity of expertise and specialist clinical infrastructure and difficulties maintaining stakeholder relationships. Notwithstanding these barriers, investigators overwhelmingly (95%) agreed there is an ethical obligation to provide post-trial access when participants individually benefit during the trial. Conclusions: On occasions when devices were explanted during or at the end of the trial, this was done out of concern for the safety and well-being of participants. Further research into common practices in the post-trial phase is needed and essential to ethical and pragmatic discussions regarding stakeholder responsibilities.

Do medical devices contribute to sustainability? The role of innovative polymers and device design.

Sustainability of a medical device has not yet become a major issue in public discussions compared to other topics with impact to material performance, clinical application, production economy and environmental pollution. Due to their unique properties, polymers (plastics) allow for multiple, flexible applications in medical device technology. Polymers are part of the majority of disposable and single use medical device and contribute with 3% to the worldwide production of plastics. The global medical polymer market size was valued 19.9 billion US-$ in 2022 and its value projection for 2023 is expected to reach 43.03 billion US-$ Here, a wider concept of related sustainability is introduced for medical devices and their polymer components. A close look on medical device specification reveals that additional properties are required to provide sustainability, such as biodegradability, quality by device design (QbD), as well as an inbuild performance service for patients, healthcare professionals and healthcare providers. The increasing global numbers for chronic and non-communicable diseases require a huge demand for single use medical devices. A careful look at polymer specification and its performance properties is needed, including possible chemical modifications and degradation processes during waste disposal. Bioengineers in charge of design and production of medical devices will only be successful when they apply a holistic and interdisciplinary approach to medical device sustainability.

Do medical devices contribute to sustainability? Environmental, societal and governance aspects.

Sustainability of a product or device is currently primarily related to its environmental footprint. Here, a wider concept of sustainability is introduced for medical devices and their components in healthcare provision. Such devices sustain healthcare and patient wellbeing due to their quality specifications for material composition, product design and performance. The term quality must be intended in the most comprehensive term, including purity and biocompatibility of materials, device reliability, limited number of recalls and reduced risks as well as acceptability for patients. A close look on medical device specification shows, however, that additional parameters, such as societal, demographic and economic factors also determine medical device sustainability. The medical device life cycle, from design phase, production process to clinical application and the final disposal, also determines its impact. Recommendations for healthcare operators and managers will complete the hypothesis of this paper, that a thoroughly outlined device choice and operation together with a careful waste management of spent medical devices and their components positively affects medical device sustainability. As an example, the limited quantity of wastes and the reduced risks for adverse reaction have a positive impact on both the environmental pollution and on the costs sustained by the healthcare organisations and by the community. These factors determine both, the success of healthcare manoeuvres and the related environmental footprint.

A numerical analysis of ventilation motion after chest surgery with a RESPIRholter device.

This case report presents a numerical evaluation of respiration in terms of biomechanical parameters of chest motion. This experimental evaluation is performed with RESPIRholter, a wearable device specifically developed to monitor the movement in the ribcage through the motion of the sixth rib whose characteristic motion is considered as representative of the motion of the thorax. Here we present test results acquired with a RESPIRholter device in a 6-h acquisition. These results characterize respiration biomechanics for diagnostic purposes in a chest surgery patient, highlighting the diagnostic utility of RESPIRholter in the identification of post-operation respiratory problem.

Connaissances et pratiques des étapes préalables à la stérilisation des dispositifs médicaux thermorésistants : Etude au Centre Hospitalo-Universitaire Sahloul, Sousse-Tunisie - 2022.

OBJECTIVES: The standard process of central sterilization is crucial for the optimal functioning of the operating room. The outcome of this process is closely linked to the steps preceding the steps prior to the sterilization step itself. These steps include pre-disinfection carried out in the operating rooms and other stages, namely washing, drying and packaging, which must be performed in the central sterilization unit. In this context, this study aimed to describe the knowledge of the staff in the operating rooms and the central sterilization unit at Sahloul University Hospital in Sousse (Tunisia) in 2022, regarding the steps prior to the sterilization of reusable thermoresistant medical devices and to describe their practices in terms of compliance with these steps. METHOD: A descriptive study was conducted from January 2022 to June 2022 with the aforementioned staff, using a self-administered questionnaire to assess their knowledge of the pre-sterilization steps and a direct observation audit of their practices with regard to these steps. Both measurement instruments were pre-tested. RESULTS: Out of 102 self-administered questionnaires (knowledge assessment) distributed to the staff concerned, only 80 were returned and correctly filled out, giving a response rate of 78.4%. Participants' responses regarding the order of steps prior to the sterilization were incorrect in 64% of cases. With regard to the evaluation of professional practices, 224 observations were made in the study area (practice audit). In 82% of these observations, the pre-disinfection step was confused with the washing step. The use of Betadine brushes and scrubbing pads for device washing was noted in 89.3%, along with the absence of swabbing of the canals and hollow parts in 9.4% of cases and the absence of drying of the canals with compressed air. CONCLUSION: Mastery of the steps prior to sterilisation of reusable thermoresistant medical devices was insufficient in our institution, suggesting the importance of reinforcing the implementation of the procedure through a continuous training program followed by action plans.

Participatory methods used in the evaluation of medical devices: a comparison of focus groups, interviews, and a survey.

BACKGROUND: Stakeholder engagement in evaluation of medical devices is crucial for aligning devices with stakeholders' views, needs, and values. Methods for these engagements have however not been compared to analyse their relative merits for medical device evaluation. Therefore, we systematically compared these three methods in terms of themes, interaction, and time-investment. METHODS: We compared focus groups, interviews, and an online survey in a case-study on minimally invasive endoscopy-guided surgery for patients with intracerebral haemorrhage. The focus groups and interviews featured two rounds, one explorative focussing on individual perspectives, and one interactive focussing on the exchange of perspectives between participants. The comparison between methods was made in terms of number and content of themes, how participants interact, and hours invested by all researchers. RESULTS: The focus groups generated 34 themes, the interviews 58, and the survey 42. Various improvements for the assessment of the surgical procedure were only discussed in the interviews. In focus groups, participants were inclined to emphasise agreement and support, whereas the interviews consisted of questions and answers. The total time investment for researchers of focus groups was 95 h, of interviews 315 h, and survey 81 h. CONCLUSIONS: Within the context of medical device evaluation, interviews appeared to be the most appropriate method for understanding stakeholder views since they provide a scope and depth of information that is not generated by other methods. Focus groups were useful to rapidly bring views together. Surveys enabled a quick exploration. Researchers should account for these methodological differences and select the method that is suitable for their research aim.

Is read-across for chemicals comparable to medical device equivalence and where to use it for conformity assessment?

Novel medical devices must conform to medical device regulation (MDR) for European market entry. Likewise, chemicals must comply with the Registration, Evaluation, Authorization and Restriction of Chemicals (REACh) regulation. Both pose regulatory challenges for manufacturers, but concordantly provide an approach for transferring data from an already registered device or compound to the one undergoing accreditation. This is called equivalence for medical devices and read-across for chemicals. Although read-across is not explicitly prohibited in the process of medical device accreditation, it is usually not performed due to a lack of guidance and acceptance criteria from the authorities. Nonetheless, a scientifically justified read-across of material-based endpoints, as well as toxicological assessment of chemical aspects, such as extractables and leachables, can prevent failure of MDR device equivalence if data is lacking. Further, read-across, if applied correctly can facilitate the standard MDR conformity assessment. The need for read-across within medical device registration should let authorities to reconsider device accreditation and the formulation of respective guidance documents. Acceptance criteria like in the European Chemicals Agency (ECHA) read-across assessment framework (RAAF) are needed. This can reduce the impact of the MDR and help with keeping high European innovation device rate, beneficial for medical device patients.

Implementation of the classification of medical devices of Ukraine in international approaches.

OBJECTIVE: Aim: To study the level of compliance of the National Classifier of Ukraine ≪Classifier of Medical Devices of Ukraine NC 024: 2023≫ with international approaches to the classification and use of medical devices. PATIENTS AND METHODS: Materials and Methods: National Classifier of Ukraine ≪Classifier of Medical Devices of Ukraine NC 024: 2023≫ and the international nomenclature of medical devices Global Medical Device Nomenclature. Methods: bibliosemantic, of content analysis and of structural-and-logical analysis. CONCLUSION: Conclusions: In the course of the study, full compliance of the national classifier of medical devices of Ukraine NC 024: 2023 with the GMDN system was established.

Transcatheter Mitral Valve Repair Using a Novel Device for a High-Surgical-Risk Patient With DMR.

Transcatheter edge-to-edge repair (TEER) has been established as a safe and effective option for treating patients with severe symptomatic degenerative mitral regurgitation (MR) who are at prohibitive surgical risk. However, the significant cost presents a considerable disease burden in low-income countries. This case details the treatment of a high-surgical-risk patient with severe degenerative MR by using the GeminiOne (Peijia Medical) system-a novel Chinese TEER device.

Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies.

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural interfaces, along with the integration of biocompatible and reliable materials and compliance with biomedical regulations for translational applications. Preclinical validation is foundational to the translational process, and we will discuss the critical aspects of such animal studies. Finally, we will focus on the patient point-of-care and challenges in neuromodulation as the ultimate goal of bioelectronic medicine. This review is a call to scientists from different fields to work together with a common endeavor: accelerate the decoding and modulation of the nervous system in a new era of therapeutic possibilities.

Research on product design of FAHP bone marrow aspiration needle.

Bone marrow aspiration is a crucial medical procedure to obtain bone marrow samples for diagnosis and treatment. However, traditional bone marrow aspiration needles face several challenges such as operational difficulties, inadequate sample acquisition, and patient discomfort. To address these issues, we aimed to design a bone marrow aspiration needle product by using fuzzy analytic hierarchical process (FAHP). The FAHP method was used to identify key factors in the design of the bone marrow aspiration needle, including technicality, usage, and application characteristics. The importance weights and priorities of each factor were determined through questionnaires and interviews with experts. A new bone marrow aspiration needle product was developed based on the results of the FAHP. The new product design considers the weights and priorities assigned to key factors, resulting in improved convenience during operation and a higher success rate of sample acquisition. This was achieved by optimising the structure and material selection of the needle. This study presents a novel bone marrow puncture needle product that effectively integrates the importance and priority of the key factors. It successfully enhances operational performance and patient experience, thereby offering an innovative solution to improve the success rate and therapeutic effect of bone marrow punctures.

Analysis of preservatives and fragrances in topical medical devices: The need for more stringent regulation.

INTRODUCTION: Medical devices (MDs) have a long history of use, and come with regulatory frameworks to ensure user safety. Although topically applied MDs in the form of gels and creams might be used on damaged skin, their composition is often similar to that of cosmetic products applicable to intact skin, especially in terms of preservatives and fragrances. However, unlike cosmetics, these products are not subject to compound-specific restrictions when used in MDs. OBJECTIVE: This study aimed to identify and quantify preservatives and fragrances in topically applied MDs and assess their safety towards the Cosmetic Regulation (EC) 1223/2009. METHOD: Sixty-nine MDs available on the EU market were subjected to previously validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) methods to identify and quantify occurring preservatives and fragrances. RESULTS: Findings revealed that 32% of the examined MDs did not provide comprehensive ingredient lists, leaving users uninformed about potential risks associated with product use. Furthermore, 30% of these MDs would not meet safety standards for cosmetic products and, most significantly, 13% of the analysed samples contained ingredients that are prohibited in leave-on cosmetics. CONCLUSION: Results highlight the pressing demand for more stringent requirements regarding the labelling and composition of MDs to enhance patient safety. Improved regulation and transparency can mitigate potential risks associated with the use of topically applied MDs.

Artificial intelligence for ultrasound scanning in regional anaesthesia: a scoping review of the evidence from multiple disciplines.

BACKGROUND: Artificial intelligence (AI) for ultrasound scanning in regional anaesthesia is a rapidly developing interdisciplinary field. There is a risk that work could be undertaken in parallel by different elements of the community but with a lack of knowledge transfer between disciplines, leading to repetition and diverging methodologies. This scoping review aimed to identify and map the available literature on the accuracy and utility of AI systems for ultrasound scanning in regional anaesthesia. METHODS: A literature search was conducted using Medline, Embase, CINAHL, IEEE Xplore, and ACM Digital Library. Clinical trial registries, a registry of doctoral theses, regulatory authority databases, and websites of learned societies in the field were searched. Online commercial sources were also reviewed. RESULTS: In total, 13,014 sources were identified; 116 were included for full-text review. A marked change in AI techniques was noted in 2016-17, from which point on the predominant technique used was deep learning. Methods of evaluating accuracy are variable, meaning it is impossible to compare the performance of one model with another. Evaluations of utility are more comparable, but predominantly gained from the simulation setting with limited clinical data on efficacy or safety. Study methodology and reporting lack standardisation. CONCLUSIONS: There is a lack of structure to the evaluation of accuracy and utility of AI for ultrasound scanning in regional anaesthesia, which hinders rigorous appraisal and clinical uptake. A framework for consistent evaluation is needed to inform model evaluation, allow comparison between approaches/models, and facilitate appropriate clinical adoption.

The performance of 11 fingertip pulse oximeters during hypoxemia in healthy human participants with varied, quantified skin pigment.

BACKGROUND: Fingertip pulse oximeters are widely available, inexpensive, and commonly used to make clinical decisions in many settings. Device performance is largely unregulated and poorly characterised, especially in people with dark skin pigmentation. METHODS: Eleven popular fingertip pulse oximeters were evaluated using the US Food and Drug Administration (FDA) Guidance (2013) and International Organization for Standardization Standards (ISO, 2017) in 34 healthy humans with diverse skin pigmentation utilising a controlled desaturation study with arterial oxygen saturation (SaO 2) plateaus between 70% and 100%. Skin pigmentation was assessed subjectively using a perceived Fitzpatrick Scale (pFP) and objectively using the individual typology angle (ITA) via spectrophotometry at nine anatomical sites. FINDINGS: Five of 11 devices had a root mean square error (ARMS) > 3%, falling outside the acceptable FDA performance range. Nine devices demonstrated worse performance in participants in the darkest skin pigmentation category compared with those in the lightest category. A commonly used subjective skin colour scale frequently miscategorised participants as being darkly pigmented when compared to objective quantification of skin pigment by ITA. INTERPRETATION: Fingertip pulse oximeters have variable performance, frequently not meeting regulatory requirements for clinical use, and occasionally contradicting claims made by manufacturers. Most devices showed a trend toward worse performance in participants with darker skin pigment. Regulatory standards do not adequately account for the impact of skin pigmentation on device performance. We recommend that the pFP and other non-standardised subjective skin colour scales should no longer be used for defining diversity of skin pigmentation. Reliable methods for characterising skin pigmentation to improve diversity and equitable performance of pulse oximeters are needed. FUNDING: This study was conducted as part of the Open Oximetry Project funded by the Gordon and Betty Moore Foundation, Patrick J McGovern Foundation, and Robert Wood Johnson Foundation. The UCSF Hypoxia Research Laboratory receives funding from multiple industry sponsors to test the sponsors' devices for the purposes of product development and regulatory performance testing. Data in this paper do not include sponsor's study devices. All data were collected from devices procured by the Hypoxia Research Laboratory for the purposes of independent research. No company provided any direct funding for this study, participated in study design or analysis, or was involved in analysing data or writing the manuscript. None of the authors own stock or equity interests in any pulse oximeter companies. Dr Ellis Monk's time utilised for data analysis, reviewing and editing was funded by grant number: DP2MH132941.

Criteria to define innovation in the field of medical devices: a Delphi approach.

Defining innovation in the field of medical devices can be extremely challenging due to the peculiarity of the products within this class. Short life-cycle, incrementality, learning curve effect, impact of the organizational setting, uncertainty of effect and level of evidence are only some of these aspects. A clear set of criteria to define innovation would be of paramount relevance in this field. Twelve criteria to define innovation were proposed to a multistakeholder panel within a consensus process. A Delphi method on two rounds was used to reach consensus. In total, 53 of the 93 (47%) invited panelists responded to the first round of the survey. Among them, 51 (96%) completed also the second round. At the first round, consensus was reached for four of the 12 proposed criteria. Three of the remaining eight criteria reached consensus at the second round. It was not possible to reach consensus for the remaining five criteria. The criteria that collected the highest scores (close to 100%) were from the clinical impact domain, namely the ability of the technology to offer significant advantages over existing alternatives in terms of improving relevant clinical outcomes, and the ability to address an unmet need defined in terms of unavailability of diagnosis/treatment alternatives. High levels of consensus (about 80%) were registered on criteria belonging to non-clinical domains of analysis and, in particular, the ability of the technology to introduce organizational benefits, and the ability of the technology to bring cost reduction providing the same clinical benefit of current alternatives.

Adverse events associated with anastomotic coupling devices in microvascular reconstruction.

OBJECTIVE: In light of the recent US Food and Drug Administration (FDA) Class 2 safety recall notice for anastomotic coupling devices, it is important to understand related adverse events. The aim of this study was to characterize adverse events in anastomotic coupling devices for microvascular reconstruction. METHODS: A retrospective cross-sectional analysis using the 2011 to 2021 US FDA Manufacturer and User Facility Device Experience (MAUDE) database. All reports of adverse events involving anastomotic coupling devices were retrieved from the MAUDE database. Descriptive statistics were used to analyze categorized events. RESULTS: There were a total of 293 documented adverse events related to anastomotic coupling devices. These adverse events resulted in 91 (31.1 %) patient injuries and 239 (81.6 %) device malfunctions. The most frequent patient problems were thrombosis/hematoma (n = 38; 41.8 %), unspecified injury (n = 31; 34.1 %), and failure to anastomose (n = 13; 14.3 %). Free flap necrosis was reported in 42 % of thrombosis/hematoma cases (n = 16). The most common malfunctions were devices operating differently than expected (n = 74; 31.0 %), connection problems (n = 41; 17.2 %), and twisted/bent material (n = 19; 7.9 %). There was no significant trend in the number of adverse events over the study period (p > 0.05). CONCLUSIONS: Adverse events from anastomotic coupling devices represent an important and modifiable factor in free tissue failure. Adverse events are predominately related to devices operating differently than expected and may result in vascular compromise of the free flap. Reconstructive surgeons should be cognizant of defective anastomotic coupling devices and be prepared to utilize traditional hand-sewn anastomosis.