Determination of pressure dependent gas properties by MEMS-structures for vacuum measurement applications

In der Vakuumtechnik müssen unterschiedliche Messverfahren eingesetzt werden, um den Druck in einem großen Druckbereich zu bestimmen, womit Bedarf sowohl an einer Messbereichserweiterung, als auch an einer Reduzierung der Gasartabhängigkeit der einzelnen Verfahren besteht. Da MEMS-basierte Sensorelemente zudem in weiteren Anwendungsbereichen eingesetzt werden könnten, wurden für die gängigsten Messverfahren die Auswirkungen einer Miniaturisierung theoretisch untersucht. Aus einem vereinfachten eindimensionalen Modell der druckabhängigen Wärmeleitfähigkeit eines Gases konnte analytisch abgeleitet werden, dass die Sensitivität eines Wärmetransport-Vakuummeters von der Oberfläche des beheizten Filaments und dessen Abstand zur Wärmesenke abhängt, und nicht von den parasitären Wärmeverlusten. Diese Vorhersagen konnten an Sensorelementen mit Filamentoberflächen von 0,3mm² bis 0,8mm² und einer bzw. zwei Wärmesenken im Abstand von 150µm, welche mittels Si-Bulk-Mikrotechnologie realisiert wurden, bestätigt werden. Im Konstant-Temperatur-Betriebsmodus umfasste der auflösbare, druckempfindliche Bereich bis zu acht Dekaden von 1e-5 mbar bis 1e3 mbar. Die Grundlage für ein miniaturisiertes Ionisations-Vakuummeter ist eine kalte Elektronenquelle, welche die durch Glühkathoden verursachten thermischen Störeffekte reduzieren würde. Als Basis hierfür wurden durch Kombination von Trockenätzung und thermischer Oxidation Feldemitter aus Si mit Verrundungsradien von etwa 20nm und Höhen von 1,1µm bis 2,5µm realisiert. Die Emitterfelder wiesen eine große Anzahl an funktionsfähigen Emittern (>90%), eine homogene Verteilung der Einsatzspannungen (Standardabweichung ~25%) und geringe Stromschwankungen (<1,5%) beim Betrieb im für p-dotierte Si-Emitter typischen Sättigungsbereich auf. Basierend auf einem System aus zwei Vakuummetern mit sich überlappenden Messbereichen, wobei einer der Messwerte gasartunabhängig ist, wurde ein Verfahren entwickelt, das es ermöglicht, Wärmetransport-Vakuummeter während der Messung softwaregestützt zu kalibrieren und somit die Gasartabhängigkeit von bis zu 50% im Bereich von 1e-3 mbar bis 10 mbar auf unter 10% zu reduzieren.In vacuum technology different measurement principles are necessary to determine pressure in a large pressure regime. Hence, an enlargement of the measuring range as well as a reduction of the gas-species dependency of the particular principles is needed. Due to the additional application areas of MEMS-based sensing elements, the effects of miniaturization on the most established principles were theoretically studied. From a simplified one-dimensional model for the pressure dependent thermal conductivity of a gas was analytically derived that the sensitivity of thermal conductivity vacuum gauges is dependent on the surface of the heated filament and its distance to the heat sink, but not to the parasitic heat losses. These predictions were experimentally proven with sensor elements with filament surfaces ranging from 0.3mm² to 0.8mm² facing one or two heat sinks in a distance of 150µm. These chips, which were fabricated by silicon technology, showed in a constant temperature operating mode a sensitivity on pressure that was detectable within up to eight orders of magnitude in a range from 1e-5 mbar to 1e3 mbar. The basic structure for a miniaturized ionization gauge is a cold electron source that reduces thermal perturbation effects caused by the conventional thermionic cathode. Therefore Si-based field emission cathodes with apex radii of about 20nm and heights of 1.1µm to 2.5µm were realized by a combination of reactive ion etching and thermal oxidation. The emitter arrays showed a high number of working emitters (>90%), a homogeneous distribution of the turn-on voltages (standard deviation ~25%) and low current fluctuations (<1.5%) when operated in a saturation regime that is typical for p-doped silicon field emitter. Based on a system of two vacuum gauges with overlapping measurement ranges, a procedure was developed to calibrate a thermal conductivity gauge during the measurement on the signal of a gas-species independent gauge. By this automated calibration procedure the gas-species dependency of up to 50% in a pressure regime of 1e-3 mbar to 10 mbar was reduced to less than 10%

Do existing real-world data sources generate suitable evidence for the HTA of medical devices in Europe? Mapping and critical appraisal.

Aim Technological and computational advancements offer new tools for the collection and analysis of real-world data (RWD). Considering the substantial effort and resources devoted to collecting RWD, a greater return would be achieved if real-world evidence (RWE) was effectively used to support Health Technology Assessment (HTA) and decision making on medical technologies. A useful question is: To what extent are RWD suitable for generating RWE? Methods We mapped existing RWD sources in Europe for three case studies: hip and knee arthroplasty, transcatheter aortic valve implantation (TAVI) and mitral valve repair (TMVR), and robotic surgery procedures. We provided a comprehensive assessment of their content and appropriateness for conducting the HTA of medical devices. The identification of RWD sources was performed combining a systematic search on PubMed with gray literature scoping, covering fifteen European countries. Results We identified seventy-one RWD sources on arthroplasties; ninety-five on TAVI and TMVR; and seventy-seven on robotic procedures. The number, content, and integrity of the sources varied dramatically across countries. Most sources included at least one health outcome (97.5%), with mortality and rehospitalization/reoperation the most common; 80% of sources included resource outcomes, with length of stay the most common, and comparators were available in almost 70% of sources. Conclusions RWD sources bear the potential for the HTA of medical devices. The main challenges are data accessibility, a lack of standardization of health and economic outcomes, and inadequate comparators. These findings are crucial to enabling the incorporation of RWD into decision making and represent a readily available tool for getting acquainted with existing information sources

Regulatory and HTA early dialogues in medical devices

Abstract Introduction: Specific guidance and examples for health technology assessment (HTA) of medical devices are scarce in medical device development. A more intense dialogue of competent authorities, HTA agencies, and manufactures may improve evidence base on clinical and cost-effectiveness. Especially as the new Medical Device Regulation requires more clinical evidence. Methods: We explore the perceptions of manufacturers, competent authorities, and HTA agencies towards such dialogues and investigate how they should be designed to accelerate the translational process from development to patient access using semi-structured interviews. We synthesized the evidence from manufacturers, competent authorities, and HTA agencies from 14 different jurisdictions across Europe. Results: Eleven HTA agencies, four competent authorities, and eight manufacturers of high-risk devices expressed perceptions on the current situation and the expected development of three types of early dialogues. Discussion: The MDR has to be taken into account when designing the early dialogue processes. Transferring insights from medicinal product regulation is limited as the regulatory pathways differ substantially. Conclusion: Early dialogues promise to accelerate the translational process and to provide faster access to innovative medical devices. However, health policy-makers should promote and fully establish regulatory and HTA early dialogues before introducing parallel early dialogues of regulatory, HTA agencies, and manufacturers. For initiating change, the legislator must create the legal basis and set the appropriate incentives for manufacturers

Improvement of Homogeneity and Aspect Ratio of Silicon Tips for Field Emission by Reactive-Ion Etching

The homogeneity of emitters is very important for the performance of field emission (FE) devices. Reactive-ion etching (RIE) and oxidation have significant influences on the geometry of silicon tips. The RIE influences mainly the anisotropy of the emitters. Pressure has a strong impact on the anisotropic factor. Reducing the pressure results in a higher anisotropy, but the etch rate is also lower. A longer time of etching compensates this effect. Furthermore an improvement of homogeneity was observed. The impact of uprating is quite low for the anisotropic factor, but significant for the homogeneity. At low power the height and undercut of the emitters are more constant over the whole wafer. The oxidation itself is very homogeneous and has no observable effect on further variation of the homogeneity. This modified fabrication process allows solving the problem of inhomogeneity of previous field emission arrays

Relevance of barriers and facilitators in the use of health technology assessment in Colombia

Objectives: Several studies, mostly from developed countries, have identified barriers and facilitators with regard to the uptake of health technology assessment (HTA). This study elicited, using best-worst scaling (BWS), what HTA experts in Colombia consider to be the most important barriers and facilitators in the use of HTA, and makes a comparison to results from the Netherlands. Methods: Two object case surveys (one for barriers, one for facilitators) were conducted among 18 experts (policymakers, health professionals, PhD students, senior HTA-researchers) from Colombia. Seven respondents were employees of the national HTA agency Instituto de Evaluación Tecnológica de Salud (IETS). In total, 22 barriers and 19 facilitators were included. In each choice task, participants were asked to choose the most and least important barrier/facilitator from a set of five. Hierarchical Bayes modeling was used to compute the mean relative importance scores (RIS) for each factor, and a subgroup analysis was conducted to assess differences between IETS and non-IETS respondents. The final ranking was further compared to the results from a similar study conducted in the Netherlands. Results: The three most important barriers (RIS >6.00) were “Inadequate presentation format”, “Absence of policy networks”, and “Insufficient legal support”. The six most important facilitators (RIS >6.00) were “Appropriate timing”, “Clear presentation format”, “Improving longstanding relation”, “Appropriate incentives”, “Sufficient qualified human resources”, and “Availability to relevant HTA research”. The perceived relevance of the barriers and facilitators differed slightly between IETS and non-IETS employees, while the differences between the rankings in Colombia and the Netherlands were substantial. Conclusion: The study suggests that barriers and facilitators related to technical aspects of processing HTA reports and to the contact and interaction between researchers and policymakers had the greatest importance in Colombia

Surrogate endpoints in health technology assessment: an international review of methodological guidelines

Decision uncertainty associated with reliance on surrogate endpoints is a risk to patients and society. HTA agencies may develop more detailed methodological guidance for consistent selection and evaluation of health technologies without definitive final patient-relevant outcome evidence at the time of the assessment

Bridging big data: procedures for combining non-equivalent cognitive measures from the ENIGMA Consortium

Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences