Regulation of risk management of medical devices and the role of litigation

Patient health often depends on medical devices and implants. Thanks to these advancements, trust in and expectations of medical technology are high. But history shows critical device failures of heart valves, breast implants, hip prostheses and heart stimulators occurring under the regulatory system for such devices which certifies their efficacy and safety similar to the drug regulation process. Thus, questions remain regarding the effectiveness of the regulatory system to minimize risk. Differences between device regulation in Europe and the USA are shown, basically entailing that Europeans have quicker access to new technology but at the price of greater risk of harm. Given the investments to develop new devices and implants and the assumed thoroughness of the regulatory system, a certified device in Europe is considered safe and meeting the state-of-the-art standards of technology. Therefore, passing successfully the road map to certification, the certificate exempts the manufacturer of liability in case the device fails. Recently, it was revealed that regulation may fail due to underestimation of risks when used in patients, mainly due to lack of impartial and effective knowledge on the part of experts involved in the certification process. Conflicts of interest of experts and clinical investigators may also result in unacceptable exposure of patients to risk of device failure. Trust and good faith still play an important role in order to make a justified risk-benefit balance and to accept 'earn as you learn' as a leading principle. The past shows that thanks to litigation and class actions, legislation can be adjusted and compliance with regulations realized. The complexity of the system and restriction of patients' rights to be compensated for harm due to risky exposure to unproven but certified technology makes criminal and civil litigation still indispensibl

The Impact of Biomedical Engineering on the Development of Minimally Invasive Cardio-Thoracic Surgery

(1) We describe the boundary conditions for minimally invasive cardiac surgery (MICS) with the aim to reduce procedure-related patient injury and discomfort. (2) The analysis of the MICS work process and its demand for improved tools and devices is followed by a description of the relevant sub-specialties of bio-medical engineering: electronics, biomechanics, and materials sciences. (3) Innovations can represent a desired adaptation of an existing work process or a radical redesign of procedure and devices such as in transcutaneous procedures. Focused interaction between engineers, industry, and surgeons is always mandatory (i.e., a therapeutic alliance for addressing ‘unmet patient or professional needs’. (4) Novel techniques in MICS lean heavily on usability and safe and effective use in dedicated hands. Therefore, the use of training and simulation models should enable skills selection, a safe learning curve, and maintenance of proficiency. (5) The critical technical steps and cost–benefit trade-offs during the journey from invention to application will be explained. Business considerations such as time-to-market and returns on investment do shape the cost–benefit room for commercial use of technology. Proof of clinical safety and effectiveness by physicians remains important, but establishing the technical reliability of MICS tools and warranting appropriate surgical skills come first

Effect of Oxygenator Size on Air Removal Characteristics: A Clinical Evaluation

During cardiopulmonary bypass (CPB), gaseous microemboli (GME) are released into the patients' arterial bloodstream. Gaseous microemboli may contribute to the adverse outcome after cardiac surgery. Recently, two oxygenator models with or without integrated arterial filter (IAF) were designed and only differ in size, leading to a change of 20% in surface area of the hollow fibers and 25% in blood velocities. The aim of this study was to assess the air removal characteristics of the inspire oxygenators with or without IAF. Sixty-eight patients were randomly assigned to four different groups: optimized adult and full adult and an additional IAF. Gaseous microemboli reduction rates were measured with a bubble counter. The number of GME reduction rates showed no differences. However, both models reduced significantly less volume of GME (optimized adult: 40.6% and full adult: 50.3%) compared with both models with IAF (88.7% and 88.5%, respectively). No significant differences of reduction rates were found between both devices without IAF and also not between both models with IAF. In conclusion, the larger inspire oxygenator tends to remove more GME. No effect from size of oxygenator device with integrated screen filter on GME reduction was observed. The inspire oxygenators with IAF may be considered as an adequate GME filte

Clinical evaluation of the air-handling properties of contemporary oxygenators with integrated arterial filter

Gaseous microemboli (GME) may originate from the extracorporeal circuit and enter the arterial circulation of the patient. GME are thought to contribute to cerebral deficit and to adverse outcome after cardiac surgery. The arterial filter is a specially designed component for removing both gaseous and solid microemboli. Integration of an arterial filter with an oxygenator is a contemporary concept, reducing both prime volume and foreign surface area. This study aims to determine the air-handling properties of four contemporary oxygenator devices with an integrated arterial filter. Two oxygenator devices, the Capiox FX25 and the Fusion, showed significant increased volume of GME reduction rates (95.03 +/- 3.13% and 95.74 +/- 2.69%, respectively) compared with both the Quadrox-IF (85.23 +/- 5.84%) and the Inspire 6F M (84.41 +/- 12.93%). Notably, both the Quadrox-IF and the Inspire 6F M as well as the Capiox FX 25 and the Fusion showed very similar characteristics in volume and number reduction rates and in detailed distribution properties. The Capiox FX25 and the Fusion devices showed significantly increased number and volume reduction rates compared with the Quadrox-IF and the Inspire 6F M devices. Despite the large differences in design of all four devices, our study results suggest that the oxygenator devices can be subdivided into two groups based on their fibre design, which results in screen filter (Quadrox-IF and Inspire 6F M) and depth filter (Capiox FX25 and Fusion) properties. Depth filter properties, as present in the Capiox FX25 and Fusion devices, reduced fractionation of air and may ameliorate GME remova

Carbon Dioxide Flush of an Integrated Minimized Perfusion Circuit Prior to Priming Prevents Spontaneous Air Release Into the Arterial Line During Clinical Use

Recently, an oxygenator with an integrated centrifugal blood pump (IP) was designed to minimize priming volume and to reduce blood foreign surface contact even further. The use of this oxygenator with or without integrated arterial filter was compared with a conventional oxygenator and nonintegrated centrifugal pump. To compare the air removal characteristics 60 patients undergoing coronary artery bypass grafting were alternately assigned into one of three groups to be perfused with a minimized extracorporeal circuit either with the conventional oxygenator, the oxygenator with IP, or the oxygenator with IP plus integrated arterial filter (IAF). Air entering and leaving the three devices was measured accurately with a bubble counter during cardiopulmonary bypass. No significant differences between all groups were detected, considering air entering the devices. Our major finding was that in both integrated devices groups incidental spontaneous release of air into the arterial line in approximately 40% of the patients was observed. Here, detectable bolus air (>500 µm) was shown in the arterial line, whereas in the minimal extracorporeal circulation circuit (MECC) group this phenomenon was not present. We decided to conduct an amendment of the initial design with METC-approval. Ten patients were assigned to be perfused with an oxygenator with IP and IAF. Importantly, the integrated perfusion systems used in these patients were flushed with carbon dioxide (CO2 ) prior to priming of the systems. In the group with CO2 flush no spontaneous air release was observed in all cases and this was significantly different from the initial study with the group with the integrated device and IAF. This suggests that air spilling may be caused by residual air in the integrated device. In conclusion, integration of a blood pump may cause spontaneous release of large air bubbles (>500 µm) into the arterial line, despite the presence of an integrated arterial filter. CO2 flushing of an integrated cardiopulmonary bypass system prior to priming may prevent spontaneous air release and is strongly recommended to secure patient safet

Optical verification and in-vitro characterization of two commercially available acoustic bubble counters for cardiopulmonary bypass systems

Gaseous microemboli (GME) introduced during cardiac surgery are considered as a potential source of morbidity, which has driven the development of the first bubble counters. Two new generation bubble counters, introduced in the early 2000s, claim correct sizing and counting of GME. This in-vitro study aims to validate the accuracy of two bubble counters using monodisperse bubbles in a highly controlled setting at low GME concentrations. Monodisperse GME with a radius of 43 µm were produced in a microfluidic chip. Directly after their formation, they were injected one-by-one into the BCC200 and the EDAC sensors. GME size and count, measured with the bubble counters, were optically verified using high-speed imaging. During best-case scenarios or low GME concentrations of GME with a size of 43 µm in radius in an in-vitro setup, the BCC200 overestimates GME size by a factor of 2 to 3 while the EDAC underestimates the average GME size by at least a factor of two. The BCC200 overestimates the GME concentration by approximately 20% while the EDAC overestimates the concentration by nearly one order of magnitude. Nevertheless, the calculated total GME volume is only over-predicted by a factor 2 since the EDAC underestimates the actual GME size. For the BCC200, the total GME volume was over-predicted by 25 times due to the over-estimation of GME size. The measured errors in the absolute sizing/counting of GME do not imply that all results obtained using the bubble counters are insignificant or invalid. A relative change in bubble size or bubble concentration can accurately be measured. However, care must be taken in the interpretation of the results and their absolute values. Moreover, the devices cannot be used interchangeably when reporting GME activity. Nevertheless, both devices can be used to study the relative air removal characteristics of CPB components or for the quantitative monitoring of GME production during CPB intervention

Sparse Graphical Vector Autoregression: A Bayesian Approach

In high-dimensional vector autoregressive (VAR) models, it is natural to have large number of predictors relative to the observations, and model selection is often a difficult issue. In this paper, we propose a model selection approach to multivariate time series of large dimension by combining graph-based notion of causality with the concept of sparsity on the structure of dependence among the variables. In particular, we build on the application of fan-in restriction for graphical models by proposing a sparsity-inducing prior distribution that allows for different prior information level about the maximal number of predictors for each equation of a VAR model. We discuss the joint inference of the temporal dependence in the observed series and the maximum lag order of the process, with the parameter estimation of the model. The applied contribution focuses on modeling and forecasting selected macroeconomic and financial time series with many predictors. Our result shows a gain in predictive performance using our sparse graphical VAR