Evidence-based Development of Trustworthy Mobile Medical Apps

abstract: Widespread adoption of smartphone based Mobile Medical Apps (MMAs) is opening new avenues for innovation, bringing MMAs to the forefront of low cost healthcare delivery. These apps often control human physiology and work on sensitive data. Thus it is necessary to have evidences of their trustworthiness i.e. maintaining privacy of health data, long term operation of wearable sensors and ensuring no harm to the user before actual marketing. Traditionally, clinical studies are used to validate the trustworthiness of medical systems. However, they can take long time and could potentially harm the user. Such evidences can be generated using simulations and mathematical analysis. These methods involve estimating the MMA interactions with human physiology. However, the nonlinear nature of human physiology makes the estimation challenging. This research analyzes and develops MMA software while considering its interactions with human physiology to assure trustworthiness. A novel app development methodology is used to objectively evaluate trustworthiness of a MMA by generating evidences using automatic techniques. It involves developing the Health-Dev β tool to generate a) evidences of trustworthiness of MMAs and b) requirements assured code generation for vulnerable components of the MMA without hindering the app development process. In this method, all requests from MMAs pass through a trustworthy entity, Trustworthy Data Manager which checks if the app request satisfies the MMA requirements. This method is intended to expedite the design to marketing process of MMAs. The objectives of this research is to develop models, tools and theory for evidence generation and can be divided into the following themes: • Sustainable design configuration estimation of MMAs: Developing an optimization framework which can generate sustainable and safe sensor configuration while considering interactions of the MMA with the environment. • Evidence generation using simulation and formal methods: Developing models and tools to verify safety properties of the MMA design to ensure no harm to the human physiology. • Automatic code generation for MMAs: Investigating methods for automatically • Performance analysis of trustworthy data manager: Evaluating response time generating trustworthy software for vulnerable components of a MMA and evidences.performance of trustworthy data manager under interactions from non-MMA smartphone apps.Dissertation/ThesisDoctoral Dissertation Computer Science 201

KnowSafe: Combined Knowledge and Data Driven Hazard Mitigation in Artificial Pancreas Systems

Significant progress has been made in anomaly detection and run-time monitoring to improve the safety and security of cyber-physical systems (CPS). However, less attention has been paid to hazard mitigation. This paper proposes a combined knowledge and data driven approach, KnowSafe, for the design of safety engines that can predict and mitigate safety hazards resulting from safety-critical malicious attacks or accidental faults targeting a CPS controller. We integrate domain-specific knowledge of safety constraints and context-specific mitigation actions with machine learning (ML) techniques to estimate system trajectories in the far and near future, infer potential hazards, and generate optimal corrective actions to keep the system safe. Experimental evaluation on two realistic closed-loop testbeds for artificial pancreas systems (APS) and a real-world clinical trial dataset for diabetes treatment demonstrates that KnowSafe outperforms the state-of-the-art by achieving higher accuracy in predicting system state trajectories and potential hazards, a low false positive rate, and no false negatives. It also maintains the safe operation of the simulated APS despite faults or attacks without introducing any new hazards, with a hazard mitigation success rate of 92.8%, which is at least 76% higher than solely rule-based (50.9%) and data-driven (52.7%) methods.Comment: 16 pages, 10 figures, 9 tables, submitted to the IEEE for possible publicatio

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 130, July 1974

This special bibliography lists 291 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1974

In silico assessment of biomedical products: the conundrum of rare but not so rare events in two case studies

In silico clinical trials, defined as “The use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention,” have been proposed as a possible strategy to reduce the regulatory costs of innovation and the time to market for biomedical products. We review some of the the literature on this topic, focusing in particular on those applications where the current practice is recognized as inadequate, as for example, the detection of unexpected severe adverse events too rare to be detected in a clinical trial, but still likely enough to be of concern. We then describe with more details two case studies, two successful applications of in silico clinical trial approaches, one relative to the University of Virginia/Padova simulator that the Food and Drug Administration has accepted as possible replacement for animal testing in the preclinical assessment of artificial pancreas technologies, and the second, an investigation of the probability of cardiac lead fracture, where a Bayesian network was used to combine in vivo and in silico observations, suggesting a whole new strategy of in silico-augmented clinical trials, to be used to increase the numerosity where recruitment is impossible, or to explore patients’ phenotypes that are unlikely to appear in the trial cohort, but are still frequent enough to be of concern

Combining Machine Learning and Formal Methods for Complex Systems Design

During the last 20 years, model-based design has become a standard practice in many fields such as automotive, aerospace engineering, systems and synthetic biology. This approach allows a considerable improvement of the final product quality and reduces the overall prototyping costs. In these contexts, formal methods, such as temporal logics, and model checking approaches have been successfully applied. They allow a precise description and automatic verification of the prototype's requirements. In the recent past, the increasing market requests for performing and safer devices shows an unstoppable growth which inevitably brings to the creation of more and more complicated devices. The rise of cyber-physical systems, which are on their way to become massively pervasive, brings the complexity level to the next step and open many new challenges. First, the descriptive power of standard temporal logics is no more sufficient to handle all kind of requirements the designers need (consider, for example, non-functional requirements). Second, the standard model checking techniques are unable to manage such level of complexity (consider the well-known curse of state space explosion). In this thesis, we leverage machine learning techniques, active learning, and optimization approaches to face the challenges mentioned above. In particular, we define signal measure logic, a novel temporal logic suited to describe non-functional requirements. We also use evolutionary algorithms and signal temporal logic to tackle a supervised classification problem and a system design problem which involves multiple conflicting requirements (i.e., multi-objective optimization problems). Finally, we use an active learning approach, based on Gaussian processes, to deal with falsification problems in the automotive field and to solve a so-called threshold synthesis problem, discussing an epidemics case study.During the last 20 years, model-based design has become a standard practice in many fields such as automotive, aerospace engineering, systems and synthetic biology. This approach allows a considerable improvement of the final product quality and reduces the overall prototyping costs. In these contexts, formal methods, such as temporal logics, and model checking approaches have been successfully applied. They allow a precise description and automatic verification of the prototype's requirements. In the recent past, the increasing market requests for performing and safer devices shows an unstoppable growth which inevitably brings to the creation of more and more complicated devices. The rise of cyber-physical systems, which are on their way to become massively pervasive, brings the complexity level to the next step and open many new challenges. First, the descriptive power of standard temporal logics is no more sufficient to handle all kind of requirements the designers need (consider, for example, non-functional requirements). Second, the standard model checking techniques are unable to manage such level of complexity (consider the well-known curse of state space explosion). In this thesis, we leverage machine learning techniques, active learning, and optimization approaches to face the challenges mentioned above. In particular, we define signal measure logic, a novel temporal logic suited to describe non-functional requirements. We also use evolutionary algorithms and signal temporal logic to tackle a supervised classification problem and a system design problem which involves multiple conflicting requirements (i.e., multi-objective optimization problems). Finally, we use an active learning approach, based on Gaussian processes, to deal with falsification problems in the automotive field and to solve a so-called threshold synthesis problem, discussing an epidemics case study