Verification, Analytical Validation, and Clinical Validation (V3): The Foundation of Determining Fit-for-Purpose for Biometric Monitoring Technologies (BioMeTs)

Digital medicine is an interdisciplinary field, drawing together stakeholders with expertize in engineering, manufacturing, clinical science, data science, biostatistics, regulatory science, ethics, patient advocacy, and healthcare policy, to name a few. Although this diversity is undoubtedly valuable, it can lead to confusion regarding terminology and best practices. There are many instances, as we detail in this paper, where a single term is used by different groups to mean different things, as well as cases where multiple terms are used to describe essentially the same concept. Our intent is to clarify core terminology and best practices for the evaluation of Biometric Monitoring Technologies (BioMeTs), without unnecessarily introducing new terms. We focus on the evaluation of BioMeTs as fit-for-purpose for use in clinical trials. However, our intent is for this framework to be instructional to all users of digital measurement tools, regardless of setting or intended use. We propose and describe a three-component framework intended to provide a foundational evaluation framework for BioMeTs. This framework includes (1) verification, (2) analytical validation, and (3) clinical validation. We aim for this common vocabulary to enable more effective communication and collaboration, generate a common and meaningful evidence base for BioMeTs, and improve the accessibility of the digital medicine field

Computerization of workflows, guidelines and care pathways: a review of implementation challenges for process-oriented health information systems

There is a need to integrate the various theoretical frameworks and formalisms for modeling clinical guidelines, workflows, and pathways, in order to move beyond providing support for individual clinical decisions and toward the provision of process-oriented, patient-centered, health information systems (HIS). In this review, we analyze the challenges in developing process-oriented HIS that formally model guidelines, workflows, and care pathways. A qualitative meta-synthesis was performed on studies published in English between 1995 and 2010 that addressed the modeling process and reported the exposition of a new methodology, model, system implementation, or system architecture. Thematic analysis, principal component analysis (PCA) and data visualisation techniques were used to identify and cluster the underlying implementation ‘challenge’ themes. One hundred and eight relevant studies were selected for review. Twenty-five underlying ‘challenge’ themes were identified. These were clustered into 10 distinct groups, from which a conceptual model of the implementation process was developed. We found that the development of systems supporting individual clinical decisions is evolving toward the implementation of adaptable care pathways on the semantic web, incorporating formal, clinical, and organizational ontologies, and the use of workflow management systems. These architectures now need to be implemented and evaluated on a wider scale within clinical settings

Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer

Lung cancer is the leading cause of cancer deaths, because ~84% of cases are diagnosed at an advanced stage. Worldwide in 2008, ~1.5 million people were diagnosed and ~1.3 million died – a survival rate unchanged since 1960. However, patients diagnosed at an early stage and have surgery experience an 86% overall 5-year survival. New diagnostics are therefore needed to identify lung cancer at this stage. Here we present the first large scale clinical use of aptamers to discover blood protein biomarkers in disease with our breakthrough proteomic technology. This multi-center case-control study was conducted in archived samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. We measured >800 proteins in 15uL of serum, identified 44 candidate biomarkers, and developed a 12-protein panel that distinguished NSCLC from controls with 91% sensitivity and 84% specificity in a training set and 89% sensitivity and 83% specificity in a blinded, independent verification set. Performance was similar for early and late stage NSCLC. This is a significant advance in proteomics in an area of high clinical need

Systems approach to assessing and improving local human research Institutional Review Board performance.

ObjectiveTo quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.MethodsOver 8000 IRB, coverage analysis and contract applications initiated between 2013 and 2016 were analyzed using traditional and machine learning analytics for a quality improvement effort to improve the time required to authorize the start of human research studies.ResultsStaffing ratios, study characteristics such as the number of arms, source of funding and number and type of ancillary reviews significantly influenced the timelines. Using key variables, a predictive algorithm identified outliers for a workflow distinct from the standard process. Improved communication between regulatory units, integration of common functions, and education outreach improved the regulatory approval process.ConclusionsUnderstanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics

London SynEx Demonstrator Site: Impact Assessment Report

The key ingredients of the SynEx-UCL software components are: 1. A comprehensive and federated electronic healthcare record that can be used to reference or to store all of the necessary healthcare information acquired from a diverse range of clinical databases and patient-held devices. 2. A directory service component to provide a core persons demographic database to search for and authenticate staff users of the system and to anchor patient identification and connection to their federated healthcare record. 3. A clinical record schema management tool (Object Dictionary Client) that enables clinicians or engineers to define and export the data sets mapping to individual feeder systems. 4. An expansible set of clinical management algorithms that provide prompts to the patient or clinician to assist in the management of patient care. CHIME has built up over a decade of experience within Europe on the requirements and information models that are needed to underpin comprehensive multiprofessional electronic healthcare records. The resulting architecture models have influenced new European standards in this area, and CHIME has designed and built prototype EHCR components based on these models. The demonstrator systems described here utilise a directory service and object-oriented engineering approach, and support the secure, mobile and distributed access to federated healthcare records via web-based services. The design and implementation of these software components has been founded on a thorough analysis of the clinical, technical and ethico-legal requirements for comprehensive EHCR systems, published through previous project deliverables and in future planned papers. The clinical demonstrator site described in this report has provided the solid basis from which to establish "proof of concept" verification of the design approach, and a valuable opportunity to install, test and evaluate the results of the component engineering undertaken during the EC funded project. Inevitably, a number of practical implementation and deployment obstacles have been overcome through this journey, each of those having contributed to the time taken to deliver the components but also to the richness of the end products. UCL is fortunate that the Whittington Hospital, and the department of cardiovascular medicine in particular, is committed to a long-term vision built around this work. That vision, outlined within this report, is shared by the Camden and Islington Health Authority and by many other purchaser and provider organisations in the area, and by a number of industrial parties. They are collectively determined to support the Demonstrator Site as an ongoing project well beyond the life of the EC SynEx Project. This report, although a final report as far as the EC project is concerned, is really a description of the first phase in establishing a centre of healthcare excellence. New EC Fifth Framework project funding has already been approved to enable new and innovative technology solutions to be added to the work already established in north London

Toward a Standardized Strategy of Clinical Metabolomics for the Advancement of Precision Medicine

Despite the tremendous success, pitfalls have been observed in every step of a clinical metabolomics workflow, which impedes the internal validity of the study. Furthermore, the demand for logistics, instrumentations, and computational resources for metabolic phenotyping studies has far exceeded our expectations. In this conceptual review, we will cover inclusive barriers of a metabolomics-based clinical study and suggest potential solutions in the hope of enhancing study robustness, usability, and transferability. The importance of quality assurance and quality control procedures is discussed, followed by a practical rule containing five phases, including two additional "pre-pre-" and "post-post-" analytical steps. Besides, we will elucidate the potential involvement of machine learning and demonstrate that the need for automated data mining algorithms to improve the quality of future research is undeniable. Consequently, we propose a comprehensive metabolomics framework, along with an appropriate checklist refined from current guidelines and our previously published assessment, in the attempt to accurately translate achievements in metabolomics into clinical and epidemiological research. Furthermore, the integration of multifaceted multi-omics approaches with metabolomics as the pillar member is in urgent need. When combining with other social or nutritional factors, we can gather complete omics profiles for a particular disease. Our discussion reflects the current obstacles and potential solutions toward the progressing trend of utilizing metabolomics in clinical research to create the next-generation healthcare system.11Ysciescopu

ERS statement on standardisation of cardiopulmonary exercise testing in chronic lung diseases

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients’ perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2–3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data.The document facilitates standardisation of conducting, reporting and interpreting cardiopulmonary exercise tests in chronic lung diseases for comparison of reference data, multi-centre studies and assessment of interventional efficacy. http://bit.ly/31SXeB