EVIDENCE REQUIRED BY HEALTH TECHNOLGY ASSESSMENT AND REIMBURSEMENT BODIES EVALUATING DIAGNOSTIC OR PROGNOSTIC ALGORITHMS THAT INCLUDE OMICS DATA.

OBJECTIVES: Multi-analyte assays with algorithmic analyses (MAAAs) use combinations of circulating and clinical markers including omics-based sources for diagnostic and/or prognostic purposes. Assessing MAAAs is challenging under existing health technology assessment (HTA) methods or practices. We undertook a scoping review to explore the HTA methods used for MAAAs to identify the criteria used for clinical research and reimbursement purposes. METHODS: This review included only non-companion (stand-alone) tests that are actionable and that have been evaluated by leading HTA or insurer/reimbursement bodies up to September 2017. RESULTS: Twenty-five reports and articles evaluating seventeen MAAAs were examined, most of which have been developed in oncology. The two main models used were the EUnetHTA Core model and the Evaluation of Genomic Applications in Practice and Prevention ACCE framework. Clinical validity and utility criteria were used, as were economic, ethical, legal, and social aspects. Economic evidence on MAAAs was scarce, and there is no consensus on whether the perspectives used are sufficiently broad to include all relevant stakeholders. CONCLUSIONS: Clinical utility and efficiency were the most used criteria, with stronger evidence needed linking the use of the algorithm with the clinical outcomes in real-life practice. HTA bodies must as well consider questions related to the analytical validity of MAAAs or with organizational aspects. The two main models, the EUnetHTA Core model and the ACCE framework, could be adapted to the assessment of MAAAs.

Formation of a stable mimic of ambient particulate matter containing viable infectious respiratory syncytial virus and its dry-deposition directly onto cell cultures.

Epidemiological associations of worse respiratory outcomes from combined exposure to ambient particulate matter (PM) and respiratory viral infection suggest possible interactions between PM and viruses. To characterize outcomes of such exposures, we developed an in vitro mimic of the in vivo event of exposure to PM contaminated with respiratory syncytial virus (RSV). Concentration of infectious RSV stocks and a particle levitation apparatus were the foundations of the methodology developed to generate specific numbers of PM mimics (PM(Mimics)) of known composition for dry, direct deposition onto airway epithelial cell cultures. Three types of PM(Mimics) were generated for this study: (i) carbon alone (P(C)), (ii) carbon and infectious RSV (P(C+RSV)), and (iii) aerosols consisting of RSV (A(RSV)). P(C+RSV) were stable in solution and harbored infectious RSV for up to 6 months. Unlike A(RSV) infection, P(C+RSV) infection was found to be dynamin dependent and to cause lysosomal rupture. Cells dosed with PM(Mimics) comprised of RSV (A(RSV)), carbon (P(C)), or RSV and carbon (P(C+RSV)) responded differentially as exemplified by the secretion patterns of IL-6 and IL-8. Upon infection, and prior to lung cell death due to viral infection, regression analysis of these two mediators in response to incubation with A(RSV), P(C), or P(C+RSV) yielded higher concentrations upon infection with the latter and at earlier time points than the other PM(Mimics). In conclusion, this experimental platform provides an approach to study the combined effects of PM-viral interactions and airway epithelial exposures in the pathogenesis of respiratory diseases involving inhalation of environmental agents.