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Fast tracking market adoption of a novel immune-based diagnostic for improving antibiotic stewardship: automation, piloting and health economics

Periodic Reporting for period 3 - AutoPilot-Dx (Fast tracking market adoption of a novel immune-based diagnostic for improving antibiotic stewardship: automation, piloting and health economics)

Reporting period: 2019-01-01 to 2019-08-31

A major driver of antibiotic misuse is the difficulty to clinically discriminate bacterial from viral infections. Antibiotic misuse leads to ineffective treatment, emergence of resistant strains of bacteria, and is estimated to cost healthcare systems worldwide tens of billions of dollars annually (Fauci and Marston, JAMA, 2014). ImmunoXpert™ is an innovative in vitro diagnostic test that leverages the world’s most accurate diagnostic system for differentiating bacteria from viruses, crafted by nature, the body’s immune system. This test measures three proprietary blood-borne immune proteins, including a novel viral-induced protein called TRAIL, which was not previously in clinical use, and employs a pattern recognition algorithm to compute viral and bacterial likelihood scores. ImmunoXpert™ was developed and clinically validated in a large-scale multicenter prospective study (`Curiosity`), enrolling over 1000 patients between 2009 and 2013 (Oved et al. 2015, Eden et al. 2016). The assay was further evaluated in a series of double-blinded external clinical studies (van Houten et al 2016, Srugo et al. 2017). ImmunoXpert™ is approved for clinical use in the EU (CE-IVD). AutoPilot-Dx is a European consortium funded under Horizon 2020, The EU Framework Programme for Research and Innovation under the Fast Track to Innovation Pilot. AutoPilot-Dx is a cross sector effort (industry, key opinion leaders, outcome researchers) aimed at driving clinical adoption of the new immune-based diagnostic: ImmunoXpert™. The project outlines a trans-disciplinary approach that includes assay automation, piloting in real-world clinical settings, utility validation and health economics. AutoPilot-Dx's far-reaching goal is to improve antibiotic stewardship, providing better care for febrile children, and help fight antibiotic resistance – a global health threat.
Each of the three objectives of the project were achieved:

1) Automation - ImmunoXpert™ was successfully transitioned onto Freedom EVO® 75 (Tecan), a fully automated laboratory workstation and the performance of the automated test validated at each participating medical center.

2) Piloting - We successfully completed recruitment of 1140 pediatric patients presenting with respiratory tract infection (RTI) or fever without source (FWS) at the emergency department (ED) and pediatric departments; 558 in Italy (49%) and 582 in Germany (51%). ImmunoXpert™ protein levels were measured in serum samples using the automated Tecan workstations on site for each of the 1,008 eligible patients. Reference standard labels were assigned based on unanimous expert panel labels for each of the 1,008 eligible patients. The sensitivity and specificity attained was greater than 90% based on a 2x2 performance analysis. In addition, to evaluate the potential clinical utility of the new test, a set of questionnaires were collected during the study that surveyed the physician’s clinical suspicion during the patient management course. The agreement (% agreement) and concordance (kappa) between the initial label given by the physician after examining a patient and the unanimous reference standard was calculated and compared to the same statistics for ImmunoXpert™ and the unanimous reference standard. ImmunoXpert™ was found to outperform the clinician’s initial suspicion.

2) Health economics and reimbursement - A cost-effectiveness health economic model was constructed to assess the value of introducing a new diagnostic test for differentiating between bacterial and viral infection on top of standard of care (SoC) to SoC, taking into account both diagnostic and treatment pathways. The model case study was set as pediatric patients with suspicion of lower tract infection (LRTI) presenting to the ED in Germany. The overarching finding is that introduction of ImmunoXpert™ is cost-saving.
The landscape for reimbursement of ImmunoXpert™ was mapped in five European target countries based on desk research (Germany, UK, France, Italy and Switzerland). Additional primary research was successfully accomplished in both Germany and the US to enable a more defined reimbursement strategy in these geographies.
AutoPilot-Dx has resulted in an automated and validated diagnostic test for distinguishing between viral and bacterial infection in pediatric patients with respiratory tract infections (RTI) and fever without source (FWS). Specifically, ImmunoXpert™ was transitioned onto the robotic platform EVO 75 and its potential clinical utility and health economics established based on data from real world settings. Successful attainment of the project’s objectives (automation, piloting and health economic analysis) was enabled by a pan-European, multi-disciplinary team, and is anticipated to drive market adoption of ImmunoXpert™ such that RTI and FWS patients receive the right treatment, at the time and place where it matters most. Fast tracking of ImmunoXpert™’s market adoption is expected to improve RTI and FWS patient outcomes (morbidity/mortality), reverse the worrying trend of increasing hospitalization, contribute to curbing antibiotic misuse (underuse and overuse), and reduce the health and economic burden of these diseases. The underlying novel premise of the proposed approach to improving antibiotic stewardship, which differentiates it from solutions that attempt to identify pathogens directly, is that ImmunoXpert™ builds on an exquisitely informative system crafted over millions of years by nature – the human immune system.
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