Title: Accuracy, impact and cost-effectiveness of prehospital clinical early warning scores for adults with suspected sepsis
Funder: Department of Health and Social Care

Abstract: Background to the research:_x000D_ Sepsis is a life-threatening condition caused by the body having an abnormal response to infection that leads to heart, lung and kidney failure. People with sepsis need urgent treatment with antibiotics and intravenous fluids, and may need treatment in intensive care. However, some features of sepsis may be seen with uncomplicated infections or other illnesses, particularly in people with underlying diseases. This can make it difficult to correctly identify who has sepsis and needs urgent treatment, and who does not._x000D_ _x000D_ Early warning scores can be used to identify patients with sepsis and prioritise their treatment in a busy emergency department. Early warning scores use simple measurements such as blood pressure, heart rate and breathing rate to determine whether a patient is likely to have sepsis. An accurate early warning score could help paramedics, doctors and nurses ensure that people with sepsis are identified and treated before other less urgent cases. However, an inaccurate early warning score might miss cases of sepsis and thus delay treatment. Alternatively, it could create a “false alarm” if it incorrectly suggests that people with other conditions have sepsis. This could result in unnecessary tests and treatments being given, and could delay the treatment of other emergency cases arriving at the same time._x000D_ _x000D_ Aims of the research:_x000D_ 1.To determine how accurately existing and potential new early warning scores identify cases of sepsis that need urgent treatment_x000D_ 2. To determine the likely impact of paramedics using early warning scores to (a) alert the emergency department so they are seen immediately on arrival, or (b) provide treatment for sepsis in the ambulance_x000D_ _x000D_ Design and methods used:_x000D_ We plan to collect data from 46,000 people who may have sepsis and are brought to hospital by emergency ambulance. We will use routinely recorded information, so that the study does not interfere with patient care. We will review hospital records to determine whether patients actually had sepsis and needed urgent treatment. We will then use the data to determine how accurately the early warning scores identified people with sepsis._x000D_ _x000D_ We will use mathematical modelling to simulate the use of early warning scores to select people with suspected sepsis for urgent treatment in a virtual ambulance service and emergency department. This will determine how many people with sepsis would be appropriately treated using different early warning scores, and the impact on the emergency department and ambulance service. We will then estimate the cost-effectiveness of using different early warning scores._x000D_ _x000D_ Patient and public involvement:_x000D_ The Sheffield Emergency Care Forum (SECF) is a patient and public group with an interest in emergency care research. Two members of SECF have helped to develop our plans and will be members of the research team. We will also ask another independent member of SECF and representatives from other organisations, such as the UK Sepsis Trust, to join the Study Steering Committee, which will independently advise and oversee the project._x000D_ _x000D_ Dissemination:_x000D_ Current sepsis guidance from the National Institute for Health and Care Excellence (NICE) has called for research into the use of early warning scores, so we expect that our findings will be used in future NICE guidance. We will also send our findings directly to ambulance services, professional organisations and patient representative groups

Lay abstract: Research question:_x000D_ What are the accuracy, impact and cost-effectiveness of prehospital early warning scores for adults with suspected sepsis?_x000D_ _x000D_ Background:_x000D_ Prehospital early warning scores can be used to prioritise treatment for people at high risk of sepsis but the accuracy of existing scores and the impact of their use is uncertain._x000D_ _x000D_ Aims and objectives:_x000D_ 1. To estimate the accuracy of early warning scores for predicting potential to benefit from time-critical treatment for sepsis_x000D_ 2. To estimate the operational consequences and cost-effectiveness of using early warning scores to guide prehospital decisions for adults with suspected sepsis_x000D_ _x000D_ Methods:_x000D_ A retrospective diagnostic cohort study using routine data sources across four acute hospitals with associated ambulance services and decision analytic modelling._x000D_ _x000D_ The target population will be adults transported to hospital by emergency ambulance with possible sepsis. Patient report form data will be used to identify eligible cases and collect pre-hospital measures used to calculate early warning scores. Cases will be linked to routine hospital data sources._x000D_ _x000D_ The index tests will be prehospital early warning scores identified through a systematic literature search and selected by an expert group, who will also create up to three additional scores._x000D_ _x000D_ The reference standard will be determined by expert review of clinical records to identify patients with infection and life-threatening organ dysfunction who received potentially life-saving treatment for sepsis. Screening will be used to select cases for expert review so that the workload is manageable but cases are not missed._x000D_ _x000D_ Receiving-operator characteristic (ROC) curves will compare sensitivity to specificity across the range of each score. We will also explore whether a clinically credible new score can be derived using multivariable logistic regression, augmented with recursive partitioning._x000D_ _x000D_ We plan to identify 46,000 cases across one year, with around 200 anticipated to be reference standard positive, allowing us to estimate sensitivity with a standard error of 2.1% and the area under the ROC curve with a standard error of 2%._x000D_ _x000D_ We will create a decision-analytic model to estimate the impact of using early warning scores to: (i) Alert the receiving hospital so that the patient is seen immediately on arrival; (ii) Provide prehospital treatment for sepsis. The model will simulate the prehospital management of a hypothetical cohort of patients with suspected sepsis and then model their flow through an ED, alongside all other patients attending the ED. The model will estimate the operational consequences of using different early warning scores, in terms of the number of attendances appropriately and inappropriately prioritised or given prehospital treatment. We will adopt a health service perspective to estimate costs and will value outcomes as QALYs to estimate the incremental cost per QALY of using different strategies and will undertake a full incremental analysis._x000D_ _x000D_ Timelines for delivery (months):_x000D_ 1-6: Set-up and approvals, identification and selection of early warning scores_x000D_ 7-12: Identification of cases and linkage to hospital data_x000D_ 13-18: Reference standard adjudication and development of model_x000D_ 18-24: Analysis, write-up and dissemination_x000D_ _x000D_ Anticipated impact and dissemination:_x000D_ The findings will inform future NICE guidance and determine how ambulance services use prehospital early warning scores for sepsis.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM