Title: The future for diagnostic tests of acute kidney injury in critical care: evidence synthesis care pathway analysis and research prioritisation
Funder: Department of Health (England)

Abstract: Acute kidney Injury (AKI) is highly prevalent in hospital in-patient populations leading to significant mortality morbidity reduced quality of life and high short and long-term healthcare costs for the NHS. Diagnosis currently relies on serum creatinine which is an imperfect biomarker rising slowly and inconsistently after initial kidney damage. New biomarker-based in-vitro-diagnostics offer an opportunity for earlier diagnosis improved risk stratification and monitoring enabling earlier specialist referral targeted intervention or intensification of therapy where indicated by the test. Candidate diagnostic tests have now been commercially developed and are being marketed to clinicians and commissioners. Evidence for their analytic and clinical validity is very variable and there is an urgent need to develop evidence for clinical utility and cost-effectiveness in order to guide informed adoption. The development of evidence for diagnostics has historically been inefficient resulting in uncertain or poor value adoption decisions. There is a time-limited opportunity to propose an efficient research strategy for AKI diagnostics in the UK. Such a strategy is required as a basis for the newly formed NIHR Diagnostic Evidence Co-operatives who will promote the development of an evidence base for diagnostic tests by academic commercial and NHS partners.Aims:1. To evaluate the potential for AKI vitro diagnostic tests to enhance the NHS care of patients admitted to critical care.2. To identify the priorities for further diagnostics development and propose efficient designs for relevant future research.Design: Systematic review care pathway analysis model-based economic evaluation and value of information analysis.Target population: (a) NHS patients admitted to critical care (level 3 care). (b) A sub-group of patients admitted to critical care following cardiac surgery.Care pathway-specific outcomes:1. Incidence prevalence and time to onset of AKI in critical care.2. AKI disease natural history (morbidity chronic kidney disease (CKD) dialysis and mortality).3. Rate duration and timing of renal replacement therapy.4. Critical care and hospital length of stay hospital-specific resource use and hospital costs.5. Post-discharge healthcare resource use and costs (primary and secondary care) quality of life patient-financial burden.Diagnostic test-specific outcomes:a. Pre-analytical analytical and biological measurement properties.b. Clinical validity (sensitivity and specificity) for relevant outcomes identified with the care pathway.c. Clinical efficacy clinical effectiveness and cost-effectiveness of test-directed care vs. standard care including patient/carer/clinician acceptability.Data sources: Outcomes will primarily be informed by the literature identified by the systematic review. Additional information will be sought from prospective UK-based datasets; patient representatives and clinical experts will be consulted in order to describe the care pathway healthcare resource use and other parameters where there is an absence of robust data. Statistical and economic analysis: The care pathway will be modelled using probabilistic decision analytic simulation techniques. Meta-analysis of diagnostic test properties will be conducted where multiple comparable studies are identified. Efficient research recommendations will rely on value-of-information analysis.`


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RENAL AND UROGENITAL