Using the kidney failure risk equation to predict end-stage kidney disease in CKD patients of South Asian ethnicity: an external validation study.

BACKGROUND: The kidney failure risk equation (KFRE) predicts the 2- and 5-year risk of needing kidney replacement therapy (KRT) using four risk factors - age, sex, urine albumin-to-creatinine ratio (ACR) and creatinine-based estimated glomerular filtration rate (eGFR). Although the KFRE has been recalibrated in a UK cohort, this did not consider minority ethnic groups. Further validation of the KFRE in different ethnicities is a research priority. The KFRE also does not consider the competing risk of death, which may lead to overestimation of KRT risk. This study externally validates the KFRE for patients of South Asian ethnicity and compares methods for accounting for ethnicity and the competing event of death. METHODS: Data were gathered from an established UK cohort containing 35,539 individuals diagnosed with chronic kidney disease. The KFRE was externally validated and updated in several ways taking into account ethnicity, using recognised methods for time-to-event data, including the competing risk of death. A clinical impact assessment compared the updated models through consideration of referrals made to secondary care. RESULTS: The external validation showed the risk of KRT differed by ethnicity. Model validation performance improved when incorporating ethnicity and its interactions with ACR and eGFR as additional risk factors. Furthermore, accounting for the competing risk of death improved prediction. Using criteria of 5 years ≥ 5% predicted KRT risk, the competing risks model resulted in an extra 3 unnecessary referrals (0.59% increase) but identified an extra 1 KRT case (1.92% decrease) compared to the previous best model. Hybrid criteria of predicted risk using the competing risks model and ACR ≥ 70 mg/mmol should be used in referrals to secondary care. CONCLUSIONS: The accuracy of KFRE prediction improves when updated to consider South Asian ethnicity and to account for the competing risk of death. This may reduce unnecessary referrals whilst identifying risks of KRT and could further individualise the KFRE and improve its clinical utility. Further research should consider other ethnicities.

Feasibility study for interactive reporting of network meta-analysis: experiences from the development of the MetaInsight COVID-19 app for stakeholder exploration, re-analysis and sensitivity analysis from living systematic reviews.

BACKGROUND: Network meta-analysis (NMA) has been increasingly adopted worldwide by Cochrane reviews, guideline developers and decision-making bodies to identify optimal treatment choices. However, NMA results are often produced statically, not allowing stakeholders to 'dig deeper' and interrogate with their own judgement. Additionally, amid the COVID-19 pandemic, unnecessary or duplicated reviews have been proposed which analyse from the same pool of evidence. We developed the 'MetaInsight COVID-19' app as a prototype for an interactive platform to eliminate such duplicated efforts, by empowering users to freely analyse the data and improve scientific transparency. METHODS: MetaInsight COVID-19 ( https://crsu.shinyapps.io/metainsightcovid/ ) was developed to conduct NMA with the evolving evidence on treatments for COVID-19. It was updated weekly between 19th May - 19th Oct 2020, incorporating new evidence identified from a living systematic review. RESULTS: The app includes embedded functions to facilitate study selection based on study characteristics, and displays the synthesised results in real time. It allows both frequentist and Bayesian NMA to be conducted as well as consistency and heterogeneity assessments. A demonstration of the app is provided and experiences of building such a platform are discussed. CONCLUSIONS: MetaInsight COVID-19 allows users to take control of the evidence synthesis using the analytic approach they deem appropriate to ascertain how robust findings are to alternative analysis strategies and study inclusion criteria. It is hoped that this app will help avoid many of the duplicated efforts when reviewing and synthesising the COVID-19 evidence, and, in addition, establish the desirability of an open platform format such as this for interactive data interrogation, visualisation, and reporting for any traditional or 'living' NMA.

MetaInsight: An interactive web-based tool for analyzing, interrogating, and visualizing network meta-analyses using R-shiny and netmeta.

BACKGROUND: Network meta-analysis (NMA) is a powerful analysis method used to identify the best treatments for a condition and is used extensively by health care decision makers. Although software routines exist for conducting NMA, they require considerable statistical programming expertise to use, which limits the number of researchers able to conduct such analyses. OBJECTIVES: To develop a web-based tool allowing users with only standard internet browser software to be able to conduct NMAs using an intuitive "point and click" interface and present the results using visual plots. METHODS: Using the existing netmeta and Shiny packages for R to conduct the analyses, and to develop the user interface, we created the MetaInsight tool which is freely available to use via the web. RESULTS: A package was created for conducting NMA which satisfied our objectives, and this is described, and its application demonstrated, using an illustrative example. CONCLUSIONS: We believe that many researchers will find our package helpful for facilitating NMA as well as allowing decision makers to scrutinize presented results visually and in real time. This will impact on the relevance of statistical analyses for health care decision making and sustainably increase capacity by empowering informed nonspecialists to be able to conduct more clinically relevant reviews. It is also hoped that others will be inspired to create similar tools for other advanced specialist analyses methods using the freely available technologies we have adopted.

Clinicians' attitude towards a placebo-controlled randomised clinical trial investigating the effect of neuraminidase inhibitors in adults hospitalised with influenza.

BACKGROUND: The value of neuraminidase inhibitors (NAIs) in reducing severe clinical outcomes from influenza is debated. A clinical trial to generate better evidence is desirable. However, it is unknown whether UK clinicians would support a placebo-controlled trial. A survey was conducted to determine the attitude of clinicians towards a clinical trial and their current practice in managing adults admitted to hospital with suspected influenza. METHODS: Senior clinicians (n = 50) across the UK actively involved in the care of patients hospitalised with severe respiratory infections and/or respiratory infection research were invited to participate in an on-line survey. Participants were asked their opinion on the evidence for benefit of NAIs in influenza, their current practice in relation to: a) testing for influenza; b) treating empirically with NAIs; and c) when influenza infection is virolologically confirmed, prescribing NAIs. RESULTS: Thirty-five (70%) of 50 clinicians completed the survey. Respondents were drawn mainly from infectious diseases, intensive care and respiratory medicine. Only 11 (31%) of 35 respondents agreed that NAIs are effective at reducing influenza mortality; 14 (40%) disagreed, 10 (28.6%) neither agreed nor disagreed. When managing adults admitted to non-ICU wards with a respiratory infection during an influenza season, 15 (51.7%) clinicians indicated they would usually perform a test for influenza in greater than 60% of patients but only 9 (31%) would treat empirically with NAIs in greater than 60% of patients. Few clinicians would either test or empirically treat patients presenting with other (non-respiratory infection related) diagnoses. If influenza infection is confirmed, 17 (64.5%) clinicians would prescribe NAIs in greater than 80% of patients with a respiratory infection treated on non-ICU wards Thirty-one (89%) clinicians agreed that a placebo-controlled clinical trial should be conducted and 29 (85%) would participate in such a trial. CONCLUSIONS: There is strong support from UK clinicians for a placebo-controlled trial of NAI treatment in adults hospitalised with suspected influenza. Current variation in medical opinion and clinical practice demonstrates collective equipoise, supporting ethical justification for a trial. Low use of NAIs in the UK suggests randomisation of treatment would not substantially divert patients towards placebo.

Quantifying the Value of Perfect Information in Emergency Vaccination Campaigns.

Foot-and-mouth disease outbreaks in non-endemic countries can lead to large economic costs and livestock losses but the use of vaccination has been contentious, partly due to uncertainty about emergency FMD vaccination. Value of information methods can be applied to disease outbreak problems such as FMD in order to investigate the performance improvement from resolving uncertainties. Here we calculate the expected value of resolving uncertainty about vaccine efficacy, time delay to immunity after vaccination and daily vaccination capacity for a hypothetical FMD outbreak in the UK. If it were possible to resolve all uncertainty prior to the introduction of control, we could expect savings of £55 million in outbreak cost, 221,900 livestock culled and 4.3 days of outbreak duration. All vaccination strategies were found to be preferable to a culling only strategy. However, the optimal vaccination radius was found to be highly dependent upon vaccination capacity for all management objectives. We calculate that by resolving the uncertainty surrounding vaccination capacity we would expect to return over 85% of the above savings, regardless of management objective. It may be possible to resolve uncertainty about daily vaccination capacity before an outbreak, and this would enable decision makers to select the optimal control action via careful contingency planning.