Bayesian sample size determination for diagnostic accuracy studies.

The development of a new diagnostic test ideally follows a sequence of stages which, among other aims, evaluate technical performance. This includes an analytical validity study, a diagnostic accuracy study, and an interventional clinical utility study. In this article, we propose a novel Bayesian approach to sample size determination for the diagnostic accuracy study, which takes advantage of information available from the analytical validity stage. We utilize assurance to calculate the required sample size based on the target width of a posterior probability interval and can choose to use or disregard the data from the analytical validity study when subsequently inferring measures of test accuracy. Sensitivity analyses are performed to assess the robustness of the proposed sample size to the choice of prior, and prior-data conflict is evaluated by comparing the data to the prior predictive distributions. We illustrate the proposed approach using a motivating real-life application involving a diagnostic test for ventilator associated pneumonia. Finally, we compare the properties of the approach against commonly used alternatives. The results show that, when suitable prior information is available, the assurance-based approach can reduce the required sample size when compared to alternative approaches.

Sample size determination for point-of-care COVID-19 diagnostic tests: a Bayesian approach.

BACKGROUND: In a pandemic setting, it is critical to evaluate and deploy accurate diagnostic tests rapidly. This relies heavily on the sample size chosen to assess the test accuracy (e.g. sensitivity and specificity) during the diagnostic accuracy study. Too small a sample size will lead to imprecise estimates of the accuracy measures, whereas too large a sample size may delay the development process unnecessarily. This study considers use of a Bayesian method to guide sample size determination for diagnostic accuracy studies, with application to COVID-19 rapid viral detection tests. Specifically, we investigate whether utilising existing information (e.g. from preceding laboratory studies) within a Bayesian framework can reduce the required sample size, whilst maintaining test accuracy to the desired precision. METHODS: The method presented is based on the Bayesian concept of assurance which, in this context, represents the unconditional probability that a diagnostic accuracy study yields sensitivity and/or specificity intervals with the desired precision. We conduct a simulation study to evaluate the performance of this approach in a variety of COVID-19 settings, and compare it to commonly used power-based methods. An accompanying interactive web application is available, which can be used by researchers to perform the sample size calculations. RESULTS: Results show that the Bayesian assurance method can reduce the required sample size for COVID-19 diagnostic accuracy studies, compared to standard methods, by making better use of laboratory data, without loss of performance. Increasing the size of the laboratory study can further reduce the required sample size in the diagnostic accuracy study. CONCLUSIONS: The method considered in this paper is an important advancement for increasing the efficiency of the evidence development pathway. It has highlighted that the trade-off between lab study sample size and diagnostic accuracy study sample size should be carefully considered, since establishing an adequate lab sample size can bring longer-term gains. Although emphasis is on its use in the COVID-19 pandemic setting, where we envisage it will have the most impact, it can be usefully applied in other clinical areas.

Patient Self-Testing of Kidney Function at Home, a Prospective Clinical Feasibility Study in Kidney Transplant Recipients.

Introduction: People with long-term health conditions often attend clinics for kidney function tests. The Self-Testing Own Kidneys (STOK) study assessed feasibility of kidney transplant recipients using hand-held devices to self-test kidney function at home and investigated agreement between home self-test and standard clinic test results. Methods: A prospective, observational, single-center, clinical feasibility study (TRN: ISRCTN68116915), with N = 15 stable kidney transplant recipients, investigated blood potassium and creatinine results agreement between index self-tests at home (patient self-testing of capillary blood, using Abbott i-STAT Alinity analyzers [i-STAT]) and reference tests in clinic (staff sampled venous blood, analyzed with laboratory Siemens Advia Chemistry XPT analyzer) using Bland-Altman and error grid analysis. Results: The mean within-patient difference between index and reference test in creatinine was 2.25 µmol/l (95% confidence interval [CI]: -12.13, 16.81 µmol/l) and in potassium was 0.66 mmol/l (95% CI: -1.47, 2.79 mmol/l). All creatinine pairs and 27 of 40 (67.5%) potassium pairs were judged clinically equivalent. Planned follow-up analysis suggests that biochemical variables associated with potassium measurement in capillary blood were predominant sources of paired test result differences. Paired patient and nurse i-STAT capillary blood test potassium results were not statistically significantly different. Conclusions: This small feasibility study observed that training selected patients to competently use hand-held devices to self-test kidney function at home is possible. Self-test creatinine results showed good analytical and clinical agreement with standard clinic test results. Self-test potassium results showed poorer agreement with standard clinic test results; however, patient self-use of i-STATs at home was not a statistically significant source of difference between paired potassium test results.

Pseudomonas meningoencephalitis masquerading as a stroke in a patient on tocilizumab.

A previously high-functioning woman presents with clinical and CT features of a subacute ischaemic stroke. Her medical history is relevant for refractory giant cell arteritis on long-term high-dose prednisolone and recent commencement of tocilizumab (interleukin-6 monoclonal antibody). The potential for stroke mimic is considered and a magnetic resonance brain scan is requested. She rapidly deteriorates within 24 hours of admission and unexpectantly dies. An autopsy reveals that she has bilateral pulmonary emboli with lower limb deep vein thrombosis and Pseudomonas meningoencephalitis with frank pus on the brain. We discuss the potential risks of immunosuppression and the role of imaging in the diagnosis of stroke.

Burn injuries inflicted on children or the elderly: a framework for clinical and forensic assessment.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the difference between battery and assault in U.S. law and the concepts of the phrase "child abuse" and "elder abuse." 2. Understand that state statutes vary and can define abuse narrowly or with great specificity, and that either definition has inherent problems for physicians treating victims of abuse and neglect. 3. Know where to find the state-specific legal criteria for child or elder abuse and neglect, along with the corresponding standards for mandatory reporting and physician accountability. 4. Understand the relevant law regarding physician-patient privilege and the repercussions of incorrect but good faith reporting and of failing to report suspected abuse or neglect of children or the elderly. 5. Understand that there are no pathognomic signs for inflicted burn injury. 6. Clinically assess burned pediatric or elderly patients within a framework that will minimize the risk of missing or inappropriately suspecting injuries that stem from abuse or neglect. SUMMARY: This article deals with burns inflicted on children and the elderly, two particularly vulnerable societal groups. Though inflicted burning is a relatively rare method of inflicting physical abuse, failure to diagnose it has far-reaching ramifications. These injuries pose both medical and forensic problems for physicians, along with unique ethical dilemmas. This article is a collaboration between surgeons and lawyers providing a holistic, workable approach to the management of inflicted burn injury. The authors first describe the legal considerations that must be appreciated by U.S. physicians, then they suggest a rational and balanced clinical approach to the assessment of burn injuries that may have been inflicted intentionally or negligently on children and the elderly.