American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2021
Using Bayesian Methods to Augment the Interpretation of Critical Care Trials: An Overview of Theory and Example Reanalysis of the Alveolar Recruitment Trial.
Most randomized trials are designed and analyzed using frequentist statistical approaches such as null hypothesis testing and P values. Conceptually, P values are cumbersome to understand, as they provide evidence of data incompatibility with a null hypothesis (e.g., no clinical benefit) and not direct evidence of the alternative hypothesis (e.g., clinical benefit). This counterintuitive framework may contribute to the misinterpretation that the absence of evidence is equal to evidence of absence and may cause the discounting of potentially informative data. ⋯ However, if priors are not defined a priori, there is a legitimate concern that priors could be constructed in a manner that produces biased results. Therefore, some standardization of priors for Bayesian reanalysis of clinical trials may be desirable for the critical care community. In this Critical Care Perspective, we discuss both frequentist and Bayesian approaches to clinical trial analysis, introduce a framework that researchers can use to select priors for a Bayesian reanalysis, and demonstrate how to apply our proposal by conducting a novel Bayesian trial reanalysis.
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Am. J. Respir. Crit. Care Med. · Mar 2021
Experimental Human Pneumococcal Colonisation in Older Adults is Feasible and Safe, Not Immunogenic.
Rationale: Pneumococcal colonization is key to the pathogenesis of invasive disease but is also immunogenic in young adults, protecting against recolonization. Colonization is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives: To establish experimental human pneumococcal colonization in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonization against autologous strain rechallenge. ⋯ Antiprotein antibody concentrations increased after successful colonization. Rechallenge with the same strain after a median of 8.5 months (interquartile range, 6.7-10.1) led to recolonization in 5/16 (31%). Conclusions: In older adults, experimental pneumococcal colonization is feasible and safe but demonstrates different immunological outcomes compared with younger adults in previous studies.