Dataset Information

Assessing Noninferiority in Treatment Trials for Severe Infectious Diseases: an Extension to the Entire Follow-Up Period Using a Cure-Death Multistate Model.

ABSTRACT: In current and former clinical trials for the development of antibacterial drugs, various primary endpoints have been used, and treatment effects are evaluated mostly in noninferiority analyses at the end of follow-up, which varies between studies. A more convincing and highly patient-relevant statement would be a noninferiority assessment over the entire follow-up period with cure and death as coprimary endpoints, while preserving the desired alpha level for statistical testing. To account for the time-dynamic pattern of cure and death, we apply a cure-death multistate model. The endpoint of interest is "get cured and stay alive over time." Noninferiority between treatments over the entire follow-up period is studied by means of one-sided confidence bands provided by a flexible resampling technique. We illustrate the technique by applying it to a recently published study and establish noninferiority in being cured and alive over a time frame of interest for the entire population, patients with hospital-acquired pneumonia, but not for the subset of patients with ventilator-associated pneumonia. Our analysis improves the original results in the sense that our endpoint is more patient benefiting, a stronger noninferiority statement is demonstrated, and the time dependency of cure and death, competing events, and different follow-up times is captured. Multistate methodology combined with confidence bands adds a valuable statistical tool for clinical trials in the context of infection control. The framework is not restricted to the cure-death model but can be adapted to more complex multistate endpoints and equivalence or superiority analyses.

SUBMITTER: Sommer H

PROVIDER: S-EPMC5740315 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Assessing Noninferiority in Treatment Trials for Severe Infectious Diseases: an Extension to the Entire Follow-Up Period Using a Cure-Death Multistate Model.

Sommer Harriet H Bluhmki Tobias T Beyersmann Jan J Schumacher Martin M

Antimicrobial agents and chemotherapy 20171221 1

In current and former clinical trials for the development of antibacterial drugs, various primary endpoints have been used, and treatment effects are evaluated mostly in noninferiority analyses at the end of follow-up, which varies between studies. A more convincing and highly patient-relevant statement would be a noninferiority assessment over the entire follow-up period with cure and death as coprimary endpoints, while preserving the desired alpha level for statistical testing. To account for ...[more]

PMID: 29061757

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Project description:PurposeTo validate the MRI grading system proposed by Mehralivand et al in 2019 (the "extraprostatic extension [EPE] grade") in an independent cohort and to compare the Mehralivand EPE grading system with EPE interpretation on the basis of a five-point Likert score ("EPE Likert").Materials and methodsA total of 310 consecutive patients underwent multiparametric MRI according to a standardized institutional protocol before radical prostatectomy was performed by using the same 1.5-T MRI unit at a single institution between 2010 and 2012. Two radiologists blinded to clinical information assessed EPE according to standardized criteria. On the basis of the readings performed until 2017, the diagnostic performance of EPE Likert and Mehralivand EPE score were compared using receiver operating characteristics (ROC) and decision curve methodology against histologic EPE as standard of reference. Prediction of biochemical recurrence-free survival (BRFS) was assessed by Kaplan-Meier analysis and log rank test.ResultsOf the 310 patients, 80 patients (26%) had EPE, including 33 with radial distance 1.1 mm or greater. Interrater reliability was fair (weighted κ 0.47 and 0.45) for both EPE grade and EPE Likert. Sensitivity for identifying EPE using EPE grade versus EPE Likert was 0.83 versus 0.86 and 0.86 versus 0.91 for radiologist 1 and 2, respectively. Specificity was 0.48 versus 0.58 and 0.39 versus 0.70 (P < .05 for radiologist 2). There were no significant differences in the ROC area under the curve or on decision curve analysis. Both EPE grade and EPE Likert were significant predictors of BRFS.ConclusionMehralivand EPE grade and EPE Likert have equivalent diagnostic performance for predicting EPE and BRFS with a similar degree of observer dependence.© RSNA, 2020Keywords: MR-Imaging, Neoplasms-Primary, Observer Performance, Outcomes Analysis, Prostate, StagingSupplemental material is available for this article.See also the commentary by Choyke in this issue.

Project description:BACKGROUND: Caused by intracellular Gram-negative bacteria Brucella spp., brucellosis is the most common bacterial zoonotic disease. Extensive studies in brucellosis have yielded a large number of publications and data covering various topics ranging from basic Brucella genetic study to vaccine clinical trials. To support data interoperability and reasoning, a community-based brucellosis-specific biomedical ontology is needed. RESULTS: The Brucellosis Ontology (IDOBRU: http://sourceforge.net/projects/idobru), a biomedical ontology in the brucellosis domain, is an extension ontology of the core Infectious Disease Ontology (IDO-core) and follows OBO Foundry principles. Currently IDOBRU contains 1503 ontology terms, which includes 739 Brucella-specific terms, 414 IDO-core terms, and 350 terms imported from 10 existing ontologies. IDOBRU has been used to model different aspects of brucellosis, including host infection, zoonotic disease transmission, symptoms, virulence factors and pathogenesis, diagnosis, intentional release, vaccine prevention, and treatment. Case studies are typically used in our IDOBRU modeling. For example, diurnal temperature variation in Brucella patients, a Brucella-specific PCR method, and a WHO-recommended brucellosis treatment were selected as use cases to model brucellosis symptom, diagnosis, and treatment, respectively. Developed using OWL, IDOBRU supports OWL-based ontological reasoning. For example, by performing a Description Logic (DL) query in the OWL editor Protégé 4 or a SPARQL query in an IDOBRU SPARQL server, a check of Brucella virulence factors showed that eight of them are known protective antigens based on the biological knowledge captured within the ontology. CONCLUSIONS: IDOBRU is the first reported bacterial infectious disease ontology developed to represent different disease aspects in a formal logical format. It serves as a brucellosis knowledgebase and supports brucellosis data integration and automated reasoning.

Dataset Information

Assessing Noninferiority in Treatment Trials for Severe Infectious Diseases: an Extension to the Entire Follow-Up Period Using a Cure-Death Multistate Model.

Publications

Assessing Noninferiority in Treatment Trials for Severe Infectious Diseases: an Extension to the Entire Follow-Up Period Using a Cure-Death Multistate Model.

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