Treatment Effect Measures for Culture Conversion Endpoints in Phase IIb Tuberculosis Treatment Trials
| Autor: | Isabelle R Weir, Sean Wasserman |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Microbiology (medical)
medicine.medical_specialty Tuberculosis MEDLINE Antitubercular Agents Article Specimen Handling Mycobacterium tuberculosis medicine Culture conversion Humans Treatment effect Intensive care medicine Tuberculosis Pulmonary biology business.industry Clinical Trials Phase II Survival analysis biology.organism_classification medicine.disease Infectious Diseases Treatment Outcome Randomized controlled trials business |
| Zdroj: | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America |
| ISSN: | 1537-6591 |
| Popis: | Phase IIb trials of tuberculosis therapy rely on early biomarkers of treatment effect. Despite limited predictive ability for clinical outcomes, culture conversion, the event in which an individual previously culture positive for Mycobacterium tuberculosis yields a negative culture after initiating treatment, is a commonly used endpoint. Lack of consensus on how to define the outcome and corresponding measure of treatment effect complicates interpretation and limits between-trial comparisons. We review common analytic approaches to measuring treatment effect and introduce difference in restricted mean survival times as an alternative to identify faster times to culture conversion and express magnitude of effect on the time scale. Findings from the PanACEA MAMS-TB trial are reanalyzed as an illustrative example. In a systematic review we demonstrate variability in analytic approaches, sampling strategies, and outcome definitions in phase IIb tuberculosis trials. Harmonization would allow for larger meta-analyses and may help expedite advancement of new tuberculosis therapeutics. |
| Databáze: | OpenAIRE |
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