Concordance of three approaches for operationalizing outcome definitions for multidrug-resistant TB

Abstract

BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.

Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis

“…Background regimens would follow WHO guidelines and local norms and would be adjusted if clinically indicated. Participants would be followed from assignment until the end of treatment, at which time treatment outcomes would be calculated on the basis of 2013 WHO guidance ( 13 , 14 ). Successful treatment, the outcome of interest, would include cure and treatment completion, whereas unsuccessful treatment would include outcomes of death, loss to follow-up, and treatment failure.…”

Low body mass index as a predictor of sputum culture conversion and treatment outcomes among patients receiving treatment for multidrug-resistant tuberculosis in Lesotho

“…The second outcome was favourable EOT outcomes. In accordance with WHO guidelines, using an algorithm, we calculated the EOT outcomes based on the available culture results at the end of treatment [ 22 ].…”

Updates in pulmonary drug‐resistant tuberculosis pharmacotherapy: A focus on BPaL and BPaLM

“…95 Although applying these definitions in practice has proven difficult for some investigators, which poses a dilemma for researchers conducting observational studies on patients with drugresistant TB. [96][97][98][99] The 2013 WHO framework for outcome definitions, mostly based on sputum culture results, has served as a resource for investigators conducting observational research studies of patients with MDR-and XDR-TB (Table 4). 100 However, several criticisms of the definitions exist, including difficulty of implementation in the clinical setting, due to lack of sputum production during the later stage of TB treatment.…”

“…As such, the WHO provides standardized outcome definitions and considerations for implementation in the 2022 operational handbook for use in observational studies and clinical trials 95 . Although applying these definitions in practice has proven difficult for some investigators, which poses a dilemma for researchers conducting observational studies on patients with drug‐resistant TB 96–99 …”