Novel Stepwise Approach to Assess Representativeness of a Large Multicenter Observational Cohort of Tuberculosis Patients: The Example of RePORT Brazil.

Abstract Background A major goal of tuberculosis (TB) epidemiologic studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on determinants of TB treatment outcomes is also important. Methods We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled into the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts. Findings 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, presence of diabetes and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts. Conclusions There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases. We compared a multicenter tuberculosis cohort enrolled from three regions of Brazil with the Brazilian National Tuberculosis Program registry, using innovative statistical approaches. The cohort was representative of TB patients overall, facilitating generalizability of study outcomes.