Totality of outcomes: A different paradigm in assessing interventions for treatment of tuberculosis

Abstract

Conventional analytic methods used for tuberculosis (TB) outcomes research use standardized outcomes definitions and assess safety and efficacy separately. These methods are subject to important limitations. Conventionally utilized outcome definitions fail to capture important aspects of patients' treatment experience and obscure meaningful differences between patients.Assessing safety and efficacy separately fails to yield an objective risk–benefit comparison to guide clinical practice. We propose to address these issues through an analytic approach based on prioritized outcomes. This approach enables a more comprehensive and integrated assessment of TB interventions. It simultaneously considers a “totality of outcomes”, including clinical benefit, adverse events, and quality of life. These composite outcomes are ranked terms of overall desirability and compared using statistical methods for ordinal outcomes. Here we discuss the application of this approach to TB research, the considerations involved with prioritizing TB treatment outcomes, and the statistical methods involved in comparing prioritized outcomes. Keywords: Tuberculosis, Treatment outcome, Risk–benefit assessment