Reply to letter to editor “methodological considerations in evaluating the effects of continuous positive airway pressure therapy on energy balance and body composition”

Dear Editor, We thank Dr. Pazarlı for the thoughtful comments regarding our randomized controlled trial evaluating the metabolic effects of continuous positive airway pressure (CPAP) therapy [1, 2]. Below, we discuss the methodological considerations that were raised in the author’s comments, and we provide clarifications related to the study design and analytical choices. The study was terminated earlier than planned because of recruitment challenges during the COVID-19 pandemic. This resulted in a smaller sample than originally targeted, which would be expected to decrease statistical precision of parameter estimates. Nonetheless, attrition was low and rarely attributable to CPAP intolerance. Primary intention-to-treat (ITT) analyses were concordant with per-protocol results, and missing data were handled conservatively using baseline observation carried forward. Secondary and exploratory endpoints were analyzed to estimate effect sizes rather than to provide confirmatory inference; accordingly, formal multiplicity adjustment was not applied. These considerations were acknowledged in the manuscript. The open-label design reflects routine clinical implementation. While sham-CPAP can address behavioral expectancy effects, it is often associated with reduced tolerance and imperfect blinding [3, 4], and prior work has shown minimal differences between sham-CPAP and conservative management for objectively or subjectively measured outcomes [5]. Importantly, our overall findings—modest weight gain without significant increases in fat mass, objectively measured energy expenditure, or physical activity—are consistent with sham-controlled trials [6, 7].