Rigor and Reproducibility: A Systematic Review of Salivary Cortisol Sampling and Reporting Parameters Used in Cancer Survivorship Research

Abstract

Salivary cortisol is a commonly used biomarker in cancer survivorship research; however, variations in sampling protocols and parameter reporting limit comparisons across studies. Standardized practices to provide rigor and reproducibility of diurnal salivary cortisol sampling and reporting are not well established. Previous systematic reviews examining relationships between diurnal salivary cortisol and clinical outcomes have resulted in mixed findings. It remains unclear which sampling protocols and reporting parameters offer the greatest utility for clinical research. This review examines diurnal salivary cortisol sampling protocols and reporting parameters to evaluate whether a standardized approach is recommended. A comprehensive search of intervention studies among adult cancer survivors including diurnal salivary cortisol resulted in 30 articles for review. Sampling protocols ranged from 1 to 4 days with the majority of studies sampling cortisol for 2 days. Sampling instances ranged from 2 to 7 times per day, with the majority collecting at 4 time points per day. Diurnal cortisol slope and cortisol awakening response (CAR) were the most commonly reported parameters associated with clinical outcomes. Flattened cortisol slopes, blunted CARs, and elevated evening cortisol concentrations were associated with poorer psychosocial and physiological outcomes. Based on our review, we propose that a rigorous, standardized diurnal salivary cortisol sampling protocol should include sampling at key diurnal times across ≥3 consecutive days to report diurnal cortisol parameters (i.e., CAR and slope) and objective measures of participant protocol adherence. Diminishing budgetary resources and efforts to minimize participant burden dictate the importance of standardized cortisol sampling protocols and reporting parameters.