Understanding the variation in salivary fluoride levels: A secondary trajectory-based analysis of trial data

This report presents the findings of a secondary analysis of the data from an RCT designed to compare salivary fluoride levels during 3 weeks of using 5000 or 1450-ppm fluoride toothpaste (n = 24/group). Following this trial phase, salivary fluoride monitoring continued for 2 weeks during which all 48 participants used 1450-ppm fluoride toothpaste in a wash-out phase. We investigated the temporal variability and longitudinal growth-based trajectories of salivary fluoride levels across study arms. During the trial phase, variability in the 5000-ppm arm exceeded that of the 1450-ppm arm. The best-fitting trajectories identified three clusters of participants following: low, medium or high salivary fluoride trajectories. Except for the 'high' cluster during the wash-out period, which featured only participants from the 5000-ppm trial arm, all clusters had participants from both trial arms. In conclusion, exploration of the variation and trajectories of salivary fluoride after 1450- and 5000-ppm fluoride toothpaste-use suggests non-constant responses to the initiation of and wash-out from the use of high-dosage fluoride toothpaste. This calls for the use of repeated period cross-over trial designs to investigate treatment effect heterogeneity. Reasons for and ways to minimize sources of individual variation in salivary fluoride levels are discussed.