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.