Fluoride Varnish in a Changing Preventive Environment: A Reanalysis and Temporal Meta-Regression of Historical and Contemporary Trials

Abstract

Historical trials of fluoride varnish reported large reductions in dental caries, but contemporary trials are often conducted against more intensive background prevention, so the incremental effect may be smaller. For positive continuous outcomes, we modeled the log ratio of treatment to control means and report the prevented fraction, $\mathrm{PF}=1-\exp (y)$. A nine-trial historical dataset was reanalyzed using REML with Hartung--Knapp inference, Bayesian hierarchical models, and sensitivity analyses; completeness was checked against all 13 Cochrane permanent-surface trials. Temporal change was examined in a 14-study dataset combining nine historical and five contemporary trials, with time specifications compared by AICc. The historical pooled PF was $39.7\%$ (95% CI $18.0\%$ to $55.6\%$), with a much wider 95% prediction interval ($-26.5\%$ to $71.2\%$). Expanding to 13 Cochrane trials barely changed the direct estimate ($0.439$ to $0.435$). The calendar coefficient was $0.0986$ log-ratio units per decade (95% CI $-0.0445$ to $0.2417$), with fitted PF declining from $34.8$ in 2005 to $20.6$ in 2025. A Bayesian model gave a similar slope (posterior median $0.091$; 95% CrI $-0.036$ to $0.231$). The intercept-only model had the lowest AICc, though the linear-time model was within two units. Adjusting for background prevention reduced the slope to $0.057$ per decade. The historical average effect is stable across modeling choices, whereas prediction for a new setting is much less certain. Contemporary evidence is compatible with attenuation of the incremental varnish effect but does not require a temporal moderator; the pattern is consistent with a changing treatment contrast rather than weakened biological action.

21 pages total, 2 figures and 6 tables