Is there an acceptable surrogate for caries clinical trials? Evidence from a systematic review of primary studies.

Background: There is currently a lack of evidence supporting the use of valid surrogates in caries clinical trials. This study aimed at examining the validity of two surrogate outcomes used in randomized clinical trials for caries prevention, pit and fissure sealants and fluoridated dentifrices, according to the Prentice criteria.

Methods: A systematic review was conducted in MEDLINE (PubMed), LILACS and Scopus databases up to 05 October 2022. The grey literature and the list of eligible studies' references were also screened. The search was conducted, selecting randomized clinical trials focussed on dental caries prevention using pit and fissure sealants or fluoridated dentifrices and with at least one surrogate endpoint for cavitated caries lesions. The risk of each surrogate endpoint and for the occurrence of cavitated caries lesions was calculated and compared. The association between each surrogate and the presence of cavitation was quantified, and each outcome was assessed graphically for validity according to the Prentice criteria.

Results: For pit and fissure sealants, from 1696 potentially eligible studies, 51 were included; while for fluoridated dentifrices, of 3887 potentially eligible studies, four were included. Possible surrogates assessed were retention of sealants, presence of white spot lesions, presence of plaque or marginal discoloration around the sealants, oral hygiene index, radiographic and fluorescence caries lesion assessments. However, only the retention of sealants and the presence of white spot lesions could be evaluated for their validity according to the Prentice criteria.

Conclusion: Loss of retention of sealants and the presence of white spot lesions do not fulfil all of the Prentice criteria. Therefore, they cannot be considered valid surrogates for caries prevention.