Potential modern alternative designs for caries clinical trials (CCTs) and how these can be validated against the conventional model.

Abstract

The main reasons that industry runs caries clinical trials (CCTs) are to provide proof of efficacy and to collect in vivo safety data on new products. In recent years, predominantly due to declining caries levels and the use of positive controls, the cost of performing these CCTs has escalated. It is now reaching the stage where it is becoming commercially prohibitive to conduct new studies. This is likely to stifle innovation of new anticaries products, and we now need new, more discriminatory, faster, and less expensive study designs. There are many ways in which the design of CCTs may be changed, such as improving diagnostic efficiency, improving data handling/statistical modeling, and using high-risk populations. However, it is paramount that the overriding principle behind CCT design validation must be that the results/conclusions from any new design are in line with those shown previously by 'conventional' CCTs, to ensure the maintenance of standards for both efficacy and safety. It is suggested that the validation of any new trial design must involve comparisons with regimens previously shown in conventional CCTs to have different anticaries efficacies. For example, since several clinical trials have shown convincing evidence for a monotonic dose response for fluoride at least up to levels of 2500 ppm F, one could choose two products, differing solely in their fluoride level. One aim for this workshop is to identify and agree on validation principles for new clinical trial designs. This will facilitate general international acceptance of novel smaller/faster CCTs designs both now and in the future. We recognize that any new design must not compromise the standard of proof of either efficacy or safety. In addition, any principles will need to take account of current understanding of the caries process, while recognizing the need for change to match future developments in cariology. Finally, the mechanism of action of the test product must be considered, in assessments of the acceptability of novel designs, if this differs markedly from the regimens used to validate the design.