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The history of clinical trials would include events in 1747 on board the Salisbury, a British Navy vessel at sea with 12 seamen critically ill with scurvy. Involving these 12 sailors in a study, an officer on board by the name of Lind evaluated six potential treatments for scurvy, and rapidly reached the conclusion that daily consumption of citrus fruits returned the men fit for duty in approximately six days (Bull, 1959). The concept of experimental randomization was first developed by Sir R.A. Fisher (1925, 1926), and the method was introduced to medical research via a study of tuberculosis treatment by Amberson and co-workers (1931), who randomized 24 TB patients into two groups, one to receive the experimental therapy, the other serving as the control. Amberson et al. also incorporated the concept of blinding into their study. Sir Austin Bradford Hill codified and built on the principles of scientific experimentation developed by Fisher, and introduced the use of random numbers in the allocation of patients in the British Medical Research Council (1948) study of the effect of streptomycin in the treatment of tuberculosis (Daniels and Hill, 1952; Hill, 1952). The first applications of clinical trial methodology for testing interventions on dental, oral, and maxillofacial diseases and conditions are more difficult to determine. For dental caries prevention, however, Chilton and Fertig (1958) and Slack and Martin (1964) were certainly among the early caries clinical trial pioneers. As clinical trials have come into the mainstream of clinical research in medicine and dentistry, a great deal of developmental work has focused on their methodological enhancement. The most successful of these efforts have come from fruitful, ongoing collaborations among clinician investigators, biostatisticians, data management specialists, biomedical ethicists, and others with an academic interest in clinical trial design and utilization. During the past 25 years, the emergence of systematic reviews and the evidence-based medicine (EBM) movement have also contributed significantly to the increasing reliance on randomized clinical trial outcomes for the advancement of better clinical practice (Richards et al., 1997; Straus and Sackett, 1998; www.cochrane.org/cochrane/ccbroch.htm#BDL, 2002).

This paper seeks to achieve four goals, each of which forms the basis for a section in the presentation. First, the rationale of risk assessment is fully described. In this section, some of the necessary conditions are identified that make disease prediction worth pursuing. The second section discusses some essential background to the understanding of risk assessment in dentistry. In this segment, attention is focused on population-based and individual-based perspectives, alternative approaches to expressing health risk, and methods for comparing the predictive accuracy of alternative risk assessment models. The third section of the paper develops a conceptual framework for risk assessment in dentistry. Particular emphasis is devoted to the identification of risk factors and their incorporation into alternative statistical models. In the fourth section, empirical data are offered by which certain comparisons of the alternative risk models can be drawn. The paper concludes with a discussion that emphasizes data and technical limitations, speculates on future applications, and suggests new avenues for research.

Caries prediction by Classification And Regression Tree (CART) analysis is an appropriate and powerful alternative or complement to the commonly used classification methods of logistic regression and discriminant analysis, both parametric and nonparametric. The binary classification tree method discussed in this article is designed for complex data and does not require assumptions about the predictor variables or about the presence or absence of interactions among the predictor variables. Furthermore, the results give insight into the structures and interactions in the data and are easy to interpret and apply. In preliminary applications of the CART algorithms to data from The University of North Carolina Caries Risk Assessment Study, the method produced prediction rules having sensitivities and specificities that were similar to or slightly better than those associated with logistic and discriminant analyses. The classification trees constructed tended to involve far fewer predictor variables than required for adequate logistic and discriminant models. For example, for first-grade children in Aiken, South Carolina, nine variables were used to define a prediction rule having 64% sensitivity and 86% specificity. Ten-fold cross-validation estimates for future data were 58% and 79%, respectively. For first-grade children in Portland, Maine, two variables were used to define a prediction rule having 62% sensitivity and 77% specificity. The cross-validation estimates for future data were 58% and 78%, respectively. A brief, and previously unavailable, explanation of the CART method is given for the special case of a dichotomous outcome variable.

Recent studies indicate that the prevalence of very mild to moderate dental fluorosis, as classified by Dean, has increased relative to that found in earlier investigations. To date, fluoridated water, fluoride supplements, the diet, fluoride dentifrices, and other topical fluoride applications have been identified as sources of systemic fluoride. Recent evidence suggests that there is a strong association between mild to moderate enamel fluorosis and the use of fluoride supplements during early childhood, and that the presently recommended supplementation schedule for U.S. children above the age of 2 years may be too high. Evidence also suggests that there is a strong association between fluoride dentifrice use during early childhood and enamel fluorosis in fluoridated populations. These findings support the need for a careful review of existing supplementation schedules and early oral hygiene practices. There is a pressing need for additional analytical epidemiological studies to confirm existing findings and to determine whether other fluoride sources may be associated with enamel fluorosis. Further, since exposure to combinations of individual risk factors has been shown to carry more than merely an additive increase in the risk of fluorosis, these studies must be multifactorial in design. There is also a need for more fluorosis prevalence and severity data to be gathered, so that the development of enamel fluorosis as a public health problem can be assessed, and so that the success of measures implemented to maximize efficacy while minimizing unwanted side-effects can be monitored.

This has been a necessarily cursory overview of three types of clinical dental caries studies: the dental survey, the randomized clinical trial, and the non-randomized comparative study. Each of these studies may be used in its appropriate place, although only the survey and the randomized clinical trial are well-grounded in scientific theory. In general, the dental survey is well-suited to gathering basic cross-sectional data on dental caries, data that serve a variety of important practical and scientific interests in the dental care system. Clinical trials and non-randomized studies are applied in evaluating a variety of therapies for dental caries. Of the two, the randomized clinical trial is by far the more powerful. As a result, the clinical trial has found a central place in dentistry. The contributions that past and present clinical caries trials have made to dental health are quite evident to most observers. It is virtually inescapable that well-conducted clinical caries trials will make even more significant contributions to dental practice in the future, thereby further improving the oral health of all.