The challenges of validating diagnostic methods relative to a conventional two-year caries clinical trial.

This paper is directed to the question, "What are the appropriate validation criteria for the use of a new clinical trial methodology as a replacement for a conventional two- to three-year caries study?" It is important to recognize that the objective of a two- to three-year randomized, controlled caries trial is to test a precisely framed hypothesis, regarding an experimental product's efficacy relative to a control product. The external validity of conventional two- to three-year caries clinical studies in determining the efficacy and safety of anti-caries products is well-accepted. However, caries clinical trials are not without limitations and have increasingly been viewed as inefficient with respect to measuring the disease process in a holistic manner. The endpoint of a caries lesion with loss of enamel integrity (cavitation) focuses on one end of the caries progression continuum at the expense of early caries initiation and progression. Several early caries detection methods have been developed that correlate with mineral loss of the tooth surface. These diagnostics differ from conventional visual-tactile and radiographic methods in that they are capable of detecting early non-cavitated lesions, and this can generate continuous data. As diagnostic methods become accepted, they will lead to study designs that diverge from the conventional two- to three-year caries studies. Modification of the existing two- to three-year conventional caries design for assessment of product effectiveness, whether by the introduction of a new diagnostic method or by modification of the overall clinical design, must result in a clinical design that is able to differentiate known treatments on the basis of caries prevention efficacy. Given that the fluoride dose response has been characterized in the literature, this should form the basis of any validation package for new methodologies. In conclusion, a minimum expectation for acceptance as a replacement to conventional testing should be that the method or design can differentiate products of known efficacy from one another and that the efficacy relationship observed in a two- to three-year conventional study can be observed with the new method or design.

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

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.

A randomised controlled trial of the efficacy of supervised toothbrushing in high-caries-risk children.

Scottish children have one of the highest levels of caries experience in Europe. Only 33% of 5-year-old children in Dundee who developed caries in their first permanent molars by 7 brushed their teeth twice a day. High-caries-risk children should benefit if they brush more often with fluoridated toothpaste. The aim of this clinical trial was to determine the reduction in 2-year caries increment that can be achieved by daily supervised toothbrushing on school-days with a toothpaste containing 1,000 ppm fluoride (as sodium monofluorophosphate) and 0.13% calcium glycerophosphate, combined with recommended daily home use, compared to a control group involving no intervention other than 6-monthly clinical examinations. Five hundred and thirty-four children, mean age 5.3, in schools in deprived areas of Tayside were recruited. Each school had two parallel classes, one randomly selected to be the brushing class and the other, the control. Local mothers were trained as toothbrushing supervisors. Children brushed on school-days and received home supplies. A single examiner undertook 6-monthly examinations recording plaque, caries (D(1) level), and used FOTI to supplement the visual caries examination. For children in the brushing classes, the 2-year mean caries increment on first permanent molars was 0.81 at D(1) and 0.21 at D(3) compared to 1.19 and 0.48 for children in the control classes (significant reductions of 32% at D(1) and 56% at D(3)). In conclusion, high-caries-risk children have been shown to have significantly less caries after participating in a supervised toothbrushing programme with a fluoridated toothpaste.

An abbreviated caries clinical trial design validated over 24 months.

Conventional caries trials last from 24 to 36 months. This study evaluated whether the previously established difference in efficacy between 1000- and 2500-ppm-fluoride dentifrices could be detected after 12 months. Caries was assessed by clinical visual assessment (CVA-simplified version of Dundee Selectable Threshold Method - DSTM), bitewing radiography, and Fiber Optic Transillumination (FOTI). Changes in status for individual surfaces were classified by means of pre-prepared matrices as 0 (unchanged), +1 (initiation or progression), or -1 (regression) and summed for each subject to yield an event score. Mean group event scores were calculated for each product. DSTM at the D(1) [enamel and dentin] threshold showed significant inter-group differences in mean event scores (p < 0.003) and D(1)MFS increment (< 0.007) at 12 months; these were confirmed at 24 months by traditional increment analysis (CVA & FOTI at the D(3) (dentin only) threshold + radiography, p < 0.03). This study confirms the validity of an abbreviated trial protocol.

An intervention programme to establish regular toothbrushing: understanding parents' beliefs and motivating children.

AIMS/OBJECTIVES: To determine the benefit of twice daily toothbrushing on newly erupted first permanent molars. To investigate, through the Health Belief Model, how parents' beliefs influence the likelihood of their children brushing twice a day. To identify aspects of a toothbrushing intervention programme that can be used in general dental practice. DESIGN: Randomised controlled trial. SETTING: Schools in deprived communities in Scotland. PARTICIPANTS: 461, 5-year-old children. INTERVENTIONS/METHODS: Supervised toothbrushing on school-days with a 1,000 ppm chalk-based fluoride toothpaste for two years. A school and home-based incentive scheme including toothbrushing charts, 6-monthly dental examinations and parental questionnaires. MAIN OUTCOME MEASURES: Caries increment and twice daily toothbrushing. RESULTS: In the control group, children who brushed once a day or less had 64% more caries than those who brushed at least twice a day (P = 0.001). In the intervention group this difference in caries was reduced to 16% (P > 0.05). The most significant parental belief explaining variation in twice-daily brushing was whether parents feel strongly that there is time to check their child's toothbrushing (P = 0.0001). The odds of these parents reporting that their child brushes twice daily are nearly three times greater. 95% of parents felt that toothbrushing charts would be a good way for dentists in practice to encourage children to brush regularly. CONCLUSIONS: The benefit of twice daily toothbrushing on caries development in newly erupted first permanent molar teeth is around 50% compared to brushing once a day or less. Parents' beliefs do influence the likelihood of their children brushing twice a day. Key parts of the intervention programme can be used when children attend general dental practice and would be welcomed by parents.

Anti-calculus activity of a toothpaste with microgranules.

OBJECTIVE: The objective of the trial was to determine the efficacy of the proven anticalculus active system (zinc citrate trihydrate [ZCT] and triclosan), when the ZCT is delivered from microgranules incorporated in a silica-based toothpaste containing 1450 ppm F as sodium fluoride. DESIGN: A monadic, single-blind, two phase design clinical trial was used to compare the effect of the test and a negative control fluoridated toothpaste on the formation of supragingival calculus. SUBJECTS AND METHODS: Male and female calculus-forming volunteers, aged 18 or over, were recruited for the study following a 2-week screening phase. All subjects were given a scale and polish of their eight lower anterior teeth at the start of both the pre-test and test phases. Subjects were supplied with a silica-based 1450 F ppm fluoridated toothpaste with no anti-calculus active for use during an 8-week pre-test phase. Calculus was assessed at the end of the pre-test and test phases using the Volpe-Manhold index (VMI). Subjects were stratified according to their pre-test VMI score (8-10, 10.5-12, > 12) and gender and then allocated at random to test or negative control toothpaste groups. Subjects with < 8 mm of calculus were excluded from further participation. MAIN OUTCOME MEASURE: The outcome variable was the mean VMI score for the test and negative control groups. RESULTS: The test toothpaste caused a statistically significant 30% reduction in calculus compared with the control paste after a 13-week use. No adverse events were reported during the study. CONCLUSION: The incorporation of the ZCT in microgranules did not adversely affect the anticalculus activity of the new formulation.

A three-year clinical trial of a combination of trimetaphosphate and sodium fluoride in silica toothpastes.

The relative efficacy of NaF silica toothpastes containing 1000 ppm fluoride and 1500 ppm fluoride in the control of dental caries is not clear-cut. Also, it has not been established that incorporation of trimetaphosphate (TMP) improves the anticaries activity of NaF toothpastes. A three-year clinical trial was conducted to test the hypotheses that: (i) the anticaries activity of NaF toothpastes containing 1500 ppm F was greater than that of NaF toothpastes containing 1000 ppm F, and (ii) inclusion of TMP improved the efficacy of NaF silica pastes. Subsidiary aims included determination of whether frequency of toothbrushing and method of rinsing after brushing were correlated with caries increments. The study involved 4196 children aged 11 to 12 years at outset. These participants had been selected from a pool of 7374 potential subjects on the basis of caries experience and dental eruption pattern. They were stratified by sex, examiner, and presence of calculus and caries, and were allocated at random to one of the four toothpastes under study. Using mirror and probe and also FOTI, we carried out clinical examinations at baseline and annually thereafter for 3 yrs. Bitewing radiographs of a subset of children were taken at baseline and at the end of the study. The outcome measure for the study, DMFS increment, was defined as the increase in caries over 3 yrs, taking into account changes occurring on individual tooth surfaces. Data for 3467 subjects were available for analyses at both baseline and year 3 examinations. Radiographs were taken for 1942 subjects at both baseline and year 3 examinations. The mean three-year clinical-only DMFS increment for the subjects using 1500-ppm-NaF pastes was 3.93, which was 6% lower than the corresponding mean of 4.19 for the 1000-ppm-NaF pastes. There was no significant difference between the mean DMFS increment for those using paste with or without TMP. Subjects who claimed to brush more frequently or who claimed not to use a tumbler to rinse after toothbrushing had lower three-year DFMS increments.

The effect of NaF and SMFP toothpastes on three-year caries increments in adolescents.

A three-year double blind clinical caries trial was undertaken to compare the anticaries efficacy of three types of active agent, namely sodium fluoride (NaF), sodium monofluorophosphate (SMFP) and the combination of NaF plus sodium trimetaphosphate (TMP), using two fluoride levels (1000 ppm F and 1500 ppm F). The prime objective of the study was to determine whether there was any difference in the anticaries efficacy between NaF and SMFP. The second objective was to assess the effect on caries protection of the incorporation of TMP into a NaF dentifrice formulation. The study was carried out to FDI protocol and involved 4,294 children aged 11-12 years at outset. These participants had been selected from a pool of 6,212 potential subjects on the basis of caries experience and dental eruption pattern. They were stratified by sex, examiner, presence of calculus and caries, and allocated at random to one of the six toothpastes under study. Clinical examinations were carried out at baseline and thereafter annually for 3 years. Bitewing radiographs of a subset of children were taken at baseline and at the end of the study. The outcome measure for the study, DMFS increment, was defined as the increase in caries over three years, taking into account changes occurring on individual tooth surfaces. After three years, clinical-only data for 3,517 children were available for the calculation of caries indices. The mean three-year DMFS increment for subjects using a dentifrice containing NaF alone was 6.4 per cent lower than for those using a dentifrice containing SMFP. The difference between the NaF+TMP users and the SMFP users was 8.1 percent.(ABSTRACT TRUNCATED AT 250 WORDS)

The oral health status and health behaviour of 12 and 15 year-old adolescents in Jakarta, Indonesia.

Indonesia is a developing country with few dental services and a population at risk to deteriorating oral health. Five hundred and ninety-one 12 and 15 year-old children drawn from a low fluoride (F- less than 0.1 ppm) urban area of Jakarta, Indonesia were examined for dental caries, fluorosis, and periodontal diseases. In addition, a questionnaire was administered investigating socio-demographic background, use of dental services, and preventive oral care. Although the severity of dental caries experience was moderate, untreated caries on the occlusal surface formed the highest proportion of the dental caries experience. CPITN examination revealed a large proportion of the subjects had calculus as their highest score, combined with a substantial number of sites which exhibited bleeding on probing. Questionnaire data revealed a high home use of fluoridated toothpaste by the subjects but a predominant use of dental services for pain relief. Findings from this study suggest a need for primary preventive programmes focusing on occlusal sealants and plaque control.

Effect of oral care habits on caries in adolescents.

Data on toothbrushing habits were collected during a 3-year caries clinical trial of sodium monofluorophosphate toothpastes in Lanarkshire, Scotland, involving 3,005 schoolchildren of mean age 12.5 years at baseline. Stated normal brushing frequency and oral rinsing method after brushing were recorded. Half the panel indicated they rinsed their mouths after toothbrushing using a beaker. The proportion of the panel brushing once per day or more increased during the trial. Differences in oral habits were observed between the sexes, with 42% of girls and 52% of boys being non-beaker rinsers and 73% of girls, but only 44% of boys, brushing their teeth at least twice per day. Twice-a-day brushers had a consistently lower caries increment than less frequent brushers. This was also seen in the baseline prevalence data, but did not account for all incremental differences noted. Subjects using beakers had consistently higher increments than non-beaker rinsers. Again, this difference could not be explained by variations in baseline prevalence. Differences in the caries increment were also observed between boys and girls, these appearing to be linked both to the cumulative effect of male/female habit variations plus a difference in the baseline caries prevalence. A dose response to the three fluoride levels, i.e 1,000, 1,500, and 2,500 ppm F, was seen for the different habit combinations which again could not be explained by differences in the baseline caries prevalence.

Periodontal awareness project in the United Kingdom: CPITN and self-assessment.

The outcome of a practitioner-orientated joint project between Unilever's Elida Gibbs and FDI, together with Elida Gibbs patient-orientated programme is described. The practitioner-orientated project concentrated on activities associated with the use of the Community Periodontal Index of Treatment Needs (CPITN) in general dental practice. These activities, involving sponsored research at a dental school and a study with UK dentists, have shown the potential of CPITN as a screening method for patients in general practice for periodontal diseases. There is evidence to show that patient-orientated programmes have increased periodontal awareness in the UK.