Effect of pH and Fluoride Concentration of Dentifrices on Caries Control: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of pH and Fluoride Concentration of Dentifrices on Caries Control (NCT01049503), a randomized phase 3 study. The primary outcome is Evaluation of the Concentration of Fluoride Incorporated Into the Biofilm Done 6 Months After Initiation of Dentifrices Use..

2. Clinical Question

This is a question about differences in a measured biofilm fluoride concentration, not a direct comparison of clinical caries outcomes. The trial’s stated aims also included evaluating the overall effects of dentifrice pH and fluoride concentration on caries control, using visual inspection and quantitative light-induced fluorescence. The posted primary results concern the biofilm measurement; they do not by themselves establish what any observed difference means for caries outcomes.

3. Trial Design

The registry identifies NCT01049503 as a randomized, quadruple-masked, parallel-group phase 3 trial. It lists the study as completed, with enrollment of 315. The listed start was 2009-11 and primary completion was 2010-12. The sponsor was University of Sao Paulo.

The arm descriptions divide participants by caries status and dentifrice formulation. Within each status category, the listed products were 550 ppm F at pH 7.0, 550 ppm F at pH 4.5, and 1100 ppm F at pH 7.0. The instructions in the arm descriptions specify one drop of liquid dentifrice 3 times/day for 12 months. Those descriptions do not establish how consistently participants followed the instructions.

The primary endpoint has a narrower reported sample than the trial enrollment. The registry says a convenience sample of 47 children was randomly selected from trial participants in the fluoridated area, then randomly divided using block allocation into 3 groups according to dentifrice type. The posted primary results list group sizes of 16, 15, and 16. The registry does not report further details of the block procedure, sequence generation, allocation concealment, or the masking procedures.

The primary outcome was assessed at 6 months. Secondary caries outcomes are described at baseline and 12 months, including clinical progression and regression measures and quantitative light-induced fluorescence outcomes. The record does not report a complete protocol description or a detailed account of how participants were retained or included in each analysis.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: From 876 children of the 5 selected schools, 487 did not fill the informed consent. From those who filled the informed consen, 74 missed the clinical examination day or filled the exclusion criteria (had participated in other researches in the last 3 months or children using orthodontic appliances). The total number of children enrolled was 315.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The sample size was calculated according to Pessan et al. (2008). From the trial participants in the fluoridated area, a convenience sample of 47 children was randomly selected. They were randomly divided (block allocation) into 3 groups, according to the type of liquid dentifrice they had been using for 6 months.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Evaluation of the Concentration of Fluoride Incorporated Into the Biofilm Done 6 Months After Initiation of Dentifrices Use., measured over 6 months.

The primary endpoint is the concentration of fluoride incorporated into dental biofilm, measured 6 months after participants began using the dentifrices. The registry reports the measure in mmol/kg and summarizes it as a mean with standard deviation. Plaque samples were analyzed for fluoride using an ion-specific electrode after diffusion with hexamethyldisiloxane-facilitated disiloxane (HMDS).

This endpoint measures fluoride found in plaque rather than caries itself. The trial description says the biofilm concentration assessment was intended to evaluate fluoride incorporation, alongside an aim of evaluating fluoride bioavailability from the formulations. A biofilm measurement can therefore address whether the formulations are associated with different fluoride concentrations at the sampled site and time. It is not interchangeable with the caries progression or regression outcomes, and a difference in this laboratory measure does not alone quantify a clinical effect on caries.

The primary endpoint population is described as a randomly selected convenience sample of trial participants. The available record does not report additional selection criteria, the timing of plaque collection within the 6-month assessment, or further measurement-quality details. Those omissions limit how fully the measurement process and the endpoint population can be assessed from the registry record.

7. Results Posted in the Registry

• 550 Ppm F, pH 4.5: mean 1.32 versus 0.80 on control; difference 0.52 (95% CI 0.40 to 0.64), standardized effect d = 3.06; z-test p = <0.001.
• 1100 ppmF , pH 7.0: mean 1.74 versus 0.80 on control; difference 0.94 (95% CI 0.82 to 1.06), standardized effect d = 5.25; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Caries Progression in Caries-active Children After 1 Year, According to the Type of Dentifrice Used

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Caries-active 550 Ppm F, pH 4.5: mean 0.97 versus 2.12 on control; difference -1.15 (95% CI -2.49 to 0.19), standardized effect d = -0.37; z-test p = 0.093.
  • Caries-active 1100 Ppm F, pH 7.0: mean 1.75 versus 2.12 on control; difference -0.37 (95% CI -1.89 to 1.15), standardized effect d = -0.11; z-test p = 0.634.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Caries-active 550 Ppm F, pH 4.5 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Caries-active 1100 Ppm F, pH 7.0 and the control. The interval gives the range of effects that remain compatible with the data.

Caries Regression in Caries-active Children After 1 Year, According to the Type of Dentifrice Used

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Caries-active 550ppmF, pH 4.5: mean 1.44 versus 1.34 on control; difference 0.10 (95% CI -0.61 to 0.81), standardized effect d = 0.06; z-test p = 0.782.
  • Caries-active 1100ppmF, pH 7.0: mean 1.84 versus 1.34 on control; difference 0.50 (95% CI -0.16 to 1.16), standardized effect d = 0.36; z-test p = 0.140.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Caries-active 550ppmF, pH 4.5 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Caries-active 1100ppmF, pH 7.0 and the control. The interval gives the range of effects that remain compatible with the data.

Caries Progression in Caries-active Children After 1 Year, According to the Type of Dentifrice Used Assessed by the Quantitative Light Induced Method (QLF)(Fluorescence Change (∆F in %))

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Caries-active 550ppmF, pH 4.5: mean -3.46 versus 2.66 on control; difference -6.12 (95% CI -9.13 to -3.11), standardized effect d = -1.29; z-test p = <0.001.
  • Caries-active 1100ppmF, pH 7.0: mean -2.72 versus 2.66 on control; difference -5.38 (95% CI -7.83 to -2.93), standardized effect d = -1.55; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Caries-active 550ppmF, pH 4.5 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Caries-active 1100ppmF, pH 7.0 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes provide a broader picture than the primary biofilm measurement: they include caries progression and regression in caries-active children, QLF measures of lesions, and progression in caries-inactive children. Across these outcomes, the direction and apparent strength of the comparisons are not uniform. The unadjusted comparisons based on group means show intervals that include zero for some outcomes, while the QLF comparisons in caries-active children have intervals that do not include zero. These patterns do not establish a consistent clinical effect across all outcome types.

The primary endpoint concerns fluoride concentration in plaque after 6 months; the secondary outcomes concern clinical or fluorescence-based caries measures at baseline and 12 months. They are related to the trial’s broader aims but are not interchangeable. A difference in biofilm fluoride concentration is not proof of a difference in caries progression, and secondary outcome patterns cannot be used to assign a clinical meaning to the primary measurement without an analysis linking them.

The registry reports Kruskal-Wallis p-values below 0.05 for the listed secondary analyses. Those are overall tests, whereas the additional pairwise values are unadjusted recalculations of mean differences. The two approaches do not answer exactly the same statistical question. Because the record does not report an adjustment for testing multiple outcomes and contrasts, isolated unadjusted results carry less weight than a prespecified, multiplicity-aware analysis would. The full set of results is best treated as exploratory evidence about several related outcomes, not as a single confirmatory conclusion.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Caries Progression in Caries-active Children After 1 Year, According to the Type of Dentifrice Used
• Caries Regression in Caries-active Children After 1 Year, According to the Type of Dentifrice Used
• Caries Progression in Caries-active Children After 1 Year, According to the Type of Dentifrice Used Assessed by the Quantitative Light Induced Method (QLF)(Fluorescence Change (∆F in %))
• Caries Progression in Caries-active Children After 1 Year, According to the Type of Dentifrice Used Assessed by the the Quantitative Light Induced Method (QLF) (Lesion Area (mm^2))
• Caries Progression in Caries-inactive Children After 1 Year, According to the Type of Dentifrice Used

9. Statistical Interpretation

10. Statistical Methods Explained

The record reports an ANOVA for the primary endpoint across the three dentifrice groups. ANOVA is a general method for assessing whether the observed data are compatible with equal group means. A result from an overall ANOVA does not, by itself, say which pairs of groups differ. The registry reports p < 0.05 for this analysis, but it does not give an ANOVA test statistic, degrees of freedom, model details, or an interval estimate for the overall test.

What do the recalculated mean differences represent?

The pairwise comparisons are unadjusted recalculations from the posted group means and standard deviations. Each mean difference expresses the mean in a dentifrice group relative to the mean in the 550 ppm F, pH 7.0 reference group. A positive difference in these comparisons means that the comparison group’s reported mean was higher. For the primary endpoint, the recalculated differences are 0.52 mmol/kg for 550 ppm F at pH 4.5 and 0.94 mmol/kg for 1100 ppm F at pH 7.0, relative to the reference.

These recalculations use separate two-group comparisons and do not reproduce every aspect of the reported ANOVA. They are not adjusted for other variables, and the registry does not report a multiple-comparison adjustment for them. The record also does not describe a covariate-adjusted primary model. The sponsor’s analysis is the reported overall analysis; the recalculated comparisons provide additional, unadjusted pairwise descriptions.

How should a confidence interval and p-value be read?

A confidence interval describes a range of effect estimates compatible with the data and the statistical procedure used, under its assumptions. It conveys uncertainty in the estimated difference, not the range within which individual children’s measurements must fall. For a difference in means, an interval that does not include zero is consistent with a difference between the group means at the corresponding confidence level. It does not establish clinical importance or remove the possibility of bias or measurement limitations.

A p-value summarizes how unusual data at least as discrepant as those observed would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry’s primary ANOVA p-value and the recalculated pairwise p-values refer to distinct analyses and should be read accordingly.

Why do distribution and spread matter?

The posted primary endpoint is continuous, and the record summarizes each group using means and standard deviations. The spread describes variation among observations around a group mean. Statistical methods that focus on means can be sensitive to assumptions about the data and the sampling process. Unequal spread, skewness, influential observations, or dependence among measurements can affect the adequacy of a simple model. General statistical practice considers these features when choosing or checking an analysis; the registry record does not report diagnostic checks for the primary endpoint.

Over-dispersion is a general concern when observed variability exceeds what a chosen model expects. In count outcomes, for example, a model that assumes too little variation can give uncertainty estimates that are too narrow. The secondary outcomes include lesion counts per child, and their posted standard deviations indicate that observations vary. The registry reports Kruskal-Wallis analyses for those outcomes, but it does not report distributional diagnostics or the rationale for that choice. This is a general explanation of why spread and model assumptions matter, not a claim that a particular assumption was violated in this trial.

What do the secondary analyses add?

For the secondary outcomes, the registry reports Kruskal-Wallis tests across the caries-active groups and reports one such test for caries progression in caries-inactive children. The Kruskal-Wallis method compares distributions across groups using ranks rather than directly testing equality of means. The registry’s reported p-values are below 0.05 for the listed analyses. The pairwise values displayed alongside secondary group summaries are unadjusted recalculations based on means and standard deviations, so they are not the same test as the sponsor-reported rank-based analysis.

That distinction matters because a rank-based overall test and an unadjusted pairwise comparison of means have different targets and assumptions. A statistically notable overall test does not show that every pair differs, while an unadjusted pairwise result does not account for the family of comparisons. The record does not report a planned hierarchy of endpoints or a multiplicity strategy.

The trial record gives limited detail about the analysis populations, missing observations, and model specifications. Those items are important for judging whether the reported estimates correspond to all randomized participants, only participants with measurements, or another analysis set. They are not reported in the registry record, so interpretation must remain tied to the posted summaries and methods rather than assumptions about an unreported statistical plan.

11. Confidence Intervals and Precision

For the primary endpoint, the recalculated mean difference for 550 ppm F at pH 4.5 versus 550 ppm F at pH 7.0 was 0.52 mmol/kg, with a confidence interval from 0.397 to 0.643. For 1100 ppm F at pH 7.0 versus 550 ppm F at pH 7.0, the difference was 0.94 mmol/kg, with a confidence interval from 0.816 to 1.064. Both intervals lie on the positive side of zero. Their width conveys the uncertainty in each estimated contrast under the unadjusted recalculation.

The interval is not a range for individual plaque measurements, nor does it incorporate every possible source of uncertainty. In particular, it does not account for selection into the endpoint sample, unreported measurement issues, or choices in the original analysis that are not described in the registry record. The reported standard deviations describe observed variation within each group, while the confidence intervals concern estimated differences between group means.

The primary endpoint group sizes were 16, 15, and 16. With this limited endpoint sample, the precision of the estimated differences depends strongly on the observed spread and on the assumptions used in the pairwise calculations. Narrow intervals do not resolve questions about representativeness or clinical meaning. The registry’s overall ANOVA result is reported as p < 0.05, but an interval for that overall analysis is not reported in the registry record.

For secondary outcomes, some pairwise intervals include zero and others do not. Their interpretation also requires attention to the distinction between the registry’s rank-based overall tests and unadjusted recalculations of mean differences. These intervals are useful for conveying uncertainty, but they do not correct for the number of outcomes and comparisons examined.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on observed effects, not the trial’s original design calculations. For these non-time-to-event outcomes, the displayed quantities are participants per arm, not total events. The listed assumptions are two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect. The original trial’s sample-size assumptions are not reported in the registry record; the primary description says its sample size was calculated according to Pessan et al. (2008), but does not give the complete design assumptions.

The 80% power column gives an illustrative number of participants per arm for a design with an 80% chance of detecting the assumed effect if that effect and the calculation assumptions were correct. The 90% power column describes the corresponding target with a higher chance of detection. These are design-planning quantities, not probabilities that the trial’s result is true or that a finding will replicate.

The planning entries use the observed effect and smaller fractions of that effect. Planning for 75% of the observed effect generally requires more participants per arm than planning for the full observed effect; planning for 50% requires still more. This follows a general statistical principle: smaller effects are harder to distinguish from sampling variation, so more information is needed to detect them with the same target power.

These calculations are not observed power. They are illustrative projections using the posted estimates and specified assumptions, and can be unstable when observed effects come from limited samples. The sample-size display should therefore be read as a planning aid, not as a retrospective verdict on whether the completed trial was adequate.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.520; pooled standard deviation σ = 0.170.
2. n = 2 × (1.96 + 0.842)² × 0.170² / 0.520² = 1.7, rounded up to 2 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.52                      # observed difference in means
sigma <- 0.169847802052511                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1049503)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 3 (80% power), 4 (90% power)
 50% of observed effect: n per arm = 7 (80% power), 9 (90% power)
power.t.test: 3 
Simulated power at n = 2 per arm: 0.394 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as an ANOVA across the three dentifrice groups, with p < 0.05. It does not provide an overall estimate, confidence interval, test statistic, or detailed model specification for that analysis. The posted group means and standard deviations allow unadjusted pairwise recalculations: each comparison uses the 550 ppm F at pH 7.0 group as its reference and reports a mean difference with a confidence interval and unadjusted p-value.

These pairwise recalculations are supplementary descriptions, not a substitute for the sponsor’s reported ANOVA. The overall analysis asks whether the group data are compatible with equal means; the recalculations ask about two specific mean contrasts. They also have different reporting detail and may not reflect any procedures used by the sponsor that are not described in the registry record.

The record marks no discrepancy between the posted summaries and the recalculated results. Even so, the recalculations should be interpreted as unadjusted comparisons from summary statistics. The registry does not report whether the sponsor’s ANOVA included covariates, how missing observations were handled, or whether any post hoc comparisons were prespecified. Those details are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The trial reports a primary endpoint and several secondary outcomes, with more than one dentifrice comparison for some outcomes. Testing multiple outcomes and contrasts increases the chance of obtaining at least one apparently notable result even when no true differences exist. A multiplicity plan may control that risk through a prespecified testing hierarchy or an adjustment to the analysis. Such a plan is not reported in the registry record.

The reported primary ANOVA is an overall test across three groups. The pairwise estimates are unadjusted recalculations and do not account for the family of comparisons. The record does not state whether the sponsor performed post hoc comparisons, whether a primary contrast was selected in advance, or whether any secondary outcomes were designated as confirmatory. Accordingly, p-values should be interpreted as reported for their individual analyses rather than as a multiplicity-adjusted set of findings.

Missing-data handling and analysis populations are also not reported in the registry record. The posted outcome summaries give endpoint-specific group sizes, but do not explain why those numbers differ across outcomes, whether all randomized participants were included, or how missing measurements were treated. The record does not identify an intention-to-treat population, a per-protocol population, or a rule for assigning participants with incomplete follow-up to an analysis set.

These omissions do not prove that missing data or multiplicity distorted the findings. They mean that the registry record does not permit an assessment of those issues. Detailed protocol and statistical-analysis documentation would be needed to determine whether the reported analyses followed prespecified procedures, how incomplete data were handled, and how the overall error rate across outcomes was considered.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The adverse-event record lists zero serious adverse events and zero other adverse events in each of the six listed safety groups. The group-specific numbers at risk are reported separately in the safety data. These entries describe what was recorded for those categories; they should not be read as proof that no other symptoms, events, or experiences occurred, or that all participants were assessed in the same way.

Deaths are not reported in the registry record: the death fields are blank rather than presented as a count. The registry also lists no serious adverse-event terms. It does not provide definitions, collection methods, follow-up details for safety, or a narrative explaining how events were solicited and classified. Thus, the safety figures are limited to the posted adverse-event categories and record entries.

The trial’s primary endpoint and main stated aims concern fluoride concentration and caries outcomes, while these safety listings are a separate part of the record. The zero entries should be reported as registry data, not interpreted as a comprehensive assessment of every potential harm.

17. What the Result Does, and Does Not, Mean

The posted primary data show differing mean concentrations of fluoride incorporated into biofilm among the three dentifrice groups at the 6-month assessment. The sponsor-reported ANOVA has p < 0.05, and the unadjusted pairwise recalculations show positive mean differences relative to 550 ppm F at pH 7.0. These statements describe the measured endpoint and statistical comparisons; they do not establish a clinical benefit or harm.

The study also records caries outcomes, but those outcomes are secondary and use different measurements and time points. The registry does not report an analysis showing that the biofilm concentration measurement predicts or explains caries progression or regression. Nor does it state a clinically important threshold for the biofilm measure. Without that context, the clinical importance of a difference in mmol/kg cannot be determined from the primary result alone.

The findings should be understood in light of the endpoint sample description: a convenience sample that was randomly selected from trial participants and then block allocated among three dentifrice groups. The registry does not fully report selection criteria, missing-data handling, analysis populations, or the sponsor’s model details. These limitations leave uncertainty about how far the posted endpoint summaries generalize and how completely the analysis can be reconstructed.

The appropriate conclusion is therefore bounded: the registry reports a difference among group means in the primary biofilm measure and an overall ANOVA result below the stated threshold. The statistical evidence does not by itself establish that a formulation changes caries outcomes, that the measured difference is important to patients, or that the results apply beyond the study sample and setting.

18. Why This Trial Matters Statistically

This trial illustrates why endpoint choice matters in clinical research. Its primary outcome is a laboratory measurement of fluoride in dental biofilm, while its broader aim concerns caries control. Those questions are connected but distinct. A biomarker-like measurement can help characterize exposure at a biological site, but it cannot stand in for a clinical outcome without evidence that links the two.

The record also illustrates the difference between an overall test and pairwise comparisons. An ANOVA asks whether there is evidence of a difference somewhere among the group means. Pairwise mean differences describe particular contrasts and require attention to multiplicity when several are examined. Reporting both kinds of analysis without a documented testing strategy leaves readers to distinguish what each result can support.

Finally, the primary endpoint comes from a selected subset rather than a clearly described analysis of the full trial enrollment. The posted estimates are informative about the measured sample, but interpretation also depends on how participants were selected, how measurements were collected, and how missing observations were handled. Those details are not reported in the registry record. The example underscores that statistical precision and clinical meaning are separate questions, and that transparent reporting of design and analysis decisions is central to evaluating both.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint is based on a convenience sample of 47 children selected from the trial participants. Although the record says they were randomly selected and block allocated into three dentifrice groups, it does not give the selection criteria, explain how the convenience sample was assembled, or describe the block procedure in detail. Representativeness of that endpoint sample is therefore difficult to judge.

The registry provides group summaries and an overall ANOVA result, but does not report the primary model specification, diagnostic checks, test statistic, or an interval estimate for the overall analysis. The pairwise estimates are unadjusted recalculations from summary statistics. The record does not say whether they correspond to analyses planned by the sponsor or whether any other post hoc procedure was used.

Several features of the clinical outcome record also limit interpretation. The registry lists secondary outcomes at baseline and 12 months, but does not explain differences in group sizes across outcome measures or how missing measurements were handled. It does not report an analysis population, adherence data, or a link between the primary biofilm measure and later caries outcomes. Further, the record does not state a clinically meaningful threshold for the primary measure or describe how multiple comparisons were addressed.

These limitations identify reporting gaps, not proof that the conduct or analysis was flawed. They mean that assessment of representativeness, missingness, multiplicity, and clinical relevance is constrained by what the registry record reports.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Effect of pH and Fluoride Concentration of Dentifrices on Caries Control — NCT01049503.
• Registry record last updated 2012-08-30; status last verified 2012-08.
• Results first posted 2012-08-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT01049503 is listed as a completed, randomized, quadruple-masked, parallel-group phase 3 trial sponsored by University of Sao Paulo, with enrollment of 315. The study compared liquid dentifrice formulations that varied in fluoride concentration and pH among children described as caries-active or caries-inactive in a fluoridated area.

The primary endpoint was fluoride concentration incorporated into dental biofilm at 6 months, measured in mmol/kg. The registry reports an ANOVA across three dentifrice groups with p < 0.05. Unadjusted recalculations show positive pairwise mean differences relative to 550 ppm F at pH 7.0. The record also lists caries progression and regression and QLF outcomes at baseline and 12 months.

Interpretation is limited by incomplete reporting of analysis populations, missing-data procedures, multiplicity, and details of the primary statistical model. The primary endpoint findings describe biofilm measurements and do not, on their own, establish a clinical effect on caries.