Efficacy and Safety Evaluation of Anti-Caries Varnish: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Evaluation of Anti-Caries Varnish (NCT04947527), a randomized phase 2 study. The primary outcome is Caries Increment.

2. Clinical Question

The clinical question is therefore a comparison between two varnish regimens, rather than a comparison with no varnish. The posted primary result concerns the endpoint population with 24-month follow-up; it should not be read as a result for every child enrolled in the trial.

3. Trial Design

This was a phase 2, randomized, quadruple-masked, parallel-group trial. The registry record lists enrollment of 274 and a status of completed. The study start date is 2022-06-04, and the primary completion date is 2024-06-19. The sponsor is Advantage Silver Dental Arrest, LLC.

Participants were assigned to the test varnish or the control varnish. The test varnish contained 10% (w/v) povidone-iodine and 5% (w/v) sodium fluoride; the control contained 5% (w/v) sodium fluoride. The record’s intervention listing includes “Placebo,” while the arm description and stated comparison identify the control as active 5% sodium fluoride varnish. The active-control description is the basis for interpreting the comparison.

“Randomized” describes assignment by chance. “Parallel” indicates that the two groups are compared as separate arms, rather than participants crossing from one treatment to another. “Quadruple” is the registry’s masking classification, but the specific people or roles masked are not reported in the registry record. Details of the randomization sequence, allocation concealment, treatment schedule, varnish application frequency, and follow-up visits are not reported in the registry record.

The primary outcome was assessed at 24 months post baseline. Its defined analysis population is all children with follow-up at that time. The outcome summaries list 121 participants in the test group and 123 in the control group. These endpoint counts are not a substitute for the full participant flow: numbers randomized, treated, lost to follow-up, and included in other analyses are not reported in the registry record. The record gives no additional information about study sites or the original design assumptions.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All children with follow-up at 24 months post-baseline.

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.

6. Primary Endpoint

The registry lists the primary outcome as Caries Increment, measured over 24 months post baseline.

The primary endpoint, caries increment, is the mean number of tooth surfaces with d2-4mfs lesions at 24 months post baseline. It counts surfaces with cavitation into enamel (d2), dentin (d3), or pulp (d4), as well as surfaces missing because of caries (m) or filled (f). The unit is number of tooth surfaces. The posted endpoint population is all children with follow-up at 24 months post baseline.

This surface-level measure captures lesion status across multiple tooth surfaces, rather than recording only whether a child has any lesion. It also includes the specified categories of cavitation, caries-related missing surfaces, and filled surfaces. In general, counting affected surfaces can describe the extent of disease observed across the dentition; that is a general explanation of the type of measure, not a claim about the trial’s design rationale.

The endpoint is reported as a mean with a standard deviation for each group. The test group mean was 9.8 surfaces, with standard deviation 10.6; the control group mean was 11.3 surfaces, with standard deviation 10.8. The registry record does not report a separate baseline-to-follow-up change score, nor does it describe how the endpoint was handled for children without follow-up at the stated time point.

7. Results Posted in the Registry

• Test Varnish: mean 9.80 versus 11.30 on control; difference -1.50 (95% CI -4.19 to 1.19), standardized effect d = -0.14; z-test p = 0.274.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary comparison is a two-sided t-test of mean final values. The outcome is recorded as a number of tooth surfaces, and the registry classifies it as a continuous measure summarized by a mean and standard deviation. The sponsor-reported analysis gives the mean difference between the test and control groups, a 95% confidence interval, and a p-value.

What does a difference in means describe?

A difference in means compares the average endpoint value in one group with the average in the other. In this trial, the reported difference is -1.5 surfaces for test varnish relative to control varnish. The negative sign indicates that the test-group mean is lower in the direction of the subtraction used for the comparison. A mean difference describes the contrast in group averages; it does not say that every participant experienced that difference, and it does not describe the full distribution of individual outcomes.

The posted means are 9.8 surfaces for the test group and 11.3 for control. Their standard deviations are 10.6 and 10.8, respectively. A standard deviation describes how spread out individual values are around a group mean. In general, larger spread makes it harder to estimate a group mean precisely when other factors are held constant. The registry record does not provide a distribution plot or report a separate analysis of the shape of these surface counts.

What does the t-test assess?

In general, a t-test compares group means while accounting for the variability in the data and the amount of information in each group. The posted method is a two-sided t-test, which assesses differences in either direction rather than testing only for a lower mean in the test group. The result reported for that test is p = 0.279. The registry record does not report whether the test included covariate adjustment, stratification, or other modifications; the listed method is “t-test, 2 sided.”

Counts of affected surfaces can have features such as skewness or over-dispersion. In general, over-dispersion means that variability is greater than would be expected under a simple count model, and it can affect the suitability of some statistical methods. This is a general methodological consideration for count outcomes, not a finding about the trial data. The registry record does not report a diagnostic assessment, a count-model analysis, or a rationale for treating the endpoint as continuous and using a t-test.

How should the p-value be read?

In general, a p-value is calculated under a statistical model that assumes no difference of the specified kind. It describes how unusual results at least as incompatible with that model would be, if the model and its assumptions were true. It is not the probability that the null hypothesis is true, the probability that the result is due to chance, or a measure of the size or clinical importance of a difference. The posted p-value is 0.279; it should be interpreted alongside the estimated difference and its confidence interval, not in isolation.

A two-sided test considers results in both directions. This fits the registry’s stated superiority comparison as a test for a difference, while the trial objective describes the test varnish as intended to be superior. The record does not report a one-sided testing plan or a pre-specified decision threshold. The analysis is therefore described according to the method actually listed in the registry, without inferring additional protocol details.

What does the confidence interval add?

A confidence interval gives a range of values for the group difference that are compatible with the data under the analysis method and its assumptions. The reported 95% interval is -4.2 to 1.2 surfaces. In general, a 95% confidence procedure would contain the true difference in 95% of repeated studies conducted under the same conditions and assumptions. It does not mean there is a 95% probability that this particular fixed difference lies in the interval. The interval’s inclusion of zero indicates that the reported data are compatible with no difference as well as with differences in either direction.

The posted recalculation is unadjusted and uses the group summary statistics. It gives a mean difference of -1.5, a 95% interval of -4.185 to 1.185, and p = 0.274. These are recalculated summary-statistic results, not a replacement for the registry-reported analysis. The registry-reported result is -1.5, with a 95% interval of -4.2 to 1.2 and p = 0.279.

The registry record does not report details of the original statistical analysis plan, baseline adjustment, model diagnostics, treatment of missing values, or any interim analyses. Accordingly, the methods explanation is limited to the stated two-sided t-test and the posted summaries. No unreported modeling choices or protocol assumptions can be established from the registry record.

10. Confidence Intervals and Precision

The registry-reported 95% confidence interval for the mean difference is -4.2 to 1.2 tooth surfaces. It gives a range of differences compatible with the posted data under the reported analysis and its assumptions. Because the interval crosses zero, it includes no difference and extends in both directions. The point estimate, -1.5 surfaces, is only one value within that wider range and should not be treated as a precise estimate of the underlying group difference.

In general, a confidence interval communicates both the direction and the precision of an estimate. A narrower interval indicates greater precision under the same method, while a wider interval indicates greater uncertainty. The posted interval allows for a range of possible differences, so the data do not pinpoint the size or direction of the underlying contrast. The standard deviations of 10.6 surfaces in the test group and 10.8 in control also describe notable variation in participant-level endpoint values, although they are not themselves confidence intervals.

The summary-statistic recalculation gives a 95% confidence interval from -4.185 to 1.185, compared with the sponsor-reported interval from -4.2 to 1.2. Both intervals include zero and tell a similar qualitative story about uncertainty. The recalculated limits retain additional decimal places because they are calculated from the posted summaries; those extra digits do not make the estimate substantively more precise than the registry-reported result.

These intervals concern the mean difference in the defined 24-month follow-up population. They do not quantify uncertainty about safety outcomes, outcomes at other time points, or children without follow-up. The registry record does not report confidence intervals for the adverse-event counts.

11. 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 planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total sample sizes or total event counts. The planning illustration uses two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect: 100%, 75%, or 50%. These are planning assumptions for an illustration; the trial’s own original design assumptions are not reported in the registry record.

For planning at 100% of the observed effect, the figures are 799 participants per arm for 80% power and 1,070 participants per arm for 90% power. At 75% of the observed effect, the figures are 1,421 participants per arm for 80% power and 1,902 participants per arm for 90% power. At 50% of the observed effect, the figures are 3,196 participants per arm for 80% power and 4,279 participants per arm for 90% power.

In general, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting an effect of the specified size at the stated significance level if that effect were real and the assumptions held. The 90% column expresses the same idea with a higher chance of detection. Higher power generally requires more participants when the other assumptions are unchanged. Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm.

These figures are planning illustrations based on the observed result, not observed power for this trial. The curve should be read as a visual representation of how the planning requirement changes with the effect size under those assumptions; it does not add evidence about the trial’s observed treatment difference.

12. 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 = -1.500; pooled standard deviation σ = 10.701.
2. n = 2 × (1.96 + 0.842)² × 10.701² / -1.500² = 799.0, rounded up to 799 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 <- -1.5                      # observed difference in means
sigma <- 10.7012936577973                     # 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(4947527)
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 = 799 (80% power), 1,070 (90% power)
 75% of observed effect: n per arm = 1,421 (80% power), 1,902 (90% power)
 50% of observed effect: n per arm = 3,196 (80% power), 4,279 (90% power)
power.t.test: 799.9 
Simulated power at n = 799 per arm: 0.798 (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.

13. Analyses Reported by the Sponsor

The registry-reported analysis gives a mean difference of -1.5 surfaces, a 95% confidence interval from -4.2 to 1.2, and p = 0.279 for the two-sided t-test. The unadjusted recalculation from the posted group summaries gives -1.5, a 95% confidence interval from -4.185 to 1.185, and p = 0.274. The estimates and interval limits are close, and both intervals include zero.

The small numerical differences arise between the reported analysis and the summary-statistic recalculation. The recalculation uses posted summary statistics and is not a reconstruction of any additional trial-level adjustment or analysis choices. The registry record does not describe further details that would explain the difference between the p-values.

The sponsor-reported result should be used as the trial’s reported analysis. The recalculated result is best understood as an unadjusted cross-check of the published group summaries, not as a correction to the sponsor’s result. Neither result establishes a clear difference in the primary endpoint, and neither should be interpreted as proof of equivalence.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint, caries increment, assessed at 24 months post baseline. It also lists adverse events as a secondary outcome, with three outcome measures and three analyses recorded, while one secondary outcome is posted. These listings do not by themselves describe how many statistical hypotheses were tested or how the analyses were organized.

Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. In general, testing many hypotheses can increase the chance of at least one apparently notable result unless the analysis plan accounts for that. The registry record does not report a multiplicity adjustment, a hierarchy of secondary outcomes, or a prespecified strategy for controlling error across analyses. It is therefore not possible to determine from the record whether or how multiplicity was addressed.

The endpoint population is described as all children with follow-up at 24 months post baseline. The registry record does not report how many participants lacked that follow-up, why any follow-up values were missing, or whether missing values were imputed. It also does not report sensitivity analyses for missing data. The posted result should be read as an analysis of the stated follow-up population, without assuming that missing outcomes were handled in a particular way.

The record does not provide a full definition of analysis populations, such as intention-to-treat, per-protocol, or safety populations. The adverse-event denominators are reported separately from the endpoint group counts, but the relationship between those populations is not described. A complete participant flow, protocol deviations, and analysis-set rules are not reported in the registry record.

Randomization and masking are listed, but details of allocation concealment and the roles masked are not reported in the registry record. The original statistical analysis plan, sample-size justification, interim analyses, and any prespecified subgroup analyses are also not reported. These absences limit assessment of whether the posted analyses align with all planned analyses; they do not establish that a particular analysis was or was not conducted.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

For serious adverse events, the registry record reports 0 affected participants among 132 at risk in the test group and 0 among 142 at risk in the control group. Deaths are reported as 0 in each group. The serious adverse event term list is empty, so no specific serious-event terms are listed in the posted results.

The “other” adverse-event counts are 42 among 132 at risk in the test group and 58 among 142 at risk in the control group. These are counts of affected participants as recorded in the registry, not counts of event episodes. The record does not provide further details about event types, severity, timing, attribution to varnish, or whether participants could contribute more than one event.

These safety denominators differ from the endpoint group counts, and the registry record does not explain the relationship between the safety and endpoint populations. The absence of reported serious adverse events in these groups is a description of the posted counts, not proof that serious events cannot occur. The figures also do not, by themselves, establish a comparative safety conclusion.

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

The main result is a registry-reported mean difference of -1.5 tooth surfaces for test varnish relative to control at 24 months post baseline. The 95% confidence interval, -4.2 to 1.2, includes zero, and the two-sided p-value is 0.279. The posted data therefore do not establish a clear difference between the groups on the primary endpoint. The result is also not a demonstration that the two varnishes are equivalent; no equivalence margin or equivalence analysis is reported.

The estimate is based on the endpoint population defined as children with follow-up at 24 months post baseline. It does not automatically describe all enrolled or randomized participants. The registry reports group means and standard deviations, but does not provide participant-level data or a full account of missing follow-up. Those limits matter when judging how broadly the result can be applied.

The trial objective concerned primary prevention in primary teeth that were sound, had only d1 lesions, or were unerupted at baseline. The primary endpoint records d2-4mfs surfaces at 24 months. The registry record does not provide enough detail to determine how closely the analyzed follow-up population matches each part of that objective beyond the stated endpoint-population description.

The safety results report no serious adverse events and no deaths in either group in the recorded safety groups, alongside other adverse-event counts. These counts describe what was posted; they do not establish that either regimen has no safety risks, nor do the figures alone show that one regimen is safer.

In general, statistical evidence about a group mean is distinct from a clinical judgment about the importance of a difference. The record does not state a threshold for a clinically important difference in tooth-surface count. The observed estimate, uncertainty, endpoint definition, follow-up population, and limitations should be considered together rather than turning the p-value into a standalone conclusion.

17. Why This Trial Matters Statistically

This trial illustrates why an estimate and its uncertainty should be read together. The point estimate is -1.5 surfaces, but the 95% confidence interval runs from -4.2 to 1.2 and includes zero. The p-value of 0.279 is consistent with the same broad interpretation: the posted primary analysis does not establish a clear difference, while the interval also shows that the data do not pin down the size or direction of the underlying difference with high precision.

The endpoint is a count of affected tooth surfaces, summarized as a mean. Counts can be variable, and the group standard deviations are 10.6 and 10.8 surfaces. This provides a practical example of how variation among individuals affects precision even when group averages are available. Statistical interpretation depends not only on the means but also on dispersion, group information, and the analysis assumptions.

The comparison is active-control rather than varnish versus no treatment: both arm descriptions include sodium fluoride, with povidone-iodine added to the test varnish. This makes it important to describe the estimate as a contrast between the two specified varnishes, rather than as an estimate of varnish versus no varnish.

The posted endpoint population requires follow-up at 24 months, while the registry record does not report missing-data methods or a complete participant flow. This highlights how the definition of the analysis population affects what a result can describe. The planning illustration also shows that sample-size requirements depend on the effect chosen for detection, under stated assumptions; it does not convert the observed result into a measure of realized power.

18. 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 result is limited to the endpoint population described as all children with follow-up at 24 months post baseline. The registry record does not provide participant flow, the number with missing follow-up, reasons for missingness, or methods for handling missing outcomes. This makes it difficult to assess how follow-up relates to the enrolled population.

The record provides the primary endpoint definition and group summaries, but no participant-level data, baseline endpoint summaries, or detailed baseline characteristics. It does not report whether the primary comparison was adjusted for baseline values or other factors. It also does not report diagnostic checks or a rationale for the listed t-test for a surface-count outcome.

The trial’s original sample-size calculation and design assumptions are not reported in the registry record. The planning figures are retrospective illustrations based on the observed effect and should not be mistaken for the trial’s original design. A statistical analysis plan, multiplicity approach, interim analyses, and complete analysis-population definitions are not reported.

The registry lists quadruple masking but does not identify which roles were masked or describe the masking procedures. Further operational details, including application schedule, follow-up procedures, study sites, and allocation concealment, are not reported. The record also does not provide confidence intervals for adverse-event counts or enough detail about the nature and attribution of other adverse events.

Finally, the primary endpoint is a specific surface-level measure at 24 months. The registry record does not establish how the result relates to outcomes at other times or to a separately defined threshold of clinical importance. These limitations concern what can be concluded from the posted registry information; they do not imply that unreported procedures or analyses were absent from the full study.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy and Safety Evaluation of Anti-Caries Varnish — NCT04947527.
• Registry record last updated 2025-10-09; status last verified 2024-08.
• Results first posted 2025-02-03.
• 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.

22. Record Summary

NCT04947527 is a completed phase 2 randomized, quadruple-masked, parallel-group trial of anti-caries varnish for primary prevention. Enrollment is listed as 274. The test varnish contained 10% (w/v) povidone-iodine and 5% (w/v) sodium fluoride; the active control contained 5% (w/v) sodium fluoride.

The primary endpoint was mean caries increment, defined as the number of tooth surfaces with d2-4mfs lesions at 24 months post baseline. The registry-reported mean difference was -1.5 surfaces, with a 95% confidence interval from -4.2 to 1.2 and p = 0.279. The posted result does not establish a clear difference between groups.

Serious adverse events and deaths were recorded as 0 in both safety groups. Other adverse-event counts were 42 in the test group and 58 in control. The registry record does not report the missing-data approach, multiplicity strategy, original sample-size assumptions, or full analysis-population definitions.