Stopping Cavities Study: Diammine Silver Fluoride: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Stopping Cavities Study: Diammine Silver Fluoride (NCT02536040), a randomized phase 3 study. The primary outcome is Dental Caries Activity.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group Phase 3 trial of topical diammine silver fluoride for dental caries arrest. Participants were assigned to 38% diammine silver fluoride or water. The active-treatment arm applied 38% diammine silver fluoride to an active cavity; the comparator arm applied fluoride-free water to an active cavity. The listed registry enrollment is 66. The posted arm summaries report 29 for the active-treatment group and 35 for the water group.

The registry classifies the study as quadruple masked. It does not identify which people or roles were masked, describe how masking was maintained, or report whether masking was assessed. The allocation is recorded as randomized, but details of sequence generation and allocation concealment are not reported in the registry record. The record describes a parallel model, meaning the trial compares groups assigned to different interventions rather than reporting a crossover comparison.

The study status is completed. Its recorded start was 2016-01 and its primary completion was 2016-07. The sponsor is Advantage Dental Services, LLC. The primary outcome was measured 14-21 days after treatment. The record describes one outcome measure and posts no secondary outcome results. It reports no analyses in the analysis listing.

These registry entries establish the broad design and comparison but do not give a complete protocol or statistical analysis plan. The original sample-size assumptions, planned analysis population, participant flow, and detailed analysis procedures are not reported in the registry record. The posted planning illustration is based on the observed effect and should not be confused with the trial’s original design rationale.

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

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 Dental Caries Activity, measured over 14-21 days.

The primary endpoint is the mean proportion of treated teeth with active decay that were classified as arrested by the treatment. It is described as a continuous measure, reported as a mean with a standard deviation. Assessment took place 14-21 days after treatment, using Nyvad criterion code 6. The criterion reflects hardness of the lesion and color change.

This endpoint translates the study’s stated question about caries arrest into an observable measure: the proportion of treated teeth meeting the registry’s definition of arrest. A proportion can convey how often the measured tooth-level criterion was met within the treatment experience represented by each group. Reporting a group mean and standard deviation also conveys the average outcome and the observed spread of values around that average.

As a general statistical point, the measurement definition matters because the result applies to the specified assessment and criterion, rather than to every possible definition of caries control. The short assessment window means the posted endpoint describes status at 14-21 days; it does not report what happened later. The registry does not provide additional detail about how multiple teeth within a participant contributed to the proportion, how the measure was aggregated across participants, or how assessors applied the criterion. Those details are not reported in the registry record.

7. Results Posted in the Registry

• Water: mean 0.05 versus 0.72 on control; difference -0.67 (95% CI -0.82 to -0.52), standardized effect d = -2.33; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is classified as continuous and summarized using a mean and standard deviation. The mean represents the average value of the measured proportion in a group. The standard deviation describes how dispersed the observed values were around that group mean. It is a measure of variability among observations, not a measure of uncertainty in the mean itself. The standard deviation is not a confidence interval, and it does not show the full shape of the outcome distribution.

What does the group mean represent?

The endpoint is the proportion of treated teeth with active decay that met the arrest criterion. The registry reports a mean for each randomized group rather than a count of arrested teeth. The active-treatment mean was 0.72 and the water mean was 0.05. These values summarize the endpoint as defined in the registry; the record does not give a detailed account of whether the proportion was calculated separately for each participant before group averaging, or how teeth were weighted in the analysis. That detail matters because teeth belonging to the same participant may not be statistically independent. The registry record does not explain whether or how any such clustering was handled.

As a general statistical consideration, proportions are bounded measures: they cannot fall below zero or above one when expressed on this scale. A mean and standard deviation can be useful summaries, but they do not reveal whether individual values are concentrated near the boundaries or whether the distribution is symmetric. The registry does not report a distributional assessment or a model specification, so no claim can be made about how those features were addressed.

What does the mean difference say?

The posted contrast is a mean difference of -0.67 for water compared with the active-treatment group. The sign indicates the direction of the subtraction as presented: the water-group mean is lower than the active-treatment-group mean. The confidence interval reported in the registry lies entirely below zero. A confidence interval is, in general, a range of values compatible with the data and the assumptions of the method used. It communicates precision as well as direction, but it is not a guarantee that the true effect lies within its endpoints.

The registry reports an unadjusted p-value of p < 0.001. An unadjusted p-value refers to the comparison as reported without a stated multiplicity adjustment. In general, a small p-value indicates that data at least as incompatible with the null model would be unusual if that model and its assumptions were correct. It is not a measure of the chance that the result is due to bias, and it does not establish that the assumptions are satisfied. The record does not report the test used to obtain the p-value, the exact null hypothesis specification, or an adjusted analysis.

Why does variability matter?

Within-group variability affects how precisely a group mean and a difference between means can be estimated. Standard deviations describe the observed spread; standard errors describe uncertainty in an estimated statistic under a particular method. The registry includes standard errors in its calculation material, but its inferential method and any dependence adjustments are not described. The outcome’s reported standard deviations are 0.38 for the active-treatment group and 0.18 for the water group. These summarize different degrees of observed spread and should not be mistaken for uncertainty bounds around the group means.

In general, over-dispersion means that observed variability is greater than a statistical model expects. When a model assumes less variability than the data contain, uncertainty can be understated and inferential conclusions can become too confident. That is a general reason to assess model fit and outcome variation, not a claim that this trial’s analysis had over-dispersion. The registry does not report a model or diagnostic checks from which to assess this issue.

What analysis details are available?

The registry identifies the study as randomized and reports one primary outcome measure. It posts the group summaries, a mean difference, a confidence interval, and an unadjusted p-value. It does not post an analysis description, a list of analysis populations, a missing-data method, or secondary outcome analyses. Although the record labels the study quadruple masked, the roles masked and any safeguards in outcome assessment are not specified. The trial’s own statistical analysis plan, including any prespecified covariate adjustment, is not reported in the registry record.

Consequently, the numerical comparison can be described as posted, but its calculation cannot be fully reconstructed from the registry entry alone. The analysis listing reports zero analyses, and no secondary results are posted. The absence of those details does not establish that a method was or was not used; it means the method is not reported in the registry record. A careful reading separates the displayed estimates from assumptions about how they were produced.

10. Confidence Intervals and Precision

The registry reports a confidence interval for the mean difference between water and 38% diammine silver fluoride. The interval lies entirely below zero, consistent in direction with the posted group means of 0.05 for water and 0.72 for the active-treatment group. The registry’s interval endpoints contain more than three decimal places, so they are not reproduced. The confidence level is not explicitly stated in the registry record.

In general, a confidence interval expresses the precision of an estimate under the statistical method and assumptions used. A narrower interval indicates less statistical uncertainty than a wider interval on the same scale, while an interval’s location indicates which values are compatible with the analysis. An interval that does not include zero is often interpreted as evidence against a zero mean difference under the corresponding testing framework. This statistical interpretation does not establish clinical importance or guarantee replication.

The interval’s precision should be considered alongside the trial’s size, the endpoint definition, and information that is not reported. The registry lists enrollment of 66 and arm summaries of 29 and 35, but does not describe the analysis population, missing outcome handling, or whether the analysis accounted for teeth nested within participants. These omissions limit how completely the displayed precision can be evaluated. The interval also pertains to the specified short-term outcome, not to later follow-up or other outcomes.

Thus, the posted estimate has a directionally clear interval, but the registry record does not provide enough methodological detail to independently assess all assumptions underlying that interval. Statistical precision and broader reliability are related but distinct considerations.

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, not total events. They are illustrations based on the observed effect, not a report of the trial’s original sample-size rationale. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is set as a stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm in the planning calculation for an 80% chance of detecting the chosen effect under those assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning number for a 90% chance. These are design calculations, not measures of what the completed trial achieved. They are not observed power.

The planning rows consider 100%, 75%, and 50% of the observed effect. For the full observed effect, the listed figures are 3 participants per arm for 80% power and 4 for 90% power. For planning at 75% of the observed effect, the figures are 6 and 7 participants per arm. For planning at 50% of the observed effect, the figures are 12 and 16 participants per arm. The general pattern is that smaller effects require more participants to reach the same target power. The associated curve is a visual representation of this planning relationship; it does not turn these assumptions into a finding about the trial’s original design.

Because the calculations use the observed effect, they should be treated cautiously as planning illustrations rather than as a basis for claiming that the study was adequately sized. The registry does not report the assumptions used when the trial was planned.

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 = -0.670; pooled standard deviation σ = 0.288.
2. n = 2 × (1.96 + 0.842)² × 0.288² / -0.670² = 2.9, rounded up to 3 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 <- -0.67                      # observed difference in means
sigma <- 0.288063613046303                     # 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(2536040)
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 = 3 (80% power), 4 (90% power)
 75% of observed effect: n per arm = 6 (80% power), 7 (90% power)
 50% of observed effect: n per arm = 12 (80% power), 16 (90% power)
power.t.test: 4.1 
Simulated power at n = 3 per arm: 0.573 (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. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure, Dental Caries Activity, and posts no secondary outcome results. It reports an unadjusted p-value for the comparison. No multiplicity adjustment is reported in the registry record. With only the posted primary comparison available, there is no basis for describing a correction across a larger family of outcomes or analyses. The number of posted outcomes alone does not establish what may have been planned or assessed but not reported.

The registry’s analysis listing reports zero analyses. It nevertheless includes group summaries and a comparison for the primary endpoint. The record does not explain this difference in reporting, and it does not provide a full analysis plan. Prespecified primary or secondary hypotheses, interim analyses, stopping rules, subgroup analyses, or selective reporting assessments are not reported in the registry record. They should not be inferred from the posted result.

Missing-data handling is also not described. The registry does not state whether every randomized participant contributed an outcome, how unavailable measurements were treated, or whether any imputation or sensitivity analysis was used. It does not identify an intention-to-treat, per-protocol, or other analysis population. Therefore the group counts in the outcome summaries cannot be assumed to represent a particular analysis principle beyond what the record explicitly reports.

As a general statistical matter, missing outcomes can affect both the estimated group difference and its precision, especially if availability is related to treatment assignment or outcome status. Multiplicity can also increase the chance of at least one apparently notable result when many hypotheses are examined. These are general considerations, not claims about what happened in this trial. The registry does not report enough detail to determine how either issue was addressed.

These gaps make it important to distinguish the posted numerical findings from a complete account of the trial’s statistical conduct. The available record supports describing the reported primary comparison, but not reconstructing unreported analysis decisions.

14. 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.

The registry reports serious adverse events for both groups. For 38% diammine silver fluoride, 0 serious adverse events were recorded among 29 at risk. For water, 0 serious adverse events were recorded among 35 at risk. The listed death count is 0 in each group. The record also reports 0 other adverse events in each group.

These are counts recorded in the registry, not proof that no adverse event occurred outside the reporting definitions or observation process. The registry gives no serious adverse event terms, and it does not describe the safety surveillance period, event collection methods, or criteria used to classify events. The primary outcome timeframe is 14-21 days, but the safety reporting window is not specified, so the outcome assessment period should not be assumed to define the full safety follow-up.

Zero recorded events means that the registry lists none in these categories for the groups and risk sets shown. It does not establish that the interventions are free of risk, nor does it allow a precise estimate of uncommon harms. These safety figures should be interpreted as registry reporting for this trial, not as medical advice or as a complete safety profile.

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

The posted results show different group means for the primary endpoint at the recorded assessment. The mean proportion classified as arrested was 0.72 in the 38% diammine silver fluoride group and 0.05 in the water group. The reported mean difference for water compared with the active-treatment group was -0.67, and the unadjusted p-value was p < 0.001. The registry’s confidence interval lies wholly below zero. Together, these values describe the direction, size, and statistical uncertainty of the reported comparison under the analysis used.

They do not establish that the same result would occur in other settings, populations, or follow-up periods. The endpoint refers to treated teeth with active decay and uses Nyvad criterion code 6, reflecting hardness and color change. The record reports assessment at 14-21 days and does not give longer-term outcome results. It also does not provide enough detail to assess all features of the measurement process or the analysis population.

A statistically notable comparison is not equivalent to a judgment about clinical importance. The registry does not define a threshold for a meaningful difference, and no such threshold should be inferred from the p-value. Likewise, the outcome is not a comprehensive measure of dental health or patient experience. The posted result pertains specifically to the registry’s primary measure.

The randomized design is relevant context, but the registry record does not report allocation procedures, detailed masking roles, missing-data methods, or a complete statistical plan. Those limits do not erase the reported findings, but they constrain how far they can be interpreted from the registry alone. No medical advice follows from these statistics. They describe what was posted for this trial and the precision and scope of that result.

16. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s operational definition is central to statistical interpretation. The primary outcome is not an abstract label of caries arrest: it is a proportion of treated teeth meeting a specified criterion, assessed using Nyvad criterion code 6 at 14-21 days. The group means and difference are meaningful only in relation to that measurement and timeframe. A different endpoint definition or later assessment would address a different statistical question.

It also demonstrates the value of reading an effect estimate alongside a p-value. The posted mean difference of -0.67 conveys the direction and magnitude of the contrast, while p < 0.001 summarizes compatibility with a null model under the reported unadjusted comparison. The confidence interval supplies further information about precision. No single statistic substitutes for the others, and none resolves questions about measurement, missing data, or generalizability.

The registry entry also provides an example of the boundary between posted results and a complete analysis record. It identifies randomization and masking, but does not describe sequence generation, masking roles, analysis populations, or methods for handling missing outcomes. The analysis listing reports zero analyses despite a posted primary comparison. Such gaps matter because statistical summaries depend on analysis choices as well as observed data.

Finally, the planning illustration shows why a calculation based on an observed effect must be distinguished from an original design justification. The record’s planning figures use the observed effect and stated assumptions; the trial’s own planning assumptions are not reported. Keeping that distinction clear avoids interpreting an illustrative calculation as evidence about the study’s prespecified design or achieved power.

17. 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 registry record leaves several trial-specific questions unresolved. It identifies dental caries and describes topical treatment of active cavities, but does not report detailed eligibility criteria, participant characteristics, number of treated teeth per participant, or the recruitment setting. The listed enrollment is 66, with outcome summaries for 29 in the active-treatment group and 35 in the water group. The record does not explain participant flow or whether the group summaries include all randomized participants.

The primary measure is defined as a proportion of treated teeth arrested according to Nyvad criterion code 6, but the record does not explain the calculation at participant level, the handling of multiple teeth from one participant, or assessor training and agreement. Although the trial is labeled quadruple masked, the identities of masked roles and the masking procedures are not reported. Allocation sequence generation and concealment are also not described.

Follow-up information is limited to the primary assessment at 14-21 days. The record does not post later outcomes, and it does not specify the safety observation window. It reports one outcome measure, no secondary results, and zero analyses in the analysis listing, but does not provide a full statistical analysis plan. Missing-data handling and the analysis population are not reported.

The planning illustration is calculated from the observed effect and does not provide the trial’s original sample-size assumptions. The registry does not report whether interim analyses or other prespecified analyses were planned. These omissions limit independent evaluation of trial conduct and statistical choices. They do not change the numerical result as posted, but they restrict the conclusions that can be drawn from the registry record alone.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Stopping Cavities Study: Diammine Silver Fluoride — NCT02536040.
• Registry record last updated 2020-01-23; status last verified 2016-08.
• Results first posted 2020-01-23.
• 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.

21. Record Summary

NCT02536040 is a completed randomized, parallel-group Phase 3 trial sponsored by Advantage Dental Services, LLC. It compared topical 38% diammine silver fluoride with topical fluoride-free water for active dental cavities. The registry records quadruple masking, enrollment of 66, a start date of 2016-01, and primary completion in 2016-07.

The primary endpoint was the mean proportion of treated teeth with active decay classified as arrested using Nyvad criterion code 6, assessed at 14-21 days. The posted means were 0.72 for the active-treatment group and 0.05 for water. The reported mean difference for water compared with the active-treatment group was -0.67, with p < 0.001. The registry reports no serious adverse events in either group and posts no secondary outcome results.

Details of the original sample-size rationale, analysis population, missing-data handling, and full statistical plan are not reported in the registry record.