Experimental Dentifrice Remineralization/Fluoride Uptake in an in Situ Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Experimental Dentifrice Remineralization/Fluoride Uptake in an in Situ Model (NCT00752089), a randomized phase 2 study. The primary outcome is Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, single-masked crossover study with enrollment of 20 participants. It is listed as completed. The study title and endpoint description identify an in situ remineralization and fluoride-uptake model using enamel specimens, rather than a clinical endpoint such as a change in dental symptoms. Participants were instructed to brush twice daily for one timed minute with the assigned dentifrice. The four treatment formulations were a sodium fluoride, potassium nitrate, and isopentane product; a sodium fluoride and potassium nitrate product without isopentane; a sodium fluoride product; and a fluoride-free placebo.

The crossover designation means treatment comparisons arise within a design in which participants receive more than one treatment. The treatment sequence, number and duration of treatment periods, washout arrangements, and how those features were incorporated in the model are not reported in the registry record. The masking is described as single, but the identity of the masked party is not reported in the registry record. Allocation concealment and the method used to generate the random sequence are also not reported in the registry record.

The primary outcome was percentage surface micro-hardness recovery over baseline to 14 days. The primary analysis population was Per-Protocol, excluding participants with major protocol deviations and requiring treatment exposure and a post-baseline efficacy assessment. Missing data were not imputed. The registry record notes differing participant counts by treatment group due to drop-outs. The reported primary comparisons use ANOVA and adjusted mean differences. Further details of the model specification, including treatment of period or sequence effects in this crossover, are not reported in the registry record.

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: Two to three days before the start of each treatment period participants got their teeth cleaned to remove all accessible plaque and calculus, and were provided with a fluoride free dentifrice for maintaining wash-out period and standardizing the oral conditions.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-Protocol (PP) population: All randomized participants who received at least one dose of study product, had at least one post-baseline efficacy assessments and no major protocol deviations. Missing data was not imputed. Due to drop-outs, there were differences in the "n" per treatment group.

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 Percentage Surface Micro-hardness Recovery (SMHR) of Enamel Specimens, measured over Baseline to 14 days.

The primary endpoint is percentage surface micro-hardness recovery, or SMHR, of enamel specimens from baseline to 14 days. Surface micro-hardness is used to assess the mineralization status of enamel: the record describes measuring indentations with a Wilson 2100 Hardness tester. A longer indentation relative to baseline indicates softening, while a shorter indentation represents re-hardening of the enamel surface.

SMHR combines indentation measurements taken at baseline, after intra-oral exposure, and after in-vitro demineralization. The stated calculation is (D-R)/(D-B)*100, where B is baseline, R is after intra-oral exposure, and D is after in-vitro demineralization. The percentage expresses recovery in relation to the difference between the demineralized specimen and its baseline measurement. It is therefore a continuous laboratory measure of enamel-specimen response, not a direct count of dental lesions or a participant-reported outcome.

Using a standardized hardness measure allows treatment groups to be compared on a common scale in this in situ model. The registry record reports least-squares means with 95% confidence intervals. How the analysis accounts for repeated observations or other features of the crossover is not reported in the registry record, so the endpoint should be interpreted within the limits of the analysis details that are posted.

7. Results Posted in the Registry

• NaF/ KNO3/ 2% Isopentane Dentifrice: mean 39.46 versus 17.26 on control; difference 22.20 (95% CI 10.56 to 33.84), standardized effect d = 1.26; z-test p = <0.001.
• NaF/KNO3/ 0% Isopentane Dentifrice: mean 38.31 versus 17.26 on control; difference 21.05 (95% CI 9.39 to 32.71), standardized effect d = 1.20; z-test p = <0.001.
• NaF Dentifrice: mean 36.17 versus 17.26 on control; difference 18.91 (95% CI 7.28 to 30.54), standardized effect d = 1.08; 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.

Adjusted Mean Change From Baseline in Enamel Fluoride Uptake

• 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:
  • NaF/ KNO3/ 2% Isopentane Dentifrice: mean 2,446 versus 661.18 on control; difference 1,785 (95% CI 1,144 to 2,425), standardized effect d = 1.83; z-test p = <0.001.
  • NaF/ KNO3/ 0% Isopentane Dentifrice: mean 2,767 versus 661.18 on control; difference 2,106 (95% CI 1,376 to 2,836), standardized effect d = 1.91; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for NaF/ KNO3/ 2% Isopentane Dentifrice 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 higher for NaF/ KNO3/ 0% Isopentane Dentifrice than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcome is adjusted mean change from baseline in enamel fluoride uptake. The group estimates show higher uptake in each active-dentifrice group than in the placebo group. The reported secondary ANOVA comparisons directly contrast the isopentane formulation with the formulation without isopentane, and the isopentane formulation with sodium fluoride alone; both adjusted intervals include zero. The registry does not post a sponsor analysis for every possible secondary pairwise contrast.

The overall direction of the uptake group estimates is compatible with the broad primary pattern of higher active-group values than placebo values, but the endpoints measure different properties. SMHR assesses re-hardening of enamel specimens, while fluoride uptake measures enamel fluoride content. Agreement in general direction does not make one endpoint a replication of the other, and neither result should be treated as a direct clinical outcome.

Secondary outcomes generally carry less weight than the primary endpoint because they are not the main prespecified basis for the study’s central question and are often considered alongside multiple outcomes or comparisons. The registry lists two outcome measures and one posted secondary outcome, but a multiplicity plan is not reported in the registry record. Without information about prespecification and multiplicity adjustment, nominal p-values for secondary analyses should be interpreted cautiously. The secondary findings can add context to the primary result, but they should not be used alone to establish a treatment effect or to rank the active formulations.

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

• Adjusted Mean Change From Baseline in Enamel Fluoride Uptake

9. Statistical Interpretation

10. Statistical Methods Explained

What does a least-squares mean represent?

A least-squares mean is a model-based estimate of a group’s mean outcome. In general, it can account for terms included in the statistical model, rather than simply taking the arithmetic average of all observed measurements. The registry reports least-squares means for the treatment groups and adjusted mean differences from ANOVA. The precise model terms and the way repeated treatment periods were handled are not reported in the registry record. For that reason, the estimates should be described as the sponsor-reported adjusted comparisons without assuming which covariates or crossover effects were included.

How should an adjusted mean difference be read?

A mean difference expresses the estimated separation between two group means in the outcome’s units. For the primary endpoint, positive posted differences for active dentifrices versus placebo indicate higher adjusted SMHR in the active-product group. The confidence interval gives a range of values compatible with the fitted analysis under its assumptions. If an interval includes zero, the data are compatible with no mean difference as well as with differences in either direction. That is the pattern for the posted active-versus-active comparisons. A p-value is a measure of how unusual results at least as incompatible with a specified null model would be, if that model and its assumptions held. It is not the probability that the null hypothesis is true, nor a measure of clinical importance.

Why distinguish adjusted results from recalculated results?

The recalculated comparisons use posted group summaries to form simple, unadjusted comparisons. They do not reproduce all aspects of the sponsor’s ANOVA. In particular, a summary-statistic calculation cannot recover model adjustments that are not encoded in the group means, confidence intervals, or other available summaries. The reported sponsor analysis is therefore the principal inferential result. The recalculated estimates can help readers understand the broad direction and approximate scale of the differences, but should not override the sponsor’s model-based findings. The discrepancy flag indicates that the two approaches do not fully agree, so the sponsor’s own analysis takes precedence.

What does a confidence interval add?

General explanation: an estimate alone does not show how much uncertainty remains. A confidence interval conveys statistical precision under the assumptions of the analysis. A relatively narrow interval indicates greater precision than a wider interval on the same scale, while an interval that spans zero leaves the direction of the difference unresolved by that interval. A 95% confidence interval is generated by a procedure that, over repeated studies under the model assumptions, would cover the target value at the stated rate. It is not a probability statement about the particular interval after it has been calculated.

For this trial, the primary sponsor-reported active-versus-placebo intervals are entirely positive, while the active-versus-active intervals span zero. That contrast between interval patterns helps distinguish evidence for a difference from uncertainty about differences between formulations. It does not answer whether a difference is important to patients, because the endpoint is an enamel-specimen measure and no threshold for a meaningful difference is reported in the registry record.

How does the crossover design affect interpretation?

General explanation: crossover studies can compare treatments within the same participant, which may reduce the influence of stable differences between participants. Their interpretation depends on the timing and order of treatments, the possibility of effects carrying into later periods, and suitable analysis of treatment, period, and sequence. The registry record identifies a crossover design but does not report the treatment sequence, washout details, or the statistical handling of these design features. The adjusted ANOVA results can be reported as the registry presents them, but the available details do not permit a fuller assessment of those assumptions.

What does the analysis population mean?

The primary result is based on the Per-Protocol population, not necessarily every randomized participant. The registry definition requires at least one dose, a post-baseline efficacy assessment, and no major protocol deviations. Such an analysis describes participants meeting those criteria and may be sensitive to exclusions if adherence or protocol deviations are related to outcomes. Missing data were not imputed. The registry does not report enough detail to determine the reasons for each exclusion, the amount or pattern of missingness, or how those factors might affect estimates.

In general, statistical significance and estimation answer different questions. A small p-value indicates incompatibility with a null model under the analysis assumptions; it does not quantify the size or practical importance of an effect. The estimate and its interval give more information about size and precision. Even together, these statistics do not make a laboratory outcome equivalent to a clinical outcome. Here, all inferential statements should remain specific to SMHR in the reported Per-Protocol analysis and to the study’s in situ model.

11. Confidence Intervals and Precision

Confidence intervals show the uncertainty around estimated treatment differences, conditional on the analysis model. For the primary sponsor-reported comparisons with placebo, the 95% intervals are positive and do not include zero. The lower and upper bounds nevertheless leave a range of plausible effect sizes, so the point estimate alone should not be treated as exact. For comparisons between active dentifrices, the intervals include zero and also span values on either side of it. Those comparisons are therefore less conclusive about whether one active formulation differs from another.

Precision depends on the amount and variability of the data, along with the design and model. The primary group estimates are based on 17 or 18 participants per treatment group in the reported analysis, and the trial enrolled 20 participants overall. This is a small study, and the crossover structure means the treatment-group counts should not be interpreted as a conventional parallel-group allocation of all participants. The registry record does not report the correlation structure or the model details needed to independently assess how the design contributed to precision.

The recalculated intervals use unadjusted summary-statistic methods and are not interchangeable with the sponsor’s adjusted intervals. Their differences illustrate why the sponsor’s model-based analysis is the primary reference when the discrepancy flag is true. Confidence intervals describe statistical precision, not the probability that a treatment is effective, and they do not establish whether a difference in this specimen-based measure is clinically meaningful. No threshold for meaningful SMHR change is reported in the registry record.

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 planning illustrations express requirements as participants per arm for 80% power and participants per arm for 90% power. They are not totals across both arms and are not event counts. The underlying planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect is a stated fraction of the observed effect. The original sample-size justification and design assumptions for the trial are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the assumed effect if that effect and the planning assumptions were correct. The 90% column uses a higher target chance of detection and generally requires more participants for the same assumed effect. The rows for 100% of the observed effect use the full observed estimate as the planning target; the rows for 75% and 50% use smaller assumed effects. Smaller effects need more participants to detect reliably, which is why the planning counts rise as the assumed effect is reduced.

These figures are forward-looking planning illustrations based on the observed estimate, not observed power. Observed power is not a useful substitute for interpreting the confidence interval and estimate from a completed study. The illustrations also do not recreate the original crossover design or establish the study’s actual planned sample size; the assumptions are those stated for these calculations, and the trial’s original design rationale is not reported in the registry record.

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 = 22.200; pooled standard deviation σ = 17.572.
2. n = 2 × (1.96 + 0.842)² × 17.572² / 22.200² = 9.8, rounded up to 10 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 <- 22.2                      # observed difference in means
sigma <- 17.5720606852642                     # 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(752089)
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 = 10 (80% power), 14 (90% power)
 75% of observed effect: n per arm = 18 (80% power), 24 (90% power)
 50% of observed effect: n per arm = 40 (80% power), 53 (90% power)
power.t.test: 10.9 
Simulated power at n = 10 per arm: 0.764 (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 sponsor’s own primary analysis is the ANOVA comparison of adjusted mean differences. It reports positive adjusted differences for each active dentifrice versus placebo, with 95% confidence intervals above zero and p-values below < 0.001. Comparisons among the active products have intervals that include zero and larger p-values. Those results are the appropriate reference for describing the registry’s reported inferential findings.

The simple recalculations use treatment-group summary statistics and produce unadjusted mean differences and intervals. They are useful as a transparent, approximate comparison of the posted summaries, but they do not reproduce the sponsor’s adjusted ANOVA. In particular, some recalculated interval bounds differ from the registry’s model-based bounds, even where the estimated difference is similar. This is a discrepancy between analytic approaches, not a reason to substitute one result for the other.

Because the discrepancy flag is true, the sponsor’s own analysis takes precedence. The recalculated results should be read as secondary descriptive checks and not as corrected trial findings. The registry record does not give enough detail about the ANOVA model to independently reconstruct the sponsor’s adjustment or determine exactly why the interval widths differ.

15. Multiplicity, Missing Data and Analysis Populations

The registry posts multiple pairwise primary comparisons and also reports a secondary endpoint. Testing several contrasts increases the chance of at least one nominally unusual result if each test is considered separately. General explanation: a multiplicity procedure can control the overall error rate across a defined family of tests, but the choice of family and method depends on the analysis plan. Whether the sponsor adjusted for multiplicity, and which comparisons were designated as primary or secondary within any testing hierarchy, are not reported in the registry record. The posted p-values should therefore be read as reported, without assuming they were adjusted.

The primary analysis population is Per-Protocol. It includes randomized participants who received at least one dose, had at least one post-baseline efficacy assessment, and had no major protocol deviations. The record states that missing data were not imputed and that drop-outs led to different participant counts by treatment group. It does not report the number or reasons for all exclusions, the timing and pattern of missing assessments, or sensitivity analyses for missing data. A Per-Protocol analysis can be affected if exclusions are related to treatment or outcome, and the available record does not allow that possibility to be assessed fully.

The record identifies a randomized, single-masked crossover design, but the treatment sequence, washout arrangements, and analysis of period or sequence effects are not reported in the registry record. These details matter because crossover estimates can depend on how within-participant measurements and potential carryover are handled. The statistical plan, interim analyses, and sample-size justification are also not reported in the registry record. Their absence from the record should not be taken to mean that such procedures were or were not used; it means the registry does not document them.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event figures report zero affected participants in each treatment group: the two fluoride and potassium nitrate formulations, sodium fluoride alone, and placebo. The groups at risk contained 17 or 18 participants. No serious adverse event terms are listed. The number of deaths is not reported in the registry record, so a blank or null entry should not be read as a documented zero.

The record also reports participants affected by other adverse events: 2 for the isopentane formulation, 3 for the formulation without isopentane, 4 for sodium fluoride alone, and 2 for placebo. These are counts, not estimates of comparative risk, and the group sizes are small. The registry summary does not provide event descriptions or a detailed account of severity, timing, or attribution. The figures therefore support only a limited description of the posted safety record. They do not establish that adverse events were absent or that the formulations differed in safety.

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

The primary results indicate that the sponsor’s adjusted analysis found higher percentage surface micro-hardness recovery for each active dentifrice than for fluoride-free placebo in this study’s Per-Protocol population. The intervals for those comparisons lie above zero. The active-versus-active comparisons are less decisive: their confidence intervals include zero, so the posted results do not clearly distinguish the active formulations on the primary endpoint.

The endpoint is a laboratory measure from enamel specimens in an in situ model over baseline to 14 days. It is not a direct measure of dental erosion symptoms, new caries, tooth survival, or a participant’s quality of life. Although the study summary refers to treatment of dental caries and the listed condition is dental erosion, the primary measure remains specimen-level SMHR. The registry record does not explain how the stated purpose relates to the listed condition or establish that this endpoint predicts a clinical outcome.

The findings apply to the study’s design, duration, and analyzed population. Enrollment was 20, while the primary treatment groups included 17 or 18 participants; missing data were not imputed and the analysis excluded major protocol deviations. The small study and incomplete reporting of crossover details, model specification, and multiplicity procedures limit how broadly the results can be interpreted.

Statistical evidence of a difference from placebo is not itself a judgment about clinical importance. The registry record does not report a threshold for a meaningful change in SMHR or enough information to translate the measured difference into a patient-level benefit. The posted data should therefore be understood as comparisons on an experimental enamel-specimen endpoint, rather than a basis for medical or dental advice.

18. Why This Trial Matters Statistically

This trial is statistically informative because it places three active dentifrice formulations alongside a fluoride-free comparator and reports both group estimates and pairwise adjusted analyses. The primary results illustrate how a study can show a clear difference between active products and placebo while leaving differences among active formulations uncertain. Those are distinct questions: evidence that treatment groups differ from placebo does not establish that one active formulation outperforms another.

The crossover designation also highlights the importance of design-specific reporting. General explanation: within-participant comparisons can reduce the impact of stable differences between participants, but interpretation depends on treatment sequence, period effects, carryover, and the analysis used. The registry identifies the design but does not provide those details. Readers can therefore interpret the reported estimates while recognizing that the design’s full statistical handling cannot be evaluated from the record.

The study also demonstrates why adjusted sponsor analyses should be distinguished from simple recalculations using group summaries. Similar point estimates can have different intervals when methods differ. The discrepancy flag makes that distinction consequential: the sponsor’s reported analysis takes precedence, while recalculations remain descriptive checks. Finally, the specimen-based primary endpoint and the posted secondary fluoride-uptake endpoint illustrate that statistical differences in laboratory measures do not automatically establish clinically meaningful effects. Clear reporting of endpoint relevance, analysis populations, missingness, and multiplicity is essential for interpreting a small exploratory study.

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.

This is a small study, with enrollment of 20 and treatment-group counts of 17 or 18 in the primary analysis. The primary analysis is Per-Protocol rather than an analysis of all randomized participants, and the record says missing data were not imputed. Drop-outs resulted in differing group counts. The registry does not report enough detail to assess the reasons for exclusions or the likely direction of any resulting bias.

The crossover design is identified, but the treatment sequence, period structure, washout arrangements, and model handling of period or carryover effects are not reported in the registry record. The single-masked designation is not accompanied by identification of who was masked. The ANOVA model terms and the original statistical plan are not reported, limiting independent assessment of the adjusted estimates.

The primary outcome is a specimen-based micro-hardness measure, not a direct clinical outcome. The registry record does not report a threshold for clinically meaningful change or explain how SMHR relates to outcomes experienced by participants. The study’s brief summary refers to dental caries, while the condition field names dental erosion; the record does not clarify the relationship.

Several primary pairwise comparisons are reported, but multiplicity adjustment is not described. The secondary outcome has fewer posted sponsor comparisons than possible treatment contrasts, and a secondary multiplicity plan is not reported. Finally, the recalculated unadjusted comparisons do not match all aspects of the sponsor’s adjusted analysis. With the discrepancy flagged, the sponsor analysis takes precedence, but the model details needed to reproduce it are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Experimental Dentifrice Remineralization/Fluoride Uptake in an in Situ Model — NCT00752089.
• Registry record last updated 2016-12-08; status last verified 2016-05.
• Results first posted 2016-12-08.
• 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

NCT00752089 is a completed Phase 2 randomized, single-masked crossover study of four dentifrices in an in situ enamel model. It enrolled 20 participants. The primary endpoint was percentage surface micro-hardness recovery over baseline to 14 days, analyzed in a Per-Protocol population; the registry also posts enamel fluoride uptake as a secondary outcome.

The sponsor-reported ANOVA found higher adjusted primary endpoint means for each active dentifrice than for placebo. Comparisons among active products had confidence intervals including zero. Because the record flags a discrepancy between the sponsor analysis and simple recalculations, the sponsor’s own results take precedence. These results concern enamel specimens and do not directly establish clinical effects on dental erosion or caries. Important details about the crossover analysis, multiplicity, and missing-data sensitivity are not reported in the registry record.