Efficacy of Three Toothpastes Using an in Situ Caries Model: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Three Toothpastes Using an in Situ Caries Model (NCT02751320), a randomized na study. The primary outcome is Percentage Surface Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks.

2. Clinical Question

The study used human enamel specimens that had first been demineralized in vitro. Two lesion types were included for each participant, and the specimens were retained beneath gauze in a modified partial denture. The primary measure, surface microhardness recovery, was assessed for the S lesion specimens after two weeks. Other outcomes assessed mineral changes in specimens over the study period, including transverse microradiography and enamel fluoride uptake.

The registry identifies the trial as randomized, single-masked, placebo-controlled and crossover, with an incomplete block design. Those design features mean the comparison is about measured changes in specimens under the study conditions. They do not establish how a toothpaste would affect caries occurrence or treatment in a broader clinical setting.

3. Trial Design

The registry describes a single-centre, randomized, blinded, placebo-controlled, six-treatment, four-period crossover study with an incomplete block design. It lists 58 enrolled participants and a completed status. The recorded start date is 2016-02-01, and the primary completion date is 2016-07-01. The original sample-size justification and the trial’s own detailed statistical plan are not reported in the registry record.

Participants were healthy adults who wore a removable bilateral mandibular partial denture. The denture was modified to hold four gauze-covered human enamel specimens that had been demineralized in vitro: two S lesions and two low-R lesions. The study summary says participants used assigned products off-site twice daily. After 14 days, the S lesion specimens were removed at the study site; after a further 14 days of product use, the low-R specimens were removed.

Participants brushed their natural teeth with a pre-wetted toothbrush and assigned dentifrice for one timed minute, taking care not to brush the retained specimens directly, then rinsed with 15ml of tap water for approximately 10s. The six intervention descriptions include formulations with 0 ppm F or 1150ppm F, and different combinations of phytate, zinc chloride and sodium citrate. The exact treatment sequence and period allocation for each participant are not reported in the registry record.

The crossover structure means a participant could contribute observations under more than one treatment, but the posted group summaries do not give a participant-level account of treatment sequences or within-participant correlations. The primary endpoint summaries list four groups, although the overall study description lists six treatments. The registry record does not explain this difference. Nor does it report details of any washout periods, the handling of period or sequence effects, or how incomplete participation across treatments was addressed.

The stated primary population was an intent-to-treat population defined as randomized participants who received study products at least once and provided at least one post-baseline efficacy assessment. The recorded enrollment should not be read as the denominator for every endpoint: the primary summaries show endpoint-specific group counts, and some posted outcomes have different counts. Detailed reasons for all missing specimen or outcome data 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: A total of 58 participants were screened, of which 45 participants were randomized and 42 completed the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population, all participants who were randomized, received the study products at least once and provided at least one post-baseline assessment of efficacy. Number of participants who missed enamel specimens were: Test product 1- \[1\], Test product 2- \[1\], Reference Product 1- \[1\], and Reference Product 2- \[1\].

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 Microhardness Recovery (SMHR) of Phyte (0% 0.425% and 0.85%) at 2 Weeks, measured over Baseline upto 2 weeks.

The primary endpoint is percentage surface microhardness recovery (% SMHR) of phytate formulations at two weeks, measured from baseline through the first two weeks. Surface microhardness testing estimates changes in the hardness of partially demineralized enamel. The registry describes measurement of indentation lengths in sound enamel at baseline, after in vitro demineralization, and after intra-oral exposure. The recovery calculation uses those three measurements to express the enamel’s change after exposure relative to its prior demineralization.

In general, surface hardness is used as a laboratory measure of mineralization-related change in enamel. It gives a continuous outcome, so a group mean describes the average measured recovery and a standard deviation describes how dispersed individual measurements were around that mean. These statistics do not show the full distribution of individual results, nor do they directly measure clinical caries events.

For this trial, the endpoint applies to enamel specimens worn by participants, not to changes in participants’ teeth. The specimens were exposed intra-orally while participants used the assigned dentifrice, but were not directly brushed. The primary summaries report means and standard deviations for Test Product 1, Test Product 2, Reference Product 1 and Reference Product 2. The sponsor’s posted analyses use ANCOVA and report adjusted mean differences for specified group contrasts. Because the registry’s recalculated comparisons and the sponsor’s reported analyses do not align, interpretation should prioritize the sponsor’s own analysis, while treating the simple comparisons as descriptive recalculations.

7. Results Posted in the Registry

• Test Product 1: mean 25.53 versus 7.41 on control; difference 18.12 (95% CI 7.65 to 28.59), standardized effect d = 0.90; z-test p = <0.001.
• Test Product 2: mean 26.81 versus 7.41 on control; difference 19.40 (95% CI 9.87 to 28.93), standardized effect d = 1.06; z-test p = <0.001.
• Reference Product 2: mean 28.88 versus 7.41 on control; difference 21.47 (95% CI 11.13 to 31.81), 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.

% SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate

• 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:
  • Test Product 2: mean 26.81 versus 28.88 on control; difference -2.07 (95% CI -12.34 to 8.20), standardized effect d = -0.11; z-test p = 0.693.
  • Test Product 3: mean 23.38 versus 28.88 on control; difference -5.50 (95% CI -16.30 to 5.30), standardized effect d = -0.27; z-test p = 0.318.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test Product 2 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 Test Product 3 and the control. The interval gives the range of effects that remain compatible with the data.

Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks

• 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:
  • Test Product 1: mean 3,055 versus 3,850 on control; difference -794.47 (95% CI -1,695 to 105.79), standardized effect d = -0.46; z-test p = 0.084.
  • Test Product 2: mean 2,773 versus 3,850 on control; difference -1,077 (95% CI -1,888 to -265.92), standardized effect d = -0.68; z-test p = 0.009.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test Product 1 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Test Product 2 than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate

• 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:
  • Test Product 2: mean 2,773 versus 2,720 on control; difference 52.96 (95% CI -513.93 to 619.85), standardized effect d = 0.05; z-test p = 0.855.
  • Test Product 3: mean 2,733 versus 2,720 on control; difference 13.33 (95% CI -569.27 to 595.93), standardized effect d = 0.01; z-test p = 0.964.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Test Product 2 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 Test Product 3 and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the assessment beyond the primary surface microhardness measure. They include additional SMHR comparisons, transverse microradiography net remineralization change at four weeks, and enamel fluoride uptake. Together, these outcomes describe several laboratory measures of enamel mineral status and fluoride uptake rather than clinical caries outcomes in participants.

The overall pattern is not uniform across the secondary summaries: estimates vary by measure and treatment contrast, and the uncertainty around several recalculated contrasts is broad. The secondary results therefore do not form a single consistent confirmation of the primary endpoint. They provide related but distinct information, because each method measures a different feature of the enamel specimens and some are assessed at a different time point.

The registry posts five secondary outcome records, but the reported-analyses lists for the secondary outcomes are empty. The numerical comparisons in the posted summaries are simple recalculations, not sponsor-reported inferential analyses. They should not be interpreted as equivalent to a prespecified confirmatory analysis or as independent proof of a treatment effect.

General: when many endpoints or contrasts are examined, the chance of at least one apparently noteworthy result can increase. Adjustment for multiplicity or a prespecified hierarchy can help control that issue, but the registry record does not report a multiplicity plan for these outcomes. Unadjusted secondary results consequently carry less weight than the primary analysis, particularly when they are exploratory, numerous, or not accompanied by a reported sponsor analysis. They can help identify patterns for further study, but they should be interpreted alongside the primary result, measurement differences, uncertainty and missing-data limitations.

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

• % SMHR of 0.85% Phytate Compared to 0% Phytate, in Presence of 1150ppm Fluoride and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm Fluoride and 0.85% Phytate
• Transverse Microradiography (TMR) Net Remineralization Change (ΔM) Value of Phytate (0% 0.452% and 0.85%) at 4 Weeks
• TMR Δm Value of 0.85% Phytate Compared to 0% Phytate, in the Presence of 1150ppm F and 0.3% ZnCl2, 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.3% ZnCl2 Compared to 0% ZnCl2 in the Presence of 1150ppm F and 0.85% Phytate
• Enamel Fluoride Uptake (EFU) of All Study Formulation Variables
• Enamel Fluoride Uptake (EFU) of All Study Formulation Variables

9. Statistical Interpretation

10. Statistical Methods Explained

What does a group mean describe?

The primary endpoint is continuous: each specimen assessment yields a percentage surface microhardness recovery value. A group mean is the average of the observed values in that group. The standard deviation describes spread around that average, rather than uncertainty in the mean itself. A large standard deviation relative to a mean suggests that observations varied considerably within the group. It does not reveal whether the distribution was symmetric, whether there were influential extreme values, or how results varied within the same participant across treatment periods.

General: in a crossover study, observations from the same participant can be correlated because they share participant characteristics. An analysis that uses this relationship may differ from a simple comparison of separate group means. The registry reports that the sponsor used ANCOVA for the primary comparisons, but the exact model terms, covariance structure and handling of period or sequence are not reported in the registry record. Therefore, the posted simple recalculations should not be treated as a reconstruction of the full crossover analysis.

What does a mean difference represent?

A mean difference expresses a contrast between two group means in the outcome’s original units. A positive or negative sign depends on the order used for the contrast. It is not a percentage change unless the endpoint and calculation specifically define it that way. The simple recalculations are unadjusted comparisons based on posted means, standard deviations and group counts. Their confidence intervals and p-values are therefore distinct from the sponsor’s ANCOVA estimates.

The registry reports that the sponsor’s method was ANCOVA and labels the estimate as a net mean difference. In general, ANCOVA compares groups while accounting for covariates included in the model. Which covariates were used and how they were selected are not reported in the registry record. Since the sponsor’s analysis is the trial’s reported analysis and the record identifies a discrepancy, it takes precedence over a simple unadjusted recalculation for interpreting the study’s formal comparison.

How should a p-value be read?

General: a p-value measures how compatible data are with a specified null model, given the assumptions of the analysis. A small p-value is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. A p-value also does not account for every source of uncertainty, such as model misspecification, missing outcomes or multiple comparisons. For this reason, the effect estimate and confidence interval should be considered alongside the p-value.

The reported ANCOVA p-values for the two experimental-product comparisons with Reference Product 2 are 0.760 and 0.355, and the interval estimates include zero. These results do not establish a difference in those comparisons. They also do not prove that the treatments are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether plausible differences fall within that margin; such information is not reported in the registry record.

Why does dispersion matter?

General: dispersion matters because individual observations can vary around their group mean. When variability is large relative to the difference being estimated, an estimate is less precise unless the study has enough informative observations. Standard deviations describe variation among observations, while standard errors and confidence intervals describe uncertainty in an estimate. They answer related but different questions.

The primary endpoint summaries report standard deviations, and the recalculations use those summaries to estimate simple mean differences and intervals. The analyses are based on posted aggregate statistics rather than participant-level measurements. They cannot account for details that are absent from those aggregates, including the correlation between repeated observations from the same participant or the exact pattern of missing specimens.

What does a crossover design change?

General: a crossover design can compare treatments within the same participant, which may reduce the influence of stable differences between participants when the analysis appropriately models repeated observations. It also introduces potential period, sequence and carryover considerations. Whether those considerations were relevant and how they were handled cannot be inferred from the design label alone. The registry record does not report the treatment sequences, any washout details, or the sponsor model specification needed to evaluate those features.

The study is described as a four-period crossover with an incomplete block design, while six treatments were included overall. This means not every participant necessarily contributed data to every treatment, but the exact allocation pattern is not reported. Endpoint-specific group counts vary, and the primary analysis population required at least one post-baseline efficacy assessment. These features make it especially important to distinguish the listed enrollment from the counts contributing to each outcome.

What can recalculation add?

The posted recalculations offer a transparent, unadjusted way to compare summary means and to illustrate how uncertainty depends on the observed effect and dispersion. They can help readers understand the scale of a contrast, but they do not replace the sponsor analysis. Here, the discrepancy flag and differences between the comparison groupings mean the recalculations should be read as descriptive checks only. The sponsor’s reported ANCOVA results take precedence for the trial’s own treatment comparisons.

11. Confidence Intervals and Precision

A confidence interval gives a range of values compatible with the observed data under the analysis assumptions. General: narrower intervals indicate greater precision; wider intervals indicate less precision. An interval crossing zero for a mean difference means that the data do not rule out zero difference at that interval’s confidence level. It does not establish that the groups are equivalent, and the interval should be interpreted in light of the analysis method and design.

For the two sponsor-reported experimental-product contrasts against Reference Product 2, the 95% confidence intervals are -8.11 to 5.94 and -10.34 to 3.74. Both include zero and also include values in either direction. The posted estimates therefore remain compatible with a range of possible differences. The Test Product 1 versus Test Product 2 interval, -4.81 to 9.23, also includes zero. These are ANCOVA intervals and take precedence over the simple unadjusted recalculations for interpreting the sponsor’s trial analysis.

The recalculated intervals are different: for example, the posted unadjusted Test Product 1 comparison has an interval of 7.653 to 28.59, while the Test Product 2 recalculation has an interval of 9.871 to 28.93. These estimates compare against the recalculation’s stated control mean and are not interchangeable with the ANCOVA contrasts. The record flags a discrepancy, so their apparently different precision or direction should not be read as a competing formal analysis.

General: confidence intervals reflect sampling uncertainty under a chosen statistical model. They do not automatically account for multiplicity, missing data, endpoint selection, model choices or all crossover-design features. The registry record does not report enough detail to assess each of those sources of uncertainty. Precision should therefore be judged from the interval width together with the analysis and reporting limitations, rather than from the p-value alone.

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 the observed effect, not the original trial’s design justification. The original design assumptions are not reported in the registry record. These figures are participants per arm, not total events. The event-count convention applies to time-to-event tables, and this outcome is continuous.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculations consider detecting the full observed effect, 75% of the observed effect, or 50% of the observed effect. For example, for the Test Product 1 recalculation, the listing gives 20 participants per arm for 80% power and 26 participants per arm for 90% power when planning for 100% of the observed effect. For 75% of the observed effect, it gives 35 and 46 participants per arm; for 50%, it gives 78 and 104.

The 80% power column describes the number of participants per arm the calculation estimates would be needed for an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true effect. The 90% column uses a higher target chance of detection, so its participant count is larger. Smaller effects need more participants because they are harder to distinguish from random variation. These illustrations are not observed power: they are planning scenarios derived from the observed effect, and observed effects can be imprecise or overestimated.

The curve should be read as a visual representation of how the planning requirement changes as the target effect changes. It does not show actual enrollment over time or establish the trial’s achieved power. The registry’s enrollment is 58, but the endpoint-specific group counts differ; the planning illustrations should not be read as a report of the number analyzed or as evidence that the study met an original power target.

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 = 18.120; pooled standard deviation σ = 20.106.
2. n = 2 × (1.96 + 0.842)² × 20.106² / 18.120² = 19.3, rounded up to 20 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 <- 18.12                      # observed difference in means
sigma <- 20.1055346857526                     # 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(2751320)
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 = 20 (80% power), 26 (90% power)
 75% of observed effect: n per arm = 35 (80% power), 46 (90% power)
 50% of observed effect: n per arm = 78 (80% power), 104 (90% power)
power.t.test: 20.3 
Simulated power at n = 20 per arm: 0.792 (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 ANCOVA as the sponsor’s method for primary comparisons and also flags a discrepancy between the recalculated and reported analyses. The recalculations use posted group summary statistics to produce simple unadjusted comparisons. They do not reproduce the sponsor’s model, and the group contrasts used in the recalculation do not match all of the sponsor-reported contrasts.

For Test Product 1 versus Reference Product 2, the sponsor reports an adjusted mean difference of -1.09, a 95% confidence interval from -8.11 to 5.94, and p = 0.760. For Test Product 2 versus Reference Product 2, the reported adjusted mean difference is -3.30, with a 95% confidence interval from -10.34 to 3.74 and p = 0.355. Both intervals include zero. These analyses are the registry’s own reported treatment comparisons and take precedence over the simple recalculations.

The recalculated contrasts against the stated control mean produce different estimates and unadjusted p-values. Their differences from the sponsor results should not be resolved by choosing whichever result appears more favorable or more precise. The appropriate reading is that the sponsor analysis is the primary reported analysis, while the recalculation is an unadjusted descriptive check. The registry record does not provide the full ANCOVA specification or participant-level data needed to reproduce the sponsor’s analysis independently.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes, with multiple treatment contrasts represented in the posted analyses. However, a prespecified multiplicity strategy—such as an adjustment, testing hierarchy or designation of selected comparisons as confirmatory—is not reported in the registry record. Without that information, the risk of false-positive findings from examining multiple endpoints and contrasts cannot be evaluated from the record alone.

The sponsor’s reported primary analyses include four ANCOVA contrasts. The registry does not state whether those comparisons were prespecified, whether p-values were adjusted for multiple testing, or whether any interim analyses were conducted. Interim analyses and stopping rules are not reported in the registry record. The secondary outcome records have no sponsor-reported analysis entries, which further limits assessment of how those results were intended to be interpreted.

The primary population is described as an intent-to-treat population consisting of randomized participants who received study products at least once and posted at least one post-baseline efficacy assessment. That definition excludes randomized participants without a post-baseline efficacy assessment, so it is not a complete randomized-population analysis in the ordinary sense. The registry record does not report the number excluded under this definition, the reasons for missing assessments, or the methods used to handle missing data.

The primary description notes participants who missed enamel specimens for Test Product 1 and Test Product 2, and begins a further entry for Reference Product 1 without giving a complete count. This indicates that specimen availability was an issue, but the full pattern is not reported. The endpoint summaries give different group counts, and details on whether missingness depended on treatment, period, lesion type or participant characteristics are not reported in the registry record.

General: missing-data methods matter because an analysis based only on observed measurements can be biased if the likelihood of having a measurement is related to the outcome. The registry does not provide enough information to determine whether that concern affected these estimates. The crossover and incomplete-block features also make the unreported treatment-sequence, period and within-participant analysis details important to understanding both missingness and precision.

16. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: invasive ductal breast carcinoma (3.6%).

The registry reports serious adverse event counts by treatment group. The at-risk counts are 28 for Test Product 1, 28 for Test Product 2, 28 for Test Product 3, 29 for Reference Product 1, 27 for Reference Product 2 and 28 for Reference Product 3. One serious adverse event is listed for Test Product 1; the serious adverse event count is zero in each of the other listed groups. The death count is zero for every listed group.

The registry lists INVASIVE DUCTAL BREAST CARCINOMA as a top serious term at 3.6%. The record does not provide enough detail to infer causation, timing, or whether the event was considered related to a study product. A serious adverse event occurring during a study is not, by itself, evidence that the product caused it.

These are treatment-group figures in a crossover study. They should not be added together to estimate a number of distinct participants, because participants may have received more than one treatment. The adverse-event summaries also do not describe non-serious events in detail or provide a full narrative for the serious event. The registry record is a limited safety summary, not a causal assessment.

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

The primary endpoint concerns changes in the hardness of enamel specimens worn in participants’ dentures. It is a laboratory measure collected under in situ conditions. It is not a measure of caries incidence, tooth preservation, symptoms or quality of life. The distinction matters: a change in a specimen-based mineralization measure cannot be translated directly into a clinical benefit for participants.

The sponsor’s ANCOVA estimates for the two experimental-product comparisons with Reference Product 2 have confidence intervals that include zero. These results do not establish a difference in those comparisons, but they do not demonstrate equivalence or rule out all potentially relevant differences. The registry record does not report an equivalence margin, a non-inferiority design, or a clinical threshold for interpreting the size of a difference.

The recalculated unadjusted contrasts give a different picture from the sponsor’s reported ANCOVA results. Because the record flags a discrepancy, the sponsor’s own analysis takes precedence. The recalculations can help illustrate how simple comparisons from posted summary statistics behave, but they cannot settle the formal treatment comparison or explain the source of the discrepancy.

The secondary measures are also specimen-based and include different mineralization methods and time frames. Their results add context about laboratory outcomes, but they do not remove the limitations of the primary endpoint or establish a clinical effect. The registry does not report multiplicity handling for the several outcomes and contrasts, so isolated secondary findings should be interpreted cautiously.

Overall, the record supports a narrow reading: it reports outcome summaries and sponsor analyses from an in situ enamel model in healthy adults. It does not establish long-term effects, effects on clinical caries, or results for populations not represented in the study. Those broader questions are not answered by these posted data.

18. Why This Trial Matters Statistically

This study is statistically interesting because it combines a crossover design with an incomplete treatment block and repeated specimen measurements. In general, crossover designs can use within-participant comparisons, but valid inference depends on how correlation, period and sequence are handled. The registry identifies the design but does not provide the model specification needed to evaluate those details.

The record also illustrates why a recalculation from group means is not necessarily the same as a trial’s own analysis. The posted unadjusted contrasts and sponsor ANCOVA results differ, and the registry flags a discrepancy. Reading the estimates alongside their methods prevents a simple calculation from being mistaken for the sponsor’s formal result. The reported ANCOVA comparisons, rather than the recalculations, are the relevant source for the trial’s own primary inferences.

Another statistical issue is the gap between a specimen-level laboratory outcome and a clinical outcome. The primary endpoint is continuous and may be useful for studying mineralization under controlled exposure conditions, but it does not directly represent caries in participants. This distinction helps keep interpretation proportional to what was measured.

Finally, the record presents multiple outcomes, several treatment contrasts, variable endpoint counts and incomplete detail on missing measurements and multiplicity. These are common reasons that precision, analysis populations and prespecification matter as much as a point estimate. The study can inform how an in situ model was used to compare formulations, while also showing why full analysis details are necessary before making broader claims.

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 outcome is measured in enamel specimens carried in dentures, rather than in participants’ natural teeth or through clinical caries outcomes. The short exposure periods and specimen-based assessment limit conclusions to the model and measures reported. The registry does not report follow-up for longer-term clinical outcomes.

The study is described as single-centre, with healthy adult participants who wore removable bilateral mandibular partial dentures. The record does not establish how representative this group is of people with different health characteristics, denture use or caries risk. Generalizability beyond the enrolled population and study setting is therefore uncertain.

The design includes six treatments across four periods in an incomplete block, but treatment sequences, any washout details and the allocation of treatments to participants are not reported. The sponsor’s ANCOVA model terms and handling of within-participant correlation, period and sequence are also not reported. These omissions limit independent assessment of the analysis.

The primary outcome counts are not identical across groups, and the primary population definition requires a post-baseline efficacy assessment. The record mentions missed enamel specimens but does not provide a complete account of missing observations, reasons for missingness or the methods used to address it. Potential effects of missingness on estimates cannot be assessed from the registry summary.

Finally, the posted simple recalculations do not agree with the sponsor’s reported primary analysis. The record flags this discrepancy, but does not provide participant-level data or a complete analysis specification that would allow the source to be resolved. The registry also does not report a multiplicity plan or detailed secondary inferential analyses. These limitations call for emphasis on the sponsor’s reported primary results and caution in interpreting exploratory secondary comparisons.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy of Three Toothpastes Using an in Situ Caries Model — NCT02751320.
• Registry record last updated 2017-10-13; status last verified 2017-07.
• Results first posted 2017-10-13.
• 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

NCT02751320 is a completed randomized, single-masked, placebo-controlled, single-centre crossover study of six toothpaste treatments in an in situ caries model. The record lists 58 enrolled healthy adults who wore removable partial dentures containing demineralized enamel specimens.

The primary outcome was percentage surface microhardness recovery through two weeks. The registry reports group means and standard deviations, simple unadjusted recalculations, and sponsor ANCOVA contrasts. Because the record flags a discrepancy, the sponsor’s reported analysis takes precedence; its two experimental-product comparisons with Reference Product 2 have confidence intervals that include zero.

Secondary outcomes include additional surface microhardness, transverse microradiography and enamel fluoride uptake measures. The registry record does not report a multiplicity plan, a complete missing-data account, or the full statistical model specification. The findings concern enamel specimens in an in situ model and do not directly establish effects on clinical caries outcomes.