The Clinical Investigation of a Zinc Based Toothpaste in Reducing Plaque and Gingivitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Clinical Investigation of a Zinc Based Toothpaste in Reducing Plaque and Gingivitis (NCT02243046), a randomized phase 2 study. The primary outcome is Gingivitis Scores.

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, parallel, controlled Phase 2 clinical trial sponsored by Colgate Palmolive. The study was intended to evaluate reduction of dental plaque and gingivitis over six months. Its listed start was 2014-12, primary completion was 2015-05, and status is completed.

There were three intervention groups: control toothpaste, experimental toothpaste, and active comparator. The control was described as 1450 ppm fluoride toothpaste; the experimental product as 1450 ppm sodium fluoride toothpaste with a zinc base; and the active comparator as 1450 ppm sodium fluoride/triclosan toothpaste. Random allocation and double masking are recorded, but the method used to generate the allocation sequence, conceal assignments, or maintain masking is not reported in the registry record.

The enrollment field lists 162, while the brief summary describes one hundred and sixty adults. The posted baseline outcome has group counts of 55 for control, 54 for experimental toothpaste, and 53 for active comparator. These figures are reported as recorded; the registry does not explain the difference between the enrollment field and the summary, or how enrollment relates to the baseline outcome counts.

The primary endpoint is titled Gingivitis Scores and is identified as a mean on a scale, with standard deviation as the measure of spread. Its stated timeframe is baseline. Although the trial title and summary describe a six-month study, a six-month primary result is not reported in the registry record. The trial's original statistical plan and sample-size justification are also 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.

Overall Study

Reasons for not completing this period:

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 Gingivitis Scores, measured over Baseline.

The primary endpoint is the mean gingivitis score at baseline, measured using the Loe and Silness Gingival Index. The registry describes the scale as running from 0 to 3 units. A score of 0 indicates no inflammation; 1 indicates mild inflammation with slight color change and little change in texture; 2 indicates moderate inflammation, with moderate glazing, redness, edema and hypertrophy and a tendency to bleed upon probing; and 3 indicates severe inflammation, with marked redness and hypertrophy and a tendency to spontaneous bleeding.

This index turns clinical observations of gingival inflammation into a continuous score. In general, a continuous measure can be summarized by its mean and standard deviation: the mean describes the group’s average recorded score, while the standard deviation describes variation among scores. Such a measure can be useful for comparing group summaries, provided that the measurement is taken at a time relevant to the comparison being asked.

Here, the stated timeframe is baseline. The posted means therefore describe initial gingivitis scores, not score changes during the six-month study. Baseline scores can show whether the groups began with similar recorded averages, but they do not show the effect of assigned toothpaste over follow-up. A follow-up value, a change-from-baseline result, or an analysis comparing outcomes over time is not reported in the registry record.

7. Results Posted in the Registry

• Experimental Toothpaste: mean 1.57 versus 1.48 on control; difference 0.09 (95% CI -0.01 to 0.19), standardized effect d = 0.35; z-test p = 0.067.
• Active Comparator: mean 1.49 versus 1.48 on control; difference 0.01 (95% CI -0.07 to 0.09), standardized effect d = 0.05; z-test p = 0.809.

8. Statistical Interpretation

9. Statistical Methods Explained

The posted results include group means and standard deviations for a continuous baseline score, an overall ANOVA result, and recalculated pairwise comparisons with confidence intervals and unadjusted p-values. These statistics answer different questions. Interpreting them requires attention to the outcome timing, the groups included in each comparison, and whether an analysis was reported by the sponsor or recalculated from the posted summaries.

What does the mean describe?

A mean is the arithmetic average of the observed scores in a group. For the baseline gingivitis score, the posted means are 1.48 for control toothpaste, 1.57 for experimental toothpaste, and 1.49 for active comparator. These are summaries of recorded scores at baseline. They are not mean reductions, because the registry identifies the timeframe as baseline and does not post a change score for the primary endpoint.

The standard deviation describes the spread of individual values around a group mean. The reported standard deviations are 0.23, 0.28, and 0.2 for control, experimental, and active comparator, respectively. In general, greater spread means individual observations vary more around the average. The standard deviation is not the same as the uncertainty in the estimated mean; that uncertainty also depends on the number of observations and the analysis assumptions.

What does the ANOVA test?

ANOVA is a general method for assessing whether group means differ, using variation within groups as a reference for variation among group means. The registry reports an ANOVA across the three study groups with p = 0.091. This is an overall test: it does not, by itself, identify which group pairs differ or estimate the size of a particular pairwise contrast. The registry does not report the ANOVA model details, degrees of freedom, or a full set of adjusted pairwise comparisons.

A p-value describes how compatible the observed test statistic is with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the probability that a product is effective. The sponsor-reported p-value is for the stated three-group ANOVA. It should not be treated as if it were the p-value for either of the two recalculated pairwise comparisons.

What do the recalculated comparisons describe?

The recalculated mean differences compare each comparator group with control using the posted summary statistics. For experimental toothpaste versus control, the difference is 0.09; for active comparator versus control, it is 0.01. The calculations are unadjusted and do not represent a reported sponsor model. The corresponding unadjusted p-values are 0.067 and 0.809. Since the outcome is a baseline score, these are baseline contrasts, not treatment-effect estimates.

In general, a two-group mean comparison asks whether the estimated difference is distinguishable from zero given its uncertainty. A positive difference means the experimental or active-comparator baseline mean is higher than the control mean under the stated contrast direction. It does not imply a favorable or unfavorable treatment effect. The registry does not report a clinically important difference threshold, so the clinical importance of a baseline difference cannot be determined from these summaries alone.

Why do the overall and pairwise tests differ?

An overall test and a pairwise contrast use different null hypotheses. The ANOVA evaluates a three-group question, while each recalculated contrast evaluates one comparator against control. The pairwise calculations also use their own standard errors and intervals. Different tests can therefore yield different p-values without being contradictory. In addition, the registry does not report whether the sponsor's analysis incorporated covariates or other modeling features. Such details should not be presumed.

Multiplicity is relevant whenever multiple comparisons are considered, because repeated testing can increase the chance of at least one false-positive finding across a family of tests. The recalculated pairwise p-values are explicitly unadjusted. The registry does not report a multiplicity procedure or identify a family of confirmatory comparisons. The overall ANOVA result does not itself supply an adjustment for the pairwise calculations.

What is and is not reported?

The registry reports six outcome measures and six analyses in its record metadata, but secondary results are not posted. The primary result available for interpretation is the baseline gingivitis score. The record does not provide a follow-up primary score, a change-from-baseline estimate, a treatment-by-time analysis, or a detailed account of missing observations. It also does not report the original sample-size justification, an interim analysis plan, or the full statistical analysis plan.

These limits matter because a trial's purpose and its posted results are not interchangeable. A six-month study intended to assess reduction would ordinarily require interpretable follow-up data for that question. Without a posted follow-up result, no treatment effect over time can be reconstructed from baseline group summaries. General statistical explanations describe how these methods work; they do not fill gaps in the registry record.

10. Confidence Intervals and Precision

A confidence interval expresses uncertainty around an estimated quantity under the calculation and assumptions used. For a mean difference, the interval gives a range of values compatible with the data and method. It is not a guarantee that the true difference lies within that particular interval, and it does not account automatically for design issues or analysis choices that are not described in the registry record.

For the experimental toothpaste versus control comparison, the recalculated mean difference is 0.09 and the confidence interval spans zero. For active comparator versus control, the recalculated mean difference is 0.01 and its confidence interval also spans zero. This means that neither unadjusted interval rules out zero difference. The intervals also allow values on either side of zero, so the direction of the underlying baseline difference is not pinned down with high precision by these calculations.

The reported standard errors are 0.031 and 0.038 for the control and experimental means, and 0.031 and 0.028 for the control and active comparator means. In general, a standard error describes the sampling uncertainty of an estimate, rather than the variability of individual scores. Confidence intervals for a difference incorporate uncertainty in both groups under the calculation used.

Precision is distinct from clinical importance. A narrow interval can still include differences that matter clinically, and a wide interval can leave substantial uncertainty about magnitude. The registry record does not report a threshold for a meaningful gingivitis-score difference. More fundamentally, these intervals concern baseline contrasts, not changes over the six-month study; precision for a baseline comparison cannot answer the treatment-effect question.

11. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm for the pairwise comparisons, not total events. The planning illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers detecting the stated fraction of the observed effect, with separate planning targets for 80% and 90% power. The figures are based on the observed baseline contrasts, not on a reported treatment effect over follow-up.

The 80% power column gives the planned number of participants per arm under those assumptions for a design that would have an 80% chance of detecting the specified effect if that effect were the true effect and the assumptions held. The 90% column applies the higher power target. Higher power generally requires more participants for a given effect. These figures are planning illustrations, not observed power.

For experimental toothpaste versus control, the illustration lists 127 participants per arm for planning around 100% of the observed effect at 80% power and 171 at 90% power. Planning around 75% of the observed effect gives 226 participants per arm for 80% power and 303 for 90% power; planning around 50% gives 508 and 681, respectively. For active comparator versus control, the corresponding 100% rows are 7,311 and 9,787 participants per arm; the 75% rows are 12,997 and 17,400; and the 50% rows are 29,243 and 39,148.

Smaller effects require more participants to distinguish them from random variation under otherwise comparable assumptions. The very different illustrations for the two contrasts reflect the different observed baseline differences used in the calculations. These are not the trial's original design targets: the original sample-size justification and assumptions are not reported in the registry record. The illustrations should not be read as proof of whether the completed study was adequately powered for a six-month treatment effect.

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 = 0.090; pooled standard deviation σ = 0.256.
2. n = 2 × (1.96 + 0.842)² × 0.256² / 0.090² = 127.0, rounded up to 127 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 <- 0.0900000000000001                      # observed difference in means
sigma <- 0.255989923867123                     # 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(2243046)
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 = 127 (80% power), 171 (90% power)
 75% of observed effect: n per arm = 226 (80% power), 303 (90% power)
 50% of observed effect: n per arm = 508 (80% power), 681 (90% power)
power.t.test: 128 
Simulated power at n = 127 per arm: 0.798 (20000 replicates)

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

13. Analyses Reported by the Sponsor

The registry reports the sponsor's own three-group ANOVA for the primary gingivitis-score outcome, with p = 0.091. The method is listed as ANOVA, and the analysis includes control toothpaste, experimental toothpaste, and active comparator. The registry does not give an effect estimate, confidence interval, or additional model details for that analysis.

The recalculated comparisons use the posted group summaries to estimate experimental toothpaste versus control and active comparator versus control. Those are unadjusted pairwise contrasts, with p-values of 0.067 and 0.809. They are not a reproduction of the sponsor's overall ANOVA, because the overall test and pairwise tests address different hypotheses. Their results should therefore be read alongside, rather than substituted for, the sponsor-reported analysis.

The registry does not identify a discrepancy between the sponsor result and the recalculations. The central limitation is the outcome timing: the posted primary score is at baseline. Neither the ANOVA nor the recalculated contrasts can establish how gingivitis changed during the six-month study. A sponsor analysis of a follow-up outcome is not reported in the registry record.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical tests are conducted and interpreted together. In general, the more tests in a family, the greater the chance that at least one result appears unusual by chance if all null hypotheses are true. Methods such as a prespecified testing hierarchy or an adjustment to significance thresholds can address this issue, but the registry record does not report a multiplicity strategy.

The posted sponsor analysis is an ANOVA across three groups. The recalculated pairwise comparisons are separate, unadjusted comparisons of each comparator with control. They should not be interpreted as multiplicity-adjusted confirmatory tests. The registry does not specify which comparisons, if any, were designated as confirmatory or how any family of tests was defined.

Missing-data handling is also not reported in the registry record. The posted baseline group counts are 55, 54, and 53, but the record does not explain whether any participants lacked baseline measurements, whether follow-up measurements were missing, or how missing observations were handled in the sponsor analysis. No imputation method, complete-case rule, or sensitivity analysis is described.

The analysis population is not specified beyond the group summaries and listed analysis. The registry does not state whether the sponsor used an intention-to-treat population, a per-protocol population, or another defined set. It also does not report exclusions from analysis or reasons for them. These details matter because analysis populations and missing-data choices can affect estimates and their uncertainty.

The record's metadata lists six outcome measures and six analyses, while secondary results are not posted. This does not establish what analyses were planned or which were conducted; the statistical analysis plan and a complete set of results are not reported in the registry record. The absence of those details limits assessment of selective reporting and the intended role of the primary and secondary outcomes.

15. 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 0% reporting threshold.

The registry lists zero participants affected by serious adverse events in each group: 0 among 55 at risk in the control toothpaste group, 0 among 54 at risk in the experimental toothpaste group, and 0 among 53 at risk in the active comparator group. The listed figures describe the registry's serious adverse event counts for the groups.

In general, a zero count in a study group means no event was recorded in that group in the reported data; it does not prove that the underlying risk is zero. The counts should be interpreted with the size and duration of observation in mind. The registry does not provide further detail about event definitions, ascertainment, exposure time, or the method used to collect safety information.

The record also lists zero participants affected by other, non-serious adverse events in each group, with the same group-specific at-risk counts. Death counts are not reported in the registry record. These safety figures do not address the efficacy question, and they do not establish that there were no unrecorded events or risks outside the reported observation.

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

The posted data establish that baseline gingivitis scores were recorded for three toothpaste groups and that the registry reports an overall ANOVA result alongside group summaries. At baseline, the experimental group's mean score was 1.57, compared with 1.48 for control and 1.49 for active comparator. The unadjusted recalculated mean differences are 0.09 for experimental versus control and 0.01 for active comparator versus control. Their confidence intervals span zero.

These results do not show that the zinc-based toothpaste reduced gingivitis, that it performed better or worse than either comparator, or that any group changed over time. The primary outcome's stated timeframe is baseline, even though the trial title describes a six-month study focused on reducing established plaque and gingivitis. A baseline result is not a follow-up efficacy result. No primary follow-up comparison or secondary result is reported in the registry record.

The baseline comparisons also do not prove that the groups were equivalent. Failure to distinguish a baseline contrast from zero is not a formal demonstration of equivalence, and the registry does not report an equivalence margin. The sponsor's ANOVA p-value of 0.091 is an overall three-group test, not a direct estimate of change or a pairwise treatment effect.

The appropriate reading is therefore narrow: the posted record describes starting gingivitis scores and gives statistical uncertainty for baseline comparisons. It does not provide enough outcome information to quantify the effect of toothpaste use over the study period. That limitation is about the available result and its timing, not a claim that a product did or did not have an effect.

17. Why This Trial Matters Statistically

This trial illustrates why an endpoint's timing is as important as its name. A gingivitis score is clinically interpretable as a measure of inflammation, but a baseline score answers a different question from a change score or follow-up comparison. Without the latter, a study described as evaluating reduction cannot be assessed for reduction from the posted primary result alone.

It also demonstrates why an overall test and pairwise contrasts should not be treated as interchangeable. The sponsor-reported ANOVA addresses a three-group question, while the recalculated mean differences compare each comparator with control. The p-values differ because the comparisons are not the same statistical test. Reading each result in relation to its specific estimand helps avoid overstating what a p-value conveys.

The sample-size illustration offers another useful statistical lesson. Planning around a smaller effect requires more participants per arm, and the required number depends strongly on the contrast used. But a calculation based on an observed baseline difference is not evidence about power for a treatment effect that was not posted. Planning figures cannot repair missing follow-up results or reveal the study's original design assumptions.

Finally, the registry record distinguishes what can be described from what remains uncertain. It reports randomized, double-blind, parallel design features and group-level baseline summaries, but does not report the full analysis plan, missing-data handling, or secondary results. Keeping those boundaries explicit is central to sound interpretation of clinical trial statistics.

18. Limitations

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

The most important trial-specific limitation is that the posted primary gingivitis outcome is measured at baseline, although the study is described as a six-month evaluation of reduction. A baseline score cannot show change during follow-up. No six-month primary result or change-from-baseline analysis is reported in the registry record.

The enrollment field lists 162, whereas the brief summary describes one hundred and sixty adults. The primary outcome lists group counts of 55, 54, and 53. The registry does not explain how these different enrollment descriptions relate to one another or whether the outcome counts represent all enrolled participants.

The registry reports an overall ANOVA p-value but no effect estimate or confidence interval for that analysis. The pairwise estimates are recalculated from posted summaries and are unadjusted. The record does not describe multiplicity control, covariate adjustment, analysis populations, missing-data procedures, or a detailed statistical analysis plan. Those omissions limit evaluation of the intended analysis and the robustness of the findings.

Although the record lists six outcome measures and six analyses, it posts no secondary results. The original sample-size justification, eligibility details, allocation procedures, and masking procedures are not reported in the registry record. Safety counts are brief and do not include event definitions or further collection details. These reporting gaps make it difficult to assess completeness, precision for follow-up effects, and the scope of conclusions that the study can support from the registry record alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: The Clinical Investigation of a Zinc Based Toothpaste in Reducing Plaque and Gingivitis — NCT02243046.
• Registry record last updated 2019-02-25; status last verified 2015-07.
• Results first posted 2016-05-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT02243046 is a completed Phase 2 randomized, double-blind, parallel clinical trial sponsored by Colgate Palmolive. The registry describes a six-month study of toothpaste interventions for dental plaque and gingivitis. The products were a 1450 ppm fluoride control, a 1450 ppm sodium fluoride toothpaste with a zinc base, and a 1450 ppm sodium fluoride/triclosan active comparator.

The primary outcome is the mean Loe and Silness Gingival Index score, with standard deviation, at baseline. The registry reports group means and a three-group ANOVA p-value of 0.091. Recalculated unadjusted pairwise comparisons have confidence intervals spanning zero. The record does not report a primary follow-up result or secondary results, so the posted statistics describe baseline scores rather than gingivitis reduction over the study.