Efficacy of Salivary Bacteria and Post Brushing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Salivary Bacteria and Post Brushing (NCT00981825), a randomized phase 3 study. The primary outcome is CFU (Colony Forming Units).

2. Clinical Question

3. Trial Design

The registry classifies the study as randomized, single-masked, and crossover, and lists its phase as PHASE3. Its stated purpose is to compare the effects of brushing with fluoride and triclosan/fluoride toothpastes on salivary bacteria after brushing. Enrollment is listed as 22. The primary outcome measure is continuous and is reported as a mean with standard deviation.

A crossover design means that treatment conditions are encountered in a sequence rather than assigned as separate parallel groups throughout the study. The registry lists sequence groups in which fluoride is used first and triclosan/fluoride second, or triclosan/fluoride first and fluoride second. The outcome arm summaries each list 22 observations. In this crossover context, those arm counts should not be added to infer the number of unique participants.

The registry labels masking as single, but the masked party or parties are not reported in the registry record. The period schedule, washout procedures, treatment duration, and details of how the order of treatments was generated are also not reported. The start is listed as 2007-10, primary completion as 2007-12, and status as completed.

The record identifies Colgate Palmolive as sponsor. It lists salivary bacteria levels as the condition and fluoride and triclosan/fluoride as the interventions. The listed design features establish the broad framework, but they do not provide enough detail to determine how period effects, carryover, or within-participant correlation were handled in the analysis.

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.

First Intervention

Washout After 1st Intervention

Second Intervention

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 CFU (Colony Forming Units), measured over 4 hours.

The primary endpoint is CFU, or colony-forming units: the total number of salivary bacterial colonies measured at the 4-hour timeframe. The registry describes the measure as a mean with standard deviation and specifies that a lower number means fewer colonies are present. The endpoint therefore expresses the bacterial count on a numeric scale, rather than recording only whether a participant did or did not have a particular outcome.

Colony-forming units are used to quantify bacteria that grow into observable colonies under the measurement procedure. A count can be compared across toothpaste conditions to describe the average measured bacterial burden at the specified time. The registry’s intended comparison is between fluoride toothpaste as the control and triclosan/fluoride toothpaste.

The reported summaries are 7.18 with a standard deviation of 0.61 for fluoride toothpaste, and 6.94 with a standard deviation of 0.4 for triclosan/fluoride toothpaste. These are group-level summaries; they do not show the distribution of individual measurements, changes from baseline, or the course of bacterial counts over time. Baseline values and additional timepoints are not reported in the registry record.

The endpoint indicates the measured count at the stated timeframe. It does not, by itself, describe symptoms, longer-term outcomes, or the clinical importance of a difference in counts. Those questions require information beyond the posted endpoint and summaries.

7. Results Posted in the Registry

• Triclosan/Fluoride Toothpaste: mean 6.94 versus 7.18 on control; difference -0.24 (95% CI -0.54 to 0.06), standardized effect d = -0.47; z-test p = 0.123.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: each observation is a numeric colony-forming-unit count, and the registry reports the group means and standard deviations. The statistical comparison summarizes the difference between the mean count under triclosan/fluoride toothpaste and the mean under fluoride toothpaste. A mean difference retains the scale of the endpoint, so its units are the units of the CFU measure.

What does the unadjusted comparison describe?

The unadjusted comparison uses the posted group summaries without adjustment for additional variables. The stated contrast is -0.24, calculated in the posted analysis as triclosan/fluoride minus fluoride. A negative value indicates a lower mean in the intervention condition on this subtraction scale. The standard deviations describe variation around each group mean; they are not standard errors and do not directly express the precision of the difference.

The registry also gives a standardized effect estimate of -0.465. A standardized effect expresses a mean contrast relative to a measure of variability, allowing a scale-free description of magnitude. It should not be confused with the endpoint’s original CFU units, and it does not communicate the uncertainty in the estimate on its own.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the observed data under the method used and its assumptions. It communicates precision as well as the estimated direction. The unadjusted interval, from -0.545 to 0.065, crosses zero. That means the interval includes no mean difference as well as values on either side of zero. It is not a probability statement that the true effect lies in the interval, and it does not demonstrate equivalence. The registry separately reports a 95% confidence level for its ANCOVA analysis, but does not provide that analysis’s interval limits.

Why can an adjusted and unadjusted result differ?

ANCOVA, or analysis of covariance, estimates a treatment contrast while accounting for covariates included in the model. Adjustment can change the estimate and its uncertainty relative to a simple unadjusted comparison. The registry names ANCOVA and reports p = 0.05, but the covariates, model specification, estimate, and interval limits are not reported in the registry record. The posted summary-based calculation is therefore not a reconstruction of the ANCOVA model.

In a crossover study, measurements can be related because the same participant receives conditions in sequence. General statistical practice may account for participant-level correlation and possible period or sequence effects. The registry record does not say how these features were handled, so no particular crossover model or adjustment should be assumed. The unadjusted summary comparison cannot verify whether the sponsor’s model accommodated those design features.

Why does over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. For count outcomes, a model that assumes too little variability can give uncertainty estimates that are too narrow. The registry reports means and standard deviations, not a count-model specification or an assessment of over-dispersion. It is therefore not possible to say whether this issue arose or how it was addressed in the sponsor’s analysis.

What does the p-value say?

A p-value describes how compatible the observed data are with a specified null hypothesis under the chosen statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The unadjusted p-value of 0.123 belongs to the summary-based comparison. The registry’s ANCOVA p-value is 0.05 and belongs to the sponsor-reported analysis. Their differing methods and incomplete model details limit direct comparison.

The record lists one outcome measure and no secondary outcomes posted. That does not establish whether other analyses were conducted or whether any multiplicity adjustment was planned. Such information is not reported in the registry record.

10. Confidence Intervals and Precision

The unadjusted mean difference is -0.24, with an interval from -0.545 to 0.065. The interval conveys the uncertainty around the estimated difference: values below zero favor a lower mean in the triclosan/fluoride condition on the stated subtraction scale, while values above zero favor a higher mean in that condition. Because zero lies within the interval, the posted calculation does not pin down the direction with high precision.

The breadth of an interval reflects both the observed variability and the amount of information available, together with the analysis method. The group standard deviations are 0.61 for fluoride and 0.4 for triclosan/fluoride. The summary-based comparison reports standard errors of 0.130 and 0.085 for the respective means. These quantities help describe variability and uncertainty, but the record does not provide individual observations or enough model detail to reproduce the sponsor’s ANCOVA interval.

The registry identifies a 95% confidence level for the ANCOVA analysis, but its lower and upper confidence limits are absent. Its p-value of 0.05 therefore cannot replace an interval estimate: a p-value does not show the range of effect sizes compatible with the data. The unadjusted interval and adjusted p-value answer related, but not identical, analytical questions.

Precision should also be considered in light of the crossover design. The registry does not report how the analysis handled correlations between measurements from the same participant, or whether period and sequence were included. Without those details, the posted summaries support a limited description of the unadjusted contrast, rather than a complete assessment of the precision of a design-specific treatment estimate.

11. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design assumptions; those original assumptions are not reported in the registry record. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row uses the stated fraction of the observed effect as the effect to detect.

For planning based on 100% of the observed effect, the figures are 73 participants per arm for 80% power and 98 participants per arm for 90% power. For 75% of the observed effect, they are 129 participants per arm for 80% power and 173 participants per arm for 90% power. For 50% of the observed effect, they are 291 participants per arm for 80% power and 389 participants per arm for 90% power.

In general, power is the chance that a study will detect an effect of a specified size under the assumed design and analysis if that effect is present. The 80% and 90% columns indicate different target chances for detecting the chosen effect under the planning assumptions. A higher target power requires more participants for a given effect size. Smaller effects need more participants because they are harder to distinguish from random variation.

These calculations are planning illustrations, not observed power and not a report of the study’s original sample-size justification. The listed assumptions describe this planning exercise; the registry record does not report the original design’s sample-size assumptions.

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 = -0.240; pooled standard deviation σ = 0.516.
2. n = 2 × (1.96 + 0.842)² × 0.516² / -0.240² = 72.5, rounded up to 73 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 <- -0.239999999999999                      # observed difference in means
sigma <- 0.515800348972352                     # 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(981825)
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 = 73 (80% power), 98 (90% power)
 75% of observed effect: n per arm = 129 (80% power), 173 (90% power)
 50% of observed effect: n per arm = 291 (80% power), 389 (90% power)
power.t.test: 73.5 
Simulated power at n = 73 per arm: 0.797 (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 analysis as ANCOVA and gives p = 0.05. It lists a 95% confidence level for that analysis, but the estimate and confidence limits are not reported in the registry record. The p-value alone does not show the direction or size of the adjusted contrast, so it cannot be placed alongside the unadjusted estimate as if both posted the same information.

The summary-based re-calculation gives an unadjusted mean difference of -0.24, an interval from -0.545 to 0.065, and an unadjusted p-value of 0.123. It is calculated from the posted group summaries and is not the ANCOVA result. An adjusted analysis may account for variables that the unadjusted comparison does not; the covariates and model details are not reported.

The record does not flag a discrepancy between the posted summaries and the re-calculation. The two results nonetheless differ in method, and the missing ANCOVA estimate and interval limit a fuller comparison. The sponsor result should be described as the registry’s reported ANCOVA p-value, while the re-calculation should be understood as a separate, unadjusted summary-based analysis.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no secondary outcomes posted. It does not report whether additional outcomes or analyses were planned, whether multiple comparisons were considered, or whether any adjustment for multiplicity was used. The number of outcomes posted does not establish the full scope of analyses performed.

Multiplicity arises when several hypotheses or outcomes are tested. As a general statistical concept, conducting multiple tests can increase the chance that at least one result appears unusual by chance. Methods for addressing this depend on the analysis plan and the questions being asked. Because an adjustment plan is not reported in the registry record, it is not possible to determine whether the reported p-values account for any multiplicity.

Missing-data handling is also not reported. The record does not describe whether outcome measurements were missing, how missing observations were handled, or whether any imputation or sensitivity analysis was performed. The outcome summaries list 22 observations for each condition, but those counts alone do not establish whether all expected measurements were available or how the analysis population was defined.

The record does not identify an intention-to-treat, per-protocol, or other analysis population. Nor does it describe exclusions, protocol deviations, or the handling of participants who did not complete both periods. These details are particularly relevant to a crossover study because interpretation can depend on which participants contribute measurements under each condition and how paired observations are modeled.

Consequently, the posted results permit a description of the listed summaries and reported ANCOVA p-value, but do not establish the completeness of the outcome data, the analysis population, or the strategy for multiplicity and missingness.

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 two sequence groups for adverse events: fluoride first followed by triclosan/fluoride, and triclosan/fluoride first followed by fluoride. For each sequence, 22 participants are listed as at risk for serious adverse events, and 0 are listed as affected. The other-adverse-event fields also list 22 at risk and 0 affected for each sequence.

These figures describe the registry’s posted counts; they do not establish that every possible adverse event was actively assessed or that no event occurred outside the reporting categories. The record does not give event terms for serious adverse events, and the top serious terms list is empty. Death counts are not reported in the registry record.

Because the study is crossover, the adverse-event groups are organized by treatment sequence. The at-risk counts for the sequence groups should not be added to infer a unique participant count. The registry does not report event timing, severity beyond the serious-event category, relatedness to treatment, or details of safety monitoring. The posted zeros should therefore be read as zero affected participants recorded in those fields, not as a complete characterization of safety.

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

The posted endpoint summaries show mean salivary CFU values of 7.18 with fluoride toothpaste and 6.94 with triclosan/fluoride toothpaste at 4 hours. The unadjusted contrast is -0.24, with the negative direction corresponding to a lower mean count for triclosan/fluoride on the stated subtraction scale. Its interval, from -0.545 to 0.065, includes zero and allows for uncertainty about the direction and size of the difference.

The registry also reports an ANCOVA p-value of 0.05, but does not report the adjusted estimate or interval limits. That result cannot be used to describe the magnitude or precision of the adjusted comparison. The unadjusted result and the sponsor analysis should be kept distinct because they use different methods.

These findings concern a measured bacterial count at the specified timeframe. They do not establish a difference in symptoms, dental health, longer-term bacterial levels, or any other outcome that is not reported. The registry does not provide a threshold for a clinically important difference, so the practical importance of the numerical contrast cannot be determined from these data alone.

The record’s crossover classification indicates that the conditions were administered in sequence, but does not describe how period effects, carryover, or within-participant correlation were addressed. Those design and analysis details affect how confidently a treatment contrast can be interpreted. The posted summaries are therefore informative as descriptive group results, but do not by themselves answer every design-specific question.

Neither the unadjusted p-value nor the sponsor’s p-value should be read as a direct measure of clinical importance. The available evidence supports a cautious description of the reported counts and their uncertainty, rather than a broad conclusion about treatment effects beyond this endpoint and timeframe.

17. Why This Trial Matters Statistically

This trial illustrates why the estimated effect, its uncertainty, and the analysis method all matter. The group means differ by -0.24 on the CFU scale, while the unadjusted interval extends from -0.545 to 0.065. The estimate gives a direction and scale; the interval shows that the data do not sharply determine the direction of the unadjusted contrast.

It also illustrates the distinction between a result calculated from posted summary statistics and a sponsor-reported adjusted analysis. The registry identifies ANCOVA and reports p = 0.05, but does not provide the estimate or confidence limits. A p-value without those quantities is a limited account of the result, especially when a separate unadjusted analysis is also available.

The crossover design makes model details important. Measurements from the same participant may be related, and treatment sequence and period can be relevant. The record does not explain whether or how those considerations were incorporated. This is a reminder that a study’s design label alone does not tell readers how its analysis used the design.

Finally, planning illustrations can help show how assumptions about effect size and target power influence sample-size requirements. They do not explain the original design unless the original assumptions are reported. The registry does not provide those original assumptions, so the planning figures should be read as illustrations rather than as evidence about the trial’s design rationale.

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 registry record leaves several trial-specific details unreported. It does not describe eligibility criteria, participant characteristics, baseline CFU measurements, brushing procedures, adherence, treatment duration, or the interval between crossover periods. Washout procedures are also not reported. Without these details, readers cannot assess how closely the study conditions match other settings or how potential carryover was considered.

Masking is classified as single, but the masked party or parties are not identified. The method used to generate treatment order and the handling of period and sequence effects are not described. These gaps limit assessment of the crossover design and of the sponsor’s ANCOVA model.

The ANCOVA estimate and confidence limits are absent, and the covariates included in that model are not reported. The unadjusted summary-based re-calculation provides a separate contrast, but cannot reproduce or validate the adjusted analysis. The record also does not report missing-data procedures, analysis-population definitions, or whether participants completed both treatment periods.

The endpoint is limited to CFU at 4 hours. Baseline and longer-term measures, additional outcomes, and a threshold for clinical importance are not reported. The safety record lists zero affected for the posted adverse-event fields, but does not provide event timing, relatedness, or broader monitoring details; deaths are not reported in the registry record.

These limitations do not negate the reported summaries, but they constrain what can be inferred about the adjusted treatment contrast, the crossover analysis, and outcomes beyond the measured endpoint.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy of Salivary Bacteria and Post Brushing — NCT00981825.
• Registry record last updated 2011-06-14; status last verified 2011-06.
• Results first posted 2009-09-22.
• 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

The registry describes a completed, randomized, single-masked crossover study comparing fluoride toothpaste with triclosan/fluoride toothpaste. Enrollment is listed as 22, and the primary endpoint is mean salivary CFU at 4 hours, with lower counts representing fewer colonies.

The posted means are 7.18 for fluoride and 6.94 for triclosan/fluoride. The unadjusted mean difference is -0.24, with an interval from -0.545 to 0.065 and p = 0.123. The registry reports an ANCOVA p-value of 0.05 but does not provide its estimate or confidence limits.

The record lists zero affected participants in the posted serious and other adverse-event fields for each sequence. Analysis details, missing-data handling, and the original sample-size assumptions are not reported in the registry record.