Adjunctive Hydrogen Peroxide for Periodontal Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjunctive Hydrogen Peroxide for Periodontal Therapy (NCT03262701), a randomized phase 4 study. The primary outcome is Periodontal Pocket Depth Reduction.

2. Clinical Question

3. Trial Design

The registry identifies NCT03262701 as a Phase 4, randomized, single-masked, parallel-group trial of adjunctive hydrogen peroxide for periodontal therapy. It lists Loma Linda University as the sponsor and chronic periodontitis as the condition. Enrollment is listed as 42. The study began on 2018-04-02, primary completion is listed as 2021-02-08, and its status is terminated. The registry record does not report why the trial was terminated.

Three groups are described. Participants in the 13-week and 26-week groups receive conventional nonsurgical therapy plus 1.7% hydrogen peroxide gel in a customized tray. The stated regimen is 0.75g, twice daily for 15 minutes, with duration differing between groups. The scaling-and-root-planing group receives conventional nonsurgical therapy without hydrogen peroxide application, in one or two visits.

Randomization and single masking are recorded, but the method used to generate or conceal assignments is not reported in the registry record. The record does not identify who was masked. It describes a parallel model, meaning the listed groups are separate treatment assignments rather than a crossover sequence. The primary endpoint is measured between baseline and Week 4. Secondary measures concern clinical attachment level and bleeding on probing between baseline and Week 26. The record lists five outcome measures, while results are posted for the primary measure and two secondary measures. It does not list reported statistical analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Periodontal Pocket Depth Reduction, measured over Change between baseline and Week 4.

The primary endpoint is periodontal pocket-depth change between baseline and Week 4, measured in millimeters. The registry describes pocket depth as the distance from the gingival margin to the bottom of the periodontal pocket, measured with a periodontal probe. This is a continuous measure: each participant’s measurement can take a range of values rather than being limited to a category such as improved or not improved.

Pocket depth is used to describe a clinical feature of periodontal disease and to track change over time. In a randomized trial, comparing changes across groups can help distinguish the pattern observed under different assigned regimens from the pattern observed under the comparator, subject to the quality of the trial and its analysis. The endpoint’s timeframe matters: the primary measure concerns change by Week 4, whereas the secondary measures are recorded at Week 26.

The posted group results are means with standard deviations. They are not individual participant results, and a group mean does not show how every participant’s measurement changed. The registry calls the endpoint “Periodontal Pocket Depth Reduction,” but the posted values include negative and positive signs. The record does not specify the calculation convention for change, so the signs should be read as reported rather than translated into a direction of clinical improvement without that convention.

7. Results Posted in the Registry

• Hydrogen Peroxide Gel for 26weeks: mean -0.16 versus -0.05 on control; difference -0.11 (95% CI -0.21 to -0.01), standardized effect d = -0.96; z-test p = 0.028.

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.

Change in Clinical Attachment Level

• 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:
  • Hydrogen Peroxide Gel for 26weeks: mean -0.42 versus -0.25 on control; difference -0.17 (95% CI -0.56 to 0.22), standardized effect d = -0.38; z-test p = 0.394.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Hydrogen Peroxide Gel for 26weeks and the control. The interval gives the range of effects that remain compatible with the data.

Change in Bleeding on Probing

• 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:
  • Hydrogen Peroxide Gel for 26weeks: mean -34.20 versus -24.10 on control; difference -10.10 (95% CI -24.19 to 3.99), standardized effect d = -0.62; z-test p = 0.160.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Hydrogen Peroxide Gel for 26weeks and the control. The interval gives the range of effects that remain compatible with the data.

The two posted secondary outcomes describe different aspects of periodontal status from the primary pocket-depth measure. Clinical attachment level and bleeding on probing are both reported as changes between baseline and Week 26, later than the primary Week 4 assessment. Their group summaries and recalculated contrasts provide additional context, but they do not answer the same question or measure the same feature as the primary endpoint.

Across these secondary outcomes, the 26-week versus 13-week gel estimates are numerically more negative than the corresponding 13-week group means. Both recalculated confidence intervals include zero, and both unadjusted p values are greater than 0.05. The intervals are broad enough to leave substantial uncertainty about the size and direction of the underlying contrasts. This pattern does not establish that the treatments are equivalent, and it does not by itself contradict the primary result: endpoint, measurement, and follow-up time differ.

Secondary results usually carry less confirmatory weight when many outcomes or comparisons are examined, because the chance of finding an apparently unusual result can increase across repeated tests. In general, a prespecified hierarchy or multiplicity adjustment can help address that issue. The registry record does not report a multiplicity plan or identify formal reported analyses for these secondary outcomes. Their unadjusted recalculations should therefore be treated as descriptive and exploratory rather than as independent confirmation of a primary finding.

The record lists five outcome measures, but only two secondary outcomes are represented in the posted secondary results. It does not explain the status of the other outcome measures or whether results were unavailable, uncollected, or omitted. The overall secondary pattern is consequently incomplete in the registry record. These results can broaden the description of observed outcomes, but they cannot resolve the uncertainty around the primary comparison or establish a comprehensive account of treatment effects.

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

• Change in Clinical Attachment Level
• Change in Bleeding on Probing

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean change represent?

A mean is the arithmetic average of the values in a group. For this trial, the primary outcome is a continuous measurement, so a mean change provides a compact description of the group’s recorded average change between baseline and Week 4. It does not show the distribution of individual changes, whether values cluster closely around the mean, or whether a small number of unusual observations affect the average. The record reports a standard deviation alongside each mean. A standard deviation describes the spread of individual observations around the mean; it is not the uncertainty of the mean itself.

The group means are -0.05, -0.16, and 0.05 millimeters, with standard deviations of 0.16, 0.05, and 0.09. Because the registry record does not specify the sign convention for change, the values should be quoted as recorded rather than given a clinical direction beyond their numerical ordering.

What is a mean difference?

A mean difference contrasts the averages in two groups. The posted recalculation compares the 26-week gel group with the 13-week gel group and gives an estimate of -0.11 millimeters. The comparison order is important: reversing the order would reverse the sign, without changing the underlying contrast. This estimate is not the trial’s reported comparison of gel with scaling and root planing alone. Although all three groups have primary-outcome summaries, the registry record does not list formal analyses of every possible group contrast.

What does a confidence interval convey?

A confidence interval describes the uncertainty around an estimated effect under the statistical method used. The recalculated primary interval extends from -0.208 to -0.012 millimeters. An interval that includes zero is compatible with no difference under the calculation; an interval that excludes zero indicates that zero is not among the values covered by that interval. Neither result establishes that an effect is clinically important, nor does a confidence interval state the probability that the true effect lies within that particular interval. The interval’s width is useful for assessing how precisely the comparison is estimated.

How should the p value be read?

The unadjusted p value for the primary recalculation is 0.028. In general, a p value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis conditions are correct. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. “Unadjusted” means that the displayed value has not been adjusted for testing multiple outcomes or contrasts. The registry record does not report whether another adjustment or analysis was planned.

Why does spread matter?

In general, greater variation among participants makes a group average less precise when group size is held fixed. The standard deviations differ across the posted groups, including a relatively small reported spread for the 26-week group. With small group sizes, unusual observations can have a substantial influence on a mean or a standard deviation. The available summaries do not allow an assessment of individual observations, distribution shape, outliers, or whether the assumptions of a particular model were checked.

What is meant by a standardized effect?

A standardized effect expresses a group contrast relative to a measure of variability, allowing outcomes measured on different scales to be described in a scale-free way. It does not replace the original-unit estimate, which is more directly tied to millimeters for the primary endpoint. The registry record does not list a reported standardized-effect analysis. The displayed sample-size planning uses the observed contrast as a planning input; it should not be mistaken for a separate clinical result.

The available comparisons are recalculated, simple, unadjusted calculations from posted summary statistics. The registry record lists no reported analyses. It therefore does not establish that these calculations reproduce a prespecified trial model, account for all design features, or match the sponsor’s intended analysis. No adjustment details, interim-analysis plan, missing-data method, or analysis-population definition are reported in the registry record. These distinctions matter: a calculation from group summaries can describe the posted numbers, but it cannot supply undocumented design or analysis decisions.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -0.11 millimeters for 26-week gel versus 13-week gel. Its 95% confidence interval runs from -0.208 to -0.012 millimeters. The interval excludes zero, while its limits remain relatively close to zero in the original measurement scale. This means the point estimate is not the only reasonable value compatible with the calculation: the range conveys uncertainty about the size of the contrast.

Precision is shaped by both the amount of information and the variability in the data. The posted primary group sizes are 11 and 13 for this comparison, and the standard deviations differ between those groups. Small groups generally provide less precise estimates than larger groups, particularly when outcomes vary. The registry record gives summary statistics but not participant-level data, so the distribution and influence of individual observations cannot be assessed from these figures.

The interval is associated with a simple recalculation from posted summaries, not an analysis listed among the trial’s reported analyses. The registry record does not report whether the trial used a different model, adjusted the comparison for other factors, or handled missing observations in a particular way. Thus, the interval quantifies uncertainty under the recalculation, not necessarily under an undocumented trial analysis.

For the secondary comparisons, the intervals are wider and include zero: -0.561 to 0.221 millimeters for clinical attachment level, and -24.19 to 3.986 percentage points for bleeding on probing. Their inclusion of zero does not demonstrate equivalence or rule out meaningful differences. Rather, the ranges show that the estimates are compatible with a range of effects under the calculations. The registry record does not define thresholds for clinical importance, so statistical precision alone cannot determine whether any estimate matters clinically.

12. Planning a Similar Trial: Sample Size

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

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

The 80% power column gives the planned number of participants per arm under which the calculation would have an 80% chance of detecting the specified effect, if the planning assumptions and effect were correct. The 90% power column represents a higher chance of detecting that same specified effect under those assumptions and therefore generally calls for more participants per arm. These are conventional planning probabilities, not guarantees for a future study.

Rows describing 100%, 75%, and 50% of the observed effect illustrate how the planned group size changes when the effect of interest is set smaller than the observed estimate. A smaller target effect is harder to distinguish from random variation, so more participants are needed. The displayed figures are not a recommendation or evidence that the observed effect will recur. This is not observed power: it is a forward-looking planning illustration, and the registry record does not report the trial’s own original sample-size justification.

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 = -0.110; pooled standard deviation σ = 0.114.
2. n = 2 × (1.96 + 0.842)² × 0.114² / -0.110² = 16.9, rounded up to 17 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 <- -0.11                      # observed difference in means
sigma <- 0.114017542509914                     # 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(3262701)
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 = 17 (80% power), 23 (90% power)
 75% of observed effect: n per arm = 30 (80% power), 41 (90% power)
 50% of observed effect: n per arm = 68 (80% power), 91 (90% power)
power.t.test: 17.9 
Simulated power at n = 17 per arm: 0.781 (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. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, timepoints, treatment contrasts, or statistical tests are considered. Even when each test uses the same nominal significance threshold, repeated testing can increase the chance of at least one result appearing statistically unusual by chance. In general, researchers may address this through a prespecified primary outcome, a testing hierarchy, or a statistical adjustment. The registry record does not report whether any such approach was planned or used.

The record identifies one primary endpoint and two secondary outcomes with posted results. It lists five outcome measures in total, but it does not provide a complete account of the other measures or explain their status. The recalculated comparisons are unadjusted. Their p values should not be interpreted as if they necessarily account for testing across the full set of outcomes, timepoints, or possible group contrasts. No formal analysis results are listed in the registry record.

Missing-data handling is also not reported in the registry record. The listed enrollment is 42, while the outcome summaries have group sizes of 11, 13, and 8. The record does not explain the relation between enrollment and the outcome-group sizes, whether all assigned participants were assessed at each timepoint, or why any outcome data may be absent. It also does not report imputation methods, sensitivity analyses, or a rule for excluding observations.

The analysis population is not reported in the registry record. It is therefore unknown whether the summaries represent all randomized participants, those who completed the assigned regimen, or another defined group. The record does not describe adherence, withdrawals, or protocol deviations. Without these details, it is difficult to assess whether the posted groups retain the benefits of randomized assignment or how missing observations may affect the estimates.

These absences do not establish that a particular method was or was not used; they mean the registry record does not document it. They limit the ability to judge prespecification, completeness, and robustness. The recalculated comparisons remain useful descriptions of the posted summaries, but they cannot substitute for a complete trial analysis and reporting plan.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists serious adverse events, other adverse events, and deaths separately for each treatment group. For the 13-week gel group, 14 participants are listed as at risk for serious adverse events and other adverse events; the affected counts are 0 for both categories, with 0 deaths. For the 26-week gel group, the corresponding at-risk counts are 17, with 0 affected for either adverse-event category and 0 deaths. For scaling and root planing, 8 are listed at risk for each category, with 0 affected and 0 deaths.

These are registry counts, not proof that no adverse events occurred outside the categories or reporting period recorded. The record does not provide event descriptions, severity details for non-serious events, follow-up completeness, or a narrative explaining how safety events were collected. No serious adverse-event terms are listed. The at-risk counts differ from the posted primary-outcome group sizes, and the registry record does not explain that difference. Safety figures should therefore be read as the reported event counts and denominators, not as a complete assessment of risk.

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

The posted results describe averages and recalculated contrasts for a small set of registry outcome summaries. For the primary Week 4 measure, the 26-week gel group has a more negative recorded mean than the 13-week gel group, with an unadjusted recalculated mean difference of -0.11 millimeters. The confidence interval excludes zero under that calculation. This is a statistical description of the posted summaries, not a stand-alone demonstration of clinical benefit or a conclusion about all treatment comparisons.

In particular, the recalculated primary contrast is 26-week gel versus 13-week gel. Although the trial includes a scaling-and-root-planing group and reports its primary mean, the recalculated comparison does not estimate either gel regimen against scaling and root planing alone. The registry record does not list formal analyses of all three groups. The difference in comparison matters when translating a statistical estimate into a question about treatment strategy.

The results do not establish that a longer course caused the observed contrast, that the result would be reproduced in another study, or that the difference is clinically important. The registry does not report a clinical-importance threshold, a detailed analysis plan, or the reason for termination. Secondary estimates are uncertain, and the handling of missing data and multiplicity is not reported. The record also does not describe the trial’s original sample-size justification.

Conversely, an interval that includes zero in a secondary comparison does not prove that the regimens have identical effects. It indicates uncertainty that includes zero under the displayed recalculation. More generally, statistical significance and clinical importance are distinct: a small p value does not by itself indicate a meaningful benefit, and a larger p value does not establish no effect.

The appropriate reading is narrow: the registry reports group-level outcome summaries, and simple unadjusted recalculations describe selected contrasts between those summaries. The information does not support medical advice or a definitive conclusion about the effectiveness or safety of hydrogen peroxide. A full assessment would require the complete trial report and its prespecified methods, analysis populations, and follow-up accounting, which are not reported in the registry record.

17. Why This Trial Matters Statistically

This trial illustrates why the comparison being estimated matters as much as the intervention labels. Three groups have primary outcome summaries, but the recalculated contrast is between two hydrogen peroxide durations. A reader interested in hydrogen peroxide added to scaling and root planing versus scaling and root planing alone needs a direct estimate for that contrast; the posted recalculation does not supply it. Statistical conclusions must stay aligned with the groups actually compared.

It also shows why effect estimates and uncertainty should be read together. The primary contrast is accompanied by a confidence interval and an unadjusted p value, but the outcome groups are small and the registry record does not list a formal trial analysis. A point estimate alone can appear more definite than the available information warrants. The interval conveys a range of values compatible with the calculation, while the absent analysis details limit confidence in how closely that calculation reflects the trial’s intended method.

The secondary outcomes add another important lesson: multiple measures and timepoints can produce a collection of estimates that need a stated interpretation plan. Without a reported multiplicity approach, unadjusted secondary results are weaker evidence for confirmatory claims. The record’s terminated status and missing information about missing data, analysis populations, and the original sample-size rationale further emphasize the importance of complete registration and results reporting.

These considerations are relevant beyond this trial. Clear reporting of comparisons, denominators, analysis choices, and uncertainty allows clinicians and researchers to distinguish observed summaries from prespecified evidence. Here, the registry supports a limited statistical reading, not a comprehensive evaluation of the intervention.

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 has important limitations for interpreting this trial. It lists status as terminated but does not report the reason. It does not explain how the enrollment figure relates to the smaller group sizes attached to the posted primary outcome, nor does it describe participant flow, withdrawals, adherence, or the completeness of follow-up. Safety denominators also differ from the primary outcome group sizes, without an explanation in the record.

The record does not report the randomization method, allocation concealment, the identity of the masked party, an analysis population, or a missing-data strategy. Although it identifies the primary endpoint, it does not list formal analyses. The primary comparison available for recalculation is between the 26-week and 13-week gel groups, not a direct comparison against scaling and root planing alone. The relationship between these recalculations and any planned analysis is not reported.

Only two secondary outcome results are posted, despite the registry listing five outcome measures. The status of the remaining measures is not reported. The registry also does not describe a multiplicity plan, a clinical threshold for important change, or the original sample-size justification. The planning illustrations are based on the observed effect and cannot resolve those omissions.

Finally, means and standard deviations cannot show individual-level distributions, outliers, or the consistency of responses. These limitations do not invalidate the posted summaries, but they constrain how far they can be generalized or interpreted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Adjunctive Hydrogen Peroxide for Periodontal Therapy — NCT03262701.
• Registry record last updated 2022-12-21; status last verified 2022-11.
• Results first posted 2022-12-21.
• 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

NCT03262701 is a randomized, single-masked, parallel Phase 4 trial of hydrogen peroxide gel used with conventional nonsurgical periodontal therapy, compared with scaling and root planing alone. The registry lists enrollment of 42 and status as terminated. The primary endpoint is periodontal pocket-depth change between baseline and Week 4.

The posted primary summaries include three groups, while the recalculated primary comparison is 26-week gel versus 13-week gel. Its mean difference is -0.11 millimeters, with a 95% confidence interval from -0.208 to -0.012 and an unadjusted p value of 0.028. The registry record does not list formal analyses, explain termination, or report the original design assumptions, missing-data methods, or multiplicity plan. The estimates therefore warrant a limited, cautious interpretation.