Safety and Efficacy of Periodontal Surgery in Supra-alveolar-type Defects With or Without Straumann® Emdogain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Periodontal Surgery in Supra-alveolar-type Defects With or Without Straumann® Emdogain (NCT01614925), a randomized phase not stated study. The primary outcome is Clinical Attachment Level.

2. Clinical Question

This is a comparison of group-level changes over time. It does not, by itself, describe the experience of every participant or establish why any individual measurement changed. The outcome is derived from Probing Pocket Depth and Gingival Margin measurements, so the primary comparison reflects both components as combined in the registry’s CAL definition. The posted group means and their uncertainty are relevant to the question, but should be considered alongside the small amount of outcome data and the absence of a registry-reported inferential analysis.

3. Trial Design

The registry describes a randomized, controlled, multicenter clinical study with a parallel-group design. Participants were assigned to periodontal surgery with Straumann® Emdogain or periodontal surgery alone. The allocation is recorded as randomized, and masking is recorded as single. The registry does not identify who was masked or provide further details about the randomization procedure, allocation concealment, or the conduct of masking.

The recorded enrollment is 35. The study began in 2012-11, and primary completion is recorded as 2014-10. Its current status is TERMINATED. The reason for termination, whether recruitment or follow-up ended as planned, and any consequences for the analysis are not reported in the registry record. The sponsor is Institut Straumann AG.

The primary outcome is mean change in Clinical Attachment Level from baseline to 12 Months. The record also lists secondary outcomes addressing Gingival Margin, Probing Pocket Depth, early wound healing, postsurgical pain, Bleeding on Probing, Root Dentin Hypersensitivity, and Plaque Index. Although the record lists these outcomes, posted numerical results are available for only selected secondary outcomes. The registry record does not report a full statistical analysis plan, analysis populations, or a reason for any difference between enrollment and the outcome-specific participant counts. Those details should not be inferred from the posted group summaries.

Arm-level primary results are reported for 14 participants in the Emdogain group and 15 in the periodontal-surgery group. Safety results use separate at-risk counts. These denominators describe the posted outcome records; they do not explain how participants were assigned, followed, excluded, or handled in 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

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 Clinical Attachment Level, measured over 12 Months.

The primary endpoint is change in Clinical Attachment Level (CAL) from baseline to 12 Months, measured in millimeters and summarized as a mean with a standard deviation. The registry defines CAL as Probing Pocket Depth (PPD) minus Gingival Margin (GM). In general, CAL combines information about the position of the gingival margin with the depth of the periodontal pocket, giving a measure used to assess periodontal attachment over time.

The comparison is based on change rather than a single measurement at 12 Months. This helps focus the outcome on how measurements differ from baseline, although interpretation still depends on how change is coded and measured. The registry’s stated objective concerns higher CAL gain with the added use of Emdogain, while the posted results express changes as negative means in both groups. It is therefore important to describe the recorded values and their contrast without silently changing their sign or assuming that a negative value has a particular clinical interpretation beyond the registry’s definition.

CAL is derived from PPD and GM, rather than measured as an independent quantity in the registry description. The resulting endpoint therefore reflects the combined measurements and the reliability of both components. The record does not report further measurement procedures, assessor training, or details about how missing baseline or follow-up measurements were handled.

7. Results Posted in the Registry

• Periodontal Surgery: mean -2.08 versus -2.91 on control; difference 0.83 (95% CI -0.12 to 1.78), standardized effect d = 0.63; z-test p = 0.088.

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 Gingival Margin (GM) From Baseline to 12 Months

• 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:
  • Periodontal Surgery: mean -0.27 versus -0.36 on control; difference 0.09 (95% CI -0.80 to 0.98), standardized effect d = 0.07; z-test p = 0.843.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Periodontal Surgery and the control. The interval gives the range of effects that remain compatible with the data.

Change in Probing Pocket Depth (PPD) From Baseline to 12 Months

• 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:
  • Periodontal Surgery: mean -2.47 versus -2.93 on control; difference 0.46 (95% CI -0.48 to 1.40), standardized effect d = 0.36; z-test p = 0.339.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Periodontal Surgery and the control. The interval gives the range of effects that remain compatible with the data.

Comparison of Post-surgical Pain at 4 Weeks After Baseline

• 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:
  • Periodontal Surgery: mean 3.47 versus 3.21 on control; difference 0.26 (95% CI -6.04 to 6.56), standardized effect d = 0.03; z-test p = 0.936.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Periodontal Surgery and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning periodontal measurements, healing, pain, and other oral-health measures. Numerical arm summaries and unadjusted comparisons are posted for Gingival Margin change, Probing Pocket Depth change, and postsurgical pain. Results for the other listed secondary outcomes are not reported in the registry record. The available secondary results do not form a consistent body of precise evidence that independently resolves the primary CAL question: the posted comparison intervals include zero and leave uncertainty about the size and direction of the contrasts.

These secondary measures are related to the primary endpoint in different ways. GM and PPD are the components used to derive CAL, so they offer context for the combined primary measurement. Pain is a different type of outcome, and the other listed measures address distinct aspects of healing or periodontal status. Agreement or disagreement among such outcomes can be informative, but it should not be treated as a direct replication of the primary endpoint.

The secondary results carry less weight because the registry labels the comparisons as unadjusted and does not report a multiplicity strategy. In general, examining multiple outcomes creates more opportunities for chance findings, particularly when results are interpreted one at a time. The record also does not report a hierarchy for secondary outcomes, a plan identifying which were confirmatory, or a sponsor analysis. Missing numerical results for some listed outcomes further limit an overall assessment. These data can provide descriptive context, but they should not override the uncertainty in the primary comparison or be treated as definitive evidence for separate outcome claims.

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

• Change in Gingival Margin (GM) From Baseline to 12 Months
• Change in Probing Pocket Depth (PPD) From Baseline to 12 Months
• Early Wound Healing Index (EHI) Assessment at 4 Weeks After Baseline
• Comparison of Post-surgical Pain at 4 Weeks After Baseline
• Change in Bleeding on Probing (BoP) From Baseline to 12 Months
• Change in Root Dentin Hypersensitivity (RDH) From Baseline to 12 Months
• Change in Plaque Index (PI) From Baseline to 12 Months

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a mean change in a measurement expressed in millimeters. For each group, the registry posts a mean and standard deviation. A mean gives the arithmetic center of the observed values, while the standard deviation describes how dispersed those values are around the mean. In general, a standard deviation is a description of variation among observations; it is not the uncertainty interval for the mean or for the difference between groups.

The comparison of interest is a difference between group means. The posted estimate uses the periodontal-surgery group minus the Emdogain group. With that ordering, a positive contrast means the surgery-alone mean is numerically higher than the Emdogain mean, and a negative contrast means it is numerically lower. That statement is about the numerical ordering of the recorded change scores. It does not settle the clinical interpretation of the signs or establish which group had a meaningful advantage.

The comparison values are unadjusted recalculations from posted summary statistics. In general, such a calculation uses the group means and their variability to estimate a difference and its uncertainty, without accounting for participant-level covariates or other design features. It is useful as a transparent description of the available summaries, but it is not a substitute for the trial’s prespecified analysis. The registry record does not report a sponsor analysis, adjustment method, or analysis plan against which to compare this recalculation. No discrepancy is flagged in the record.

A confidence interval describes a range of estimates compatible with the observed data under the method’s assumptions. It conveys more about uncertainty than a point estimate alone. If the interval includes zero, that indicates that the estimated data do not clearly distinguish the contrast from zero at the corresponding confidence level. It does not show that the groups are identical, and it does not tell whether any possible difference is clinically important. The interval’s width also matters: a broad interval leaves substantial uncertainty about the size and direction of the underlying difference.

The unadjusted p-value is another summary of compatibility between the observed result and a statistical model that assumes no group difference. In general, a small p-value can indicate that the data would be relatively unusual under that model, but it is not a measure of effect size or the probability that a treatment hypothesis is true. A p-value should be interpreted with the estimate, interval, endpoint definition, and study limitations rather than used as a stand-alone verdict.

The registry states that CAL is derived from PPD and GM, with CAL defined as PPD minus GM. This matters because a derived endpoint depends on the measurements that form it. General measurement error in either component can affect the derived value. The record does not report whether the primary analysis adjusted for baseline CAL, how repeated measurements were modeled, or how values that were unavailable at follow-up were addressed.

In general, statistical inference also depends on assumptions about the observations and analysis. For a simple comparison of means, methods commonly rely on suitable treatment of variation, independence, and the distribution of the data or of the estimator. The registry does not report diagnostic checks or details that would establish how those assumptions were evaluated. With limited outcome counts, the estimate and its uncertainty may be sensitive to individual observations; participant-level data are not reported, so that sensitivity cannot be assessed from the group summaries.

The primary and secondary endpoints create a multiplicity issue in general: testing or interpreting multiple outcomes increases the chance of finding an apparently notable result by chance if each is considered separately. Whether and how that issue was handled in this trial is not reported in the registry record. The secondary p-values are labeled unadjusted, and no multiplicity adjustment is reported. These limitations are reasons to treat secondary findings as exploratory rather than as independent confirmation of the primary result.

Finally, an analysis population is the set of participants whose observations are included under a stated analysis rule. Common approaches can differ in how they handle participants who do not complete follow-up or who lack an outcome measurement. The registry does not report the population definition or missing-data procedure for the posted means. The outcome-specific group counts should therefore be read as the counts attached to those summaries, not as evidence of a particular intention-to-treat, per-protocol, or other analysis strategy.

11. Confidence Intervals and Precision

For the primary CAL contrast, the unadjusted mean difference is 0.83 mm, with a 95% confidence interval from -0.124 to 1.784 mm. The interval includes zero and extends to values on either side of it. Thus, while the point estimate gives one direction and size for the contrast, the data are compatible with other values as well. The interval does not establish equivalence, and it does not show that any value within the interval is equally plausible or clinically important.

In general, confidence intervals communicate precision by showing the range of estimates supported by the data and the assumptions of the calculation. A narrower interval indicates greater statistical precision; a wider interval leaves more uncertainty about the contrast. Precision is distinct from clinical importance: even a precisely estimated difference would require context to judge whether it matters, while an imprecise estimate may include both small and potentially important differences. The registry does not report a threshold for clinical importance for CAL.

The primary arm means are based on 14 participants in the Emdogain group and 15 in the periodontal-surgery group. The standard deviations are 1.3 mm and 1.32 mm, respectively. The group-level summaries do not reveal the individual measurements or their distribution, and the registry record does not report an adjusted interval or an interval from a prespecified sponsor analysis. Precision should therefore be read as conditional on the unadjusted recalculation and the posted summaries.

The secondary comparison intervals are also broad. Taken together, their uncertainty cautions against interpreting small or near-zero point estimates as proof that the groups do not differ. Likewise, the primary interval’s inclusion of zero is not proof of no effect. The estimates remain uncertain, and the registry record does not report additional analyses that would narrow or otherwise qualify this uncertainty.

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 figures are planning illustrations based on the observed effect, not the trial’s original design assumptions. For these continuous outcomes, the values are participants per arm, not total events. The planning calculation assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects set at the stated fractions of the observed effect. The trial’s own original sample-size justification and design assumptions are not reported in the registry record.

The 80% power column represents a planning target for the chance of detecting the specified effect under the calculation’s assumptions if that effect were present. The 90% power column uses a higher target chance of detection for the same specified effect. These are design concepts, not guarantees about what a future study will find. The displayed participant requirements depend on the observed effect used as the planning reference and on the stated assumptions.

Rows that plan for a smaller fraction of the observed effect require more participants per arm. This follows from a general statistical principle: smaller differences are harder to distinguish from random variation, so a larger study is generally needed to detect them at the same power target. The curve represents this planning relationship across effect assumptions; it does not establish that the observed effect is the true or expected effect in another study.

These figures are not observed power. They do not describe the probability that the completed trial detected an effect after the results were known. The calculation is an illustration for planning and should not be read as evidence that the trial was adequately or inadequately sized according to its original protocol, which is not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.830; pooled standard deviation σ = 1.310.
2. n = 2 × (1.96 + 0.842)² × 1.310² / 0.830² = 39.1, rounded up to 40 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 <- 0.83                      # observed difference in means
sigma <- 1.31040847462552                     # 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(1614925)
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 = 40 (80% power), 53 (90% power)
 75% of observed effect: n per arm = 70 (80% power), 94 (90% power)
 50% of observed effect: n per arm = 157 (80% power), 210 (90% power)
power.t.test: 40.1 
Simulated power at n = 40 per arm: 0.805 (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

The registry lists a primary endpoint and multiple secondary outcomes, but it does not report how the study handled multiplicity. In general, when several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is judged using an unadjusted threshold. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory outcomes can help frame interpretation. None of those details is reported in the registry record. The posted secondary comparisons are unadjusted, so they should not be treated as if a multiplicity correction had been applied.

The registry record does not report a full statistical analysis plan, the exact analysis population, or the rules for including participants in each endpoint analysis. It also does not report how missing observations were handled, whether any imputation was used, or whether sensitivity analyses were conducted. These omissions matter because estimates can depend on which participants contribute data and on assumptions about observations that are unavailable. The available group counts alone cannot identify the reason an outcome is missing or establish that missingness had no effect.

There is also no reported account of interim analyses, stopping rules, or the statistical rationale for terminating the study. The record gives a TERMINATED status but does not provide the reason. No conclusion about the timing or statistical consequences of termination should be inferred from that status alone.

These gaps do not invalidate the descriptive means and standard deviations, but they limit assessment of how the reported results relate to the trial’s intended confirmatory analysis. The registry does not report whether the primary analysis was adjusted for baseline values, center, or other factors, nor whether assumptions were checked. Consequently, the unadjusted comparison is best understood as a summary-based recalculation rather than a complete account of the trial’s statistical analysis.

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.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among the participants listed as at risk in each group. It reports one other adverse event in each group. The at-risk counts are 18 for Emdogain and 17 for periodontal surgery, which differ from the group counts attached to the primary outcome summaries. The record does not explain these denominator differences, so the safety counts should be read using their own at-risk denominators rather than substituted for the primary outcome counts.

The registry does not list serious adverse-event terms, and deaths are not reported in the record. The absence of a posted serious-event count is not evidence that an event could not occur outside the recorded observation or reporting process. The registry does not provide further detail about event definitions, severity grading, timing, duration, relatedness assessments, or how events were collected. These figures are a limited account of the safety data in the record and do not establish the overall safety profile of either treatment approach.

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

The posted results show a difference between the group mean CAL changes, with an unadjusted estimate of 0.83 mm for periodontal surgery minus Emdogain. The 95% confidence interval ranges from -0.124 to 1.784 mm and includes zero. The data therefore do not give a precise estimate of the difference, and the interval leaves room for contrasts in either direction. The point estimate should not be treated as a definitive measure of what would occur in a larger or different population.

The registry’s objective was to evaluate whether adding Emdogain would result in higher CAL gain. The outcome values are recorded as changes with negative means, and the record defines how CAL is derived. Interpretation should preserve that reported coding rather than assume that the numerical sign directly answers the stated objective. The posted group summaries alone do not establish a clinical benefit, lack of benefit, or equivalence.

The trial record also does not provide enough information to assess all aspects of conduct and analysis. It does not report the detailed eligibility criteria, analysis populations, missing-data methods, full statistical plan, or reason for termination. These omissions constrain the conclusions that can be drawn from the summaries, especially given the outcome-specific participant counts and wide intervals.

These results describe this trial record and its reported measurements. They do not predict an individual’s outcome, establish causation beyond the randomized comparison as implemented, or support medical advice. They should not be generalized automatically to other populations, types of periodontal defects, procedures, or settings that the record does not describe.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate is not enough to assess a treatment comparison. The observed CAL contrast has a clear numerical direction, but its confidence interval spans zero and leaves uncertainty about the size and direction of the underlying difference. Reporting the estimate alongside its interval is more informative than relying on the mean values alone or reducing the result to a p-value.

It also shows how outcome definitions influence interpretation. CAL is constructed from PPD and GM, so the primary outcome brings together two periodontal measurements. The registry reports results for these components as secondary outcomes, but they do not replace a clearly specified primary analysis. Understanding the endpoint’s construction helps readers see what the primary contrast captures and what it may not capture on its own.

The record provides a useful example of the distinction between posted descriptive results and a trial’s prespecified analysis. Arm means and standard deviations allow an unadjusted comparison to be recalculated, but the registry does not report the sponsor’s full analysis, the analysis populations, or missing-data methods. The recalculated comparison therefore offers a transparent reading of the summaries, not a reconstruction of every analytic decision.

Finally, the planning illustrations demonstrate how assumptions about the effect to detect affect sample-size requirements. A smaller target effect requires more participants per arm under the stated planning approach. Such illustrations can inform future planning, but they do not reveal the completed trial’s original justification or establish the adequacy of its design.

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 describes a terminated study but does not state why it was terminated. It reports enrollment of 35, while the primary outcome summaries include 14 participants in the Emdogain group and 15 in the surgery group. Safety counts use different at-risk denominators. The record does not explain these differences or report the flow of participants through recruitment, follow-up, and analysis.

The record identifies the design as randomized, single-masked, and parallel, but does not say who was masked or describe randomization and allocation procedures. Detailed eligibility criteria, the number or identity of centers, baseline group characteristics, and the statistical analysis plan are not reported. The absence of those details limits assessment of balance, generalizability, and potential sources of bias.

Only selected secondary outcomes have posted numerical results. The registry does not report numerical results for the other listed secondary outcomes, a multiplicity strategy, or inferential analyses from the sponsor. Missing-data handling, analysis populations, baseline adjustment, and sensitivity analyses are also not reported. The unadjusted recalculation cannot address those gaps.

The outcome is derived from PPD and GM, but the record does not provide further measurement or assessor-reliability details. The primary confidence interval is broad and includes zero, so the comparison is imprecise. These limitations are specific to interpreting this registry record; they do not establish that the underlying trial necessarily had any particular methodological flaw.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety and Efficacy of Periodontal Surgery in Supra-alveolar-type Defects With or Without Straumann® Emdogain — NCT01614925.
• Registry record last updated 2020-12-01; status last verified 2020-11.
• Results first posted 2020-12-01.
• 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

NCT01614925 is a randomized, controlled, multicenter, parallel-group study comparing periodontal surgery with Straumann® Emdogain against periodontal surgery alone in supra-alveolar-type defects. The registry records single masking, enrollment of 35, and a TERMINATED status. The primary endpoint is mean change in CAL from baseline to 12 Months, defined as PPD minus GM.

The posted primary means are -2.91 mm for Emdogain and -2.08 mm for periodontal surgery. The unadjusted recalculated difference is 0.83 mm, with a 95% confidence interval from -0.124 to 1.784 mm and an unadjusted p-value of 0.088. The interval includes zero and indicates substantial uncertainty about the contrast. Selected secondary outcomes and adverse-event counts are posted, but analysis-plan details, the reason for termination, and important information about missing data and analysis populations are not reported in the registry record.