Clinical Study Comparing Submerged Versus Trans-mucosal Healing of P.004 Implants in the Anterior Mandible and Maxilla: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Study Comparing Submerged Versus Trans-mucosal Healing of P.004 Implants in the Anterior Mandible and Maxilla (NCT00906425), a randomized na study. The primary outcome is Mean Change in Bone Level (Distance B) After 6 Months Compared to Baseline (=Surgery).

2. Clinical Question

3. Trial Design

This was a randomized, controlled clinical study with a parallel-group design. It compared submerged healing with trans-mucosal healing after placement of Straumann Bone Level Implants. The registry lists no masking, so the study was unmasked. Its status is completed, and the listed phase is NA. Institut Straumann AG is identified as the sponsor.

The registry gives enrollment as 145 and identifies the condition as partially edentulous jaw. The study title places the implants in the anterior maxilla and mandible. The listed study start is 2006-10, and primary completion is listed as 2008-06. These record dates and status describe the trial entry; they do not provide a detailed account of recruitment, follow-up, or the conduct of each study visit.

The primary outcome was mean change in bone level, in millimeters, between baseline at surgery and 6 months. The record reports the outcome for the ITT population and lists group summaries for submerged healing and trans-mucosal healing. The arm counts for this outcome are 65 and 59, respectively. The record does not explain how these analysis counts relate to the enrollment figure or whether any participants lacked an outcome measurement.

The registry also lists implant survival rate among secondary outcomes, with the same outcome label appearing twice. It records 3 outcome measures and 0 analyses. It does not give further details about the randomization procedure, concealment, visit schedule, or the original statistical analysis plan. Those omissions limit how fully the design and analysis can be reconstructed from 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

Analysis population for the primary outcome, as defined in the registry: ITT population

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 Mean Change in Bone Level (Distance B) After 6 Months Compared to Baseline (=Surgery), measured over Baseline and 6 months.

The primary endpoint is mean change in bone level, measured in millimeters, from baseline at surgery to 6 months. The registry describes measurement at the mesial and distal aspects of the implant, with the implant shoulder serving as the reference point. The endpoint is listed as a mean with standard deviation, and the analysis population is identified as ITT.

Bone-level change is a continuous measurement: it can take a range of values rather than being limited to categories such as event or no event. A group mean summarizes the average measured change among the participants included in that group’s outcome summary. The standard deviation describes how spread out individual measurements are around that group mean. The means and standard deviations therefore describe both the average observed change and the variability in the measurements.

Comparing the change between healing approaches addresses whether the groups had different average measured changes over the stated interval. The comparison is expressed as a mean difference, with the trans-mucosal-healing group compared with the submerged-healing group. The endpoint is relevant to the study’s stated aim because it directly summarizes bone-level change around the implants during the period specified in the registry. It does not, on its own, describe implant survival or other clinical outcomes.

The registry does not provide a detailed measurement manual, information about assessor training, or a description of how measurements from the mesial and distal aspects were combined for the reported outcome. These details are not reported in the registry record.

7. Results Posted in the Registry

• Trans-mucosal Healing: mean -0.29 versus -0.32 on control; difference 0.03 (95% CI -0.12 to 0.18), standardized effect d = 0.07; z-test p = 0.685.

8. Statistical Interpretation

9. Statistical Methods Explained

The registry presents a continuous primary outcome and a comparison of group means. The main result is the mean difference for trans-mucosal healing relative to submerged healing. The accompanying confidence interval and unadjusted p-value are different ways to summarize uncertainty about that comparison. They should be considered together with the endpoint definition, group sizes, and limitations of the record.

What does a mean difference represent?

For a continuous outcome, each group’s mean is an average of the measurements in that group. A mean difference compares those averages, with the direction depending on which group is subtracted from which. Here, the comparison is trans-mucosal healing relative to submerged healing: the estimate is 0.03 millimeters. A positive value indicates a higher group mean for trans-mucosal healing under that ordering; it does not by itself say whether the difference is important. The clinical meaning depends on the measurement and on a threshold for meaningful change, which is not reported in the registry record.

The group means are -0.32 and -0.29 millimeters, and the group standard deviations are 0.47 and 0.35 millimeters. A standard deviation describes the spread of individual measurements around a group mean. It is not the same as the uncertainty in the mean or the uncertainty in the difference between means. The uncertainty in a comparison also depends on the number of observations and the variability within groups.

How should the p-value be read?

The unadjusted p-value is 0.685. In general, a p-value measures how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null model is true, and it does not measure the size or importance of the observed difference. The word “unadjusted” indicates that this value is not adjusted for multiple comparisons. The registry does not provide a broader testing plan that would clarify how this endpoint relates to other planned tests.

A large p-value is not proof of no effect. It can occur when the estimate is close to zero, when uncertainty is substantial, or both. For this result, the confidence interval provides the direct range of values compatible with the reported analysis. A conclusion of equivalence would need an appropriate margin and analysis, neither of which is reported in the registry record.

What does the confidence interval add?

The reported interval for the mean difference is -0.115 to 0.175 millimeters. In general, a confidence interval is a range produced by a statistical procedure that reflects uncertainty in an estimate. It is not a guarantee that the true value lies within that particular interval, nor does it give the probability that a specific value is true. Here, the interval includes zero and values on both sides of zero. Its width is important: it shows that the estimate does not pinpoint a single small difference.

The registry does not describe whether the comparison used a particular variance assumption, adjustment for baseline measurements, or another covariate-adjusted model. It also does not state whether there were interim analyses. Those analysis details are not reported in the registry record, so further assumptions about the model should not be made from the summary alone.

Why can variation matter?

In general, greater variation among individual measurements makes it harder to estimate a group average precisely, all else being equal. If variation is not adequately represented by the analysis, the reported uncertainty can be misleading. The posted arm standard deviations summarize the observed spread, but the record does not report diagnostic checks, distributional plots, or an assessment of unusual observations. The calculated displays may help readers see the posted summaries, but they cannot supply unreported details about the statistical model.

Randomization is intended to support a fair comparison by reducing systematic differences between groups at assignment. It does not guarantee that every other aspect of the study was unbiased, and it does not remove uncertainty from a finite set of observations. The record identifies the study as randomized but does not describe sequence generation or allocation concealment. The study was unmasked, and the record does not explain whether outcome assessors were masked.

The comparison is therefore best read as a summary of the posted data, with the stated uncertainty and the reporting limitations kept in view. The registry entry does not include enough detail to reproduce all analytic choices or assess every assumption independently.

10. Confidence Intervals and Precision

The mean difference is 0.03 millimeters, with a 95% confidence interval from -0.115 to 0.175 millimeters. The interval crosses zero, so the posted estimate does not distinguish confidently between a small difference in one direction, no difference, or a difference in the other direction. This is a statement about statistical uncertainty, not a conclusion that the possible differences are clinically equivalent.

Precision is about how narrowly the data locate the estimated comparison. A narrower interval would indicate more precise estimation; a wider interval leaves more values compatible with the analysis. The reported interval has a meaningful span relative to the point estimate, so the estimate should not be presented as an exact measure of the difference between the approaches. The site’s plots and tables can make the estimate and interval easier to inspect, but they do not change the underlying uncertainty.

The group outcome counts are 65 for submerged healing and 59 for trans-mucosal healing. The standard deviations are 0.47 and 0.35 millimeters, respectively. These counts and spreads are relevant to the precision of the comparison. The registry enrollment is 145, and the record does not explain the difference between enrollment and the arm counts contributing to the posted outcome. It does not state how missing measurements were handled or whether the confidence interval reflects any adjustment for missingness.

Confidence intervals also do not answer whether the range they contain is clinically important. The registry does not report a threshold for an important bone-level difference, a non-inferiority or equivalence margin, or a formal precision target. Thus, the interval can be described statistically, but its clinical acceptability cannot be determined from the record alone.

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 sample-size table and curve are planning illustrations based on the observed effect, not a report of the trial’s original sample-size calculation. The figures are participants per arm, not total participants or total events. They compare planning for 100%, 75%, and 50% of the observed effect and show separate columns for 80% and 90% power. For example, The table shows 3,037 participants per arm for 80% power and 4,066 participants per arm for 90% power when planning for 100% of the observed effect. The other rows show the corresponding illustrations for smaller fractions of that effect.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. Under these assumptions, the 80% power column represents a design with an 80% chance of detecting the chosen effect if that effect were the true one, while the 90% power column represents a design with a 90% chance under the same planning framework. These are design probabilities, not probabilities that the observed result is true.

Smaller effects are harder to distinguish from random variation, so the planning illustrations require more participants per arm as the effect fraction becomes smaller. The table is not observed power: it does not describe the probability that this completed trial detected an effect after seeing its results. The registry’s own original design assumptions and sample-size justification are not reported in the registry record. These illustrations should therefore not be treated as evidence about the trial’s original planning or as an explanation for its enrollment.

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 = 0.030; pooled standard deviation σ = 0.417.
2. n = 2 × (1.96 + 0.842)² × 0.417² / 0.030² = 3,037.0, rounded up to 3,037 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 <- 0.03                      # observed difference in means
sigma <- 0.417276493624009                     # 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(906425)
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 = 3,037 (80% power), 4,066 (90% power)
 75% of observed effect: n per arm = 5,400 (80% power), 7,228 (90% power)
 50% of observed effect: n per arm = 12,148 (80% power), 16,263 (90% power)
power.t.test: 3037.9 
Simulated power at n = 3,037 per arm: 0.800 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists implant survival rate twice among its secondary outcomes, records 3 outcome measures, and records 0 analyses. The primary outcome is mean change in bone level. The record does not give a complete hierarchy of outcomes or a statistical analysis plan identifying which comparisons were primary, secondary, or exploratory. The duplicate secondary-outcome wording does not establish whether two distinct survival measures were intended.

Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. In general, the more tests considered, the greater the chance that at least one result may appear noteworthy by chance if no adjustment or prespecified strategy is used. The posted p-value is explicitly unadjusted. The registry does not report a multiplicity adjustment, a gatekeeping strategy, or another plan for interpreting multiple tests. The result should therefore be understood as an unadjusted comparison, rather than as one protected by a documented family-wide testing procedure.

The primary outcome is labeled ITT, but the record does not define the precise analysis population or explain how participants were handled after randomization. It reports 65 participants for submerged healing and 59 for trans-mucosal healing on the primary outcome, compared with enrollment of 145. Reasons for the different counts, missing measurements, withdrawals, protocol deviations, and the treatment of missing data are not reported in the registry record. The ITT label alone does not show how these issues were addressed.

The record also does not report imputation methods, sensitivity analyses, a per-protocol analysis, or an explanation of whether all randomized participants were included in the analysis. It does not describe interim analyses or stopping rules. These gaps do not establish that such procedures were absent; they mean they are not reported in the registry record. Readers should avoid inferring details of the analysis population or missing-data strategy from the posted group summaries alone.

14. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: uterine cancer (1.4%).

The registry lists serious adverse events for 73 participants at risk in the submerged-healing group and 72 at risk in the trans-mucosal-healing group. It records 2 affected participants in the submerged group and 0 in the trans-mucosal group. For other adverse events, the at-risk counts are 73 and 72, and the affected counts are 8 and 10, respectively. These are the figures to use when reading the posted safety summary; they are not the primary bone-level outcome.

The registry identifies Uterine Cancer as a top serious adverse event term and lists 1.4%. The entry does not assign this term to an arm in the information, so it should not be attributed to either healing group. The deaths field is not populated; deaths are not reported in the registry record.

These counts are descriptive. The registry excerpt does not provide event-level narratives, timing, severity grading beyond the serious-event category, or a statistical comparison of adverse events. The at-risk counts are not the same as the primary-outcome counts, and the record does not explain the relationship between them. Readers should not infer causation or comparative safety from the counts alone.

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

The result describes the average bone-level change reported for the two healing groups between surgery and 6 months. The group means are -0.32 millimeters for submerged healing and -0.29 millimeters for trans-mucosal healing. The estimated mean difference is 0.03 millimeters, with a 95% confidence interval from -0.115 to 0.175 millimeters and an unadjusted p-value of 0.685. These findings show a small point estimate relative to the range of uncertainty, but they do not establish that the approaches have the same effect.

The study summary states an aim of demonstrating no difference. A result that does not provide strong evidence against a no-difference model is not the same as evidence that differences are absent or unimportant. A formal claim of equivalence would require an appropriate equivalence margin and analysis. Neither is reported in the registry record. Because the interval includes values on both sides of zero, the posted result remains compatible with differences in either direction.

The endpoint concerns measured bone-level change over the specific interval reported. It does not answer whether the healing approaches differ in longer-term bone-level outcomes, implant survival, or other outcomes. Although implant survival rate appears among the listed secondary outcomes, the record does not provide a posted analysis of that outcome. It also does not give a threshold for interpreting bone-level differences as clinically meaningful.

Interpretation is further limited by the unexplained gap between the enrollment count and the primary outcome counts, and by the lack of detail about missing data and analysis procedures. The result is a registry-based summary, not a substitute for a full account of trial conduct. It should not be used on its own to make treatment decisions. It supports a cautious statistical reading of the measured outcome, not a broad conclusion about clinical benefit, harm, or interchangeability.

16. Why This Trial Matters Statistically

This trial is statistically interesting because its stated purpose was to demonstrate no difference, while its posted result is an ordinary estimate of a mean difference with a confidence interval and unadjusted p-value. That distinction matters: a failure to show a difference is not, by itself, evidence of equivalence. The interval and the absence of a reported equivalence margin make clear why interpretation should focus on the uncertainty rather than the point estimate alone.

The outcome is continuous, and the registry reports both group means and standard deviations. This gives readers more context than a result expressed only as a binary test outcome. The mean difference conveys direction and size on the measurement scale, while the interval shows the range of values compatible with the analysis. Together they make the precision of the estimate visible.

The record also illustrates how reporting details shape statistical interpretation. Randomization is reported, but sequence generation and allocation concealment are not. The study was unmasked, yet assessor masking is not described. The outcome is labeled ITT, but the analysis counts do not match the enrollment count and the record does not explain missing-data handling. These are not minor details when assessing how directly the reported comparison reflects the randomized study.

Finally, the sample-size illustrations are distinct from the trial’s original design. Their large participant requirements follow from planning around the observed effect and the stated assumptions; they do not show what the investigators planned before the results were known. Separating retrospective planning illustrations from prospective design decisions is essential to avoid treating a post-result calculation as evidence that the study was adequately or inadequately planned.

17. 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 important design and analysis details unspecified. It identifies the study as randomized and unmasked, but does not report how the allocation sequence was generated, whether assignments were concealed, or whether outcome assessors were masked. It also does not provide a detailed protocol or a statistical analysis plan. The trial’s original sample-size justification, any equivalence margin, and any interim-analysis plan are not reported in the registry record.

The primary endpoint counts are 65 for submerged healing and 59 for trans-mucosal healing, while the enrollment figure is 145. The record does not explain the difference, state how many participants had missing bone-level measurements, or describe any missing-data method. Although the endpoint is labeled ITT, the information available does not establish exactly how that population was defined or implemented.

The posted comparison is unadjusted, and the registry does not explain whether baseline values or other variables were included in the analysis. It does not provide diagnostics, detailed measurement procedures, or enough information to reproduce the calculation independently. The reported confidence interval can be interpreted as posted, but the model assumptions behind it are not fully described in the record.

The record lists implant survival rate twice as a secondary outcome, but does not provide an analyzed comparison for that outcome in the results. It also gives limited detail about adverse events, including no event-level context for the listed serious-event term. Finally, the primary outcome covers baseline and 6 months only; longer-term outcomes are not reported in the registry record. These limits constrain what can be concluded from this entry.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Clinical Study Comparing Submerged Versus Trans-mucosal Healing of P.004 Implants in the Anterior Mandible and Maxilla — NCT00906425.
• Registry record last updated 2016-03-30; status last verified 2016-03.
• Results first posted 2012-08-31.
• 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.

21. Record Summary

This completed, randomized, parallel-group study compared submerged with trans-mucosal healing after placement of Straumann Bone Level Implants in the anterior maxilla and mandible. It was unmasked, had enrollment of 145, and was sponsored by Institut Straumann AG.

The primary outcome was mean change in bone level from surgery to 6 months, measured in millimeters and reported for the ITT population. The group means were -0.32 for submerged healing and -0.29 for trans-mucosal healing. The mean difference was 0.03, with a 95% confidence interval from -0.115 to 0.175 and an unadjusted p-value of 0.685.

The interval includes zero and leaves uncertainty about the direction and size of the difference. The record does not report an equivalence margin, detailed missing-data methods, or the trial’s original sample-size justification. The result should be read as an uncertain comparison of the posted six-month bone-level outcome, not as proof of equivalence.