CATER: Comprehensive Alveolar and Tooth Esthetic Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CATER: Comprehensive Alveolar and Tooth Esthetic Replacement (NCT04082143), a randomized phase 3 study. The primary outcome is Percent Change in Volume of Alveolar Ridge as Measured by 3D Intraoral Scanning.

2. Clinical Question

3. Trial Design

CATER was a phase 3, randomized, parallel-group trial with no masking. Participants were assigned to implant placement with prophylactic allograft or implant placement without prophylactic allograft. The registry records enrollment of 39, a start date of 2019-08-25, primary completion on 2022-07-01, and a completed status. The primary outcome summaries use 19 participants in the allograft group and 18 in the group without allograft.

The study summary describes graft assignment on the day of implant surgery. Participants were also asked to complete an oral health questionnaire. Follow-up described in the record included a clinic visit about 8 weeks after surgery for digital crown impressions, crown placement at 11-13 weeks after surgery, and an implant evaluation at 1 year. At the final appointment, the study planned x-rays and a 3D intraoral scan for alveolar volume measurement, assessment of mucosal health by bleeding upon probing, and a satisfaction questionnaire.

The registry lists the University of Illinois Chicago as sponsor and Dental Implant Failure Nos as the condition. It identifies the primary endpoint as percentage change in alveolar ridge volume at 12 months post implant surgery. The registry record does not report the original statistical analysis plan, allocation ratio, masking rationale, or detailed eligibility criteria. Although the study is marked completed, a completed status alone does not describe how participants were handled in the analyses or whether all planned measurements were available.

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 Percent Change in Volume of Alveolar Ridge as Measured by 3D Intraoral Scanning, measured over 12 months post implant surgery.

The primary endpoint is the mean percentage change in alveolar ridge volume measured by 3D intraoral scanning at 12 months post implant surgery. It is a continuous outcome: each participant’s measurement contributes to a group mean, and the registry reports a standard deviation to describe variation among participants. The endpoint is intended to quantify change in the volume of the ridge around the implant, rather than a binary outcome such as whether an implant survived.

In general, a measurement of tissue volume can help describe structural change over follow-up. Comparing the group means estimates how much the average percentage change differed between the assigned approaches. The endpoint is relevant to the study’s stated purpose of evaluating implant health and appearance, and the registry specifically describes obtaining a 3D scan to measure alveolar volume. The record does not report the exact calculation used to derive each participant’s percentage change, the baseline measurement procedure, or how scans were processed. Those details matter for understanding how the recorded change was constructed and how measurement variability may affect the result.

The posted means were 15.5 for the allograft group and 16.8 for the group without allograft. The posted comparison is expressed as the mean difference for the group without allograft relative to the allograft group. The interval around that estimate is broad, which limits the precision with which the trial distinguishes plausible group differences.

7. Results Posted in the Registry

• Implant Without Prophylactic Allograft: mean 16.80 versus 15.50 on control; difference 1.30 (95% CI -28.59 to 31.19), standardized effect d = 0.03; z-test p = 0.932.

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.

Marginal Bone Levels (MBLs)

• 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:
  • Implant Without Prophylactic Allograft: mean -0.01 versus -0.17 on control; difference 0.16 (95% CI 0.00 to 0.32), standardized effect d = 0.64; z-test p = 0.046.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Implant Without Prophylactic Allograft than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Vertical Tissue Change as Measured by 3D Intraoral Scanning

• 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:
  • Implant Without Prophylactic Allograft: mean 0.16 versus 0.18 on control; difference -0.02 (95% CI -0.21 to 0.17), standardized effect d = -0.07; z-test p = 0.835.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Implant Without Prophylactic Allograft and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes provide a broader view of measurements recorded at follow-up, including marginal bone levels and vertical tissue change. The registry also lists implant survival as a secondary outcome, but the posted numerical summaries include continuous results for the tissue measures. Taken together, the secondary outcomes do not create a single, uniformly clear pattern that resolves the uncertainty in the primary volume result. Each measure describes a different aspect of implant-related tissue or outcome, so agreement or disagreement among them should not be assumed.

The relationship to the primary result is contextual rather than confirmatory. The primary endpoint directly measures percentage change in alveolar ridge volume; the secondary measures do not substitute for that endpoint. Where secondary estimates appear more suggestive, they still do not establish that the primary outcome has been precisely determined. Differences among measures may reflect their distinct scales, variability, and underlying constructs, and the registry record does not report a plan for synthesizing them.

The registry provides no reported analyses for the secondary outcomes. The posted comparisons are unadjusted recalculations and should be treated as exploratory. Multiple outcomes create more opportunities for apparently notable findings to arise by chance when each is considered separately. The registry record does not report whether a multiplicity adjustment was planned or whether any outcome was designated for confirmatory interpretation beyond the primary endpoint. For that reason, unadjusted secondary results carry less inferential weight than a prespecified, fully reported primary analysis.

Secondary findings can still be useful for generating questions and for understanding the range of measured outcomes. They are best considered alongside the primary estimate, its uncertainty, and the incomplete reporting of analysis methods. They do not, on their own, demonstrate a consistent effect across outcomes or establish why any measures might differ.

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

• Percentage of Implant Survival
• Marginal Bone Levels (MBLs)
• Vertical Tissue Change as Measured by 3D Intraoral Scanning

9. Statistical Interpretation

10. Statistical Methods Explained

The posted group summaries report means and standard deviations for continuous outcomes. The comparisons are unadjusted recalculations from those summary statistics. They describe differences between group averages without accounting for any additional participant characteristics or a model-based adjustment. The registry record does not report a sponsor analysis for the primary or secondary comparisons, nor does it provide a full statistical analysis plan.

What does a mean difference represent?

For the primary outcome, the mean difference is calculated as the group without allograft minus the group with allograft. Its sign therefore identifies which group had the larger reported mean: a positive estimate means the mean was higher in the group without allograft, while a negative estimate means it was lower. The estimate is expressed in the endpoint’s measurement scale. Since the outcome is percentage change, the difference is expressed in percentage points, not as a relative percentage increase or decrease.

A mean difference condenses the two group averages into one contrast, but it does not show how values are distributed within each group. Standard deviations describe the spread of observations around their respective means. When variability is large relative to a mean difference, the estimated contrast can be uncertain. The primary outcome standard deviations differ substantially between groups, so the group averages should be read alongside the spread and the interval for the comparison.

How should the interval be read?

A confidence interval describes a range of values compatible with the observed data under the calculation’s assumptions. It reflects uncertainty in the estimated contrast; it is not a range containing a stated proportion of individual participant measurements. For the primary outcome, the reported interval extends from -28.59 to 31.19. Because that range includes zero, the data do not pin down the direction of the mean difference. Its breadth also shows that the point estimate of 1.3 is not precise. The confidence level used for the reported interval is not reported in the registry record.

In general, an interval that crosses zero does not prove that the groups are identical. It indicates that the data are compatible with no difference as well as with differences on either side of zero, within the interval’s stated range. Conversely, an interval that excludes zero is not by itself proof of clinical importance, sound measurement, or a prespecified finding. Those judgments depend on design, context, analysis choices, and the size and relevance of the measurement difference.

What does the p-value add?

The primary unadjusted p-value is 0.932. In general, a p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be under that hypothesis and the model assumptions. It is not the probability that the null hypothesis is true, and it does not measure the probability that a result will replicate. The registry record does not report a primary analysis plan or a decision threshold for the trial, so the p-value should be treated as a descriptive part of the unadjusted recalculation rather than as a complete account of the trial’s planned inference.

The planning illustration states a two-sided significance level of 0.05 for sample-size calculations. That assumption belongs to the planning illustration and does not establish that the trial’s own analysis used the same threshold. The trial’s original design assumptions and statistical plan are not reported in the registry record.

Why does variability matter?

In general, greater outcome variability makes a group mean harder to estimate precisely for a given amount of information. When the observed spread is large compared with the difference between group means, the interval for the difference tends to be wider. The unusually different standard deviations in the primary summaries also raise the importance of understanding the measurement distribution and the analysis method. The registry record does not report diagnostic checks, transformations, robust methods, or other approaches to address unequal variability.

Over-dispersion is a general issue when observed variability is greater than an analysis model expects. If a model underestimates variability, uncertainty can appear smaller than it should be. The primary summaries report standard deviations directly, but no model checks or variance-handling approach are reported. This is a reason to avoid treating the recalculated comparison as a full analysis of the trial.

What is and is not reported about the analysis?

The registry record lists no reported analyses for the primary outcome and no reported analyses for the posted secondary continuous outcomes. It does not report adjustment for baseline measurements, covariates, missing outcome data, protocol deviations, or repeated measurements. It also does not identify whether summaries represent all randomized participants, only participants with available measurements, or another analysis population. These details are important because they affect the population represented by the estimates and the assumptions needed for inference.

Randomization supports a comparison of assigned groups, but it does not, by itself, determine how missing measurements or deviations should be handled. In general, analyses based on only participants with observed outcomes may be biased if outcome availability is related to group assignment or outcome values. The registry record does not report whether missingness occurred or how it was addressed, so its effect cannot be evaluated from the posted results.

11. Confidence Intervals and Precision

The primary mean difference is 1.3 percentage points, with a reported interval from -28.59 to 31.19. The interval is wide relative to the point estimate and crosses zero. It therefore leaves substantial uncertainty about both the direction and size of the difference. The reported values do not support a precise estimate of how the groups differed in mean percentage change in alveolar ridge volume.

The group standard deviations also help explain the uncertainty. The allograft group had a standard deviation of 19.0, compared with 62.0 in the group without allograft. The larger spread in the latter group indicates that its individual measurements varied considerably around the mean. A mean can still be calculated in the presence of such variation, but the mean difference is less precisely determined when the data are dispersed and the outcome group sizes are limited.

The confidence level for the posted interval is not reported in the registry record. The interval should therefore be interpreted as the range stated by the registry recalculation, without assigning it a confidence level that is not documented. In general, an interval is a useful measure of precision because it displays a range of estimates compatible with the data and method. It is not a guarantee that the true difference lies within its limits.

The primary endpoint’s precision is a separate question from whether the point estimate is close to zero. A small point estimate can coexist with considerable uncertainty, as in this result. The interval includes negative and positive values, so the posted summary does not isolate one direction. Additional precision would require better information about the outcome distribution, available measurements, and analysis method; those details are not reported in the registry record.

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 illustration gives participants per arm for the continuous outcomes in this trial. It does not report a total number of events. Its 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 set at the stated fraction of the observed effect. These are planning assumptions for the illustration; the registry record does not report the trial’s original sample-size assumptions or justification.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the corresponding per-arm planning number for a 90% chance. Power is a design property tied to an assumed effect size and analysis, not a measure of how likely the observed result is to be true. These figures are not observed power.

Rows describe planning for 100%, 75%, or 50% of the observed effect. A smaller assumed effect is harder to distinguish from random variation, so the required number of participants per arm increases as the effect to detect becomes smaller. The values are illustrations based on the observed effect, not evidence that the trial was designed around that effect. The registry does not report whether its original planning used a different target effect, endpoint variance, allocation, or method.

The sample-size curve should be read in the same way: it represents planning under the stated assumptions as the effect size changes. It is not a reconstruction of the trial’s enrollment target or a forecast of what another study must enroll. The calculation uses a normal approximation and does not describe potential losses to follow-up, missing data, multiplicity, or other design features unless those are explicitly included in the stated assumptions.

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 = 1.300; pooled standard deviation σ = 45.307.
2. n = 2 × (1.96 + 0.842)² × 45.307² / 1.300² = 19,067.1, rounded up to 19,068 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 <- 1.3                      # observed difference in means
sigma <- 45.3072053556921                     # 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(4082143)
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 = 19,068 (80% power), 25,526 (90% power)
 75% of observed effect: n per arm = 33,898 (80% power), 45,379 (90% power)
 50% of observed effect: n per arm = 76,269 (80% power), 102,102 (90% power)
power.t.test: 19068.1 
Simulated power at n = 19,068 per arm: 0.801 (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 outcome and several secondary outcomes, but the record does not report a multiplicity strategy. When multiple outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each is interpreted separately. In general, a prespecified hierarchy, adjustment method, or clearly exploratory framing can help readers distinguish confirmatory results from findings that are better treated as hypothesis-generating. No such strategy is reported in the registry record.

The posted secondary comparisons are unadjusted, and no reported analyses are listed for the primary or secondary outcomes. The registry record does not say whether the primary endpoint was the sole confirmatory test, whether secondary outcomes were intended to support the primary question, or whether adjustments were considered. The planning illustration’s two-sided significance level of 0.05 is not evidence of the threshold or multiplicity approach used in the trial’s original analysis.

Information about missing data and analysis populations is also not reported. The registry does not say how many participants had each outcome measured, whether any measurements were missing, why measurements might have been missing, or how missingness was handled. It does not specify whether results were based on all randomized participants, participants with available outcome measurements, or another population. Outcome summaries give group counts, but those counts alone do not describe the analysis population or explain departures from the randomized groups.

In general, missing outcomes can affect estimates if availability differs between groups or is related to the measured result. Appropriate handling depends on the reason for missingness and the analysis plan. Without a reported flow of participants through follow-up, a missing-data approach, and sensitivity analyses, readers cannot judge whether the posted summaries are robust to missing outcomes. These are reporting limitations; they do not establish that data were missing or that any particular bias occurred.

The record also does not report protocol deviations, prespecified covariate adjustment, or sensitivity analyses. Those omissions constrain assessment of how faithfully the posted comparisons represent the trial’s planned inference. The recalculated unadjusted results are useful descriptions of the posted summary statistics, but they do not replace a complete analysis report.

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 adverse-event record reports zero serious adverse events among 19 participants at risk in the allograft group and zero among 20 participants at risk in the group without allograft. It also reports zero other adverse events in each group and zero deaths in each group. The safety denominators differ from the primary outcome summary counts, which are 19 and 18; the registry record does not explain the difference.

These figures describe events recorded in the registry for the reported at-risk groups. A zero count means no event of that category was recorded in those groups; it does not establish that an event is impossible or that the approaches have identical safety profiles. Event counts are difficult to interpret without information about how events were defined, how they were collected, the observation period for adverse events, and whether all participants were monitored in the same way. Those details are not reported in the registry record.

The trial’s safety summaries should be read as descriptive, not as a definitive comparison of risks. The record does not report a comparative statistical analysis of adverse events. The absence of recorded events in these summaries does not support a broader claim beyond the counts and denominators reported.

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

The posted primary result is a comparison of mean percentage change in alveolar ridge volume at 12 months post implant surgery. The observed means were 15.5 with prophylactic allograft and 16.8 without it. The unadjusted mean difference was 1.3 percentage points, with an interval from -28.59 to 31.19. This interval spans differences in both directions and is broad, so the estimate does not precisely identify the size or direction of a group difference.

The result does not establish that the approaches are equivalent. An interval that includes zero can reflect limited precision as well as a small underlying difference. It also does not establish a meaningful advantage for either group: the point estimate is only one part of the evidence, and its uncertainty is substantial. The p-value of 0.932 should not be interpreted as the probability that there is no difference or as a measure of clinical importance.

The trial’s randomized, parallel-group design is relevant to the intended comparison, but the registry record does not report a complete statistical analysis, missing-data handling, or the analysis population. The available comparisons are unadjusted recalculations. Consequently, the posted results should be understood as descriptive estimates rather than as a complete account of the trial’s planned inferential analysis.

The secondary summaries and adverse-event counts offer additional observations but do not remove the limitations of the primary result. Secondary comparisons are unadjusted, multiplicity handling is not reported, and the registry’s safety summaries record no events in the stated categories. None of these registry entries justifies a broad conclusion about treatment effectiveness or safety. The results apply to the outcomes and participants described in the registry, with the uncertainty and reporting gaps noted above.

In general, evidence about a clinical intervention is strongest when the design, outcome definitions, analysis plan, participant flow, and uncertainty are all clear. Here, the randomized design and posted measurements can be described, but several analytic details are absent from the registry record. The appropriate interpretation is therefore limited to what the reported estimates and their precision show.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison needs to be read together with its uncertainty and reporting context. The primary mean difference is close to zero as a point estimate, but its interval is broad and includes values on either side. Looking only at the observed difference would understate uncertainty; looking only at the p-value would also miss the range of compatible estimates. The interval and the notably different group standard deviations make precision central to interpretation.

The posted primary endpoint is a continuous structural measurement rather than a simple event count. Continuous outcomes can preserve information about the degree of change, but they also require attention to measurement procedures, variability, and analysis assumptions. The registry gives the outcome definition and measurement approach but does not report key details such as the percentage-change calculation or scan-processing methods. Those details would help readers evaluate how measurement choices affect the estimate.

The record also demonstrates the distinction between an observed result and a planning illustration. Sample-size figures based on the observed effect are not evidence of the trial’s original design assumptions and are not observed power. Keeping planning assumptions separate from the original study plan prevents a retrospective calculation from being mistaken for a prospective justification.

Finally, the secondary outcomes and safety summaries show why outcome multiplicity and complete reporting matter. Separate unadjusted findings should not be treated as independent confirmations, and zero recorded adverse events should not be taken as proof of no risk. Transparent reporting of prespecified analyses, missing-data handling, participant flow, and outcome definitions would make the clinical and statistical interpretation more secure.

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 primary comparison has limited precision: the interval extends from -28.59 to 31.19, and the group standard deviations differ substantially. The registry record does not provide a confidence level for the interval or the analysis method used in the original trial. The posted comparison is an unadjusted recalculation from group summaries, so it may not match an analysis specified by the investigators.

Details needed to assess measurement quality are not reported in the registry record. The study summary identifies 3D intraoral scanning as the method for measuring alveolar volume, but does not describe the formula for percentage change, scan processing, assessor procedures, or reproducibility. The outcome population field is blank. Eligibility criteria and fuller participant characteristics are also not reported.

The registry does not report a participant flow, outcome-specific missingness, handling of missing data, or the population used for analysis. Outcome counts and safety denominators differ for the group without allograft, but the reason is not reported in the registry record. The record also provides no reported analyses, adjustment strategy, or sensitivity analyses.

The secondary comparisons are unadjusted, and multiplicity handling is not reported. The original sample-size justification and design assumptions are not reported; planning figures based on the observed effect are illustrative only. The record’s completed status does not answer these analytic questions. These limitations do not establish that the study was conducted improperly, but they constrain what can be concluded from the posted results.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: CATER: Comprehensive Alveolar and Tooth Esthetic Replacement — NCT04082143.
• Registry record last updated 2025-02-28; status last verified 2025-02.
• Results first posted 2025-02-28.
• 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

CATER is a completed, randomized, parallel-group phase 3 trial sponsored by the University of Illinois Chicago. It compared dental implant placement with prophylactic allograft mucosal enhancement against implant placement without an allograft. The registry records enrollment of 39, with a start date of 2019-08-25 and primary completion on 2022-07-01. No masking is recorded.

The primary outcome was mean percentage change in alveolar ridge volume measured by 3D intraoral scanning at 12 months post implant surgery. The posted unadjusted mean difference, without allograft relative to with allograft, was 1.3 percentage points, with an interval from -28.59 to 31.19 and an unadjusted p-value of 0.932. The interval is broad and includes differences in either direction.

The registry also posts continuous results for marginal bone levels and vertical tissue change. No reported analyses are listed. Missing-data handling, the analysis population, multiplicity approach, original statistical plan, and original sample-size justification are not reported in the registry record. Adverse-event summaries record zero serious events, zero other events, and zero deaths in the reported groups.