Changes of Soft and Hard Tissues After Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Changes of Soft and Hard Tissues After Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot (NCT03331185), a randomized phase 2, phase 3 study. The primary outcome is Overall Horizontal Change in Alveolar Ridge Width.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group clinical trial with no masking. The study is listed as phase 2 and phase 3, and its status is completed. The registry records an enrollment of 26. The arm-level results are reported separately for Freeze Dried Bone Allograft and L-PRF Clot.

For the allograft arm, the registry describes the socket as filled with Mineralized Cortical Freeze Dried Bone Allograft. For the L-PRF arm, the socket was filled with L-PRF Clot. The official title identifies the trial as a comparison of alveolar ridge preservation approaches with a d-PTFE membrane, while the arm descriptions specify the socket-filling materials. Further procedural details are not reported in the registry record.

The recorded study start was 2018-01-03, and primary completion was 2019-04-02. The sponsor is the University of Manitoba. The trial addresses alveolar bone loss and tooth loss, with the stated purpose of comparing effects on gum and jaw-bone volume during healing and on pain or swelling after extraction.

The registry does not report the randomization method, allocation concealment procedures, or a detailed protocol for the imaging assessments. It records no masking, so readers should not assume that participants, clinicians or outcome assessors were blinded. The original design assumptions, including any planned sample-size justification, are not reported in the registry record. The analysis population and handling of participants who may not have contributed outcome data are also not described.

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 Overall Horizontal Change in Alveolar Ridge Width, measured over Difference reported on horizontal changes comparing CBCT analysis 11weeks after extraction and grafting compared to CBCT following extraction and grafting.

The primary endpoint is the overall horizontal change in alveolar ridge width, measured in millimeters. The registry describes it as a mean calculated from post-operative CBCT measurements of horizontal alveolar bone width changes following extraction and alveolar ridge preservation. Its timeframe compares CBCT analysis 11weeks after extraction and grafting with CBCT following extraction and grafting.

This endpoint is used to describe dimensional change in the ridge during healing. A signed change can indicate the direction of change according to the registry's measurement convention: a negative reported mean represents a decrease on that scale. The mean summarizes the group's average change, while the standard error describes the estimated precision of that mean. It is not a description of every participant's result, and it does not show how individual outcomes were distributed.

The registry reports means and standard errors for both arms and an unadjusted comparison. It does not report the detailed CBCT measurement protocol, assessor reliability, or a more complete account of how the endpoint was calculated. Those omissions limit how fully the measurement process can be evaluated from the registry record alone.

7. Results Posted in the Registry

• L-PRF Clot: mean -2.21 versus -1.34 on control; difference -0.87 (95% CI -1.97 to 0.23), standardized effect d = -0.61; z-test p = 0.120.

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.

Post-operative Pain and Swelling

• 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:
  • L-PRF Clot: mean 0.23 versus 0.22 on control; difference 0.01 (95% CI -0.22 to 0.24), standardized effect d = 0.03; z-test p = 0.931.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between L-PRF Clot and the control. The interval gives the range of effects that remain compatible with the data.

The registry identifies two secondary topics: buccolingual change in width of keratinized soft tissue and post-operative pain and swelling. A posted numerical result is available for pain and swelling, while a result for keratinized soft-tissue width is not reported in the registry record. The available secondary information therefore covers less than the full set of listed secondary outcomes.

The pain and swelling result shows very similar arm means and an unadjusted comparison near zero. Broadly, this does not supply a clear signal of a pronounced difference across the available secondary measure. The primary and secondary outcomes address different aspects of healing and post-operative experience, however, so a similar or dissimilar pattern would not by itself confirm or refute the primary result. Their scales, measurement methods and timing differ.

The secondary result should carry less weight than a prespecified primary outcome when drawing an overall statistical conclusion. The registry does not report a multiplicity plan or adjustments for testing several outcomes. When multiple outcomes are examined, the chance of observing an apparently unusual result by chance can increase, and results may be less persuasive if they were not prespecified or are selectively reported. The record does not report enough information to determine the outcome hierarchy or how secondary analyses were selected.

Secondary findings can still help describe the trial and identify questions for further study. They should be interpreted as supportive or exploratory evidence rather than as independent confirmation of the primary comparison. Since no analyses are listed as reported, and one listed secondary outcome lacks posted numerical results, the breadth and consistency of secondary evidence cannot be fully assessed from the registry record.

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

• Buccolingual Change in Width of Keratinized Soft Tissue
• Post-operative Pain and Swelling

9. Statistical Interpretation

10. Statistical Methods Explained

The posted results describe a continuous outcome as a group mean. A mean gives a single summary of the observed values within an arm. It is useful for comparing average change, but it can conceal variation among individuals and can be influenced by unusually high or low measurements. The registry reports standard errors alongside the primary means. A standard error concerns the precision of an estimated mean, not the spread of individual measurements; it should not be read as a description of the range of participant outcomes.

What does the mean difference represent?

The reported mean difference compares L-PRF Clot with Freeze Dried Bone Allograft. Its negative sign follows the registry's ordering and signed outcome scale. A negative contrast means the L-PRF arm's reported mean is lower on that scale; because the outcome is a signed change, lower values correspond to a more negative change. The contrast is an estimate from the posted group summaries, not a guaranteed difference that would be observed in every participant or setting.

The comparison is unadjusted. That means it is not presented as a model-based estimate controlling for other variables. Randomization is intended to support fair comparisons between assigned groups, but the registry does not report details of the randomization method or analysis model. The available record therefore does not establish whether any covariate adjustment, alternative model, or sensitivity analysis was used.

How should a confidence interval be read?

A confidence interval expresses uncertainty around an estimated effect under the method used to construct it. Its endpoints describe values compatible with the observed data and the procedure's assumptions; they are not a range containing every individual participant's outcome. For the primary comparison, the interval runs from -1.966 to 0.226. It includes zero, meaning that the posted interval does not rule out no average difference. It also includes values on either side of zero, so the direction of the underlying difference remains uncertain.

The confidence level and the full method used to form the interval are not reported in the registry record. Accordingly, the interval can be discussed as posted, but its exact inferential calibration cannot be independently assessed from the registry entries. A confidence interval should be considered alongside the point estimate, outcome definition and trial design rather than interpreted in isolation.

What does the p-value say?

The unadjusted p-value for the primary comparison is 0.12. In general, a p-value describes how unusual data at least as incompatible with a specified null model would be if that model and the test assumptions held. It does not give the probability that the null hypothesis is true, and it does not state the probability that a finding will replicate. It also does not measure clinical importance. Here, the registry does not give a full account of the test or its assumptions, so the p-value should be read as a reported unadjusted statistic rather than as a complete analysis description.

A non-small p-value does not demonstrate equivalence. Establishing equivalence or non-inferiority requires a prespecified margin and an analysis designed around that question; such details are not reported in the registry record. Likewise, a p-value alone cannot tell whether the estimated difference matters in the context of the procedure or patient experience.

Why do standard errors and standard deviations differ?

The primary outcome is reported with standard errors, whereas the secondary pain and swelling outcome is reported with standard deviations. A standard deviation describes variation among observed values. A standard error describes the uncertainty in an estimated mean and is generally affected by both variability and the amount of information contributing to that mean. The two quantities answer different questions and should not be compared as if they were interchangeable measures of participant variability.

For the secondary pain and swelling outcome, the posted means are 0.22 and 0.23, with standard deviations of 0.29 and 0.3. Its mean difference is 0.01, with an unadjusted p-value of 0.931. The registry does not report the score's possible range or its interpretation, limiting assessment of what a given score difference would mean.

What information is missing from the statistical record?

The registry lists no reported analyses. It does not describe an analysis plan, the test used for the primary comparison, missing-data procedures, an intention-to-treat or per-protocol population, or any adjustment for multiplicity. It also does not report interim analyses, a stopping rule, or the assumptions used to design the trial. These details matter because analysis choices affect how estimates and uncertainty should be interpreted. Their absence means that the posted results can be described, but the full statistical workflow cannot be reconstructed from the registry record.

11. Confidence Intervals and Precision

The primary mean difference is -0.87 millimeters, with a reported confidence interval from -1.966 to 0.226. The interval includes zero and covers negative and positive values. This means the posted estimate is compatible with a range of possible underlying average differences, including no difference. The interval is broad enough that the direction and size of the underlying contrast are not sharply determined by these results.

The group means are -1.34 for Freeze Dried Bone Allograft and -2.21 for L-PRF Clot. Their standard errors are 0.38 and 0.41, respectively. These standard errors describe the precision of the estimated arm means; they do not describe the range of change among individual participants. No interval for either arm mean is reported in the registry record.

The confidence level and interval-construction method are not reported in the registry record. The interval should therefore be interpreted as the posted estimate of uncertainty, without assuming additional methodological details. Its inclusion of zero is not proof that the treatments have identical effects, just as the point estimate alone is not proof of a consistent difference. More precise evidence would require an interval narrow enough to resolve the range of differences that matter for the research question, but no such threshold is reported for this trial.

The reported p-value of 0.12 also reflects uncertainty, but it does not replace the interval. The interval communicates plausible effect sizes and direction; the p-value compresses information into a measure tied to a null model and test assumptions. Neither statistic establishes clinical importance, equivalence, or the probability that a particular result is true.

12. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm, not total events. They are illustrations computed from the observed effect, not the trial's original design calculation. The listed 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. The original trial's design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the planning assumptions, if that effect and those assumptions were correct. The 90% power column uses a higher chance of detection, and therefore requires more participants for the same assumed effect. These are design-planning quantities, not descriptions of what happened in the completed trial.

The rows use the full observed effect, 75% of the observed effect and 50% of the observed effect. As the assumed effect becomes smaller, the planning figures rise: a smaller difference is harder to distinguish from random variation, so more participants are needed to detect it at the same power and significance level. For the primary outcome, the figures range from 42 participants per arm for 80% power at 100% of the observed effect to 168 participants per arm for 80% power at 50% of the observed effect. The corresponding 90% figures are 57 and 225. These illustrations are not observed power, and they do not establish that the trial was designed around the observed result.

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 = -0.870; pooled standard deviation σ = 1.421.
2. n = 2 × (1.96 + 0.842)² × 1.421² / -0.870² = 41.9, rounded up to 42 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 <- -0.87                      # observed difference in means
sigma <- 1.42112044997366                     # 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(3331185)
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 = 42 (80% power), 57 (90% power)
 75% of observed effect: n per arm = 75 (80% power), 100 (90% power)
 50% of observed effect: n per arm = 168 (80% power), 225 (90% power)
power.t.test: 42.9 
Simulated power at n = 42 per arm: 0.795 (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 secondary outcomes, but it does not report a statistical analysis plan explaining how multiple outcomes were handled. No multiplicity adjustment is reported. When several outcomes are tested, repeated testing can increase the chance of at least one result appearing noteworthy even if there is no underlying effect. This is a general statistical concern, not evidence that a particular reported result is spurious. Without a stated hierarchy, adjustment method or prespecified decision rule, secondary results should be treated cautiously.

The registry reports no analyses in its analysis listing. It does not identify the statistical test or model used for the posted comparisons, whether analyses were prespecified, or whether there were interim analyses. A stopping rule is also not reported in the registry record. These omissions prevent a full assessment of whether the posted estimates follow an analysis plan established before the results were known.

Missing-data methods and analysis populations are not reported. The registry does not state whether all randomized participants were included in an intention-to-treat analysis, whether a per-protocol analysis was conducted, or how unavailable outcome measurements were handled. Arm-level outcome counts are listed, but the record does not explain why those counts may differ from other trial counts or whether any missing measurements occurred. No conclusions about attrition or its effect on the comparison can be drawn from the available record.

The original sample-size assumptions and justification are also not reported. The planning illustrations use the observed effect and specified planning assumptions, but they are not evidence of the study's original design rationale. The registry record does not explain whether the enrollment target was based on a clinically meaningful difference, expected variability, or another consideration.

These absences do not change the arithmetic of the posted summaries, but they limit how fully the analysis can be evaluated. They also mean that readers cannot determine from the registry alone whether all planned outcomes and analyses are represented in the posted results.

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.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each arm and zero deaths in each arm. These are reported counts for the groups at risk: 14 for Freeze Dried Bone Allograft and 12 for L-PRF Clot. The record lists no serious adverse-event terms. These figures describe what is recorded in the registry; they do not establish that no unrecorded events occurred or that the materials have no safety risks.

Other adverse events were reported for 7 participants in the Freeze Dried Bone Allograft arm and 3 in the L-PRF Clot arm. The registry does not provide event descriptions, severity categories, timing, or a detailed account of whether events were judged related to treatment. Definitions and collection procedures for adverse events are not reported in the registry record.

Safety counts should be interpreted descriptively, especially in a trial with the reported enrollment and arm-level counts. They do not provide a precise estimate of uncommon risks, and the registry does not report a statistical comparison of adverse events. The counts alone cannot establish a causal difference between the arms.

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

The posted primary result describes an average horizontal ridge-width change that was more negative in the L-PRF Clot arm than in the Freeze Dried Bone Allograft arm. The estimated mean difference is -0.87 millimeters, but its confidence interval includes zero and extends to values on both sides of zero. The evidence therefore leaves substantial uncertainty about the direction and size of the underlying difference.

This result does not show that the materials are equivalent. Equivalence requires a prespecified range of differences considered sufficiently small and an analysis designed to evaluate that range; neither is reported in the registry record. Nor does the result establish that one material is superior. The point estimate is only one component of the evidence, and its uncertainty is important.

The finding also does not answer every question about alveolar ridge preservation. The trial reports a primary measure of horizontal bone-width change, while soft-tissue width and post-operative pain and swelling are separate outcomes. A difference, or lack of a clear difference, in one outcome cannot automatically be extended to all dimensions of healing or to all patient experiences.

The registry's summary describes a study intended to compare maintenance of gum and jaw-bone volume and pain or swelling after extraction. The posted results provide a limited statistical account of those questions. Details about eligibility, measurement procedures, analysis populations, missing data and outcome interpretation are not reported in the registry record. These limitations constrain generalization beyond the recorded comparison.

The most defensible reading is descriptive: the observed arm means and unadjusted contrast point in a particular direction, while the confidence interval shows that the data do not define the underlying difference precisely. The findings should not be interpreted as medical advice or as a conclusive judgment about the materials.

17. Why This Trial Matters Statistically

This trial is statistically useful as an example of the distinction between an estimated effect and the uncertainty around it. The primary comparison has a nonzero point estimate, but the confidence interval includes zero and spans values in both directions. Reading the point estimate without the interval would make the evidence appear more decisive than it is.

It also illustrates why a p-value is not a complete summary. The unadjusted p-value is 0.12, but it does not describe the range of effect sizes compatible with the results, establish clinical relevance, or demonstrate equivalence. Considering the estimate, interval and outcome definition together gives a more informative account of the evidence.

The record also highlights the difference between trial planning and post-result planning illustrations. The posted sample-size figures are based on fractions of the observed effect under stated assumptions. They help show how planning requirements change when the effect of interest is smaller, but they do not explain the trial's original design or demonstrate the study's ability to detect an effect after completion.

Finally, the incomplete analysis details matter. The registry does not report a statistical analysis plan, missing-data approach, analysis populations or multiplicity handling. These omissions do not make the posted summaries unusable, but they limit independent assessment of how the results were generated and how much weight secondary findings should receive. Clear reporting of these details is part of interpreting clinical evidence, not a technical afterthought.

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 gives limited detail about trial procedures and statistical methods. It identifies randomization and a parallel design but does not describe the random sequence generation or allocation concealment. It records no masking, and does not specify whether outcome assessors were masked. These reporting gaps make it difficult to evaluate possible sources of bias in allocation and measurement.

The primary outcome is described using CBCT measurements, but the registry does not report the imaging protocol, measurement reproducibility, assessor training, or handling of measurement disagreement. The timeframe description refers to CBCT after extraction and grafting and again 11weeks later, but the precise timing and measurement procedures are not elaborated. The clinical meaning of a given change on the scale is also not defined.

Analysis details are sparse: no reported analyses are listed, and no model, missing-data method, analysis population, or multiplicity strategy is described. It is not possible to determine from the registry whether all randomized participants contributed to each endpoint or how unavailable measurements were handled. The original sample-size assumptions and rationale are not reported.

Secondary outcome reporting is incomplete. The registry lists keratinized soft-tissue width and post-operative pain and swelling, but a numerical result for the soft-tissue measure is not reported in the registry record. The pain and swelling score's range and interpretation are not posted in the record, limiting assessment of its magnitude. Adverse-event descriptions and definitions are likewise not reported.

These limitations concern what can be evaluated from the registry record; they do not establish that particular procedures were absent or that errors occurred. They narrow the claims that can be made from the posted results and leave questions that would require fuller trial reporting to resolve.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Changes of Soft and Hard Tissues After Alveolar Ridge Preservation: Freeze-dried Bone Allograft vs. L-PRF Clot — NCT03331185.
• Registry record last updated 2020-04-30; status last verified 2020-04.
• Results first posted 2020-04-30.
• 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

NCT03331185 is a completed, randomized, parallel-group trial with no masking, sponsored by the University of Manitoba. It compares Freeze Dried Bone Allograft with L-PRF Clot for alveolar ridge preservation following tooth extraction. The registry lists phase 2 and phase 3 and an enrollment of 26.

The primary outcome is mean overall horizontal change in alveolar ridge width measured in millimeters using CBCT. The reported arm means are -1.34 for Freeze Dried Bone Allograft and -2.21 for L-PRF Clot; the unadjusted mean difference is -0.87, with an interval that includes zero. The registry also lists secondary outcomes concerning keratinized soft-tissue width and post-operative pain and swelling, but not all secondary results are reported.

The record reports zero serious adverse events and zero deaths in each arm, alongside other adverse-event counts. It does not report the statistical analysis plan, missing-data methods, analysis populations, multiplicity approach, or original sample-size assumptions. The posted estimates are therefore best read as a limited and uncertain account of the trial comparison.