Management of Traumatic Bone Defects in Tibial Plateau Fractures With Antibiotic-Impregnated Biodegradable Calcium Sulfate Beads: A Prospective Clinical Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Management of Traumatic Bone Defects in Tibial Plateau Fractures With Antibiotic-Impregnated Biodegradable Calcium Sulfate Beads: A Prospective Clinical Trial (NCT02456194), a na na study. The primary outcome is Resorption of Study Device.

2. Clinical Question

3. Trial Design

This is a prospective clinical trial of calcium sulfate beads mixed with antibiotics and used with internal fixation for tibial plateau fractures. Its stated clinical context is traumatic bone defects associated with these fractures. The registry lists one intervention group, Calcium Sulfate + Antibiotics + Internal Fixation, and classifies the trial model as single group.

There is no randomized allocation: allocation is recorded as NA, and masking is listed as NONE. With no separate control group, the trial describes outcomes among participants receiving the intervention; it cannot estimate a treatment contrast against another group from this design. Its prospective nature means the trial was planned to follow participants over time, but the registry record does not report the detailed visit schedule or the procedures used for outcome assessment beyond the primary outcome's six-month CT timeframe.

Enrollment is listed as 30. The study started in 2015-09, reached primary completion in 2019-04, and is recorded as COMPLETED. Phase is listed as NA. Ross Leighton is named as sponsor. The registry describes STIMULAN Rapid Cure as the graft material selected for the study, and says that the calcium sulfate graft can be mixed with antibiotics and molded into bead sizes for implantation into bone defects.

The registry lists 34 outcome measures, including the primary measure of visible device on CT and secondary measures involving knee pain, range of motion, joint-surface subsidence and symptoms. Detailed outcome results and analyses are not reported in the registry record. The listed enrollment is not, by itself, evidence about how many participants contributed data to a particular outcome.

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 Resorption of Study Device, measured over 6 months.

The primary endpoint is the number of participants with any study device remaining visible on CT at 6 months. It is expressed as a count of participants, not as a continuous measurement of the amount of material remaining. A participant qualifies for this endpoint if any of the study device is still visible on the CT assessment at the specified time.

The measure is relevant to the study's stated interest in resorption and remodeling of the device into bone. CT visibility provides an imaging-based way to assess whether device material remains detectable at follow-up. It does not, by itself, describe how much material remains, whether the material has remodeled into bone, or how the participant is functioning. Those questions require separate measurements and interpretation.

The registry does not report the observed count for this endpoint, the number of participants assessed at 6 months, or a confidence interval. It also does not report the detailed CT reading rules, such as how visibility was defined or how images were reviewed. As a result, the endpoint's definition can be described, but its observed value and precision cannot be assessed from the registry record.

In general, a count is most informative when accompanied by the number assessed and a clear account of missing observations. Without those details, the count alone may not convey how representative the observed assessments are of the enrolled group. Those endpoint-specific details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study estimates outcomes observed among people receiving the study intervention. It can describe the course of events and document measured outcomes in the enrolled group. It cannot directly estimate a between-group treatment effect because there is no concurrent comparator group in this record. The absence of random allocation also means there is no randomized basis for balancing factors that could affect outcomes across treatment groups.

For this trial, the registry lists one intervention combining calcium sulfate, antibiotics and internal fixation. The separate contributions of those components cannot be identified from a design in which they are administered together. Nor can outcomes distinguish effects of the study device from the effects of fracture care or the course of recovery without a suitable comparison and a more detailed analysis.

What does the primary count represent?

In general, a count endpoint records how many participants meet a defined condition. Here, that condition is any study device remaining visible on CT at 6 months. The endpoint does not quantify the amount of visible material, and it does not directly measure remodeling quality or joint function. Interpretation also depends on how many participants were assessed and whether those with missing CT assessments differ from those assessed.

A proportion may sometimes be used to place a count in context, but the registry record does not report the primary count or the number assessed. No proportion or interval can therefore be interpreted from the posted primary outcome information. No new estimate can be derived from enrollment alone because enrollment is not the same as the number with an observed endpoint.

Why does precision matter?

In general, a confidence interval describes the range of estimates compatible with the observed data under the method used. It conveys uncertainty as well as the estimated value. A narrow interval indicates greater statistical precision than a wide interval, while neither guarantees that the study design or measurements avoid bias. The registry does not report a primary endpoint confidence interval, so the precision of the endpoint estimate cannot be assessed.

For a count or proportion, precision is affected by the amount of available outcome information. Missing observations can reduce that information and can also introduce bias if missingness is related to the outcome. The number assessed and the handling of missing data for the primary endpoint are not reported in the registry record.

What can the safety entries establish?

In general, adverse-event counts describe reported events or affected participants over a defined observation period. They need clear definitions, consistent follow-up and appropriate denominators for meaningful interpretation. Counts in an intervention group do not by themselves establish whether an event was caused by the intervention. Comparative assessment ordinarily requires an appropriate comparison group and sufficient information about exposure and follow-up.

The registry records serious and other adverse-event figures for the single intervention group, as well as a death count. These entries can be described as registry-reported counts, but the record does not give the event narratives, timing, severity criteria, attribution, or completeness of follow-up needed for fuller interpretation. The listed serious-event term and percentage should likewise be read as a registry entry, not as a causal conclusion.

How should planning calculations be read?

In general, sample-size calculations estimate how much information a future study might need under chosen assumptions. They are planning illustrations, not observed power and not evidence that a study detected a true effect. A planning exercise based on an observed effect can be especially uncertain when that effect comes from a small, single-group study, because the observed estimate may not represent the effect that would occur in a new study.

The registry record describes planning assumptions involving a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect set as a stated fraction of the observed effect. It also says that non-time-to-event planning figures are expressed as participants per arm. These assumptions describe an illustrative two-arm calculation, not the design of this single-group trial. Since no observed primary effect estimate or planning values are reported in the record, the calculations cannot be evaluated as evidence about the trial's results or used to infer its power.

More generally, statistical tests and intervals depend on their assumptions, including how outcomes are distributed and how observations are related. Over-dispersion, for example, means that variability exceeds what a chosen model expects; if ignored, uncertainty may be understated. The record does not report a model for the primary count or evidence that over-dispersion was assessed, so no claim about the model's adequacy is possible.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Calcium Sulfate + Antibiotics + Internal Fixation")
n      <- c(30)
events <- c(4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Calcium Sulfate + Antibiotics + Internal Fixation  30  4  13.3  3.8  30.7  5.3  29.7  5.5  29.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 34 outcome measures, including several secondary measures related to knee pain, range of motion, joint-surface subsidence and knee symptoms. When many outcomes or repeated assessments are considered, the chance of at least one apparently notable result can increase. In general, a prespecified testing strategy or adjustment can address some multiplicity concerns, but interpretation depends on which outcomes were primary, which comparisons were planned, and how the analysis was conducted.

The record identifies the primary endpoint and its 6-month timeframe, but a detailed statistical analysis plan, multiplicity strategy and analysis populations are not reported in the registry record. The record lists 0 analyses in its analysis summary. This does not provide a basis for reconstructing the methods used or for determining whether secondary outcomes were adjusted for multiple testing.

Missing-data handling is also not reported. For the primary CT outcome, the number assessed and the number with missing or unevaluable scans are not given. The registry does not state whether analyses used all enrolled participants, only those with an available assessment, or another population. These distinctions matter because a result based only on observed assessments can be biased if the probability of having an assessment is related to outcome status.

Without outcome-specific denominators and analysis details, the extent of missingness, the impact of missing observations and the control of multiplicity cannot be evaluated. No imputation method, sensitivity analysis, interim analysis plan or protocol-based analysis population is reported in the registry record.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: articular surface apoptosis (3.3%).

The registry records 1 participant affected by a serious adverse event among 30 at risk in the Calcium Sulfate + Antibiotics + Internal Fixation group. It records 6 participants affected by other adverse events among 30 at risk and 0 deaths. These are separate registry entries; they should not be added together because the record does not state whether categories overlap or how event counts relate to affected participants.

The most frequently listed serious-event term is articular surface apoptosis, recorded as 3.3%. The registry does not provide a detailed description of the term, event timing, severity criteria, relatedness assessment or follow-up duration. The percentage should therefore be read as the registry's reported value, not as a basis for a broader risk estimate.

These figures describe the intervention group and do not establish that the intervention caused an event or that it changed risk. There is no control group for comparison, and the record does not report enough detail to assess how completely adverse events were collected. The figures are descriptive registry reports, not a comparative safety analysis.

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

The trial addresses a practical question about a calcium sulfate graft mixed with antibiotics and used with internal fixation for tibial plateau fractures involving traumatic bone defects. It prospectively identifies device resorption and remodeling as a main interest, with visible device on CT at 6 months as the registered primary measure. The record also identifies joint-surface subsidence and several functional or symptom outcomes as areas of interest.

What the record does not establish is the observed primary outcome. No count of participants with visible device, endpoint denominator, confidence interval or detailed analysis is reported. The presence of an endpoint definition is not evidence of an observed outcome. Similarly, the registry's list of secondary outcomes does not tell whether those outcomes changed or how precisely they were measured.

The single-group design can describe the treated cohort but cannot separate intervention effects from other influences on recovery. It cannot show what the outcomes would have been under an alternative treatment or under care without the study device. Consequently, the registry information does not support a causal comparison or a conclusion that the intervention does or does not work.

The adverse-event figures provide limited descriptive safety information, including 0 deaths, but lack the detail and comparison needed for a thorough safety assessment. Study completion and enrollment of 30 do not fill those evidence gaps. A complete interpretation would require outcome values, denominators, uncertainty estimates, missing-data information and a clear account of analyses. Those details are not reported in the registry record.

14. Why This Trial Matters Statistically

Statistically, this trial illustrates the distinction between a clearly named outcome and an interpretable result. The registry defines a concrete imaging endpoint: any study device visible on CT at 6 months. Such a definition helps identify what was intended to be measured. But without the observed count, denominator and uncertainty, readers cannot assess the outcome's frequency or precision.

The design also matters. A prospective single-group study can document outcomes under a specified treatment approach, but it does not furnish the counterfactual comparison needed to estimate the difference between treatment strategies. This distinction is important when registry outcomes are read as evidence: detailed outcome measurement alone does not remove the limitations of a non-comparative design.

The study highlights the importance of reporting data completeness. For imaging outcomes, knowing how many participants had an evaluable scan and how missing assessments were handled is essential to understanding the observed result. The same principle applies to functional and symptom outcomes. Without denominators, analysis populations and missing-data methods, the potential for selection effects cannot be assessed.

Finally, a list of many outcome measures makes prespecification and multiplicity handling relevant. The registry identifies 34 measures, but detailed analyses and a multiplicity strategy are not reported. This prevents readers from distinguishing planned confirmatory tests from other outcome summaries. The record is therefore useful for understanding the study question and design, while also demonstrating why outcome estimates and analysis details are necessary for statistical interpretation.

15. 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 most important limitation of the registry record for interpretation is the absence of the primary endpoint result. Although the measure and timeframe are defined, the observed count, assessment denominator and precision estimate are not reported in the registry record. The same applies to detailed numerical results for the listed secondary outcomes.

The single-group design has no concurrent comparator, and allocation is recorded as NA. Outcomes cannot therefore be used to estimate a comparative treatment effect. Because the intervention combines calcium sulfate, antibiotics and internal fixation, the contribution of each component is also not separately identifiable from this design.

Participant eligibility and baseline characteristics are not reported in the registry record, limiting assessment of how the enrolled cohort was selected and to whom its descriptive outcomes might apply. Outcome-specific follow-up, CT assessment procedures and missing-data handling are also not reported. These omissions prevent evaluation of measurement consistency and the possible effect of incomplete follow-up.

The registry lists 34 outcome measures but does not report detailed analyses, a statistical analysis plan, multiplicity handling or analysis populations. The safety entries likewise lack event narratives, timing, attribution and follow-up details. These limitations concern what can be concluded from the registry record; they do not establish that such information was never collected or considered elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Management of Traumatic Bone Defects in Tibial Plateau Fractures With Antibiotic-Impregnated Biodegradable Calcium Sulfate Beads: A Prospective Clinical Trial — NCT02456194.
• Registry record last updated 2023-09-21; status last verified 2022-11.
• Results first posted 2023-09-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT02456194 is a completed, prospective, single-group clinical trial of calcium sulfate beads mixed with antibiotics and used with internal fixation for tibial plateau fractures. Enrollment is listed as 30. The study started in 2015-09 and primary completion was 2019-04. Phase is recorded as NA, allocation as NA, and masking as NONE.

The primary outcome is the number of participants with any study device visible on CT at 6 months. The registry also lists secondary outcomes involving knee pain, range of motion, joint-surface subsidence and knee symptoms. The primary result and detailed outcome analyses are not reported in the registry record.

For the intervention group, the record lists 1 serious adverse event affected among 30 at risk, 6 other adverse events affected among 30 at risk and 0 deaths. The listed serious-event term articular surface apoptosis is recorded as 3.3%. These entries are descriptive and do not provide a controlled safety comparison.