Phase 1/2a Study on Allogeneic Osteoblastic Cells Implantation in Delayed-Union Fractures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1/2a Study on Allogeneic Osteoblastic Cells Implantation in Delayed-Union Fractures (NCT02020590), a na phase 1, phase 2 study. The primary outcome is Percentage of Responders at 6 Months (Efficacy of ALLOB).

2. Clinical Question

The study asked whether ALLOB® implantation could be evaluated for safety and efficacy in people with delayed-union fractures of long bones. It was described as a pilot, multicentre, open proof-of-concept study, with one treatment group and no control group.

The responder definition combines clinical and imaging criteria with a rescue-surgery rule. A patient was classified as a failure if rescue surgery occurred, or if both the patient-reported Global Disease Evaluation score on a visual analogue scale failed to improve by at least 25% and the Tomographic Union Score on CT failed to increase by at least two points versus baseline. The primary outcome is the percentage of responders at 6 months. The registry record does not report that percentage or its confidence limits, so the central efficacy question cannot be answered from the posted results alone.

3. Trial Design

This was a Phase 1/2a, multicentre, open proof-of-concept study of ALLOB® implantation for non-infected delayed-union fractures. The registry lists a single-group model, no masking, and allocation as not applicable. The one arm received ALLOB® implantation; no concurrent control group is described. Enrollment was 25, and the record lists the study as completed. The recorded start was 2014-02 and primary completion was 2017-09.

The single-group design means the study can describe outcomes among participants who received the intervention, but it does not directly compare their outcomes with outcomes under another treatment or no intervention. Open conduct means masking was absent. Consequently, the study’s primary responder outcome includes measures that may be affected by knowledge of treatment: one is a patient-reported score, and another is an assessment based on CT. The registry does not report further details about how these assessments were conducted or protected from bias.

The study’s stated purpose was to evaluate safety and efficacy in a pilot setting. A pilot or proof-of-concept label does not itself establish what sample-size justification, stopping rule, or interim review was used. Those details are not reported in the registry record. Nor does the record describe a randomized allocation process; allocation is listed as not applicable, consistent with the single-group design.

The efficacy population is described as the Per Protocol population, with 21 treated patients and a note that one patient was excluded because of a major protocol deviation. The registry gives safety counts for 22 participants at risk. These analysis populations and denominators are not identical, and the record does not explain the relationship among them. Enrollment, efficacy, and safety figures should therefore be read in the context of the population specified for each result rather than treated as interchangeable counts.

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.

Before assignment: Of the 25 patients enrolled in the study (ICF signature), 22 patients were treated: * 2 patients were considered as non eligible before treatment * 1 patient withdrew consent before prior to Day 0

Overall Study

Analysis population for the primary outcome, as defined in the registry: The efficacy analysis was conducted on the Per Protocol population (21 treated patients; one patient being excluded from the analysis due on a major protocol deviation)

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.

Population: Safety population (all patients treated)

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Responders at 6 Months (Efficacy of ALLOB), measured over 6 months.

The primary endpoint is the percentage of responders at 6 months. It is intended to summarize whether participants met the study’s operational definition of not failing under treatment, rather than to report one isolated measurement. A responder had to avoid rescue surgery and satisfy the combined clinical and imaging rule specified in the registry.

Under that rule, rescue surgery counted as failure. Without rescue surgery, failure required both that the patient’s Global Disease Evaluation score on a visual analogue scale had not improved by at least 25% and that the CT-based Tomographic Union Score had not increased by at least two points compared with baseline. Thus, not meeting both improvement thresholds was not by itself the stated failure rule: the record links the two thresholds with “and.”

Using a defined responder outcome can make a complex clinical question easier to summarize as a proportion. It also depends on the chosen thresholds, the measurement procedures, and how missing assessments or rescue surgery are handled. The registry does not report the observed responder percentage, the number of responders, or the confidence interval limits. The stated dispersion is a 90% confidence interval, but its values are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary responder classification summarized as a percentage. Each participant is classified according to the stated criteria, and the group result is the proportion meeting the responder definition. In general, a percentage gives an interpretable summary of how common an outcome was within the analyzed population. It does not, by itself, show why the outcome occurred or what would have happened under a different treatment.

What does the confidence interval express?

In general, a confidence interval describes statistical uncertainty around an estimate. For a responder percentage, it gives a range of values compatible with the observed data under the method used to construct the interval. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The registry specifies a 90% confidence interval for the primary endpoint, but does not report its limits or the responder estimate. The precision of the primary result therefore cannot be judged from the posted results.

A confidence interval is not a guarantee that the true value lies within the particular interval, and it does not address every source of uncertainty. In this study, the design and measurement process also matter: the study was open and had no control group. Statistical uncertainty around a group percentage would not remove those design limitations. The registry record does not state the exact procedure used to calculate the primary confidence interval.

Why does the analysis population matter?

The registry says that efficacy was analyzed in the Per Protocol population, described as 21 treated patients, and notes that one patient was excluded because of a major protocol deviation. A Per Protocol analysis focuses on participants meeting the protocol-related criteria for inclusion in that analysis. This can be informative about outcomes in the analyzed group, but exclusions can affect how representative that group is of everyone enrolled or treated. The record does not give enough detail to assess the consequences of the exclusion or to reproduce the population definition.

The safety results use 22 participants at risk. The efficacy and safety denominators should be interpreted separately because they refer to different analyses. The record does not explain the full participant flow or why these denominators differ. It also does not report how missing endpoint measurements, if any, were handled. No assumption about missing outcomes should therefore be attributed to the analysis.

What can a single-group estimate establish?

A single-group analysis estimates outcomes in the participants observed in that group. It does not provide a randomized comparison with another group. General statistical interpretation of a proportion must therefore distinguish description from causal attribution: the observed responder percentage, if reported, would describe the analyzed participants, but would not by itself show how outcomes compare with an alternative. The open design also means that masking was absent, a relevant consideration for a composite outcome involving patient-reported and imaging-based assessments.

How should planning illustrations be read?

Any sample-size planning illustration based on the observed effect is not the trial’s original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Those are planning assumptions, not observed trial results. The study itself is listed as single-group, so a two-arm illustration does not describe its allocation or an actual comparison made in the trial. The registry does not report the trial’s own sample-size justification.

In general, sample-size calculations estimate how many participants may be needed to detect a specified effect under stated assumptions. They are not observed power, do not demonstrate that a result is true, and do not replace an estimate with its uncertainty. The registry record does not report an interim analysis plan, detailed statistical model, or full procedure for the primary endpoint analysis. Such details should not be inferred from the outcome definition or from planning assumptions.

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("ALLOB® Implantation")
n      <- c(21)
events <- c(21)
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  ALLOB® Implantation  21  21  100.0  83.9  100.0  84.5  100.0  84.6  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis. That count does not establish whether the protocol specified additional outcomes, repeated assessments, or other analyses that could affect interpretation. A multiplicity strategy for handling several statistical tests is not reported in the registry record. The record also does not describe interim analyses or stopping rules.

The primary endpoint is defined using a six-month responder classification, with rescue surgery and two improvement thresholds contributing to the failure rule. The registry does not report how missing visual analogue scale scores, CT assessments, or other endpoint information were handled. It does not state whether participants with missing assessments were classified as responders, failures, or excluded, nor does it describe sensitivity analyses. These choices can affect a percentage estimate, so the absence of a stated approach limits assessment of the result even apart from the missing estimate itself.

The efficacy analysis is described as Per Protocol, with 21 treated patients and a note that one patient was excluded because of a major protocol deviation. The record does not provide a full definition of this analysis population or describe an alternative analysis population. It also does not explain the relationship between the efficacy population and the 22 participants at risk in the safety results. Enrollment was 25, but the registry does not provide enough detail to account for every participant across these populations.

These omissions do not show that particular methods were or were not used; they mean that the methods are not reported in the registry record. As a result, readers cannot assess the influence of missing data, exclusions, or multiplicity decisions from this record alone.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: implant site infection (4.5%), angioedema (4.5%), urticaria (4.5%).

The safety record lists 22 participants at risk for both serious and other adverse events. It reports 2 affected by serious adverse events and 9 affected by other adverse events, with 0 deaths. These are participant counts as presented in the registry, not a comparison between treatment groups. There is only one treatment group, and the record gives no control-group safety data.

The listed serious adverse event terms are implant site infection, angioedema, and urticaria, each reported at 4.5%. These terms indicate the events named in the registry; the listed percentages do not establish that ALLOB® caused them. The record does not give further detail about timing, severity beyond the serious-event classification, relatedness assessments, or the number of occurrences for each term.

Counts and percentages should be read with their stated denominators and population. The record reports 22 participants at risk for safety, whereas efficacy is described for a Per Protocol population of 21 treated patients. Safety figures are descriptive and cannot establish comparative risk or rule out uncommon events. The registry record does not report additional context needed to interpret the event listings, such as a detailed event-level account.

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

The registry record describes a pilot, open, single-group study and defines a six-month responder outcome, but it does not report the primary responder percentage or its 90% confidence interval. Consequently, the posted results do not quantify the primary efficacy outcome or show how precisely it was estimated. The endpoint definition clarifies what would count as a response, but a definition is not an observed result.

The available safety data report 2 participants affected by serious adverse events, 9 affected by other adverse events, and 0 deaths among 22 at risk. The named serious adverse event terms and their listed percentages add descriptive information, but there is no control group for comparison. These findings cannot establish whether an event was caused by the intervention or how event occurrence compares with another approach.

More generally, outcomes observed in one treated group cannot by themselves separate the intervention’s contribution from other influences. The open design also matters because participants and assessors were not masked, and the primary endpoint includes patient-reported and CT-based assessments. The registry record does not provide the detailed assessment procedures or analysis methods needed to examine these issues further.

The enrollment total of 25, the efficacy population description, and the safety denominator refer to distinct parts of the record. They should not be treated as a single analysis population. Missing-data handling, the detailed population definitions, and the relationship among these counts are not reported in the registry record.

Accordingly, the record supports a description of the study design, the endpoint rule, and selected safety counts. It does not support a conclusion about the magnitude or precision of the primary efficacy outcome, a comparative treatment effect, or a causal interpretation of adverse events.

14. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition and the reported endpoint result must be considered separately. The registry gives a detailed rule for classifying a responder at 6 months, including rescue surgery and thresholds for patient-reported and CT-based measures. Yet the percentage of responders and the stated 90% confidence interval are not reported. Knowing the rule alone does not reveal how many participants met it or the uncertainty around that estimate.

It also highlights the distinction between a study’s aim and what its design can establish. A single-group, open proof-of-concept study can describe outcomes and safety events in the treated group. Without a concurrent comparator, it cannot directly estimate how those outcomes differ from an alternative group. This distinction is important when interpreting a percentage that might otherwise appear to be a straightforward measure of efficacy.

The record also presents different analysis populations for efficacy and safety. The efficacy description refers to the Per Protocol population and a protocol-deviation exclusion, while safety counts use 22 participants at risk. Understanding which participants contribute to each analysis is essential for interpreting denominators and considering possible selection effects. The registry does not fully explain how these populations relate.

Finally, the record shows why missing statistical details matter. The confidence interval limits, missing-data approach, multiplicity handling, and sample-size justification are not reported. Without these details and the primary estimate, readers cannot evaluate precision, robustness, or the basis for the study’s planned size. The study is therefore informative about its stated design and outcome framework, while important information needed for statistical interpretation remains unavailable in the registry record.

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.

Several limitations specific to this record constrain interpretation. The most direct is that the primary result is missing: no responder percentage, responder count, or 90% confidence interval limits are reported. Thus the central six-month outcome cannot be numerically evaluated, even though its classification rule is described.

The single-group, open design offers no concurrent comparator and no masking. A treated-group outcome cannot establish a treatment contrast, and the absence of masking is relevant to an endpoint that includes a patient-reported score and an assessment based on CT. The registry record does not describe procedures intended to limit assessment bias.

The analysis populations are not fully reconciled. Enrollment was 25, efficacy is described as a Per Protocol population of 21 treated patients with a note about one exclusion for a major protocol deviation, and safety counts use 22 participants at risk. The record does not give a full accounting of participant flow, a detailed population definition, or an explanation of the different denominators.

Important analytic details are also not reported in the registry record. These include the method for calculating the confidence interval, handling of missing endpoint information, multiplicity strategy, interim analysis plan, and sample-size justification. The record also does not provide event-level detail or further information on the serious adverse event assessments. These limitations describe gaps in the registry information and should not be taken as evidence that a particular procedure was or was not used.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1/2a Study on Allogeneic Osteoblastic Cells Implantation in Delayed-Union Fractures — NCT02020590.
• Registry record last updated 2021-11-10; status last verified 2021-11.
• Results first posted 2021-09-28.
• 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.

19. Record Summary

The registry describes NCT02020590 as a completed Phase 1/2a, multicentre, open proof-of-concept study of ALLOB® implantation for non-infected delayed-union fractures of long bones. It used a single-group design, listed enrollment of 25, and had no comparator arm.

The primary outcome was the percentage of responders at 6 months, using a failure definition based on rescue surgery or the combined absence of specified patient-reported and CT score improvements. The efficacy analysis was described as Per Protocol, involving 21 treated patients, with a note about one exclusion for a major protocol deviation. The primary responder estimate and 90% confidence interval are not reported in the registry record.

Safety information lists 22 participants at risk, 2 affected by serious adverse events, 9 affected by other adverse events, and 0 deaths. The record does not report a detailed statistical analysis plan, missing-data procedures, or the rationale for the planned sample size.