Pre-market Study to Evaluate Safety and Performance of GreenBone Implant (Long Bone Study): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pre-market Study to Evaluate Safety and Performance of GreenBone Implant (Long Bone Study) (NCT03884790), a na na study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The study was designed as a pre-market clinical investigation of a Class III medical device. The broad clinical question is whether safety and performance can be evaluated when the device is used for surgical repair of long bone defects. In statistical terms, the single-arm design can describe observed events among enrolled participants, but it cannot by itself establish how those outcomes compare with a different device, procedure or usual care. The registry record does not report the clinical characteristics needed to assess how representative the enrolled group was of other patients with long bone defects.

3. Trial Design

This was a prospective, multicenter, international, open-label, single-arm, first-in-human clinical investigation of GreenBone Implant for surgical repair of long bone defects. The allocation and masking fields are recorded as not applicable and none, respectively. The study enrolled 16 participants. The listed intervention was surgical repair of long bone defects, with the GreenBone Bone Substitute implanted during surgery. No comparator arm is recorded.

The registry record describes follow-up at prescheduled visits for up to 12 months after surgery. Assessments were to include adverse events, pain, quality of life, functional parameters, X-ray and CT scan. The listed secondary outcomes include bone union and bone regeneration evaluated through the modified Lane and Sandhu radiological scoring system, pain, quality of life, global tolerability and reinterventions. The record does not provide results for these secondary outcomes in the registry record for this analysis.

The brief study description says the initial phase contemplated defects up to 3 cm. It also describes an adaptive interim analysis after the first 7 participants completed the 6-month follow-up, with a Data Safety Monitoring Board review of safety and a recommendation to stop or continue. If continued, the plan described recruiting up to 25 participants and including at least 5 participants with defects longer than 3 cm and up to 6 cm. These are features described in the study plan; the registry record does not report whether that interim analysis occurred, what the board recommended, or how many participants had defects in each range.

The study start date is 2019-01-22, and the primary completion date is 2023-06-08. The registry status is terminated. The reason for termination and whether enrollment reached a planned target are not reported in the registry record. The listed enrollment is 16, which should be understood as the recorded enrollment rather than proof that every planned study procedure or follow-up assessment was completed.

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.

Population: Only patients treated for bone defect repair were included in the analysis population (16 participants).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over Overall study period up to 12 months.

The primary endpoint is the number of participants with adverse events during the overall study period, up to 12 months. It is a participant-level safety measure: it concerns whether participants experienced an adverse event, rather than the total number of separate events. A participant may experience more than one event, so the number of events and the number of participants with events are different quantities. The registry record does not report the total number of adverse events or a single overall count of participants with any adverse event in the registry record for this analysis.

Safety endpoints are used in device investigations to describe harms observed during use and follow-up. Counting participants affected can make the scope of the experience easier to interpret than a raw event count alone, because repeated events in one person do not increase the number of affected participants. However, a count still needs context: the observation period, the population assessed, the event definitions and how missing follow-up was handled all affect interpretation. The stated timeframe is up to 12 months, but the registry record does not report participant-specific follow-up duration or a detailed event-classification procedure.

The endpoint is descriptive in this single-arm study. It can characterize the recorded safety experience among participants in the study, but it cannot isolate the effect of the implant from surgery, the underlying defect or other influences. The serious and other adverse-event counts are reported separately; the record does not establish that these categories are mutually exclusive.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a count of participants with an event. This is a binary outcome at the participant level: each participant either had at least one event in the relevant category during the observation period or did not. A participant can have multiple events but still contributes once to a participant count. This distinction is important when reading the serious and other adverse-event totals, since totals of affected participants are not totals of event episodes.

What does a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical method. A narrow interval indicates greater precision under that method; a wide interval indicates less precision. For participant-event counts, uncertainty is influenced by the number of participants and the number with an event. With only 16 participants enrolled, estimates from this study would be limited in precision. No confidence interval for the adverse-event findings is reported in the registry record, so no interval can be interpreted as an observed result.

A confidence interval would not remove the limitations of the design. It quantifies sampling uncertainty for an estimate under its assumptions; it does not correct for selection, incomplete follow-up, outcome misclassification or the absence of a comparator. It also does not establish that an event was caused by the device. In a single-arm investigation, even a precisely estimated event frequency would remain a description of the study group rather than a randomized comparison.

Why does the single-arm design matter?

A single-arm design observes outcomes in participants who receive the intervention without a concurrent control group. This can be useful for describing what happened during an early device investigation, particularly when the aim includes collecting initial safety information. But there is no direct estimate of how many events would have occurred in a comparable group receiving another treatment or no device. Differences from historical experience, if considered, would depend on how comparable those other patients and their follow-up were; the registry record does not report such a comparison.

The study is open-label, with masking recorded as none. In general, open-label assessment means participants and investigators are not masked to treatment assignment. This can influence reporting or assessment of outcomes that require judgment, such as pain, tolerability or radiological scoring. The record does not report whether outcome assessors were independently masked, or what procedures were used to reduce assessment bias.

How should counts and percentages be read?

For an event count to be interpreted, the denominator and the observation period need to be clear. The serious and other event listings each record 16 participants at risk, alongside the numbers affected. These counts describe participants, not event rates over time. The follow-up plan was up to 12 months, but individual follow-up completion and duration are not reported. The serious-event term percentages are listed without a clear denominator in the registry record for this analysis; they cannot safely be interpreted as the percentage of participants affected or as the percentage of all events.

General statistical methods for binary outcomes may include an estimated event proportion and a confidence interval. A comparative analysis would require a suitable comparison group and a defined contrast. Neither a comparative effect estimate nor a confidence interval is reported in the registry record. The stated outcome is descriptive, and the registry entries do not identify a specific statistical test or model used for the adverse-event analysis.

What do the planning illustrations mean?

The planning illustrations are described as calculations based on the observed effect, not as the trial's own design justification. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrations are framed as participants per arm for 80% or 90% power; time-to-event illustrations use a total event count. These are planning quantities, not observed participant counts and not evidence that the study had a particular probability of detecting an effect.

In general, a sample-size calculation estimates the amount of information needed for a planned comparison under specified assumptions. It depends on the target effect, variability or event frequency, significance level, power and design. A planning illustration based on an observed effect can be especially sensitive to the effect estimate used; estimates from small studies can be unstable. It cannot be interpreted as observed power, and it does not show that a study was adequately designed or that an effect was present. The registry record does not report a trial-specific sample-size justification or a comparative hypothesis for this single-arm study.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability exceeds what a chosen model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not allow for the extra variation. This is relevant to some count outcomes, especially when event counts vary substantially among participants or clusters. The primary endpoint is a participant count with an event, not a reported recurrent-event count, and the registry record does not report a model or an over-dispersion assessment. There is therefore no basis for saying that over-dispersion was tested or handled in the analysis.

More broadly, the registry record does not report the statistical analysis plan, analysis population, missing-data method, or methods for handling repeated events. These omissions limit assessment of how the published counts were defined and whether all enrolled participants contributed to each outcome. General statistical explanations can clarify what methods would mean, but they do not establish that any particular method was used in this study.

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("Surgical Repair of Long Bone Defects")
n      <- c(16)
events <- c(16)
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  Surgical Repair of Long Bone Defects  16  16  100.0  79.4  100.0  80.6  100.0  80.5  99.9

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary safety outcome and several secondary outcomes: bone union and bone regeneration assessed through the modified Lane and Sandhu radiological scoring system, pain, quality of life, global tolerability and reinterventions. Examining multiple outcomes creates a general multiplicity issue: when many statistical questions are considered, the chance of at least one apparently unusual result can increase if each is tested separately. This concern is most relevant when interpreting multiple hypothesis tests. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed statistical plan, so it is not possible to determine how multiplicity was handled.

The registry lists one analysis, but does not specify the analysis method or clarify how that listing relates to the individual outcomes. No results for the listed secondary outcomes are included in the registry record for this analysis. Their absence should not be interpreted as evidence that no events or changes occurred; it means those results are not reported in the registry record.

Missing-data handling is also not reported. The study planned follow-up visits up to 12 months, but the record does not state how many participants completed each visit, whether any outcome assessments were missing, or how missing observations were treated. In general, missingness can affect an estimate if participants with missing outcomes differ from those with observed outcomes. The extent and direction of any such effect cannot be assessed without information on follow-up completion and the analysis population.

The registry record does not define whether the primary analysis included all enrolled participants, only those who received the implant, or those with available follow-up. It also does not report how adverse events were attributed, coded, or grouped for the participant counts. These details matter for reproducibility and interpretation. The record's stated enrollment and event counts alone do not resolve these questions.

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: fixation system breakage (31.2%), fracture non-union (6.2%), open reduction with external fixation (6.2%), pseudarthrosis (6.2%), muscle abscess (6.2%).

The serious adverse-event listing records 8 affected participants among 16 at risk. The other adverse-event listing records 12 affected among 16 at risk. The record also lists 0 deaths. These are separate entries: it is not reported whether participants with serious events are also counted among participants with other events, so the two affected-participant counts should not be combined. They should also not be confused with the number of event episodes.

The serious-event terms include fixation system breakage at 31.2%, and fracture non-union, open reduction with external fixation, pseudarthrosis and muscle abscess at 6.2% each. The registry record does not specify the denominator or clarify whether these percentages refer to participants or events. They are best read as percentages attached to the listed terms, not as confirmed risks for an individual participant. The list does not necessarily represent every serious event recorded.

Event counts need a defined observation period and complete follow-up for full context. The planned follow-up was up to 12 months, but the record does not state individual follow-up durations or completion. It also does not report detailed severity grading, onset timing, relatedness assessments or management for each event. The counts therefore describe what is recorded without establishing cause, comparative risk or the duration over which each participant was observed.

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

The registry record describes adverse events observed in a prospective, open-label, single-arm study of GreenBone Implant for surgical repair of long bone defects. It records serious adverse events affecting 8 of 16 participants at risk, other adverse events affecting 12 of 16, and 0 deaths. These counts provide a compact description of the recorded safety experience, but the record does not report a single overall participant count for any adverse event or clarify overlap between the serious and other categories.

The findings do not show how the event experience compares with another device, procedure or usual care. Without a comparison group, there is no randomized estimate of a difference attributable to the intervention. The recorded events also cannot be assigned to the implant alone from these counts: the registry information does not provide the detail needed to separate effects of the device, surgery, underlying condition or other causes.

The serious-event terms and percentages add descriptive detail, but their denominator is not specified in the registry record for this analysis. The percentages therefore should not be interpreted as individual participant probabilities. The record also does not provide event timing, individual follow-up, or detailed results for pain, quality of life, function, radiological outcomes, tolerability or reinterventions.

The status is terminated, but the reason is not reported in the registry record. The study description includes a planned interim safety review, yet does not report whether it occurred or what recommendation followed. Those gaps prevent the status from being used to infer why the study ended. The results should be understood as registry-reported counts from a limited single-arm investigation, not as a definitive comparative assessment of safety or performance.

In general, early device studies can contribute descriptive information and help identify questions for later evaluation. Their findings are most informative when read with attention to study size, follow-up, event definitions and the lack of a control group. The available record supports reporting the event counts and their limitations; it does not establish a treatment benefit or a comparative safety conclusion.

14. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early device research: safety outcomes can be important to describe even when the study is too small and lacks a comparison group for estimating relative risk. A count of participants with adverse events gives a direct account of how many people in the study were affected, while still leaving uncertainty about how the same participants might have fared under another treatment or procedure.

The single-arm design is aligned with descriptive observation, not a randomized estimate of treatment effect. This distinction matters because a count can be clinically consequential without answering a causal question. The study’s open-label conduct also makes outcome definitions and assessment procedures relevant, particularly for measures that involve judgment. The registry record does not report all details needed to evaluate those procedures.

The planned interim safety review is another statistically important feature. A monitoring body can review accumulating safety information and make recommendations, but the registry record does not say whether the planned review occurred or what decision was made. It would be inappropriate to infer the conduct or result of an interim analysis from the description of the plan alone.

The listed enrollment of 16 and follow-up plan of up to 12 months help frame the scale and intended observation period. However, the record does not report follow-up completion or the reason for termination. Those omissions constrain interpretation of both the event counts and the study’s progression. The serious-event term percentages also lack a stated denominator in the available information, underscoring why labels and counts need clear definitions.

Statistically, the central lesson is to separate what descriptive safety counts can establish from what they cannot. They can record events among study participants; without a comparator and fuller analysis details, they cannot quantify a comparative effect or settle causal attribution. Clear reporting of populations, follow-up, event definitions and missing data is essential to making such findings interpretable.

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 study affect interpretation of the reported safety information. First, it is a single-arm investigation with no control group. The adverse-event counts therefore cannot show whether the observed experience differs from that in a comparable group receiving another treatment or procedure. There is also no randomized basis for attributing events to the implant rather than surgery, the underlying defect or other factors.

Second, the recorded enrollment is 16, limiting the amount of information available for describing uncommon events and making estimates less precise. The registry record does not report confidence intervals for the adverse-event counts. It also does not report individual follow-up duration or completion, although visits were planned for up to 12 months. If follow-up varied, participants may have had different opportunities for events to be observed.

Third, the serious and other adverse-event counts are not described as mutually exclusive, and the overall number of participants with any adverse event is not reported in the registry record for this analysis. The denominator for the serious-event term percentages is also not stated. Event onset, duration, severity details, attribution and the process for coding or grouping events are not reported.

The study is marked terminated, but the reason is not reported in the registry record. The record describes a planned interim safety review but does not report whether it occurred or its outcome. Nor does it provide a trial-specific sample-size justification, a detailed statistical analysis plan, missing-data methods or a clearly defined analysis population. These omissions limit assessment of how the recorded counts were produced and how completely they represent the enrolled participants.

Finally, although several secondary outcomes are listed, their results are not reported in the information available for this analysis. The available safety counts should not be generalized beyond the study group without additional evidence about participant characteristics, follow-up and comparative outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pre-market Study to Evaluate Safety and Performance of GreenBone Implant (Long Bone Study) — NCT03884790.
• Registry record last updated 2025-04-10; status last verified 2024-06.
• Results first posted 2025-04-10.
• 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 record describes a prospective, multicenter, international, open-label, single-arm, first-in-human investigation of GreenBone Implant for surgical repair of long bone defects. It lists 16 participants enrolled and a planned follow-up period of up to 12 months. The study status is terminated; the reason is not reported in the registry record.

The primary endpoint concerns the number of participants with adverse events. The serious-event listing records 8 affected participants among 16 at risk, and the other-event listing records 12 among 16 at risk. The record lists 0 deaths. It does not clarify overlap between the event categories or the denominator for percentages attached to serious-event terms.

No comparator group is recorded, and detailed information on follow-up completion, missing data, analysis methods, event attribution and secondary-outcome results is not reported in the registry record for this analysis. The counts describe the recorded experience in this study; they do not provide a comparative treatment effect.