This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1) (NCT02718131), a randomized na study. The primary outcome is RUST Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02718131 |
| Phase | NA |
| Condition | NF1, Congenital Pseudarthrosis of Tibia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 5 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of Alabama at Birmingham |
| Results posted | Yes |
2. Clinical Question
Population
Children with neurofibromatosis type 1 (NF1) and tibial pseudarthrosis who required surgery. The registry record reports an enrollment of 5 and identifies 2 evaluable participants for the primary outcome; 3 participants withdrew for various reasons.
Intervention
INFUSE Bone Graft, containing BMP-2, added to the surgical protocol for tibial pseudarthrosis repair. The study’s stated aims included assessing bone healing and documenting safety in a pediatric NF1 population.
Comparator
A control group receiving the standard surgical protocol without BMP-2. The control description includes resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod, and autogenous bone graft from the iliac crest.
Primary question
Does adding BMP-2 at surgery improve bone healing, assessed by the RUST score 12 mos post surgery, compared with surgery without BMP-2? The posted primary outcome gives scores for the BMP-2 group but no evaluable control-group score.
The clinical question is about the added use of an osteogenic agent during repair, not about surgery versus no surgery. The study summary describes the intended comparison as surgical repair with BMP-2 against a control group treated surgically without BMP-2. The primary endpoint is radiographic: it scores the appearance of the tibial bone cortex on anterior-posterior and lateral X-rays. The study also listed other outcomes, including time to healing, refracture, walking time, pain, and quality-of-life scores.
The registry record identifies the study as randomized, single-masked, and parallel-group. It does not report the specific masking procedure or allocation ratio. Although the primary outcome data include 2 evaluable participants in the BMP-2 group, the control group has no posted evaluable primary outcome values. As a result, the posted primary results do not answer the intended between-group question.
3. Trial Design
This was a randomized, single-masked, parallel-group study of INFUSE Bone Graft (BMP-2) in the treatment of tibial pseudarthrosis in children with NF1. The registry record lists the phase as NA. The planned comparison was between BMP-2 added to surgical repair and a control protocol consisting of surgery without BMP-2. The intervention is classified as a device and the control as a procedure.
The registry record reports enrollment of 5. It identifies 2 participants as evaluable for the primary outcome and says 3 participants withdrew for various reasons. The study was closed to further enrollment due to poor recruitment, and the record says it was closed after the last participant completed study procedures. Its status is terminated. The specific reasons for the withdrawals are not reported in the registry record.
The study’s stated aims were to assess whether BMP-2 at surgery would improve bone healing, document safety in a pediatric NF1 population, and collect biologic specimens for future studies. The control description specifies resection of abnormal pseudarthrotic tissue, placement of a rigid intramedullary rod, and autogenous bone graft from the iliac crest. The intervention description says INFUSE was added to the surgical protocol; further details of that arm’s surgical procedures are not fully reported in the registry record.
Randomized allocation describes how assignment was intended to occur, but it does not by itself establish that the final outcome groups were balanced or that an arm comparison can be calculated. The primary outcome record contains values for the BMP-2 arm only. The number randomized to each group, the allocation ratio, and the specific masking procedures are not reported in the registry record. Consequently, the design description should be distinguished from the limited outcome data available for assessing the planned comparison.
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
| Stage | INFUSE Bone Graft (BMP-2) | Control Group |
|---|---|---|
| STARTED | 5 | 0 |
| Completed 12 Months | 2 | 0 |
| COMPLETED | 2 | 0 |
| NOT COMPLETED | 3 | 0 |
Reasons for not completing this period:
| Reason | INFUSE Bone Graft (BMP-2) | Control Group |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Adverse Event | 1 | 0 |
| Data was incomplete. Patient was inevaluable | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The population consisted of 2 evaluable participants. Three (3) participants withdrew for various reasons (see participant flow). The study was closed for further enrollment due to poor recruitment. The study was closed after the last participant completed study procedures.
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: Randomization resulted in 0 participants for the Control Group
| Characteristic | Unit | INFUSE Bone Graft (BMP-2) | Control Group | Total |
|---|---|---|---|---|
| Participants analysed | 5 | 0 | 5 | |
| Age, Categorical: <=18 years | Participants | 5 | 0 | 5 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 3.4 (SD 3.1) | — | 3.4 (SD 3.1) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Male | Participants | 4 | 0 | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | — | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | — | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | — | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | — | 2 |
| Race (NIH/OMB): White | Participants | 1 | — | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 | — | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | — | 1 |
| Region of Enrollment: United States | participants | 4 | — | 4 |
| RUST score | scores on a scale | 11 (10 to 12) | — | 11 (10 to 12) |
6. Primary Endpoint
The registry lists the primary outcome as RUST Score, measured over 12 mos post surgery. The score at 12 mos post surgery will be used to determine success of healing and is the score reported..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | score on a scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the RUST score 12 mos post surgery. RUST means Radiographic Union Score for Tibial fractures. It was developed as a measure of tibial fracture healing and, according to the registry record, has been validated in the NF1 population. The score uses radiographic assessments of the bone cortex on anterior-posterior and lateral X-rays.
Each of four visible tibial cortices receives a score from 1 to 3: 1 represents no healing, 2 some callus, and 3 healing of the cortex. The four cortex scores are combined into a total score ranging from 4 to 12. For this study, a score from 9 to 12, with at least 2 evaluable cortices scoring 3, was considered healed; scores from 5 to 8 represented partial healing, and a score of 4 represented no healing.
The posted outcome is the median and full range at the specified follow-up time. The BMP-2 group has a reported median of 12 and full range of 12 to 12 among 2 evaluable participants. A score of 12 falls within the study’s healed category. No control-group RUST value is posted, so the endpoint data do not provide a comparison of healing scores between the study groups.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome record reports a median RUST score of 12, with a full range of 12 to 12, for 2 evaluable participants assigned to INFUSE Bone Graft (BMP-2). The score was assessed 12 mos post surgery. The study’s definition classifies a total score from 9 to 12 as healed when at least 2 evaluable cortices score 3. A total score of 12 is within that range. The record reports no evaluable control-group score for the primary outcome.
This is a description of the available observations, not an estimate of the effect of BMP-2 compared with the control procedure. Without a control-group value, the posted primary outcome cannot quantify a difference between treatment groups. It also cannot show whether the observed scores would have differed from scores under the surgical protocol without BMP-2. The randomized design does not supply that missing comparison by itself.
The small number of evaluable participants is important when reading the outcome. The primary endpoint population consisted of 2 participants, while the registry reports total enrollment of 5 and 3 withdrawals. A median and range describe the recorded values, but with so few observations they cannot characterize the range of outcomes that might occur in a broader population. The equal reported values do not establish that outcomes would be equally consistent in other patients.
No statistical analysis is posted for the primary between-group comparison. The record lists no analyses and states that values are missing or not estimable for a two-arm comparison for this endpoint. There is therefore no reported treatment-effect estimate or inferential result for the comparison. A confidence interval, which in general describes a range of estimates compatible with the data under a specified method, is not reported in the registry record for this comparison.
The result should also be read in the context of study completion. Recruitment was poor, enrollment stopped, and 3 participants withdrew for various reasons. The available endpoint data come from the 2 participants identified as evaluable, and the control arm has no posted primary outcome values. These features limit what can be learned from the posted results about the intended comparison, regardless of the numerical RUST scores observed in the BMP-2 group.
The record includes safety counts for the BMP-2 group, but they do not resolve the missing efficacy comparison. Safety events and radiographic healing are distinct outcomes, and the small observed groups do not support a broad comparative conclusion. Overall, the posted data document RUST scores in a small evaluable BMP-2 group; they do not establish a comparative effect or provide a precise estimate of one.
9. Statistical Methods Explained
The primary endpoint is a score formed by combining radiographic assessments of four tibial cortices. In general, a composite score can make multiple component observations easier to summarize, but interpretation depends on the scoring rules and the meaning of the components. Here, the registry explains the scale: each cortex is scored from 1 to 3, and the four scores are totaled. Higher totals correspond to more radiographic evidence of healing under the study’s definitions.
The registry reports the median and full range rather than a mean and standard deviation. In general, the median is the middle value after observations are ordered, and the range gives the smallest and largest observed values. These summaries can be useful for a small sample or a score whose distribution may not be well represented by a mean. They describe the observations; they do not adjust for other factors or estimate a causal effect. For the BMP-2 group, the posted median is 12 and the full range is 12 to 12, based on 2 evaluable participants.
What does the randomized design establish?
Randomization is intended to make treatment assignment independent of participants’ prognostic characteristics, on average, and can support a fair comparison when outcomes are observed and analyzed for the randomized groups. It does not guarantee balance in every small study, and it cannot substitute for missing outcomes in a comparison arm. In this record, the primary outcome data include no evaluable control-group values. Therefore, the randomized design does not yield a posted primary endpoint contrast.
What can be inferred from a median and range?
General statistical interpretation distinguishes descriptive summaries from estimates of a treatment effect. A median and range describe the values observed among the participants included in that summary. They do not, on their own, say how the same participants would have fared under the alternative treatment. To estimate a comparative effect, both groups need outcome information and a stated comparison method. A confidence interval would communicate uncertainty around an estimate under its assumptions; no such estimate or interval is reported for the primary two-arm comparison.
The RUST criteria also need to be kept distinct from the statistical analysis. The registry defines a total score from 9 to 12, together with the requirement for at least 2 evaluable cortices scoring 3, as healed. That is the study’s endpoint classification. It is not itself a test of whether one group did better than the other. The observed BMP-2 scores lie at the upper end of the scale, but there are no control scores with which to compare them.
What do the planning assumptions mean?
The registry’s planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. For time-to-event outcomes, its convention is to give the total number of events using the Schoenfeld approach; for other outcomes, it gives participants per arm. These are general planning assumptions, not evidence about the trial’s actual design or its recruitment target. The planning illustration is not observed power. The numerical planning estimates and a trial-specific sample-size justification are not reported in the registry record.
In general, sample-size planning estimates how much information a future study might need under chosen assumptions. Such estimates depend on assumptions about the target effect, variability or event frequency, allocation, and statistical method. A planning exercise based on an observed effect can be especially uncertain when the observed data are sparse. It should not be treated as a reliable estimate of the sample needed unless its assumptions are justified independently. No inference about the adequacy of the original enrollment target can be made from the planning assumptions alone.
Why does over-dispersion matter in general?
For outcomes analyzed with count-based models, over-dispersion means that variability is greater than the model’s basic assumptions allow. If it is ignored, uncertainty can be understated and interval estimates or tests can be too optimistic. The registry record does not report a count model or an analysis addressing over-dispersion for the primary RUST endpoint. This is a general statistical consideration, not a description of a method used in this trial.
More broadly, method choice should match the endpoint, design, and amount of available data. A score with a bounded range, repeated measurements, time-to-event outcome, and event count each raise different analytic questions. The registry lists multiple types of secondary outcomes, but the analysis details for them are not reported. No adjusted model, covariate set, or prespecified primary comparison procedure is described in the registry record. Accordingly, the posted outcome summaries should be interpreted descriptively rather than as results of a documented comparative statistical analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 12 outcome measures and 11 posted secondary outcomes, in addition to the primary RUST endpoint. The secondary outcomes include time to healing, refracture outcomes, a timed walk, pain intensity, and quality-of-life scores. When a study considers multiple outcomes or multiple tests, the chance of at least one apparently unusual result can increase. In general, multiplicity methods can address that issue by controlling a chosen error rate or by defining a hierarchy of outcomes. A multiplicity strategy is not reported in the registry record.
No analyses are listed for the outcomes. Details of any planned analysis hierarchy, prespecified contrasts, or adjustment for multiple comparisons are not reported in the registry record. The absence of posted analyses means there is no set of reported inferential results from which to assess how multiplicity was handled.
Missing data are central to interpretation of the primary endpoint. The record identifies 2 evaluable participants and reports that 3 participants withdrew for various reasons. The specific reasons and timing of withdrawal, the availability of any partial outcome measurements, and the approach to missing outcomes are not reported in the registry record. The primary endpoint summary is therefore based on the evaluable participants, but the record does not describe a broader analysis population or a method for handling missing values.
The control group has no posted evaluable RUST value. The record states that values are missing or not estimable for a two-arm comparison for this endpoint. It does not report whether participants were analyzed according to randomized assignment, whether any participants changed groups, or how withdrawals were included in safety or efficacy populations. Those details are not reported in the registry record, so no intention-to-treat or per-protocol analysis can be identified from the posted results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| INFUSE Bone Graft (BMP-2) | 1 | 5 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| INFUSE Bone Graft (BMP-2) | 0 of 5 |
| Control Group | 0 of 0 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| INFUSE Bone Graft (BMP-2) | 2 of 5 |
| Control Group | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | INFUSE Bone Graft (BMP-2) | Control Group |
|---|---|---|---|
| Surgical and Medical procedure - revision of Rush rod | Surgical and medical procedures | 1 of 5 | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | INFUSE Bone Graft (BMP-2) | Control Group |
|---|---|---|---|
| New fracture tibia | Musculoskeletal and connective tissue disorders | 1 of 5 | 0 of 0 |
| Femur fracture | Injury, poisoning and procedural complications | 1 of 5 | 0 of 0 |
Serious events with the highest arm-level rate: surgical and medical procedure - revision of rush rod (20.0%).
For the INFUSE Bone Graft (BMP-2) group, the registry reports 5 participants at risk for serious adverse events and 1 affected. It reports 5 at risk for other adverse events and 2 affected. Deaths are reported as 0. The control group has 0 participants at risk in the posted safety data, so these figures do not support a comparison of safety between groups.
The most frequent serious-event term listed is “Surgical and Medical procedure - revision of Rush rod,” reported as 20.0%. This term describes the event recorded; the registry does not establish from this figure that the intervention caused it. The serious-event count is a participant count in the group at risk, while the listed term is presented as a percentage. They are different summaries and should not be treated as interchangeable measures of risk.
In general, adverse-event counts need to be interpreted alongside how events were defined, collected, and attributed, as well as the amount of follow-up. The registry record does not provide further detail about attribution, event severity beyond the serious classification, or comparative statistical analysis. The small safety population and absence of control-group participants at risk in the posted results make the figures descriptive rather than a basis for a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The posted primary result is that the 2 evaluable participants in the INFUSE Bone Graft (BMP-2) group had a median RUST score of 12 and a full range of 12 to 12 at 12 mos post surgery. Under the study’s scoring definition, a total score of 12 is within the healed category. This describes the radiographic endpoint values recorded for those evaluable participants.
The result does not show how those participants’ outcomes compare with outcomes under the control procedure. No control-group primary endpoint values are posted, and no two-arm analysis is reported. It is therefore not possible to interpret the observed scores as an estimated benefit or disadvantage of adding BMP-2. The registry record does not report a comparative effect estimate or confidence interval for the primary outcome.
The result also does not establish what would happen in a larger or different population. The primary endpoint population contains 2 evaluable participants, and 3 participants withdrew for various reasons. The record does not provide the withdrawal details or a missing-data analysis. These limitations leave substantial uncertainty about how representative the observed scores are of the participants initially enrolled or of children with NF1 and tibial pseudarthrosis more broadly.
The study’s aims included safety documentation and collection of biologic specimens, as well as bone healing. The posted safety counts describe the BMP-2 group, but the control group has no participants at risk in the posted safety figures. Those counts therefore do not establish a comparative safety profile. The registry also lists several secondary outcomes, but their analysis details are not reported.
In general, a clinical trial’s result is strongest when the endpoint, analysis population, comparison, and uncertainty are all clearly reported. In this record, the primary score is interpretable as a descriptive observation against the RUST scale, but the intended randomized comparison cannot be assessed from the posted endpoint values. The result should not be extended beyond that narrow description.
13. Why This Trial Matters Statistically
This trial illustrates the difference between a randomized study design and a usable randomized comparison. Randomization is a design feature intended to support comparison, but the primary outcome data still need to be available for both groups. Here, the posted RUST summary is for 2 evaluable participants in the BMP-2 group, while the control group has no evaluable primary outcome values. The intended comparative question therefore remains unanswered by the posted endpoint data.
The record also demonstrates why enrollment, evaluability, and analysis population are not interchangeable. Enrollment was 5, the primary endpoint population was 2 evaluable participants, and 3 participants withdrew. Without details about withdrawals and analysis populations, readers cannot determine how the endpoint summary relates to everyone enrolled or assigned to treatment.
Small studies can be valuable for feasibility, outcome measurement, and collecting information in uncommon clinical settings. But sparse data place limits on both precision and comparative interpretation. In general, a single-group summary, even when its values fall in a favorable category on a predefined scale, cannot answer a between-group question without an adequate comparator outcome.
The record’s termination after poor recruitment is also statistically relevant: limited recruitment can leave a study unable to produce the planned comparison, irrespective of the clinical importance of its question. The stated aims extended beyond the primary endpoint to safety and future biologic research. The posted data should therefore be read as a limited record of the study’s progress and observed outcomes, not as a complete evaluation of its intended treatment comparison.
14. 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 main trial-specific limitation is the lack of a posted control-group primary outcome. The registry reports a RUST median and range for 2 evaluable participants in the BMP-2 group, but no control-group value. No two-arm analysis is reported, so the primary endpoint cannot estimate a comparative effect.
The evaluable population was small relative to the reported enrollment: 2 participants were evaluable for the primary outcome, and 3 withdrew for various reasons. The reasons, timing, and handling of those withdrawals are not reported in the registry record. The record also does not report the number randomized to each arm or whether all randomized participants were included in any defined analysis population.
Recruitment was poor, and the study was closed to further enrollment. The registry says the study closed after the last participant completed study procedures, but does not report a recruitment target or trial-specific sample-size justification. A planning illustration based on observed effects does not establish what sample size the study originally intended to recruit.
Masking is listed as single, but the masked party and procedures are not reported in the registry record. The allocation ratio and details of sequence generation are also not reported. Analysis methods, confidence intervals, multiplicity procedures, and missing-data handling are not reported. These gaps limit assessment of both the reliability of the estimates and the process by which outcomes were analyzed.
Safety information is posted for the BMP-2 group, with no participants at risk in the control group. It therefore does not provide a comparative safety assessment. The intervention-arm description is also incomplete in the registry record, limiting interpretation of the exact surgical protocol beyond the stated addition of INFUSE.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of INFUSE Bone Graft (BMP-2) in the Treatment of Tibial Pseudarthrosis in Neurofibromatosis Type 1 (NF1) — NCT02718131.
- Registry record last updated 2021-10-27; status last verified 2021-09.
- Results first posted 2021-10-27.
- 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.
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18. Record Summary
NCT02718131 studied INFUSE Bone Graft (BMP-2) added to surgical repair of tibial pseudarthrosis in children with NF1, compared with a control surgical protocol without BMP-2. The record describes a randomized, single-masked, parallel-group study and lists its phase as NA. Enrollment was 5; 2 participants were evaluable for the primary outcome, and 3 withdrew for various reasons. The study was terminated and closed to further enrollment due to poor recruitment.
The primary endpoint was median RUST score 12 mos post surgery. The BMP-2 group had a reported median of 12 and full range of 12 to 12 among 2 evaluable participants. No control-group RUST values or primary comparison analysis are posted. Safety figures report 1 serious adverse-event participant among 5 at risk, 2 participants with other adverse events among 5 at risk, and 0 deaths in the BMP-2 group; the control group has no participants at risk in the posted safety data.
The posted results are descriptive and do not establish a between-group effect. Analysis methods, missing-data handling, and trial-specific sample-size justification are not reported in the registry record.