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 Study Evaluating InductOs in Diaphyseal Tibia Fractures (NCT00161616), a randomized phase 4 study. The primary outcome is Number of Patients With Healed Fractures.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00161616 |
| Phase | Phase 4 |
| Condition | Tibial Fractures |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | Single |
| Enrollment | 277 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wyeth is now a wholly owned subsidiary of Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
People with open diaphyseal tibia fractures treated with reamed, locked intramedullary nail fixation. The registry says all randomized patients were analyzed, but does not give further eligibility details in the outcome description.
Intervention
InductOs, described as rhBMP-2/ACS 1.5 mg/ml, implanted once at the time of definitive fracture coverage and surgical fixation.
Comparator
Standard of Care, described as surgical fixation only. Both groups are associated with reamed, locked intramedullary nailing in the trial summary.
Primary question
Does adding InductOs to reamed, locked intramedullary nailing result in a different proportion of patients categorized as having healed fractures, compared with nailing alone, at the assessed follow-up times of 13 and 20 weeks?
The registry frames the study objective as demonstrating a larger proportion with healed fractures in the InductOs group. That stated objective is not itself evidence of a difference. The posted record does not give the group-specific primary outcome results or a comparative estimate, so the observed size and precision of any difference cannot be described from this record.
3. Trial Design
The registry describes a Phase 4, randomized, controlled, stratified study of InductOs in people with open diaphyseal tibia fractures treated with reamed, locked intramedullary nail fixation. Allocation is listed as randomized and masking as single. The record does not specify who was masked, how the stratification was conducted, or how the random sequence was generated. Its model classification is listed as single group, despite the randomized allocation and descriptions of an InductOs group and a Standard of Care group. This classification does not resolve the discrepancy; additional design details are not reported in the registry record.
The study record lists enrollment of 277 and describes the intervention as a single implantation of rhBMP-2/ACS 1.5 mg/ml at definitive fracture coverage and surgical fixation. The comparator is surgical fixation only. The registry reports study start in 2003-09, primary completion in 2008-07, and status as completed. These dates and completion status do not supply the missing outcome results.
The primary outcome is the number of patients with healed fractures, assessed at 13 and 20 weeks. The record also lists a secondary outcome: the number of patients achieving a combined clinical and radiographic endpoint. It indicates two outcome measures and three analyses, but does not provide the analysis details needed to understand how the outcome measures and analyses relate to each other. The statistical plan, including the planned primary comparison and handling of the stratification, is not reported in the registry record.
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: Assessment of the fractured limb was performed 24 hours before surgical fixation. Patients were stratified by severity of fracture (using Gustilo-Anderson Classification).
Overall Study
| Stage | rhBMP-2/ACS | Standard of Care |
|---|---|---|
| STARTED | 139 | 138 |
| COMPLETED | 113 | 119 |
| NOT COMPLETED | 26 | 19 |
Reasons for not completing this period:
| Reason | rhBMP-2/ACS | Standard of Care |
|---|---|---|
| Withdrawal by Subject | 6 | 5 |
| Physician Decision | 1 | 0 |
| Death | 1 | 1 |
| Lost to Follow-up | 17 | 13 |
| Protocol deviation | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All patients randomized were analyzed.
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.
| Characteristic | Unit | rhBMP-2/ACS | Standard of Care | Total |
|---|---|---|---|---|
| Participants analysed | 139 | 138 | 277 | |
| Age Continuous | years | 39.48 (SD 15.40) | 37.54 (SD 14.87) | 38.52 (SD 15.14) |
| Sex: Female, Male: Female | Participants | 26 | 27 | 53 |
| Sex: Female, Male: Male | Participants | 113 | 111 | 224 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients With Healed Fractures, measured over 13 and 20 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | patients |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of patients categorized by the investigator as healed, not healed, or having no outcome, assessed at 13 and 20 weeks. The registry describes criteria for the healed category that combine clinical and imaging findings: absence of tenderness at the fracture site or pain with weight bearing, bridging callus or disappearance of fracture lines, no hardware failure, and no secondary intervention to promote healing. The not-healed category includes delayed union or nonunion, hardware failure, a recommended or performed secondary procedure to promote fracture healing, or a procedure that may interfere with healing. Patients meeting neither category are classified as having no outcome.
This kind of endpoint is used to summarize healing using more than one type of evidence, rather than relying on a single imaging or symptom measure. Combining clinical and radiographic criteria can make the endpoint relevant to the overall healing assessment, while also making interpretation dependent on the stated definitions and investigator categorization. The no-outcome category matters: it is not equivalent to healed or not healed and should not be silently treated as either. The registry says all randomized patients were analyzed, but does not report how patients in each category were distributed or how the primary comparison handled the categories. Results by group and follow-up time are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies the clinical question and defines how investigators classified fracture healing, but it does not provide the primary outcome counts or a group comparison at 13 and 20 weeks. Consequently, it is not possible to describe whether the posted results favored either group, quantify the observed difference, or assess its precision. The study objective expresses an intended demonstration; it cannot substitute for a reported result.
The endpoint has three possible classifications: healed, not healed, and no outcome. A valid interpretation needs to account for all of them and for each assessed time point. In particular, the no-outcome category could affect a comparison depending on its frequency and the analysis method. Neither the category counts nor the method for handling them is reported in the registry record. The fact that all randomized patients were analyzed does not, by itself, show how incomplete endpoint information was treated.
The registry lists adverse-event information for rhBMP-2/ACS and Standard of Care, including 31 and 25 under serious adverse events, and 127 and 123 under other adverse events, respectively. At-risk denominators are not reported in the registry record. These counts therefore do not establish comparative event rates or allow a precise assessment of relative safety. The listed serious-event terms include Infection at 10.8%, Pain at 5.0%, Accidental injury at 2.9%, Fracture delayed union at 2.9%, Fracture nonunion at 2.9%, and Fracture malalignment at 2.2%. The record does not clarify the denominators or provide comparative estimates for these percentages, so they should be read as registry-reported event information rather than as treatment effects.
No confidence intervals or p-values for the primary endpoint are reported in the registry record. A confidence interval, as a general statistical concept, describes a range of values compatible with the data under the analysis assumptions; without a posted estimate and interval, the uncertainty around a treatment comparison cannot be judged. Likewise, the listed count of analyses does not reveal whether they were planned, adjusted, or exploratory. The registry record does not report an analysis plan or a sample-size justification. Overall, the record supports a description of the study question and endpoint, but not a conclusion about the magnitude, precision, or statistical significance of the primary comparison.
9. Statistical Methods Explained
What does randomization contribute?
In general, random allocation is intended to make treatment groups comparable with respect to both measured and unmeasured characteristics at the start of a study. This supports a causal comparison when allocation is implemented as intended, outcome assessment and follow-up are appropriately handled, and the analysis respects the design. The registry lists randomized allocation and describes intervention and comparator groups. It also uses the word stratified in the official title, but the stratification factors and procedures are not reported in the registry record. The model classification is listed as single group, which does not align straightforwardly with the randomized, controlled description. The record does not explain this inconsistency, so it is not possible to reconstruct the intended analysis structure from the classification alone.
How should the endpoint categories be understood?
The primary outcome is categorical: patients are classified as healed, not healed, or having no outcome, at 13 and 20 weeks. For a categorical endpoint, an analysis commonly compares the distribution of categories between groups or focuses on a prespecified category, such as healed. These are general possibilities, not a description of the analysis used in this study. The registry record does not report which comparison was used, whether the categories were analyzed jointly, or how the two follow-up assessments were incorporated. Because the endpoint is defined using clinical and radiographic criteria, consistent assessment and clear handling of indeterminate or absent outcome information are important to interpretation.
Why do denominators matter?
A count alone does not show how frequently an outcome occurred unless the number of people at risk or assessed is also known. This general principle applies to both healing outcomes and adverse events. The adverse-event record gives counts but does not provide at-risk denominators. The primary endpoint counts by group and category are not reported in the registry record. Without the relevant denominators, event proportions cannot be established from the posted information; without a reported comparative estimate, the size of a group difference cannot be assessed.
What does precision mean?
In general, a point estimate describes the observed comparison, while a confidence interval communicates its statistical uncertainty. A narrow interval indicates more precision under the model assumptions; a wide interval indicates less. An interval that includes values representing no difference may be compatible with a range of effects, and interpretation should consider that range rather than rely only on a significance threshold. These concepts explain how a complete results report could be read, but the registry record does not report a primary estimate, confidence interval, or p-value. Precision and statistical significance therefore cannot be evaluated for the primary endpoint.
What is over-dispersion, and does it apply?
Over-dispersion is a general issue in count data when the observed variability is greater than a model assumes. It can make standard errors too small and uncertainty appear overstated if the model does not account for that extra variation. The primary endpoint is described as patient counts in outcome categories, not as a rate or repeated count process, and no model specification is reported. The registry record therefore does not support a claim that over-dispersion was assessed or that a particular count model was used. The concept is relevant only if an analysis uses a model whose assumptions require it.
How should planning illustrations be read?
Sample-size calculations are planning tools, not evidence about the observed treatment effect. The registry’s stated assumptions describe an illustration based on the observed effect, two-sided significance level 0.05, equal allocation between the two arms, a normal approximation, and effects defined as fractions of the observed effect. The record says non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations use a total number of events. These assumptions do not establish the trial’s original design rationale or its planned power. The registry record does not report the trial’s sample-size justification, and any planning illustration should not be interpreted as observed power. No specific planning results are available in the registry record for interpretation.
What can the analysis count tell us?
The record lists three analyses and two outcome measures. Those counts alone do not identify the model, contrasts, covariates, handling of stratification, or whether multiplicity was controlled. A statistical analysis plan would be needed to distinguish the primary confirmatory comparison from secondary or exploratory analyses. That plan is not reported in the registry record. Recalculation from summary statistics is also not possible for the primary outcome because the necessary group-specific results are absent. No recalculated estimate should therefore be treated as a substitute for a sponsor analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures, three analyses, and two primary assessment times, 13 and 20 weeks. It does not report how the primary endpoint was prioritized across the time points, how the secondary outcome related to the primary analysis, or whether the analyses were prespecified. It also does not report a multiplicity adjustment or a strategy for controlling the chance of false-positive findings across several comparisons. Without this information and the outcome results, the statistical interpretation of any individual comparison cannot be assessed from the registry record.
The primary endpoint includes a no-outcome category, but the registry does not give the number of patients in that category or explain how missing or unevaluable information was handled. General approaches can include treating missingness according to a prespecified rule, using a model that accommodates available observations, or conducting sensitivity analyses under different assumptions. These are possibilities in general, not methods reported for this study. The record says all randomized patients were analyzed; it does not specify the analysis population beyond that statement, give a flow of participants through assessment, or explain whether the endpoint was available for every randomized patient.
The registry does not report an intention-to-treat analysis label, a per-protocol population, or details of exclusions. It also does not report interim analyses or stopping rules. Those omissions limit assessment of how analysis choices, incomplete outcome data, and multiple testing may have influenced any treatment comparison. They do not establish that a particular issue occurred; they indicate that the relevant methods are not reported in the registry record.
11. What the Result Does, and Does Not, Mean
The registry record establishes that this study addressed whether adding InductOs to surgical fixation was associated with a higher proportion of patients categorized as having healed fractures. It also specifies the endpoint criteria, the two assessment times, and the intended comparator. These details help define the question, but they do not answer it. Group-specific primary outcome results and a comparative estimate are not reported in the registry record.
Accordingly, the posted information does not support a claim that InductOs increased, decreased, or had no effect on the proportion classified as healed. It also does not support a judgment about the size or clinical importance of a difference, or whether a difference was statistically distinguishable from chance. Such judgments would require the outcome counts, denominators, comparative analysis, and measures of uncertainty. The stated study objective is not a finding.
The adverse-event counts and listed terms add descriptive safety information, but missing denominators prevent their interpretation as comparative risks. The listed percentages do not have their denominators explained in the registry record. They should not be converted into group risk comparisons or used to claim a treatment-related difference.
In general, a result from a randomized study is interpreted in light of its design, conduct, outcome measurement, missing data, analysis choices, and uncertainty. The registry record does not provide enough information to evaluate all of those elements for this study. The absence of a reported primary result is not evidence that the groups were the same, nor is it evidence that one treatment was better. It means that the primary treatment comparison cannot be determined from the posted record.
12. Why This Trial Matters Statistically
This trial is statistically notable because its primary endpoint combines clinical and radiographic criteria and retains a separate no-outcome category. That structure makes the definition of healing central to interpretation. Reporting only a single summary without explaining how the categories were handled could obscure clinically relevant distinctions, while treating no outcome as equivalent to either healed or not healed would require an explicit rationale.
The assessment at 13 and 20 weeks also creates an interpretation question: the record needs to clarify whether each time point represents a separate primary comparison, a repeated assessment, or part of another prespecified analysis. The registry names both times but does not report the analysis strategy. Because more than one outcome measure and analysis are listed, a transparent hierarchy and multiplicity approach would help readers distinguish confirmatory conclusions from secondary findings.
The record also illustrates why group counts require denominators and estimates of uncertainty. Adverse-event counts alone do not convey comparative frequency, and an endpoint count alone would not convey the precision of a treatment contrast. A complete report would ordinarily allow readers to connect the observed category distribution to the planned analysis and its uncertainty. Those primary results are not reported in the registry record.
Finally, the registry combines a randomized controlled description with a single-group model classification. That inconsistency makes the analysis structure harder to reconstruct and underscores the value of clear design and analysis reporting. These issues do not establish that the trial was conducted improperly. They identify limits in what the registry record permits readers to assess about the treatment comparison.
13. 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 for interpreting this study from the registry record is the absence of the primary outcome results. There are no group-specific counts for healed, not healed, or no outcome at either assessment time, and no comparative effect estimate or confidence interval. This prevents assessment of both the direction and precision of the primary comparison.
The record does not explain the discrepancy between the randomized, controlled description and the single-group model classification. It also does not describe the stratification factors, randomization procedures, masking details, or statistical model. The intended handling of the two assessment times and the secondary combined clinical and radiographic endpoint is not reported. The record does not provide participant flow, outcome availability by group, or specific rules for missing endpoint information.
Adverse-event counts are listed without at-risk denominators, and the denominators for the reported serious-event percentages are not specified. The record therefore does not permit rate comparisons. It also does not report a detailed analysis plan, sample-size justification, multiplicity strategy, interim analyses, or stopping rules. These gaps limit statistical assessment; they do not establish that the methods were absent or that a particular bias occurred.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Study Evaluating InductOs in Diaphyseal Tibia Fractures — NCT00161616.
- Registry record last updated 2009-09-07; status last verified 2009-07.
- Results first posted 2009-09-07.
- 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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17. Record Summary
NCT00161616 is a completed Phase 4 study of InductOs for open diaphyseal tibia fractures treated with reamed, locked intramedullary nail fixation. The registry describes randomized allocation and single masking. The intervention was rhBMP-2/ACS 1.5 mg/ml implanted once at definitive fracture coverage and surgical fixation; the comparator was surgical fixation only. Enrollment is listed as 277.
The primary outcome classifies patients as healed, not healed, or having no outcome at 13 and 20 weeks, using investigator-assessed clinical and radiographic criteria. All randomized patients were analyzed according to the record. A secondary outcome concerns a combined clinical and radiographic endpoint. Primary outcome group results and a comparative estimate are not reported in the registry record. The record also lists adverse-event counts without at-risk denominators, limiting comparative interpretation.