Neurodevelopmental Outcomes in Craniosynostosis Repair: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neurodevelopmental Outcomes in Craniosynostosis Repair (NCT04072783), a na na study. The primary outcome is Assessment of Brain Development Via Diagnostic Imaging.

2. Clinical Question

The scientific question concerns both measurement and change. The investigators aimed to examine white-matter tracts and brain development in children with craniosynostosis, using imaging and developmental assessments at planned time intervals. The summary describes observations before and after cranial vault remodeling, with age-matched controls as a proposed point of comparison. It also describes a broader aim of building a normative white-matter development curve in children under 4 years of age.

These aims need to be distinguished from what the registry record can establish. The recorded design is a single-group study, and the listed arm is patients with craniosynostosis. The registry record does not report a completed control-group comparison or numerical outcome results. It states that the prespecified number of scans needed for analysis was not reached and that completion was insufficient to support robust statistical analysis. Therefore, the central question remains an intended research question rather than a question answered by interpretable comparative estimates in the registry record.

3. Trial Design

The registry describes a prospective study of patients diagnosed with craniosynostosis who were expected to undergo open or endoscopic cranial vault remodeling. Surgery was described as standard care. Participants were to have imaging before and after surgery, with MRI sequences at set time intervals, and neurodevelopmental testing at corresponding intervals. The imaging intervention is listed as MRI, DTI, and functional MRI.

The recorded design is single-group, with no allocation or masking listed. The registry lists 9 participants enrolled and gives the study status as terminated. Its recorded primary completion date is 2024-12-31. The registry record does not report a randomized treatment assignment or a like-for-like treatment comparison. Although the study summary refers to age-matched controls, the recorded arm information describes patients with craniosynostosis and does not describe a control arm. These records therefore do not support treating the study as a controlled comparison.

The primary outcome is described as assessment of brain development through diagnostic imaging, with a timeframe from 2 months age to 4 years of age. The stated aim was to use DTI fractional anisotropy maps to establish a normative white-matter change curve from infancy to preschool age. A secondary outcome concerns neurodevelopmental test results in patients with craniosynostosis. The registry lists 3 outcome measures overall, but further numerical results and analysis details are not reported in the registry record.

The record says the prespecified number of scans required for analysis was not reached. It consequently characterizes the study as lacking sufficient completion for robust statistical analysis. It does not report why enrollment or scan completion fell short, whether the planned follow-up schedule was changed, or what decisions led to termination. The registry record also does not report a statistical analysis plan or a sample-size justification for the study’s own design.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The pre-specified number of scans required for analysis was not reached. Consequently, the study did not achieve a sufficient completion rate to support a robust statistical analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Assessment of Brain Development Via Diagnostic Imaging, measured over From 2 months age to 4 years of age.

The primary endpoint is described as brain development assessed through diagnostic imaging. The planned imaging included DTI, with fractional anisotropy (FA) maps used to characterize white-matter integrity and to develop a normative curve of white-matter change from infancy to preschool age. The stated timeframe is from 2 months age to 4 years of age. The study summary also describes MRI sequences before and after surgery and at set time intervals, with the aim of quantifying white-matter tract maturity.

FA is a DTI parameter. In general, DTI describes properties of water diffusion in tissue, and FA is used as an imaging measure related to white-matter integrity. A curve across age can help describe how a measured imaging feature changes during development. Such a curve is descriptive unless its design and analysis support further comparisons or inferences. It does not by itself establish that surgery caused a change, nor does an imaging measure automatically establish a clinical or developmental benefit.

The registry states that the prespecified number of scans needed for analysis was not reached. It reports no numerical FA values, estimates of change, uncertainty intervals, or completed curve. Thus the endpoint’s intended measurement and rationale are described, but a resulting developmental pattern is not reported in the registry record. The registry does not specify a single summary value, the exact analytic model, or how repeated measurements would have been combined.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a prospective, single-group study. In general, a prospective design specifies measurements to be collected over time, rather than relying solely on records assembled after those measurements. Repeated imaging and developmental assessments can describe within-person trajectories, but valid interpretation depends on consistent timing, sufficient observations, and an analysis that accounts for repeated measurements. The registry describes planned imaging before and after surgery and at set intervals, but does not report the achieved measurement schedule or the statistical model used.

What does a single-group design allow?

A single-group study can describe the characteristics and outcomes observed among its participants. It can also provide feasibility information about recruiting participants, collecting scans, and administering assessments. However, when outcomes are measured before and after an intervention, changes over time cannot automatically be attributed to the intervention. Development, elapsed time, measurement familiarity, clinical differences, and other factors may also influence observations. A comparison group can help address some questions, but only if it is actually defined, measured appropriately, and included in the analysis.

The summary mentions age-matched controls, while the recorded design is single-group and the listed arm describes patients with craniosynostosis. The registry record does not report how controls were selected, whether controls were enrolled, or whether a comparison was analyzed. Accordingly, a control-based effect estimate cannot be interpreted from this record. The record also lists no allocation and no masking. Those entries describe what is registered; they do not provide details about operational procedures beyond the recorded design.

How should repeated imaging be understood?

Repeated scans from the same participant are related observations, not independent observations. General statistical methods for longitudinal data account for this dependence when estimating average change and uncertainty. The choice of model can also affect how differences in follow-up timing, incomplete observations, or variation between participants are handled. The registry does not report the planned or fitted model, the handling of repeated observations, or the number of usable observations at each interval. Therefore, it is not possible to assess those analytic choices from the registry record.

The proposed endpoint uses fractional anisotropy from DTI. In general, an imaging measure is an operational definition: it turns an aspect of a biological signal into a quantity that can be analyzed. Its interpretation depends on acquisition procedures, quality control, image processing, and the relationship between the measure and the biological construct of interest. The registry describes FA as a main DTI parameter sensitive to white-matter integrity, but does not report acquisition settings, quality-control rules, processing details, or analytic definitions. These technical details matter because measurement variation can affect observed patterns and their uncertainty.

What is a normative curve?

In general, a normative curve describes the expected pattern of a measurement across a reference population or age range. Constructing one requires observations that cover the intended range and a model capable of representing the relationship between age and the measure. The registry’s objective was to establish a curve of white-matter tract development in normal children under 4 years of age. It also describes a study of patients with craniosynostosis. The record does not explain how the proposed normative sample related to the listed patient group or how reference observations would be obtained. It states that the prespecified scan requirement was not met, so the planned robust analysis was not supported.

In general, confidence intervals communicate the range of effect estimates compatible with the data and model, subject to the assumptions used. A narrow interval indicates greater precision than a wide interval; neither interval alone resolves bias or limitations in the design. No estimate or confidence interval is reported for the primary outcome, so its precision cannot be assessed. A p-value, if reported, would address compatibility with a specified null model under assumptions; it would not by itself measure clinical importance or prove causality. No p-value is reported in the registry record.

Why does scan completion matter?

Incomplete follow-up can reduce the information available for analysis and can also introduce bias if the participants with missing measurements differ systematically from those with observed measurements. In general, statistical methods can use assumptions about the missingness process, but those assumptions need to be stated and assessed where possible. A completion shortfall does not reveal why data are missing or whether missingness is related to outcomes. The registry states only that the required number of scans was not reached and that completion was insufficient for robust statistical analysis. It does not report the amount, timing, or reason for missing data, nor any method for handling it.

Over-dispersion is a general issue that arises when observed variability is greater than a chosen model expects. If it is ignored, uncertainty can be understated. For imaging and developmental data, variability may arise from participant differences, measurement conditions, and follow-up timing. Whether over-dispersion was relevant to this study cannot be determined because no outcome distribution or fitted model is reported. More generally, model diagnostics and sensitivity analyses can show whether conclusions depend on particular assumptions; such analyses are not reported in the registry record.

What can planning calculations say?

In general, sample-size calculations use assumptions about the effect to be detected, variability, significance level, allocation, and analysis method. A planning illustration based on an observed effect is not evidence that the study had a particular probability of finding an effect, and it is not observed power. It also cannot replace an analysis of the collected data. The registry record does not report a sample-size justification for the study’s own design, and the stated scan shortfall means the intended analysis was not robustly supported. Any planning illustration should therefore be read only as a hypothetical planning exercise, not as a result of this study.

For a two-group comparison, equal allocation and a normal approximation are assumptions sometimes used in planning exercises; those assumptions do not turn this recorded single-group study into a two-group trial. The registry’s recorded design remains the relevant description of the study. No trial-specific inferential model, adjustment strategy, or full statistical analysis plan is reported. Because the registry lists no analyses, there are no sponsor-reported estimates to reconcile with any recalculation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, including the primary imaging outcome and a secondary outcome concerning neurodevelopmental test results. The study summary also describes multiple imaging modalities, repeated measurement intervals, and developmental assessments. When a study examines multiple outcomes, time points, or measures, the chance of finding an apparently notable result by chance can increase if many tests are conducted without a plan. General strategies include prespecifying a primary contrast, controlling a family-wise error rate, or emphasizing estimation and uncertainty rather than isolated significance tests. The registry record does not report a multiplicity strategy or identify the specific contrasts planned for each outcome.

The registry states that the required number of scans was not reached and that completion was insufficient for robust statistical analysis. It does not report how many participants completed each assessment, how many scans were usable, or the reasons for incomplete data. A total enrollment figure does not establish completeness for every outcome or visit. The amount and pattern of missing data are therefore not reported in the registry record.

In general, analysis populations specify which participants or observations contribute to a particular analysis. They may be defined according to enrollment, treatment exposure, or availability of outcome measurements, depending on the design and question. The registry record does not define analysis populations or state how participants with incomplete scans or assessments would have been handled. It also does not report imputation, a complete-case approach, or sensitivity analyses. These omissions prevent assessment of how missing observations might have affected any planned estimates.

Because the registry lists no analyses and reports no numerical outcome estimates, there are no reported multiplicity-adjusted findings or missing-data analyses to interpret. The absence of a reported adjustment is not evidence that a particular method was or was not used outside the registry; those details are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists 9 participants at risk in the craniosynostosis group for both serious and other adverse events. It records 0 participants affected by serious adverse events and 0 affected by other adverse events; deaths are also listed as 0. These are the counts entered in the registry record for this group.

Zero recorded events does not establish that an event is impossible or that a procedure has no risk. In general, a small observed group can provide limited information about less common events, and event counts depend on definitions, observation duration, and completeness of reporting. The registry record does not provide detailed event definitions, the observation period for safety reporting, or a comparison group. It therefore cannot support a comparative safety estimate.

The surgery is described as standard care, while MRI, DTI, and functional MRI are listed as diagnostic tests. The adverse-event entries should be read as registry-reported counts for the listed participants, not as a complete accounting of all possible consequences of care or as a conclusion about safety. They do not change the record’s stated limitation that scan completion was insufficient for robust statistical analysis of the planned outcomes.

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

The central result is a limitation on what can be concluded: the registry says that the prespecified number of scans required for analysis was not reached and that the study did not achieve sufficient completion to support robust statistical analysis. The record describes the intended primary imaging outcome and a neurodevelopmental secondary outcome, but it does not report numerical outcome findings. There is therefore no reported estimate of the amount or direction of change in white-matter measures, and no estimate of change in developmental test results.

This absence of results should not be interpreted as evidence that there was no change, no association, or no difference. Those conclusions would require data and analyses that are not reported. Nor can the registry establish whether cranial vault remodeling caused an observed change: the recorded design is single-group, and a completed control comparison is not reported. Even if before-and-after observations had been available, separating change associated with surgery from development over time would require an appropriate design and analysis.

The record does establish the scope of the intended work. It aimed to study imaging and neurodevelopment in children with craniosynostosis, described use of DTI and FA maps to characterize white-matter development, and included imaging around surgery. It also establishes that the registry lists enrollment of 9 participants and marks the study as terminated. These are design and conduct details, not evidence that the planned endpoint was successfully estimated.

The adverse-event entries record 0 serious adverse events and 0 other adverse events among the 9 participants listed as at risk. These observations are limited to the registry’s recorded group and reporting. They do not amount to a comparative assessment or establish the absence of risk.

Accordingly, the record is most informative as a description of a research objective and its stated feasibility limitation. It does not answer whether the planned developmental curve can be estimated, whether imaging changes differ by age or surgery, or how neurodevelopmental test outcomes compare with an age-matched control group. Those results and comparisons are not reported in the registry record.

13. Why This Trial Matters Statistically

This study addresses a statistical problem that arises when a research question requires measurements across development. A normative curve depends on observing enough participants and measurements across the intended age range. When scan completion falls short of the prespecified requirement, the result may be too incomplete or unstable to support a robust description. The registry explicitly reports that this study did not reach the required number of scans for analysis.

The study also illustrates the importance of aligning the scientific question with the recorded design. The summary refers to age-matched controls and to pre- and postoperative measurements, while the registry records a single-group design and lists only patients with craniosynostosis in the arm description. A proposed comparison and a recorded comparison are not interchangeable. Clear definitions of the population, comparator, time points, and primary contrast are necessary to interpret an eventual estimate.

Measurement is another central issue. DTI and FA offer quantitative ways to characterize aspects of white-matter development, but analysis depends on consistent image acquisition, processing, and quality control. The registry states the intended imaging approach and endpoint concept, while technical and analytic details are not reported. Statistical precision cannot compensate for measurement uncertainty, and a well-defined measure cannot compensate for insufficient data.

Finally, the record distinguishes an intended research program from an informative outcome analysis. The listed enrollment and zero recorded adverse-event counts are useful descriptive information, but they do not answer the primary developmental question. No analyses or numerical outcome estimates are reported. The statistical importance of this record is therefore not a treatment-effect finding; it is the documented gap between the planned imaging analysis and the completion needed to support it.

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 most direct limitation is stated in the registry: the prespecified number of scans required for analysis was not reached, and study completion was insufficient to support robust statistical analysis. No numerical primary or secondary outcome results are reported. The record does not show the number of completed visits, the quantity of usable imaging data, or how many participants contributed to each measure.

The registry records a single-group design and one listed patient arm. Although the summary mentions age-matched controls, the registry record does not describe a control arm or report a completed control comparison. This limits interpretation of any potential before-and-after change, which can reflect development over time as well as other influences. The record does not report an analysis capable of distinguishing these explanations.

The primary outcome description focuses on a normative white-matter curve in normal children under 4 years of age, while the listed arm comprises patients with craniosynostosis. How the proposed normative sample relates to the enrolled group is not explained in the registry record. The registry also does not specify the primary summary measure, the statistical model for repeated imaging, or the technical procedures for image processing and quality control.

Further limitations include absent reporting of analysis populations, missing-data methods, multiplicity procedures, confidence intervals, p-values, and effect estimates. The record does not provide a study-specific sample-size justification or explain the reason for termination and the shortfall in scan completion. The absence of these details prevents a fuller assessment of bias, precision, and the intended inferential framework. These are reporting limitations in the registry record; they do not establish what procedures may have been used outside it.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Neurodevelopmental Outcomes in Craniosynostosis Repair — NCT04072783.
• Registry record last updated 2026-04-22; status last verified 2026-02.
• Results first posted 2026-04-22.
• 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.

18. Record Summary

The registry describes a prospective, single-group study of children with craniosynostosis undergoing standard-care cranial vault remodeling. Its intended assessments included pre- and postoperative MRI, DTI, functional MRI, and neurodevelopmental testing. The primary outcome concerned brain development assessed through diagnostic imaging, including a proposed FA-based normative curve from 2 months age to 4 years of age.

The record lists enrollment of 9 participants, no masking, and terminated status. It reports that the prespecified number of scans required for analysis was not reached and that completion was insufficient to support robust statistical analysis. No analyses or numerical outcome estimates are reported. The registry lists 0 serious adverse events, 0 other adverse events, and 0 deaths among the 9 participants at risk. The summary’s reference to age-matched controls is not accompanied by a recorded control arm or reported comparative analysis.