Measuring Brain Activity of School Age Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Measuring Brain Activity of School Age Children (NCT03407729), a registered phase not stated study. The primary outcome is Structural Integrity of Dopaminergic Circuits.

2. Clinical Question

3. Trial Design

NCT03407729, titled “Measuring Brain Activity of School Age Children,” is an observational study sponsored by Case Western Reserve University. Its official title is “Structure & Function of Dopaminergic Brain Networks Following Postnatally-Occurring Hypoxic Insults.” The registry lists the study as completed, with a start date of 2018-06-08 and primary completion on 2020-02-17. Enrollment was 21.

The study compares children with different birth and newborn-period histories. The post-hypoxic former preterm group is described as children born in 2005-2009 at 23-28 weeks gestation, with birth weight appropriate for gestational age, and with continuously recorded oxygen saturation data from the first day of life to 8 weeks postnatal age. The description gives a group count of 11. The healthy term-born group is described as children born in 2005-2009 at 38 weeks gestation or later, with birth weight appropriate for term gestation, and without a history of respiratory difficulty suggesting hypoxic exposure. The description gives a group count of 10 and says they were matched by age, sex, and race to participating cohort children.

The registry describes MRI and cognitive performance testing. The design is not a randomized comparison, and allocation is not stated. Group membership reflects participants’ birth histories rather than an assigned study treatment. As a result, observed group differences, if reported, would be comparisons between these selected groups and would not by themselves establish that hypoxic exposure caused any difference. The registry record does not report further details about recruitment, matching procedures, or how potential differences between groups were handled in analysis.

The listed enrollment and the group counts describe the study overall and its cohorts, but do not establish how many participants contributed data to each outcome. The primary outcome population is defined as all participants with a usable structural MRI scan. The number meeting that definition 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who had a usable structural magnetic resonance imaging (MRI) scan

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 Structural Integrity of Dopaminergic Circuits, measured over 30 minutes.

The primary endpoint is titled “Structural Integrity of Dopaminergic Circuits.” It is a continuous measurement expressed in mm^3, summarized as a mean with standard deviation. The assessment concerns circuits originating in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). It includes the right and left nucleus accumbens, right and left mamillary body, and right and left hippocampus. The registry describes measurement using T1-weighted magnetization prepared rapid gradient echo (MPRAGE) scans and three-dimensional volumetric analysis. The stated timeframe is 30 minutes.

In general, a structural MRI endpoint quantifies anatomical features using imaging rather than relying on a participant’s subjective report. Volumetric measurements allow the study to describe structures in physical units, while the mean gives a group-level summary and the standard deviation describes the spread of individual measurements around that mean. These summaries can help characterize whether measured volumes vary across participants and groups.

The endpoint is used to examine structural features of brain regions identified in the registry as part of dopaminergic circuits. The registry record does not report the observed mean or standard deviation for either group, nor does it give a combined endpoint definition or explain how the listed anatomical measurements contribute to a single primary result. It therefore does not permit assessment of the magnitude or precision of the structural findings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measurement summarized by a mean and standard deviation. In general, a mean represents the arithmetic center of measured values, while the standard deviation describes how dispersed individual observations are around that center. These two summaries answer different questions: the mean locates the group average, and the standard deviation describes participant-to-participant variability. Neither summary alone gives the uncertainty in a comparison between groups.

A comparison of group means commonly focuses on an estimated difference, together with an interval estimate and a test of compatibility with a null hypothesis. In general, a confidence interval communicates the range of values that remain compatible with the observations and the model assumptions. A p-value describes how unusual data at least as incompatible with the null hypothesis would be under that null model; it does not measure the probability that the null hypothesis is true or establish clinical importance. The registry record does not report a primary contrast, confidence interval, or p-value, so these quantities cannot be interpreted for this study.

Standard deviation and standard error should not be conflated. The standard deviation describes variability among participants. The standard error describes the sampling uncertainty of an estimated statistic under a particular analysis. A narrow spread of observed measurements does not automatically imply a precise group comparison, and a wide spread does not by itself show that a comparison is uninformative. Group size, data completeness, the model, and the relationship between observations all matter. The registry record identifies the endpoint summary as mean and standard deviation but does not give the outcome values or the analysis model.

The endpoint is measured using structural MRI volumetrics. In general, volumetric measures depend on the image acquisition and the procedures used to define and quantify the anatomical regions. The registry names T1-weighted MPRAGE scans and three-dimensional volumetric analysis, and lists the right and left nucleus accumbens, mamillary body, and hippocampus. Details such as image processing, quality control, reader procedures, and handling of measurements from both sides are not reported in the registry record. No assumptions about those procedures can therefore be made from the record.

The comparison is observational. In general, random assignment can make groups comparable in expectation with respect to measured and unmeasured characteristics, whereas membership in an observational group is linked to participants’ existing characteristics or histories. Here, the cohort categories are based on birth and newborn-period histories. The registry describes matching by age, sex, and race for the term-born children, but does not report the matching method or whether the statistical analysis accounted for matching. It also does not report an adjusted model, covariates, or methods for addressing confounding. A group difference would therefore be an association in the analyzed sample, not automatically a causal effect.

Planning calculations are distinct from outcome analysis. The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the intended effect is described as a fraction of the observed effect. Such calculations can illustrate the participants per arm associated with a chosen planning target under stated assumptions. They do not describe the number actually analyzed, and they are not observed power. The registry record does not report a sample-size justification from the study’s original design. No numerical planning result should be interpreted as a trial finding.

For a continuous outcome, the assumptions behind a planning calculation and the assumptions behind an analysis matter. General considerations can include the variability of the endpoint, the chosen effect to detect, the allocation pattern, the significance threshold, and whether the approximation adequately reflects the data. If data are skewed, unusually dispersed, or dependent within participants, a simple normal approximation may not capture the analysis’s actual uncertainty. These are general statistical considerations; the registry record does not report diagnostics or a distributional assessment for this endpoint.

Multiplicity concerns arise when more than one outcome or comparison is examined. In general, examining many hypotheses can increase the chance that at least one result appears noteworthy by chance if no correction or prespecified hierarchy is used. The record lists three outcome measures and one analysis, but does not report how the outcomes were prioritized, whether they were tested separately, or whether any multiplicity approach was used. It is not possible to determine from that information whether multiplicity adjustments were planned or applied.

Missing data also affect interpretation. In general, an analysis restricted to participants with usable scans can differ from an analysis of all enrolled participants if scan usability or outcome availability is related to participant characteristics or measurements. The primary endpoint population is defined as participants with a usable structural MRI scan, but the number of such participants, reasons for unavailable scans, and any missing-data methods are not reported in the registry record. The record also does not describe whether cognitive testing had a separate analysis population.

Finally, the number of adverse-event observations does not supply a method for evaluating the primary endpoint. Safety counts concern reported events in their stated groups and denominators, while the imaging endpoint concerns continuous structural measurements among participants with usable scans. They answer different questions and have distinct analysis populations. The registry record does not report how the primary endpoint analysis was conducted or whether any additional sensitivity analyses were performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including a secondary outcome of Cognitive Performance-Fine Motor Function, and reports one analysis. The primary endpoint is structural integrity of dopaminergic circuits. The registry record does not report a prespecified hierarchy among outcomes, whether each measure was analyzed separately, or whether the study used any statistical adjustment for multiple comparisons. In general, multiplicity matters when several outcomes or hypotheses are examined because the chance of at least one chance finding can increase. Without the analysis plan or full results, it is not possible to assess how this issue was handled.

The primary outcome population consists of participants with a usable structural MRI scan. The number of participants with usable scans is not reported in the registry record. The record does not describe reasons for missing or unusable scans, whether missingness differed by group, or whether any imputation or sensitivity analysis was used. It also does not report how missing cognitive performance data were handled. These gaps make it difficult to determine how closely the analyzed populations correspond to the enrolled cohorts.

The registry describes matching by age, sex, and race, but does not report how matched participants were selected or whether the analysis accounted for matched sets. An adjusted analysis, covariate selection, and any prespecified subgroup analyses are not reported in the registry record. The record also does not provide a statistical analysis plan or enough information to evaluate departures from one.

Consequently, the posted information does not establish whether multiplicity, missing outcome data, or matching were incorporated into the analysis. These are limitations in what can be concluded from the registry record, not evidence that any particular procedure was or was not used outside the reported information.

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 reports serious and other adverse-event counts separately for the two groups. For post-hypoxic former preterm participants, the serious-event denominator is 9 and the reported serious-event count is 0; the other-event denominator is 9 and the reported other-event count is 0. For healthy term-born children, the serious-event denominator is 7 and the reported serious-event count is 0; the other-event denominator is 7 and the reported other-event count is 0. Deaths are reported as 0 in both groups. No top serious-event terms are listed.

These are event counts within the stated denominators, not results for the structural MRI endpoint. The denominators are not the same as the cohort counts in the group descriptions, and the registry record does not explain the difference. The counts should therefore be read with their stated denominators rather than treated as covering every enrolled participant. Zero reported events means that none are listed in these registry fields; it does not establish that the study could rule out uncommon events or that no events occurred outside the scope of the reported record. No incidence percentages or further safety interpretation can be derived without adding calculations. The posted safety information is limited to these counts and does not describe event ascertainment or follow-up details.

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

The record describes an observational comparison of post-hypoxic former preterm children and healthy term-born children, with structural MRI as the primary assessment. It identifies the anatomical regions, measurement units, summary format, and the population intended for the primary endpoint. Those details clarify what the study set out to measure. They do not supply the numerical outcome findings.

The registry record does not report group means, standard deviations, a between-group estimate, an interval estimate, or a significance test for the primary endpoint. Therefore, the direction, magnitude, and precision of a difference cannot be determined from the posted results. The record does not support a conclusion that the groups did or did not differ in structural integrity. It also does not report enough information to assess the secondary cognitive performance outcome.

Even a complete numerical comparison would need to be interpreted in light of the observational design. The groups are defined by different birth histories, rather than random allocation. The record describes matching on age, sex, and race, but does not explain whether other characteristics were adjusted for or how matching was incorporated in analysis. A measured association would not by itself show that hypoxic exposure caused a structural difference.

The listed enrollment and group descriptions establish the overall scale and cohort composition described in the record, but the primary analysis population is participants with usable scans. The number of such participants and the handling of missing data are not reported. This limits assessment of how representative the analyzed participants are of the enrolled groups.

In general, a registry entry documents selected study details and results, but absence of a reported result in the record is not equivalent to a finding of no effect. Here, the appropriate reading is that the research question and measurement approach are described, while the outcome evidence needed to answer the question is not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why the distinction between a research question and a reported result matters. The registry identifies a biologically focused imaging endpoint and compares children whose birth histories differ, but the primary outcome values and statistical comparison are not reported. Without those findings, readers cannot estimate the observed group contrast or judge its precision. A clear endpoint description is useful, but it cannot substitute for numerical outcome reporting.

The design also highlights how comparison groups shape statistical interpretation. Matching is described for age, sex, and race, yet the record does not say how matching was performed or incorporated into analysis. General statistical reasoning distinguishes descriptive similarity from adjustment in a model: knowing that groups were matched does not, by itself, reveal how the analysis treated that structure. Nor does matching establish balance on characteristics that were not included.

The primary outcome’s usable-scan population raises another general issue: the population enrolled and the population analyzed may not be identical. The record does not report the number with usable scans, so readers cannot evaluate the extent of outcome availability. Reporting denominators for each outcome and group is essential for understanding which participants contributed to a result.

Finally, planning calculations and observed results answer different questions. Planning illustrations can show how assumptions about an effect and analysis translate into a participant target. They are not observed power and cannot establish that a study detected or failed to detect an effect. For this study, the registry record does not provide a protocol-based sample-size justification or the primary numerical outcome results. Keeping those distinctions explicit prevents planning assumptions from being mistaken for evidence.

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 registry record leaves several trial-specific questions unresolved. It describes enrollment of 21 and group descriptions of 11 post-hypoxic former preterm children and 10 healthy term-born children, but does not report the number of participants with a usable structural MRI scan. Since the primary endpoint population is defined by scan usability, the analyzed sample for that endpoint cannot be identified from the record.

The primary outcome is described as a mean volumetric measure in mm^3, with standard deviation, across named dopaminergic circuit structures. The record does not report the values for either group, how the listed structures were combined or reported, or a statistical comparison. This prevents evaluation of the observed effect and its uncertainty. The secondary cognitive performance outcome is named, but its result is not reported in the registry record.

The groups are not randomized. Although the record describes matching by age, sex, and race, it does not report matching procedures or analysis adjustments. It also does not report the analysis model, covariates, outcome distribution, missing-data approach, or sensitivity analyses. Consequently, the possible influence of group differences other than the exposure history cannot be assessed from the record.

The study descriptions include birth-year and gestational-age criteria, but the available record does not provide further detail on recruitment, participant flow, scan quality control, or assessment procedures. The adverse-event denominators are smaller than the cohort counts, and the reason is not reported. These limitations constrain interpretation of both the outcome population and the safety counts, without establishing why the differences occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Measuring Brain Activity of School Age Children — NCT03407729.
• Registry record last updated 2022-10-10; status last verified 2022-10.
• Results first posted 2022-10-10.
• 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.

18. Record Summary

NCT03407729 is a completed observational study sponsored by Case Western Reserve University. It enrolled 21 participants and compares post-hypoxic former preterm children with healthy term-born children. The listed assessments are Magnetic Resonance Imaging and Cognitive Performance Testing.

The primary outcome is structural integrity of dopaminergic circuits, assessed by MRI volumetrics and summarized as a mean with standard deviation in mm^3. The endpoint description names structures in the nucleus accumbens, mamillary body, and hippocampus. The primary outcome population is participants with usable structural MRI scans.

The registry record does not report the primary outcome values, a group comparison, or its uncertainty. The number of participants with usable scans, details of the statistical analysis, and handling of missing data are also not reported in the registry record. Serious and other adverse-event counts are reported as zero in each group, with stated denominators of 9 for the post-hypoxic former preterm group and 7 for the healthy term-born group.