Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy (NCT02003183), a registered phase not stated study. The primary outcome is Distribution Volume Ratio (DVR).

2. Clinical Question

The underlying clinical motivation is that the record describes CTE as a progressive degenerative brain disease associated with repetitive traumatic brain injury, with possible personality, behavioral, mood, cognitive, and motor symptoms. It also notes that definite diagnosis was possible through neuropathological examination after death. The project was intended to study imaging in living people at risk, not to establish a randomized treatment effect or to report whether an imaging result can diagnose CTE. Its central question is therefore descriptive: what [F-18]FDDNP-PET patterns are observed in this selected group? The record does not report a diagnostic threshold, comparison with a definitive diagnosis, or results establishing diagnostic accuracy.

3. Trial Design

The record identifies this study as NCT02003183, titled “Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy,” with the official title “FDDNP-PET Imaging in Persons at Risk for Chronic Traumatic Encephalopathy.” The sponsor is the University of California, Los Angeles. Its status is completed, and the recorded start and primary completion dates are 2013-03 and 2018-10.

The study objective was to determine brain imaging patterns with [F-18]FDDNP-PET in people with suspected CTE. The described group consisted of 22 participants with suspected CTE. Each received clinical and neuropsychological assessments, [F-18]FDDNP-PET scans, and magnetic resonance imaging (MRI) scans. Computed tomography scans were used for participants who could not tolerate MRI, to assist in identifying PET regions of interest.

The total enrollment is listed as 24, while the arm description says 22 participants were studied. The disposition of the remaining participants, and the reason for the difference between these figures, are not reported in the registry record. The record does not state allocation. It does not describe a randomized comparison, and its listed groups should not be interpreted as equivalent randomized arms. Military personnel and players are named as groups in the adverse-event information, but their role in the study design beyond that safety listing is not reported in the registry record.

The primary outcome is a continuous measure recorded at baseline. The registry lists one outcome measure and one analysis. It does not report the analysis method, the statistical model, covariate adjustment, or a comparison between groups. Details of recruitment criteria, follow-up beyond the baseline outcome timeframe, and a protocol-defined sample-size justification are not reported in the registry record. The available description supports interpreting this as an imaging study in a suspected-CTE group, rather than as a test of treatment efficacy.

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:

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: All participants had suspected CTE because of a history of traumatic brain injury and cognitive and/or mood symptoms. Of the 24 participants, 2 were lost to follow up and not included in the data analysis.

6. Primary Endpoint

The registry lists the primary outcome as Distribution Volume Ratio (DVR), measured over Baseline.

The primary endpoint is Distribution Volume Ratio (DVR), measured at baseline. It is defined as the volume of [F-18]FDDNP bound in a region of interest divided by the amount of [F-18]FDDNP in the cerebellum, which serves as the reference region. The record describes higher ratios as indicative of higher levels of tau and amyloid proteins within the region of interest. DVR is a continuous measure, and the listed summary measure is the mean with standard deviation.

As a general statistical explanation, a ratio can express a target-region measurement relative to a reference region, helping describe the imaging signal in a way that accounts for the selected reference. The meaning of any particular DVR value depends on the measurement procedure, the regions being evaluated, and the context of the study. The registry record does not give observed means or standard deviations, region-specific results, or a threshold for interpreting an individual participant’s value.

The endpoint was used to characterize tracer binding patterns, not to report a clinical diagnosis or a treatment response. Although the study’s motivation concerns identifying imaging tools for research in living people at risk, diagnostic performance is not reported in the registry record. There are no reported sensitivity, specificity, predictive values, or direct comparisons against neuropathological examination. The posted information therefore defines what DVR measures and why it was collected, but does not quantify the observed endpoint or show how well it separates people with and without CTE.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is DVR?

The registry identifies DVR as a continuous outcome summarized by a mean and standard deviation. A continuous variable can take values along a measurement scale rather than being limited to categories. The mean describes the central value of a set of measurements, while the standard deviation describes how dispersed individual measurements are around that mean. These are general statistical definitions. The actual mean and standard deviation for this study are not reported in the registry record, so the distribution and variability of its observed DVR values cannot be assessed from the posted results.

The endpoint is a ratio: tracer binding in a region of interest relative to binding in the cerebellum. As a general matter, ratios can be useful when the scientific question concerns a relative measurement, but their interpretation depends on the numerator, reference, measurement procedures, and study context. Here, the registry defines the biological interpretation of a higher ratio, but it does not provide region-specific estimates or details sufficient to evaluate measurement reliability.

What does a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical procedure. It helps readers distinguish a relatively precise estimate from one that is compatible with a broader range of values. A confidence interval is not reported for the primary outcome in the registry record. Consequently, the precision of the DVR estimate cannot be judged from the recorded information. The absence of an interval is not evidence that the estimate is precise or imprecise; it means that the interval-based assessment is unavailable.

Why does study design matter?

For a randomized comparison, allocation can support a causal interpretation when the study is otherwise appropriately conducted and analyzed. This record is not a randomized comparison, and allocation is not stated. The group labels in the safety information do not establish a randomized design or a control condition. As a general principle, differences between non-randomly formed groups may reflect differences in who entered each group, how they were measured, or other factors, rather than an effect attributable to a study intervention. No group comparison of DVR is reported in the registry record.

The study description includes assessments and imaging in the suspected CTE group. MRI or, when MRI could not be tolerated, computed tomography was used to assist PET region-of-interest identification. Those details explain the imaging context, but the record does not report whether region selection was blinded, how reproducibility was evaluated, or how missing or unusable scans were handled.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. Such an illustration is a planning exercise, not a report of achieved power and not evidence that the original study was designed around those assumptions. The record does not provide the planning outputs or a protocol-based sample-size justification in the registry record for this study.

In general, a sample-size calculation estimates how many observations might be needed under specified assumptions to detect a particular effect with a chosen statistical operating characteristic. The result depends on assumptions about the effect, variability, allocation, significance level, and analysis. If an assumed effect is based on an observed estimate, uncertainty in that estimate can affect the usefulness of the illustration. No planning illustration should be read as observed power: observed power is not a substitute for reporting an effect estimate and its uncertainty.

What statistical analysis is reported?

The registry lists one outcome and one analysis, but the specific analysis procedure is not reported in the registry record. There is no stated test, regression model, adjustment set, or inferential result in the available information. It is therefore not possible to determine whether the reported analysis used a particular distributional assumption, addressed repeated or regional measurements, or adjusted for covariates. General statistical concepts can explain why those choices matter, but they cannot fill in an analysis method that the record does not state.

Over-dispersion is a general issue when data vary more than a statistical model assumes. If a model underestimates variability, its standard errors and intervals may be too small, making results appear more precise than they are. This concept cannot be evaluated for this continuous endpoint without the observed data and model details. The record does not report evidence of over-dispersion or a method used to assess it.

Similarly, multiple testing can increase the chance of at least one apparently notable result when many outcomes, regions, or comparisons are examined. This is a general reason to identify prespecified analyses and any multiplicity adjustment. Although one outcome measure and one analysis are listed, the registry record does not describe the full analysis plan, whether additional exploratory analyses occurred, or any multiplicity procedure. No conclusion about adjustment can be drawn from the count of listed outcomes alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and one analysis. It does not report the complete statistical analysis plan, whether additional regions or exploratory outcomes were evaluated, or whether any multiplicity adjustment was used. A single listed outcome does not establish that only one statistical comparison was conducted. In general, multiplicity matters when researchers evaluate multiple outcomes, regions, time points, or subgroups, because repeated testing can increase the chance of a seemingly unusual result. Whether that issue arose in this study is not reported in the registry record.

The primary outcome timeframe is baseline. The record does not report missing primary-outcome values, the number of participants contributing DVR measurements, reasons for missing measurements, or an approach to missing data. Overall enrollment is listed as 24, while 22 participants with suspected CTE are described as studied; the reason for this difference is not reported in the registry record. It should not be assumed that either count is the denominator for every outcome analysis.

The analysis population is also not specified. The registry record does not state whether analyses included all enrolled participants, only those with usable scans, or another defined group. It does not describe exclusions after enrollment or any imputation procedure. In general, missing-data handling and the analysis population can affect how an estimate should be interpreted, particularly if the availability of a measurement is related to participant characteristics or the outcome. Without participant-flow and analysis details, the extent and potential implications of missing data cannot be assessed.

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 serious adverse-event fields list Military Personnel with 7 at risk and 0 serious adverse events, and Players with 15 at risk and 0 serious adverse events. The record lists 0 deaths for each group. It also records 0 other adverse events in each group. These are the counts entered in the registry record; they describe the recorded safety information, not proof that no events occurred outside the reported categories or observation period.

The listed safety groups should not be treated as randomized arms or as like-for-like comparison groups. The registry record does not explain the relationship between these safety categories and the 22 participants described as studied, nor does it report the safety observation period, event-collection procedures, or detailed non-serious event terms. The absence of listed serious adverse-event terms does not provide information about the completeness of event ascertainment.

In general, adverse-event counts are interpreted in relation to the number of people observed, duration of observation, and methods used to collect events. Those details are not reported in the registry record. The zero counts should therefore be read narrowly as the entries recorded for these groups, rather than as a broad conclusion about safety or a comparison of risk.

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

The study addresses an important measurement question: whether [F-18]FDDNP-PET can characterize imaging patterns in people suspected of having CTE. The registry record defines DVR as a regional tracer-binding ratio and explains that higher ratios indicate higher levels of tau and amyloid proteins within the region of interest. It also documents a study involving clinical and neuropsychological assessments, PET, and structural imaging. These details establish the study’s purpose and the type of measurement collected.

They do not establish what DVR values were observed. The primary outcome results are not reported in the registry record. Without those values and their uncertainty, readers cannot judge the magnitude, precision, or distribution of the imaging measure in the studied participants. Nor can the record support a claim that imaging patterns distinguished people with CTE from people without it: no control comparison or diagnostic-accuracy results are reported.

The study’s stated motivation is research into methods that could assist detection in living people at risk, given the record’s description of definite diagnosis through neuropathological examination after death. That motivation is not itself evidence of diagnostic validity. Establishing diagnostic performance would require information such as comparison with an appropriate reference diagnosis and reported measures of classification performance; these are not reported in the registry record.

The record also does not describe a randomized intervention comparison. [F-18]FDDNP is listed as a radiation intervention in this imaging study, but the available information does not support interpreting it as a treatment test. No claim about treatment benefit, prevention, or clinical outcomes follows from the listed study objective.

The most defensible interpretation is therefore limited: this completed registry record describes baseline imaging intended to characterize suspected CTE, but it does not report the primary outcome results needed to evaluate what the study found. The safety counts are limited to the recorded categories and groups, and the difference between enrollment and the number described as studied is unexplained. These limits leave the central empirical findings unresolved in the registry record.

13. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the difference between a clearly defined measurement question and a reported result. The registry record identifies DVR, its reference region, its baseline timeframe, and the intended biological interpretation of higher values. That definition helps readers understand what the endpoint represents. But a definition is not an estimate: without observed values and measures of uncertainty, readers cannot evaluate the endpoint’s behavior in this study.

The design context is equally important. The stated objective concerns imaging patterns in people with suspected CTE, and the record does not describe a randomized comparison or state allocation. Recognizing that distinction prevents a descriptive imaging study from being read as evidence of a causal treatment effect or a controlled diagnostic comparison. The military personnel and players listed in safety information do not supply a control comparison by themselves.

It also matters that the record identifies an intended use in research while leaving diagnostic performance unreported. A candidate imaging measure can be scientifically interesting without the registry record establishing whether it classifies individuals accurately or predicts outcomes. Keeping the measurement question separate from claims about diagnosis or clinical utility is central to sound interpretation.

Finally, the enrollment and study counts, absent outcome results, and unspecified analysis population show why participant flow and analysis reporting matter. Statistical conclusions depend not only on the endpoint’s definition but also on who contributed data, how uncertainty was handled, and what comparisons were made. Those details are not reported in the registry record. The record is useful for understanding the study’s aim and measurement framework, but it does not provide enough outcome information to assess the primary empirical result.

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 for interpretation is that primary DVR results are not reported in the registry record. No means, standard deviations, region-specific estimates, confidence intervals, or inferential results are available in the record details. The size and precision of the measured signal therefore cannot be assessed.

The design description does not identify a like-for-like control group. Allocation is not stated, and the study is not a randomized comparison. The safety categories of Military Personnel and Players do not establish a comparative imaging design. As a result, the record does not support conclusions about differences attributable to a particular exposure or intervention.

The record lists overall enrollment as 24 and describes 22 participants with suspected CTE as studied, without explaining the difference. It does not state the number contributing to the primary outcome or identify the analysis population. Participant flow, scan usability, missing outcome data, and any exclusions are not reported in the registry record.

Further imaging and analysis details are also absent. The record does not report region-specific results, assessment of measurement reliability, the analysis model, covariate adjustment, or whether region selection was blinded. The complete statistical plan and any approach to multiplicity are not reported. The registry’s stated aim and endpoint definition cannot substitute for these details.

Finally, the record does not report diagnostic-accuracy comparisons against a reference diagnosis or longitudinal predictive results. Its rationale concerns detection research in living people, but the posted information does not establish diagnostic performance, clinical usefulness, or effects on patient outcomes. These are limits of what can be concluded from this registry record, not proof that the study did or did not produce additional analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy — NCT02003183.
• Registry record last updated 2020-03-03; status last verified 2020-02.
• Results first posted 2019-11-27.
• 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.

18. Record Summary

NCT02003183 is a completed University of California, Los Angeles study titled “Traumatic Brain Injury and Risk for Chronic Traumatic Encephalopathy.” Its stated aim was to determine [F-18]FDDNP-PET imaging patterns in participants with suspected CTE. The record lists enrollment of 24 and describes 22 participants with suspected CTE as studied. Participants received clinical and neuropsychological assessments, PET, and MRI or computed tomography to assist in PET region identification.

The primary outcome is baseline Distribution Volume Ratio, a continuous measure summarized as a mean and standard deviation. The registry record defines the ratio but does not report its observed results. It does not describe a randomized comparison, and allocation is not stated. The safety entries list no serious adverse events or deaths in the Military Personnel and Players groups, with the limits of those recorded categories. The disposition difference, analysis population, missing-data handling, and detailed statistical plan are not reported in the registry record.