Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol (NCT01013870), a randomized phase 2 study. The primary outcome is Rivermead Post-Concussion Symptoms Questionnaire, at 3 Months After Injury..

2. Clinical Question

The broader protocol aimed to improve assessment of problems after mTBI and included three observational studies involving mental-function and behavior testing, brain imaging, and blood samples. Its fourth study tested atorvastatin. The registry’s stated rationale notes the challenge of distinguishing symptoms associated with head injury from symptoms associated with other conditions, including post-traumatic stress disorder (PTSD). The drug comparison therefore sits within a larger diagnostic and translational research effort; the reported primary outcome addresses post-concussion symptoms, not the full set of diagnostic aims.

The clinical question is limited to the recorded 3-month RPQ outcome in the two randomized groups. Other listed outcomes include mental and physical health scores, PTSD symptoms, resilience, depression, memory, and processing-speed measures. The registry lists these as secondary outcomes, but their results are not reported in the record summarized for this analysis.

3. Trial Design

This was a phase II, randomized, parallel-group trial comparing atorvastatin with placebo in participants with mTBI. The registry classifies masking as quadruple. It lists Baylor College of Medicine as the sponsor and records the study as terminated. The start date is 2010-02, and the primary completion date is 2015-03. A reason for termination is not reported in the registry record.

The registry reports an enrollment of 52. The arm descriptions, however, refer to a plan involving 200 mTBI subjects and assignment of 100 to each arm. Those descriptions therefore do not describe the enrollment recorded for this trial. The registry does not explain the relationship between the planned numbers in the arm descriptions and the recorded enrollment of 52, nor does it report a reason for any difference.

The atorvastatin description specifies a daily weight-based dose of 1mg/kg, up to 80 mg, for seven days, beginning within 24 hours of mTBI. The placebo is described as an inert preparation visually indistinguishable from the active agent. The placebo description is truncated, so its complete administration schedule is not reported in the registry record. Details such as the randomization procedure, concealment method, and masking procedures are also not reported in the registry record.

The primary outcome was the RPQ at 3 months after injury. The primary-outcome population described in the record consists of 27 participants in the atorvastatin group and 22 in the placebo group. The safety summaries use different group counts, which are described separately in the safety interpretation. The registry does not report a detailed statistical analysis plan, the intended analysis population for all outcomes, or how missing outcome data were to be handled.

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 analysis population includes all 27 patients in the atorvastatin group who completed the study and the 21 placebo group patients who completed the study plus one lost to follow-up at 6 months but had completed all of the outcome assessments for the primary and secondary outcomes at 3 months (for a total of 22 placebo group patients).

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 Rivermead Post-Concussion Symptoms Questionnaire, at 3 Months After Injury., measured over 3 months after injury.

The primary endpoint is the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) score at 3 months after injury. The RPQ is a 16-item self-report measure covering commonly reported symptoms after concussion. For each item, the participant rates the current symptom in relation to the level before injury. This comparison is intended to distinguish new symptoms or worsening of pre-existing symptoms from symptoms that were already present at the same level before the injury.

Each item is scored from 0 to 4, with 0 meaning the symptom was not experienced and higher item scores representing increasing severity, up to a severe problem. The total score sums symptoms that are new or have worsened compared with pre-injury levels. The stated total-score range is 0-64. A higher total therefore represents a greater reported burden of new or exacerbated symptoms on this measure.

Using a symptom questionnaire gives the trial a defined way to summarize participants’ reported post-concussion problems at a specified follow-up time. A 3-month assessment captures symptoms after the immediate injury period, while remaining a self-report outcome rather than a direct measure of brain injury or a diagnostic test. It also cannot by itself establish why a particular symptom occurred. In the registry record, the endpoint is summarized by the median and full range for each group, rather than by a reported adjusted comparison or confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is reported as a median and full range. This choice describes a typical observed score and the span of scores in each group without requiring the reader to assume that scores follow a symmetric, bell-shaped distribution. The RPQ is bounded and consists of summed symptom ratings, so a median can be a useful descriptive summary when scores are unevenly distributed or include a concentration of low values alongside some larger values.

What does the median tell us?

In general, the median is the middle value when observations are ordered. It is less influenced by unusually high or low observations than the mean, but it does not describe the shape of the full distribution. Here, the reported medians are 2.0 for atorvastatin and 3.5 for placebo. They summarize the center of the observed scores in each group; they do not alone quantify uncertainty in the difference between groups or show how many participants had scores near either median.

What does the full range tell us?

In general, a full range reports the smallest and largest observed values. The atorvastatin group’s reported range is 0.0 to 49.0, and the placebo group’s is 0.0 to 54.0. A range can make the spread of observations visible, but it depends on just the two most extreme values and does not describe how scores are distributed between them. It is not a confidence interval. The registry does not report a measure of spread such as an interquartile range for this outcome.

Why is a confidence interval useful?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity, such as a difference between group outcomes. Its width reflects how precisely that quantity has been estimated under the method used. The registry record does not report a confidence interval for the primary comparison. Without one, readers cannot use the posted summaries to assess the range of values that remain compatible with an estimated group contrast. A confidence interval would not, by itself, resolve questions about bias, missing data, or whether the analysis was prespecified.

Why does the analysis population matter?

In general, an analysis population defines which participants contribute to a particular result. The population described for the primary outcome includes 27 participants in the atorvastatin group and 22 in the placebo group. The record explains that the placebo count includes 21 participants who completed the study and one participant lost to follow-up at 6 months but with 3-month primary and secondary outcome assessments completed. The stated population therefore uses 3-month assessment availability for that participant rather than requiring completion through the later follow-up. The registry does not report a full account of all randomized participants by arm or the handling of any other missing observations.

What can the planning illustrations show?

In general, sample-size calculations describe how many participants would be needed under stated assumptions to detect a chosen effect with a chosen level of statistical power. They are planning illustrations, not evidence that a trial actually had a particular probability of finding a result. The registry’s stated illustration method uses a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. The registry does not report that these assumptions were the trial’s original design plan, and the displayed calculations should not be read as observed power.

Sample-size estimates based on an observed effect are especially dependent on that estimate. In general, an observed effect from a small study can be imprecise, so planning estimates derived from it can also be unstable. The posted illustrations can be read as conditional planning scenarios rather than as a definitive statement about the study’s original design or its ability to answer the clinical question. The registry does not report an original sample-size justification.

Why might score distributions matter?

In general, statistical methods that assume normally distributed outcomes can perform poorly if data are highly skewed, clustered near a scale boundary, or contain a small number of extreme observations. For such data, robust or rank-based methods may be considered, depending on the estimand and analysis plan. This is a general methodological consideration, not a claim about the unreported individual RPQ scores in this trial. The posted medians and ranges do not provide enough detail to assess the shape of the score distributions or determine which comparison method was used.

The registry reports no primary comparison analysis, adjustment model, or uncertainty interval. It also does not report whether any interim analyses occurred, whether covariates were planned, or how the stopping status related to statistical decisions. Those details are not reported in the registry record, so no particular method should be attributed to the study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight secondary outcomes in addition to the primary RPQ outcome. These include mental and physical health scores, a civilian PTSD checklist, resilience, depression, memory, and oral and written symbol-digit scores. Considering multiple outcomes can create a multiplicity issue: in general, the more statistical tests performed, the greater the chance that at least one result appears notable by chance if each test is interpreted separately. Researchers may address this through a prespecified hierarchy, adjusted significance thresholds, or other strategies. The registry record does not report a multiplicity strategy, an outcome hierarchy, or results for the listed secondary measures.

The registry reports no analysis count for posted outcome analyses, and it does not provide a detailed statistical analysis plan. It is therefore not possible to determine whether the primary outcome was analyzed according to a prespecified plan, whether all intended analyses were reported, or whether any multiplicity adjustment was used. These details are not reported in the registry record.

Missing-data handling also affects interpretation. For the primary outcome, the record describes 27 participants in the atorvastatin group and 22 in the placebo group. The latter includes 21 participants who completed the study and one participant who was lost to follow-up at 6 months but had completed the 3-month primary and secondary assessments. This documents one follow-up distinction, but it does not establish how all missing outcomes were handled or whether there were other missing observations. The registry does not report the number randomized to each arm, a complete participant flow, or sensitivity analyses for missing data.

In general, analyses restricted to participants with observed outcomes can differ from analyses that include all randomized participants, particularly if the chance of having an observed outcome is related to the outcome itself. The record does not give enough information to judge whether missingness could have influenced these summaries. The endpoint population should therefore be read as the described observed-outcome population, not assumed to represent a particular intention-to-treat or per-protocol strategy.

11. Safety Results

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

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The safety summaries report zero serious adverse events among 28 participants at risk in the atorvastatin group and zero among 24 at risk in the placebo group. These are counts of serious adverse events, not proof that no serious event could occur or that the groups have identical safety profiles. The record does not report a list of serious adverse-event terms; no serious terms are listed.

Other adverse events are reported for 11 of 28 participants at risk in the atorvastatin group and 10 of 24 at risk in the placebo group. These are participant counts as represented in the registry summary, not a complete description of event types, severity, timing, or recurrence. The registry does not report those additional details in the safety information.

The safety denominators differ from the primary-outcome group counts: the safety summary has 28 and 24 participants at risk, while the primary outcome has 27 and 22 participants. The reasons for these differences are not reported in the registry record. Death counts are not reported in the registry record. The safety data should be interpreted as limited descriptive counts; they do not provide a formal comparative safety analysis or establish whether any event was related to study treatment.

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

The posted results establish that the registry records 3-month RPQ medians of 2.0 for the atorvastatin group and 3.5 for the placebo group, with full ranges of 0.0 to 49.0 and 0.0 to 54.0, respectively. They also establish the sizes of the described primary-outcome populations: 27 in the atorvastatin group and 22 in the placebo group. These are descriptive findings for the participants with the outcome assessments represented in the registry.

They do not establish that atorvastatin caused a change in symptoms, that one group had a statistically reliable advantage, or that the groups were equivalent. The registry does not report an estimated between-group contrast, confidence interval, or p-value. Without these, the precision of a comparison cannot be assessed from the posted outcome summaries alone. The medians do not show how much participants’ scores changed from before injury, because the registry reports the group-level endpoint summaries rather than individual changes.

The results also do not resolve the broader diagnostic aims of the integrated protocol. The protocol description includes observational work on mental functions and behavior, brain imaging, and blood samples, but the outcome summaries described for this analysis concern the RPQ and safety counts. The registry lists eight secondary measures, but their results are not reported in the registry record.

The study status is terminated, and the reason is not reported in the registry record. Overall enrollment is 52, while arm descriptions refer to a planned 200 participants. The record does not explain this difference. These registry entries are relevant context when considering the amount of information available, but they do not explain why the study was terminated or establish the quality or direction of any treatment effect.

The results should therefore be read as limited registry-reported summaries of symptoms and adverse events, not as a complete account of the trial’s statistical evidence. Additional outcome distributions, a clearly specified comparative analysis, uncertainty estimates, participant flow, and the reason for termination are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registry record places a randomized drug comparison inside a broader integrated protocol. The larger stated aim was to improve diagnosis after mTBI and assess a drug in a setting where symptoms may also be associated with conditions such as PTSD. The primary endpoint is a symptom questionnaire, which captures participants’ reported symptom burden but does not by itself distinguish the cause of symptoms.

The contrast between the overall enrollment of 52 and the 200 participants described in the arm descriptions makes the relationship between intended and recorded enrollment important context. The registry does not explain the difference or the reason for termination. Those gaps limit how fully readers can reconstruct the study’s conduct and planned scope from the registry record.

The outcome is presented with medians and ranges rather than an estimate of the between-group contrast and its uncertainty. This illustrates a key statistical distinction: descriptive summaries tell readers what was observed in each recorded group, while an inferential comparison estimates how compatible the data are with different underlying group effects. The former is available; the latter is not reported in the registry record.

The primary-outcome and safety populations also differ. This emphasizes why denominators need to be tied to the outcome being described rather than treated as interchangeable. The recorded 3-month assessments include a placebo participant who was lost to follow-up at 6 months, while the safety counts use larger group totals. These details affect the interpretation of who contributed to each summary.

Finally, the registry lists multiple secondary outcomes but does not report their results or a strategy for handling multiple comparisons. The case therefore highlights the importance of complete outcome reporting, analysis-plan transparency, and uncertainty estimates when interpreting randomized-trial results. These statistical considerations help define what the record can support without extending the findings beyond the reported information.

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 gives only a limited account of the trial’s statistical methods. It does not report the primary between-group analysis, the estimate used for comparison, a confidence interval, or a p-value. It also does not report whether any covariate adjustment was planned or used. Consequently, the posted medians and ranges cannot be converted into a formal conclusion about the comparative effect.

The recorded primary-outcome population is modest in size, with 27 atorvastatin participants and 22 placebo participants. The record does not give the number randomized to each arm or a complete participant-flow account. It reports an overall enrollment of 52, whereas the arm descriptions refer to 200 participants. The reason for this difference is not reported. The study is listed as terminated, but its reason and timing are not reported.

Only group medians and full ranges are reported for the primary outcome. Individual-level scores, additional distribution summaries, and changes from pre-injury levels are not reported. Thus, readers cannot assess distribution shape, identify how many observations lie near the extremes, or evaluate within-participant change from these summaries.

The record describes a placebo participant who was lost to follow-up at 6 months but had completed 3-month primary and secondary assessments. It does not describe the handling of other missing data, provide sensitivity analyses, or explain whether the analysis population followed an intention-to-treat principle. The safety population also differs from the primary-outcome population, and the reason is not reported.

Although eight secondary outcomes are listed, their results and the approach to multiplicity are not reported in the registry record. The safety information gives counts but not event descriptions, timing, severity, or treatment relatedness. These limitations restrict the conclusions that can be drawn from the registry summaries and prevent a complete evaluation of the trial’s statistical and safety evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Mission Connect Mild Traumatic Brain Injury (TBI) Integrated Clinical Protocol — NCT01013870.
• Registry record last updated 2017-01-09; status last verified 2016-11.
• Results first posted 2016-11-17.
• 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 Mission Connect Mild Traumatic Brain Injury Integrated Clinical Protocol is recorded as a phase II, randomized, quadruple-masked, parallel-group study sponsored by Baylor College of Medicine. It compared atorvastatin with placebo in a drug study for people with mTBI. The registry lists an enrollment of 52, a start date of 2010-02, a primary completion date of 2015-03, and a terminated status.

The primary outcome was the RPQ at 3 months after injury. The median was 2.0, with a full range of 0.0 to 49.0, for 27 atorvastatin participants; the placebo median was 3.5, with a full range of 0.0 to 54.0, for 22 participants. The registry does not report a formal comparison or uncertainty estimate for these summaries. Serious adverse events were reported for zero participants in each safety group; other adverse events were reported for 11 of 28 atorvastatin participants and 10 of 24 placebo participants.

The registry does not report the reason for termination, a complete statistical analysis plan, or results for the listed secondary outcomes. It also does not explain why the arm descriptions refer to 200 participants while the recorded enrollment is 52.