This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Neuroimaging of the Effects of Concerta in the Treatment of ADHD (NCT00778310), a randomized phase 4 study. The primary outcome is Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00778310 |
| Phase | Phase 4 |
| Condition | Attention Deficit Disorder With Hyperactivity |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 76 |
| Arms in the primary outcome | n/a |
| Lead sponsor | The University of Texas Health Science Center at San Antonio |
| Results posted | Yes |
2. Clinical Question
The registry describes a study of whether brain activity during a face-and-shape matching task differed between a Concerta scan and a placebo scan in participants with ADHD. The intended comparison concerns the face-versus-shape BOLD signal difference in the fusiform gyrus and amygdala. The registry’s study summary also states a hypothesis about activity in frontal and cingulate regions and the amygdala, and a possible association between brain changes and clinical improvement. However, the listed primary endpoint is specifically described as the fusiform-gyrus and amygdala signal comparison, and the registry does not report numerical results for it.
Population
Participants with ADHD, including adults and children in the registry’s safety groups. The primary outcome description refers to those who completed both fMRI sessions, but the number completing both is not reported in the registry record.
Intervention
The participant’s usual dose of OROS methylphenidate, identified as Concerta, administered on the morning of an fMRI scan.
Comparator
Placebo administered on the morning of the other fMRI scan. The registry describes both scan conditions as double blind in the arm descriptions.
Primary question
How did the face-versus-shape BOLD signal difference in the fusiform gyrus and amygdala compare between the Concerta and placebo scan conditions?
This is a within-participant question because the planned outcome refers to each subject completing scans under both conditions. A paired comparison can account for stable differences between participants, but the registry does not say which statistical test or model was used. Nor does it provide an estimated contrast, uncertainty interval, or test result. The clinical question can therefore be described from the endpoint definition, but the direction, size, and precision of any observed difference cannot be assessed from the registry record.
3. Trial Design
This is a Phase 4, randomized, triple-masked crossover study. The registry lists an enrollment of 76 and a completed status. It identifies ADHD as the condition under study and lists OROS methylphenidate and placebo as the interventions. In a crossover design, participants receive or are assessed under more than one condition; in this record, each participant’s Concerta and placebo conditions correspond to separate fMRI scan days.
The arm descriptions state that the participant would receive their usual dose of Concerta on the morning of the fMRI scan or receive placebo on the morning of the scan, in a double-blind fashion. The registry separately classifies the overall masking as triple. It does not explain which roles were masked, how masking was maintained, or whether participants, investigators, imaging assessors, or analysts remained unaware of assignment at every stage.
The endpoint timeframe is described as the placebo and drug day, 1-2 weeks apart. The outcome population description says the number who completed both fMRI scans one week apart. These are the registry’s two descriptions; a more precise interval is not reported in the registry record. The record does not describe the order of treatment conditions, the method of random sequence generation, allocation concealment, a washout period, adherence, or how deviations from the intended sequence were handled.
The primary outcome is continuous: a mean face-shape BOLD signal difference, with standard deviation specified as the dispersion measure. Each participant viewed faces and shapes on multiple trials and matched them. The endpoint description says BOLD activity during shape trials was subtracted from activity during face trials, and this value was compared between drug and placebo trials. The number of participants completing both scans, the numerical outcome results, and the statistical analysis are not reported in the registry record. The record lists one outcome measure and zero analyses.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Psychiatric assessment was performed to confirm the diagnosis of ADHD. Fifteen (15) patients were screen failures. Five (5) patients did not respond to an open label trial of Concerta were excluded. 11 withdrew consent or lost to follow up. (1) withdrew to claustrophobia. 43 were exposed to study drug (Concerta and placebo) in crossover design.
Overall Study
| Stage | Adults | Children |
|---|---|---|
| STARTED | 17 | 26 |
| Usable Data | 14 | 21 |
| COMPLETED | 17 | 26 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The number who completed both fMRI one week apart (crossover study, scanned twice
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Adults | Children | Total |
|---|---|---|---|---|
| Participants analysed | 17 | 26 | 43 | |
| Age, Categorical: <=18 years | Participants | 0 | 26 | 26 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 | 0 | 17 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 22.2 (SD 1.78) | 11.3 (SD 2.1) | 15.6 (SD 5.7) |
| Sex: Female, Male: Female | Participants | 2 | 8 | 10 |
| Sex: Female, Male: Male | Participants | 15 | 18 | 33 |
| Region of Enrollment: United States | participants | 17 | 26 | 43 |
6. Primary Endpoint
The registry lists the primary outcome as Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo, measured over Placebo and Drug day, 1-2 weeks apart.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Face-Shape BOLD signal difference |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is titled as the brain oxygenation level dependent signal in the fusiform gyrus and the amygdala on Concerta versus placebo. Its unit is a face-shape BOLD signal difference. In the task, participants viewed faces and shapes and matched the presented items. The endpoint description defines the signal by subtracting BOLD activity during shape trials from activity during face trials, then comparing that value between the Concerta and placebo scan conditions.
BOLD is an fMRI signal used to characterize changes associated with brain activity. In general, a task contrast such as face trials minus shape trials can focus an analysis on differences in the measured signal between task conditions, rather than on either task condition alone. The registry identifies the fusiform gyrus and amygdala as the regions of interest for this listed primary outcome. It does not report region-specific estimates or clarify whether the regions were analyzed separately or jointly.
The registry specifies a mean as the summary parameter and standard deviation as the dispersion measure, indicating a continuous outcome. A mean can describe the average signal contrast, while a standard deviation describes variation in measurements. Neither quantity is numerically reported for the Concerta or placebo condition, and no treatment contrast or confidence interval is available in the registry record. The registry also does not report the completed-scan population size, the processing steps used to derive BOLD values, or how the outcome was handled if a participant’s scan or task data were unusable.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes what comparison the investigators intended to make, but it does not provide the numerical evidence needed to interpret that comparison. There is no reported mean for either condition, no estimated within-participant contrast, no confidence interval, and no p-value. Consequently, the direction and magnitude of any difference in the listed BOLD endpoint cannot be determined from the registry record. The absence of those results in the record is not evidence that the conditions produced identical measurements or that no effect occurred.
The design is a crossover, so the key comparison would ordinarily concern measurements from the same participant under Concerta and placebo. That structure may control for stable participant characteristics when estimating a condition difference. In general, however, a crossover interpretation also depends on the treatment sequence, period effects, carryover, missing scans, and the statistical model. Those details are not reported in the registry record. It is not possible to determine whether such issues were evaluated or how they may have affected the findings.
The outcome is a task-related fMRI signal contrast, not a direct measure of symptoms or day-to-day functioning. The study summary proposes that brain changes could be associated with clinical improvement, but the listed primary endpoint is the BOLD signal difference in specified brain regions. No clinical symptom endpoint or relationship between symptom change and brain activity is reported among the registry entries available in the registry record. The stated hypothesis should therefore not be treated as a reported finding.
Precision also cannot be judged. A confidence interval would show the range of values compatible with the estimated contrast under the analysis assumptions. Because no estimate or interval is reported, readers cannot distinguish a precisely estimated small contrast from an imprecisely estimated larger one. The registry’s enrollment figure does not resolve this issue: the number completing both scans is not reported, and the number contributing to the primary endpoint cannot be inferred.
The record indicates a completed study and lists one outcome measure, but it records zero analyses. This means the posted record does not supply an analysis result to evaluate. It does not establish whether analyses were performed elsewhere, whether results were submitted outside the registry, or what the investigators concluded. Any substantive claim about the observed brain signal difference, its uncertainty, or its clinical meaning would go beyond the reported information.
The safety figures are also limited to the registry’s listed groups and event categories. They show zero reported serious adverse events and zero reported other adverse events in the listed adult and child groups, while death values are null. These entries describe the registry record; they should not be read as a complete assessment of every possible adverse effect or as proof that no events occurred outside the reported categories or observation period.
9. Statistical Methods Explained
What does the crossover design compare?
In general, a crossover design exposes participants to more than one study condition and compares measurements across conditions within the same participants. Here, the registry describes a Concerta scan and a placebo scan for each participant who completed both fMRI sessions. A within-participant contrast can reduce the influence of characteristics that remain stable across sessions, because each participant serves as their own comparator. It does not automatically remove effects that change over time or arise from the order of conditions.
For a crossover analysis, the treatment contrast is typically informed by each participant’s measurement under one condition relative to that participant’s measurement under the other condition. This differs from treating all observations as independent. The registry does not identify the test, model, or variance assumptions used, so no particular crossover analysis can be attributed to this study. It also does not report whether sequence, period, or carryover effects were assessed.
What does the endpoint’s mean and standard deviation describe?
The registry identifies the endpoint as a mean of a continuous measure and names standard deviation as its dispersion measure. In general, a mean describes the central average of observed values, while standard deviation describes how spread out individual values are around that average. A standard deviation is not the uncertainty of the mean; that uncertainty depends on the analysis and the number of usable observations. The registry does not report the condition-specific means or standard deviations, so neither the values nor their variability can be reviewed.
The endpoint is formed from task conditions: the shape-trial BOLD activity is subtracted from face-trial activity. In general, subtraction creates a contrast that emphasizes the difference between two measured conditions. The resulting contrast is then compared between the Concerta and placebo scan conditions. Interpretation depends on the region and signal-processing choices, and the registry record does not provide those processing details or numeric values.
Why does a confidence interval matter?
In general, a confidence interval expresses the uncertainty around an estimated effect under the assumptions of the statistical procedure. It helps readers judge which effect sizes are reasonably compatible with the data, rather than relying only on whether a significance threshold was crossed. A narrow interval indicates greater precision than a wide interval, though precision alone does not establish clinical importance or rule out bias. No treatment contrast or confidence interval is reported in this registry record, so the precision of the primary comparison cannot be assessed.
A p-value, if reported, would quantify how unusual data at least as incompatible with a specified null model would be, assuming that model and its assumptions. It would not measure the probability that the null hypothesis is true or the size of a treatment effect. No p-value or test statistic is reported. There is therefore no basis in the registry record for describing the primary comparison as statistically significant or nonsignificant.
What is over-dispersion, and is it reported?
General explanation: over-dispersion occurs when observed variability exceeds what a statistical model assumes. If a model understates variability, standard errors can be too small and intervals or tests can appear more certain than warranted. This issue is especially relevant to some count-data models; the listed primary endpoint is continuous, and the record does not report an over-dispersion assessment or a model. It would not be appropriate to claim that over-dispersion occurred in this study.
What can be inferred from the design labels?
Randomization is intended, in general, to reduce systematic differences in assigned treatment order. Triple masking is a registry design classification intended to indicate masking across multiple roles, but the registry does not specify those roles or the masking procedures. The arm descriptions say the scan-day Concerta and placebo administration was double blind. These labels alone do not establish that allocation or masking was successfully maintained, nor do they disclose the sequence-generation method or allocation concealment.
What does the sample-size planning information mean?
The registry’s planning description says the sample-size illustration is based on the observed effect rather than the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. It also distinguishes planning outputs for time-to-event data from those for other outcomes. These assumptions describe a planning illustration, not observed power and not the analysis plan used for this crossover study. No planning output values are reported in the registry entries, and the illustration cannot substitute for a reported treatment estimate or uncertainty interval.
The registry does not report an analysis plan, handling of repeated measurements, adjustment for multiple testing, missing-data method, or the population included in the final endpoint analysis. Thus, general statistical principles can explain what the design and outcome terms mean, but they cannot establish which methods the investigators actually used.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and zero analyses. It does not report the statistical analysis plan, a hierarchy of outcomes, adjustments for multiple comparisons, or whether the fMRI regions and task contrasts were selected before examining the data. The study summary mentions several brain regions and clinical improvement, while the listed primary endpoint names the fusiform gyrus and amygdala. The record does not clarify how those broader hypotheses relate to the prespecified outcome or whether additional exploratory comparisons were conducted.
In general, multiplicity arises when multiple outcomes, regions, time points, or analyses are tested. Repeated testing can increase the chance of finding an apparently notable result by chance unless the analysis strategy accounts for the set of comparisons. This general concern cannot be quantified for this study because the full analysis set and any adjustment procedure are not reported in the registry record.
Missing-data handling is also not reported. The outcome description refers to participants who completed both fMRI sessions, but the number who did so is not stated. The record does not provide reasons for non-completion, the amount of unusable scan data, or an approach to missing observations. It is therefore not possible to assess whether the analyzed participants differed from those who did not complete both sessions.
The analysis population is not specified beyond the endpoint’s reference to completing both scans. There is no reported intention-to-treat, per-protocol, or other analysis-population definition, and no account of how treatment sequence deviations were handled. These omissions limit assessment of the risk of selection bias and the reproducibility of the reported analysis, which is itself not included in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Adults | 0 | 17 | 0.0% |
| Children | 0 | 26 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Adults | 0 of 17 |
| Children | 0 of 26 |
The registry lists safety figures separately for adults and children. For adults, it reports 17 at risk for serious adverse events and 0 affected; it also reports 17 at risk for other adverse events and 0 affected. For children, it reports 26 at risk for serious adverse events and 0 affected; it also reports 26 at risk for other adverse events and 0 affected. No serious adverse-event terms are listed.
These figures describe the entries in the registry, not a complete safety profile. The record does not provide event definitions, observation duration, severity details beyond the serious-versus-other categories, attribution to treatment, or a breakdown by Concerta and placebo period. It is not reported whether participants could contribute safety information under both conditions or how events were counted across periods.
Death entries are null for both groups. A null value is not the same as a reported zero; deaths are not reported in the registry record. The zero affected entries refer to the listed event categories and should not be interpreted as proof that no adverse effects of any kind occurred. They also do not establish comparative safety between Concerta and placebo, because condition-specific safety results are not reported.
12. What the Result Does, and Does Not, Mean
The registry record identifies a randomized, triple-masked crossover study designed to compare a task-related fMRI signal under Concerta and placebo conditions. It defines a continuous endpoint based on the difference between face-trial and shape-trial BOLD activity, with the comparison focused on the fusiform gyrus and amygdala. These details establish the study question and some features of its design.
They do not establish what the study found. No condition-specific endpoint values, treatment contrast, confidence interval, p-value, or analysis result is reported. The registry therefore does not support a conclusion about the direction, size, or precision of a brain-signal difference. The absence of a reported result should not be interpreted as evidence for no difference.
The endpoint is a brain-imaging measure, not a direct clinical outcome. Although the study summary describes a hypothesis linking brain changes with clinical improvement, the registry does not report such an association or a clinical symptom result. A difference in an imaging measure, if established, would not by itself show a change in symptoms or functioning.
The safety entries report zero affected in the stated serious and other adverse-event categories for the adult and child groups. They do not provide condition-specific comparisons, and null death values do not report an observed zero. These entries should be understood within the scope of what the registry records, rather than as a comprehensive statement about all safety outcomes.
Overall, the record allows a careful description of the intended comparison, design, endpoint, and limited safety entries. It does not allow evaluation of treatment effect, statistical significance, clinical importance, precision, or robustness. Those judgments require outcome estimates and details of the analysis that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study raises a statistical question that differs from a straightforward comparison of separate treatment groups. Because the registry describes a crossover and an endpoint based on participants completing both scans, the relevant contrast is within participants. That design can make use of paired measurements, but valid interpretation depends on sequence and period considerations as well as the handling of incomplete scan pairs. The record identifies the design but does not report the analysis used to address those issues.
The endpoint also illustrates the distinction between a measured signal and a clinical outcome. It is a task-based fMRI contrast created from face and shape trials, compared across Concerta and placebo sessions. Statistical evidence about this signal would answer a question about the imaging measure; it would not alone answer whether symptoms changed or whether any brain-signal change was clinically meaningful. The registry’s summary mentions clinical improvement as a hypothesis, but no such result is reported.
Precision is central to interpreting a continuous endpoint. A point estimate without uncertainty can be misleading, and a significance result without an estimate would not describe the magnitude of a contrast. In this record, neither is available. The endpoint definition and design labels are informative, but they cannot replace a numerical estimate, interval, and clear account of the analysis population.
The record also demonstrates why registration details and posted outcome data need to be read separately. It reports an enrollment of 76 and completed status, yet does not report the number with both scans or any analysis result. Enrollment alone does not identify the information available for the primary comparison. The missing result and analysis details limit both interpretation and reproducibility.
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.
Several limitations specific to this record restrict interpretation. The numerical results for the primary BOLD endpoint are not reported, and the registry lists zero analyses. There is no estimate of the difference between Concerta and placebo, no confidence interval, and no test result. The record therefore cannot establish the observed direction, magnitude, or precision of the primary comparison.
The primary outcome description refers to participants who completed both fMRI sessions, but the size of that population is not reported. The enrollment figure does not show how many participants completed both scans or contributed usable data. Reasons for missing or unusable scans and methods for handling missing data are also not reported in the registry record.
The crossover design is identified, but sequence generation, treatment order, allocation concealment, washout, period effects, and carryover handling are not described. The record gives two slightly different descriptions of scan spacing: the endpoint timeframe says placebo and drug days were 1-2 weeks apart, while the population description says the scans were one week apart. A more precise timing is not reported in the registry record.
The registry labels the study triple-masked, while the arm descriptions state double-blind administration on scan days. It does not identify which roles were masked or describe how masking was maintained. It also does not report the statistical model, analysis population, multiplicity strategy, imaging-processing methods, or whether additional regions or outcomes were analyzed. These gaps limit assessment of bias, analytical choices, and reproducibility.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Neuroimaging of the Effects of Concerta in the Treatment of ADHD — NCT00778310.
- Registry record last updated 2012-07-13; status last verified 2012-04.
- Results first posted 2012-07-13.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The record describes NCT00778310, a completed Phase 4 randomized, triple-masked crossover study of Concerta and placebo in ADHD. Enrollment is listed as 76. Participants were to receive their usual Concerta dose or placebo on the morning of an fMRI scan, with scans under both conditions described in the primary outcome information.
The primary endpoint is a mean face-shape BOLD signal difference in the fusiform gyrus and amygdala, comparing activity during face and shape trials between Concerta and placebo conditions. Standard deviation is identified as the dispersion measure. The registry lists one outcome measure and zero analyses; numerical outcome results and the number completing both scans are not reported in the registry record.
Safety entries list zero serious and zero other adverse events affected in the adult and child groups. Death values are null rather than reported zeros. The record does not include a statistical analysis plan or enough outcome information to assess the treatment contrast, its uncertainty, or its clinical meaning.