Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach (NCT01678209), a randomized phase 4 study. The primary outcome is Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task.

2. Clinical Question

3. Trial Design

The registry identifies this as a Phase 4, randomized, quadruple-masked, parallel study of ADHD treatments and functional imaging. The sponsor is Icahn School of Medicine at Mount Sinai. The study began in 2012-10, had a primary completion date of 2018-04-30, and is recorded as completed. Enrollment is 127. The registry record does not provide the number enrolled in each arm or a detailed account of the randomization procedure.

The study included an atomoxetine arm and a methylphenidate arm, both involving initial evaluation, baseline functional magnetic resonance imaging, flexible dose titration for 6-8 weeks, and a post-treatment scan. The atomoxetine description also mentions optional post-study stabilization visits. The healthy control group had an initial evaluation and two scans 6-8 weeks apart. The registry lists fMRI scans as an intervention as well as the two drug arms.

The primary outcome is a continuous measure: percentage of correct inhibition on the Go-No go task. It is described as a mean with standard deviation, assessed at baseline and at 6 weeks. The record also lists secondary measures covering ADHD symptoms, clinical global severity, attention-task response time, continuous performance, digit span and finger windows. It does not report the detailed protocol, the sample-size justification, the masking procedures, or a prespecified statistical analysis plan. Those details should not be inferred from the trial’s design labels or the listed outcomes.

The overall design places behavioral task performance and imaging in the context of treatment and control observations. The registry’s descriptions do not establish whether all participants completed each assessment, how each outcome was analyzed, or which comparison was designated as the primary treatment contrast.

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 in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. Thirty-one (N=31) controls were scanned twice for this project, but the second scan data for 1 subject was excluded from the analysis for motion. Thus, 31 control subjects were included in the analyses of

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: Only participants with usable data were included in the data results

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task, measured over Baseline and at 6 weeks.

The primary endpoint is the percentage of correct inhibition on a Go-No go task performed inside the scanner. In this task, participants respond to designated go stimuli and withhold a response to no-go stimuli. The registry describes the endpoint as a mean with standard deviation and gives baseline and 6-week assessment times. It also describes the outcome as a comparison of Go-No go performance at 6 weeks from baseline.

In general, an inhibition task is used to assess the ability to withhold a response when a stimulus calls for no response. Correct inhibition therefore represents task performance under that specific instruction. The endpoint is a behavioral measure collected during functional imaging; it is not itself a direct measure of a neural network or of treatment mechanism. Imaging and task performance can address related but distinct questions.

The trial’s rationale concerns possible common and distinct neural mechanisms associated with stimulant and non-stimulant treatments, and whether changes may involve normalization or other adaptations in brain function. The registry record does not report the observed endpoint means, standard deviations, treatment contrasts, confidence intervals, or p-values. It also does not give enough detail to identify the exact primary-outcome comparison. Without those results, the magnitude and precision of any difference in task performance cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as continuous, summarized by a mean and standard deviation. This describes the type of outcome and its planned summary, not the full analysis method. The statistical analysis plan, model specification, handling of repeated measurements and exact primary contrast are not reported in the registry record. The following explanations are general and do not imply that a particular method was used in this trial.

What does a mean and standard deviation describe?

In general, the mean is the arithmetic average of measured values in a group. The standard deviation describes how much individual values vary around that average. For a task outcome expressed as percentage correct inhibition, the mean would describe average task performance, while the standard deviation would describe participant-to-participant variability. A mean and standard deviation alone do not show whether groups differ, how uncertain a difference estimate is, or whether a result is clinically important. Those questions require a defined comparison and an estimate with appropriate uncertainty.

Why does the comparison matter?

General statistical interpretation depends on what is compared. A between-group comparison at 6 weeks answers a different question from a comparison of change from baseline, and both differ from a model using repeated observations over time. The registry describes baseline and 6-week assessments and refers to comparison at 6 weeks from baseline, but does not provide the precise estimand or model. It also does not state which groups form the primary contrast. Without that information and the results, the target effect cannot be reconstructed.

In general, randomization can help balance measured and unmeasured characteristics across assigned groups, but the benefit depends on how allocation was conducted and on the analysis preserving the randomized comparison. The record labels the study randomized, but does not report sequence generation, concealment, stratification, or allocation details. The label alone does not establish that every potential source of bias was prevented.

How should uncertainty be read?

General statistical practice often reports an effect estimate with a confidence interval. The estimate indicates the observed contrast on the outcome scale; the interval conveys its precision under the analysis assumptions. A p-value may also be reported for a specified hypothesis, but does not quantify the effect’s size or establish practical importance. The registry record does not report a primary effect estimate, confidence interval, or p-value. It is therefore not possible to determine the observed magnitude or statistical uncertainty from this record.

The registry gives a description of sample-size planning assumptions for an illustration based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are described as planning assumptions, not as the trial’s original design justification. The record does not report the sample-size justification used to design the trial. A planning illustration is not observed power and cannot replace the trial’s outcome estimates or their uncertainty.

Why can variability affect analysis?

General: variability describes differences among measured values beyond a group average. If observations vary more than a model assumes, standard errors and tests based on that model may not accurately represent uncertainty. Over-dispersion is one such mismatch, when observed variability exceeds what a model’s assumed distribution allows. Appropriate modeling may then require a method that accommodates the extra variation. The registry record does not report a dispersion assessment or a model for this endpoint, so there is no basis for saying over-dispersion occurred in this trial.

Repeated measurements can also be statistically related: a participant’s baseline and follow-up observations are not necessarily independent. General methods for repeated measures account for that dependence, whereas treating observations as unrelated can misstate uncertainty. The registry records baseline and 6-week assessments, but does not report whether the primary analysis used a repeated-measures model, a change score, or a single follow-up comparison. The analysis method should not be inferred from the time points alone.

What does masking contribute?

In general, masking can reduce the influence of expectations on assessments and decisions, depending on who is masked and how masking is maintained. The record labels the study quadruple-masked, but does not identify the masked roles or describe procedures. It is not possible to assess masking success from that label. The registry also does not report details of adherence, treatment exposure or any treatment-related departures from the planned procedures.

Finally, statistical interpretation requires transparent reporting of the analysis population, missing observations, outcome definitions and any multiplicity procedures. These details matter because analytic choices can affect estimates and uncertainty. The registry record leaves these aspects unreported for the primary endpoint; no specific model, correction, or missing-data method should be attributed to the trial on the basis of the available record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary Go-No go endpoint and secondary measures including the Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale, Clinical Global Impressions-Severity, Response Time in Attention Networks Test, Continuous Performance Test, Digit Span and Finger Windows. The record also reports 7 outcome measures and 0 analyses. It does not report which secondary outcomes were analyzed, their results, or how the primary and secondary questions were prioritized.

In general, testing several outcomes, time points or group contrasts creates a multiplicity concern: the chance of at least one apparently notable result can increase when many hypotheses are examined. Statistical approaches can control or otherwise address this issue, but the choice depends on the analysis plan and the questions being tested. Any multiplicity adjustment or testing hierarchy is not reported in the registry record. The record’s note that the primary outcome was not reduced to one comparison because it involved several categories or time points makes the absent analysis details particularly relevant.

The primary-outcome description states that the control group analysis included the subject who could not be scanned twice. It also says 31 controls were scanned twice, but the second scan for 1 subject was excluded from analysis for motion. These statements describe a specific control-group imaging issue; they do not fully explain missing-data handling for the endpoint or treatment arms. The analysis populations for the atomoxetine and methylphenidate arms, the number with usable endpoint data, and any imputation or sensitivity analyses are not reported in the registry record.

In general, missingness can affect interpretation when the availability of an outcome is related to participant characteristics or observed performance. The record does not explain the reasons for missing observations beyond the control scan excluded for motion, or how the analysis accounted for missing data. It is therefore not possible to judge whether the reported analysis population, if any, represents all randomized participants.

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.

Most frequent non-serious adverse event terms

The registry reports serious adverse event counts of 0 in the fMRI Scans group, 0 in the Atomoxetine Arm and 0 in the Methylphenidate Arm. The corresponding numbers at risk are 47, 22 and 22. Deaths are recorded as 0 in each group. These are the posted counts; they do not describe the severity or nature of non-serious events.

For other adverse events, the record lists 3 affected in the fMRI Scans group, 6 in the Atomoxetine Arm and 4 in the Methylphenidate Arm. The numbers at risk are 47, 22 and 22, respectively. No serious adverse event terms are listed. These counts should be read as the registry’s reported figures, not as rates or comparisons; no rates or comparative estimates are reported in the registry record.

In general, a count does not show how events were defined, when they occurred, whether participants experienced more than one event, or how completely events were collected. The record does not provide that detail. Zero reported serious events does not establish that there was no risk, and the other-event counts alone do not establish a treatment effect or a difference in safety between groups.

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

The registry record establishes that the study was designed to examine ADHD treatment and functional imaging, with Go-No go inhibition performance as its primary outcome. It also documents a randomized, quadruple-masked, parallel design, an enrollment of 127, and treatment and control procedures. These details describe the research question and study structure, but they do not constitute evidence about the size or direction of an outcome difference.

The primary endpoint is a behavioral measure collected at baseline and at 6 weeks. In general, a reported group contrast could describe differences in average task performance, with its precision conveyed by an interval or other uncertainty measure. The registry record does not report those estimates. It therefore does not establish whether the groups differed, how large any difference was, or how precisely it was estimated.

The trial rationale discusses shared and distinct neural mechanisms and asks whether improvement might reflect normalization or other adaptive changes. Those are mechanistic questions, not conclusions that follow from the trial’s registration details. A task score, even if a result were available, would not by itself identify a neural mechanism. The record does not report the imaging analyses or results needed to evaluate those mechanistic questions.

The safety counts provide limited descriptive information: serious adverse event and death counts are recorded as zero in each group, while other adverse event counts are also listed. They do not by themselves quantify comparative risk or establish that a treatment is safe or unsafe. The registry record does not supply detailed event descriptions or comparative analyses.

Overall, the posted record supports a description of the study’s aims, assessments, design and recorded safety counts. It does not support a conclusion about treatment efficacy, the presence or absence of a primary-outcome difference, or a treatment mechanism. Those conclusions require outcome estimates and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study brings together treatment, behavioral task performance and functional imaging in a question about possible common and distinct mechanisms of stimulant and non-stimulant ADHD treatment. Statistically, that combination makes it important to distinguish the behavioral endpoint from imaging outcomes and from mechanistic interpretation. Each requires its own clearly defined estimand and analysis; one measure cannot automatically stand in for another.

The design includes two medication arms and a healthy control group, with baseline and follow-up assessments described in the registry. Such a structure can raise questions about which group contrasts and time points address the central research question. The registry record does not report the exact primary contrast or analysis plan. That absence limits the ability to connect the broad mechanistic rationale to a specific statistical test or estimate.

The study also illustrates why registration details and outcome results serve different purposes. Design labels, outcome definitions and timeframes explain what researchers intended to study. Estimates, uncertainty intervals, analysis populations and missing-data methods are needed to evaluate what the observed data indicate. The registry record includes the former but does not report primary-outcome numerical results or analyses.

For clinical researchers and statisticians, the case underscores the importance of transparent reporting across behavioral and imaging outcomes, particularly when a study considers multiple groups, time points and mechanistic questions. Without complete results and analysis methods, readers cannot assess effect magnitude, precision, multiplicity handling or the robustness of conclusions. The statistical importance of the trial is therefore also a reporting lesson: a well-defined question is necessary, but interpretation depends on accessible estimates and methods.

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 does not report numerical results for the primary endpoint, including group means, standard deviations, effect estimates, confidence intervals or p-values. It also says the primary outcome was not reduced to one comparison because it involved several categories or time points. The exact contrast and analysis method are not reported, preventing trial-specific interpretation of the primary question.

Important design and analysis details are absent from the registry record. These include the sample-size justification, allocation procedure, identities of the masked roles, prespecified statistical plan, analysis populations for the treatment arms, missing-data methods and multiplicity procedures. The record’s planning-illustration assumptions do not establish the trial’s original sample-size rationale or actual analysis approach.

The primary-outcome description includes a control-group scan excluded for motion and says the control analysis included the subject who could not be scanned twice. It does not provide a complete account of missing endpoint data across all groups, or explain how the analysis handled incomplete observations. The record also lists no outcome analyses in its posted results.

The registry includes secondary outcome names and adverse event counts, but does not report results for the secondary measures or detailed event descriptions. The healthy control group and treatment arms have different stated procedures, and the record does not specify the principal treatment comparison. These limitations constrain interpretation to the study’s registered design and reported counts; they do not establish that unreported procedures or analyses were not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach — NCT01678209.
• Registry record last updated 2020-07-24; status last verified 2020-07.
• Results first posted 2020-07-24.
• 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

NCT01678209 is a completed Phase 4 randomized, quadruple-masked, parallel study sponsored by Icahn School of Medicine at Mount Sinai, with enrollment of 127. It began in 2012-10 and had primary completion on 2018-04-30. The study examined atomoxetine and methylphenidate alongside a healthy control group, using functional imaging and behavioral assessments.

The primary outcome is mean percentage of correct inhibition on a Go-No go task at baseline and 6 weeks. Secondary measures include ADHD symptom, clinical severity, attention, continuous performance, digit span and finger windows assessments. The registry record reports serious adverse event and death counts of 0 in each group and other adverse event counts of 3, 6 and 4 for the fMRI Scans, Atomoxetine Arm and Methylphenidate Arm, respectively.

Numerical primary-outcome results, outcome analyses, the detailed statistical plan and several analysis and missing-data details are not reported in the registry record.