Atomoxetine PBPK-PD Clinical Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Atomoxetine PBPK-PD Clinical Study (NCT03154359), a registered phase not stated study. The primary outcome is Number of Participants Classified as Responders and Non-responders to Intervention.

2. Clinical Question

The study’s broader aims concern the relationship between atomoxetine exposure and clinical outcomes, while also monitoring side effects and categorizing participants by their ability to tolerate atomoxetine. Those aims frame the research question, but the registry record does not provide the results needed to quantify those relationships.

The primary endpoint is a classification based on change from baseline, not a direct comparison of atomoxetine with a control treatment. The record identifies the analysis population as individuals who completed the 6 week milestone. It does not report how many participants met that criterion or provide the responder and non-responder counts. Accordingly, the research question can be described, but its primary outcome cannot be answered from the registry record.

3. Trial Design

The registry record describes an open-label, single- and multi-dose study of atomoxetine in children with ADHD. Its official title specifies interest in pharmacokinetics, pharmacodynamics, and clinical outcomes among CYP2D6 extensive, intermediate, and poor metabolizers. Atomoxetine hydrochloride is the listed drug intervention. The record identifies Children's Mercy Hospital Kansas City as the sponsor and gives the study status as completed.

The recorded enrollment is 51. The study start date is 2017-12-12, and the primary completion date is 2022-06-01. These administrative details describe the registered study; they do not indicate how many participants contributed to each outcome or analysis.

The primary outcome is a count of participants classified as responders and non-responders, with a 6 weeks timeframe. The analysis population is described as individuals who completed the 6 week milestone. Allocation is not stated. The registry also cautions that this was not a randomized comparison and that the arms are not a like-for-like control comparison. It would therefore be inappropriate to interpret the design as a randomized treatment-versus-control trial.

The registry lists 13 outcome measures and 14 analyses. Those counts alone do not reveal which analyses were primary, how outcomes were prioritized, or whether any statistical adjustment was applied. Details about treatment schedules, the number of groups contributing to each analysis, and the specific statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 51 participants were enrolled in the study. All participants completed a screening visit, and 9 participants screenfailed/were determined to be ineligible.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Individuals who completed 6 week milestone

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 Number of Participants Classified as Responders and Non-responders to Intervention, measured over 6 weeks.

The primary endpoint counts participants classified as responders and non-responders at 6 weeks. The registry defines response as a reduction of at least 40% in the total National Initiative for Children's Healthcare Quality (NICHQ) Vanderbilt Assessment Scale, 3rd edition, score from baseline. The registry identifies the population for this measure as individuals who completed the 6 week milestone.

The scale assesses the presence and severity of 18 DSM-V criteria for ADHD symptoms. Symptoms are rated on a 4-point Likert-type scale, from 0, “Never,” to 3, “Very Often”; the maximum total symptom score is 54. The measure also includes 8 questions assessing functional impairment, called “Performance,” rated on a 5-point scale from 1, “Excellent,” to 5, “Problematic.” The endpoint description defines response by change in the total score, but the registry does not further explain how the performance questions enter that total.

A responder classification makes the outcome interpretable as a count of people meeting a stated threshold, rather than as an average score change. Such a threshold can be useful when the clinical question concerns how many participants cross a predefined response boundary. However, it discards information about the size of score changes within each category: participants just below and well below the threshold are both classified as non-responders. The registry does not report the observed counts, so the endpoint’s results cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a binary primary outcome: participants are classified as responders or non-responders. The endpoint is reported as a count of participants, and its timeframe is 6 weeks. The population is individuals who completed the 6 week milestone. The outcome definition uses a threshold based on change from baseline in the NICHQ Vanderbilt Assessment Scale score.

What does a responder count represent?

In general, a binary endpoint converts an underlying measure into categories using a specified rule. Here, the rule is a reduction of at least 40% in total score from baseline. A count can communicate how many people fall into each category, but interpretation also depends on the denominator: the number of people who could have been classified. The registry does not report the responder or non-responder counts or the number who completed the milestone. It is therefore not possible to calculate or describe an observed response frequency from this record.

Threshold-based outcomes simplify interpretation but lose detail about the original measurement. People on opposite sides of a cutoff may have similar score changes, while people in the same category may have quite different changes. General statistical practice is to consider both the threshold outcome and the underlying score when those results are available. The registry record does not report the underlying score changes for this endpoint.

What can be concluded from the design?

The study is described as open-label, and allocation is not stated. The record cautions that it is not a randomized comparison and that arms are not a like-for-like control comparison. In general, randomization helps balance measured and unmeasured factors across comparison groups, while an open-label design means treatment assignment is not masked from participants and study personnel. Without a randomized control comparison, observed group differences cannot automatically be attributed to treatment. The registry does not provide enough information to assess adjusted comparisons or other methods used to address differences between groups.

The official title identifies extensive, intermediate, and poor CYP2D6 metabolizer groups and describes study aims involving pharmacokinetics, pharmacodynamics, and clinical outcomes. That describes the scientific focus, not the statistical model used. The specific methods for relating exposure or metabolizer group to outcome are not reported in the registry record.

What do the analysis counts and planning assumptions tell us?

The registry lists 13 outcome measures and 14 analyses. These are counts of registered measures and analyses, not a description of the statistical methods. They do not indicate whether analyses were adjusted, whether a hierarchy of outcomes was used, or how many comparisons were tested. The multiplicity plan is not reported in the registry record.

The sample-size planning assumptions describe an 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 stated effect to detect is a specified fraction of the observed effect. These assumptions describe planning illustrations, not the trial’s own design or an observed-power calculation. The planning values and the observed effect needed to interpret them are not reported in the registry record. A sample-size illustration should be read as a scenario under stated assumptions, not as evidence that the study had a particular probability of detecting an effect.

In general, confidence intervals express the range of effect estimates compatible with the data under a statistical model, and their width conveys precision. A p-value addresses how unusual data would be under a specified null model; it is not a measure of clinical importance. Neither an interval nor a p-value for the primary endpoint is reported in the registry record. No statistical model, confidence-interval method, or test for the primary endpoint is specified there.

For count outcomes, the observed counts and the population at risk are both needed to interpret frequency. When modeling event counts across groups, over-dispersion can matter if variability exceeds what a chosen model expects; in general, ignoring it can make uncertainty estimates unreliable. The registry identifies the primary measure as a participant count, but it does not report an over-dispersion assessment or count-model method. No such method should be inferred from the outcome type alone.

The record describes the study as completed, but completion status is not a statistical result. The number enrolled does not establish the number included in any particular analysis, and no inference about analysis populations should be made without the relevant counts and methods. Those details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 14 analyses. These counts indicate that multiple outcomes and analyses are registered, but they do not show which analyses were primary, how outcomes were ordered, or whether statistical testing was adjusted to account for multiple comparisons. A multiplicity strategy is not reported in the registry record.

In general, when several hypotheses are tested, the chance of obtaining at least one apparently notable result can increase. Adjustment methods or a prespecified hierarchy can address that issue, but neither should be assumed. The record does not identify interim analyses, decision rules, or a statistical analysis plan.

The primary analysis population is described as individuals who completed the 6 week milestone. The number of such individuals is not reported, nor are the numbers missing the milestone or excluded from analysis. The registry record does not describe how missing scale measurements, incomplete follow-up, or other missing data were handled. It also does not specify whether the analysis included all enrolled participants, only participants with outcome data, or another defined population beyond the stated milestone-completer description.

These omissions limit interpretation of the primary count. Missingness can affect both the denominator and the representativeness of participants whose outcomes are observed. General statistical approaches include describing missingness, specifying analysis populations, and assessing how conclusions might change under plausible assumptions. The registry record does not report whether such steps were taken. The reported outcome and analysis counts cannot substitute for those details.

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 2.5% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety summary lists 42 participants at risk for serious adverse events and 0 affected. It also lists 0 deaths. No serious adverse-event terms are listed among the top serious terms. These are the reported serious-event figures; they do not indicate how serious events were defined or how monitoring was conducted.

The summary separately lists 42 participants at risk and 37 affected in the other adverse-event category. That category is distinct from the serious-event count in the record and should not be confused with the primary responder outcome. The registry does not provide event descriptions or further detail about the other category in the registry record for this account.

In general, an observed count of zero means no events were recorded in the stated group during the reported period; it does not establish that an event is impossible or that the underlying risk is zero. The registry gives no uncertainty interval for these safety counts. The figures describe what is recorded, not a comparison with another treatment, since the study is not presented as a like-for-like randomized control comparison.

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

The primary outcome is clearly defined as a threshold-based classification at 6 weeks, but the registry record does not report the numbers classified as responders or non-responders. Consequently, it is not possible to state the observed response frequency, assess its precision, or compare the primary result across metabolizer groups using this record. Study completion and enrollment do not fill that gap.

The title and brief description show that the study was designed to examine relationships among atomoxetine exposure, pharmacodynamics, and clinical outcomes, with side effects and tolerability also of interest. The existence of those aims does not establish what the analyses found. The record does not report effect estimates, uncertainty intervals, or tests for these relationships.

The design also shapes what can be inferred. The record describes an open-label study, does not state allocation, and cautions that this is not a randomized comparison between like-for-like arms. Results from any groups should therefore not be read as randomized evidence of a causal treatment effect. Details needed to evaluate potential group differences or adjusted analyses are not reported in the registry record.

The safety counts are separate from efficacy or symptom-response findings. Zero serious adverse events and zero deaths are the recorded counts among the stated at-risk group; the other adverse-event category is also reported. These figures alone cannot establish comparative safety or characterize the full range of possible events.

In general, a study result is most informative when its estimate, denominator, uncertainty, analysis population, and methods are considered together. For this trial, the endpoint definition and broad design are available, while key outcome and analysis details are not. The record therefore supports a description of what the study asked, but not a conclusion about the magnitude, precision, or causal meaning of its primary result.

13. Why This Trial Matters Statistically

This study raises a statistically important question about how drug exposure, metabolizer classification, and clinical outcomes relate to one another. The registry’s focus on CYP2D6 extensive, intermediate, and poor metabolizers makes the grouping relevant to the study’s stated scientific aims, while the primary endpoint translates a scale change into a responder classification.

The endpoint illustrates a common tradeoff in clinical research. A threshold can make an outcome easier to communicate as a count of participants meeting a definition, but it also removes information about the size and distribution of score changes. For statistical interpretation, both the cutoff and the underlying measurement matter. The registry record defines the cutoff but does not report the outcome counts or underlying changes.

The study also highlights why design details matter. Its open-label status and the absence of a stated allocation method, together with the registry’s warning that the arms are not a like-for-like control comparison, constrain causal interpretation. The registered counts of outcome measures and analyses make the absence of a reported multiplicity plan relevant as well: those counts do not reveal how multiple results were handled.

Finally, this record demonstrates the difference between a registered research question and a reported result. A clear endpoint definition helps readers understand what was intended to be measured, but it cannot replace counts, denominators, uncertainty estimates, and analysis methods. The primary result and its precision are not reported in the registry record, so the scientific aims cannot be treated as findings.

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 limitation for interpreting the primary endpoint is that the registry record does not report responder or non-responder counts. It also does not report the number of participants who completed the 6 week milestone, even though that is the stated analysis population. The enrollment figure cannot be substituted for that denominator.

The endpoint is threshold-based, and the record does not report the underlying score changes or clarify how the Performance questions enter the total score used for the response classification. This limits assessment of how much score information is retained by the responder definition.

The study is open-label, allocation is not stated, and the registry cautions that this is not a randomized comparison with like-for-like arms. The record does not report group-level outcome estimates or adjustment methods that could help readers assess differences between groups. The statistical analysis plan, multiplicity approach, missing-data methods, and analysis populations beyond the milestone-completer description are not reported in the registry record.

The listed counts of 13 outcome measures and 14 analyses do not identify prespecified hypotheses or explain how analyses were selected and interpreted. The record also does not provide uncertainty estimates for the primary endpoint. Safety figures are reported as counts, but further event details and uncertainty estimates are not included in the information. These limitations mean the record supports description of the design and definitions, but not a detailed evaluation of the primary result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Atomoxetine PBPK-PD Clinical Study — NCT03154359.
• Registry record last updated 2023-08-08; status last verified 2023-08.
• Results first posted 2023-08-08.
• 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

NCT03154359 is the completed, open-label Atomoxetine PBPK-PD Clinical Study sponsored by Children's Mercy Hospital Kansas City. The record gives an enrollment of 51, a start date of 2017-12-12, and a primary completion date of 2022-06-01. Its stated focus is the relationship between atomoxetine pharmacokinetics, pharmacodynamics, and clinical outcomes in children with ADHD across CYP2D6 metabolizer groups.

The primary outcome counts responders and non-responders at 6 weeks, using a reduction of at least 40% in NICHQ Vanderbilt Assessment Scale score from baseline to define response among individuals who completed the milestone. The responder counts and milestone-completer count are not reported in the registry record. Safety figures include 0 serious adverse events among 42 at risk, 0 deaths, and 37 affected in the other adverse-event category among 42 at risk. The record lists 13 outcome measures and 14 analyses, but does not report the statistical analysis plan or missing-data and multiplicity methods.