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 An Italian Study of the Efficacy of Atomoxetine in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Oppositional Defiant Disorder (ODD). (NCT00192023), a randomized phase 3 study. The primary outcome is Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00192023 |
| Phase | Phase 3 |
| Condition | Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 139 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD). The study description focuses on patients who had not responded to a previous psychological intervention with parent support. The primary analysis population is described as randomized patients with at least a post-baseline value for the primary endpoint, with last observation carried forward applied.
Intervention
Atomoxetine was given by mouth once daily. The described regimen began at 0.5 mg/kg/day for 1 week, followed by 1.2 mg/kg/day for 7 weeks, then 1.2–1.4 mg/kg/day for up to 1.5 years or until marketing approval.
Comparator
Placebo was given by mouth once daily for 8 weeks. After that period, the placebo group could switch to atomoxetine, beginning at 0.5 mg/kg/day for 1 week and then moving to 1.2–1.4 mg/kg/day for up to 1.5 years or until marketing approval.
Primary question
The primary measure concerns change from baseline to the 8-week endpoint in the SNAP-IV ADHD subscale. The trial aimed to evaluate atomoxetine’s effects on ADHD and ODD symptoms in this population. However, the registry record flags the primary outcome as involving several categories or time points and does not reduce it to a single comparison. It does not report the numerical estimates needed to describe the size or precision of a primary effect.
3. Trial Design
The registry identifies this as a randomized, parallel-group, quadruple-masked study and lists its phase as Phase 3. The study description calls it a phase IIIb, multicentre, randomized, placebo-controlled trial. Its stated focus was paediatric patients with ADHD and ODD, with the primary aim of evaluating symptom changes after a previous psychological intervention with parent support had not produced a response.
The registry lists atomoxetine and placebo as the interventions. In the atomoxetine regimen, treatment began at 0.5 mg/kg/day for 1 week and then increased to 1.2 mg/kg/day for 7 weeks. The described longer-term regimen was 1.2–1.4 mg/kg/day for up to 1.5 years or until atomoxetine received marketing approval. The placebo group received placebo for 8 weeks, after which participants had the possibility of switching to atomoxetine. The registry therefore describes a placebo comparison during the initial endpoint period and a possible later treatment phase; it does not report results for that later period.
Enrollment is recorded as 139. The primary endpoint’s population description refers to all randomized patients with at least a post-baseline value, specifying 105 + 32 = 137 patients in total, and says that last observation carried forward was applied. The registry does not report the reason for the difference between the enrollment figure and the stated endpoint population. It also does not report allocation ratios, details of the masking procedures, or the statistical plan.
The primary endpoint was measured at baseline and the 8-week endpoint. Other listed measures address ADHD severity, oppositional symptoms, anxiety, depression, parent- and teacher-rated symptoms, and child health and illness profile. Their presence indicates a broad set of clinical domains, but the registry record does not give their numerical results in the information available for interpretation.
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: Study Period I=Screening. Study Period II=Standardized behavioral management program for parents (156 entered, 17 discontinued). Study Period III=Double-Blind (randomization). Two patients did not have post-baseline values for the primary endpoint and were not included in Baseline or efficacy analyses. Study Period IV=Optional open-label phase.
Period III - Double-Blind
| Stage | Atomoxetine | Placebo |
|---|---|---|
| STARTED | 107 | 32 |
| COMPLETED | 100 | 32 |
| NOT COMPLETED | 7 | 0 |
Reasons for not completing this period:
| Reason | Atomoxetine | Placebo |
|---|---|---|
| Adverse Event | 3 | 0 |
| Physician Decision | 2 | 0 |
| Parent/Caregiver Decision | 2 | 0 |
Period IV - Optional Open-Label
| Stage | Atomoxetine | Placebo |
|---|---|---|
| STARTED | 124 | 0 |
| COMPLETED | 49 | 0 |
| NOT COMPLETED | 75 | 0 |
Reasons for not completing this period:
| Reason | Atomoxetine | Placebo |
|---|---|---|
| Adverse Event | 6 | 0 |
| Lack of Efficacy | 7 | 0 |
| Patient/Caregiver Decision | 46 | 0 |
| Lost to Follow-up | 2 | 0 |
| Protocol Violation | 1 | 0 |
| Withdrawal by Subject | 4 | 0 |
| Physician Decision | 9 | 0 |
Analysis population for the primary outcome, as defined in the registry: Efficacy Population (All 139 randomized patients with at least a post-baseline value for the primary endpoint, i.e, 105 + 32 = 137 patients in total). Last Observation Carried Forward was applied.
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 | Atomoxetine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 105 | 32 | 137 | |
| Age Continuous | years | 9.7 (SD 2.2) | 10.0 (SD 2.4) | 9.8 (SD 2.3) |
| Sex: Female, Male: Female | Participants | 7 | 3 | 10 |
| Sex: Female, Male: Male | Participants | 98 | 29 | 127 |
| Region of Enrollment: Italy | participants | 105 | 32 | 137 |
| Race/Ethnicity: Caucasian | participants | 104 | 29 | 133 |
| Race/Ethnicity: Hispanic | participants | 1 | 3 | 4 |
| Height | centimeters | 140.1 (SD 15.2) | 141.6 (SD 15.3) | 140.4 (SD 15.1) |
| Weight | kilograms | 39.3 (SD 15.8) | 41.4 (SD 14.1) | 39.8 (SD 15.4) |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to 8 Week Endpoint in Swanson, Nolan and Pelham Questionnaire (SNAP-IV): Attention-Deficit/Hyperactivity Disorder (ADHD) Subscale, measured over Visit 8 (baseline) and Visit 14 (8 weeks).
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from baseline to the 8-week endpoint in the ADHD subscale of the Swanson, Nolan and Pelham Questionnaire, or SNAP-IV. The registry describes the measure as covering the inattention and hyperactivity/impulsivity symptom subsets drawn from DSM-IV criteria for ADHD. Ratings use a 0-to-3 scale, from not at all to very much, and the total subscale score ranges from 0 to 54.
As a continuous measure, the endpoint represents symptom ratings on a scale rather than a count of events. A change score expresses how a participant’s recorded score at follow-up differs from their baseline score. In general, a lower follow-up score on this rating scale represents less frequent or less pronounced reported symptoms; the meaning of a group-level change still depends on its estimated size, uncertainty, and the analysis used.
The registry specifies a mean as the summary measure and standard deviation as the measure of dispersion. A mean describes the group’s average score or change, while a standard deviation describes how spread out individual values are around that average. The registry gives the measurement visits and says last observation carried forward was applied to the efficacy population. It does not report the group means, standard deviations, change estimates, confidence intervals, or a single primary comparison. As a result, the endpoint definition can be described, but the magnitude and precision of the primary result cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The endpoint is a change in a continuous symptom rating, and the registry’s stated summary is a mean with a standard deviation. Interpreting a trial result for this endpoint would ordinarily require the group-level changes, a between-group contrast, and a measure of uncertainty such as a confidence interval. Those numerical results are not reported in the registry record. No conclusion about the size, direction, or precision of a between-group effect can therefore be drawn from the available endpoint description.
The registry record also flags the primary outcome as involving several categories or time points and says it was not reduced to one comparison. This matters because a trial’s primary question is easiest to interpret when the primary endpoint, time point, and contrast are explicit. Without a single reported comparison, it is unclear which specific estimate should be treated as the main answer to the trial’s primary question. The registry does not report an adjusted or unadjusted p-value, a confidence interval, or the sponsor’s numerical primary analysis.
The endpoint population is described as randomized patients with at least a post-baseline primary-endpoint value, with last observation carried forward applied. The record gives the population as 105 + 32 = 137 patients in total, while enrollment is 139. The record does not explain this difference. Last observation carried forward uses an earlier recorded value in place of a later missing value. This creates an analysis dataset but does not make the missing follow-up value known; the validity of the resulting estimate depends on assumptions about what would have happened after the last observed value.
The record lists secondary measures across several symptom and health domains, including anxiety, depression, oppositional symptoms, and parent- and teacher-rated scales. It does not report their numerical findings here, and the presence of multiple outcomes does not establish whether they were confirmatory or exploratory. Nor does the record describe a multiplicity adjustment. Findings across multiple outcomes would need to be interpreted with attention to the chance of false-positive results when many comparisons are examined.
The available safety figures report no participants affected by serious adverse events in either listed group. They do report participants affected by other adverse events. These counts are descriptive safety information, not evidence by themselves about comparative risk or causation. Group sizes, follow-up, event definitions, and the way events were collected all matter when comparing safety. The record does not give serious-event terms or death counts.
Overall, the record describes the design, endpoint, and some safety counts, but not the numerical primary efficacy result. That distinction is important: a clearly specified endpoint is not itself evidence of a particular treatment effect, and a lack of reported estimates cannot be interpreted as a null result.
9. Statistical Methods Explained
The registry describes a randomized, parallel-group trial. In general, random assignment is intended to reduce systematic differences between groups at the start of a study, while a parallel design follows assigned groups over the same study period rather than crossing participants between treatments during the primary comparison. The registry also records quadruple masking. Masking is generally intended to reduce the influence of treatment knowledge on participants, study staff, outcome assessment, or analysis; the record does not explain which people were masked or how the masking was maintained.
What does a mean change describe?
The primary outcome is a continuous SNAP-IV ADHD subscale score, summarized using a mean and standard deviation. A mean change gives the average difference between baseline and the 8-week endpoint within a group. A comparison of mean changes between groups can describe how far the groups’ average trajectories differ. That contrast is distinct from comparing each group’s change separately: improvement within one group does not, by itself, show that the groups differed.
The standard deviation describes variation among individual scores around the group mean. It is not the same as the standard error or a confidence interval. A confidence interval, in general, gives a range of values compatible with the data and the statistical model at a stated confidence level. It helps show precision, whereas a p-value addresses compatibility with a specified null hypothesis under model assumptions. The registry record does not report the primary confidence interval or p-value, so neither the precision nor the inferential result can be assessed.
Why does the scale matter?
The SNAP-IV rating is based on symptom frequency or severity ratings from 0 to 3, with the primary subscale score ranging from 0 to 54. Continuous-score analyses retain the scale information instead of converting scores into categories. The clinical meaning of a numerical difference depends on the measure, the population, and the context. The registry does not state a threshold for a clinically important change, so a statistical difference, if one were reported, could not automatically be equated with a meaningful difference for patients.
What does last observation carried forward do?
The efficacy population description says last observation carried forward was applied. In general, this method substitutes a participant’s last recorded value for a later missing value. It can allow a complete analysis dataset under the chosen approach, but it treats the earlier observation as if it represented the unobserved later endpoint. That assumption may not fit a participant whose symptoms would have changed after the last recorded visit. Missing-data methods rely on assumptions, and different assumptions can lead to different estimates. The record does not report reasons for missing values, the number of missing endpoint values by group, sensitivity analyses, or the rationale for using this method.
What is the role of the analysis population?
The primary population is described as randomized patients with at least a post-baseline primary-endpoint value. This is not described as an analysis of every randomized patient regardless of post-baseline data. The record gives the population as 105 + 32 = 137 patients in total, while enrollment is 139, but does not explain the distinction. It does not report whether other analysis populations were used or whether results were checked under alternative population definitions. Consequently, the influence of excluding or imputing observations cannot be evaluated from the registry description alone.
How should multiple outcomes be considered?
The record lists a primary outcome and several secondary outcomes addressing different domains and raters. When a study evaluates multiple outcomes, time points, or comparisons, the chance of at least one apparently unusual result can increase if all are interpreted as separate confirmatory tests. Statistical approaches can control that multiplicity, but the registry does not report whether any such approach was specified or used. The primary outcome is also flagged as involving several categories or time points without a single comparison. The exact hierarchy of outcomes and the intended confirmatory contrast are therefore not reported in the registry record.
What do the sample-size illustrations mean?
The record describes sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The registry does not report the trial’s own sample-size justification or design assumptions. Without the numerical effect estimate and illustration values, the required participant counts for any particular planning scenario cannot be assessed.
These general concepts explain how the stated outcome and design might be analyzed; they do not establish which models, adjustments, tests, or sensitivity analyses were used in this trial. The statistical plan is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary SNAP-IV ADHD subscale outcome and lists secondary measures covering ADHD severity, oppositional symptoms, anxiety, depression, parent and teacher ratings, and child health and illness profile. It also records 10 outcome measures and 14 analyses. Having several outcomes or analyses can create multiplicity: when many comparisons are examined, some results may appear statistically notable by chance even if there is no underlying difference. In general, prespecifying a primary comparison and explaining any adjustment can help readers distinguish confirmatory findings from exploratory ones.
The registry record flags the primary outcome as involving several categories or time points and says it was not reduced to one comparison. It does not report a multiplicity strategy, the hierarchy among secondary outcomes, or which analyses were considered confirmatory. Numerical results for the primary comparison and secondary outcomes are not reported in the information available for interpretation. Accordingly, the extent to which multiplicity affects any reported inference cannot be determined.
Missing data are relevant because the endpoint population is defined as randomized patients with at least a post-baseline primary-endpoint value, and last observation carried forward was applied. The registry specifies the population as 105 + 32 = 137 patients in total; enrollment is recorded as 139. It does not report why the population differs from enrollment, how much endpoint data were missing in each group, or the reasons for missingness. It also does not report sensitivity analyses using other missing-data assumptions.
In general, missingness can affect estimates if participants with unavailable outcomes differ from those with observed outcomes, or if the unobserved results would have differed from values carried forward. The record does not provide enough detail to judge whether the chosen method’s assumptions were plausible. It also does not report the full analysis plan or whether results from alternative populations or methods were considered.
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 |
|---|---|---|---|
| Atomoxetine | 0 | 107 | 0.0% |
| Placebo | 0 | 32 | 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 |
|---|---|
| Atomoxetine | 79 of 107 |
| Placebo | 12 of 32 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Atomoxetine | Placebo |
|---|---|---|---|
| Anorexia | Metabolism and nutrition disorders | 26 of 107 | 1 of 32 |
| Headache | Nervous system disorders | 18 of 107 | 4 of 32 |
| Somnolence | Nervous system disorders | 18 of 107 | 2 of 32 |
| Vomiting | Gastrointestinal disorders | 14 of 107 | 1 of 32 |
| Nausea | Gastrointestinal disorders | 14 of 107 | 0 of 32 |
| Abdominal pain upper | Gastrointestinal disorders | 9 of 107 | 4 of 32 |
| Abdominal pain | Gastrointestinal disorders | 11 of 107 | 1 of 32 |
| Influenza | Infections and infestations | 9 of 107 | 0 of 32 |
| Decreased appetite | Metabolism and nutrition disorders | 9 of 107 | 0 of 32 |
| Nervousness | Psychiatric disorders | 6 of 107 | 1 of 32 |
The safety record lists two groups. In the atomoxetine group, 107 participants were at risk for serious adverse events and 0 were affected; 107 were at risk for other adverse events and 79 were affected. In the placebo group, 32 participants were at risk for serious adverse events and 0 were affected; 32 were at risk for other adverse events and 12 were affected.
These figures distinguish serious adverse events from other adverse events. A recorded count of 0 affected participants means that the registry lists no participants affected by a serious adverse event in those groups; it does not establish that serious events are impossible or rule out unrecorded events. The record does not list serious-event terms. Death counts are not reported in the registry record.
The counts for other adverse events are descriptive. They do not by themselves establish that an event was caused by the assigned intervention or that the groups had different underlying risks. Interpretation depends on the event definitions, collection procedures, observation period, and completeness of follow-up. The registry does not provide those details here, and the counts alone do not support a causal or comparative safety conclusion.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a randomized, quadruple-masked, parallel-group study comparing atomoxetine with placebo in children and adolescents with ADHD and ODD. It describes an eight-week primary endpoint based on change in the SNAP-IV ADHD subscale and says that last observation carried forward was applied to the stated efficacy population. It also lists a range of secondary symptom and health measures and provides group-level safety counts.
What the record does not establish is the numerical size or precision of the primary treatment contrast. The record does not report group means, standard deviations, mean changes, a confidence interval, or a p-value for a single primary comparison. It flags the primary outcome as involving several categories or time points and not reduced to one comparison. The missing numerical result is not evidence that the groups were the same, and it is not evidence that one group had a better result. It means that the primary effect cannot be evaluated from the information reported in the registry record.
Even when a group difference is reported, interpretation should distinguish statistical evidence from clinical importance. A score difference on a rating scale does not automatically show that a change is meaningful to patients. That judgment depends on context, including the scale and an accepted threshold for an important change. The registry does not report such a threshold.
The safety figures indicate zero participants affected by serious adverse events in each group and participants affected by other adverse events in both groups. These counts describe what is recorded; they do not on their own establish causation, comparative risk, or the absence of harm. Details about event definitions and follow-up are not reported in the registry record.
The record’s endpoint population and use of last observation carried forward also matter when interpreting any estimate. The analysis population is stated as 105 + 32 = 137 patients in total, whereas enrollment is 139; the reason is not reported. The imputation method relies on an assumption about unobserved endpoint values that cannot be evaluated without further information. Thus, the registry supports a description of the study question and methods, but not a conclusion about the magnitude, precision, or clinical significance of the primary result.
13. Why This Trial Matters Statistically
This trial is statistically notable for the combination of a randomized placebo comparison and a symptom-rating endpoint in a population selected for ADHD with comorbid ODD. Randomization and masking are design features intended, in general, to reduce some sources of bias. The primary measure is defined on a continuous scale and is recorded at baseline and the 8-week endpoint, giving a clear outline of the intended measurement framework.
The record also illustrates why an outcome definition is not enough to interpret a trial. Readers need the actual group summaries, the between-group estimate, and its uncertainty. In this case, the registry flags a primary outcome involving several categories or time points without reducing it to a single comparison, and does not report numerical estimates for that primary result. The distinction between a prespecified question and a usable effect estimate is central to transparent trial reporting.
There are additional statistical considerations in the record: the primary population excludes randomized patients without a post-baseline value, last observation carried forward was applied, and multiple outcome measures and analyses are listed. These features raise questions about missing-data assumptions and multiplicity. The record does not provide enough detail to assess how those issues were handled beyond the stated imputation approach.
The safety counts provide descriptive information but cannot replace a full comparative safety analysis. Likewise, the planning illustrations described in the record are not observed power and should not be treated as the trial’s original sample-size justification. Taken together, the study is a useful example of how trial design, endpoint choice, analysis population, missing-data handling, and reporting completeness all shape what can be inferred. Here, the design and measurement plan are described more fully than the primary numerical 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 most important limitation for interpreting efficacy is that the registry record does not report a single numerical primary comparison. It identifies the SNAP-IV ADHD subscale and the 8-week endpoint, but provides no group means, standard deviations, mean changes, confidence interval, or p-value for a primary contrast. It also flags the primary outcome as involving several categories or time points without reducing it to one comparison. The direction, magnitude, and precision of the primary effect therefore cannot be assessed.
The endpoint population is stated as randomized patients with at least a post-baseline primary-endpoint value, with last observation carried forward. The record gives the population as 105 + 32 = 137 patients in total and separately records enrollment as 139. The reason for this difference is not reported in the registry record. Nor are the amount and pattern of missing outcome data, reasons for missingness, or results from alternative missing-data analyses reported. The assumptions behind the imputation cannot be checked.
The record lists multiple secondary outcomes and analyses but does not report a statistical plan, the hierarchy of outcomes, or any multiplicity adjustment. It is therefore not possible to determine how secondary findings were intended to support the primary question. The registry also does not report the trial’s own sample-size justification, allocation ratio, or detailed masking procedures.
For safety, the record gives group counts for serious and other adverse events but does not list serious-event terms, explain event definitions, or report deaths. The observation period and event-collection details are not specified in the information available for interpretation. These omissions limit what can be concluded from the safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Italian Study of the Efficacy of Atomoxetine in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Oppositional Defiant Disorder (ODD). — NCT00192023.
- Registry record last updated 2010-01-18; status last verified 2009-12.
- Results first posted 2010-01-18.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed, randomized, quadruple-masked, parallel-group study in children and adolescents with ADHD and comorbid ODD. It lists enrollment as 139 and identifies the primary endpoint as change from baseline to the 8-week endpoint in the SNAP-IV ADHD subscale. The efficacy population is described as 105 + 32 = 137 patients in total, with last observation carried forward applied.
Atomoxetine was compared with placebo during the initial eight-week period, with a possible later switch from placebo to atomoxetine. Secondary measures covered several symptom and health domains. The registry record lists 10 outcome measures and 14 analyses, but does not report a single numerical primary comparison or the statistical plan. The safety record lists 0 participants affected by serious adverse events in each group and reports other adverse events in both groups. Death counts are not reported in the registry record.