Quetiapine and Concerta in the Treatment for ADHD and Aggressive Behavior.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quetiapine and Concerta in the Treatment for ADHD and Aggressive Behavior. (NCT00550147), a na phase 2 study. The primary outcome is RAAPP: Rating of Aggression Against People and/or Property Scale.

2. Clinical Question

The question is about change during treatment in one selected group, not about whether the combination outperforms a control. Because participants and clinicians were not masked and there was no concurrent comparison group, any change in ratings would not by itself establish that the added drug caused the change. The registry record does not report the timing of individual RAAPP assessments, the observed scores, or an estimated treatment effect.

3. Trial Design

This was a Phase 2, open-label study with a single group receiving Oros methylphenidate and quetiapine. The registry lists allocation as not applicable and masking as none. No separate control arm is described, so the design is not a randomized comparison. The sponsor was Indiana University. The registry lists the study as completed, with a start date of 2004-02 and primary completion in 2005-11.

The brief summary describes a thirteen-week study. Its stated purpose was to test the hypothesis that quetiapine added to Oros methylphenidate would reduce aggressive symptoms in children and adolescents who had shown an inadequate response to Oros methylphenidate alone. The primary endpoint population is described as participants who qualified for augmentation on the basis of inadequate response. Details of the criterion used to define inadequate response are not reported in the registry record.

The registry lists enrollment of 30. That enrollment figure should not be treated as the number analyzed for every outcome: the primary outcome description specifies an analysis population, while the safety record lists 24 at risk for each of its reported event categories. The registry does not explain the difference between these figures or provide a complete participant flow.

The primary endpoint is a continuous measure, reported as a mean with standard deviation. Four additional outcome measures are named: the Clinical Global Improvement Scale, Modified Overt Aggression Scale, SNAP-IV Oppositional-Defiant Disorder Subscale, and ADHD Rating Scale-IV Parent Version. Although the record lists five outcome measures and five analyses, detailed results and analysis procedures are not reported in the registry record. The primary outcome timeframe refers to repeated measures but does not identify the assessment visits in the available record.

Medication doses, adherence procedures, visit schedule, inclusion and exclusion criteria, and the handling of treatment discontinuation are not reported in the registry record. The record also does not report a sample-size justification or describe interim 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: All eligible subjects were assigned to the first phase of treatment (Oros MPH alone).

OROS Methylphenidate Monotherapy

Reasons for not completing this period:

Quetiapine Addition Treatment Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants were those who qualified for the augmentation portion of the study (inadequate response to Oros MPH alone). Analysis was per protocol (intent-to-treat, LOCF).

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 RAAPP: Rating of Aggression Against People and/or Property Scale, measured over See Arm/Group - Repeated Measures.

The primary endpoint was the Rating of Aggression Against People and/or Property Scale (RAAPP), a clinician-completed global rating of aggression based on interview and observation data. Its stated range runs from 1, indicating no aggression reported, to 5, indicating intolerable behavior. The registry expresses the outcome in units on a scale and identifies the summary measure as a mean with standard deviation.

A clinician rating can combine information from interviews and observations into a structured assessment of behavior. A scale also allows change to be described numerically rather than only as a general impression. These are general reasons a rating scale may be used as an outcome; the registry does not report validation details or explain why this particular scale was selected.

The primary outcome population is described as participants who qualified for augmentation because of inadequate response to Oros methylphenidate alone. The record labels the analysis per protocol and also includes the terms intent-to-treat and last observation carried forward (LOCF). It does not clarify how these labels were reconciled or give the exact analysis denominator.

The timeframe is described as repeated measures, with the detailed timing deferred to the arm/group description. Specific assessment times, baseline and follow-up means, standard deviations, changes, confidence intervals, and statistical tests are not reported in the registry record. Without those results, the direction, magnitude, and precision of any change on RAAPP cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized as a mean and standard deviation. A mean represents the average score in an analysis group. A standard deviation describes how spread out individual scores are around that average. These summaries answer different questions: the mean describes the group's central level, while the standard deviation describes variation among participants. Neither number is reported for the RAAPP outcome in the registry record.

What does a repeated-measures outcome mean?

Repeated measures means that an outcome is assessed at more than one time point for participants. In general, this can describe how scores change over time while accounting for the fact that measurements from the same participant are related. The primary timeframe refers to repeated measures, but the specific visits and statistical model are not reported in the registry record. It is therefore not possible to determine how the repeated observations were combined or what time contrast was intended.

How should a change estimate be read?

In general, a change estimate describes the difference between measurements or the modeled change over time. Its interpretation depends on the scale direction, which measurements are compared, the analysis population, and how missing observations are handled. The RAAPP scale ranges from 1 for no aggression reported to 5 for intolerable behavior, but the registry record does not report a change estimate or clarify the contrast used in the analysis. No direction or size of change should be inferred from the endpoint description alone.

A confidence interval is a statistical interval intended to express uncertainty around an estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. This is a general explanation; the registry record does not report a confidence interval for the primary outcome. A p-value, when used, addresses compatibility between data and a specified null model under assumptions. It does not by itself measure the size or practical importance of an effect. No primary-outcome p-value or testing procedure is reported in the registry record.

What does the design allow?

This study is described as open-label and single-group, with no masking and no concurrent comparator. In general, a single-group before-and-after analysis can describe observed changes within the enrolled group. It cannot, on its own, distinguish a treatment-related change from time trends, regression to the mean, changes in other care, or measurement effects. Regression to the mean is a general statistical tendency for unusually high or low measurements to be less extreme on a later measurement, even without a specific intervention effect. The registry does not report whether or how such issues were addressed.

Masking can reduce the influence of treatment knowledge on assessment and reporting. Since masking is listed as none, expectations could potentially affect a clinician-rated outcome; this is a general risk in an open-label design, not evidence that ratings were biased. The registry record does not describe steps to standardize assessments or assess rating reliability.

How should missing-data methods be understood?

The primary analysis description includes last observation carried forward (LOCF). In general, LOCF fills a missing later measurement with a participant's last observed value. This produces a complete data set for some analyses, but it assumes that the last observed value is an appropriate stand-in for the unobserved value. If the outcome would have changed after dropout, that assumption may not hold. LOCF can therefore affect estimated means and uncertainty. The registry record does not report how many measurements were missing, why they were missing, or whether other missing-data analyses were performed.

The same description calls the analysis per protocol and also uses the terms intent-to-treat and LOCF. These labels refer to different aspects of analysis: intent-to-treat usually refers to retaining participants according to their assigned group, while per-protocol generally concerns participants who meet specified adherence or eligibility conditions. This general distinction makes the combined wording difficult to interpret without further detail. There is no randomized assignment in the described single-group study, and the registry does not clarify the exact population or rules used for the primary analysis.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on an observed effect, rather than the trial's own design. It states a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of the observed effect. These are planning assumptions, not evidence that this single-group trial enrolled randomized arms or used those assumptions to set its enrollment. The illustration is not observed power. The numerical planning results and the effect values needed to interpret them are not reported in the registry record.

In general, planning calculations estimate how many participants may be needed to detect a chosen effect under specified assumptions. They depend on the outcome's variability, the effect size, the testing threshold, allocation, and analysis method. A planning estimate is not proof that a study was adequately powered, and a calculation based on an observed effect can be uncertain. No sample-size justification or prospective design calculation is reported in the registry record.

The record names five outcome measures and five analyses, but does not describe a multiplicity strategy. In general, assessing multiple outcomes or time points can increase the chance of at least one apparently notable result if each is tested separately. Adjustments or a prespecified hierarchy can address that issue, but neither is described in the registry record. Since outcome estimates and test results are also not reported, the consequences of multiplicity cannot be evaluated.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Baseline", "Visit 5 - MPH Monotherapy - Week 4", "Visit 10 - MPH+Quetiapine - Week 13")
n   <- c(24, 24, 24)
m   <- c(4.3, 3.2, 2)
sp  <- c(0.4, 0.6, 0.8)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Baseline  24  4.300  0.400  4.131  4.469
CARM  Visit 5 - MPH Monotherapy - Week 4  24  3.200  0.600  2.947  3.453
CARM  Visit 10 - MPH+Quetiapine - Week 13  24  2.000  0.800  1.662  2.338

11. Multiplicity, Missing Data and Analysis Populations

The registry names five outcome measures and five analyses. The RAAPP is identified as the primary outcome; the named secondary measures are the Clinical Global Improvement Scale, Modified Overt Aggression Scale, SNAP-IV Oppositional-Defiant Disorder Subscale, and ADHD Rating Scale-IV Parent Version. The record does not describe how the primary and secondary measures were prioritized analytically, whether multiple time points were tested, or whether any adjustment for multiple comparisons was planned. A prespecified hierarchy or multiplicity adjustment can help control the risk of emphasizing a chance finding when several outcomes are assessed; this is a general statistical consideration, not a description of this study's procedure.

The primary outcome analysis is described as per protocol and also includes the terms intent-to-treat and LOCF. The record does not define the exact analysis population, the handling of participants who did not complete treatment, or how these analysis labels were applied together. It also does not report how many observations were missing, the reasons for missingness, or sensitivity analyses under alternative missing-data assumptions.

LOCF uses a participant's last observed value in place of a later missing value. In general, this approach can be misleading if the outcome changes after the last assessment, and it does not fully account for uncertainty about the unobserved value. Its impact in this study cannot be assessed without missingness details and outcome results.

The registry does not report participant flow, outcome-specific denominators, or the analysis method for the repeated measures. It therefore remains unclear how many participants contributed data at each assessment and how incomplete follow-up affected the reported estimates. No multiplicity adjustment, missing-data sensitivity analysis, or detailed analysis-population definition is reported in the registry record.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 4% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists 24 participants at risk for serious adverse events, with 0 affected. It separately lists 24 at risk for other adverse events, with 23 affected. These are counts in the registry record, not rates calculated for comparison with another group. The record describes one group receiving Oros methylphenidate and quetiapine and does not provide a concurrent control group for safety comparison.

The serious-event figure indicates that no serious adverse events were recorded among those listed at risk in this record. It does not establish that the combination has no serious risks: the study is a single-group study, and the safety information is limited to the recorded observation period and reporting. The registry record does not provide event descriptions for serious events, and its list of top serious-event terms is empty.

The other-adverse-event figure indicates that 23 of the 24 listed at risk were recorded as affected. The record does not provide the specific other-event terms, severity, timing, duration, or outcome. A participant-level affected count does not show how many events occurred or their clinical importance.

Deaths are listed as null, so death information is not reported in the registry record; null should not be read as a reported count of zero. These figures also do not establish comparative risk or causation. No conclusions about individual care should be drawn from these summary counts.

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

The registry record defines a study question: whether aggressive symptoms changed when quetiapine was added to Oros methylphenidate for children and adolescents who had not responded adequately to Oros methylphenidate alone. It identifies RAAPP as the primary measure and describes its scale and intended analysis population. However, numerical primary results are not reported in the registry record. The observed direction and magnitude of change, and the precision of any estimate, therefore cannot be stated.

The design also limits what any within-group change could establish. With one open-label group and no concurrent comparator, observed change would not isolate the contribution of quetiapine from other explanations. The study can be described as an open-label investigation of the combination, but it cannot supply a randomized comparison with Oros methylphenidate alone on the basis of the design described in the registry.

The listed enrollment is 30, while the safety record gives 24 at risk for its event categories. The record does not explain the relationship between these figures or provide a full account of follow-up. The primary analysis description refers to participants who qualified for augmentation and includes both per-protocol and intent-to-treat wording, with LOCF. The exact analysis population and missing-data impact are not reported in the registry record.

In general, an estimate should be read together with its uncertainty and the design that generated it. Here, no primary estimate, confidence interval, or primary test result is reported, so statistical evidence about change cannot be assessed. The sample-size planning description is explicitly an illustration based on an observed effect, not the trial's own design, and it is not observed power.

The safety record reports 0 serious adverse events among 24 at risk and 23 affected by other adverse events among 24 at risk; deaths are not reported in the registry record. These counts do not provide a comparison with another treatment group, and details of the other events are absent. The study's stated hypothesis is a research question, not an outcome finding. The posted information is insufficient to claim either benefit or lack of benefit.

14. Why This Trial Matters Statistically

Statistically, this study illustrates why the design and the outcome results must be read together. A clinician-rated scale can quantify aggression, and repeated assessments can describe how scores change over time. But without a concurrent comparator, a within-group change would not identify what caused the change. Open-label assessment also leaves the possibility that knowledge of treatment could influence ratings, a general concern for subjective or clinician-rated outcomes.

The record makes the intended analysis population and missing-data approach important to interpretation. It describes participants who qualified for augmentation, labels the analysis per protocol while also using intent-to-treat wording, and mentions LOCF. These terms do not by themselves provide a reproducible definition of who was analyzed or how missing outcomes were handled. Clear definitions of populations, follow-up, and missing data are necessary to understand the meaning of a reported estimate.

The study also names multiple outcome measures. In general, multiple endpoints and repeated assessments require a clear strategy for distinguishing primary evidence from exploratory findings. The registry does not report a multiplicity approach or outcome results, so it is not possible to assess how the analyses were prioritized or interpreted.

Finally, the record separates enrollment from safety counts and leaves the relationship unexplained. Recognizing that different analyses can have different denominators is important: a total enrollment figure is not automatically the denominator for every endpoint or safety outcome. In this case, participant flow and outcome-specific counts are not reported in the registry record.

The main statistical lesson is that a detailed endpoint description does not replace estimates and uncertainty. Without RAAPP results, the study question remains unanswered by the posted outcome information. The record is useful for identifying the design and the intended measurement, while its limitations prevent a quantitative assessment of the primary finding.

15. 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.

This trial's single-group design is the central limitation for interpreting change. There is no concurrent control group, and allocation is listed as not applicable. As a result, any change over repeated assessments would not by itself distinguish a treatment-related effect from time trends, regression to the mean, changes in other care, or other influences. These are general limitations of within-group interpretation, not claims about what occurred among participants.

The study was open-label with no masking. The primary outcome was a clinician rating based on interview and observation data, so treatment knowledge could potentially influence assessment. The registry record does not report assessor training, inter-rater reliability, or procedures intended to reduce this risk.

The primary analysis population is described as participants who qualified for augmentation after an inadequate response to Oros methylphenidate alone. The registry does not give the qualifying rule, the number meeting it, or the number included in the analysis. The analysis description combines per-protocol and intent-to-treat terminology, leaving the population definition unclear. It also does not explain the relationship between enrollment of 30 and the 24 participants listed at risk in the safety record.

Although the primary timeframe refers to repeated measures and the study summary describes thirteen weeks, the assessment schedule and detailed follow-up are not reported in the registry record. Dose information, adherence, participant disposition, reasons for withdrawal, and outcome-specific denominators are also not reported. These omissions restrict assessment of how the measurements were collected and who contributed data.

LOCF is named, but the extent and reasons for missing data are not reported, and no alternative missing-data analysis is described. The record also does not report the primary outcome estimate, uncertainty, test, multiplicity strategy, or sample-size justification. These limitations prevent evaluation of the magnitude and precision of the primary result, as well as the robustness of any conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Quetiapine and Concerta in the Treatment for ADHD and Aggressive Behavior. — NCT00550147.
• Registry record last updated 2015-05-13; status last verified 2015-05.
• Results first posted 2015-05-13.
• 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.

19. Record Summary

The registry record describes NCT00550147, a completed Phase 2, open-label, single-group study sponsored by Indiana University. It lists enrollment of 30 and a study start of 2004-02, with primary completion in 2005-11. The brief summary describes a thirteen-week study of quetiapine added to Oros methylphenidate in children and adolescents with ADHD and aggressive behavior who had an inadequate response to Oros methylphenidate alone.

The primary measure was the clinician-rated RAAPP, described as a repeated-measures outcome with a mean and standard deviation. The primary population was those who qualified for augmentation; the analysis description includes per-protocol, intent-to-treat, and LOCF terminology. Four secondary measures are named. Numerical outcome results, assessment timings, detailed analysis methods, and participant flow are not reported in the registry record.

The safety record lists 0 serious adverse events among 24 at risk and 23 affected by other adverse events among 24 at risk. Deaths are not reported in the registry record. The single-group design does not provide a concurrent treatment comparison.