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 Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders (NCT01302964), a randomized phase 3 study. The primary outcome is Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01302964 |
| Phase | Phase 3 |
| Condition | Autism Spectrum Disorders |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 30 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Children and adolescents with pervasive developmental disorders, described in the registry summary as including autistic disorder, Asperger's disorder, and pervasive developmental disorder. The primary outcome population is all randomized study participants.
Intervention
Mirtazapine, with a starting daily dose of 7.5 mg and a maximum daily dose of 45 mg.
Comparator
Placebo capsules described as identical in size and appearance to the study-drug capsules and containing inactive ingredients.
Primary question
How did the mean Pediatric Anxiety Rating Scale 5-item total score change over the double-blind phase in each randomized group, and what precision does the registry report for those mean changes?
The study record describes a randomized comparison of mirtazapine and placebo for anxiety in children and adolescents with pervasive developmental disorders. The main reported outcome is change in the Pediatric Anxiety Rating Scale (PARS) 5-item total score over the 10-week assessment period. The measure is clinician-rated and covers anxiety symptoms commonly associated with social anxiety, separation anxiety, and generalized anxiety disorders.
The displayed results give a model-estimated mean change and a confidence interval separately for each group. They do not give a direct estimate or statistical test of the difference between groups. That distinction matters: the group-specific changes describe outcomes over time within each randomized group, while the clinical comparison of interest is the contrast between the groups. The registry record does not report that contrast.
3. Trial Design
The registry describes a phase 3, randomized, parallel-group trial with quadruple masking. Participants were assigned to mirtazapine or placebo. The record lists an enrollment of 30 and a completed status. The recorded study start is 2010-08, and primary completion is dated 2017-10-10.
The mirtazapine arm description gives a starting dose of 7.5 mg daily and a maximum daily dose of 45 mg. Participants assigned to placebo were to receive capsules matching the study-drug capsules in size and appearance, with inactive ingredients. The registry record does not provide further details about dose adjustment, adherence, or treatment discontinuation.
The primary outcome is the mean change in PARS 5-item total score during the double-blind phase, assessed at baseline and weeks 2, 4, 6, and 10. The outcome population is defined as all randomized study participants. The posted arm-specific outcome figures list 20 participants for mirtazapine and 10 for placebo; the registry does not explain in the outcome description how those figures relate to missing measurements or the model’s handling of incomplete follow-up.
The record lists two outcome measures and no secondary outcome results. It also contains no analysis entries. Although the primary outcome description specifies the model used for its estimates, a broader statistical analysis plan, eligibility details, recruitment procedures, allocation-concealment procedures, and interim-analysis information are not reported in the registry record. The completed status establishes that the record marks the trial as completed, but does not by itself explain why the recorded study period extended from the listed start to primary completion.
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
| Stage | Mirtazapine | Placebo |
|---|---|---|
| STARTED | 20 | 10 |
| COMPLETED | 19 | 10 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Mirtazapine | Placebo |
|---|---|---|
| Adverse Event | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All randomized study participants
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 | Mirtazapine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 10 | 30 | |
| Age, Continuous | years | 10.9 (SD 3.6) | 11.3 (SD 4.1) | 11.0 (SD 3.7) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 6 |
| Sex: Female, Male: Male | Participants | 17 | 7 | 24 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 2 | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 16 | 8 | 24 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 17 | 9 | 26 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Region of Enrollment: United States | participants | 20 | 10 | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Mean 10-Week Change in Pediatric Anxiety Rating Scale 5-Item Total Score, Double-blind Phase, measured over Weeks Baseline, 2, 4, 6, and 10.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is mean change in the Pediatric Anxiety Rating Scale 5-item total score during the double-blind phase. PARS is a clinician-rated instrument that assesses anxiety symptoms commonly associated with social anxiety, separation anxiety, and generalized anxiety disorders. Its scaled score ranges from 0 to 25, with higher scores indicating more severe anxiety symptoms.
A change score describes how the measured score differs from baseline over the assessment period. In this trial, the registry reports estimated mean changes for the mirtazapine and placebo groups across visits at weeks 2, 4, 6, and 10. The endpoint is therefore intended to capture change in rated anxiety symptoms over time, rather than a single measurement at one follow-up visit.
Repeated measurements can use information from several scheduled visits and describe the pattern across the study period. The registry’s model accounts for study week and for the possibility that the groups’ patterns over time differ. It assumes a common mean between groups at baseline. The use of a clinician-rated scale offers a structured way to quantify symptoms, but the endpoint remains a score on that instrument; it is not itself a direct measure of every aspect of participants’ functioning or experience.
The registry record does not report a threshold for a clinically important change or a responder definition. The numerical score changes should therefore be read as changes on the specified scale, not as counts of participants who did or did not meet a separate clinical criterion.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports a mean change of -4.9 points for mirtazapine, with a 95% confidence interval from -7.3 to -2.6. For placebo, the reported mean change is -3.2 points, with a 95% confidence interval from -6.5 to 0.2. The negative values indicate decreases in the measured score from baseline; the scale description says higher scores indicate more severe anxiety symptoms. These are model-estimated group-specific changes, not a direct estimate of the treatment contrast.
The confidence intervals communicate uncertainty around each estimated mean change. The mirtazapine interval is entirely below zero, while the placebo interval includes zero. Those observations concern the uncertainty around each group’s estimated change. They do not establish whether the groups differ from one another: the registry record does not report a between-group estimate, confidence interval, or p-value for the primary outcome. It would be inappropriate to infer a treatment comparison by contrasting the two separate intervals or by calculating a difference from the arm estimates.
The reported intervals account for a Bonferroni correction for selection of two primary outcomes, according to the outcome description. That adjustment concerns multiplicity in the confidence intervals. It does not supply the missing direct group comparison or a complete account of the trial’s statistical plan. The record reports two outcome measures, but does not post results for another primary outcome in the registry record for this interpretation.
These results describe the posted estimates in the randomized groups and their stated precision. They do not show how the results would change under alternative assumptions about missing observations, nor do they establish that the observed changes were caused by treatment. Randomization supports a comparative design, but the registry’s posted primary figures are not themselves the randomized contrast needed to quantify the difference between assigned groups.
The arm-specific sample sizes listed with the endpoint are 20 for mirtazapine and 10 for placebo. They indicate the group sizes attached to these outcome results, but the record does not explain whether they represent all randomized participants, participants with complete measurements, or another model-specific analysis population. The endpoint states that all randomized study participants are the population of interest, while details on handling incomplete measurements are not reported in the registry record.
Overall, the posted data show decreases in estimated mean PARS score in both groups, with the intervals. The result is more limited than a complete efficacy comparison: the registry does not provide a numerical estimate of the difference between mirtazapine and placebo, its uncertainty, or a test of that contrast. The group-specific estimates should be interpreted on that basis.
9. Statistical Methods Explained
The outcome description specifies a repeated-measures linear regression model. In general, repeated-measures methods are used when the same participants are assessed at multiple visits. Rather than treating each visit as an unrelated result, the model represents the measurements over time and estimates mean patterns for the groups. This can make use of the planned sequence of observations, but the interpretation depends on the model specification and the availability and handling of measurements.
What does the model include?
The stated model includes treatment group, study week as categories, and the interaction between treatment group and study week as covariates. Treatment group represents the randomized assignment. Treating week as categories allows the estimated mean at each scheduled time to differ without requiring a straight-line change over time. The interaction allows the pattern across visits to vary by group. In general, an interaction is important when a model allows the relationship between time and the outcome to differ according to treatment assignment.
The model assumes a common mean between treatment groups at baseline. This is a modeling assumption stated in the outcome description, not a claim that every participant began with the same score. A common baseline mean anchors the group trajectories at baseline within the fitted model. The registry record does not report further diagnostics or alternative models used to assess this assumption.
What does a mean change estimate represent?
A mean is an average score change for the group as estimated by the specified model. A negative mean change indicates a lower score relative to baseline, and the PARS description identifies lower scores as less severe symptoms on the scale. This is a group-level summary; it does not tell how much each individual changed or how changes were distributed among participants.
The reported estimates are model-based and use repeated measurements from the specified assessment schedule. They should not be read as simple arithmetic averages unless the registry explicitly identifies them that way. The record does not provide the participant-level observations, model coefficients, or further computational details needed to reproduce the estimates.
How should the confidence intervals be read?
A confidence interval expresses uncertainty in an estimated quantity under the statistical model and its assumptions. A narrower interval indicates greater precision than a wider interval for the same type of estimate. The reported intervals are for each group’s mean change, not for the difference between groups. They therefore cannot be used as a substitute for a confidence interval for the randomized treatment contrast.
The outcome description says the intervals reflect a Bonferroni multiple-testing correction accounting for selection of two primary outcomes. In general, a Bonferroni adjustment is intended to limit the overall risk of false-positive conclusions across a set of tests by making individual inference more conservative. The record does not report the unadjusted intervals or additional details about how the selection of outcomes was handled.
What can the analysis establish?
Random allocation is a design feature intended to support fair comparison between assigned groups. To quantify that comparison, a result would ordinarily report the estimated contrast between groups, with its uncertainty and an appropriate test if one was performed. The posted primary figures give the estimated mean change and interval separately for each group; they do not report the contrast or its test. No comparison should be reconstructed by subtracting the two arm estimates.
The registry record lists no analysis entries. It does, however, describe the model used to estimate the primary outcome and the correction applied to its confidence intervals. Other aspects of the statistical plan, including any procedures for missing data, sensitivity analyses, interim analyses, or analysis adjustments beyond those described for the endpoint, are not reported in the registry record.
How do planning illustrations differ from observed evidence?
Sample-size illustrations based on an observed effect are planning calculations, not evidence that a study had a particular probability of detecting an effect. The registry’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. Such calculations depend on their assumptions and do not add a new observed result. They should not be described as observed power, and they do not replace the trial’s reported outcome estimates or an unreported between-group comparison.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome description states that the confidence intervals use a Bonferroni correction accounting for selection of two primary outcomes. This is the multiplicity information reported for the endpoint. The registry record does not provide a broader description of the testing hierarchy, any prespecified order of outcomes, or whether other analyses were adjusted for multiple comparisons. The record lists two outcome measures and no secondary outcome results.
The outcome population is described as all randomized study participants. The arm-specific result figures list 20 participants in the mirtazapine group and 10 in the placebo group. However, the registry record does not explain the relationship between these numbers and the number with measurements at each visit, nor does it say how incomplete follow-up was handled in the repeated-measures model. A planned population and the observations contributing information to a model are not necessarily identical; the record does not clarify that distinction for this result.
Methods for imputation, assumptions about missingness, sensitivity analyses, and reasons for missing observations are not reported in the registry record. Without those details, readers cannot assess from the posted information how robust the estimates are to missing outcomes. The registry also has no analysis entries, so it does not provide additional analysis-level documentation beyond the primary outcome description.
The stated Bonferroni correction addresses the described selection of two primary outcomes, but it does not resolve uncertainty about missing data or clarify which participants contributed to each visit-specific estimate. These are separate considerations: multiplicity concerns inference across outcomes or tests, while missing-data methods concern incomplete observations and the assumptions used to analyze them.
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 |
|---|---|---|---|
| Mirtazapine | 0 | 20 | 0.0% |
| Placebo | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Mirtazapine | 0 of 20 |
| Placebo | 0 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Mirtazapine | 20 of 20 |
| Placebo | 10 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Mirtazapine | Placebo |
|---|---|---|---|
| Sedation/Drowsiness | General disorders | 12 of 20 | 6 of 10 |
| Appetite increase | General disorders | 10 of 20 | 2 of 10 |
| Irritability | Psychiatric disorders | 7 of 20 | 3 of 10 |
| Nausea | Gastrointestinal disorders | 6 of 20 | 3 of 10 |
| Stomach or abdominal discomfort | Gastrointestinal disorders | 5 of 20 | 4 of 10 |
| Aggression | Psychiatric disorders | 5 of 20 | 4 of 10 |
| Diarrhea | Gastrointestinal disorders | 5 of 20 | 2 of 10 |
| Vomiting | Gastrointestinal disorders | 3 of 20 | 4 of 10 |
| Sadness | Psychiatric disorders | 4 of 20 | 3 of 10 |
| Constipation | Gastrointestinal disorders | 3 of 20 | 3 of 10 |
The serious adverse event figures report zero affected participants in the mirtazapine group and zero in the placebo group. The deaths figures are also zero in each group. These are the serious-event and death counts recorded for the trial; they do not establish that no events of any kind occurred.
The registry’s other-adverse-event fields list 20 affected participants among 20 at risk in the mirtazapine group and 10 affected participants among 10 at risk in the placebo group. These figures are separate from the serious adverse event counts. The registry record does not list top serious adverse event terms, and the record does not provide further detail about the nature, timing, severity, or attribution of the other adverse events.
Safety counts should be read in light of the group sizes and the way events were defined and collected. Zero recorded serious events is not proof that the risk is absent, particularly when the trial is small. The registry figures alone also do not establish whether an event was caused by a study intervention. They describe what was recorded, not a complete safety assessment or a recommendation about treatment.
12. What the Result Does, and Does Not, Mean
The results show model-estimated decreases in mean PARS score from baseline in both randomized groups over the assessed period. The mirtazapine estimate is -4.9, with a 95% confidence interval from -7.3 to -2.6; the placebo estimate is -3.2, with a 95% confidence interval from -6.5 to 0.2. The scale description associates higher scores with more severe anxiety symptoms, so a decrease represents a lower score on this measure.
These estimates do not, on their own, answer whether the groups differed. The registry record does not report the estimated difference between groups, its confidence interval, or a p-value for that comparison. Nor should separate group-specific confidence intervals be treated as a direct test of the randomized contrast. The posted results therefore support a description of each group’s estimated change and its precision, but not a numerical conclusion about the comparative effect.
The endpoint is a clinician-rated score, not a complete account of anxiety, daily functioning, or each participant’s experience. The record does not provide a threshold for a clinically important change or a responder definition. A mean change also cannot show whether all participants changed in the same direction or whether individual outcomes varied widely.
The trial’s randomized, masked design is relevant to how a direct comparison would be interpreted, but the result available in the registry is incomplete for that purpose. Missing-data methods, detailed analysis documentation, and a between-group result are not reported in the registry record. The sample-size illustrations are planning calculations based on stated assumptions, not observed power or additional trial outcomes.
In short, the posted figures describe changes in a symptom scale within each group, with confidence intervals adjusted for the stated selection of two primary outcomes. They do not establish the size or precision of the difference between assigned treatments, and they should not be taken as medical advice or as a recommendation.
13. Why This Trial Matters Statistically
This trial illustrates why outcome estimates and treatment comparisons are not interchangeable. A randomized study is designed to compare assigned groups, but the posted primary result gives a mean change for each group rather than a direct estimate of the difference between them. A reader can describe the two estimates and their intervals, while recognizing that the central comparative quantity is not reported in the registry record.
It also shows how the analysis description affects interpretation. The endpoint uses repeated measurements over several visits, a treatment-by-week interaction, and a common baseline mean assumption. Those details indicate that the reported changes are model-based rather than simple summaries at one follow-up. The confidence intervals also reflect a Bonferroni correction for selection of two primary outcomes, making the multiplicity handling part of the result’s interpretation.
The record offers a useful distinction between statistical uncertainty and clinical meaning. The intervals describe precision for estimated mean changes, but the record does not define a clinically important change threshold or a responder criterion. A numerical reduction on a symptom scale does not by itself communicate the range of individual experiences or establish the importance of that change.
Finally, the absence of details about missing-data handling, analysis entries, and the between-group contrast limits what can be learned from the registry result alone. These are not reasons to discard the reported estimates; they define the boundary of what those estimates can support. Careful statistical reading means preserving that boundary rather than filling gaps with assumptions.
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 interpretation is that the registry reports group-specific mean changes but no direct comparison between mirtazapine and placebo. There is no posted treatment-contrast estimate, confidence interval, or p-value for the primary endpoint. The arm-specific results cannot replace those quantities, and no difference should be calculated from them.
The outcome description identifies a repeated-measures linear regression model and its covariates, but the registry record does not report a complete statistical analysis plan or analysis entries. It does not describe methods for missing outcomes, sensitivity analyses, model diagnostics, or procedures beyond the stated Bonferroni correction. The relationship between the all-randomized population and the arm-specific outcome sample sizes is also not explained.
The record does not provide the underlying participant-level data or the distributions of scores and changes. As a result, the mean estimates do not show variation among participants, and the confidence intervals do not describe the range of individual outcomes. No clinically important change threshold or responder definition is reported.
The registry lists an enrollment of 30 and arm-specific endpoint sample sizes of 20 and 10. These are the only relevant group-size figures; the record does not explain attrition or the reasons for any difference between the planned population and the outcome figures. Details of eligibility criteria, baseline characteristics, adherence, and treatment exposure are not reported in the registry record.
The safety record lists no serious adverse events or deaths in either group, but the posted counts do not establish absence of risk or causation. The record does not provide further serious-event terms. These limitations mean the available registry information supports a cautious description of the posted outcome and safety counts, not a complete assessment of comparative benefit or harm.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders — NCT01302964.
- Registry record last updated 2018-11-07; status last verified 2018-10.
- Results first posted 2018-11-07.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed, randomized, quadruple-masked, parallel-group phase 3 trial of mirtazapine versus placebo in children and adolescents with pervasive developmental disorders. Enrollment is listed as 30. The primary endpoint is mean change in the PARS 5-item total score during the double-blind phase, assessed at baseline and weeks 2, 4, 6, and 10.
The model-estimated mean change is -4.9 for mirtazapine, with a 95% confidence interval from -7.3 to -2.6, and -3.2 for placebo, with a 95% confidence interval from -6.5 to 0.2. These are group-specific estimates; a direct between-group comparison is not reported in the registry record. The outcome description states that confidence intervals account for selection of two primary outcomes using a Bonferroni correction.
The registry also records zero serious adverse events and zero deaths in each group. Missing-data methods, further analysis details, and a numerical treatment contrast are not reported.