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 Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD) (NCT01825798), a randomized phase 3 study. The primary outcome is Change in Body Mass Index Z-score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01825798 |
| Phase | Phase 3 |
| Condition | Overweight, Autism Spectrum Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 60 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Holland Bloorview Kids Rehabilitation Hospital |
| Results posted | Yes |
2. Clinical Question
The trial asks whether metformin, compared with placebo, changes body mass index (BMI) z-score over 16 weeks in young people with autism spectrum disorders who are taking atypical antipsychotic medication. The registry describes the study purpose as assessing safety and effectiveness for weight or weight gain in this population. The primary outcome is a continuous measure: change in BMI z-score from baseline to 16 weeks.
Population
Young people with autism spectrum disorders and overweight, currently taking atypical antipsychotic medication. The registry record does not report the participants’ age range or further eligibility criteria.
Intervention
Metformin. Dose, dosing schedule, and other details of how the intervention was administered are not reported in the registry record.
Comparator
Placebo, described in the arms as Placebo Hydrochloride Oral Solution. The registry record does not provide further details about the placebo regimen.
Primary question
What was the mean change in BMI z-score from baseline to 16 weeks in each randomized arm? The posted results report arm-specific means and confidence intervals; they do not report an estimable two-arm comparison for this continuous endpoint.
This distinction matters: a result for each arm separately is not itself an estimate of the difference between the randomized groups. The reported values describe the observed changes in the two groups, while a direct treatment comparison would quantify how far apart those changes were, with uncertainty around that contrast. That comparison is not reported in the registry record.
3. Trial Design
This was a Phase 3, randomized, parallel-group study with quadruple masking. The registry lists enrollment of 60 participants and identifies Holland Bloorview Kids Rehabilitation Hospital as the sponsor. The study status is completed. Its recorded start was 2013-04, and its primary completion was 2015-06.
Participants were assigned to metformin or placebo. The posted primary-outcome data include 28 participants in the metformin arm and 32 in the placebo arm. These are the arm counts associated with the reported outcome; the registry record does not explain whether any participants were excluded from that outcome analysis or why the counts differ. Random allocation supports a comparison between groups in principle, but details of the sequence generation and allocation concealment are not reported in the registry record.
Quadruple masking indicates that the record classifies the study as masked at four levels, but it does not identify those roles or describe how masking was maintained. The registry record does not report the intervention dose, treatment schedule, adherence, use of concomitant care, or the full protocol. The primary outcome timeframe is baseline to 16 weeks. The record lists body-composition and fasting metabolic measures among secondary outcomes, including weight, BMI, abdominal and hip circumference, total cholesterol, LDL, and HDL.
These design features describe the intended comparison and the reported setup; they do not establish that all participants followed the same treatment course or contributed complete data. Information about deviations, withdrawals, recruitment flow, and analysis populations is not reported in the registry record. The posted arm-specific outcome estimates therefore need to be read alongside the uncertainty about those operational details.
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 | Placebo Hydrochloride Oral Solution | Metformin |
|---|---|---|
| STARTED | 32 | 28 |
| COMPLETED | 30 | 23 |
| NOT COMPLETED | 2 | 5 |
Reasons for not completing this period:
| Reason | Placebo Hydrochloride Oral Solution | Metformin |
|---|---|---|
| Adverse Event | 1 | 5 |
| Lost to Follow-up | 1 | 0 |
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 | Placebo Hydrochloride Oral Solution | Metformin | Total |
|---|---|---|---|---|
| Participants analysed | 32 | 28 | 60 | |
| Age, Categorical: <=18 years | Participants | 32 | 28 | 60 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 12.7 (SD 2.64) | 12.9 (SD 2.85) | 12.8 (SD 2.7) |
| Sex: Female, Male: Female | Participants | 8 | 7 | 15 |
| Sex: Female, Male: Male | Participants | 24 | 21 | 45 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 | 0 | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 29 | 28 | 57 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 2 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 3 | 4 |
| Race (NIH/OMB): White | Participants | 28 | 22 | 50 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 2 |
| Region of Enrollment: Canada | participants | 8 | 8 | 16 |
| Region of Enrollment: United States | participants | 24 | 20 | 44 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Body Mass Index Z-score, measured over Baseline, 16 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | 16-wk change in BMI z-score |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in body mass index z-score from baseline to 16 weeks. BMI is a weight-for-height measure. A z-score expresses a measurement relative to a reference distribution, making it a standardized way to describe BMI in a population such as young people, where body size changes with age and development. The registry record does not identify the reference standard or give further details about how the z-score was calculated.
A change score describes how much the measured value moved between the specified assessments. A negative change indicates a lower BMI z-score at follow-up than at baseline; a positive change indicates a higher value. The posted mean change for each arm is an average across the participants included in that arm’s outcome data. An average does not show how much individual participants varied, and the registry record does not report participant-level values or a measure of spread such as a standard deviation.
Using a standardized BMI measure can make weight-related change more interpretable in a young population than relying on raw BMI alone. It remains a surrogate measure of body size, not a direct measure of health or functioning. The registry record does not report a threshold for a clinically important change or explain how this endpoint was selected. The result should therefore be read as a statistical description of change in BMI z-score, not as evidence by itself about broader outcomes.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The placebo arm had a reported mean 16-wk change in BMI z-score of 0.02, with a 95% confidence interval from -0.03 to 0.06. The metformin arm had a reported mean change of -0.08, with a 95% confidence interval from -0.13 to -0.04. These are arm-specific estimates. The registry record does not report an estimable two-arm comparison for this continuous endpoint, so the posted results do not give a direct estimate or confidence interval for the difference between the randomized groups.
The confidence interval for the placebo arm includes zero, while the metformin-arm interval lies below zero. This describes the location of each arm’s estimate and its interval, not whether the arms differ from one another. In particular, comparing two separate confidence intervals is not a substitute for a confidence interval around the between-arm contrast. No p-value for that contrast is reported in the registry record.
The arm counts associated with the primary result are 32 for placebo and 28 for metformin. The registry record does not explain the difference between these counts or report the number randomized to each arm separately from the numbers contributing to the outcome. It also does not report the analysis population, handling of missing measurements, or adjustment variables. These omissions limit interpretation of how the estimates were obtained.
The 95% confidence intervals communicate uncertainty about the arm-specific mean changes under the analysis used. They do not describe the range of changes among individual participants, and they do not account for uncertainty introduced by unreported design or analysis choices. The record also does not provide an explicitly stated threshold for a meaningful change in BMI z-score. Statistical interpretation should therefore remain focused on the reported mean changes and their precision, rather than labeling the changes as clinically important or asserting a treatment effect.
The registry lists secondary measures related to body composition and fasting metabolic parameters, but the record does not report a full set of secondary results in the registry record for this analysis. The primary endpoint is consequently only one part of the study’s intended assessment. It cannot, on its own, resolve questions about other outcomes, adverse effects, or the overall balance of results.
9. Statistical Methods Explained
The primary outcome is continuous, and the registry reports a mean change for each arm with a 95% confidence interval. The record identifies the parameter as a mean and the dispersion as a confidence interval. It does not describe the specific statistical model, estimation procedure, or assumptions used for the reported endpoint analysis. General explanations below describe how these statistical quantities are usually interpreted; they should not be taken as confirmation of an unreported analysis plan.
What does a mean change describe?
In general, a mean change is the average of participants’ changes between baseline and follow-up. It provides a compact description of the group’s average movement on the measure. Individual participants can have changes that differ substantially from the mean, and the mean alone does not show that distribution. The registry record does not report the standard deviation, individual observations, or another measure of participant-to-participant variability for the primary endpoint.
The reported placebo mean is 0.02 and the metformin mean is -0.08. Those estimates describe each arm separately. The scientific comparison in a randomized trial is generally the difference in outcome between groups, because that contrast uses the randomized allocation to assess how the groups’ observed outcomes compare. No estimable two-arm comparison is reported for this continuous endpoint in the registry record. It would not be appropriate to construct a contrast, uncertainty interval, or test result from the arm summaries in this explanatory text.
How should a confidence interval be read?
In general, a confidence interval gives a range of values compatible with the data and the method used to estimate a quantity, subject to the method’s assumptions. A 95% confidence interval is not a guarantee that the true value lies inside the specific interval, nor is it the range containing 95% of individual participants’ outcomes. It describes uncertainty about the estimated mean, not individual variation.
For placebo, the reported interval is -0.03 to 0.06; for metformin, it is -0.13 to -0.04. The placebo interval includes zero, and the metformin interval does not. This is a description of each interval relative to zero. It does not establish whether the two arm means differ: a direct between-arm estimate and its uncertainty are needed for that question. A confidence interval also does not determine whether a change matters clinically. The registry record does not state a clinically important threshold for this endpoint.
Why does the between-arm estimate matter?
In general, treatment comparisons are evaluated using a contrast such as the difference in mean change between arms. Its confidence interval indicates the precision of that contrast, while a statistical test may assess compatibility with a specified null hypothesis. The reported arm-level means and intervals do not replace that calculation. The registry record marks the continuous two-arm comparison as not estimable and gives no test result for the primary contrast. Accordingly, neither a between-arm effect size nor its statistical significance is available in the record.
General statistical reasoning also cautions against treating a change within one arm as evidence of an intervention effect. Changes can reflect many influences, including time and factors shared by both groups. Randomized comparisons are designed to distinguish the groups’ outcomes, subject to the study’s implementation and analysis. The record does not provide enough detail to characterize those factors or the assumptions applied.
What do the planning assumptions mean?
The stated planning illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, and describes effects as fractions of the observed effect. These are assumptions for an illustrative sample-size calculation, not a report of the trial’s original design justification. The record does not report the trial’s own sample-size justification. Planning values describe how many participants per arm might be needed under specified assumptions; they are not observed power and do not indicate the probability that a result is true. No additional sample-size values are restated.
In general, sample-size planning depends on the effect targeted, outcome variability, significance level, desired power, and design assumptions. Changing those assumptions changes the planning result. An illustration based on an observed effect is particularly dependent on that estimate, which may itself be uncertain. It should not be confused with the number enrolled in this trial or treated as proof that the study was adequately powered for its primary comparison.
What statistical details remain unknown?
The registry record does not report the model used for the primary endpoint, whether the analysis adjusted for baseline BMI z-score or other covariates, how repeated measurements were handled, whether the analysis followed intention-to-treat principles, or how missing outcome values were treated. It also does not report interim analyses, a statistical analysis plan, or a prespecified method for the primary between-arm comparison. These details are important for understanding the exact estimand and the robustness of the reported estimates.
General statistical methods can explain what a mean, confidence interval, or planning assumption means, but they cannot fill in those missing trial-specific details. The most defensible reading is limited to the arm-specific mean changes and intervals reported, with no claim about an unreported direct comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 secondary outcomes, including changes in absolute and relative weight, absolute BMI, abdominal and hip circumference, and fasting total cholesterol, LDL, and HDL. The primary endpoint is change in BMI z-score. Evaluating multiple outcomes can raise multiplicity concerns: in general, the more hypotheses tested, the greater the chance that some results appear noteworthy by chance. Whether and how to address that issue depends on the prespecified analysis plan, including any outcome hierarchy or adjustment procedure. Such a plan is not reported in the registry record.
The record does not provide complete secondary outcome results in the registry record for this analysis, so no conclusions about those outcomes are drawn. It also does not report whether analyses were prespecified, whether subgroup analyses were conducted, or whether any multiplicity adjustment was used.
Missing-data handling is not reported in the registry record. The primary outcome counts are 32 for placebo and 28 for metformin, but the record does not explain whether these counts represent all randomized participants, participants with observed follow-up, or another analysis population. It does not report missingness by visit, reasons for missing data, withdrawals, imputation, or sensitivity analyses.
Analysis populations are likewise not described. The record does not say whether the primary result used all randomized participants, participants who completed treatment, or another defined group. These omissions matter because the analysis population and missing-data assumptions can affect estimates and their uncertainty. They cannot be resolved from the reported means and confidence intervals alone.
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 |
|---|---|---|---|
| Placebo Hydrochloride Oral Solution | 1 | 32 | 3.1% |
| Metformin | 0 | 28 | 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 |
|---|---|
| Placebo Hydrochloride Oral Solution | 32 of 32 |
| Metformin | 28 of 28 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo Hydrochloride Oral Solution | Metformin |
|---|---|---|---|
| Aggression | Psychiatric disorders | 1 of 32 | 0 of 28 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo Hydrochloride Oral Solution | Metformin |
|---|---|---|---|
| Overall | Gastrointestinal disorders | 19 of 32 | 24 of 28 |
| Overall | Infections and infestations | 19 of 32 | 14 of 28 |
| Diarrhea | Gastrointestinal disorders | 13 of 32 | 17 of 28 |
| Overall | General disorders | 14 of 32 | 13 of 28 |
| Overall | Psychiatric disorders | 13 of 32 | 14 of 28 |
| Overall | Nervous system disorders | 10 of 32 | 12 of 28 |
| Overall | Respiratory, thoracic and mediastinal disorders | 12 of 32 | 8 of 28 |
| Upper respiratory tract infection | Infections and infestations | 11 of 32 | 6 of 28 |
| Overall | Metabolism and nutrition disorders | 8 of 32 | 8 of 28 |
| Irritability | General disorders | 7 of 32 | 7 of 28 |
Serious events with the highest arm-level rate: aggression (3.1%).
The serious adverse event figures are reported separately by arm. In the placebo arm, 1 of 32 participants at risk was recorded as affected by a serious adverse event; in the metformin arm, 0 of 28 was recorded as affected. These are counts, not estimates of a comparative risk. The registry record does not report a formal statistical comparison of serious adverse events, and the small counts do not support a precise conclusion about differences between arms.
Aggression is listed among the top serious adverse event terms with a reported value of 3.1%. The registry record does not clarify the event count or arm attribution associated with this listed term in the registry record for this analysis. The record also lists other adverse events as affecting 32 of 32 participants in the placebo arm and 28 of 28 in the metformin arm. Those figures do not describe the severity, duration, or number of events per participant.
Deaths are recorded as null, so mortality information is not reported in the registry record. More broadly, adverse event counts should be interpreted as safety reporting, not as proof that an event was caused by a study intervention. The registry record does not provide enough detail about event definitions, collection methods, timing, or attribution to answer those questions.
12. What the Result Does, and Does Not, Mean
The posted primary result describes mean change in BMI z-score within each randomized arm over 16 weeks. The placebo mean was 0.02, with a 95% confidence interval from -0.03 to 0.06. The metformin mean was -0.08, with a 95% confidence interval from -0.13 to -0.04. The confidence intervals convey uncertainty around those separate arm means.
These estimates do not provide a direct treatment contrast. The registry record marks the two-arm comparison for this continuous endpoint as not estimable, and it reports no contrast estimate or p-value. The arm-specific intervals cannot be used as a substitute for a between-arm confidence interval. Consequently, the posted primary data do not establish the magnitude or precision of a difference between metformin and placebo.
The result also does not establish whether a change is clinically meaningful. The record does not give a threshold for an important change in BMI z-score, and the endpoint is a measure of body size rather than a direct report of broader health or functioning. Nor do the primary results answer questions about the secondary body-composition or metabolic outcomes, for which complete results are not reported in the registry record.
Safety information is limited to the adverse event counts and term listing. Those figures do not establish causation or provide a complete assessment of risk. The registry record does not report the details needed to assess the analysis population, missing data, intervention dose, adherence, or statistical plan. Such unknowns should not be replaced by assumptions.
In general, a randomized comparison can be informative when the group contrast is reported and the analysis is sufficiently transparent. In this record, the principal numerical information is the mean change in each arm and its confidence interval. The appropriate interpretation is therefore descriptive and bounded: it characterizes the posted arm-level results but does not support a definitive comparative claim.
13. Why This Trial Matters Statistically
This trial is statistically notable because it concerns a continuous outcome in a randomized, parallel-group design, yet the registry record reports arm-specific estimates without an estimable two-arm comparison. The distinction illustrates why the central quantity in a trial is usually the contrast between randomized groups, not whether a change within one group can be distinguished from zero. Separate arm means and confidence intervals describe the groups, but do not answer the comparative question with the same directness.
The result also shows why precision and clinical importance are distinct. Confidence intervals convey statistical uncertainty about a mean. Judging whether a change matters to participants requires a meaningful-change threshold or other clinical context; none is reported for this endpoint. A standardized BMI measure is useful for describing body-size change in young people, but it remains one outcome among the trial’s listed measures.
The study record includes a set of secondary body-composition and fasting metabolic outcomes, raising the general issue of multiplicity. Without a reported analysis plan, it is not possible to tell how outcome priorities or multiple tests were handled. Likewise, the lack of information about missing data and analysis populations makes the relationship between enrollment and outcome counts unclear.
These points are broadly relevant to reading registry results: identify the estimand, distinguish arm-level summaries from a randomized contrast, inspect uncertainty, and separate statistical interpretation from clinical judgment. Here, the posted information supports a focused description of the primary arm means and their confidence intervals, while leaving important parts of comparative inference undocumented.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record does not report a direct estimate or confidence interval for the primary between-arm comparison, despite listing arm-specific mean changes. It also does not explain why 32 placebo participants and 28 metformin participants contribute to the reported primary outcome, or how those counts relate to the total enrollment of 60. The analysis population and handling of missing measurements are not reported.
Further interpretation is constrained by the absence of details about the BMI z-score reference standard, the statistical model, baseline adjustment, and other analysis decisions. The record does not report the intervention dose, schedule, adherence, or treatment discontinuations. It also does not give the participants’ age range or fuller eligibility criteria beyond the condition and overweight descriptions.
The registry record lists 11 secondary outcomes but the registry entries summarized for this analysis do not include their complete results. The statistical plan, multiplicity procedures, interim analyses, and sample-size justification are not reported. The planning assumptions described for an illustration should not be treated as evidence of the original design rationale or as observed power.
Safety interpretation is limited by sparse serious adverse event counts, the lack of event-level detail, and the absence of reported mortality information. The registry record does not explain the listed aggression term’s arm attribution or provide detail about adverse event collection and causality. These are limitations of the available record; they do not establish that the unreported procedures or information were absent from the trial itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD) — NCT01825798.
- Registry record last updated 2025-07-16; status last verified 2018-01.
- Results first posted 2018-02-22.
- 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
NCT01825798 is a completed Phase 3 randomized, quadruple-masked, parallel-group trial sponsored by Holland Bloorview Kids Rehabilitation Hospital. It enrolled 60 participants and compared metformin with placebo in young people with autism spectrum disorders and overweight who were taking atypical antipsychotic medication. The recorded study start was 2013-04, with primary completion in 2015-06.
The primary endpoint was change in BMI z-score from baseline to 16 weeks. The placebo mean change was 0.02 (95% confidence interval: -0.03 to 0.06), and the metformin mean change was -0.08 (95% confidence interval: -0.13 to -0.04). A direct two-arm comparison for this continuous endpoint is not reported as estimable. Serious adverse events affected 1 of 32 participants in the placebo arm and 0 of 28 in the metformin arm. The record does not report the statistical plan, missing-data methods, analysis populations, or a full set of secondary outcome results.