A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms (NCT00541346), a non-randomized phase 3 study. The primary outcome is Change in Attention Deficit Hyperactivity Disorder Rating Scale - IV (ADHD-RS-IV) Total Score From Baseline to 8-week Follow-up Visit.

2. Clinical Question

The clinical question is framed as change over time within one treated group, rather than a comparison between treatment and control. The primary measure was a parent rating of ADHD symptom frequency based on DSM-IV criteria. The registry describes raw scores from 0-54, with higher scores indicating more frequent ADHD symptoms.

The study also named behavioral, participation, family, and caregiver-assistance measures as secondary outcomes. Those measures broadened the planned assessment beyond ADHD symptoms alone, but the registry record does not report numerical results for them. It also does not report a numerical change, variability estimate, confidence interval, or p-value for the primary measure. Consequently, the record establishes what the investigators intended to assess, but does not give the numerical result needed to describe the size or precision of change.

Because the study had no control group, a change between baseline and follow-up would describe the observed course of scores among participants in this study. By itself, such a change would not separate treatment effects from other explanations for change over time. This limitation applies even if a before-and-after difference is statistically precise.

3. Trial Design

The registry identifies this as a Phase III, non-randomized, single-group study with no masking. Its title calls it a pilot study, and its brief summary describes an open-label assessment of methylphenidate transdermal system in children with autism spectrum disorders and symptoms of inattention, hyperactivity, and impulsivity. These labels describe different aspects of the record: the title uses “pilot,” while the phase field identifies Phase III.

The enrollment field reports 16 participants. The brief summary says twenty patients would be enrolled and treated, so the planned number in that narrative differs from the enrollment recorded for the completed study. The registry status is completed. The start is recorded as 2007-09 and primary completion as 2009-05.

The intervention was described as 10mg for one week, followed by weekly stepwise increases to 15mg, 20mg, and 30mg for additional 7 weeks if symptom reports remained elevated. The arm description also states that titration decreased one stepwise dosage; further criteria for reducing a dose are not reported in the registry record. The summary describes treatment for a total of eight weeks.

With one group and no masking, the design can describe scores and events among participants receiving the intervention, but it cannot make a randomized, concurrent comparison. The registry record does not report a control arm, an allocation ratio, or a blinding procedure beyond identifying masking as none. It also does not report a detailed sample-size justification, recruitment procedures, or the reasons that enrollment was 16 rather than the twenty described in the brief summary.

The intervention was a drug, and the primary assessment compared baseline with the 8-week follow-up. The record does not report whether other care was restricted or how concomitant treatments were handled. That information would matter when interpreting changes over time, because the record does not establish that the study treatment was the only influence on participants' symptoms.

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.

Baseline

Follow-up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to Treat (ITT). Bayesian posterior-predictive imputation of the 8th-week follow-up assessment was used to handle missing data for a single drop-out participant who left the study after a 2nd follow-up visit.

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 Change in Attention Deficit Hyperactivity Disorder Rating Scale - IV (ADHD-RS-IV) Total Score From Baseline to 8-week Follow-up Visit, measured over Baseline, 8 weeks.

The primary endpoint was change in the total score on the Attention Deficit Hyperactivity Disorder Rating Scale - IV (ADHD-RS-IV) from baseline to the 8-week follow-up visit. The measure is described as a parent rating scale that assesses frequency of ADHD symptoms using DSM-IV criteria. Raw scores range from 0-54, and higher scores indicate a higher frequency of ADHD symptoms. The analyses were to use raw scores.

A parent rating scale offers a structured way to capture reported symptoms across the assessment period. Repeating the same measure at baseline and follow-up makes it possible to describe how ratings changed within the study group. The endpoint is continuous, and its stated summary measure is a mean with standard deviation. In general, a mean describes the group’s average score, while a standard deviation describes the spread of individual scores around that average.

The registry record identifies the assessment times and the scale, but does not report the baseline mean, the follow-up mean, the mean change, or its standard deviation. It therefore does not show the direction, size, or precision of the primary endpoint result. The measure reflects parent ratings on the specified scale; it is not, by itself, a complete account of every aspect of behavior or functioning.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary measure analyzed as a mean, with standard deviation as the dispersion measure. It also identifies an intention-to-treat population and Bayesian posterior-predictive imputation for one missing 8th-week follow-up assessment. The numerical primary outcome results and the detailed statistical plan are not reported in the registry record.

What does a mean and standard deviation describe?

In general, a mean is the arithmetic average of participants’ scores and gives a measure of the group’s central value. A standard deviation describes how widely individual scores vary around that mean. These quantities answer different questions: the mean describes average level, while the standard deviation describes variation among participants. A standard deviation is not the same as the uncertainty in the estimated mean or mean change.

For a baseline-to-follow-up endpoint, the mean change would summarize average within-participant change if calculated from paired assessments. The registry record identifies change as the primary endpoint but does not give the mean change or explain the exact calculation used to derive it. It does not report a confidence interval for the change. In general, a confidence interval describes a range of values compatible with the data under the statistical model and conveys estimation uncertainty; it is not a guarantee that the true value lies in the interval.

What does the single-group design allow?

This study has one group, no random allocation, and no masking. In general, a single-group pre-post analysis can describe change among participants who were assessed over time. Without a concurrent control group, it cannot distinguish the effect of treatment from other explanations for change. Randomization is commonly used to make treatment groups comparable in expectation, while masking can limit some influences of treatment knowledge on assessment. Neither feature is reported for this trial.

The analysis of change may account for the fact that two measurements come from the same participant. However, the registry record does not report the specific model or test used, so the exact statistical procedure cannot be identified. It also does not report model assumptions, covariate adjustment, or the handling of all possible deviations from the planned assessment schedule.

How should the missing-data method be understood?

The primary outcome population is identified as intention to treat. The record says Bayesian posterior-predictive imputation was used for the 8th-week assessment of a single participant who left after a 2nd follow-up visit. In general, imputation replaces a missing value with a value drawn or estimated using a statistical model, allowing an analysis to include a participant whose outcome was not observed at the specified time. A posterior-predictive approach uses a Bayesian model’s predictive distribution for the missing observation.

Imputation does not recover a directly observed score. Its validity depends on the model and assumptions used to represent missing outcomes. The registry record does not report the priors, model variables, number of imputations, or sensitivity analyses for alternative missing-data assumptions. It also does not report how many participants had any other incomplete assessments. These absent details limit independent evaluation of the imputation procedure.

What do planning calculations mean?

In general, a sample-size calculation estimates how many participants may be needed under specified assumptions about the effect to detect, variability, significance level, allocation, and statistical method. The planning illustration associated with this study uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is based on a stated fraction of the observed effect. Those assumptions describe an illustration, not the design of this single-group study.

The planning calculations are not observed power. Observed power is not a substitute for reporting an effect estimate and its uncertainty. A planning illustration based on the observed effect is especially dependent on the estimated effect, which can be imprecise in a small study. The registry record does not report a sample-size justification for the original design, and the planning assumptions should not be interpreted as evidence that the trial was designed with two treatment arms.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a model assumes. It can make uncertainty estimates too small if the model does not accommodate the extra variation. This issue is most commonly discussed for count or binary outcomes, rather than a continuous rating-scale total analyzed as a mean. The registry record does not report an over-dispersion analysis for this trial, and no conclusion about its presence can be drawn from the recorded methods.

What can be said about multiplicity and interim analyses?

The registry records 11 outcome measures and 11 analyses. It identifies the ADHD-RS-IV total score as primary and lists secondary measures of behavior, participation, family functioning, and caregiver assistance. In general, testing or examining multiple outcomes raises a multiplicity concern: without a prespecified adjustment or hierarchy, the chance of at least one apparently unusual result can increase. Whether an adjustment was planned or used is not reported in the registry record. Interim analyses are also not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies the ADHD-RS-IV total score as the primary outcome and records 11 outcome measures and 11 analyses. Secondary measures include ABC Hyperactivity, Irritability, Lethargy, Stereotypy, and Inappropriate Speech scores; the Lifetime Participation Scale total score; the Family III General Scale summed score; and the Pediatric Evaluation Disability Inventory Caregiver Assistance: Self-Care measure. The registry record does not report whether the analyses followed a testing hierarchy or used an adjustment for multiple comparisons.

Multiplicity matters because examining several outcomes can make isolated findings difficult to interpret as confirmatory. In general, a prespecified strategy can help distinguish a primary test from exploratory analyses and can address the increased chance of false-positive findings across multiple tests. The registry record does not report such a strategy, so it is not possible to assess how multiplicity was handled.

The primary analysis population is described as intention to treat. The record states that Bayesian posterior-predictive imputation was used for the 8th-week assessment of one participant who left after a 2nd follow-up visit. The model details and sensitivity analyses are not reported in the registry record. It is also not reported whether missing values occurred for other outcomes or how those outcomes were handled.

Intention to treat generally refers to analyzing participants according to their assigned or enrolled group, but this was a single-group study and the registry’s description does not provide further operational details. Interim analyses and stopping rules are not reported in the registry record. No assumptions about them can be made from the completed status alone.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tic (6.2%).

The registry records 16 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it records 16 at risk and 14 affected. These are counts of participants, not a measure of symptom improvement or treatment effect. The registry record does not provide event-level details, duration, severity grading, or a comparison group for these figures.

The top serious adverse-event term is tic, listed at 6.2%. A listed term does not by itself show that the event was caused by the intervention. The registry record does not give further details about the event, its timing, or the basis for classifying it as serious. It also does not report a numeric death count; the death entry is not reported in the registry record, so it should not be interpreted as a confirmed count of zero.

Serious and other adverse events are separate categories in the registry record. The figures should not be added together or treated as a count of unique events: the record does not explain whether participants could be represented in both categories or whether multiple events occurred in one participant. With 16 participants at risk, these safety observations describe this study group only and do not estimate comparative risk against a control group.

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

The record establishes that a completed, open-label, single-group study assessed transdermal methylphenidate in children with autism and ADHD symptoms. It identifies the ADHD-RS-IV total score change from baseline to 8-week follow-up as the primary endpoint and describes how to interpret the scale. It also records safety counts and several secondary outcome measures.

The record does not report the numerical primary endpoint result. It therefore does not establish whether the average score increased or decreased, how large any change was, or how precisely it was estimated. The same limitation applies to the listed secondary outcomes: numerical results are not reported in the registry record. The study’s stated hypothesis is not evidence that the hypothesized result occurred.

Even if numerical pre-post results were available, this single-group, non-randomized, unmasked design would not isolate a causal treatment effect. A within-group change can be affected by the natural course of symptoms, expectations, assessment conditions, or other care. Without a concurrent comparison group, the observed course under treatment cannot be directly contrasted with what would have occurred without it.

The study’s size and the imputation of one missing follow-up assessment are also relevant to precision and interpretation. The registry record does not report the primary estimate or its uncertainty, the detailed imputation model, or a sample-size justification. Thus, neither the magnitude nor the robustness of an estimated change can be evaluated from the record.

The safety figures describe participants affected within this group; they do not establish causation or comparative safety. The overall meaning is therefore limited to the study’s design, planned measurements, and recorded adverse-event counts. The available registry information does not support a conclusion about the size of symptom change or about a causal effect of treatment.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design and reporting determine what an estimate can mean. A repeated symptom scale can describe change over time, but the single-group design does not provide a treatment-versus-control contrast. That distinction remains important even when a study has a defined primary endpoint and a completed status.

The primary endpoint is clearly named and its scoring direction is described: higher ADHD-RS-IV raw scores indicate more frequent ADHD symptoms. That definition helps interpret a numerical change if reported. But the registry record does not give the scores or estimated change, illustrating the difference between registering an outcome and reporting its result. Without an estimate and a measure of uncertainty, the magnitude and precision of the outcome cannot be judged.

The record also documents an intention-to-treat population and imputation for one missing 8th-week assessment. These details matter because missing outcomes can affect the analysis, and model-based imputation depends on assumptions. The registry does not provide enough model detail to evaluate those assumptions or the sensitivity of results to them.

Finally, the registry records 11 outcome measures and 11 analyses. This makes the reporting of prespecified priorities and multiplicity methods important for distinguishing confirmatory from exploratory evidence. Those methods are not reported. The trial therefore highlights several core statistical questions for clinical research: whether the design supports causal inference, whether the primary estimate and its uncertainty are available, how missing data were handled, and how multiple outcomes were interpreted. The registry record leaves these questions partly unanswered, so interpretation must remain descriptive and bounded.

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 principal limitation is the absence of numerical primary-outcome results in the registry record. Baseline and follow-up ADHD-RS-IV means, mean change, standard deviation of change, confidence interval, and p-value are not reported in the registry record. Numerical results for secondary outcomes are also not reported in the registry record. Consequently, the amount and precision of change cannot be assessed.

The study was non-randomized, single-group, and unmasked. There was no concurrent control group, so the design cannot distinguish treatment-associated change from other changes over time. Parent ratings were used for the primary measure, and the open-label design means the assessment was not masked to treatment status. The record does not report whether other treatments or care changed during follow-up.

The enrollment field records 16 participants, while the brief summary describes an intention to enroll twenty. The registry record does not explain this difference. The record also does not report a sample-size justification for the original study, so the intended precision or detectable effect cannot be assessed from the design description.

Missing primary follow-up data for one participant were handled using Bayesian posterior-predictive imputation, but details of the model and sensitivity analyses are not reported in the registry record. Whether other outcomes had missing data, and how any such values were handled, is not reported in the registry record. The record does not report whether multiplicity adjustment or interim analyses were planned.

Safety information is limited to participant counts and a listed serious-event term. The registry record does not report detailed event timing, event descriptions, causality assessments, or a numeric death count. These limitations restrict both efficacy and safety interpretation to the descriptive information recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms — NCT00541346.
• Registry record last updated 2014-02-06; status last verified 2013-12.
• Results first posted 2014-02-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry identifies a completed Phase III, open-label, non-randomized, single-group study of methylphenidate transdermal system in children with autism and ADHD symptoms. Enrollment is recorded as 16. The primary endpoint was change in ADHD-RS-IV total score from baseline to the 8-week follow-up; higher raw scores indicate more frequent ADHD symptoms.

The primary analysis population is identified as intention to treat, with Bayesian posterior-predictive imputation for one missing 8th-week assessment. The registry also records 11 outcome measures and 11 analyses. It does not report numerical primary or secondary outcome results, a detailed statistical plan, or a sample-size justification.

For safety, 1 participant was affected by a serious adverse event and 14 by other adverse events, among 16 at risk in each category. Tic is listed at 6.2% among the top serious terms. A numeric death count is not reported in the registry record. The single-group design supports description of outcomes over time, but not a randomized comparison or an isolated causal estimate.