Study of Medication Patch to Treat Children Ages 6-12 With ADHD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Medication Patch to Treat Children Ages 6-12 With ADHD (NCT00586157), a randomized phase 4 study. The primary outcome is Efficacy Defined as Change From Baseline on the Investigator Rated DSM-IV Based ADHD Rating Scale, Over the Course of the Day..

2. Clinical Question

3. Trial Design

This was a Phase 4 study listed as randomized, triple-masked, and crossover. The two interventions were Methylphenidate Transdermal System (MTS) and placebo. A crossover design means that participants receive both study conditions in different periods, allowing comparisons within a participant as well as across treatment periods. The registry record does not report the treatment sequence, period lengths, washout arrangements, or how those features were handled in the primary analysis.

The study enrolled 36 and is marked completed. The recorded start was 2006-09 and primary completion was 2008-12. Massachusetts General Hospital is listed as sponsor. These registry entries describe the study, but do not establish how many participants contributed usable observations to every endpoint or analysis.

The primary outcome is an investigator-rated DSM-IV based ADHD Rating Scale measure of change from baseline, with a timeframe of baseline and 4 weeks. The posted arm summaries contain 30 for MTS and 29 for placebo. The secondary outcome describes investigator and parental/self-report rating scales and questionnaires; the registry posts one secondary results entry.

The sponsor's recorded analysis is a Z-test, with a reported p-value of <.001 for the primary comparison. The registry record does not report an estimate or confidence interval for that analysis. The separately recalculated unadjusted comparison is based on posted arm summary statistics and should not be mistaken for a reconstruction of a crossover model. Details of the trial's planned statistical model, analysis populations, missing-data methods, and sample-size justification are not reported in the registry record.

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: 36 subjects signed consent, and 6 discontinued/withdrew consent prior to completing one week of treatment. The remaining 30 subjects were included in data analyses and thus reported.

First Intervention

Reasons for not completing this period:

Second Intervention

Reasons for not completing this period:

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 Efficacy Defined as Change From Baseline on the Investigator Rated DSM-IV Based ADHD Rating Scale, Over the Course of the Day., measured over Baseline and 4 weeks.

The primary endpoint is described as change from baseline on the investigator-rated DSM-IV based ADHD Rating Scale, over the course of the day. The registry describes a scale whose items range from 0 to 3 in severity, with 0 the least severe item score and 3 the most severe; the total possible scale range is 0 to 54. It identifies the measure as a mean and reports standard deviations for the arm summaries.

Rating scales turn observations about symptoms into structured scores that can be summarized and compared. An investigator-rated measure offers a standardized assessment from the investigator's perspective. The study's stated early-morning focus makes symptom ratings relevant to the question of functioning before school or summertime routines, although the registry's primary endpoint title refers to the course of the day.

The scale description clarifies the direction of severity for scale scores: higher scores indicate greater severity. However, the record does not explain the precise sign convention used for change from baseline, such as whether a reduction is represented by a negative change. Consequently, the reported mean changes and their contrast can be described numerically, but their coding should not be inferred beyond the registry description.

The measure is useful for comparing reported scores, but it does not by itself describe every aspect of a child's experience or establish the clinical importance of a difference. The record does not report a threshold for a clinically meaningful change.

7. Results Posted in the Registry

• MTS (Drug A): mean 14.76 versus 28.33 on control; difference -13.57 (95% CI -21.30 to -5.84), standardized effect d = -0.90; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Efficacy Defined as Change From Baseline on Investigator and Parental/Self-report Based Rating Scales and Questionnaires

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • MTS (Drug A): mean 12.76 versus 31.37 on control; difference -18.61 (95% CI -27.41 to -9.81), standardized effect d = -1.08; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for MTS (Drug A) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry posts one secondary results entry describing investigator and parental/self-report based rating scales and questionnaires. Its numerical pattern is in the same direction as the primary summary: the posted mean change value is lower for MTS than for placebo. The entry also reports an unadjusted comparison with a confidence interval that excludes zero and a p-value of <0.001. Those findings are consistent with the broad direction of the primary result, but do not independently settle the primary outcome's coding or crossover-analysis limitations.

The entry's title refers to rating scales and questionnaires, but the record does not provide a broader set of posted secondary results from which to judge consistency across multiple secondary endpoints. It is therefore not appropriate to describe the full family of secondary measures as uniformly positive or to infer that every scale supported the same conclusion.

Unadjusted secondary results carry less weight when the record does not describe how multiple comparisons were handled. In general, testing several outcomes can increase the chance of finding at least one apparently strong result by chance. A prespecified hierarchy or multiplicity adjustment can address that issue, but neither is reported in the registry record. The secondary result is best understood as supportive information, not as a separately confirmed finding. The endpoint's measurement and analysis details are not sufficient to determine how ratings from different sources were combined or whether the result reflects a particular informant or scale.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Efficacy Defined as Change From Baseline on Investigator and Parental/Self-report Based Rating Scales and Questionnaires

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a numeric scale score summarized by a mean and standard deviation. A mean gives the arithmetic average of the reported values, while a standard deviation describes how spread out those values are around the mean. In this record, the reported arm means are 14.76 for MTS and 28.33 for placebo, with standard deviations of 14.48 and 15.75, respectively. These summaries do not show the full distribution of scores or how individual participants' scores changed between treatment periods.

What does the mean difference represent?

The recalculated comparison subtracts the placebo mean from the MTS mean. Its estimate is -13.57. A negative value means the MTS summary mean is numerically lower under that subtraction convention. The scale description says higher scale scores represent greater severity, but the endpoint is change from baseline and the registry does not explain the sign convention for change. The difference therefore should be read as a contrast in posted mean change values, not as a standalone statement about the amount of symptom reduction.

The recalculation is unadjusted: it uses arm-level summary statistics rather than participant-level data or a model incorporating the trial's crossover structure. That distinction matters because crossover observations from the same participant are related. General statistical principle: when outcomes measured in the same person are correlated, an analysis that treats them as independent may not represent the uncertainty of the within-person comparison. The registry does not report enough detail to determine whether the sponsor's Z-test accounted for this dependence, periods, or treatment sequence.

How should the confidence interval and p-value be read?

The recalculated 95% confidence interval for the mean difference is -21.3 to -5.843. In general, a confidence interval expresses the uncertainty around an estimate under the assumptions of the method used. This interval does not include zero, which is consistent with the recalculated unadjusted p-value of <0.001. The sponsor separately reports a Z-test p-value of <.001. These p-value formats are not identical, but both are reported as below 0.001 in their respective forms. Neither p-value indicates the probability that a treatment is effective or that the null hypothesis is true.

The standard deviations are substantial relative to the means, but describing spread is not the same as judging clinical meaning. General statistical principle: high variability can make an estimate less precise, particularly when the amount of available information is limited. The displayed confidence interval provides one way to assess uncertainty in the recalculation. It does not incorporate unreported aspects of the design or analysis.

Why does the crossover design matter?

A crossover trial compares treatments received by the same participants in separate periods. This can be efficient because each participant can serve as their own comparison, reducing some differences between people. The design also introduces specific considerations: treatment sequence, period effects, carryover, and within-participant correlation. A period effect is a change associated with timing rather than treatment; carryover is an effect from an earlier treatment that remains into a later period. These are general concepts, not claims that such effects occurred in this trial.

The registry record identifies the trial as crossover but does not report the sequences, period details, washout, model terms, or any assessment of carryover. The arm-level means and standard deviations are not sufficient to reconstruct a paired analysis. Thus, the displayed unadjusted difference is informative as a summary-statistic comparison, while its standard error and interval should not be assumed to reproduce a fully specified crossover analysis.

What do the secondary statistics add?

The secondary outcome is continuous and is reported as a mean with standard deviation. Its recalculated comparison is also unadjusted. General statistical principle: multiple outcome assessments create more opportunities for a nominally small p-value to arise by chance if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity strategy, so the secondary result should be treated as supportive and exploratory rather than as independent confirmation.

In general, interpretation also depends on who was included, how missing measurements were handled, and whether the analysis followed a prespecified plan. The record does not report the primary analysis population, missing-data procedure, or the original sample-size assumptions. Those unknowns cannot be filled in from the summary statistics.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -13.57, with a 95% confidence interval from -21.3 to -5.843. The interval gives a range of estimates compatible with the posted summaries under the recalculation's assumptions. It excludes zero, indicating that the unadjusted comparison is not centered on no difference. It also spans values that are meaningfully separated from one another, so the point estimate should not be treated as an exact effect.

In general, confidence intervals are a way to communicate statistical precision: a narrower interval indicates less sampling uncertainty under the method used, while a wider interval indicates more. This interval reflects an unadjusted comparison of arm-level summaries. It does not necessarily account for the paired structure of a crossover trial, because the registry record does not provide within-participant correlations or full model details.

The sponsor reports a Z-test p-value of <.001 but no sponsor estimate or confidence interval. The recalculated p-value is <0.001. Both indicate strong incompatibility with a no-difference null under their respective tests, but a p-value does not show the size, clinical relevance, or precision of an effect by itself. The interval is more informative about the range of effect estimates supported by the recalculation, while still carrying the limitations of that calculation.

The registry reports standard deviations of 14.48 for MTS and 15.75 for placebo. These describe variability among the posted values, not uncertainty in the mean difference. The reported counts, 30 for MTS and 29 for placebo, also do not by themselves explain the effective information available for a crossover comparison. The record does not report how missing observations or within-person dependence affected precision.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They illustrate sample sizes under stated assumptions rather than report the trial's original design target. The registry record does not report the original sample-size justification or design assumptions.

The illustration assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set at a stated fraction of the observed effect. The rows therefore represent planning for 100%, 75%, or 50% of the observed effect; they are not claims about effects the trial actually observed beyond its posted estimate.

The 80% power column gives the participants per arm associated with an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one. The 90% power column gives the corresponding number for a 90% chance. These are planning probabilities under a statistical model, not guarantees for a future study. The illustration gives 20 and 27 participants per arm for planning at 100% of the observed effect; 35 and 47 for 75%; and 78 and 105 for 50%, for 80% and 90% power respectively.

Smaller effects are harder to distinguish from random variation, so planning for a smaller fraction of the observed effect requires more participants per arm in this illustration. These figures are not observed power: observed power is not a useful substitute for interpreting the confidence interval and the uncertainty around an observed estimate. The planning values also do not adjust for unreported crossover design features or establish what assumptions were used to plan this trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -13.570; pooled standard deviation σ = 15.117.
2. n = 2 × (1.96 + 0.842)² × 15.117² / -13.570² = 19.5, rounded up to 20 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -13.57                      # observed difference in means
sigma <- 15.1171980602552                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(586157)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 20 (80% power), 27 (90% power)
 75% of observed effect: n per arm = 35 (80% power), 47 (90% power)
 50% of observed effect: n per arm = 78 (80% power), 105 (90% power)
power.t.test: 20.5 
Simulated power at n = 20 per arm: 0.790 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor's own recorded primary analysis is a Z-test with a reported p-value of <.001. The record does not include the sponsor's estimated treatment contrast or a confidence interval, so the sponsor's estimate cannot be compared directly with the recalculated estimate of -13.57 or its 95% confidence interval.

The recalculation uses the posted means and standard deviations to form an unadjusted comparison. It gives a p-value of <0.001, consistent in broad statistical direction with the sponsor's reported p-value. The record does not indicate a discrepancy between the sponsor result and the recalculation. Still, agreement between p-values does not establish that the analyses used the same model or addressed the crossover structure in the same way.

The sponsor analysis is the trial's reported analysis. The recalculation is a transparent summary-statistic calculation, not a replacement for participant-level analysis. Since the registry record does not specify the sponsor's model details, population, or treatment of period and sequence, it is not possible to determine precisely how the Z-test was applied or how it relates to the crossover design.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports a primary outcome and a secondary outcome entry, but the record does not describe a statistical hierarchy among outcomes, a multiplicity adjustment, or a prespecified strategy for interpreting several tests. In general, when multiple outcomes or comparisons are examined, the chance of at least one apparently small p-value can increase. Adjustment methods or a clearly defined priority order can help control that issue. Without such information, the secondary result should be treated cautiously and should not be read as an independent confirmation of the primary finding.

Missing-data methods are not reported in the registry record. The primary summaries list 30 for MTS and 29 for placebo, while the study enrollment is listed as 36. These figures alone do not explain participant flow, whether every participant contributed data in both crossover periods, or why the analysis counts differ from enrollment. The record does not say whether missing values were excluded, imputed, or addressed by another method.

The analysis population is also not reported in the registry record. There is no description of whether the sponsor used all randomized participants, participants with outcome data, or another defined set. This matters because different analysis populations can answer different questions and can be affected differently by missing observations.

Finally, although the trial is identified as crossover, the registry does not report whether its analysis accounted for period, sequence, or within-participant correlation. These are not assertions that the analysis was inadequate; they are limits on what can be established from the posted record. A full statistical plan, analysis population definition, participant flow, and missing-data explanation would be needed for a more complete assessment.

16. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted serious adverse event figures are 0 among 30 participants at risk in the MTS group and 0 among 29 participants at risk in the placebo group. These are the registry's reported counts for serious adverse events in the listed groups. A count of zero in these summaries means no serious adverse events are recorded for those groups in this results entry; it does not establish that no serious events could occur or that the treatments have equivalent safety.

The registry also lists other adverse events separately, but those counts are not serious adverse event counts and should not be conflated with them. The death fields are not populated, so deaths are not reported in the registry record. The record does not provide further detail about event definitions, follow-up completeness, or the timing of adverse events.

Safety counts in a trial should be read in light of the number observed, the duration and completeness of follow-up, and the way events were collected. The registry entry does not provide enough information to assess those features fully. These figures describe what is recorded and are not a comprehensive safety assessment.

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

The posted primary summaries show a lower mean change value for MTS than for placebo, with a recalculated unadjusted mean difference of -13.57 and a 95% confidence interval from -21.3 to -5.843. The sponsor's reported Z-test p-value is <.001. Taken together, these results indicate a clear statistical contrast in the posted summaries under the analyses reported.

That contrast does not by itself establish the clinical importance of the difference. The registry record does not report a threshold for meaningful change, and its description does not clarify the sign convention for change from baseline. Although the scale description says higher scores indicate greater severity, the direction of a change value depends on how change was coded. The numerical contrast should therefore be interpreted with that qualification.

The result also does not show that every child had the same response, nor does an average describe the full spread of individual outcomes. It cannot establish effects beyond the study's setting and enrolled population. The record describes children ages 6–12 with ADHD, but does not provide enough detail about recruitment, participant characteristics, adherence, or outcome completion to assess broader applicability.

The trial is listed as crossover, yet the registry does not report how the sponsor accounted for repeated observations, treatment periods, or sequence. The unadjusted recalculation is not a substitute for a complete crossover analysis. Nor do the posted results resolve questions about missing data, multiplicity, or the trial's original sample-size rationale.

Finally, the serious adverse event summary records zero events in each listed group, but those counts do not establish absence of risk or equivalence between treatments. The result is best read as a statistical comparison in the registry record, with important limits on clinical interpretation and on reconstruction of the underlying analysis.

18. Why This Trial Matters Statistically

This trial is statistically notable because it combines a randomized comparison with a crossover design. A crossover can allow participants to receive both conditions, but the analysis must account for the relationship between observations from the same participant and may need to consider treatment period and sequence. The registry identifies the design but does not give enough analysis detail to determine how these features were handled.

The difference between a sponsor-reported test and a recalculation from arm-level summaries illustrates why estimates, intervals, and methods all matter. The sponsor reports a Z-test p-value, while the recalculation provides a mean difference and confidence interval. The reported p-values are both below 0.001, but that agreement does not show that the analyses used equivalent assumptions or that the recalculated interval captures crossover dependence.

The record also illustrates the value of separating statistical evidence from clinical meaning. A confidence interval that excludes zero supports a contrast under the recalculation, but the registry does not state a threshold for meaningful change or clarify change-score coding. Precision and statistical significance cannot answer those questions alone.

Finally, planning illustrations based on an observed effect are not the same as the trial's original sample-size rationale. The record does not report that rationale. Keeping the observed estimate, its uncertainty, and planning assumptions distinct avoids treating a post hoc illustration as evidence that the original trial was designed around those assumptions.

19. 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.

Several limitations specific to this record constrain interpretation. The primary outcome is described as change from baseline on a severity scale, but the registry does not state the change-score sign convention. As a result, the reported contrast can be described numerically, while a direct translation into change in symptom severity remains uncertain from the record alone.

The trial is identified as crossover, but treatment sequence, period details, washout arrangements, and the statistical model are not reported. The recalculated comparison uses arm-level means and standard deviations and cannot recover the within-participant correlation needed to reproduce a paired or otherwise crossover-aware analysis. It should therefore be viewed as an unadjusted summary-statistic calculation.

The registry lists enrollment of 36, while the primary arm summaries report 30 and 29. It does not explain participant flow, missing outcome data, the analysis population, or whether participants contributed observations in both periods. No missing-data method or original sample-size justification is reported.

The record posts one secondary results entry and does not describe a multiplicity plan. That limits confidence in treating the secondary result as confirmatory. The outcome descriptions also do not provide a threshold for clinically meaningful change. Finally, the serious adverse event entry does not provide event timing or follow-up completeness, and the death fields are not populated. These omissions limit what can be concluded from the registry results without implying that the underlying study did not collect the information.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study of Medication Patch to Treat Children Ages 6-12 With ADHD — NCT00586157.
• Registry record last updated 2012-11-16; status last verified 2012-11.
• Results first posted 2011-01-25.
• 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.

23. Record Summary

The registry record describes a completed Phase 4 randomized, triple-masked crossover study of MTS versus placebo in children ages 6–12 with ADHD. Enrollment is listed as 36. The primary outcome is investigator-rated change from baseline on the DSM-IV based ADHD Rating Scale, with a baseline and 4 weeks timeframe.

The posted primary summaries show mean change values of 14.76 for MTS and 28.33 for placebo. The recalculated unadjusted difference is -13.57, with a 95% confidence interval from -21.3 to -5.843 and p <0.001. The sponsor reports a Z-test p-value of <.001.

Interpretation is limited by unreported change-score coding, crossover-analysis details, analysis populations, missing-data methods, and multiplicity handling. The record reports zero serious adverse events in each listed group; deaths are not reported in the registry record.