Long Acting Stimulant Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Young Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long Acting Stimulant Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Young Children (NCT00754208), a na phase 4 study. The primary outcome is Change in Attention Deficit Hyperactivity Disorder Rating Scale-IV Parent Version Investigator-Scored (ADHD-IV-Parent: Inv) Total Score..

2. Clinical Question

The sponsor's stated hypotheses were that Ritalin LA would be effective and reasonably well-tolerated for ADHD in children aged 4 and 5 years. Those are study aims, not findings. With no control group, any observed change would describe the course of scores during treatment in this group; it would not by itself isolate a treatment effect from other influences. The record does not report the endpoint estimates needed to assess even that within-group change.

3. Trial Design

This was a completed Phase 4 pilot study sponsored by the University of Nebraska. The registry records enrollment of 7 and describes the design as single-group, with allocation not applicable and no masking. The intervention was open-label methylphenidate, described in the study summary as Ritalin LA. The record gives the study start as 2008-09-18 and primary completion as 2010-01-01.

A single-group study follows participants receiving the intervention without a concurrent control arm. It can describe outcomes observed during the study, but it does not provide a direct randomized contrast against an untreated group, placebo, or another treatment. The absence of masking also means the record does not describe an effort to keep participants or study personnel unaware of treatment assignment. No assignment was made between treatment groups in this registered design.

The primary outcome was assessed at an 8-week timeframe and was defined as change from baseline to endpoint in the investigator-scored, parent-version ADHD Rating Scale-IV total score. The record also lists changes in Clinical Global Impression-Severity and Children's Global Assessment Scale score, and Clinical Global Impression-Improvement as secondary outcomes. Four outcome measures are listed overall. The registry record does not report visit schedules, the treatment dose, adherence, or the detailed procedures for collecting and scoring the outcomes.

The enrollment figure describes the registry's recorded enrollment; it should not be treated as confirmation of how many participants contributed to each outcome analysis. The analysis population and numbers included in endpoint analyses are not reported in the registry record. The record also does not describe a protocol for handling treatment discontinuation or incomplete follow-up. These omissions limit interpretation of both the design's execution and the results that could be inferred from it.

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: Please see inclusion and exclusion criteria.

Overall Study

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 Parent Version Investigator-Scored (ADHD-IV-Parent: Inv) Total Score., measured over 8 weeks.

The primary endpoint is change from baseline to endpoint in the investigator-scored, parent-version ADHD Rating Scale-IV total score, with an 8-week timeframe. The scale contains 18 items, each rated 0, 1, 2 or 3. Its total score ranges from 0 to 54, and higher scores indicate greater symptom severity. The endpoint is expressed in units on the scale.

A change score is intended to describe how a participant's measured score differs between the baseline assessment and the endpoint assessment. A continuous score retains gradations in symptom severity rather than reducing the assessment to a simple yes-or-no category. The registry specifies the mean as the outcome parameter and the standard deviation as the measure of dispersion. In general, the mean describes the average score change, while the standard deviation describes how spread out individual changes are around that average.

The direction of the endpoint is clinically interpretable because higher scale scores represent greater severity. However, the registry record does not report the mean change, its standard deviation, or an uncertainty interval. It therefore does not reveal the observed direction, magnitude, or precision of the primary outcome. The endpoint definition alone is not evidence that scores improved or worsened.

The record describes a parent-version scale scored by an investigator. It does not report details about who posted ratings at each visit, whether the same informant contributed at baseline and endpoint, or how incomplete item responses were handled. Such details can matter when interpreting change, but they are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

The registered primary parameter is a mean for a continuous outcome. For each participant with the required measurements, a change score represents the difference between the endpoint and baseline total scores, as described in the registry. A group mean summarizes those changes, but it does not show whether every participant changed in the same direction. The standard deviation describes variation in individual change scores around the mean; it is not the same as the uncertainty in the estimated mean.

In general, the standard error reflects uncertainty in an estimated mean and is used to construct a confidence interval or conduct a test. The registry specifies a standard deviation as the dispersion measure, but it does not report the observed standard deviation, standard error, confidence interval, or test result. No recalculation of the endpoint is possible from the registry record.

Why does the single-group design matter?

The registered model is single-group, and allocation is recorded as not applicable. This means the design does not include a randomized comparison between treatment arms. A within-group baseline-to-endpoint change can summarize the trajectory of scores among participants with measurements, but it is not equivalent to the difference in changes between a treatment group and a control group. That distinction matters because the treatment effect is ordinarily interpreted through a comparison that helps account for changes that could occur without the intervention.

The intervention is described as open-label and masking is listed as none. In general, masking can reduce the influence of expectations on some aspects of measurement or reporting. The registry does not give enough detail to determine how expectations may have affected ratings in this study. This is a design consideration, not evidence that a particular rating was biased.

How should uncertainty be understood?

In general, a confidence interval combines an estimate with its statistical uncertainty. It helps readers distinguish a relatively precise estimate from one that is compatible with a broad range of values. A p-value, when reported, measures how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the test. It does not give the probability that the null hypothesis is true, nor does it measure clinical importance. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record.

Statistical significance and the size of an effect answer different questions. A test result alone would not show whether a change was large, meaningful, or precisely estimated. Here, the record does not include the endpoint estimate or inferential results, so neither the size nor the statistical evidence for a change can be assessed. The same limitation applies to the secondary outcomes.

What do the planning assumptions mean?

The record's sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is framed around detecting a stated fraction of an observed effect. Those assumptions describe a hypothetical planning calculation; they do not change the registered trial design, which is single-group. The registry does not report a sample-size justification for the actual study design.

Any sample-size figures based on these assumptions are planning illustrations, not observed power. They do not show that the completed study had a particular probability of detecting an effect. In particular, a two-arm planning setup should not be read as evidence that participants were randomized between two arms. The observed primary effect used as the basis for such an illustration is not reported in the registry record, so the underlying effect and the planning calculation cannot be independently assessed from this record.

A normal approximation is a general method that uses a normal distribution to approximate the behavior of a statistic. Whether an approximation is suitable depends on the design and data; no diagnostic information is reported in the registry record. The listed assumptions should therefore be read as the stated basis of a planning illustration, not as a description of an analysis performed in this single-group study.

What can be inferred from the safety counts?

Safety counts describe events recorded during the study, and their interpretation depends on definitions, observation time, and ascertainment. The registry lists the number at risk and the number affected for serious and other adverse events, along with deaths. These counts do not provide a randomized comparison or a rate adjusted for follow-up. The record does not report event terms for serious adverse events, nor does it give enough detail to assess duration, severity, or relatedness of the other events. General statistical interpretation should therefore remain descriptive.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Group 1")
n   <- c(7)
m   <- c(-20.1)
sp  <- c(13.87)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Group 1  7  -20.100  13.870  -32.928  -7.272

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary ADHD Rating Scale-IV change outcome and secondary outcomes for Clinical Global Impression-Severity, Children's Global Assessment Scale score, and Clinical Global Impression-Improvement. Four outcome measures are listed overall. When several outcomes are examined, general statistical practice considers whether a prespecified hierarchy or adjustment is needed to manage the chance of false-positive findings across tests. The registry record does not report a multiplicity strategy, an analysis plan, or outcome-specific analysis results. No claim about statistical significance across outcomes can be assessed.

Missing data are important for a baseline-to-endpoint change outcome because a change generally requires measurements at both time points. The registry record does not report the number with endpoint measurements, the amount or pattern of missing data, reasons for missingness, or a method for handling missing observations. It also does not report sensitivity analyses examining how conclusions might vary under different assumptions about missing data. These omissions mean that completeness of follow-up and the potential influence of missing outcomes cannot be evaluated.

The analysis population is not reported in the registry record. The enrollment figure of 7 does not establish how many participants contributed to each outcome or which participants were included in any analysis. Although the record lists no analysis records, it does not provide an analysis population definition or an account of exclusions. As a result, it is not possible to determine whether analyses followed a prespecified population rule or to assess the relationship between enrollment and outcome reporting.

12. Safety Results

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

Deaths

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 registry's adverse-event summary lists one methylphenidate group, with 7 at risk for serious adverse events and 0 affected. It records 7 at risk for other adverse events and 7 affected, and reports 0 deaths. These are the safety counts recorded for this group; they are not comparative estimates because the study has no control arm.

The serious-event count does not establish that no adverse events of any kind occurred: the summary separately records other adverse events. Conversely, the count of other adverse events does not by itself describe their nature or clinical importance. The registry record does not list serious-event terms and does not give details on the other adverse events, such as their type, severity, timing, or relationship to treatment.

The counts are descriptive. The registry record does not report further information about the safety analysis population, observation completeness, or how events were collected and classified. Accordingly, these figures should not be used to compare risks with another treatment or to infer safety beyond the events recorded in this study.

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

The registry record documents a completed pilot study of open-label methylphenidate in young children with ADHD and defines a continuous primary outcome measured over 8 weeks. It also records safety counts, including 0 serious adverse events and 0 deaths in the listed group, alongside 7 affected by other adverse events. These details describe the registered study and recorded safety summary.

The record does not report the primary endpoint estimate, its standard deviation, a confidence interval, or a statistical test. It therefore does not show whether the mean score change was in a particular direction, how large it was, or how precisely it was estimated. The stated hypotheses are aims rather than results. The secondary outcome results are also not reported in the registry record.

Even if a within-group change estimate were available, the single-group, open-label design would not establish that treatment caused the change. Without a randomized comparator, the study cannot directly distinguish a treatment-associated change from other influences over time. This does not negate the descriptive value of the study; it defines the limits of causal interpretation.

The safety counts likewise do not establish comparative risk. The record gives no detailed event descriptions and no comparison group. The missing analysis population and outcome-completeness information further limit interpretation of how well the reported counts represent the enrolled group. The appropriate reading is therefore narrow: the registry provides the study design, endpoint definition, and recorded adverse-event counts, but it does not provide the numerical efficacy results needed to judge the primary outcome.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between an outcome question and an outcome result. The registry defines a parent-version ADHD Rating Scale-IV score and a baseline-to-endpoint change, but the numerical result is not reported. A clear endpoint definition is necessary for interpretation, yet it cannot substitute for an estimate and a measure of uncertainty.

The single-group design also makes the target of inference important. A baseline-to-endpoint summary would describe observed change within the treated group. It would not supply the counterfactual comparison needed to estimate what would have happened over the same period without treatment. The open-label design is another feature that readers should consider when interpreting parent-reported, investigator-scored outcomes, while avoiding unsupported assumptions about actual bias.

The record highlights why analysis details matter alongside enrollment. The recorded enrollment is 7, but the analysis population, endpoint completeness, and handling of missing data are not reported in the registry record. Without those details, readers cannot assess how the analyzed observations relate to enrollment or how missing measurements may affect a change estimate.

Finally, the sample-size assumptions describe a hypothetical two-arm planning illustration, whereas the registered study is single-group. Keeping planning assumptions separate from actual design prevents a misleading impression that the study included a comparator or that a planning calculation demonstrates observed power. Taken together, these features make the record useful for understanding design and reporting limitations, while leaving the primary statistical result unavailable.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The central limitation for interpreting the primary question is that the registry record does not report the primary endpoint estimate or its uncertainty. The study's stated aim to evaluate effectiveness and tolerability cannot be treated as evidence of either. Without numerical endpoint results, the observed direction and magnitude of score change remain unknown.

The single-group design has no concurrent control arm, and the study is open-label. It therefore cannot provide a randomized comparison, and within-group change alone would not establish causation. The registry record also does not report dose, adherence, detailed eligibility criteria, or further information about the population that completed outcome assessments.

The record does not report the analysis population, the number contributing to each outcome, or how missing measurements were handled. This limits assessment of follow-up completeness and the relation between enrollment and any outcome estimate. The absence of analysis records also leaves the analysis methods and prespecification unclear; a statistical plan is not reported in the registry record.

Four outcome measures are listed, but the record does not describe how multiplicity was addressed or provide secondary outcome results. Safety reporting is similarly limited: serious adverse events and deaths are recorded as zero, while other adverse events are recorded for the group, but event details are not reported. The safety counts cannot be interpreted as comparative risks.

The planning assumptions describe an equal-allocation, two-arm normal-approximation illustration, not the registered single-group design. They are not observed power, and the registry record does not provide the observed effect or actual sample-size justification. These limitations mean the posted information supports only a constrained description of the study and its recorded safety counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long Acting Stimulant Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in Young Children — NCT00754208.
• Registry record last updated 2023-10-05; status last verified 2023-09.
• 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.

19. Record Summary

NCT00754208 is a completed Phase 4, single-group, open-label study sponsored by the University of Nebraska. It records enrollment of 7 and evaluates methylphenidate, described in the summary as Ritalin LA, in children aged 4 and 5 years with ADHD. The primary outcome is change in the investigator-scored, parent-version ADHD Rating Scale-IV total score over 8 weeks.

The registry lists three secondary outcomes and four outcome measures overall. It records 0 serious adverse events, 7 affected by other adverse events, and 0 deaths in the intervention group. The primary endpoint result, secondary outcome results, analysis population, missing-data methods, and statistical analysis plan are not reported in the registry record. The single-group design does not provide a randomized control comparison.