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 A Study of Dex-methylphenidate Extended Release in Children (6-12 Years) With Attention-Deficit/Hyperactivity Disorder (ADHD) (NCT00564954), a randomized phase 4 study. The primary outcome is Change From Pre-dose (0 hr [Hour]) on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) Rating Scale Combined Score at 0.5 Hour During the 8- Hour Laboratory Classroom Day.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00564954 |
| Phase | Phase 4 |
| Condition | Attention Deficit Hyperactivity Disorder |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 86 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Children aged 6-12 years with attention-deficit/hyperactivity disorder (ADHD) were studied in a laboratory classroom setting. The primary outcome population is described as the Intent to Treat (ITT) population: randomized patients who received at least one dose of study medication and had at least one post-dose efficacy measurement.
Intervention
Dex-methylphenidate hydrochloride extended release (Focalin XR) was given as a 20 mg capsule orally once a day for 7 days.
Comparator
Placebo was given orally once a day for 7 days. The study is described as a randomized, multi-center, double-blind, crossover comparison; the registry separately lists masking as triple.
Primary question
What was the change from pre-dose in the SKAMP combined score at 0.5 hour post-dose, and how did the estimated change with dex-methylphenidate compare with the estimate with placebo?
The endpoint concerns classroom behavior during an 8-hour laboratory classroom day. The SKAMP combined score includes questions on attention and deportment, and higher scores represent greater impairment because the response scale runs from normal, no impairment, to maximum impairment. The posted least-squares mean change was -0.969 with dex-methylphenidate and 3.336 with placebo. The estimated mean difference, expressed as dex-methylphenidate minus placebo, was -4.305 points.
This is a comparison at a specific post-dose timepoint, not a summary of all timepoints or of the entire study period. Other outcomes included SKAMP scores at additional times and measures of performance on a math test. Results for those secondary outcomes should not be inferred from the primary result. The registry record does not report the treatment sequence or any washout arrangement for the crossover periods, so those details cannot be used to further specify the clinical question.
3. Trial Design
The registry describes a Phase 4, randomized, multi-center, double-blind, crossover study of dex-methylphenidate extended release compared with placebo. The official title also describes the study as double-blind, while the registry masking field lists triple masking. Children aged 6-12 years with ADHD were studied in a laboratory classroom setting. The registry lists enrollment as 86.
Participants received dex-methylphenidate hydrochloride extended release (Focalin XR) as a 20 mg oral capsule once a day for 7 days and placebo orally once a day for 7 days. A crossover design compares interventions within a participant across treatment periods, rather than assigning each participant to only one intervention for the entire study. However, the record does not report the order in which interventions were given, how treatment sequence was assigned, or whether a washout period was used. No detail on adherence or period-specific completion is reported in the registry record.
The study compared efficacy and safety during an 8-hour laboratory classroom day. The primary outcome was change from pre-dose in SKAMP combined score at 0.5 hour post-dose. The reported primary measure is a least-squares mean, with standard error as its dispersion measure. The outcome population is defined as randomized patients who received at least one study dose and had at least one post-dose efficacy measurement.
The record gives start and primary completion as 2007-10 and 2007-11, respectively, and status as completed. It does not report the original sample-size justification, the intended treatment sequence, or details of the statistical model. Those omissions limit how fully the crossover design and the reported least-squares means can be reconstructed from the registry record alone.
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.
Period 1- 1 Week
| Stage | Dex-methylphenidate Hydrochloride (Focalin XR) Then Placebo | Placebo Then Dex-methylphenidate Hydrochloride (Focalin XR) |
|---|---|---|
| STARTED | 44 | 42 |
| COMPLETED | 44 | 42 |
| NOT COMPLETED | 0 | 0 |
Period 2- 1 Week
| Stage | Dex-methylphenidate Hydrochloride (Focalin XR) Then Placebo | Placebo Then Dex-methylphenidate Hydrochloride (Focalin XR) |
|---|---|---|
| STARTED | 44 | 42 |
| COMPLETED | 44 | 42 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) population: All randomized patients who had at least one dose of study medication and who had at least one post-dose efficacy measurement.
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 | Dex-methylphenidate Hydrochloride (Focalin XR) Then Placebo | Placebo Then Dex-methylphenidate Hydrochloride (Focalin XR) | Total |
|---|---|---|---|---|
| Participants analysed | 44 | 42 | 86 | |
| Age Continuous | years | 9.5 (SD 2.0) | 9.4 (SD 1.4) | 9.5 (SD 1.7) |
| Sex: Female, Male: Female | Participants | 16 | 17 | 33 |
| Sex: Female, Male: Male | Participants | 28 | 25 | 53 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Pre-dose (0 hr [Hour]) on the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) Rating Scale Combined Score at 0.5 Hour During the 8- Hour Laboratory Classroom Day, measured over 0 hr and 0.5 hr post-dose.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change from pre-dose (0 hr) in the Swanson, Kotkin, Agler, M-Flynn & Pelham (SKAMP) Rating Scale Combined Score at 0.5 hour during the 8-hour laboratory classroom day. It is a continuous score, and the registry reports a least-squares mean for each intervention, with standard error as the measure of dispersion.
The SKAMP scale evaluates classroom behavior through 13 questions: 7 questions on attention and 6 on deportment. Each answer ranges from 0, meaning normal with no impairment, to 6, meaning maximum impairment; the possible combined score ranges from 0 to 78. Because larger scores correspond to greater impairment, a negative change indicates a lower score than the pre-dose value, while a positive change indicates a higher score. This describes the direction of the score, not a conclusion about clinical benefit.
A combined measure offers a single summary of the two behavioral domains rather than separate attention and deportment results. The 0.5-hour timepoint focuses on an early post-dose assessment. The endpoint is therefore suited to the stated question about classroom behavior at that specific time, but it does not by itself describe scores at later assessments, the full 8-hour profile, or other outcomes such as math-test performance. The record does not report why this timepoint was chosen or how the endpoint was selected.
7. Results Posted in the Registry
- Dex-methylphenidate Hydrochloride (Focalin XR): mean -0.97 versus 3.34 on control; difference -4.30 (95% CI -6.82 to -1.79), standardized effect d = -0.51; z-test p = <0.001.
Mean difference: Dex-methylphenidate Hydrochloride (Focalin XR)
95% CI: -6.82 to -1.79
Recalculated from the posted summary statistics
8. Statistical Interpretation
The reported least-squares mean change from pre-dose was -0.969 for dex-methylphenidate and 3.336 for placebo at 0.5 hour. The estimated mean difference was -4.305 points, calculated in the reported comparison as dex-methylphenidate minus placebo. On the SKAMP scale, where higher values indicate greater impairment, the negative direction means the estimated change was lower in the dex-methylphenidate condition than in the placebo condition. This is a description of the posted score estimates, not a claim about treatment effectiveness.
The confidence interval for the mean difference extends from -6.822 to -1.788, and the unadjusted p-value is <0.001. The interval gives a range of values compatible with the data and the analysis assumptions; it is not a range containing a known true value with certainty. The reported interval is entirely below zero, which is consistent with the direction of the point estimate under the stated comparison. The p-value describes how unusual a result at least this incompatible with a zero difference would be under a particular null model and its assumptions. It does not measure the probability that the null hypothesis is true, or the size or importance of the result.
The estimated difference is expressed in score points, so its interpretation remains tied to the SKAMP scale. The registry record does not report a threshold for a clinically meaningful difference. No such threshold can be inferred from the numerical result alone. Also, a result at 0.5 hour does not establish the direction or size of the effect at the other assessment times, or on the secondary outcomes.
The reported group values are least-squares means, rather than plain arithmetic means. Such estimates can arise from a statistical model, but the model specification, included terms, and treatment of period or sequence are not reported in the registry record. The crossover structure makes those details relevant to understanding the estimate. Without them, the estimate and its uncertainty can be described as posted, but the analysis cannot be independently reconstructed from the record.
The ITT population definition requires at least one dose and at least one post-dose efficacy measurement, in addition to randomization. This definition excludes randomized participants with no post-dose measurement from the stated primary outcome population. The registry does not report how many participants were excluded for that reason, how missing measurements were handled, or whether other analysis populations were used. The posted result should therefore be understood in the context of that stated population and the missing-data details that are not reported.
The sample-size planning figures are illustrations based on the observed effect and stated assumptions, not a report of the trial's original design justification. They do not replace the estimated difference, its confidence interval, or the trial's own analysis. The record does not report an interim analysis plan or whether any interim analyses took place. Nor does it report how the primary and secondary outcomes were handled as a family of statistical tests. Consequently, the unadjusted p-value should not be interpreted as accounting for multiple outcome comparisons.
9. Statistical Methods Explained
What does the mean difference represent?
The primary outcome is continuous: it records change in a score, rather than whether an event did or did not occur. The registry reports least-squares mean changes of -0.969 with dex-methylphenidate and 3.336 with placebo. The contrast is -4.305, defined in the posted comparison as the dex-methylphenidate estimate minus the placebo estimate. A negative contrast therefore means the estimated change is lower in the dex-methylphenidate condition. Since higher SKAMP scores indicate greater impairment, this direction describes a lower change in impairment score relative to placebo at the measured timepoint.
In general, a difference in means expresses the separation between two average outcomes in the measurement's original units. Its meaning depends on the direction and scale of the measure. Here, the unit is a point on the SKAMP combined score. The estimate is not a percentage change and does not give the score for every participant. It summarizes the contrast between model-based group estimates.
Why is the result described as a least-squares mean?
A least-squares mean is generally a model-based estimate of an average. Depending on the analysis, it can account for specified factors in the model. The registry identifies the primary measure as a least-squares mean but does not identify the model terms, covariance structure, or estimation procedure. It would therefore be inappropriate to state which variables were adjusted for or how the crossover structure entered the model. The posted estimates can be interpreted as least-squares means, while the details needed to reproduce their calculation are not reported in the registry record.
The record also lists standard errors of 0.909 for the dex-methylphenidate estimate and 0.907 for the placebo estimate. A standard error describes the estimated uncertainty of a statistic across repeated samples under the analysis assumptions; it is not the spread of individual participants' scores. The record does not report standard deviations for the outcome groups. The separate pooled standard deviation in the comparison is marked as approximate, and it should not be mistaken for a directly reported outcome dispersion measure.
What does the p-value say?
The unadjusted p-value is <0.001. In general, a p-value measures how inconsistent the observed data are with a specified null hypothesis, assuming that hypothesis and the analysis model are true. It is not the probability that the null hypothesis is true, and it does not communicate the size of the estimated difference. The mean difference and confidence interval give information about magnitude and precision; the p-value is a different summary of evidence relative to a null comparison.
The value is explicitly unadjusted. The record lists one primary outcome and five secondary outcomes, but does not report a multiplicity adjustment plan. No inference about a family-wise error rate or an adjusted p-value can be made from the unadjusted result. The registry record also does not report whether other analyses or interim looks were planned.
Why does the crossover structure matter?
In general, a crossover design allows a participant's outcomes under different interventions to be compared, potentially reducing the influence of stable differences between participants. It also requires attention to treatment period, sequence, and possible carryover effects. These are general design considerations, not claims about the conduct or analysis of this trial. The record identifies a randomized crossover study but does not report sequence, washout, period effects, carryover assessment, or the model used to account for within-participant correlation. The implications of these choices for the reported standard error cannot be assessed from the registry record.
The planning illustration states equal allocation between the two arms, but that assumption does not establish how allocation or treatment sequence was implemented in the crossover trial. In a crossover, the numbers associated with each intervention should not automatically be read as separate, non-overlapping participant groups. The registry lists 86 for each intervention; those entries alone do not give a basis for adding the two values to claim a count of distinct participants.
What can be inferred from the endpoint scale?
The SKAMP combined score aggregates attention and deportment ratings across 13 questions. Its possible range is 0 to 78, with individual question responses from 0 to 6. In general, combining related items can summarize a broader construct, but a combined score can also conceal differences between its components. The posted primary result does not show whether the attention and deportment components changed in the same way. Those components appear among secondary outcomes, but the registry record does not include their numerical results in this record.
Change from pre-dose compares a post-dose score with the participant's pre-dose value. This can focus the estimand on change rather than the post-dose level alone. The registry specifies the timeframe as 0 hr and 0.5 hr post-dose, but does not report the exact calculation at participant level, handling of baseline values in the model, or missing-data method. Accordingly, the definition can be described as a change endpoint, while implementation details remain unreported.
Overall, the most direct statistical reading is the estimated difference in least-squares mean change, together with its confidence interval and unadjusted p-value. Broader claims about model adjustment, robustness, missing-data sensitivity, or multiplicity would require methods not reported in the registry record.
10. Confidence Intervals and Precision
The estimated mean difference in primary SKAMP change was -4.305 points, with a confidence interval from -6.822 to -1.788. The interval conveys uncertainty around the estimated contrast: values within it are compatible with the observed data under the analysis assumptions and the method used to construct the interval. It is not a guarantee that the true difference lies within those limits.
The interval lies on the negative side of zero, matching the negative direction of the estimated contrast. Its width shows that the posted estimate is not an exact value known without uncertainty. The interval also gives more information than a p-value alone because it shows a range of plausible effect sizes on the SKAMP score scale. The registry record does not state the confidence level or the method used to calculate this interval, so those details should not be assumed.
The posted standard errors for the least-squares mean changes are 0.909 for dex-methylphenidate and 0.907 for placebo. These quantify uncertainty in the individual estimates, not the variability of individual scores. The record does not give confidence intervals for each intervention's estimate. The confidence interval for the contrast is the relevant interval for comparing the interventions.
Precision depends on the data and the analysis method, including assumptions about the crossover design and correlations between repeated observations. Since the registry does not report the fitted model or its treatment of within-participant dependence, the reported uncertainty cannot be independently checked from this record. A narrow or wide interval should be interpreted in relation to the score scale and the question being asked; the record does not supply a threshold for a clinically meaningful difference.
11. 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.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 61 | 81 |
| 75% of the observed effect | 107 | 143 |
| 50% of the observed effect | 241 | 322 |
The planning figures are expressed as participants per arm for 80% power and participants per arm for 90% power. They are not total event counts: the posted outcome is continuous, and the planning assumptions specify participants per arm for this type of outcome. The estimates use the observed effect as their reference and show planning for 100%, 75%, and 50% of that observed effect.
The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. Under those assumptions, the figures indicate the number of participants per arm that a hypothetical study would plan for to attain the named power target. The 80% column refers to the chance of detecting an effect of the specified size under the assumed model if that effect is present; the 90% column uses a higher target chance and consequently requires more participants for each displayed effect assumption.
The displayed planning estimates are 61 and 81 participants per arm for planning for 100% of the observed effect; 107 and 143 for planning for 75% of the observed effect; and 241 and 322 for planning for 50% of the observed effect, respectively for the 80% and 90% targets. Smaller effects need more participants to detect under the same assumptions, which is why the planning figures increase as the assumed fraction decreases.
These are planning illustrations computed from the observed effect, not observed power. They do not establish the trial's original sample-size target or its design assumptions. The original design assumptions are not reported in the registry record. The equal-allocation and normal-approximation assumptions also should not be taken as a full description of how the crossover trial was designed or analyzed.
12. 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 z1−α/2 = 1.960) and the desired power (z1−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
- Observed difference Δ = -4.305; pooled standard deviation σ = 8.420.
- n = 2 × (1.96 + 0.842)2 × 8.4202 / -4.3052 = 60.1, rounded up to 61 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 <- -4.305 # observed difference in means
sigma <- 8.42045070052667 # 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(564954)
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 = 61 (80% power), 81 (90% power)
75% of observed effect: n per arm = 107 (80% power), 143 (90% power)
50% of observed effect: n per arm = 241 (80% power), 322 (90% power)
power.t.test: 61
Simulated power at n = 61 per arm: 0.799 (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.
13. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and five secondary outcomes. The secondary outcomes concern SKAMP combined, attention, and deportment scores, along with Permanent Product Measure of Performance (PERMP) math-test scores. Several are measured at multiple timepoints. The record does not report a prespecified strategy for controlling the chance of false-positive findings across these outcomes or timepoints. The primary comparison's p-value is unadjusted, so it should not be read as a multiplicity-adjusted result.
The registry reports no analysis records, although it does post the primary outcome statistics. This means the record does not contain separate analysis entries with further statistical details; it does not establish that no statistical analysis was performed. The analysis model, handling of crossover sequence and period, and any sensitivity analyses are not reported in the registry record. The number of secondary outcomes with posted numerical results in this record is five, but their results are not included in the registry record used for this explanation.
The primary outcome population is described as randomized patients who received at least one dose of study medication and had at least one post-dose efficacy measurement. This definition is narrower than a definition that would include every randomized participant regardless of receipt of treatment or availability of an efficacy measurement. The record does not state how many randomized participants lacked a post-dose measurement, how missing observations were handled, or whether imputations were used.
It is also not reported whether all randomized participants were analyzed according to an assigned treatment sequence, how participants with incomplete crossover periods were handled, or whether analyses used additional populations. The term ITT is used in the record, but the posted definition should guide interpretation rather than a broader assumption about the analysis set. No interim analysis plan or stopping rule is reported in the registry record.
These gaps matter because multiplicity, missingness, and the choice of analysis population can affect uncertainty and interpretation. They do not invalidate the posted estimate, but they limit what can be concluded about its robustness or about other outcomes. Such details should not be filled in by assuming a conventional protocol or standard analysis approach.
14. 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 |
|---|---|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | 0 | 86 | 0.0% |
| Placebo | 0 | 86 | 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 |
|---|---|
| Dex-methylphenidate Hydrochloride (Focalin XR) | 0 of 86 |
| Placebo | 0 of 86 |
The registry reports 86 participants at risk for serious adverse events in each intervention group, with zero serious adverse events affected in each group. It also reports 86 at risk for other adverse events in each group, with zero other adverse events affected in each group. These are the reported counts for the safety entries; they do not establish that no events occurred outside the registry's recorded categories or reporting period.
The serious adverse event terms list is empty. The death entries are null, so deaths are not reported as a numeric count in this record; null should not be read as a confirmed count of zero. The registry does not provide further detail on event definitions, event collection periods, severity, relatedness, or withdrawals due to adverse events.
In general, an adverse-event count describes events recorded under a study's definitions and observation procedures. A zero in a posted count does not prove that an intervention has no risk, and a comparison based on these entries is limited by the information recorded. The entries should be read as registry-reported safety counts, not as a complete safety assessment or a basis for medical advice.
15. What the Result Does, and Does Not, Mean
The primary result describes a lower estimated change in SKAMP combined score with dex-methylphenidate than with placebo at 0.5 hour post-dose: the estimated mean difference was -4.305 points, with a confidence interval from -6.822 to -1.788. The unadjusted p-value was <0.001. Because higher SKAMP scores indicate greater impairment, the direction of the estimate is interpretable as a lower impairment-score change relative to placebo at this measurement time. It remains a statistical comparison of score changes in the stated study population.
The finding does not by itself establish the clinical importance of the difference. The record gives no threshold for a clinically meaningful change, and the interpretation of a score-point difference depends on the scale and context. Nor does the primary result answer whether differences persisted across the 8-hour laboratory classroom day. It concerns the 0.5-hour timepoint only. It also does not supply results for the secondary SKAMP or PERMP outcomes, so those cannot be inferred from the primary endpoint.
The results are from a randomized, multi-center, double-blind crossover study in children aged 6-12 years with ADHD, using a laboratory classroom setting. They should not be generalized automatically to other populations, settings, durations, or outcomes. The treatment schedule was 7 days for each intervention, and the primary measurement was made at 0.5 hour post-dose. The registry record does not report treatment sequence, washout, or important analysis details that would help assess the crossover comparison.
The result also does not establish that one intervention is safe or unsafe. The registry safety entries report zero serious adverse events and zero other adverse events affected in each group, while death counts are not reported as numeric values. Those entries are limited to what the record captures and do not constitute a complete safety profile.
In short, the posted statistics support a description of the estimated score contrast and its uncertainty at the specified timepoint. They do not resolve clinical importance, longer-term outcomes, all secondary endpoints, or generalizability beyond the studied context.
16. Why This Trial Matters Statistically
This trial is statistically notable as a crossover comparison with a continuous behavioral score measured at a defined post-dose timepoint. Crossover designs can use within-participant comparisons, which in general may reduce the influence of stable between-participant differences. They also require appropriate handling of treatment sequence, period, and possible carryover. Those considerations are important for interpreting the precision of a crossover estimate, yet the registry record does not report the model or the design details needed to evaluate them.
The primary result includes both an estimated mean difference and a confidence interval. That combination is more informative than a significance statement alone: it communicates the direction and size of the contrast on the SKAMP scale, alongside uncertainty. The unadjusted p-value is <0.001, but the registry also lists multiple secondary outcomes and repeated timepoints without reporting a multiplicity strategy. This makes it important to distinguish the primary comparison from a broader collection of possible findings.
The planning illustrations demonstrate a general sample-size principle: planning for smaller effects requires more participants per arm under the same assumptions. They are based on the observed effect and do not describe the study's original design rationale. Keeping planning calculations separate from the observed trial result avoids confusing hypothetical future-study requirements with evidence from this study.
Finally, the record illustrates why statistical interpretation depends on more than the point estimate. The endpoint definition, analysis population, score direction, uncertainty, missing-data handling, and crossover methods all affect what the result can support. Several of those methods are not reported in the registry record. A careful reading can still describe the posted result precisely while recognizing those limits.
17. 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 contains limited detail on the crossover implementation. Although the study is identified as randomized and crossover, treatment order, sequence allocation, washout, and period-specific details are not reported. Potential carryover and within-participant correlation therefore cannot be assessed from the record. The least-squares means are posted, but the model specification and the terms used to obtain them are not reported.
The stated primary outcome population requires randomization, at least one dose, and at least one post-dose efficacy measurement. The record does not say how many randomized participants lacked an eligible post-dose measurement, how missing data were addressed, or whether participants with incomplete treatment periods were included. The presence of a defined ITT population should not be taken to mean that every randomized participant contributed to this endpoint.
The primary endpoint focuses on change at 0.5 hour. It cannot summarize the full 8-hour classroom day or establish the pattern of change at other timepoints. Although five secondary outcomes are identified, their numerical results and multiplicity plan are not reported in the registry record used for this account. The clinical meaning threshold for SKAMP points is also not reported.
The study was conducted in a laboratory classroom setting in children aged 6-12 years with ADHD, with each intervention scheduled once daily for 7 days. The record does not provide enough detail to determine how well these findings apply to other settings, populations, or durations. Safety details are similarly limited: the posted event counts are zero for reported serious and other events, but definitions and detailed event records are not given, and deaths are not reported as numeric counts.
The original sample-size rationale, interim analysis plan, and detailed statistical analysis plan are not reported in the registry record. The planning illustrations are based on the observed effect and stated assumptions, not on that missing design rationale.
18. Related Tutorials
19. Related Statistical Calculators
20. Sources
- ClinicalTrials.gov: A Study of Dex-methylphenidate Extended Release in Children (6-12 Years) With Attention-Deficit/Hyperactivity Disorder (ADHD) — NCT00564954.
- Registry record last updated 2012-04-27; status last verified 2012-04.
- Results first posted 2009-03-30.
- 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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21. Record Summary
The registry record describes NCT00564954, a completed Phase 4 randomized, multi-center, double-blind crossover study of dex-methylphenidate extended release and placebo in children aged 6-12 years with ADHD. The official title describes Focalin XR 20 mg versus placebo at the 0.5-hour timepoint in a laboratory classroom setting. The treatment schedule lists each intervention once daily for 7 days.
The primary outcome was change from pre-dose in SKAMP combined score at 0.5 hour. The posted least-squares mean changes were -0.969 with dex-methylphenidate and 3.336 with placebo; the mean difference was -4.305, with a confidence interval from -6.822 to -1.788 and an unadjusted p-value of <0.001.
The registry lists five secondary outcomes, reports zero affected for serious and other adverse events in each intervention group, and does not give numeric death counts. Important details—including crossover sequence, missing-data handling, analysis-model specification, multiplicity strategy, and original sample-size justification—are not reported in the registry record.