Efficacy and Safety of Lisdexamfetamine Dimesylate (LDX) in Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Lisdexamfetamine Dimesylate (LDX) in Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) (NCT00735371), a randomized phase 3 study. The primary outcome is Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks.

2. Clinical Question

3. Trial Design

This was a Phase III randomized, double-blind, multicenter, parallel-group, placebo-controlled study of LDX in adolescents aged 13–17 with ADHD. The official title also describes forced-dose titration and quadruple masking. Four groups were listed: LDX 30 mg, LDX 50 mg, LDX 70 mg, and placebo. The registry record gives enrollment as 314 and the study status as completed. The start date was 2008-10-08, and primary completion was 2009-04-06.

The primary outcome was change from baseline in ADHD-RS-IV total score at up to 4 weeks, with assessments at baseline and 1, 2, 3, and 4 weeks. The primary analysis population was the Full Analysis Set, defined by having taken at least one dose and having a valid baseline assessment plus at least one post-baseline assessment of the primary outcome. Outcome-specific group counts were 78 for LDX 30 mg, 76 for LDX 50 mg, 78 for LDX 70 mg, and 77 for placebo. These counts describe the primary outcome analysis and should not be treated as the overall enrollment count.

The posted secondary outcomes were the number of participants with improvement on Clinical Global Impression-Improvement (CGI-I) scores and Youth Quality of Life-Research Version (YQOL-R) total score. The registry record does not report the detailed titration schedule, allocation ratio, site count, or additional design features in the registry record for this analysis. The design labels alone do not establish how masking was maintained or how participants were assigned to specific doses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) is defined as all subjects who took at least one dose of study medication and had a valid Baseline and at least one post-Baseline follow-up assessment of the primary outcome measure (ADHD-RS-IV Total Score)

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 From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at up to 4 Weeks, measured over Baseline and 1, 2, 3 and 4 weeks.

The primary endpoint was change from baseline in ADHD-RS-IV total score at up to 4 weeks. The scale has 18 items, each scored from 0 (no symptoms) to 3 (severe symptoms), and a total score ranging from 0 to 54. A change below zero means the follow-up score was lower than the baseline score. In the posted results, each group’s mean change was below zero.

A symptom rating scale provides a standardized way to quantify change across participants and compare group averages. The study’s endpoint captures symptom ratings over a short follow-up period, with assessments scheduled at baseline and 1, 2, 3, and 4 weeks. It therefore describes change during that observed period, not longer-term outcomes. The registry record describes the primary result as a least-squares mean with standard error and defines the Full Analysis Set used for the primary measure.

As a general statistical point, a group mean describes the average change, not the experience of every participant. The group summaries do not show the full distribution of individual responses. Nor does a mean score by itself describe changes in functioning, quality of life, or safety. Those are distinct questions; the registry record lists CGI-I and YQOL-R as secondary outcomes, but it does not provide a posted YQOL-R result in the registry record for this analysis.

7. Results Posted in the Registry

• Lisdexamfetamine Dimesylate (LDX) 30 mg: mean -18.30 versus -12.80 on control; difference -5.50 (95% CI -8.96 to -2.04), standardized effect d = -0.50; z-test p = 0.002.
• LDX 50 mg: mean -21.10 versus -12.80 on control; difference -8.30 (95% CI -11.81 to -4.79), standardized effect d = -0.75; z-test p = <0.001.
• LDX 70 mg: mean -20.70 versus -12.80 on control; difference -7.90 (95% CI -11.36 to -4.44), standardized effect d = -0.72; 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.

Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Lisdexamfetamine Dimesylate (LDX) 30 mg: 56.4% (44/78) versus 39.0% (30/77) on control; risk difference 17.4 percentage points (95% CI 2.0 to 32.9), risk ratio 1.45 (1.03–2.04); unadjusted two-proportion z-test p = 0.030.
  • LDX 50 mg: 69.7% (53/76) versus 39.0% (30/77) on control; risk difference 30.8 percentage points (95% CI 15.8 to 45.8), risk ratio 1.79 (1.30–2.46); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Lisdexamfetamine Dimesylate (LDX) 30 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for LDX 50 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry record lists two secondary outcomes: the number of participants with CGI-I improvement and YQOL-R total score. The posted CGI-I summaries show a descriptive pattern in which more participants in the active-dose groups were recorded as improved than in placebo. The available comparisons and sponsor tests cover LDX 30 mg and LDX 50 mg versus placebo; the registry record does not list a corresponding comparison test for LDX 70 mg. A numerical YQOL-R result is not reported in the registry record.

The CGI-I direction is broadly consistent with the primary endpoint pattern in that the active groups’ posted summaries are more favorable by their respective outcome definitions. The outcomes are not interchangeable: ADHD-RS-IV measures symptom severity on a continuous scale, while CGI-I improvement is a participant count based on a global rating. Agreement in direction across outcomes can be informative, but does not make one outcome a substitute for another or resolve the limits of the analysis.

The posted secondary analyses include unadjusted recalculated comparisons and sponsor-reported Cochran-Mantel-Haenszel p-values for two LDX groups. The registry record does not report a multiplicity adjustment for these analyses or describe a hierarchy controlling the chance of false-positive findings across outcomes and comparisons. When several outcomes, doses, and time points are examined, a small unadjusted p-value does not account for the number of opportunities to observe a result. For that reason, unadjusted secondary findings generally carry less confirmatory weight than a clearly specified primary analysis.

The secondary information adds context but remains incomplete: the YQOL-R result is absent, and the posted CGI-I testing does not cover every active-dose comparison. The registry record does not report enough detail to determine how secondary outcomes were prioritized or whether additional analyses were conducted but not posted.

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

• Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores
• Youth Quality of Life-Research Version (YQOL-R) Total Score

9. Statistical Interpretation

10. Statistical Methods Explained

The posted primary outcome is a continuous measure: ADHD-RS-IV total score. Its arm summaries are least-squares means of change from baseline, accompanied by standard errors. A least-squares mean is a model-based group estimate; the registry record identifies the summary type but does not provide the model details or covariates used to obtain the sponsor’s estimates.

What does the mean difference describe?

The mean difference compares the change-from-baseline mean in an LDX group with the corresponding mean in the placebo group. A negative difference means the LDX group’s mean change is more negative than placebo’s mean change. For example, the recalculated contrast uses the posted group means. It is an unadjusted comparison, not the sponsor’s ANCOVA estimate. The primary endpoint values and the contrast are expressed in units on the ADHD-RS-IV scale.

What is a standard error?

A standard error describes uncertainty in an estimated mean due to sampling variation, under the statistical model or approximation used. It is not the spread of individual participant scores. The posted arm summaries report standard errors, not standard deviations. The unadjusted recalculations approximate pooled standard deviations from those standard errors and group counts; this approximation is stated because it affects the calculated contrasts and intervals. A confidence interval built from such a calculation should therefore be read as an approximate, unadjusted interval rather than as the sponsor’s model-based interval.

How should the confidence intervals be read?

A confidence interval gives a range of values compatible with the data under the calculation and assumptions used. In repeated use of the same procedure under its assumptions, the stated confidence level describes the long-run coverage of the procedure; it is not the probability that a particular fixed effect lies in one realized interval. For the recalculated comparisons, the intervals describe plausible values for the mean difference under the unadjusted approximation. They do not convey the likelihood that a particular participant will have a given outcome.

What do the sponsor analyses add?

The registry record lists ANCOVA for the three primary comparisons with placebo and reports p-values, but does not report the sponsor’s estimated contrasts or confidence limits. ANCOVA is a general analysis-of-covariance approach that can compare groups while accounting for specified covariates. Which covariates and model specifications were used is not reported in the registry record. Consequently, the reported sponsor p-values cannot be used to reconstruct the sponsor’s effect estimates or intervals from the available information.

The recalculations and sponsor analyses answer related but not identical statistical questions. The former compare posted summary means using an unadjusted approximation; the latter are the registry’s reported ANCOVA tests. Their p-values should not be treated as interchangeable, nor should the unadjusted calculations be mistaken for the trial’s full analysis plan.

Why does over-dispersion matter?

As a general statistical concept, over-dispersion occurs when variability in observed data exceeds what a chosen model expects. A model that understates variability can produce standard errors that are too small and uncertainty intervals that are too narrow. The primary endpoint is continuous, and the posted summaries include standard errors, but the registry record does not report a specific over-dispersion assessment. This concept is not a claim that over-dispersion occurred in this trial.

For binary outcomes, such as the number of participants with CGI-I improvement, analyses compare counts or proportions rather than means of a continuous score. The registry record identifies Cochran-Mantel-Haenszel analyses for the posted CGI-I comparisons. In general, this method can combine evidence across strata, but the registry record does not state which strata were used. The method name alone does not reveal the magnitude of the effect or the clinical importance of the outcome.

Finally, statistical tests depend on the analysis population, outcome definition, model, and handling of missing observations. The Full Analysis Set definition is reported for the primary endpoint, but the missing-data procedure and further details of the primary analysis model are not reported in the registry record. Those omissions limit how completely the sponsor’s results can be reproduced from the posted summaries.

11. Confidence Intervals and Precision

The recalculated 95% confidence intervals for the mean differences versus placebo are −8.965 to −2.035 for LDX 30 mg, −11.81 to −4.793 for LDX 50 mg, and −11.36 to −4.435 for LDX 70 mg. These intervals are all below zero, in keeping with the negative mean differences. Their widths express uncertainty about the unadjusted differences, rather than the range of individual participant outcomes.

These are approximate intervals derived from posted summary means and standard errors, using an approximate pooled standard deviation. They are not the sponsor’s ANCOVA confidence intervals. The registry record reports 95% confidence levels for the sponsor analyses but does not give their estimates or confidence limits. The sponsor’s p-values therefore cannot be paired with the recalculated intervals as if both came from one model.

Precision is not the same as importance. A confidence interval can help show which effect sizes are relatively compatible with the observed data under its method, but it does not determine whether a difference matters to patients or predicts an individual response. The estimates also refer to change in the ADHD-RS-IV score over the study’s reported follow-up, not to outcomes beyond that timeframe. The registry record does not report a threshold for interpreting the clinical importance of a score difference.

As a general point, estimates based on finite samples have uncertainty, and larger standard errors generally correspond to less precise estimates. The posted arm standard errors are similar in size, while the contrasts also depend on group counts and the approximate variability used in the recalculation. The limited outcome summaries do not provide the full participant-level distribution needed to assess heterogeneity of response or other features of the data.

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 estimates are participants per arm for comparisons of two groups; they are not total events. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each planning illustration, the effect to detect is a stated fraction of the observed effect. These assumptions describe the planning calculations, not the trial’s original design. The trial’s own sample-size justification and original design assumptions are not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to provide an 80% chance of rejecting the null hypothesis under the calculation’s assumptions if the specified effect is the true effect. The 90% power column gives the corresponding estimate for a 90% chance. These are planning probabilities under assumed conditions, not guarantees about the result of a future study.

Separate estimates are given for planning around the full observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller effect is harder to distinguish from random variation, so the planning calculation requires more participants per arm to reach the same power target. The estimates are illustrations based on observed effects and should not be read as the trial’s actual enrollment target or proof that a particular design would succeed.

This is not observed power. Observed power is not a useful substitute for interpreting the effect estimate and its uncertainty after results are known. The planning figures instead illustrate how required sample size changes when the assumed effect size or target power changes, with the stated approximation and allocation assumptions held in place.

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 = -5.500; pooled standard deviation σ = 11.004.
2. n = 2 × (1.96 + 0.842)² × 11.004² / -5.500² = 62.8, rounded up to 63 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 <- -5.5                      # observed difference in means
sigma <- 11.0044925466443                     # 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(735371)
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 = 63 (80% power), 85 (90% power)
 75% of observed effect: n per arm = 112 (80% power), 150 (90% power)
 50% of observed effect: n per arm = 252 (80% power), 337 (90% power)
power.t.test: 63.8 
Simulated power at n = 63 per arm: 0.798 (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 reported primary comparisons use ANCOVA and give p=0.006 for LDX 30 mg versus placebo, and p< 0.001 for LDX 50 mg and LDX 70 mg versus placebo. The registry record gives a 95% confidence level for these analyses but does not report the sponsor’s estimated differences or confidence limits.

The unadjusted recalculations use posted arm means and standard errors, with an approximate pooled standard deviation. They give mean differences and approximate confidence intervals that are useful for describing the magnitude and uncertainty of simple comparisons, but they are not a reproduction of the sponsor’s ANCOVA model. The sponsor’s p-values and the recalculated p-values need not match exactly because they arise from different methods and information.

Both sets of results show a pattern of lower mean change scores in the active-dose groups than in placebo, and both report small p-values for the primary comparisons. The sponsor’s analysis is the trial’s reported analysis; the recalculations add an explicitly unadjusted perspective based on summary statistics. Model covariates, detailed specifications, and a complete analysis plan are not reported in the registry record, so the sponsor’s results cannot be fully reconstructed from the posted information.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several statistical tests are conducted, for example across multiple doses, outcomes, or assessment times. As a general statistical principle, more testing can increase the chance that at least one result appears notable by chance if no adjustment or prespecified testing strategy is used. This trial includes three active-dose comparisons for the primary outcome and lists secondary outcomes; assessments were scheduled over several weeks. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a detailed plan for controlling error across those tests. The absence of such information in the registry record does not establish whether a procedure was or was not used outside the posted record.

The Full Analysis Set definition is reported for the primary outcome. It includes participants who took at least one dose and had a valid baseline assessment and at least one post-baseline primary outcome assessment. The registry record does not report the number excluded from this set, the reasons for missing assessments, or the procedures used to handle missing outcome data. It also does not describe sensitivity analyses for missingness. These details matter because conclusions from a repeated-measures outcome can depend on which observations are included and how incomplete follow-up is handled.

ANCOVA is listed for the sponsor’s primary comparisons, but the registry record does not identify covariates, model terms, or other analysis specifications. Nor does it report interim analyses or the protocol’s complete statistical analysis plan. These items should therefore be treated as unknown, rather than inferred from the study design or the posted p-values.

Without the missing multiplicity, missing-data, and model details, the posted results support a description of the reported estimates and tests, but not a complete audit of the analysis strategy. In particular, the reported p-values should be interpreted in the context of the specified comparisons and the information that is actually recorded.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry record lists zero serious adverse events for each group. The numbers at risk for those safety summaries were 78 for LDX 30 mg, 77 for LDX 50 mg, 78 for LDX 70 mg, and 77 for placebo. These are safety-group counts; they are not identical to every outcome-specific analysis count. The record also lists other adverse events affecting participants, but those counts do not change the interpretation of the serious-event entries.

A zero count in a study group means no serious adverse event was recorded in that group during the reported safety summary. It does not establish that the risk is zero, particularly when group sizes and follow-up are limited. The registry record does not report serious adverse event terms, and the deaths count is not reported in the registry record. Therefore, the serious-event summary should not be used to infer more than the posted counts show.

Safety counts are descriptive and do not by themselves establish comparative safety. The study’s primary endpoint was symptom-score change, and the safety figures are a separate outcome. The registry record does not provide enough detail about event definitions, timing, or exposure duration to support a more detailed safety interpretation.

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

The posted primary results describe mean change in ADHD-RS-IV total score through up to 4 weeks. Each group’s mean change was negative, and the active-dose means were more negative than the placebo mean. The recalculated unadjusted mean differences and the sponsor’s reported ANCOVA tests likewise describe comparisons favoring larger mean reductions in the active-dose groups than in placebo over this study period.

These statistical results do not state that every participant experienced a reduction, nor do they show how much responses varied between individuals. Group averages can conceal a range of individual outcomes. The registry record does not report an interpretation threshold for deciding whether a score difference is clinically important, and the p-values alone cannot supply that judgment.

The findings also do not establish a ranking of the active doses. The posted comparisons test each dose against placebo; they do not provide direct tests between LDX 30 mg, LDX 50 mg, and LDX 70 mg. Nor do the reported results establish durability beyond the stated follow-up, generalize automatically to populations not described in the record, or answer the unreported YQOL-R result.

Statistical significance and clinical importance are different concepts. A p-value measures compatibility of data with a statistical null model under the method’s assumptions; it is not the probability that the null hypothesis is true, a measure of effect size, or evidence about an individual’s likely outcome. The confidence intervals add information about uncertainty in the estimated differences, but the recalculated intervals are approximate and unadjusted.

These results are a description of one completed randomized study in adolescents aged 13–17. They are not medical advice and do not determine whether a particular treatment is appropriate for an individual.

18. Why This Trial Matters Statistically

This trial offers a useful setting for distinguishing an arm-level change from a treatment-versus-control contrast. All groups had mean decreases from baseline, so the relevant comparative question is not whether scores changed within an active group alone, but how those changes compare with the placebo group. The posted summaries make that distinction visible through both the group means and the between-group estimates.

The trial also illustrates why the analysis method matters. The registry reports sponsor ANCOVA p-values, while a simple recalculation from arm summaries gives approximate unadjusted contrasts and intervals. These results are related, but they are not the same analysis. Separating them helps readers avoid treating a summary-statistic recalculation as a reconstruction of the sponsor’s model.

Precision and interpretation matter alongside statistical significance. The approximate confidence intervals describe uncertainty about group mean differences, while the standard errors describe uncertainty in the arm means. Neither is a measure of individual response variability. The planning illustrations further show, in general terms, that smaller assumed effects require more participants per arm for a given power target; they do not reveal the trial’s original sample-size rationale.

Finally, the registry record captures important limits: short follow-up, incomplete details of model specification and missing-data handling, no reported multiplicity strategy, and no numerical YQOL-R result. Recognizing these limits is part of sound statistical interpretation, not a reason to disregard the recorded findings.

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 trial-specific limitations affect how fully the findings can be interpreted from the registry record. The primary endpoint covers baseline through 4 weeks, with assessments at 1, 2, 3, and 4 weeks. The record does not provide longer-term outcomes, so the posted estimates describe only this short follow-up period.

The sponsor’s primary ANCOVA p-values are recorded, but its effect estimates, confidence limits, model covariates, and full model specifications are not. The unadjusted recalculations use approximate pooled standard deviations derived from standard errors; they should not be treated as sponsor estimates. The registry record also does not report methods for handling missing observations, sensitivity analyses, or the number and characteristics of participants omitted from the Full Analysis Set.

The registry record does not describe multiplicity control across doses, outcomes, or assessment times. The secondary results are incomplete: YQOL-R is listed but a numerical outcome is not reported, and the posted CGI-I comparisons do not include a test for every active dose. This makes the secondary evidence less complete than the primary outcome summaries.

The record does not report a clinical-importance threshold for ADHD-RS-IV differences, a direct statistical comparison among the LDX doses, or a detailed titration schedule. The serious adverse event counts are posted, but serious event terms and the deaths count are not reported in the registry record. These gaps constrain interpretation; they do not imply that unreported procedures, outcomes, or events were absent.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Lisdexamfetamine Dimesylate (LDX) in Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) — NCT00735371.
• Registry record last updated 2021-06-14; status last verified 2021-06.
• Results first posted 2010-02-23.
• 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

NCT00735371 is a completed Phase III randomized, quadruple-masked, parallel-group, placebo-controlled study of LDX in adolescents aged 13–17 with ADHD. Enrollment was 314. The primary endpoint was change from baseline in ADHD-RS-IV total score at up to 4 weeks, analyzed in a Full Analysis Set defined by medication exposure and availability of baseline and follow-up outcome assessments.

Posted mean changes were −18.3 for LDX 30 mg, −21.1 for LDX 50 mg, −20.7 for LDX 70 mg, and −12.8 for placebo. Sponsor-reported ANCOVA p-values were 0.006, < 0.001, and < 0.001 for the respective dose comparisons with placebo. Approximate unadjusted recalculations give negative mean differences for all three comparisons, with confidence intervals below zero.

The registry also lists CGI-I and YQOL-R secondary outcomes. A numerical YQOL-R result is not reported in the registry record. Serious adverse event counts were zero in each group; the deaths count is not reported in the registry record. Important analysis details, including multiplicity procedures and missing-data methods, are not reported in the registry record.