Electrophysiological Effects of Guanfacine Extended Release in Attention Deficit Hyperactivity Disorder (ADHD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Electrophysiological Effects of Guanfacine Extended Release in Attention Deficit Hyperactivity Disorder (ADHD) (NCT01069523), a randomized phase 4 study. The primary outcome is Dupaul ADHD Rating Scale.

2. Clinical Question

3. Trial Design

This was a Phase 4, randomized, quadruple-masked, parallel-group study comparing guanfacine extended release with placebo. The registry records enrollment of 42 and lists children aged 6-12 with ADHD as the study population. The study start is recorded as 2010-03, primary completion as 2011-08, and status as completed.

The study description outlines baseline ADHD assessment followed by an ERP assessment. Participants were then randomized to placebo or GXR for a 4-week treatment period, with a follow-up ERP assessment at the end of treatment. The medication dose was described as flexibly adjusted according to response or side effects, in a range of 1-4 mg. The arm descriptions state that treatment began at 1 mg and that a physician blind to drug status titrated medication during week 2-3, up to 4 mg.

The stated primary endpoint was not an ERP measure. It was the DuPaul ADHD Rating Scale, a continuous symptom score, with a timeframe listed as baseline and follow-up. The registry also lists Clinical Global Impression-Improvement as a secondary outcome. It reports group counts of 9 for the primary outcome summaries in each arm, while the adverse-event summaries use at-risk counts of 13 for placebo and 16 for GXR. These are different reported quantities; the registry does not explain their relationship to the enrollment figure or to one another.

Details such as the randomization sequence method, allocation concealment, prespecified statistical analysis plan, and sample-size justification are not reported in the registry record. The design labels establish the broad structure of the trial, but do not supply those operational or analysis details.

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: After diagnostic assessment and confirmation that subjects meet study criteria, subjects were scheduled for a baseline EEG and they performed the Stop Signal Task while ERP data was obtained. 42 subjects completed baseline evaluation,13 did not complete baseline EEG, leaving 29 to be randomized to drug

Overall Study

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 Dupaul ADHD Rating Scale, measured over Baseline and Follow up.

The primary endpoint was the DuPaul ADHD Rating Scale, described as a 54-point scale assessing ADHD symptoms dimensionally. A score of 0 represents no ADHD symptoms and 54 represents severe symptoms; the registry identifies 18 or below as the normative range. The endpoint is therefore a continuous measure in which the numerical score conveys symptom severity rather than assigning each participant only to a category.

Continuous symptom scales can capture differences across a range of severity and are commonly used to summarize symptom burden. Comparing group means can describe the average score in each arm, while standard deviations describe how dispersed individual scores are around each group mean. These summaries do not, by themselves, show how much participants changed over time or whether an observed difference is statistically precise.

The registry lists the outcome timeframe as baseline and follow-up but does not clarify which time point is represented by the posted arm means. It also does not report a change score or an adjusted comparison. The reported means are 31.4 for placebo and 13.6 for guanfacine; the corresponding standard deviations are 16.5 and 9.7. Because the registry states that values were missing or not estimable for a two-arm comparison of the continuous endpoint, these descriptive statistics should not be treated as a completed inferential comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as continuous and reports an arm mean and standard deviation for each group. These are descriptive statistics. A mean locates the center of the observed scores, while a standard deviation describes how much the scores vary around that center. Neither statistic alone indicates whether a difference between arms is compatible with sampling variation or precisely estimated.

What would a comparison estimate?

In a randomized parallel-group trial, an analysis of a continuous endpoint can estimate a contrast between the assigned groups. Depending on the prespecified approach and available measurements, that contrast might concern follow-up scores, change from baseline, or follow-up scores adjusted for baseline. Those approaches answer related but not identical questions. The registry gives a timeframe of baseline and follow-up, but does not identify which of these approaches was used or which time point the posted means summarize. The analysis specification is not reported in the registry record.

The registry states that values were missing or not estimable for a two-arm comparison of the continuous endpoint and records zero analyses. Thus, there is no posted comparative estimate to interpret. The group summaries cannot be substituted for a formal analysis because they do not describe baseline balance, within-participant change, or the uncertainty of a between-group contrast.

How should uncertainty be understood?

In general, a confidence interval gives a range of estimates compatible with the observed data under the analysis assumptions. Its width reflects precision: wider intervals indicate greater uncertainty, and narrower intervals indicate greater precision. A confidence interval for a treatment contrast is not reported in the registry record. The reported standard deviations describe variation among participants, not uncertainty around the difference between groups.

In general, a p-value assesses how compatible the data are with a specified null hypothesis under a statistical model. It does not measure the size or clinical importance of an effect. No p-value for the primary two-arm comparison is reported in the registry record. No statistical significance conclusion can therefore be drawn from the posted summaries.

What does the sample-size illustration represent?

Any planning illustration based on the observed effect is a hypothetical design calculation, not an observed trial result and not observed power. In general, such a calculation asks how many participants per arm might be needed under stated assumptions to detect a chosen effect at a stated significance level and power. It depends on the chosen effect, allocation, outcome variability, and model assumptions. The registry's stated illustration assumptions specify a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions do not establish that the original trial used the same design rationale; the trial's own sample-size justification is not reported in the registry record. No planning count is necessary to interpret the observed data, and a planning figure cannot repair the missing endpoint comparison.

What does the randomized design contribute?

In general, random assignment aims to make treatment groups comparable in expectation, reducing systematic differences in measured and unmeasured baseline characteristics. Masking can reduce the influence of knowledge about assignment on treatment delivery, assessment, or reporting. The registry records randomized allocation and quadruple masking, but does not give further details on sequence generation, concealment, or which parties were masked. Randomization does not remove uncertainty arising from small outcome counts, missing measurements, or an unspecified analysis.

The record describes a parallel-group comparison and flexible dose titration. Those features define the treatment strategy being compared, rather than a fixed dose at a single level. The primary outcome remains a symptom scale, while ERP assessments are described in the study summary. The registry does not explain how the electrophysiological measurements were analyzed or connect them to the posted primary scale summaries.

Why can event counts not replace an endpoint analysis?

Adverse-event counts address safety reporting and are distinct from the continuous symptom outcome. A count of participants affected does not convey event severity, duration, recurrence, or a comparative risk estimate. In general, event counts can be affected by how events are defined, collected, and attributed. The registry provides at-risk and affected counts, but not event-level descriptions for the non-serious events or a statistical comparison. They should be interpreted descriptively.

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("Placebo", "Guanfacine")
n   <- c(9, 9)
m   <- c(31.4, 13.6)
sp  <- c(16.5, 9.7)
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  Placebo  9  31.400  16.500  18.717  44.083
CARM  Guanfacine  9  13.600  9.700  6.144  21.056

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and identifies Clinical Global Impression-Improvement as a secondary outcome. It reports zero analyses. A statistical analysis plan specifying which outcomes were confirmatory, how outcome time points were selected, or whether multiplicity adjustments were planned is not reported in the registry record.

Multiplicity arises when several outcomes, time points, or comparisons are tested. In general, testing many hypotheses can increase the chance of finding an apparently notable result by chance, so prespecified methods may control or describe that issue. The record does not state whether any such method was used. Since no inferential analysis is posted for the primary endpoint, the registry does not support a comparison of primary and secondary results or an assessment of multiplicity handling.

Missing-data counts, reasons for missingness, and methods for handling missing observations are not reported in the registry record. The endpoint note says values were missing or not estimable for a two-arm comparison of the continuous outcome, but does not specify whether data were absent, excluded, or unsuitable for the planned analysis. It does not describe imputation, sensitivity analyses, or a model for incomplete repeated measurements.

The analysis population is also not reported in the registry record. The outcome summaries list 9 participants per arm, while the adverse-event summaries list at-risk counts of 13 for placebo and 16 for GXR, and overall enrollment is 42. These counts refer to different reporting fields, and the registry does not explain their relationship. It is therefore not possible to determine from the record whether the primary summaries use an intention-to-treat, per-protocol, or other population, or why the analysis counts differ from enrollment.

12. 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 reports serious adverse events for participants at risk in each arm. In the placebo group, 0 of 13 participants at risk were affected; in the GXR group, 0 of 16 participants at risk were affected. The serious-event terms list is empty. These figures describe the registry's recorded counts; they do not establish that no serious events occurred outside the reporting period or outside the definitions used for this record. Death counts are not reported in the registry record.

For other adverse events, 5 of 13 participants at risk in the placebo group and 10 of 16 in the GXR group were affected. These counts do not identify the event types, their severity, timing, duration, or whether individuals experienced more than one event. The registry does not report an inferential comparison, so the counts should not be interpreted as evidence of a statistically reliable difference between groups.

In general, adverse-event summaries are descriptive safety information. At-risk denominators indicate the group counts used in the report, but cannot by themselves explain exposure duration, completeness of follow-up, or the method of event collection. Those details are not reported in the registry record.

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

The registry documents a randomized, quadruple-masked, parallel-group study of GXR and placebo in children with ADHD. It reports mean DuPaul ADHD Rating Scale scores of 31.4 for placebo and 13.6 for guanfacine, with standard deviations of 16.5 and 9.7. These are descriptive summaries. Because the record does not identify whether they represent baseline, follow-up, or change, they do not define a clear treatment contrast.

The registry specifically states that values were missing or not estimable for a two-arm comparison of the continuous endpoint, and it records zero analyses. Accordingly, the posted information does not provide an estimate of the primary treatment effect, its confidence interval, or a p-value. It does not establish the precision of any between-group difference. The scale's stated score range and normative threshold give context for interpreting an individual score, but they do not resolve the missing comparison.

The study description includes ERP assessments, but the primary outcome reported is a symptom-rating scale. The registry does not post an analysis of the electrophysiological assessment. It also lists Clinical Global Impression-Improvement as a secondary outcome without a posted analysis.

The safety counts indicate no participants recorded as affected by a serious adverse event in either arm, and report other adverse events in both groups. The registry does not provide enough detail to characterize those other events or compare them statistically. Its adverse-event information should not be mistaken for a complete assessment of all possible harms.

Overall, the record supports a description of the study design and the posted group summaries, but not a conclusion about the comparative effect of treatment on the primary endpoint. The absence of an estimable analysis is a limit of what the registry record can establish; it is not itself evidence of benefit, lack of benefit, or equivalence.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between descriptive reporting and comparative inference. Group means and standard deviations can describe observed scores, but a randomized trial's central statistical question concerns a defined contrast between groups and the uncertainty around that contrast. Here, the registry provides summary values for the continuous primary outcome while stating that a two-arm comparison was missing or not estimable. The distinction matters because readers might otherwise treat the arm summaries as if they were the result of a completed treatment-effect analysis.

The record also highlights why endpoint definition and timing must be clear. The DuPaul ADHD Rating Scale is listed for baseline and follow-up, but the posted means are not tied to either time point or to change from baseline. Those possible summaries answer different questions. An unambiguous time point and analysis definition would help readers understand what the group statistics represent.

Reporting counts also need context. The registry lists overall enrollment, outcome-summary counts, and adverse-event at-risk counts, but does not explain their relationship. These quantities should not be treated as interchangeable. In general, reporting the analysis population and reasons for missing observations helps readers judge how the results relate to the randomized groups.

Finally, the record separates a study description that includes ERP assessments from a posted primary endpoint based on symptom ratings. Clear reporting of the relationship between these measures, the prespecified analysis, and any secondary results would help readers distinguish the trial's scientific questions. The case is statistically informative because it shows how a completed trial status and numerical summaries do not, by themselves, guarantee that a primary comparative result is available.

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.

A central limitation is that the registry does not identify which time point or summary type is represented by the primary-outcome means. Although the timeframe is listed as baseline and follow-up, there is no indication whether the figures refer to baseline scores, follow-up scores, or change. This prevents a clear interpretation of the group summaries as a treatment contrast.

The record says the continuous endpoint values were missing or not estimable for a two-arm comparison and lists zero analyses. It does not explain the reason, report a comparative estimate, or describe an alternative analysis. The analysis population and missing-data handling are not reported in the registry record. The outcome summary counts also differ from the enrollment and adverse-event reporting counts, without an explanation of how the populations relate.

The registry does not report the randomization sequence method, allocation concealment, a detailed statistical analysis plan, or a sample-size justification. Although randomization and quadruple masking are recorded, the roles included in masking and operational details are not described. Flexible dose adjustment is described, but the record does not report the actual dose distribution or treatment exposure by arm.

The secondary outcome is listed without a posted analysis. The ERP assessments are part of the study description, but no electrophysiological results or analysis methods are reported in the record. Safety reporting gives affected counts but does not identify non-serious event types, provide detail on event timing or severity, or report death counts. These limitations leave substantial uncertainty about the completeness and interpretation of both efficacy and safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Electrophysiological Effects of Guanfacine Extended Release in Attention Deficit Hyperactivity Disorder (ADHD) — NCT01069523.
• Registry record last updated 2012-09-03; status last verified 2012-08.
• Results first posted 2012-09-03.
• 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

The registry describes a completed Phase 4 randomized, quadruple-masked, parallel-group trial of guanfacine extended release versus placebo in children aged 6-12 with ADHD. Treatment lasted 4 weeks, with flexible dosing described within a range of 1-4 mg. The primary outcome was the DuPaul ADHD Rating Scale, assessed at baseline and follow-up according to the registry description.

The posted primary-outcome summaries list 9 participants per arm. Mean scores were 31.4 for placebo and 13.6 for guanfacine; standard deviations were 16.5 and 9.7. The registry does not specify which time point these summaries represent and states that values were missing or not estimable for a two-arm comparison. No analyses are reported.

Clinical Global Impression-Improvement is listed as a secondary outcome. Serious adverse-event counts were 0 of 13 at risk for placebo and 0 of 16 at risk for GXR; other adverse-event counts were 5 of 13 and 10 of 16. Event details and death counts are not reported in the registry record.