Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia (NCT01156051), a randomized phase 4 study. The primary outcome is Change in Polysomnographic Total Sleep Time (TST).

2. Clinical Question

The study summary also describes an interest in daytime ADHD symptoms and nighttime sleep, assessed with questionnaires and sleep tests. The primary endpoint reported in the registry record is specifically change in total sleep time measured by polysomnography. It is therefore important to separate the broad study aim from the primary statistical comparison: the primary result concerns a measured sleep-duration outcome, rather than a combined assessment of sleep and daytime symptoms.

The intervention was adjusted according to ADHD symptom improvement and medication tolerability, as described in the study summary. The registry record does not report enough detail to establish how dose adjustment may have affected the primary comparison or how individual dose levels were represented in the analysis.

3. Trial Design

The registry describes a Phase 4, randomized, quadruple-masked, parallel-group study comparing guanfacine extended-release tablets with placebo. Its status is listed as terminated. The recorded enrollment is 29. The study began in 2010-06, and primary completion is recorded as 2012-02. A reason for termination is not reported in the registry record.

The study summary describes screening for ADHD and sleep problems, including sleep evaluation and confirmation of the ADHD diagnosis. Children who passed screening were to enter a double-blind, placebo-controlled investigation. Treatment was described as flexible-dose optimization, with dose adjustment between 1 to 4 mg over the course of four weeks. ADHD and sleep questionnaires and sleep tests were to be repeated at the end of medication adjustment, at week 4 or 5. The summary also describes tapering medication over the following 3-10 days.

The primary endpoint results are based on 11 participants in the guanfacine group and 16 in the placebo group. The primary outcome description notes that one treatment participant was lost to follow-up and one placebo participant was discontinued because of protocol noncompliance. The registry does not report the full flow of participants from screening through each analysis, or a detailed definition of the population used for every outcome.

Randomization and masking are features of the design intended to reduce systematic differences in treatment assignment and assessment. The registry record does not report the sequence-generation procedure, allocation concealment details, or the specific roles covered by quadruple masking. It also does not report the trial's original sample-size justification, planned analysis populations, or a complete statistical analysis plan. Those omissions limit how fully the design and analysis can be reconstructed from the record.

4. Participant Flow and Accounting

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

Before assignment: Medications for ADHD, that would affect sleep/alertness, or that had psychoactive properties were discontinued prior to polysomnography. Of the 35 who entered screening, 29 were enrolled. Children were disquialified for not meeting diagnostic criteria or for having disqualifying conditions (e.g., depression, heart pathology).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 29 children were enrolled, one (treatment) was lost to follow up an one (placebo) was discontinued due to noncompliance with protocol.

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.

Population: 29 enrollees, but two were excluded due to (1) lost to follow up, and (2) noncompliance with the protocol.

6. Primary Endpoint

The registry lists the primary outcome as Change in Polysomnographic Total Sleep Time (TST), measured over Baseline to last observation carried forward (after at least one week of dose stability).

The primary endpoint is change in polysomnographic total sleep time, measured in minutes. Polysomnography is an objective sleep test, and total sleep time represents the duration of sleep recorded during the assessment. The registry describes the endpoint as change from baseline to the last observation carried forward after at least one week of dose stability.

Change scores express how an outcome differs from its baseline value over the stated assessment period. Comparing mean change between randomized groups is intended to estimate the difference in average change associated with assignment to the study groups, subject to the study's design and analysis assumptions. The registry reports a mean and standard deviation for each group, and the comparison is expressed as a mean difference.

Objective measurement is useful because it does not rely solely on a participant's or caregiver's perception of sleep. It does not, by itself, capture every aspect of sleep quality or daytime functioning. Nor does a change in total sleep time alone establish whether the overall sleep experience improved. The direction and clinical interpretation of a change depend on the baseline context and on how the measure relates to the study's clinical aims.

The registry record does not report a clinically important threshold for change in total sleep time, nor does it state a threshold by which a difference would be considered meaningful to children or families. The statistical comparison should therefore be read as an estimate of the difference in measured change, not as a direct determination of clinical importance.

7. Results Posted in the Registry

• Guanfacine Extended-Release Tablets: mean -57.32 versus 31.32 on control; difference -88.64 (95% CI -148.87 to -28.41), standardized effect d = -1.22; z-test p = 0.004.

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.

Change in Baseline to Treatment ADHD-Rating Scale IV Total Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Guanfacine Extended-Release Tablets: mean -18.27 versus -1.69 on control; difference -16.58 (95% CI -24.63 to -8.53), standardized effect d = -1.65; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Guanfacine Extended-Release Tablets than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change in Baseline to Treatment Latency to Persistent Sleep (LPS)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Guanfacine Extended-Release Tablets: mean 10.54 versus -19.94 on control; difference 30.48 (95% CI -28.13 to 89.09), standardized effect d = 0.44; z-test p = 0.308.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Guanfacine Extended-Release Tablets and the control. The interval gives the range of effects that remain compatible with the data.

Change in Baseline to Treatment Minutes of Wake Time After Sleep Onset (WASO)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Guanfacine Extended-Release Tablets: mean 21.80 versus -3.90 on control; difference 25.70 (95% CI 11.89 to 39.51), standardized effect d = 1.45; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Guanfacine Extended-Release Tablets than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover ADHD symptom ratings and additional sleep measures, including latency to persistent sleep and wake time after sleep onset. Together they provide a broader set of observations than total sleep time alone, but they do not all point in the same statistical direction or have the same degree of precision. The registry's reported analyses and the simple recalculations should be considered outcome by outcome; an overall pattern should not be mistaken for a single combined endpoint.

The registry reports nominal comparisons for these secondary measures. Because the record does not report a multiplicity-adjustment strategy, the p-values should be regarded as unadjusted for the number of outcomes assessed. When several outcomes are examined, the chance of at least one apparently notable result from random variation can increase. This makes isolated secondary p-values less persuasive than a result supported by a prespecified analysis plan and an appropriate approach to multiple testing.

The secondary outcomes can help contextualize the primary result, but they are not interchangeable with total sleep time. A rating-scale measure and objective sleep measurements capture different aspects of the study aims. Their results may support questions for further study, but they cannot by themselves confirm or overturn the primary finding. The registry record does not report a hierarchy for testing secondary outcomes or identify any confirmatory status for them.

These results also come from small analyzed groups, and the registry record does not provide enough information to evaluate the stability of every secondary estimate. The overall pattern is therefore best read as exploratory: it indicates that the study collected several types of symptom and sleep information, while leaving uncertainty about how reliably any one secondary difference would reproduce in another study.

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

• Change in Baseline to Treatment ADHD-Rating Scale IV Total Score
• Change in Baseline to Treatment Latency to Persistent Sleep (LPS)
• Change in Baseline to Treatment Minutes of Wake Time After Sleep Onset (WASO)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary comparison is a comparison of means for a continuous outcome. Total sleep time is measured in minutes, and the registry reports mean change and standard deviation by group. A mean describes the average observed change in a group. A standard deviation describes how spread out participant changes are around that group's mean; it is not the uncertainty in the mean difference itself.

What the mean difference represents

The mean difference compares the average change in the guanfacine group with the average change in the placebo group. The reported recalculation is -88.64 minutes. A negative value means the estimated mean change was lower in the guanfacine group than in the placebo group, given the comparison's direction. The estimate does not mean every participant changed by that amount. Individual changes may vary, and the group summaries do not show their full distribution.

The recalculated comparison is an unadjusted calculation from the posted group summaries. It does not account for participant-level information that is unavailable in those summaries. It should be read as a simple descriptive inferential comparison, not as a reproduction of every detail of the trial's analysis.

What an interval communicates

An interval around an estimate communicates uncertainty about the location of the underlying group difference under the method's assumptions. A narrower interval indicates greater precision, while a wider interval leaves more uncertainty about the plausible magnitude. For the primary recalculation, the interval runs from -148.9 to -28.41. The registry record does not report the interval's confidence level or the method used to construct it, so those details should not be inferred.

An interval that does not include zero is consistent with a difference between group means under the interval method. This is not the same as evidence of clinical importance. The interval also does not describe the range of outcomes for individual children. Individual outcome variability is reflected more directly by the group standard deviations, which are 89.17 minutes for guanfacine and 59.54 minutes for placebo.

How to read a p-value

The recalculated p-value for the primary comparison is 0.004. A p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null model is true, and it does not measure the size or clinical value of the observed difference. A small p-value can occur alongside substantial uncertainty about the size of an effect, particularly when the interval is wide.

The registry's reported primary analysis is an ANOVA with p = 0.005. ANOVA is a method for comparing group means within a model. The registry gives no additional ANOVA estimate, interval, or model details. The reported p-value and the recalculated result are close, but they should not be treated as outputs of the same fully specified analysis.

Why variability matters

Participant responses can vary considerably, even when the average difference is noticeable. When variability is large relative to the group sizes, estimates are less precise. The primary outcome's standard deviations and the small numbers analyzed in each group illustrate why both the point estimate and its interval matter. Looking only at the p-value would hide the range of uncertainty in the estimated difference.

Some continuous outcomes can show over-dispersion, meaning their variability is greater than a particular model expects. In general, over-dispersion can make standard errors too small if the analysis does not accommodate it, which can make intervals too narrow and p-values too small. The registry record does not report a specific over-dispersion assessment for this trial, and the continuous outcome summaries alone do not establish whether over-dispersion was present.

What randomization contributes

Random assignment is intended to make treatment groups comparable on average at the point of assignment, including factors that are not measured. It does not guarantee that small groups will be balanced on every characteristic. The record does not report baseline characteristics in the information available for this analysis, so balance cannot be assessed from the outcome summaries alone. Masking is also intended to reduce the influence of expectations on care and assessment, but the registry does not describe how masking was implemented or maintained.

The reported analysis is based on group summaries and an ANOVA p-value. The registry does not report covariate adjustment, the complete model specification, the approach to protocol deviations, or whether the analysis followed intention-to-treat principles. These details matter because an adjusted model or a different analysis population could yield different estimates and uncertainty.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -88.64 minutes, with an interval from -148.9 to -28.41. The interval provides a range of uncertainty around the estimated difference, rather than a range within which individual children's changes are expected to fall. Its limits are both negative, but the width leaves uncertainty about the magnitude of the difference. The interval's confidence level is not reported in the registry record.

Precision is affected by both variability and the amount of outcome information. The primary outcome group standard deviations are 89.17 minutes for guanfacine and 59.54 minutes for placebo. The analyzed groups include 11 and 16 participants, respectively. With sizeable variation across participants and relatively small groups, the estimate can be sensitive to the observed values. This is why the interval should be considered alongside the point estimate.

The interval and p-value answer related but different questions. The interval conveys plausible values for the mean difference under its calculation method, while the p-value assesses compatibility with a null model. Neither establishes clinical importance. The registry does not report a threshold for a meaningful difference in sleep duration, so the interval cannot be classified as clinically important or unimportant using a trial-defined criterion.

The trial's own reported ANOVA p-value is 0.005, whereas the simple recalculation gives an unadjusted p-value of 0.004. The small numerical difference does not resolve uncertainties about the unreported analysis details. The registry record also does not give the confidence level or construction method for the recalculated interval. Precision should therefore be interpreted as an indication of uncertainty around a summary-statistic estimate, not as a complete account of the trial's model-based inference.

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.

For these continuous outcomes, the planning figures are participants per arm, not total events. The planning illustration assumes two-sided significance level 0.05, equal allocation between the two arms, and a normal approximation. It uses the observed effect as a reference and considers planning for 100%, 75%, and 50% of that observed effect. The original trial's own design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes the estimated number of participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under the listed assumptions. The 90% power column gives the corresponding planning number for a 90% chance. These are planning calculations, not guarantees; actual power depends on whether the assumptions about the effect, variability, allocation, and analysis are appropriate.

Smaller target effects generally require more participants to distinguish them from random variation. This pattern can be seen by comparing planning for 100% of the observed effect with planning for 75% or 50% of it. The calculations are illustrations based on the observed effect, not evidence that the original study was designed around that effect or those assumptions. They are not observed power.

Each endpoint has its own variability and observed estimate, so planning figures differ across outcomes. A planning calculation based on a large observed effect may suggest fewer participants than one based on a smaller fraction of that effect. Because estimates from small studies can be unstable, using the observed effect without considering a more conservative target can make a future design appear smaller than it needs to be.

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 = -88.640; pooled standard deviation σ = 72.853.
2. n = 2 × (1.96 + 0.842)² × 72.853² / -88.640² = 10.6, rounded up to 11 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 <- -88.64                      # observed difference in means
sigma <- 72.8527454527281                     # 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(1156051)
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 = 11 (80% power), 15 (90% power)
 75% of observed effect: n per arm = 19 (80% power), 26 (90% power)
 50% of observed effect: n per arm = 43 (80% power), 57 (90% power)
power.t.test: 11.6 
Simulated power at n = 11 per arm: 0.778 (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 registry's own primary analysis reports an ANOVA p-value of 0.005. The unadjusted recalculation from the posted group means and standard deviations gives a mean difference of -88.64 minutes, an interval from -148.9 to -28.41, and p = 0.004. The recalculated p-value is close to the sponsor-reported value, but it comes from a summary-statistic calculation rather than a reconstruction of the ANOVA model.

The registry does not report the sponsor analysis's model specification, adjusted estimate, or interval. The two p-values therefore should be described as results from different presentations of the comparison, rather than as exact duplicates. The recalculated estimate helps express the direction and approximate magnitude of the group difference, while the sponsor's reported analysis is the trial's own inferential result.

There is no flagged discrepancy between the reported and recalculated results. The numerical agreement is not proof that the methods are identical, nor does it resolve missing information about the analysis population, handling of missing outcomes, or model assumptions. Both results concern the primary mean-change comparison and neither alone determines clinical importance.

15. Multiplicity, Missing Data and Analysis Populations

The registry record reports one primary endpoint and three secondary outcomes. It does not report whether the statistical plan specified a hierarchy for testing them, adjusted p-values, or another method to control the increased chance of false-positive findings when multiple outcomes are assessed. In the absence of a reported approach, secondary p-values are unadjusted and should be interpreted cautiously. The record also does not clarify whether any other outcomes were collected but not posted.

The primary endpoint timeframe specifies last observation carried forward after at least one week of dose stability. This identifies a missing-data approach in the outcome description, but the registry does not report how many observations were carried forward, the timing of those observations, or the assumptions used to justify the method. Carrying a prior observation forward can fail to reflect a participant's later outcome if the measure would have changed over time. The record does not describe sensitivity analyses using alternative missing-data assumptions.

The primary outcome description notes one treatment participant lost to follow-up and one placebo participant discontinued because of protocol noncompliance. The outcome group sizes are 11 and 16. The registry record does not explain all differences between enrollment and the analyzed groups, provide a complete participant disposition, or state whether every randomized participant was included in each analysis.

The analysis populations are not reported in sufficient detail to determine whether results use an intention-to-treat, per-protocol, or other defined population. The record also does not provide a complete plan for protocol deviations or missing secondary outcomes. These gaps matter because exclusions and missing outcomes can affect group comparability and the estimated treatment contrast.

The registry reports an ANOVA for the primary comparison and for the secondary comparisons, but does not give full model details. It does not report whether analyses were prespecified, whether there were interim analyses, or how the original sample size was justified. These items are not reported in the registry record and should not be inferred from the posted outcome results.

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

For serious adverse events, the registry reports 0 among 12 participants at risk in the guanfacine group and 0 among 17 participants at risk in the placebo group. These figures describe the posted counts during the recorded safety assessment. They do not establish that serious adverse events cannot occur, and the group sizes limit how much can be concluded about uncommon events.

The registry also reports other adverse events in 9 of 12 participants at risk in the guanfacine group and 11 of 17 participants at risk in the placebo group. These are counts of participants with other adverse events, not measures of severity or causal attribution. The record does not provide event-level details in the serious adverse event terms, and it does not report death counts in the posted results.

Safety counts should be interpreted in light of the recorded groups at risk, the study's terminated status, and the limited size of the study. The registry figures describe what was recorded; they do not establish comparative safety for a broader population or replace a full clinical assessment.

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

The primary result describes a difference in average change in polysomnographic total sleep time between the guanfacine and placebo groups. The estimated difference is negative, meaning the average change was lower in the guanfacine group. The interval and p-value indicate that the posted summary-statistic comparison is not centered around no difference, but they do not determine whether the observed difference is beneficial, harmful, or important to participants.

A lower change in total sleep time is not automatically an improvement. Interpretation depends on baseline sleep, the meaning of the change for the children enrolled, and other aspects of sleep and daytime functioning. The registry does not report a clinically important threshold or enough contextual information to establish the clinical meaning of the estimated change. The study summary's broader aim included ADHD symptoms and sleep, but the primary endpoint is one specific sleep-duration measure.

Statistical evidence is also distinct from certainty about an individual response. The group estimate does not predict what will happen to a particular child, and the registry record does not describe individual response patterns. Nor does a difference between randomized groups establish that the same result would occur in other settings, age groups, or clinical circumstances.

The result should be interpreted with the small analyzed groups, variability in the outcome, the use of last observation carried forward, and the study's terminated status in mind. The registry does not report the reason for termination, the original sample-size justification, or a complete analysis plan. Those limits make it difficult to assess the intended evidential role of the study and the robustness of its results.

Accordingly, the record supports a statistical description of the posted outcome comparison, not a recommendation about treatment. It does not establish overall effectiveness, clinical benefit, or a complete balance of potential benefits and harms.

18. Why This Trial Matters Statistically

This trial is statistically instructive because its primary measure is objective, yet objective measurement does not eliminate uncertainty about interpretation. Polysomnographic total sleep time yields a measurable change in minutes, but a numerical difference alone does not tell whether the change matters clinically. Clear interpretation requires attention to the direction of change, baseline context, variability, and a clinically meaningful threshold. The registry does not report such a threshold.

The result also shows why effect estimates and intervals add information beyond a p-value. The reported analysis gives an ANOVA p-value, while the recalculation expresses the group contrast as a mean difference with an interval. The p-value alone does not communicate the range of plausible magnitudes. Reading the estimate and interval together makes the uncertainty more visible, while the absence of the interval confidence level and full model details remains important.

Small outcome groups and substantial standard deviations make precision a central issue. Planning figures based on the observed effect also illustrate why future sample-size choices depend on the effect a study aims to detect. A design intended to detect a smaller effect generally requires more participants. Such planning should not be mistaken for evidence that the original trial was adequately powered or that its observed effect is stable.

Finally, the study's multiple sleep and symptom outcomes raise questions about multiplicity, missing data, and analysis populations. The registry record does not report enough detail to resolve those questions. This makes the study useful as an example of how randomized design and posted results can coexist with important gaps in the statistical record.

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.

The registry lists the study as terminated but does not report why it was terminated. Without that information, readers cannot determine whether termination was related to recruitment, operations, safety, efficacy, or another reason. The recorded enrollment is 29, while the primary outcome summaries use groups of 11 and 16. The outcome description notes one loss to follow-up in the treatment group and one placebo discontinuation due to protocol noncompliance, but a full participant-flow account is not reported.

The primary endpoint uses last observation carried forward. The record does not state how many values were carried forward, whether timing differed between groups, or whether analyses under alternative missing-data assumptions were conducted. The analysis populations and handling of protocol deviations are also not reported. These omissions limit assessment of the robustness of the estimated difference.

Although the registry reports ANOVA p-values, it does not provide the complete statistical model, adjusted estimates, or a detailed analysis plan. The confidence level and construction method for the recalculated interval are not reported in the registry record. The original sample-size justification, interim analysis plan, and multiplicity strategy are also not reported.

The study enrolled a small number of children, and the outcome groups are correspondingly small. The primary outcome standard deviations indicate notable variation in observed changes. This makes the estimated group difference less precise and potentially sensitive to individual observations. The record does not include a clinically important threshold for total sleep time, so clinical relevance cannot be established from statistical results alone.

Finally, the primary endpoint focuses on total sleep time, while the study summary describes a broader interest in ADHD symptoms and several aspects of sleep. Separate results across multiple outcomes require caution, particularly when adjustment for multiple testing is not reported. These limitations do not invalidate the posted results, but they constrain how strongly and broadly they can be interpreted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Effect of Guanfacine Extended-Release on Attention Deficit Hyperactivity Disorder (ADHD)-Associated Insomnia — NCT01156051.
• Registry record last updated 2014-08-11; status last verified 2014-07.
• Results first posted 2014-08-11.
• 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

NCT01156051 is a randomized, quadruple-masked, parallel-group Phase 4 study of guanfacine extended-release versus placebo in children with ADHD-associated sleep problems. The registry lists 29 enrolled participants and a terminated status. The primary endpoint is change in polysomnographic total sleep time from baseline to the last observation carried forward after at least one week of dose stability.

The reported group means were -57.32 minutes for guanfacine and 31.32 minutes for placebo. The unadjusted recalculated mean difference was -88.64 minutes, with an interval from -148.9 to -28.41 and p = 0.004. The registry reports an ANOVA p-value of 0.005. The result describes a lower mean change in the guanfacine group; clinical importance is not established by the registry record.

Important details, including the reason for termination, original sample-size justification, complete analysis populations, and multiplicity plan, are not reported in the registry record.