Treatment of Acute Migraine Headache in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Acute Migraine Headache in Children (NCT00355394), a randomized phase 2 study. The primary outcome is The Number of Subjects With a Numeric Rating Scale Score (NRS) of Zero at Two Hours..

2. Clinical Question

The question is about short-term headache freedom after treatment in an emergency-care context, rather than a general measure of migraine prevention or longer-term control. The registry’s description identifies two hours as the primary assessment time. It also lists assessments at one hour and 24 hours, along with changes in headache intensity from baseline at those assessment times. Those additional outcomes provide related, but not identical, views of headache status and intensity.

The randomized comparison can estimate a difference between groups in the observed trial, but its interpretation depends on the number of participants, the outcome definitions, and the precision of the estimates. The registry record identifies the study as Phase 2 and records enrollment of 31. Those details describe the trial’s scale and stage; they do not by themselves establish the certainty or broader applicability of its findings. The posted outcome counts are the basis for the statistical comparison, while the sponsor’s reported analysis uses Fisher Exact testing.

3. Trial Design

The registry identifies NCT00355394 as a completed, randomized, parallel-group, Phase 2 trial sponsored by Children's Hospital of Philadelphia. Its title is “Treatment of Acute Migraine Headache in Children.” The registry records the start as 2006-08 and primary completion as 2010-03. Enrollment is recorded as 31.

The trial compared metoclopramide with placebo. Both groups received standard care including intravenous fluid; the metoclopramide group also received metoclopramide, while the placebo group did not. The registry classifies the allocation as randomized and the masking as quadruple. The brief summary describes the study as prospective, double-blind, and placebo-controlled. The registry record therefore uses different masking descriptions in those two places; details explaining the difference are not reported in the registry record.

The primary outcome was the number of participants with a Numeric Rating Scale score of zero at two hours. The scale is described as ranging from 0 to 10, with 0 representing no headache and 10 representing severe headache. The primary outcome population is described as all participants included. The posted primary outcome counts are 5 for placebo and 12 for metoclopramide.

The registry lists five secondary outcomes, including headache freedom at one hour and 24 hours and changes in headache intensity from baseline. Results are posted for three of these outcomes. The registry record does not report why results are unavailable for the other listed outcomes. Details such as the trial’s original sample-size justification, allocation implementation, or prespecified statistical analysis plan are not reported in the registry record. The status is recorded as completed, but that status alone does not supply those design 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants included.

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 The Number of Subjects With a Numeric Rating Scale Score (NRS) of Zero at Two Hours., measured over 2 hours.

The primary endpoint counts participants whose Numeric Rating Scale score was zero at two hours. A score of zero represents no headache on the registry’s stated 0-to-10 scale. This makes the endpoint a binary status at a specified assessment time: each participant either meets the stated zero-score criterion or does not. The posted results express that status as counts in the placebo and metoclopramide groups.

A headache-free endpoint gives a direct measure of an outcome that matters to the trial’s acute-treatment question. It differs from measuring average change in headache intensity: someone may have a reduction in intensity without reaching zero, while the endpoint counts only those who reach the defined threshold. The registry also lists change in intensity as a secondary outcome, so the two outcome types address related but distinct aspects of symptoms.

Using a specific time point makes the outcome interpretable as a snapshot at two hours. It does not describe how long any headache-free state lasted, whether symptoms returned later, or the full course of headache between assessments. The registry separately lists headache-free status at one hour and 24 hours, but those assessments do not change the definition of the primary endpoint. The registry record does not report additional operational details about how the scale was administered or how missing two-hour assessments were handled.

7. Results Posted in the Registry

• Metoclopramide: 75.0% (12/16) versus 33.3% (5/15) on control; risk difference 41.7 percentage points (95% CI 9.7 to 73.6), risk ratio 2.25 (1.04–4.86); unadjusted two-proportion z-test p = 0.020.

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.

The Number of Subjects With a NRS Score of Zero at One Hour.

• 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:
  • Metoclopramide: 56.2% (9/16) versus 6.7% (1/15) on control; risk difference 49.6 percentage points (95% CI 22.2 to 77.0), risk ratio 8.44 (1.21–58.84); unadjusted two-proportion z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Metoclopramide than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The Number of Subjects With a NRS Score of Zero at 24 Hours.

• 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:
  • Metoclopramide: 43.8% (7/16) versus 26.7% (4/15) on control; risk difference 17.1 percentage points (95% CI -16.0 to 50.1), risk ratio 1.64 (0.60–4.49); unadjusted two-proportion z-test p = 0.320.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Metoclopramide and the control. The interval gives the range of effects that remain compatible with the data.

Change in Headache Intensity as Measured by the NRS Score From Baseline to the One Hour Assessment.

• 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:
  • Metoclopramide: mean -6.80 versus -2.50 on control; difference -4.30 (95% CI -6.28 to -2.32), standardized effect d = -1.52; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Metoclopramide than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes give a mixed picture across time and outcome type. The posted binary results include headache-free status at one hour and 24 hours, while the continuous secondary result concerns change in headache intensity at one hour. The one-hour findings point in a direction consistent with the observed two-hour primary result; the 24-hour binary comparison is less conclusive, with its recalculated interval including zero and the registry’s reported test not indicating a clear difference. The intensity outcome is a distinct measure and uses a different sponsor-reported test.

This overall pattern should be understood as supportive context, not as a set of independent replications of the primary finding. The secondary assessments concern related symptoms in the same trial and may be correlated. A difference at one time point does not establish that the difference persists, while an uncertain result at another time point does not establish equality. The results describe the measurements at their specified assessment times only.

The registry lists five secondary outcomes, and results are posted for three. It does not explain in the registry record why results are not available for the remaining listed outcomes. The absence of those results limits how completely the planned symptom profile can be assessed. The record also does not report a multiplicity adjustment or a hierarchy for interpreting secondary tests. When several outcomes or time points are examined, the chance of at least one apparently notable result can rise. General statistical principle: unadjusted secondary p-values therefore carry less weight than a prespecified primary analysis and should be interpreted cautiously, especially when the analysis plan and multiplicity strategy are not reported.

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

• The Number of Subjects With a NRS Score of Zero at One Hour.
• The Number of Subjects With a NRS Score of Zero at 24 Hours.
• Change in Headache Intensity as Measured by the NRS Score From Baseline to the One Hour Assessment.
• Change in Headache Intensity as Measured by the NRS Score From Baseline to the Two Hour Assessment.
• Change in Headache Intensity as Measured by the NRS Score From Baseline to the 24 Hour Assessment.

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary because it records whether a participant had an NRS score of zero at two hours. For a binary outcome, a group proportion is the number meeting the criterion relative to the group size. The registry posts counts and group sizes, and the recalculation compares the resulting proportions. The risk difference is the metoclopramide-group proportion minus the placebo-group proportion. A positive risk difference therefore represents a greater observed proportion meeting the criterion in the metoclopramide group. The recalculated primary risk difference is 0.417.

What does the confidence interval describe?

The 95% confidence interval for the recalculated primary risk difference runs from 0.097 to 0.736. In general, a confidence interval describes uncertainty around an estimate under the method used to construct it. It is not a guarantee that the true value lies within the particular interval, and it does not account for every source of uncertainty, such as unreported design or analysis choices. Here, the interval is entirely on the positive side of zero, but it is broad. The registry’s own analysis does not provide a confidence interval for this comparison, so this interval belongs to the unadjusted recalculation rather than the sponsor-reported analysis.

Why are there different p-values?

The registry reports Fisher Exact testing for the primary binary outcome, with p = 0.03. The recalculated result gives p = 0.02 using an unadjusted calculation from posted summary statistics. These results need not match exactly because they are not identified as the same analysis. Fisher Exact testing evaluates the association in a two-group table using an exact procedure. The recalculated comparison is a separate, simple unadjusted estimate and test. No discrepancy is flagged for this trial, but that does not make the two methods interchangeable or imply that they answer every inferential question in the same way.

A p-value is conditional on the null hypothesis and the procedure’s assumptions. It is not an effect-size measure. The risk difference conveys the estimated absolute contrast in the observed proportions, while the p-value gives a test result under a null model. Reading both alongside the confidence interval is more informative than treating any one statistic as a complete account of the evidence.

How do the secondary outcome methods differ?

The secondary binary outcomes also count participants meeting a stated criterion at a time point. Their recalculated risk differences describe differences between group proportions. The change-in-intensity outcome is continuous: the posted group summaries are means and standard deviations, and the recalculation reports a mean difference. For that one-hour intensity comparison, the recalculated mean difference is -4.3, with a 95% confidence interval from -6.277 to -2.323. The sponsor-reported test is Wilcoxon (Mann-Whitney), with p = 0.002, while the recalculation reports p < 0.001. The Wilcoxon test is a rank-based method rather than a direct test of a difference in means, so those results represent different analytical summaries.

For binary outcomes, small counts can make estimates and test results sensitive to a small number of observations. For continuous outcomes, the mean and standard deviation summarize central tendency and spread, but they do not show the full distribution of observations. The registry does not report individual participant data or enough distributional detail to evaluate that shape. General statistical principle: when sample sizes are limited, estimates can be unstable and confidence intervals can remain wide even when a test result is relatively small.

What can be said about the analysis plan?

The registry record reports the sponsor’s test methods and results but does not report the original statistical analysis plan, prespecified covariate adjustments, interim analyses, or the multiplicity strategy. Those omissions mean that the recalculations should be understood as unadjusted comparisons based on the posted summary statistics, not as a reconstruction of every planned analysis. The record also does not provide enough information to assess missing-data procedures or whether the analysis population followed an intention-to-treat definition. The primary population is described only as all participants included.

General statistical principle: over-dispersion matters when count data vary more than a chosen probability model expects, because standard errors and confidence intervals may then be too small if the extra variation is ignored. That issue is not directly established by this binary endpoint; the registry provides counts rather than a model for over-dispersed repeated counts. No over-dispersion model is reported. The distinction illustrates why methods should be matched to the outcome structure and why unreported modeling choices should not be inferred from summary values.

11. Confidence Intervals and Precision

The recalculated primary risk difference is 0.417, with a 95% confidence interval from 0.097 to 0.736. The interval is entirely above zero, but it covers a substantial range of possible positive differences. That breadth signals limited precision: the point estimate should not be mistaken for a highly exact estimate of the contrast. The registry reports a Fisher Exact p-value of 0.03, but does not report a confidence interval for its own primary analysis.

In general, a confidence interval represents the uncertainty produced by a statistical method under its assumptions. It is not a range in which every value is equally plausible, and a 95% interval does not mean there is a 95% probability that the true effect is inside this particular interval. Its interpretation also does not incorporate possible biases, outcome measurement issues, or unknown analysis decisions. The available interval belongs to the unadjusted recalculation from the posted group summaries.

For the 24-hour headache-free outcome, the recalculated risk-difference interval ranges from -0.160 to 0.501. It includes zero, so the posted data are compatible with no difference as well as with differences in either direction under that interval procedure. The reported Fisher Exact p-value is 0.46. That result should be described as uncertain, not as proof that the groups are equivalent. No equivalence margin or noninferiority analysis is reported in the registry record.

Precision is affected by the scale of the observed outcome and by the amount of information in the groups. A relatively small trial can leave considerable uncertainty, especially for binary outcomes where only some participants meet the endpoint. The posted summaries do not allow a reader to inspect individual responses, missingness patterns, or alternative adjustments. Consequently, the interval quantifies only one part of the uncertainty relevant to interpretation.

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 sample-size figures are planning illustrations based on the observed effects, not the trial’s original design assumptions. The registry record does not report the original sample-size justification. For these illustrations, the stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The figures are participants per arm, not total participants or total events. The exception noted in the planning assumptions applies to time-to-event displays, which give total events; no time-to-event outcome is posted for this trial.

The 80% power column gives the illustrated participants per arm for a design that would have 80% power under those assumptions to detect the selected effect. The 90% power column gives the corresponding per-arm planning figure for 90% power. Power is a property of a hypothetical design under assumed conditions; it is not a measure of how likely the observed result is true.

The rows vary the effect used for planning: 100%, 75%, and 50% of the observed effect. Smaller effects require more participants per arm under the stated assumptions. For the primary outcome, the illustration at 100% of the observed effect is 22 participants per arm for 80% power and 28 for 90% power. At 75% of the observed effect, the figures are 39 and 52; at 50%, they are 88 and 118. These are planning scenarios rather than estimates of what the trial enrolled or evidence that the observed analysis had a particular probability of detecting an effect. This is not observed power.

Because the observed effect itself is uncertain, planning directly from it can yield optimistic figures. The illustrations do not replace a prospective design calculation based on a justified target effect, outcome assumptions, and planned analysis.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.333; treatment proportion p₁ = 0.750; average p̄ = 0.542.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7046 = 1.3811.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6401 = 0.5387.
4. n = (1.3811 + 0.5387)² / (0.4167)² = 21.2, rounded up to 22 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
p0 <- 0.333333333333333                          # control proportion
p1 <- 0.75                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(355394)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 22 (80% power), 28 (90% power)
 75% of observed effect: n per arm = 39 (80% power), 52 (90% power)
 50% of observed effect: n per arm = 88 (80% power), 118 (90% power)
power.prop.test: 21.2 
Simulated power at n = 22 per arm: 0.817 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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

For the primary endpoint, the registry reports the sponsor’s Fisher Exact analysis with p = 0.03. The recalculation from posted group counts reports a risk difference of 0.417, a 95% confidence interval from 0.097 to 0.736, and an unadjusted p-value of 0.02. The recalculation is not a reproduction of the sponsor’s full analysis; it is a simple unadjusted analysis from the posted summary statistics. The registry does not report a confidence interval alongside its Fisher Exact result.

The two p-values are close but are not identical. They arise from distinct analyses, so the recalculated p-value should not replace the registry’s reported test. No discrepancy is flagged for this trial. The sponsor’s result is the reported registry analysis, while the recalculation adds an interpretable effect estimate and interval based on the posted counts.

The same distinction applies to the posted secondary outcomes. For example, the sponsor uses Wilcoxon (Mann-Whitney) testing for the change-in-intensity outcome, while the recalculation presents a mean difference and an unadjusted p-value. Those methods summarize evidence differently. The registry record does not report enough detail to determine whether other adjustments or analysis decisions were included in the sponsor’s analyses.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and five secondary outcomes. The posted results include the primary endpoint and three secondary outcomes. The record does not report a multiplicity adjustment, a testing hierarchy, or a rule for how secondary results were to be interpreted. It is therefore not possible to determine whether the sponsor controlled the overall chance of false-positive findings across outcomes and assessment times.

Multiplicity arises when several hypotheses are tested. In general, conducting more tests can increase the chance that at least one result appears notable even if there is no true difference for any of them. This does not make the secondary results meaningless; it means they should be treated as exploratory or supportive unless the analysis plan establishes otherwise. No such status or plan is reported in the registry record.

The primary outcome population is described as all participants included. The registry does not report an explicit intention-to-treat definition, a per-protocol population, participant flow by analysis, or the handling of missing endpoint values. The posted primary groups contain 15 participants in the placebo arm and 16 in the metoclopramide arm, but the record does not specify whether those counts represent everyone randomized, everyone treated, or everyone with an evaluable two-hour outcome. The allocation is randomized, but that fact alone does not establish how missing observations were handled.

Interim analyses, stopping rules, covariate adjustment, and the original statistical analysis plan are not reported in the registry record. Without those details, the posted analyses can be described, but the degree to which they match prespecified decisions cannot be assessed. The registry also lists five secondary outcomes while results are posted for three; reasons for that difference are not reported. These are reporting uncertainties, not evidence that any particular procedure was or was not used.

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 1% reporting threshold.

The registry’s adverse-event figures list zero serious adverse events for the placebo group, with 15 at risk, and zero for the metoclopramide group, with 16 at risk. It also lists zero other adverse events in each group, with the same respective at-risk counts. These are the registry’s posted counts and should be read as such.

The death entries are null for both groups, rather than a numeric count. A null entry is not the same as a reported zero, so deaths cannot be characterized as absent on the basis of these fields. The registry provides no serious adverse-event terms in its list of top serious terms. Details about adverse-event definitions, ascertainment, timing, severity grading, or completeness of reporting are not reported in the registry record.

Zero recorded events in a small trial does not establish that a treatment has no safety risks. These figures describe what the registry reports for this study; they do not provide a precise estimate of uncommon events or a comparison capable of ruling out risks. Safety interpretation also depends on duration of follow-up and ascertainment, which are not described in the adverse-event details.

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

The posted primary data show that more participants in the metoclopramide group than in the placebo group had an NRS score of zero at two hours. The unadjusted recalculation estimates a positive risk difference, and its 95% confidence interval is above zero. The registry’s own Fisher Exact analysis reports p = 0.03. Together, these describe an observed between-group difference in this trial under the stated outcome definition.

That finding does not establish that metoclopramide will produce the same result in every setting or for every child with acute migraine. The trial is recorded as Phase 2, and enrollment is 31. The posted group results are limited in scale, and the confidence interval leaves substantial uncertainty about the size of the difference. The result also does not answer whether headache relief lasted beyond the measured times, because the primary endpoint is a status at two hours and the registry’s related assessments occur at specified time points.

The result does not show that all participants benefited, nor does it mean that a participant who did not reach zero had no improvement. Headache freedom is a threshold outcome; the separate intensity-change outcome captures another aspect of symptoms. Similarly, the uncertain 24-hour comparison is not evidence that the groups are equivalent. The registry record does not report an equivalence or noninferiority framework.

Safety findings must be kept separate from the efficacy-style outcome comparison. The adverse-event figures record zero serious and zero other adverse events in both groups, but death entries are null, and safety ascertainment details are not reported. Those registry counts cannot establish the absence of risk.

In general, a randomized comparison can help estimate a treatment contrast, but a single small trial and incomplete reporting leave important limits on certainty and generalizability. The posted data support describing what was observed, not making a guarantee about individual outcomes or a broad clinical recommendation.

18. Why This Trial Matters Statistically

This trial illustrates why effect estimates, uncertainty intervals, and reported tests should be read together. The sponsor’s Fisher Exact result gives a test outcome for the primary binary endpoint, while the recalculation adds an absolute risk-difference estimate and confidence interval. That combination makes clear both the direction of the observed contrast and the range of values compatible with the unadjusted analysis. A p-value alone would not convey the magnitude or precision of the estimated difference.

The trial also shows the importance of distinguishing an endpoint’s meaning from other plausible measures. A score of zero at two hours is a clear threshold for headache freedom, but it is not interchangeable with change in intensity or headache status at another time. Those outcomes can provide useful context without serving as repeated confirmations of one primary result.

Its small scale makes the limitations of precision visible. The planning illustrations show how sample-size requirements change when a smaller effect is selected, under stated hypothetical assumptions. They do not establish the adequacy of the trial’s original design, because the original sample-size justification is not reported. This is a useful distinction between a retrospective planning illustration and a prospective design decision.

Finally, the record demonstrates the value of transparent reporting. The registry identifies randomization, masking, treatment groups, outcomes, and sponsor tests, while leaving the analysis plan, missing-data procedures, multiplicity approach, and some outcome results unreported. These gaps limit what statistical readers can verify. Careful interpretation separates the observed numerical results from assumptions or methods that the record does not document.

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 interpretation. The study is small, with registry enrollment of 31 and posted primary group sizes of 15 and 16. The resulting primary risk-difference interval is broad, so the observed estimate is not highly precise. The registry record does not provide a sample-size justification, making it impossible to assess the original design target or its assumptions.

The record contains different descriptions of masking: the structured design information says quadruple masking, while the brief summary describes the study as double-blind. The registry does not explain this difference. It also does not provide operational detail about allocation concealment, the masking procedures, or how the NRS assessments were administered.

Information about missing data and analysis populations is limited. The primary population is described as all participants included, but the registry does not define that phrase or report participant flow, missing endpoint counts, or imputation procedures. The posted group sizes do not by themselves resolve those questions. The statistical analysis plan, interim analyses, and multiplicity strategy are also not reported.

Five secondary outcomes are listed, but results are posted for three. The registry record does not explain the unposted results. The adverse-event summary records zero serious and other events in both groups, but provides no descriptive detail about ascertainment or follow-up; death entries are null. These limitations constrain interpretation of safety reporting as well as the secondary findings.

Finally, the trial assesses headache status at set times and does not establish duration of relief or outcomes outside the reported measures. Broader applicability cannot be determined from the registry entries alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Treatment of Acute Migraine Headache in Children — NCT00355394.
• Registry record last updated 2015-11-30; status last verified 2015-10.
• Results first posted 2013-08-30.
• 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.

23. Record Summary

NCT00355394 is a completed, randomized, parallel-group, Phase 2 trial of metoclopramide plus standard care compared with placebo plus standard care for acute migraine headache in children. The registry records quadruple masking and enrollment of 31; its brief summary describes the study as double-blind. The primary endpoint is the number of participants with an NRS score of zero at two hours.

The posted primary counts are 5 for placebo and 12 for metoclopramide. The registry reports Fisher Exact p = 0.03. The unadjusted recalculation estimates a risk difference of 0.417, with a 95% confidence interval from 0.097 to 0.736 and p = 0.02. Results are also posted for three secondary outcomes. The record does not report the original sample-size justification, multiplicity plan, missing-data procedures, or full statistical analysis plan.