A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children (NCT03292588), a randomized phase 2 study. The primary outcome is Number of Asthma Exacerbations During the Treatment Period.

2. Clinical Question

3. Trial Design

The registry describes NCT03292588, “A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children,” as a phase 2 study. Its official title is “Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (ICAC-30).” Asthma is the listed condition, and the sponsor is the National Institute of Allergy and Infectious Diseases (NIAID). The study status is completed.

The design was randomized, triple masked, and parallel. One group received mepolizumab plus guidelines-based standard of care asthma treatment; the other received placebo for mepolizumab plus the same stated standard care. The registry lists enrollment of 335. The recorded study start was 2017-11-07 and primary completion was 2021-04-20. Those dates describe the registry record and do not, by themselves, describe the duration of treatment for each participant.

The primary outcome population is described as all participants who were randomized and received at least one dose of study treatment. The primary outcome timeframe was up to 12 months. The outcome was the number of asthma exacerbations, summarized at the arm level as a mean with standard error and analysed in the sponsor's reported analysis using negative binomial regression. The registry also lists secondary measures involving asthma severity, participant quality of life, lung function, exacerbation rates in two omalizumab-dosing subgroups, and time to first exacerbation.

The registry record does not report further details about the randomization sequence, masking procedures, allocation concealment, original sample-size justification, or the trial's full statistical analysis plan. Those matters cannot be inferred from the design labels alone.

4. Participant Flow and Accounting

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

Before assignment: 335 people were enrolled in the study (signed a consent and were assigned a unique participant number). However, 45 participants dropped out before receiving treatment bringing the total to 290 participants who started treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who were randomized and received at least one dose of study treatment

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: Intent-to-treat population with available data

6. Primary Endpoint

The registry lists the primary outcome as Number of Asthma Exacerbations During the Treatment Period, measured over Up to 12 months.

The primary endpoint counts asthma exacerbations during treatment, with follow-up described as up to 12 months. The registry defines an exacerbation as a clinician's prescription of systemic corticosteroids, a participant's initiation of a systemic corticosteroid course, or hospitalization for asthma. A participant-initiated course without clinician involvement counted only if the study clinician agreed that treatment was warranted and the specified dose condition was met: prednisone, prednisolone, or methylprednisolone at a daily dose of at least 20 mg for 3 of 5 consecutive days, or dexamethasone at a single daily dose of at least 10 mg. A corticosteroid burst prescribed by a non-ICAC clinician counted regardless of dose.

This is a recurrent-event count outcome: a participant can contribute more than one exacerbation during follow-up. That makes the outcome relevant to the trial's prevention question, because it describes the burden of events across the treatment period rather than only whether a first event occurred. It is not equivalent to a measure of asthma symptoms, lung function, or quality of life. The registry reports group means of 0.96 for mepolizumab and 1.3 for placebo, with standard errors of 0.1 and 0.13. These summaries describe the observed endpoint in the stated analysis population; they do not alone establish how the trial's model accounts for the count distribution or other features of the data.

7. Results Posted in the Registry

• Mepolizumab: mean 0.96 versus 1.30 on control; difference -0.34 (95% CI -0.66 to -0.02), standardized effect d = -0.24; z-test p = 0.038.

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.

Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.

• 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 errors.
• Result:
  • Mepolizumab: mean 1.11 versus 1.31 on control; difference -0.20 (95% CI -0.84 to 0.44), standardized effect d = -0.12; z-test p = 0.540.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Mepolizumab and the control. The interval gives the range of effects that remain compatible with the data.

Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.

• 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 errors.
• Result:
  • Mepolizumab: mean 0.87 versus 1.30 on control; difference -0.43 (95% CI -0.87 to 0.01), standardized effect d = -0.29; z-test p = 0.053.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Mepolizumab and the control. The interval gives the range of effects that remain compatible with the data.

Time to First Asthma Exacerbation

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Regression, Cox); it was not recalculated.
• Result:
  • Mepolizumab vs Placebo: hazard ratio 0.86 (95% CI 0.63–1.18), reported p = 0.359 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Mepolizumab vs Placebo and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several domains, including asthma severity, participant quality of life, lung function, exacerbation rates in two subgroups defined by fit to the FDA-approved omalizumab dosing table, and time to first exacerbation. The registry lists 22 outcome measures, 21 analyses, and 12 posted secondary outcomes. Across the secondary exacerbation analyses with results recorded, the estimates do not all give the same degree of statistical clarity: one subgroup result has an interval that includes the risk-ratio null, another has an interval below that null, and the time-to-first-event interval includes the hazard-ratio null.

This mixed pattern is compatible with the primary result but does not independently provide a uniform confirmation across all secondary domains. Secondary analyses may address different questions, use different models, and involve smaller or otherwise different analysis populations. The subgroup comparisons also concern populations defined by omalizumab dosing-table fit; they should not be generalized to all participants without qualification. Results for the other named secondary outcomes are not detailed in the record summarized by these results, so no broader claim about their direction or precision is warranted.

Unadjusted secondary p-values carry less weight when many outcomes and analyses are considered. General statistical explanation: testing multiple hypotheses increases the chance that at least one result will appear unusual by chance, even if every null hypothesis is true. A multiplicity procedure can address this issue, but the registry record does not report whether an adjustment was planned or used. The secondary p-values should therefore be read as individual reported tests, not as a family-wise-confirmed set of findings. They provide context for the primary result, not a substitute for it.

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

• Composite Asthma Severity Index (CASI)
• Participant Quality of Life Measured Using the Physician Global Assessment Tool
• Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14
• Lung Function as Assessed by Spirometry
• Lung Function as Assessed by Impulse Oscillometry
• Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.
• Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.
• Time to First Asthma Exacerbation

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is a count of exacerbations, and the posted arm summaries report means and standard errors. A mean gives the average count in an arm; a standard error describes the sampling uncertainty around that estimated mean. The registry's reported primary comparison is not simply a test of those two means. It uses negative binomial regression and reports a risk ratio. This distinction matters because a count model can represent the event-count structure directly, while a mean difference is an absolute-scale summary.

Why use negative binomial regression for a count outcome?

General statistical explanation: count data are often nonnegative integers, and their variability may not fit the assumptions of a simple Poisson model. Over-dispersion means that the observed variation is greater than such a model would expect from its mean. A negative binomial model can accommodate over-dispersion through an additional dispersion component. This can make it a useful approach for recurrent event counts. The registry names negative binomial regression for the primary result, but does not report a diagnostic assessment of over-dispersion, the model specification, covariates, or the way follow-up time was incorporated. Those details should not be assumed.

The primary model reports a risk ratio of 0.73, a 95% confidence interval from 0.56 to 0.96, and p = 0.027. The risk-ratio scale is relative: its null value is 1, which represents equal modeled rates. Values below 1 indicate a lower modeled rate in the mepolizumab group relative to placebo, according to the model's comparison. The confidence interval communicates uncertainty in that relative estimate. It does not mean that the true value has a 95% probability of being inside the particular interval.

What does the simple recalculation represent?

The simple recalculation uses the posted arm means and standard errors to estimate an unadjusted mean difference. It gives a mean difference of -0.34, a 95% confidence interval from -0.661 to -0.018, and p = 0.038. This estimate is on an absolute scale: it expresses the difference in mean counts, not a relative rate. It does not reproduce the regression model, incorporate unreported covariates, or replace the sponsor's analysis. It is useful as a check on the direction and approximate scale of the arm summaries, but the model-based result is the registry's reported primary analysis.

General statistical explanation: a confidence interval describes a range of values compatible with the estimate under the method's assumptions. A p-value measures how surprising the observed data, or more extreme data, would be under a specified null hypothesis and model. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. Different methods can produce different estimates, intervals, and p-values because they use different scales and assumptions; the risk ratio and mean difference should not be expected to match numerically.

The registry lists standard errors for each arm's mean: 0.1 for mepolizumab and 0.13 for placebo. It does not give arm-specific confidence intervals for those means. The recalculated interval belongs to the unadjusted difference, not to either mean separately. The model-based interval belongs to the sponsor's risk-ratio estimate. Keeping these estimands and intervals distinct prevents a descriptive summary from being mistaken for the reported regression analysis.

How should the secondary models be distinguished?

The secondary subgroup results use different named methods. The subgroup that did not fit the FDA-approved omalizumab dosing table was analysed with mixed models, with a reported risk ratio of 0.85, a 95% confidence interval from 0.55 to 1.31, and p = 0.458. The subgroup that fit the dosing table was analysed with negative binomial regression, with a reported risk ratio of 0.67, a 95% confidence interval from 0.47 to 0.95, and p = 0.025. The time-to-first-exacerbation outcome was analysed with Cox regression and reported as a hazard ratio of 0.86, a 95% confidence interval from 0.63 to 1.18, and p = 0.359.

General statistical explanation: a hazard ratio compares event hazards over time, whereas a risk ratio compares modeled rates and a mean difference compares absolute averages. They answer related but distinct questions and depend on different model assumptions. The time-to-event endpoint also uses information about when the first event occurred; it is not a count of all recurrent exacerbations. The registry gives median times of 241.0 days for mepolizumab and 224.0 days for placebo, with full ranges of 1.0 to 380.0 and 1.0 to 378.0 days, respectively. Those medians do not replace the Cox-model comparison.

The registry reports 22 outcome measures, 21 analyses, and 12 posted secondary outcomes. It does not report enough detail in the record to reconstruct every analysis decision or determine whether all intended analyses are represented. The available method labels and estimates should therefore be read as the analyses recorded, not as a complete account of the trial's statistical plan.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate, not whether an estimate is clinically important. The primary model-based risk ratio is 0.73, with a 95% confidence interval from 0.56 to 0.96. The interval stays below the risk-ratio null value of 1, but it spans estimates ranging from a more pronounced relative reduction to one closer to the null. The reported p-value is 0.027. Together, these statistics describe evidence under the model; they do not make the estimate exact.

The unadjusted recalculated mean difference is -0.34, with a 95% confidence interval from -0.661 to -0.018 and p = 0.038. Its interval is on the absolute mean-count scale and lies below zero, with an upper bound close to zero. The mean-difference interval and the risk-ratio interval cannot be compared as though they measured the same quantity. The former is calculated from group summaries; the latter comes from the registry's negative binomial regression.

The secondary subgroup and time-to-event intervals illustrate additional uncertainty. The interval for participants who did not fit the FDA-approved omalizumab dosing table, 0.55 to 1.31, includes the risk-ratio null of 1. The interval for those who fit the dosing table, 0.47 to 0.95, lies below 1. The time-to-first-event hazard-ratio interval, 0.63 to 1.18, includes its null value of 1. These estimates should be interpreted in their own analysis populations and on their own scales.

The registry does not report confidence intervals for the individual primary arm means. The standard errors of 0.1 and 0.13 indicate sampling uncertainty in those means, but do not by themselves describe every source of uncertainty, such as missing outcomes or model misspecification. Confidence intervals are conditional on the analysis and its assumptions; they do not capture every limitation of a trial record.

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 illustrations use the observed effect as a reference and show how a hypothetical future study's size changes when the effect to detect is set at 100%, 75%, or 50% of that observed effect. For the primary count outcome, the figures are participants per arm, not total participants. The time-to-first-exacerbation planning figures instead refer to total events. These are different planning quantities and should not be read interchangeably.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original trial's own sample-size justification and design assumptions are not reported in the registry record; the displayed planning approach is an illustration based on the observed result, not evidence of the original design method.

The 80% power column describes the hypothetical participants per arm, or total events for the time-to-event outcome, required under those assumptions to have an 80% chance of detecting the specified effect if that effect were the true one. The 90% column uses the corresponding higher target chance. Power is tied to a particular effect size, test, and assumptions; it is not the probability that the treatment works. Smaller target effects require more participants or events, which is why planning for 75% or 50% of the observed effect produces larger requirements than planning for the full observed effect. These are planning illustrations, not observed power.

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 = -0.340; pooled standard deviation σ = 1.394.
2. n = 2 × (1.96 + 0.842)² × 1.394² / -0.340² = 263.9, rounded up to 264 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 <- -0.34                      # observed difference in means
sigma <- 1.39406579631108                     # 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(3292588)
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 = 264 (80% power), 354 (90% power)
 75% of observed effect: n per arm = 470 (80% power), 629 (90% power)
 50% of observed effect: n per arm = 1,056 (80% power), 1,414 (90% power)
power.t.test: 264.9 
Simulated power at n = 264 per arm: 0.795 (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 analysis is the negative binomial regression result: risk ratio 0.73, 95% confidence interval from 0.56 to 0.96, and p = 0.027. The registry's arm-level means are 0.96 for mepolizumab and 1.3 for placebo. A simple unadjusted recalculation from those summaries gives a mean difference of -0.34, with a 95% confidence interval from -0.661 to -0.018 and p = 0.038.

These are not competing estimates of precisely the same parameter. The recalculation compares arithmetic means on an absolute scale, while the sponsor's model reports a relative rate comparison from negative binomial regression. The methods can therefore yield different numerical estimates, intervals, and p-values without indicating an error. The registry's discrepancy indicator is false. The sponsor's own model-based analysis is the primary reported result; the recalculation is a transparent, unadjusted comparison that helps describe the posted arm summaries, not a replacement for that analysis.

The registry record does not give the full regression specification or enough detail to independently reproduce the sponsor's model. Interpretation of the primary result should therefore retain its status as the analysis reported in the record, while recognizing that the recalculation answers a narrower descriptive question.

15. Multiplicity, Missing Data and Analysis Populations

The registry records multiple outcomes and analyses: 22 outcome measures, 21 analyses, and 12 posted secondary outcomes. It identifies a primary endpoint, which helps distinguish the principal trial question from additional questions. However, the registry record does not report a multiplicity adjustment or state how the family of secondary comparisons was handled. Without that information, the secondary p-values should not be treated as if they collectively had the same error rate as a single prespecified test. Findings among multiple secondary analyses are appropriately considered supportive or exploratory unless a more complete analysis plan establishes otherwise.

The registry describes the primary population as all participants randomized and receiving at least one dose of study treatment. It does not report how many randomized participants did not receive treatment, how many had missing primary outcome data, or how missing data were handled. The record also does not state whether the sponsor used imputation, complete-case analysis, sensitivity analyses for missingness, or another approach. Missing outcomes can affect an analysis when their occurrence is related to treatment or outcome, so the absence of these details limits assessment of robustness.

The record does not report the full statistical analysis plan, the timing of analysis decisions, interim analyses, or the original sample-size justification. It also does not provide enough information to determine whether every analysis was prespecified or how deviations, if any, were managed. These details are not established by the randomized, triple-masked design description. The available results support interpretation of the statistics that are reported, but they do not resolve these unreported aspects of analysis conduct.

The sponsor reports negative binomial regression for the primary endpoint and provides a relative estimate with a confidence interval and p-value. The registry does not provide full model diagnostics, covariate details, or a complete reproducibility account. These omissions do not negate the recorded estimate, but they limit independent evaluation of model assumptions and sensitivity to analysis choices.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tachycardia (0.7%), chest pain (0.7%), suicidal ideation (0.7%), cardio-respiratory arrest (0.7%), abdominal pain (0.7%).

The registry lists serious adverse events for 4 participants at risk in the mepolizumab group and 2 participants at risk in the placebo group. The corresponding at-risk counts are 146 and 144. It also lists other adverse events affecting 53 participants in the mepolizumab group and 42 in the placebo group, with the same respective at-risk counts. Deaths are listed as 1 and 0. These are descriptive registry counts and should be read separately from the efficacy analysis.

The listed serious adverse event terms include tachycardia, chest pain, suicidal ideation, cardio-respiratory arrest, abdominal pain, and major depression, each recorded as 0.7%. The record does not provide enough detail in these figures to establish the timing, relatedness to study treatment, duration, severity beyond the serious-event classification, or whether listed terms occurred in the same participant. The percentages are quoted as recorded and should not be added together or treated as mutually exclusive categories.

These event counts do not by themselves establish comparative safety. The registry record does not supply a full clinical narrative, adjusted comparison, or causal attribution for the events in these summaries. The figures describe what is recorded, within the listed at-risk groups, and are not a basis for medical advice.

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

The primary result addresses a specific question: the number of registry-defined asthma exacerbations during up to 12 months of treatment among participants who were randomized and received at least one dose. The posted arm means are 0.96 for mepolizumab and 1.3 for placebo. The sponsor's negative binomial analysis reports a risk ratio of 0.73, with a 95% confidence interval from 0.56 to 0.96 and p = 0.027. The unadjusted mean-difference recalculation is -0.34, with a 95% confidence interval from -0.661 to -0.018 and p = 0.038.

Those statistics describe the observed trial data under the stated outcome definition and analysis methods. They are evidence of a difference in the measured exacerbation outcome in this trial, with uncertainty represented by the reported intervals. They do not identify one exact effect, establish that every participant would have the same outcome, or answer every question about asthma control. The endpoint is not a direct measure of symptoms, quality of life, lung function, or long-term outcomes.

The results also do not establish that the effect applies to populations or care settings beyond the trial's stated population and design. The registry describes children with asthma, but does not give further demographic detail in the registry record. The record's secondary results vary in their uncertainty, and the registry does not report multiplicity handling, full missing-data methods, or the complete model specification. Those limits matter when interpreting the result alongside the primary estimate.

Statistical evidence is not the same as a clinical recommendation. These registry results should be understood as a report of a randomized comparison under its recorded conditions, not as medical advice or a guarantee of benefit or harm for an individual.

18. Why This Trial Matters Statistically

This trial illustrates why a clinical outcome and its statistical scale need to be considered together. Asthma exacerbations are counted events, and participants may experience recurrent events. The registry reports both arm-level mean counts and a negative binomial regression result expressed as a risk ratio. The unadjusted mean difference and the model-based risk ratio communicate related but distinct aspects of the comparison. Distinguishing them prevents a convenient summary calculation from being confused with the sponsor's primary analysis.

It also shows why uncertainty deserves attention alongside a point estimate. The primary model interval remains below the risk-ratio null, while its range still allows a span of effect sizes. The secondary analyses do not all have the same precision or pattern. This is a useful reminder that one primary analysis can be the central result without making every related analysis equally conclusive.

The registry's broad outcome list makes multiplicity relevant. Several outcome domains and subgroup questions are recorded, while the multiplicity approach is not reported. Readers therefore need to give greater interpretive weight to the designated primary endpoint and avoid treating a secondary p-value as a standalone confirmation. The missing information about sample-size justification, missing-data handling, and model details also demonstrates why registration summaries do not always provide a complete statistical audit trail.

Finally, the planning illustrations show how sample-size requirements depend on the effect being targeted and on specified assumptions. They are not a retrospective measure of the trial's success or observed power. Taken together, the trial is statistically informative both for its primary count-model comparison and for the questions that remain unresolved in the registry 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.

Several limitations specific to this trial affect interpretation of the posted results. The registry gives enrollment of 335, while the primary outcome arm summaries list 146 participants in the mepolizumab group and 144 in the placebo group. The record does not explain the relationship between these figures or detail the flow from enrollment through randomization, treatment receipt, and endpoint analysis. The primary analysis population is defined as randomized participants who received at least one dose, rather than all enrolled participants.

The primary event definition combines corticosteroid prescriptions, participant-initiated courses subject to stated conditions, and asthma hospitalizations. This captures clinically consequential events as specified, but the record does not report separate results by event type, adjudication procedures, or inter-rater consistency. It also does not report how follow-up duration varied among participants or how that was handled in the model.

The registry names negative binomial regression for the primary analysis but does not report its full specification, covariates, diagnostics, or sensitivity analyses. The simple recalculation uses summary means and standard errors and is not a substitute for those model details. The record also does not report missing outcome counts or missing-data methods, an original sample-size justification, or a multiplicity procedure. These omissions limit independent assessment of robustness and the interpretation of secondary findings.

The trial is identified as phase 2 and its results should be read in that context. The registry record does not provide further demographic detail in the stated details, and the subgroup analyses concern specific omalizumab dosing-table categories. The results therefore do not, by themselves, establish how estimates apply across populations or settings not described in the record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children — NCT03292588.
• Registry record last updated 2022-07-20; status last verified 2022-06.
• Results first posted 2022-06-21.
• 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

NCT03292588 is a completed, randomized, triple-masked, parallel phase 2 trial of mepolizumab plus guidelines-based standard asthma care versus placebo plus the same standard care. The registry lists enrollment of 335 and identifies the primary endpoint as the number of asthma exacerbations during up to 12 months among participants randomized and receiving at least one dose.

The sponsor's primary negative binomial regression reported a risk ratio of 0.73, a 95% confidence interval from 0.56 to 0.96, and p = 0.027. The posted arm means were 0.96 and 1.3; the unadjusted recalculation of the mean difference was -0.34, with a 95% confidence interval from -0.661 to -0.018 and p = 0.038. The secondary results vary in precision, and the registry record does not report several details needed to assess multiplicity, missing data, sample-size justification, and the full analysis specification.