A Study of 2 Doses of MAP0010 in Asthmatic Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of 2 Doses of MAP0010 in Asthmatic Children (NCT00697697), a randomized phase 3 study. The primary outcome is Number of Patients With Treatment Emergent Adverse Events Related to Study Drug.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group Phase 3 extension study of MAP0010 in children with asthma. Its official title identifies a 40-week investigation of the safety and efficacy of two doses, while the brief summary emphasizes examining safety. The title describes the age range as 12 months to 8 years at enrollment into the MAP0010-CL-P301 study; the registry record does not further explain the relationship between enrollment in that study and entry into this extension.

The two listed interventions were 0.135mg and 0.25mg MAP0010, each described as unit dose budesonide administered by nebulization twice daily for 40 weeks. The record lists 192 participants enrolled. The posted arm results give 94.0 for the 0.135mg arm and 98.0 for the 0.25mg arm. The registry does not explain how those arm counts relate to the enrollment figure or provide a participant-flow account.

The official title calls the study active-controlled, but the posted interventions and arms identify only the two MAP0010 doses. The listed comparison is the higher dose against the lower dose; a separate comparator is not reported in the registry record. The study status is terminated, and the primary completion date is recorded as 2009-08. A reason for termination is not reported in the registry record. Randomization details, including the sequence-generation and allocation-concealment methods, are not reported in the registry 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients who received any study drug and who had at least one post safety evaluation were included in the adverse event analysis.

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: Subjects were randomly assigned to treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Treatment Emergent Adverse Events Related to Study Drug, measured over 40 weeks.

The primary endpoint is the number of patients with treatment-emergent adverse events related to study drug, with a timeframe of 40 weeks. A treatment-emergent adverse event is defined in the registry as one whose start date falls on or after the date of first administration of study drug during the study. The endpoint therefore counts participants who experienced at least one qualifying event; it is not a count of every event, an event rate over time, or a measure of severity.

The specified analysis population includes patients who received any study drug and had at least one post-safety evaluation. The registry gives the number with an event and the arm size for each dose: 6.0 of 94.0 in the 0.135mg arm and 4.0 of 98.0 in the 0.25mg arm. These are the posted endpoint counts, not a full account of all adverse events or of missing safety evaluations.

A safety endpoint of this kind is used to describe observed adverse-event experience during treatment. It helps distinguish events that began after treatment started from events that were already present, according to the registry definition. However, the relatedness criterion means the posted primary result concerns events judged related to study drug, rather than every treatment-emergent event. The registry record does not report how relatedness was assessed or who made those judgments.

7. Results Posted in the Registry

• 0.25mg MAP0010: 4.1% (4/98) versus 6.4% (6/94) on control; risk difference -2.3 percentage points (95% CI -8.6 to 4.0), risk ratio 0.64 (0.19–2.19); unadjusted two-proportion z-test p = 0.473.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the risk difference describe?

A risk difference contrasts the proportions of participants with an event in two groups. In this comparison, the stated direction is the 0.25mg arm against the 0.135mg arm. The estimate is -0.023, so the observed event proportion is lower in the higher-dose arm by the amount indicated by the estimate. This is an unadjusted recalculation from the posted event counts and arm sizes; it is not an adjusted treatment effect. The endpoint is binary at the participant level: a participant either met the definition of having at least one qualifying event or did not.

The risk difference is expressed on the absolute scale, which makes it possible to read the contrast as a difference in proportions rather than as a relative measure. It does not describe the number of events per participant, the timing of events, or their clinical severity. The registry does not report a time-to-event analysis for this endpoint.

How should the p-value be read?

The unadjusted p-value is 0.473. In general, a p-value summarizes how compatible the observed data are with a specified statistical null model; it is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. A larger p-value does not show that the groups are identical. In this record, the p-value accompanies a small observed difference and an interval that includes zero, so it does not provide strong evidence of a difference under the unadjusted comparison.

The registry record does not report the statistical test or model used for an original sponsor analysis. The posted comparison is identified as a recalculated unadjusted comparison, so the interpretation should remain attached to that calculation rather than being attributed to an undocumented sponsor method.

Why use a confidence interval?

A confidence interval describes uncertainty around an estimate under the assumptions of the method used. For the risk difference, the interval runs from -0.086 to 0.040. Values on either side of zero are included, so the data are compatible with a lower event proportion in the higher-dose arm, little or no difference, or a higher event proportion in that arm, within the range represented by this interval and method. It is not a range containing individual participants' outcomes.

Intervals are useful alongside point estimates because the same point estimate can be more or less precise depending on the amount and distribution of information. Here, the interval spans both negative and positive values. That width signals uncertainty about the direction and size of the difference, rather than a definitive conclusion that the doses have equal effects.

What does unadjusted mean?

An unadjusted comparison uses the posted group summaries without accounting for additional covariates or other model terms. It is transparent as a direct contrast of the observed counts and group sizes, but it does not address possible imbalance in participant characteristics or other sources of variation. Randomization is reported, yet the record does not provide the randomization procedure, baseline characteristics, or an adjusted analysis that would help assess those issues.

The registry lists 0 analyses. That means the record does not contain posted analysis records describing a sponsor model, covariate adjustment, or inferential procedure for the outcome. The statistical comparison available in the posted results should not be mistaken for an unreported prespecified analysis plan.

How do related and treatment-emergent events differ?

The endpoint requires an event to begin on or after first study-drug administration and to be counted as related to study drug. Treatment emergence is a timing definition; relatedness is a separate judgment. Thus, a treatment-emergent event need not necessarily be considered related, and the primary endpoint is narrower than a count of all events that began during follow-up. The record does not report the method for adjudicating relatedness, whether event reviewers were masked, or how recurrent events were handled.

Because the endpoint counts participants, a participant with more than one qualifying event contributes to the participant count as a participant with an event, rather than adding multiple entries to the primary result. The posted summary does not report event-level details, so it cannot describe recurrence, duration, or the distribution of event types beyond the serious-event term listing.

10. Confidence Intervals and Precision

The risk-difference estimate is -0.023, and its 95% confidence interval extends from -0.086 to 0.040. The interval includes zero and extends to values on both sides of it. This means the summary is not precise enough to determine the direction of the between-dose difference with confidence under this unadjusted method. The point estimate alone should not be read as a settled difference.

A confidence interval is an uncertainty summary for an estimated group contrast, conditional on the method and its assumptions. It does not say that a specified proportion of participants had outcomes within the interval, and it is not a prediction interval for an individual. Its width reflects the limited information available for estimating the contrast from the posted event counts and arm sizes. The registry record does not report an alternative interval from a sponsor model or any adjustment that might change the estimate or its precision.

The interval is compatible with a lower event proportion in the 0.25mg group, no difference, or a higher event proportion in that group. Consequently, the posted result does not demonstrate equivalence or rule out potentially meaningful differences. Equivalence would require a prespecified margin and an analysis designed to assess it; such a margin and analysis are not reported in the registry record. The unadjusted p-value of 0.473 is consistent with the interval's inclusion of zero, but neither statistic establishes that the arms are the same.

Precision also depends on what the endpoint captures. This result is a participant-level count of related treatment-emergent events, not a complete description of adverse-event type, severity, recurrence, or timing. The summary therefore has limited precision both for the size of the risk difference and for characterizing the safety experience in detail.

11. 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 figures are illustrations based on the observed effect, not the trial's own design calculations. For this binary endpoint, the figures refer to participants per arm, not total events. The stated 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 set to the stated fraction of the observed effect. The registry record does not report the original trial's sample-size assumptions or justification.

The 80% power column describes the number of participants per arm that the planning calculation associates with an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the corresponding planning number for a 90% chance. These are prospective planning quantities for hypothetical studies, not observed characteristics of this trial. This is not observed power.

The planning display includes scenarios for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For 100% of the observed effect, the listed figures are 1,469 participants per arm for 80% power and 1,966 participants per arm for 90% power. For 75% of the observed effect, they are 2,747 and 3,677 participants per arm, respectively. For 50% of the observed effect, they are 6,485 and 8,681 participants per arm, respectively. Smaller effects need more participants because they are harder to distinguish from random variation under the same assumptions.

These calculations use the observed effect as their starting point, so they should be treated cautiously: the observed estimate itself is uncertain, as reflected by its confidence interval. The planning figures do not establish that a future study would achieve the stated power if its design, allocation, endpoint definition, or analysis differed from these assumptions.

12. 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 = 0.064; treatment proportion p₁ = 0.041; average p̄ = 0.052.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.3149 = 0.6172.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.3145 = 0.2647.
4. n = (0.6172 + 0.2647)² / (-0.0230)² = 1,468.5, rounded up to 1,469 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 <- 0.0638297872340425                          # control proportion
p1 <- 0.0408163265306122                          # 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(697697)
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 = 1,469 (80% power), 1,966 (90% power)
 75% of observed effect: n per arm = 2,747 (80% power), 3,677 (90% power)
 50% of observed effect: n per arm = 6,485 (80% power), 8,681 (90% power)
power.prop.test: 1468.5 
Simulated power at n = 1,469 per arm: 0.798 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures, but it does not post secondary outcomes in the results metadata. The identity and results of any other measure are not reported in the registry record. No analysis records are posted, so the record does not describe a statistical analysis plan, a hierarchy of outcomes, or which comparisons were intended to be confirmatory.

Multiplicity arises when several outcomes, comparisons, or analyses are considered. In general, evaluating many hypotheses can increase the chance of observing an apparently notable result by chance. The registry record does not report whether any multiplicity adjustment was planned or used, and the single unadjusted comparison should not be treated as evidence that other potential analyses were controlled for. The available information is insufficient to determine how the primary endpoint fit within any broader testing strategy.

The primary endpoint population is described as patients who received any study drug and had at least one post-safety evaluation. The arm counts in the endpoint summary are 94.0 and 98.0. The registry record does not provide a participant-flow account, the number excluded from the safety analysis, reasons for exclusion, or details of missing safety evaluations. It also does not report a missing-data method or sensitivity analysis.

The analysis population definition is therefore narrower and more specific than a general statement that all randomized participants were analyzed. The record does not state whether the primary analysis followed an intention-to-treat principle, how protocol deviations were handled, or whether participants were analyzed according to assigned dose or received dose. Those details are not reported in the registry record. Without them, it is not possible to assess the influence of missing observations or exclusions beyond noting the population definition that was posted.

14. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acquired hydrocele (1.0%).

The serious adverse-event figures are reported as serious events related to study drug: 0 in the 0.135mg MAP0010 arm and 1 in the 0.25mg arm. The registry also lists acquired hydrocele at 1.0% among the top serious-event terms. The term listing does not give further clinical detail or identify an arm for that term in the information reported.

These serious-event figures are separate from the primary endpoint, which counts participants with treatment-emergent adverse events related to study drug and includes events that are not necessarily serious. The adverse-event summary also reports other related adverse events in 71 participants in the 0.135mg arm and 85 in the 0.25mg arm. These counts do not show how many events occurred per participant, when they occurred, or their severity.

Deaths are not reported in the registry record. The record does not provide event narratives, a complete listing of serious events by arm, or the method used to determine seriousness and relatedness. The reported figures should therefore be read as registry summaries, not as a complete account of individual safety outcomes.

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

The posted results describe a randomized comparison of two MAP0010 doses in children with asthma, with safety assessed over 40 weeks. For the primary endpoint, the higher-dose arm had 4.0 participants with a treatment-emergent adverse event related to study drug among 98.0, compared with 6.0 among 94.0 in the lower-dose arm. The unadjusted risk difference is -0.023, with a 95% confidence interval from -0.086 to 0.040 and an unadjusted p-value of 0.473.

Those results show the observed counts and the uncertainty around a direct comparison between the two dose groups. They do not establish that one dose is safer, that the doses are equivalent, or that MAP0010 caused or prevented any event. There is no placebo or untreated comparison listed in the posted arms, and the results cannot determine how the event experience compares with no study drug.

The primary outcome concerns related events that began on or after the first dose. It does not capture every adverse event under the endpoint definition, and it does not convey severity, recurrence, duration, or timing beyond the onset criterion. The separate serious-event summary reports 0 related serious adverse events in the 0.135mg arm and 1 in the 0.25mg arm, but the sparse summary does not support a broader conclusion about serious-event risk.

The registry record does not report the reason the study was terminated, the original statistical plan, missing-data methods, or an adjusted sponsor analysis. It also does not provide enough information to evaluate the effects of exclusions or incomplete follow-up. Interpretation should therefore remain limited to the posted endpoint counts, the unadjusted recalculation, and the safety summaries actually reported.

16. Why This Trial Matters Statistically

This trial illustrates why the point estimate, its uncertainty, and the outcome definition all matter in a clinical safety comparison. The raw endpoint counts are small, and the risk-difference interval spans zero. Reading only the negative point estimate could suggest a directional difference, while the interval makes clear that the direction and size remain uncertain under the unadjusted comparison.

It also shows the importance of separating an adverse-event count from a broader safety conclusion. The primary endpoint counts participants with related events that began after study drug was first administered. Separate serious-event figures and other related-event counts describe different aspects of safety; they are not interchangeable with the primary endpoint. Without event-level detail, a participant-level count cannot describe recurrence, severity patterns, or the timing of events.

The comparison is between two doses rather than between treatment and no treatment. That design question shapes what the data can answer: the posted result addresses the observed contrast between the listed dose arms, not the effect of receiving MAP0010 versus receiving no study drug. The official title describes an active-controlled study, but no separate comparator is listed in the posted arms.

Finally, this record demonstrates the value of transparent reporting of analysis populations, missing data, and statistical methods. The endpoint population is described, but details such as exclusions, missingness, adjustment, and the original analysis plan are not reported. Those omissions constrain the strength and scope of statistical interpretation even when the arm counts and an unadjusted comparison are available.

17. 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 record has limited detail about how the trial was conducted and how the posted results were analyzed. Although randomization and triple masking are reported, the allocation method, concealment procedures, and identities of masked parties are not. The reason for termination is not reported, so the status alone cannot establish whether follow-up or planned analyses were affected.

The safety analysis population is defined as patients who received any study drug and had at least one post-safety evaluation, but participant flow and exclusions are not described. Missing-data quantities, reasons, handling methods, and sensitivity analyses are not reported. The record also does not specify the original statistical model, adjustment strategy, or analysis plan; the available risk difference and p-value are unadjusted recalculations from posted summaries.

The primary endpoint relies on both treatment-emergent timing and a relatedness judgment. The record does not explain how relatedness was assessed, whether events were independently adjudicated, or how repeated events were treated. Since the outcome counts participants rather than every event, the result does not describe recurrence or the range of event types. The serious-event listing is also brief and does not report event narratives or arm-specific detail for the listed term.

The registry lists two outcome measures but posts no secondary outcomes in the results metadata and no analysis records. The full set of planned outcomes and any multiplicity strategy are therefore not reported in the registry record. These limitations do not change the posted counts, but they restrict conclusions about completeness, analysis choices, and the broader safety profile.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study of 2 Doses of MAP0010 in Asthmatic Children — NCT00697697.
• Registry record last updated 2014-01-09; status last verified 2013-12.
• Results first posted 2013-10-23.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

NCT00697697 is a randomized, triple-masked, parallel-group Phase 3 extension study of two MAP0010 doses in children with asthma. The official title describes a 40-week study and an age range of 12 months to 8 years at enrollment into the MAP0010-CL-P301 study. The registry lists 192 participants enrolled and records the study status as terminated.

The primary endpoint is the number of patients with treatment-emergent adverse events related to study drug. The posted counts are 6.0 of 94.0 in the 0.135mg arm and 4.0 of 98.0 in the 0.25mg arm. The unadjusted risk difference is -0.023, with a 95% confidence interval from -0.086 to 0.040 and an unadjusted p-value of 0.473. The registry record does not report analysis records, secondary outcomes in the results metadata, or the reason for termination.