Fall Epidemic Viral Pediatric Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fall Epidemic Viral Pediatric Study (NCT01192178), a randomized phase 4 study. The primary outcome is Total Number of Asthma Exacerbations Reported During the Treatment Period.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 4 study of two inhaled treatments for children with asthma. The registry records triple masking, randomized allocation, and a parallel model. The study summary describes an exploratory 16-week, multi-centre trial in pediatric participants 4 to 11 years of age with a history of seasonal asthma exacerbations. It planned a 1:1 random assignment to ADVAIR DISKUS 100/50 mcg BID or FLOVENT DISKUS 100 mcg BID. The posted enrollment was 339.

The registry lists the study as completed. The recorded study start was 2010-08 and primary completion was 2010-12. The study summary says that participants would be identified for eligibility starting in April 2010 and invited back for randomization in August 2010. These dates describe the registry record; additional details about recruitment, sites, adherence, treatment exposure, or protocol conduct are not reported in the registry record.

The primary outcome was the total number of asthma exacerbations during treatment, with the endpoint timeframe defined as baseline at Week 1 through the end of treatment, up to Week 16. The study summary says the exploratory objective was to assess whether ADVAIR was more effective at reducing exacerbation risk and asthma impairment associated with viral respiratory tract infections during the fall season than FLOVENT. The registry lists seven secondary outcomes concerning symptoms, worsening episodes, exacerbations in viral contexts, and asthma-control or symptom-free days.

The registry does not report a sample-size justification for the trial, nor does it describe interim analyses or the planned statistical analysis strategy in enough detail to establish how all outcomes were to be handled. The statistical planning illustrations associated with the posted secondary results are not the trial’s original design calculations.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: all participants randomized to treatment. Only those participants who reported \>=1 exacerbation were analyzed.

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 Total Number of Asthma Exacerbations Reported During the Treatment Period, measured over From Baseline (Week 1) until the end of treatment (up to Week 16).

The primary endpoint was the total number of asthma exacerbations reported during treatment, from baseline at Week 1 until the end of treatment, up to Week 16. The registry defines an exacerbation as deterioration of asthma requiring outpatient oral or parenteral corticosteroids, or an urgent-care, hospitalization, or emergency-room visit due to asthma that required oral or parenteral corticosteroids. This definition aims to count clinically consequential worsening that prompted systemic corticosteroid treatment, rather than every change in symptoms.

The registry says that two exacerbations out of a total of 51 were excluded from the endpoint count: one occurring within 7 days of the resolution of an earlier exacerbation was combined with that earlier event, according to the protocol, and one occurred after treatment. These exclusions affect the event accounting described in the record.

The primary results include 24 exacerbations among 21 participants in the ADVAIR group and 25 among 20 participants in the FLOVENT group. The registry states that the primary population was the Intent-to-Treat population, defined as all participants randomized to treatment, but also says only participants who reported at least one exacerbation were analyzed. That restriction means the displayed event counts and the reported analysis should not be read as a complete summary of event experience for every randomized participant.

Counting exacerbations is useful when the question concerns recurrent events, but the registry’s reported comparison uses a Cox regression hazard ratio. The record does not explain in detail how the time-to-event analysis accommodated repeated events or participants without an event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods and calculations require a distinction between the registry’s reported analysis and the simple recalculations associated with selected secondary outcomes. The primary result is a sponsor-reported Cox regression hazard ratio. The secondary mean comparisons are labeled recalculated and are unadjusted comparisons based on the posted summary statistics. They are not replacements for a sponsor analysis and do not account for covariates or other modeling choices that are not reported.

What does a hazard ratio describe?

In general, a hazard ratio compares the event hazard between groups over the period represented by the analysis. The reported primary hazard ratio is 0.971, with a 95% confidence interval of 0.519 to 1.819. A value corresponding to no difference lies within that interval. In general, a confidence interval is a range of estimates compatible with the observed information under the model and its assumptions. A wide interval indicates uncertainty about the size and direction of the contrast. The registry identifies Cox regression as the method but does not report the model details needed to assess its assumptions or reproduce the estimate.

The endpoint is described as a count of exacerbations, yet the reported comparison is a Cox hazard ratio. These summaries represent different statistical views of events. A count records how many qualifying events occurred; a Cox analysis uses event timing under a time-to-event framework. The record does not explain whether or how recurrent events were represented in that analysis, so no more specific interpretation of the model is warranted. Also, the primary analysis population is described as randomized participants, while the record says that only participants reporting at least one exacerbation were analyzed. This limits what can be inferred from the posted event counts about the randomized population as a whole.

How should the recalculated mean comparisons be read?

For the posted secondary continuous outcomes, the recalculated mean difference is an unadjusted contrast between the two group means. The confidence interval reflects uncertainty in that contrast under the calculation used for the posted results. In general, if an interval includes zero for a mean difference, the data are compatible with no mean difference as well as with differences in either direction within the interval. These calculations use the group means, standard errors, and participant counts reported for each outcome. They should not be confused with adjusted analyses or with formal findings from a prespecified statistical plan.

The secondary results report standard errors rather than standard deviations. In general, a standard error describes the precision of an estimated mean, while a standard deviation describes variability among individual observations. They answer different questions. The displayed recalculations use the reported standard errors and sample sizes; the registry does not report a sponsor comparison for these secondary outcomes. The associated unadjusted p-values likewise do not account for testing multiple outcomes.

Over-dispersion is a general concern when analyzing event counts: the variability in counts may exceed what a simple count model expects. In general, this can make standard errors and inferential conclusions unreliable if the model does not accommodate the extra variability. The registry does not report a count-model specification or dispersion assessment for the primary endpoint. It would therefore be inappropriate to claim that over-dispersion was assessed or corrected in this study.

What do the planning illustrations mean?

The planning illustrations are calculations based on observed secondary effects, not the study’s own design justification. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For each comparison, the effect to detect is specified as a fraction of the observed effect. The displayed quantities are participants per arm for 80% power or participants per arm for 90% power. They are planning illustrations, not observed power, and they do not establish that the trial had adequate or inadequate power. The registry does not report the assumptions used for the original study design.

For example, the duration-of-worsening comparison has planning illustrations for 100% of the observed effect of 6,386 participants per arm for 80% power and 8,549 participants per arm for 90% power. The registry also gives illustrations for 75% and 50% of that observed effect. Such calculations can be extremely sensitive when an observed difference is small, because a smaller target effect requires more participants under the stated assumptions. This general principle does not turn the illustrations into a retrospective assessment of the trial’s power.

The registry’s primary analysis is not accompanied by a comparable two-arm planning illustration because the primary outcome is a count endpoint and the posted results indicate values missing or not estimable for a two-arm comparison of that kind. The record’s planning note says time-to-event illustrations use total events under the Schoenfeld approach and other illustrations use participants per arm. No conclusion about the original target sample size can be drawn from those secondary-based calculations.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as Cox regression, with a hazard ratio of 0.971, a 95% confidence interval of 0.519 to 1.819, and p = 0.928. This is the principal inferential result for the primary endpoint in the posted record. It should be distinguished from the simple recalculated comparisons for selected secondary mean outcomes, which are unadjusted and based on posted summary statistics.

The primary endpoint results also list 24 exacerbations among 21 ADVAIR participants and 25 among 20 FLOVENT participants. These counts do not by themselves reproduce the Cox hazard ratio: event timing and the analysis model matter, and the registry does not give enough detail to reconstruct the analysis. The record also says only participants reporting at least one exacerbation were analyzed, despite describing the primary population as all randomized participants.

The discrepancy indicator is false, so no disagreement between a sponsor result and a recalculated result is identified for this record. There is no recalculated primary count comparison to set against the reported Cox result. The reported analysis and the raw event totals should therefore be read as distinct summaries, with the model result providing the registry’s stated primary comparison.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures overall, including the primary endpoint, and seven posted secondary outcomes. It reports one analysis for the primary comparison. It does not report whether the secondary outcomes were prespecified in a formal testing hierarchy, whether their analyses were adjusted for multiplicity, or how any family of hypotheses was defined. The posted secondary p-values are unadjusted. When multiple outcomes are examined, unadjusted testing can increase the chance of observing a nominally notable result by chance. In general, multiplicity procedures or a prespecified hierarchy can help control how confirmatory conclusions are drawn. Their use in this study is not reported in the registry record.

Missing-data methods are also not reported in the registry record. The record does not explain how missing outcome observations, incomplete follow-up, or participants who discontinued treatment were handled in the primary or secondary analyses. It does not state whether any imputation or sensitivity analyses were used. These details matter because the interpretation of an estimate can depend on which observations contributed and on the assumptions used for unobserved outcomes.

The primary population is described as the Intent-to-Treat population, meaning all participants randomized to treatment, but the endpoint description adds that only participants who reported at least one exacerbation were analyzed. The record does not clarify how participants without a reported exacerbation entered the model or how censoring was handled. This distinction makes the scope of the primary analysis less transparent than the Intent-to-Treat label alone might imply.

The registry does not report interim analyses, stopping rules, an original sample-size justification, or a detailed statistical analysis plan. Those omissions prevent assessment of whether the testing approach was prespecified, whether recruitment targets were linked to a chosen effect size, and whether any repeated looks at accumulating data were planned. The absence of these details should not be filled by assumptions. It is a limitation on what can be concluded from the registry record, not evidence that a particular procedure was or was not used.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: syncope (0.6%), gastroenteritis (0.6%), pneumonia respiratory syncytialviral (0.6%), respiratory distress (0.6%), status asthmaticus (0.6%).

The registry lists serious adverse events for 171 participants at risk in the ADVAIR group and 168 in the FLOVENT group. Serious adverse events affected 2 participants in the ADVAIR group and 1 in the FLOVENT group. Other adverse events affected 85 participants at risk of 171 in the ADVAIR group and 84 at risk of 168 in the FLOVENT group. These are the posted counts; they should not be converted into comparative rates without a clearly defined analysis and appropriate context.

The serious-event terms listed include syncope, gastroenteritis, pneumonia respiratory syncytialviral, respiratory distress, and status asthmaticus, each reported as 0.6%. The registry does not provide enough information in these entries to assign each listed term to a treatment group or to determine whether events were considered related to treatment. The figures therefore describe reported safety events, not causal effects.

Deaths are not reported in the registry record. The serious adverse event counts are small, and the record does not provide a statistical comparison of safety between groups. These results are not sufficient on their own to establish a difference in safety or to rule one out. They should be read alongside the limited safety detail and the study’s specific population and treatment period, without implying medical advice.

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

The primary result is a Cox regression hazard ratio of 0.971 with a 95% confidence interval of 0.519 to 1.819 and p = 0.928. The estimate does not show a statistically clear separation between the groups in the reported primary analysis. The confidence interval is broad and includes the value corresponding to no difference, so the result leaves substantial uncertainty about the magnitude and direction of a possible contrast.

This does not demonstrate that ADVAIR and FLOVENT are equivalent. Equivalence requires a prespecified margin and an analysis designed to assess whether the treatment difference lies within that margin. The registry does not report such a framework. Nor does the result prove that no difference exists; a non-significant p-value is not proof of sameness. It says that the reported analysis did not provide strong statistical evidence against its null model.

The outcome definition also matters. The primary endpoint counts corticosteroid-requiring exacerbations or qualifying urgent-care, hospitalization, or emergency-room events. It does not represent every asthma symptom or every feature of the viral season. The secondary measures address other dimensions, but the registry does not report multiplicity adjustment for those comparisons. Their recalculated, unadjusted results should not be treated as confirmatory evidence that overturns or resolves the primary result.

The study was described as exploratory, and the registry does not report the original sample-size justification or detailed analysis plan. Those omissions limit the ability to judge how precisely the study was designed to estimate the primary effect, how missing observations were handled, and how secondary findings were intended to be interpreted. The posted findings are best understood as a set of registry-reported estimates with important uncertainty and reporting limitations, not as a definitive conclusion about comparative treatment effects.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definition and analysis population are central to interpreting clinical results. The primary endpoint is a count of exacerbations that meet a treatment-based definition, while the reported comparison is a Cox regression hazard ratio. The distinction between the total event counts, the number of participants with events, and a model-based comparison is essential: these quantities answer related but not identical questions.

It also illustrates the importance of reading confidence intervals alongside p-values. The hazard ratio estimate is close to the value corresponding to no difference, but the interval extends on both sides and is broad. The p-value alone cannot convey that uncertainty, and neither statistic establishes equivalence. For researchers, the example underscores the need to explain both the estimated contrast and its precision.

The record’s description of an Intent-to-Treat population alongside an analysis restricted to participants reporting at least one exacerbation raises a useful reporting question. A population label does not substitute for a clear account of who contributed to each analysis and how participants without events were handled. Transparent reporting is especially important for recurrent-event outcomes and time-to-event methods.

Finally, the study has multiple secondary outcomes, but their results are unadjusted and no testing hierarchy is reported. This makes the distinction between exploratory description and confirmatory inference important. Statistical interpretation depends not only on estimates, but also on the analysis plan, multiplicity strategy, missing-data handling, and design assumptions. Several of those details are not reported in the registry record, limiting what readers can infer about the strength and intended role of the findings.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry does not report the original sample-size justification, so the planned precision or target effect for the primary endpoint cannot be assessed. The study is described as exploratory, but the record does not give a detailed statistical analysis plan, a multiplicity strategy, or interim-analysis information. These omissions constrain interpretation of both the primary and secondary findings.

The primary endpoint is a total count, but the reported comparison is a Cox regression hazard ratio. The registry does not describe how recurrent events were modeled, how time at risk was defined, how participants without an event were represented, or what model assumptions were assessed. It also says that only participants reporting at least one exacerbation were analyzed, while defining the primary population as all randomized participants. This leaves uncertainty about the exact analysis population and treatment of participants without an event.

Two exacerbations were excluded from the endpoint accounting for specified reasons: one was combined with an earlier event under the protocol rule, and one occurred after treatment. The registry does not provide further detail about other event adjudication or completeness. Missing-data handling, treatment adherence, discontinuations, and sensitivity analyses are not reported in the registry record.

The secondary comparisons are recalculated and unadjusted, and the record does not report sponsor inferential analyses for them. They cover different outcomes and, in several cases, specific viral or symptom contexts. Their results should not be treated as a single confirmatory body of evidence. The limited safety entries likewise do not establish causal relationships or comparative safety. These are reporting limitations specific to the available registry record; they do not establish that unreported procedures were absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fall Epidemic Viral Pediatric Study — NCT01192178.
• Registry record last updated 2017-01-18; status last verified 2016-11.
• Results first posted 2011-11-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01192178, the Fall Epidemic Viral Pediatric Study, was a completed randomized, double-blind, parallel-group Phase 4 study comparing ADVAIR DISKUS 100/50 mcg BID with FLOVENT DISKUS 100 mcg BID in children with asthma. The registry describes an exploratory 16-week study in children 4 to 11 years of age with a history of seasonal asthma exacerbations. Enrollment was 339.

The primary outcome was the total number of qualifying asthma exacerbations from baseline at Week 1 through the end of treatment, up to Week 16. The reported Cox regression hazard ratio was 0.971, with a 95% confidence interval of 0.519 to 1.819 and p = 0.928. The interval includes the value corresponding to no difference and leaves substantial uncertainty about the contrast.

Seven secondary outcomes were posted. Their recalculated comparisons are unadjusted, and multiplicity handling is not reported in the registry record. Missing-data methods, the original sample-size justification, and detailed analysis-plan information are also not reported in the registry record.