Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry. (NCT01498679), a randomized phase 3 study. The primary outcome is Mean Change From Baseline (BL) in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period.

2. Clinical Question

The primary endpoint focuses on change rather than a single follow-up measurement. Baseline was derived from the last 7 days of the daily diary before randomization, and the treatment-period measure averaged daily evening PEF across Weeks 1-12, up to Day 84. The posted group estimates are least-squares means, with standard errors, and the registry reports an ANCOVA comparison.

The record lists 311 participants enrolled. The primary endpoint analysis included only participants meeting its stated diary completeness criteria: PEF data for at least 4 days in the baseline week and at least 4 days after randomization. Thus, enrollment and the endpoint analysis population are not interchangeable. The registry record does not report further detail about how missing diary observations were handled.

3. Trial Design

The registry describes a Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicentre study of fluticasone furoate/vilanterol inhalation powder for asthma. The record lists 311 participants enrolled and the trial status as completed. The study began in 2012-01, and primary completion was recorded in 2013-07.

Participants were adolescent and adult subjects of Asian ancestry currently treated with low- to mid-strength inhaled corticosteroid or low-strength combination therapy. The active group received fluticasone furoate/vilanterol 100/25 µg once daily; the comparator group received placebo. The planned treatment duration described in the record was 12 weeks. Double masking means the registry labels the study as double-blind, but the record does not describe the practical masking procedures or who specifically remained unaware of allocation.

For the primary endpoint, the registry identifies an Intent-to-Treat population as participants randomized to treatment who received at least one dose of trial medication. The endpoint analysis had an additional diary-data eligibility rule: participants needed PEF data on at least 4 days in the baseline week and at least 4 days after randomization. The posted primary endpoint estimates list 151 participants in the placebo group and 153 in the fluticasone furoate/vilanterol group. These endpoint counts need not equal total enrollment because the analysis population and endpoint-specific data availability are distinct.

The registry identifies analysis of covariance, or ANCOVA, with baseline, region, sex, age, and treatment as covariates for the primary endpoint. It does not report the trial's original sample-size justification, allocation ratio, detailed randomization method, handling of missing data, or a full statistical analysis plan. The planning illustrations accompanying the posted summary statistics are not a substitute for those original 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.

Before assignment: At screening, participants who met all of the inclusion criteria entered a 2-week Run-in Period. Participants continued on inhaled corticosteroid (ICS) therapy throughout the Run-in Period. At the end of the Run-in Period, participants meeting the randomization criteria entered a 12-week Treatment Period and received one of the two treatments.

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 who received \>=1 dose of trial medication. The primary endpoint analysis only included participants who had PM PEF data for \>=4 days in the BL week prior to randomization and \>=4 days after randomization. Only participants available at the indicated time point were assessed.

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 Mean Change From Baseline (BL) in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period, measured over Baseline and Weeks 1-12 (up to Day 84).

The primary endpoint is mean change from baseline in daily evening (PM) peak expiratory flow, averaged over the 12-week treatment period and measured in liters per minute. PEF is the maximum airflow during a forced expiration that starts with the lungs fully inflated. The endpoint therefore measures airflow rather than symptoms, rescue medication use, or quality of life.

Baseline was derived from the last 7 days of daily diary entries before randomization. Change from baseline was defined as the averaged daily PM PEF over the treatment period minus baseline. Using change makes the comparison relative to each participant's starting measurement, while averaging repeated daily readings represents airflow across the treatment period rather than a single day's value.

The registry reports least-squares means from an ANCOVA model that included baseline, region, sex, age, and treatment. Such adjustment accounts for the listed covariates in estimating the treatment-group means and their contrast. The endpoint analysis required at least 4 days of PEF data in the baseline week and at least 4 days after randomization. The registry does not report further details about diary-data imputation or other missing-data procedures, so the estimates should be read in the context of that stated analysis population and the available record.

7. Results Posted in the Registry

• Fluticasone Furoate/Vilanterol 100/25 µg Once Daily: mean 39.20 versus -11.80 on control; difference 51.00 (95% CI 42.27 to 59.73), standardized effect d = 1.31; z-test p = <0.001.

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.

Mean Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period

• 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:
  • Fluticasone Furoate/Vilanterol 100/25 µg Once Daily: mean 43.60 versus -9.30 on control; difference 52.90 (95% CI 44.25 to 61.55), standardized effect d = 1.37; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Fluticasone Furoate/Vilanterol 100/25 µg Once Daily than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change From Baseline in the Percentage of Rescue-free 24- Hour (hr) Periods During the 12-week Treatment Period

• 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:
  • Fluticasone Furoate/Vilanterol 100/25 µg Once Daily: mean 30.10 versus 8.30 on control; difference 21.80 (95% CI 14.61 to 28.99), standardized effect d = 0.68; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Fluticasone Furoate/Vilanterol 100/25 µg Once Daily than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change From Baseline in the Percentage of Symptom-free 24- Hour (hr) Periods During the 12-week Treatment Period

• 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:
  • Fluticasone Furoate/Vilanterol 100/25 µg Once Daily: mean 24.80 versus 9.00 on control; difference 15.80 (95% CI 9.41 to 22.19), standardized effect d = 0.55; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Fluticasone Furoate/Vilanterol 100/25 µg Once Daily than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Across the posted secondary outcomes with results, the active group has larger mean changes than placebo for morning PEF, the percentage of rescue-free 24-hour periods, and the percentage of symptom-free 24-hour periods. This overall direction is consistent with the primary endpoint's reported group contrast, while the secondary measures address different aspects of airflow, rescue medication use, and symptoms. They provide complementary outcome context rather than a replication of the same endpoint.

The registry lists change in total Asthma Quality of Life Questionnaire score at Week 12 as another secondary outcome, but a result for it is not reported in the registry record. The absence of a posted result means its direction and precision cannot be assessed from this record. The secondary evidence should therefore be understood as applying to the reported outcomes, not to every outcome named in the study description.

The secondary recalculations have unadjusted p-values, and the registry does not list sponsor-reported analyses for them. Multiple outcomes create a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently noteworthy result can increase if no adjustment or prespecified hierarchy is used. The record does not report whether the secondary analyses were adjusted for multiplicity, whether they were prespecified in a hierarchy, or whether they were intended to support confirmatory claims.

For that reason, the secondary results carry less inferential weight than the prespecified primary result as reported by the sponsor. Their coherent direction can be described, but it should not be taken as proof that each endpoint independently establishes an effect. The registered record also does not provide enough information to judge the complete set of analyses performed, so the posted secondary findings are best read as supportive descriptive evidence rather than a multiplicity-controlled family of tests.

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

• Mean Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period
• Mean Change From Baseline in the Percentage of Rescue-free 24- Hour (hr) Periods During the 12-week Treatment Period
• Mean Change From Baseline in the Percentage of Symptom-free 24- Hour (hr) Periods During the 12-week Treatment Period
• Change From Baseline in Total Asthma Quality of Life Questionnaire (AQLQ) Score at Week 12

9. Statistical Interpretation

10. Statistical Methods Explained

The primary analysis is described as ANCOVA, with baseline, region, sex, age, and treatment as covariates. ANCOVA models an outcome while accounting for selected variables measured at baseline or used to characterize participants. In this study, the outcome is change from baseline in daily evening PEF averaged across the treatment period. The model produces least-squares means, which are covariate-adjusted group estimates, and a least-squares mean difference between the treatment groups.

What does the reported contrast represent?

The reported primary contrast is the adjusted mean difference between fluticasone furoate/vilanterol and placebo. The registry reports 51.0 liters per minute, a 95% confidence interval of 42.2 to 59.7, and p < 0.001. The group means are not simply an unadjusted description when they come from the stated ANCOVA; they are estimates from a model that includes its listed covariates. This distinction matters because model-adjusted results can differ from a calculation based only on the displayed group summary estimates.

A recalculated contrast is an unadjusted re-calculation from posted summary statistics. For continuous outcomes, the simple mean difference compares the displayed group means. A recalculated standard error or confidence interval may rely on assumptions about the variation in each group and the relationship between the estimates. It does not reproduce an ANCOVA unless the needed individual-level data and model details are available. The registry reports no discrepancy between the primary recalculation and sponsor analysis, but that does not make the two analyses identical in method.

What does a p-value say?

In general, a p-value measures how incompatible the observed data are with a specified null hypothesis, under the statistical model and its assumptions. A small p-value is not the probability that the null hypothesis is true, and it does not quantify the size or practical importance of an effect. For the primary endpoint, the sponsor's model-based result is p < 0.001. The recalculated unadjusted result is also reported as p < 0.001. The registry does not report enough detail to assess every model diagnostic or assumption.

In general, ANCOVA relies on an appropriate model for the continuous outcome, a suitable relationship between covariates and outcome, and valid treatment-group comparisons. It also depends on how the analysis handles incomplete observations. The record names the covariates and eligibility rule but does not report diagnostic checks, model specification details beyond those covariates, or the missing-data procedure. Those omissions limit independent assessment of the model's implementation.

Why distinguish adjusted and unadjusted estimates?

Adjustment can improve precision or account for chance differences in variables included in the model, when the model is appropriate. An unadjusted estimate is easier to reconstruct from group summaries, but it does not account for baseline, region, sex, or age as the sponsor's model does. The sponsor's ANCOVA estimate is consequently the primary registry-reported result; the recalculation is supplementary and should be interpreted as a simple summary-statistic comparison.

For the secondary continuous endpoints, the posted group means and recalculated comparisons describe morning PEF, rescue-free periods, and symptom-free periods. The record lists no sponsor-reported secondary analyses for these endpoints. Their p-values are therefore unadjusted recalculated results, not confirmation that the sponsor used the same model or analysis strategy for each secondary outcome. The registry reports that four secondary outcomes were posted, but the result for the Asthma Quality of Life Questionnaire is not included in the endpoint results listed in the record.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a statistical model expects. It is especially relevant to outcomes such as counts or binary events when a model assumes a narrower distribution than the data support; underestimating variability can make uncertainty look too small. The posted primary and secondary efficacy outcomes are continuous measures summarized by means and standard errors. The registry record does not report an over-dispersion analysis, and such a diagnosis should not be inferred from these summaries.

The endpoint definition also affects interpretation. PEF was recorded in daily diaries, and the primary analysis required a minimum amount of baseline and post-randomization diary data. The effect estimate therefore pertains to participants meeting that endpoint-specific requirement under the registry's analysis definition. Without details on missing diary entries and participants excluded from the endpoint analysis, the extent to which incomplete recording could affect the result cannot be assessed from the registry record.

11. Confidence Intervals and Precision

The sponsor-reported primary least-squares mean difference is 51.0 liters per minute, with a 95% confidence interval from 42.2 to 59.7. A confidence interval is a range of values compatible with the observed data and the statistical model at the stated confidence level. In general, it conveys uncertainty about the estimated contrast rather than a range containing a fixed proportion of individual participants' outcomes.

The interval is entirely on the positive side of zero, consistent with the reported p < 0.001 for a comparison whose null value is no difference. Its width also matters: estimates nearer the center are more compatible with the data than values near or beyond the interval limits, under the model. The interval does not show the distribution of individual responses and cannot by itself establish whether the estimated difference is clinically important. The registry does not report a threshold for interpreting clinical importance.

The recalculated unadjusted comparison has a 95% interval from 42.27 to 59.73. That interval is based on posted summary statistics and should be distinguished from the sponsor's adjusted ANCOVA interval. The sponsor's analysis takes precedence as the registry-reported model-based analysis; the recalculation provides a separate, transparent summary-statistic comparison.

Precision depends on the amount and variability of the outcome data, as well as the analysis model. The displayed standard errors describe uncertainty in the group least-squares mean estimates, while the confidence interval for the difference describes uncertainty in the contrast. The registry record does not report individual-level data or model diagnostics, so precision cannot be independently assessed beyond the posted summaries and reported interval.

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 illustrations are planning calculations based on the observed effect in each posted outcome, not the trial's original design calculations. For these continuous outcomes, the figures are participants per arm, not total participants across both groups. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculations consider detecting the stated fraction of the observed effect.

The 80% power column means the illustrated number of participants per arm would give an 80% chance of detecting the assumed effect under the planning assumptions, if that effect and model assumptions were correct. The 90% power column describes the corresponding planning target for a 90% chance. These are design illustrations, not guarantees about the results of a future study. They are not observed power.

Rows for 100% of the observed effect use the full effect estimate from the posted data. Rows for 75% and 50% consider smaller target effects. Smaller effects are harder to distinguish from random variation, so the illustrations require more participants per arm for the same power target. The figures can therefore help show how planning changes with the effect one aims to detect, but they do not establish that the observed effect is the effect a future study should expect.

The trial's original sample-size assumptions and justification are not reported in the registry record. The planning calculations should not be read as evidence about what the investigators planned, nor as proof that the completed trial was adequately or inadequately sized. They use the observed effect as their starting point, so their estimates are especially dependent on the size of that observed effect.

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 = 51.000; pooled standard deviation σ = 38.835.
2. n = 2 × (1.96 + 0.842)² × 38.835² / 51.000² = 9.1, rounded up to 10 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 <- 51                      # observed difference in means
sigma <- 38.8352223550251                     # 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(1498679)
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 = 10 (80% power), 13 (90% power)
 75% of observed effect: n per arm = 17 (80% power), 22 (90% power)
 50% of observed effect: n per arm = 37 (80% power), 49 (90% power)
power.t.test: 10.2 
Simulated power at n = 10 per arm: 0.793 (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-reported primary analysis is ANCOVA and gives a least-squares mean difference of 51.0 liters per minute, with a 95% confidence interval from 42.2 to 59.7 and p < 0.001. This is the registry's model-based primary result, adjusted for baseline, region, sex, age, and treatment as described in the record.

The recalculation uses posted group summary statistics to produce a simple unadjusted comparison. It gives a mean difference of 51.0 and a 95% interval from 42.27 to 59.73, with p < 0.001. The agreement in the reported point estimate does not mean the methods are interchangeable: the sponsor's ANCOVA incorporates the listed covariates, while the recalculation does not reproduce that model from individual participant data.

The registry record identifies no discrepancy between the primary recalculation and sponsor result. The sponsor's analysis remains the principal result because it is the reported ANCOVA analysis specified for the primary endpoint. Recalculation is useful as a check on the broad summary contrast, but it is not a substitute for the adjusted analysis or a full independent reanalysis. No sponsor-reported analyses are listed for the secondary outcomes discussed in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, comparisons, time points, or subgroups. In general, testing multiple hypotheses without an adjustment or an explicit testing hierarchy can increase the chance of false-positive findings across the collection of tests. The registry lists a primary endpoint and four secondary outcomes. It does not report whether the secondary tests were adjusted for multiplicity, how they were ordered, or whether a testing hierarchy was prespecified. The status of multiplicity control is therefore not reported in the registry record.

The primary endpoint has a sponsor-reported ANCOVA result. For the posted secondary outcomes with estimates, the displayed recalculations use unadjusted comparisons; no sponsor-reported secondary analyses are listed. The p-values for those secondary re-calculations should not be read as if they were adjusted for the full set of outcomes. Nor does the available record establish that the endpoints were selected after results were known; it simply does not provide enough information to assess the prespecified analysis plan.

Missing data are another important consideration because the primary analysis required diary PEF data on at least 4 days in the baseline week and at least 4 days after randomization. The registry identifies that eligibility condition but does not describe imputation, sensitivity analyses, or the reasons participants may not have met it. The number excluded from the primary endpoint analysis and the effect of missing diary observations are not reported in the registry record. Consequently, the posted result applies to the stated analysis population, and the impact of missingness cannot be evaluated from the record alone.

The record describes an Intent-to-Treat population as randomized participants who received at least one dose, with the primary endpoint analysis restricted by diary-data availability. This differs from a claim that every randomized participant contributed an endpoint observation. Details on how other analysis populations were defined, whether all randomized participants were included in safety summaries, and how protocol deviations were handled are not reported in the registry record. These gaps constrain assessment of analysis-population sensitivity and the robustness of the conclusions.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (0.7%), enteritis (0.7%).

The registry lists serious adverse events for 0 participants in the placebo group, with 154 at risk, and 2 participants in the fluticasone furoate/vilanterol group, with 153 at risk. These are counts and denominators as recorded, not a comparison adjusted for exposure time or other participant characteristics. The registry also lists atrial fibrillation and enteritis as serious adverse event terms, each at 0.7%; the record does not assign those terms to a specific group in the information presented.

Other adverse events are listed for 27 participants in the placebo group and 24 in the active group, with 154 and 153 at risk, respectively. The registry does not provide enough detail in these summary fields to characterize event duration, severity beyond the serious/non-serious distinction, relatedness to treatment, or whether individuals experienced more than one event. Death counts are not reported in the registry record.

These figures describe recorded events during the study; they are not, by themselves, a complete safety assessment or evidence that the groups had equivalent risk. The study's 12-week treatment period and the information available in the registry record limit what can be inferred about less common or longer-term events.

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

The primary result describes a difference between group means in change from baseline in evening PEF averaged over the 12-week treatment period. The sponsor's adjusted analysis reports a least-squares mean difference of 51.0 liters per minute, with a 95% confidence interval from 42.2 to 59.7 and p < 0.001. This indicates a statistically clear group contrast for the measured primary endpoint under the reported ANCOVA model.

It does not establish that every participant experienced an improvement, that the group means describe any one individual's response, or that the observed difference is clinically important. The registry does not report a threshold for clinical importance. Nor does the primary endpoint alone resolve questions about symptoms, quality of life, safety, or outcomes beyond the trial's treatment period. The posted secondary findings add information on certain other measures, but their unadjusted status and multiplicity context warrant caution.

The findings apply to the study population and setting described in the registry: adolescent and adult subjects of Asian ancestry with asthma who were currently using low- to mid-strength inhaled corticosteroid or low-strength combination therapy. The available record does not establish that the same results apply to other populations, treatment histories, or longer treatment durations. Generalizability cannot be assumed from the trial description alone.

The record documents randomization and double masking, features intended in general to reduce some forms of bias. However, details about the randomization procedure, masking implementation, missing-data methods, and full statistical plan are not reported in the registry record. These limitations do not erase the posted result, but they qualify how fully its conduct and analysis can be independently evaluated.

18. Why This Trial Matters Statistically

This trial illustrates the difference between an adjusted primary analysis and a summary-statistic recalculation. The registry reports an ANCOVA least-squares mean difference that accounts for baseline, region, sex, age, and treatment. A simple recalculation from group summaries is easier to inspect but does not reproduce that covariate-adjusted model. Keeping the two analyses distinct helps readers understand why the registry-reported result is the principal estimate and what the supplementary calculation can and cannot check.

It also demonstrates why endpoint definitions and analysis populations matter. The primary endpoint averages repeated evening PEF readings over the treatment period, uses a diary-based baseline, and requires a minimum amount of recorded data. The resulting estimate therefore depends not only on the measured outcome but also on which diary observations and participants contribute to the analysis. Missing-data handling is not reported in the registry record, making transparency about the analysis rule particularly important.

The posted secondary outcomes broaden the statistical picture beyond airflow, including rescue-free and symptom-free periods. Their shared direction is informative, but unadjusted secondary testing across multiple outcomes carries less confirmatory weight than the primary analysis. The distinction between a coherent pattern and multiplicity-controlled evidence is central to responsible interpretation.

Finally, planning illustrations based on observed effects show how sample-size targets change when the target effect is smaller. They are not the trial's original design rationale and are not observed power. Separating prospective planning assumptions from retrospective calculations prevents the observed result from being treated as if it had been known when the trial was designed.

19. Limitations

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

The registry record leaves several trial-specific uncertainties. Although it identifies a randomized, double-blind design, it does not describe the randomization procedure, the details of masking, or how departures from the intended treatment were handled. The trial's original sample-size justification and statistical analysis plan are not reported in the registry record, so it is not possible to confirm from this record how the original design addressed precision, missing data, or multiplicity.

The primary endpoint relies on daily diary PEF and excludes participants who did not meet the stated minimum-data rule. The record does not report the number of participants who failed that criterion, reasons for incomplete diary data, imputation methods, or sensitivity analyses. This leaves uncertainty about the impact of missing measurements on the primary estimate. The registry lists an Intent-to-Treat population definition, but the endpoint-specific data requirement means the analyzed set is narrower than all participants randomized and treated.

For secondary endpoints, sponsor-reported analyses are not listed, and the posted comparisons are unadjusted recalculations. The registry does not report multiplicity control or a testing hierarchy. The Asthma Quality of Life Questionnaire is listed as a secondary outcome, but its result is not reported in the registry record. These gaps limit a complete assessment of the secondary-outcome evidence.

The record describes a 12-week treatment period and does not establish what happened after that period. Safety summaries are limited to the posted counts and terms; deaths, detailed event attribution, exposure-adjusted rates, and longer-term safety information are not reported in the registry record. Finally, the specific population and prior treatment context constrain generalization beyond adolescent and adult subjects of Asian ancestry receiving the stated background therapy.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Evaluating the Efficacy and Safety of Fluticasone Furoate/Vilanterol Trifenatate in the Treatment of Asthma in Adolescent and Adult Subjects of Asian Ancestry. — NCT01498679.
• Registry record last updated 2017-03-08; status last verified 2017-01.
• Results first posted 2014-04-01.
• 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

The registry record describes a completed Phase 3 randomized, double-blind, placebo-controlled, parallel-group, multicentre trial of once-daily fluticasone furoate/vilanterol 100/25 µg for asthma in adolescent and adult subjects of Asian ancestry. The planned treatment period was 12 weeks, and enrollment was 311.

The primary endpoint was mean change from baseline in daily evening PEF averaged over the treatment period. The sponsor-reported ANCOVA difference was 51.0 liters per minute, with a 95% confidence interval from 42.2 to 59.7 and p < 0.001. The posted secondary results with estimates generally favored the active group in direction, but the secondary analyses are unadjusted recalculations and multiplicity procedures are not reported in the registry record.

The primary diary-data eligibility rule, missing-data methods, original sample-size rationale, and complete statistical plan are not reported in the registry record. Safety counts include 2 serious adverse event participants in the active group and 0 in the placebo group; deaths are not reported in the registry record.