Efficacy and Safety Study of Fluticasone Proponate Inhalation Solution in Adult and Adolescent Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Study of Fluticasone Proponate Inhalation Solution in Adult and Adolescent Asthma (NCT01687283), a randomized phase 3 study. The primary outcome is Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population.

2. Clinical Question

The primary endpoint was the change from baseline in morning peak expiratory flow (AM PEF), measured in litres per minute. The registry describes daily diary measurements and an average over the treatment period. It also lists secondary outcomes covering evening PEF, symptom-free and rescue-free periods, symptom scores, rescue medication use, forced expiratory volume in one second, and fluticasone pharmacokinetics.

The statistical question is about the between-group contrast in the endpoint, not simply whether either group changed from baseline. The posted summaries show positive mean changes in both groups. The registry’s ANCOVA analysis reports a net mean difference and a confidence interval. The record classifies this analysis as non-inferiority or equivalence, but the non-inferiority margin and the decision criterion are not reported in the registry record. The numerical estimates therefore describe the comparison; by themselves, they do not establish a formal non-inferiority conclusion.

3. Trial Design

This was a phase III, randomized, single-blind, active-controlled, parallel-group study. It was conducted as a multicenter local registration study in Chinese adult and adolescent patients with severe persistent asthma. The registry lists the condition as asthma and the sponsor as GlaxoSmithKline. Enrollment was 316. The study is marked completed.

Participants were assigned to nebulized fluticasone propionate inhalation solution, 1 mg BID, or nebulized budesonide suspension, 2 mg BID. The treatment period was 12 weeks. The registry describes the study as single-blind but does not identify which participants or study personnel were masked. More detailed information about the allocation procedure and concealment is not reported in the registry record.

The primary outcome was change from baseline in morning PEF over the treatment period. The primary analysis population was the intent-to-treat population, although the registry notes that only participants available at the specified time points were analyzed. The outcome description says participants recorded the best of three peak-flow attempts in diary cards. Baseline was the assessment at Visit 2, and the daily AM PEF was averaged over the treatment period.

The registry lists additional clinical outcomes, including evening PEF, symptom-free and rescue-free periods, symptom scores, rescue medication use, and FEV1. It also lists steady-state plasma pharmacokinetic outcomes for fluticasone, including time to maximum observed concentration and maximum observed concentration. The study start date was 2012-09-27, and primary completion was 2013-11-07. The original sample-size justification, detailed protocol assumptions, and further information about conduct 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.

Before assignment: Out of 460 screened participants, 109 were screen failures and 34 were run-in failures. Out of 317 participants, two participants did not receive the study drug and 315 participants received the study drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population. Only those participants available at the specified time points 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.

Population: The analysis was performed on intent-to-treat population. This population comprised of all participants randomized to treatment and who received at least one dose of study medication. Only the participants present at the indicated time point were analyzed.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline (Day 1 of Treatment Period/Visit 2) in Morning Peak Expiratory Flow (AM PEF) Over 12 Weeks in Intent-to-treat Population, measured over Baseline (Visit 2) and up to Week 12.

Morning peak expiratory flow measures the maximum speed at which a person can breathe air out. The registry describes a peak-flow meter issued to participants, who recorded their morning measurement before study drug and rescue medication. Participants made three attempts and entered the best result in diary cards. The baseline measurement was taken at Visit 2, and the primary endpoint was change from that baseline in daily AM PEF averaged over the 12-week treatment period. The unit was litres per minute.

PEF is a measure of airflow that can be collected repeatedly outside a clinic visit, which makes it suitable for observing patterns over a treatment period. The comparison of changes between randomized groups asks whether the average change differed between the assigned treatment strategies. The endpoint is not itself a direct measure of every aspect of asthma symptoms, daily functioning, or safety; the registry listed several of those as separate outcomes.

The endpoint description specifies that a mean was considered missing if fewer than 4 days were recorded during the baseline week before randomization or fewer than 4 days were recorded after randomization. This rule affects which diary data could contribute to the average. The registry states that the analysis used ANCOVA and that only participants available at the specified time points were analyzed. Further details about how missing observations were handled are not reported in the registry record.

7. Results Posted in the Registry

• BUD 2 mg BID: mean 14.51 versus 12.71 on control; difference 1.80 (95% CI -8.44 to 12.04), standardized effect d = 0.04; z-test p = 0.731.

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 of Evening PEF From Baseline Over 12 Weeks

• 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:
  • BUD 2 mg BID: mean 15.16 versus 12.39 on control; difference 2.77 (95% CI -6.89 to 12.43), standardized effect d = 0.06; z-test p = 0.574.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between BUD 2 mg BID and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks

• 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:
  • BUD 2 mg BID: mean 21.15 versus 21.77 on control; difference -0.62 (95% CI -7.14 to 5.90), standardized effect d = -0.02; z-test p = 0.852.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between BUD 2 mg BID and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks

• 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:
  • BUD 2 mg BID: mean 24.01 versus 19.27 on control; difference 4.74 (95% CI -2.48 to 11.96), standardized effect d = 0.15; z-test p = 0.198.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between BUD 2 mg BID and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary estimates cover several kinds of outcome: evening PEF, symptom-free and rescue-free periods, symptom scores, rescue medication use, FEV1, and fluticasone pharmacokinetics. Numerical between-group results are posted for some secondary outcomes, while the record’s list includes additional outcomes without numerical results in the posted results. Across the outcomes with numerical estimates, the overall pattern is not one of consistent, clearly separated group results.

The secondary outcomes offer context alongside the primary AM PEF endpoint. Evening PEF is another airflow measure, while symptom-free and rescue-free periods and medication use reflect different aspects of day-to-day experience and management. FEV1 is a separate lung-function measure. These outcomes are related to the study question but are not interchangeable with the primary endpoint; a pattern in one does not automatically establish a pattern in another.

The registry reports ANCOVA analyses for the secondary outcomes with posted results. Unadjusted recalculations are simple comparisons based on posted summaries and should not be treated as the sponsor’s adjusted analyses. The record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. When multiple outcomes are analyzed, chance variation can produce apparently notable findings even if there is no underlying difference. Without a reported strategy for controlling that issue, individual unadjusted secondary results carry less weight than the prespecified primary analysis.

These secondary results may help characterize the range of outcomes assessed, but they do not resolve the uncertainty in the primary comparison or establish a formal non-inferiority conclusion. The registry’s planned pharmacokinetic outcomes are specific to fluticasone; the numerical pharmacokinetic findings are not reported in the registry record summarized by the posted results.

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

• Mean Change of Evening PEF From Baseline Over 12 Weeks
• Mean Change in Percentage of Symptom-free 24-hour Periods From Baseline Over 12 Weeks
• Median Day-time and Night-time Symptom Scores Per Participant Over 12 Weeks
• Mean Change in Percentage of Rescue-free 24-hour Periods From Baseline Over 12 Weeks
• Median Number of Times Rescue Medication Use Over 12 Weeks
• Change of Clinical Lung Function Measurement Forced Expiratory Volume in One Second (FEV1) From Baseline Over 12 Weeks
• Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution- Time to Maximum Observed Plasma Concentration (Tmax)
• Steady-state Plasma Pharmacokinetics of Fluticasone Propionate Inhalation Solution-maximum Observed Plasma Concentration (Cmax)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is a measurement on a scale of litres per minute, summarized as a mean change from baseline. For a continuous outcome, a mean describes the average result in a group, while the between-group mean difference describes the contrast between group averages. The direction of a difference depends on which group is subtracted from which. The registry’s arm order and the recalculation’s BUD-minus-FP contrast are not the same as the sponsor’s reported net contrast, so the signs differ without implying a conflict in the underlying results.

What does ANCOVA contribute?

The registry reports an analysis of covariance (ANCOVA) for the primary endpoint. In general, ANCOVA estimates a group contrast while accounting for selected covariates in a statistical model. Adjustment can make the comparison more precise when the covariates explain variation in the outcome, but the exact covariates and model specification are not reported in the registry record. The posted sponsor estimate is therefore the result to use when describing the registered analysis, while the unadjusted recalculation is a separate, simpler comparison.

The outcome is described as a least-squares mean with standard error. In general, a least-squares mean is a model-based mean, adjusted according to the fitted analysis. A standard error describes the uncertainty in an estimated mean; it is not the same thing as the spread of individual participant measurements. The posted values for the arms are 12.71 with standard error 3.677 for FP 1 mg BID, and 14.51 with standard error 3.714 for BUD 2 mg BID. These are estimated group changes, not individual responses.

What does a confidence interval tell the reader?

A confidence interval describes the range of values compatible with the data and the statistical model at the stated confidence level. It communicates precision as well as direction. For the sponsor’s primary estimate, the 95% confidence interval runs from -12.19 to 8.59 around a net mean difference of -1.80. Because the interval crosses zero, the data are compatible with no average difference as well as with differences on either side of zero. The interval’s width also shows that the estimated contrast is not highly precise.

A p-value measures how unusual the observed data, or more extreme data, would be under a specified null model and its assumptions. It does not give the probability that the null hypothesis is true, and it does not measure clinical importance. The sponsor’s primary p-value is 0.733. A value of this size does not establish equality; it indicates that the observed contrast is not statistically distinguishable from zero by this test. The registry’s exact testing and modeling details beyond the stated ANCOVA are not reported in the registry record.

How should the recalculated comparisons be understood?

The recalculated comparisons are simple, unadjusted estimates derived from the posted arm summaries. They are useful as a check on the direction and approximate scale of the contrast, but they do not reproduce the sponsor’s covariate-adjusted model. For the primary endpoint, the recalculated BUD-minus-FP estimate is 1.8 and the reported sponsor net estimate is -1.80. The sign difference reflects the contrast orientation. Their confidence intervals and p-values are also not identical because the estimates are not calculated using the same analysis.

The standard deviations used for the recalculations are marked as approximate in the statistical derivation. In general, this matters because a standard deviation describes individual-level variability, whereas the posted arm dispersion is a standard error of the mean. Recovering variability from summary information requires assumptions and can introduce approximation. The recalculated results should therefore be treated as rough, unadjusted checks rather than replacements for the registered analysis.

Why can over-dispersion matter?

For count outcomes, over-dispersion means that observed variability is greater than a simple count model expects. In general, accounting for it can prevent uncertainty from being understated. The primary endpoint is continuous, and the posted primary analysis is ANCOVA; the registry record does not report a count model or an over-dispersion assessment for this endpoint. This concept should not be mistaken for a reported feature of the primary analysis.

The record says that diary means were considered missing when fewer than 4 days were recorded during the baseline week or after randomization. It also says that only participants available at the relevant time points were analyzed. These statements indicate that the available observations contributed to the analysis, but do not establish the method used to handle all missing data. Imputation methods, sensitivity analyses, and the assumptions underlying missing-data handling are not reported in the registry record.

Finally, the primary outcome is one among multiple registered outcomes. In general, testing many outcomes increases the chance that some results appear unusual by chance. Whether and how that issue was controlled is not reported in the registry record. As a result, secondary findings should be interpreted as supportive or exploratory unless the prespecified analysis plan and multiplicity procedures are available.

11. Confidence Intervals and Precision

The sponsor’s primary estimate is a net mean difference of -1.80, with a 95% confidence interval from -12.19 to 8.59. The interval spans zero and extends in both directions, so it does not isolate a single direction of average difference. Its width indicates that the registered analysis leaves substantial uncertainty about the size and direction of the group contrast.

The confidence interval is more informative than the p-value alone because it shows a range of estimates compatible with the data under the model. It includes values consistent with a difference favoring either group as expressed by the sponsor’s contrast. Since the record does not report a non-inferiority margin, the interval cannot be compared with such a margin to verify whether a non-inferiority criterion was met.

The recalculated unadjusted interval for the primary comparison is -8.443 to 12.04 for BUD minus FP. It also includes zero. The sponsor and recalculated estimates use different adjustment and contrast conventions, so their intervals should not be treated as interchangeable. For the registered result, the sponsor’s ANCOVA estimate and interval are the relevant reported analysis.

Precision is also affected by the analysis population and outcome availability. The registry notes that only participants available at specified time points were analyzed, and it sets a diary-recording threshold for calculating means. The record does not report the missing-data method or sensitivity analyses, so the extent to which missing observations affect the interval cannot be assessed from the registry record. The interval describes statistical uncertainty under the analysis; it does not account for every possible limitation in study conduct or reporting.

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 figures are expressed as participants per arm for 80% power and participants per arm for 90% power. They are not total event counts. The assumptions for this planning illustration 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 trial’s own original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under those assumptions, if that effect and the model assumptions were correct. The 90% power column gives the corresponding planning target for a higher chance of detecting that effect. These are planning illustrations, not observed power.

Rows for planning at 100%, 75%, or 50% of the observed effect vary the assumed effect size. A smaller effect is harder to distinguish from random variation, so the planning calculation requires more participants per arm. The observed effect is estimated from this study and may be unstable, especially when the estimated contrast is small or uncertain. The planning figures therefore should not be read as a recommendation or as evidence that a future study would achieve the stated power.

The sample-size curve applies the same planning logic across effect sizes. Its estimates depend on the stated assumptions and do not account for unreported design features, missing outcomes, or any adjustments not specified in the planning description. The registry’s initial design target and the reasons for selecting it are not reported in the registry record.

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 = 1.800; pooled standard deviation σ = 45.784.
2. n = 2 × (1.96 + 0.842)² × 45.784² / 1.800² = 10,155.8, rounded up to 10,156 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 <- 1.8                      # observed difference in means
sigma <- 45.7837203160006                     # 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(1687283)
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 = 10,156 (80% power), 13,596 (90% power)
 75% of observed effect: n per arm = 18,055 (80% power), 24,171 (90% power)
 50% of observed effect: n per arm = 40,624 (80% power), 54,384 (90% power)
power.t.test: 10156.8 
Simulated power at n = 10,156 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 ANCOVA, with a net mean difference of -1.80, a 95% confidence interval from -12.19 to 8.59, and p = 0.733. The unadjusted recalculation gives a BUD-minus-FP mean difference of 1.8, a 95% confidence interval from -8.443 to 12.04, and p = 0.731. The estimates express the contrast in opposite directions, which accounts for the opposite signs.

The recalculation is based on posted summary statistics and is not the same as the sponsor’s covariate-adjusted analysis. Its interval and p-value are close to, but not identical to, the sponsor’s results. The sponsor’s analysis is the registered analysis to emphasize; the recalculation is a simple check, not a competing adjusted estimate. The registry records no discrepancy flag.

The analysis is classified in the registry as non-inferiority or equivalence. The non-inferiority margin, any equivalence bounds, and the decision rule are not reported in the registry record. Therefore, the sponsor’s estimate and interval can be described, but the available record is insufficient to confirm whether a formal non-inferiority or equivalence criterion was satisfied.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and 12 analyses. Several outcomes address different aspects of airflow, symptoms, rescue medication, and pharmacokinetics. Testing multiple outcomes creates a multiplicity concern: even when there is no underlying group difference, some results may appear unusual by chance. The record does not report whether the analyses were organized hierarchically, whether an adjustment for multiple comparisons was used, or how secondary results were intended to support the primary question. These procedures are not reported in the registry record.

The primary endpoint description gives a rule for determining when the diary-based mean was missing: fewer than 4 recorded days in the baseline week or fewer than 4 days after randomization. It also says that only participants available at specified time points were analyzed. These details identify a threshold for computing means and describe availability for analysis, but they do not specify how missing outcome data were handled in the statistical model.

Imputation, complete-case handling beyond the stated availability rule, sensitivity analyses, and assumptions about the reasons for missingness are not reported in the registry record. The number of participants contributing to an analysis can vary by outcome and time point; the registry does not provide a complete account of missingness patterns in the registry record recorded for these results. Consequently, the potential influence of missing observations on estimates cannot be fully assessed.

The primary population is described as intent-to-treat, with the qualification that only participants available at the specified time points were analyzed. The registry does not give further detail on how this population was operationalized, or on whether other analysis populations were used for particular outcomes. The study’s original statistical analysis plan, including multiplicity and missing-data procedures, is not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (1.3%), infection (0.6%), lung infection (0.6%), spondylolisthesis (0.6%), nephrotic syndrome (0.6%).

The serious adverse event figures are reported by group alongside the number listed at risk. For FP 1 mg BID, serious adverse events affected 4 of 158 participants at risk; for BUD 2 mg BID, they affected 2 of 157 participants at risk. The registry also reports 1 death in the FP group and 0 in the BUD group. These are descriptive counts and should not be interpreted as evidence that treatment caused an event or death.

The record lists serious adverse event terms and percentages, including Asthma at 1.3%, Infection at 0.6%, Lung infection at 0.6%, Spondylolisthesis at 0.6%, and Nephrotic syndrome at 0.6%. The terms describe events recorded in the safety data, not necessarily events judged related to study treatment. Attribution, timing, severity detail beyond the serious-event classification, and the causes of death are not reported in the registry record.

These figures do not capture every aspect of safety, and differences in counts alone do not establish a comparative safety profile. The registry figures should be considered as reported event information, with the limitations of the available detail in mind.

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

The posted primary results show mean AM PEF changes of 12.71 litres per minute in the FP 1 mg BID group and 14.51 litres per minute in the BUD 2 mg BID group. The sponsor’s ANCOVA estimate is a net mean difference of -1.80, with a 95% confidence interval from -12.19 to 8.59 and p = 0.733. The interval includes zero and is wide enough to leave uncertainty about the direction and size of the average difference.

These results do not establish that the treatments are identical. A result that is not statistically distinguishable from zero is not proof of equivalence. Nor does the available record establish a formal non-inferiority conclusion: the registry does not report the margin or decision rule needed to interpret the analysis in that way. The results describe the observed comparison and its uncertainty under the reported analysis.

The study compared two active nebulized treatments over 12 weeks in Chinese adult and adolescent patients with severe persistent asthma. Its endpoint was a diary-based measure of airflow, and the registry also lists other clinical and pharmacokinetic outcomes. The primary result does not answer every question about symptoms, longer-term outcomes, safety, or treatment effects in populations not described in the record.

Safety figures report serious adverse events and deaths, but they do not establish causality. Secondary findings offer additional context but carry less weight when multiplicity procedures and a hierarchy are not reported. Overall, the registry supports a careful description of the primary estimate, its uncertainty, and the limits of the available analysis details—not a broad claim about treatment benefit or lack of benefit.

18. Why This Trial Matters Statistically

This trial illustrates why a group average and its uncertainty should be considered together. Both groups had positive mean changes in morning PEF, but the main inferential question is the estimated difference between the randomized groups. The sponsor’s confidence interval includes zero and spans values on either side, so the result does not pinpoint the comparative effect with high precision. Reporting only the arm means, or only the p-value, would hide important information about that uncertainty.

It also illustrates the distinction between a conventional test for a difference and a non-inferiority question. A non-inferiority conclusion depends on a margin established for the study and on a decision rule that relates the confidence interval to that margin. The registry classifies the primary analysis as non-inferiority or equivalence, but does not report the margin or criterion. The label alone is not enough to reconstruct the decision.

The registry’s ANCOVA result and the unadjusted recalculation answer related but not identical statistical questions. Adjustment and contrast orientation matter when interpreting estimates. The simple recalculation is useful for context, but the registered model is the sponsor’s reported analysis. This distinction is important whenever summaries are used to recreate a comparison from posted results.

Finally, the record shows how multiple outcomes and incomplete detail affect interpretation. Secondary measures broaden the clinical picture, but unreported multiplicity procedures limit the weight of individual findings. The diary recording rule and availability-based analysis are relevant to missing data, while the exact handling of missing observations is not reported. These features make transparency about analysis plans and assumptions essential when assessing trial results.

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 details unavailable. Although the study is described as single-blind, it does not identify who was masked. Details of the randomization sequence and allocation concealment are not reported in the registry record. These omissions prevent a full assessment of those design features from the available information.

The primary endpoint depends on diary entries, and the registry specifies a minimum of 4 recorded days for the baseline week and after randomization. It also says that only participants available at the specified time points were analyzed. The number and pattern of missing diary observations, the method used to handle missing outcomes, and sensitivity analyses are not reported. Those gaps limit assessment of how missingness might affect the endpoint estimates.

The registry classifies the primary analysis as non-inferiority or equivalence but does not report the margin, the rationale for that margin, or the decision criterion. The original sample-size justification and the trial’s own design assumptions are also not reported. The planning illustrations based on observed effects are not substitutes for the original design rationale.

More generally, the registry does not report the full ANCOVA specification, its covariates, or the planned multiplicity approach. Some listed secondary outcomes do not have numerical results in the posted results, and the available safety details do not include attribution or event timing. These limitations do not change the reported estimates, but they narrow the conclusions that can be drawn from them.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety Study of Fluticasone Proponate Inhalation Solution in Adult and Adolescent Asthma — NCT01687283.
• Registry record last updated 2018-10-11; status last verified 2018-09.
• Results first posted 2017-06-20.
• 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

This completed phase III randomized, single-blind, active-controlled, parallel-group study enrolled 316 Chinese adult and adolescent patients with severe persistent asthma. It compared nebulized fluticasone propionate 1 mg BID with nebulized budesonide 2 mg BID over 12 weeks.

The primary endpoint was change from baseline in morning PEF, analyzed using ANCOVA in the intent-to-treat population, with only participants available at specified time points analyzed. The sponsor reported a net mean difference of -1.80, a 95% confidence interval from -12.19 to 8.59, and p = 0.733. The registry classifies the analysis as non-inferiority or equivalence, but the margin and decision criterion are not reported.

Secondary outcomes covered airflow, symptoms, rescue medication, FEV1, and fluticasone pharmacokinetics. Serious adverse events and deaths were recorded by group. The original sample-size justification, full analysis specifications, missing-data procedures, and multiplicity strategy are not reported in the registry record.