Clinical Study Evaluating Safety and Efficacy of Fluticasone Furoate in People With Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Study Evaluating Safety and Efficacy of Fluticasone Furoate in People With Asthma (NCT01436071), a randomized phase 3 study. The primary outcome is Change From Baseline in Clinic Visit Evening (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 12-week Treatment Period.

2. Clinical Question

The central statistical question is whether the posted endpoint estimates distinguish the treatment group’s change from the placebo group’s change with useful precision. The registry record gives least-squares mean changes for both groups, a recalculated unadjusted mean difference and confidence interval, and a separate sponsor-reported ANCOVA result. Those estimates describe the trial’s primary lung-function outcome; they do not by themselves establish how meaningful a change would be to an individual participant.

The record also identifies secondary outcomes involving rescue-free periods, symptom-free periods, morning and evening peak expiratory flow, and withdrawal due to lack of efficacy. Results are posted for three of those outcomes. The listed questions are related to asthma symptoms and lung function, but they are not substitutes for the primary endpoint. The registry record does not report a clinical threshold for interpreting the size of a change in FEV1.

3. Trial Design

This was a randomized, parallel-group, phase 3 study with quadruple masking. The official title describes a double-blind, placebo-controlled, multi-centre study, while the registry design fields identify masking as quadruple. The record does not explain the operational meaning of that masking designation. Both study arms received inhalation powder delivered by a Novel Dry Powder Inhaler; one arm received fluticasone furoate 50mcg and the other placebo. Rescue medication is part of the study description.

The registry lists enrollment as 248 and the study status as completed. The study started in 2011-09, with primary completion in 2012-06. The stated population was adults and adolescents with persistent asthma who were not currently receiving inhaled corticosteroids. The primary endpoint describes clinic FEV1 at baseline and Week 12, at the end of the 12-week treatment period.

The endpoint analysis groups do not include every enrolled participant: the primary arm counts are 106 for placebo and 108 for FF 50 µg OD. The posted secondary endpoint groups have counts of 110 and 111. These counts reflect the participants included in the respective posted outcome summaries; the record does not give a full accounting that reconciles each endpoint population with the total enrollment.

The registry describes the primary analysis population as randomized participants who received at least one dose of study medication, except for participants associated with one investigator who were excluded after good clinical practice issues were identified during a site audit. It then says that only participants with non-missing covariates and—before the description ends. The complete additional eligibility condition for that analysis population is not reported in the registry record. Details of allocation concealment, the original sample-size justification, and the trial’s full statistical plan 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: Participants meeting eligibility criteria at the Screening visit entered a 2-week Run-in Period for Baseline safety evaluations and to obtain measures of asthma status. Participants were then randomized to a 12-week Treatment Period. A total of 449 participants were screened; 248 were randomized, and 242 received \>=1 dose of study treatment.

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 (par.) randomized to treatment who received \>=1 dose of study medication, except for the par. of one investigator (excluded after good clinical practice \[GCP\] issues identified during a site audit). Only those par. with non-missing covariates and a post-Baseline FEV1 measurement 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 Change From Baseline in Clinic Visit Evening (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 12-week Treatment Period, measured over Baseline and Week 12.

The primary endpoint is change from baseline in evening clinic FEV1 at the end of the 12-week treatment period, measured in liters. FEV1 is the maximal amount of air that can be forcefully exhaled in one second, and is used as a measure of lung function. The endpoint focuses on a clinic measurement taken in the evening before bronchodilator and before the dose. The record says that pre-dose and pre-rescue albuterol/salbutamol trough measurements were made electronically by spirometry at baseline through Week 12 clinic visits, and that the highest of three technically acceptable measurements was recorded.

Baseline was the pre-dose value at Visit 2. Change was defined as the Week 12 value minus the baseline value. In general, analysing change from baseline expresses each participant’s follow-up measurement relative to their starting measurement, while comparing groups helps distinguish changes observed during the study from changes also seen under placebo. The registry’s primary analysis used ANCOVA, with baseline and other listed covariates included in the model.

FEV1 offers a continuous measure of lung function, so the reported group estimates retain information about the magnitude of change rather than reducing the result to a yes-or-no event. However, the registry record does not report a threshold for a clinically important FEV1 change or an interpretation rule linking the estimate to a meaningful benefit for participants. The result should therefore be read as an estimate on the recorded lung-function scale, with its uncertainty, rather than as a standalone judgment about clinical importance.

7. Results Posted in the Registry

• FF 50 µg OD: mean 0.16 versus 0.04 on control; difference 0.12 (95% CI 0.03 to 0.21), standardized effect d = 0.35; z-test p = 0.011.

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.

Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods 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:
  • FF 50 µg OD: mean 28.70 versus 17.10 on control; difference 11.60 (95% CI 3.91 to 19.29), standardized effect d = 0.40; z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FF 50 µg OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (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:
  • FF 50 µg OD: mean 22.80 versus 19.50 on control; difference 3.30 (95% CI -6.98 to 13.58), standardized effect d = 0.08; z-test p = 0.529.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between FF 50 µg OD and the control. The interval gives the range of effects that remain compatible with the data.

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:
  • FF 50 µg OD: mean 34.50 versus 22.90 on control; difference 11.60 (95% CI 1.50 to 21.70), standardized effect d = 0.30; z-test p = 0.024.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for FF 50 µg OD than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results give a mixed but broadly positive pattern in their point estimates: the recalculated differences favor the FF 50 µg OD group for rescue-free periods, morning PEF, and evening PEF. Their precision differs, and the evening PEF interval spans values on both sides of zero. These outcomes address related but distinct aspects of asthma status, so consistency in direction does not make them interchangeable with the primary FEV1 measure.

The secondary outcomes named in the registry also include the percentage of symptom-free 24-hour periods and the number of participants who withdrew due to lack of efficacy. Those outcomes are not included among the posted secondary result summaries. Their results are not reported in the registry record. The posted secondary summaries therefore do not cover every secondary outcome named in the record.

In general, secondary outcomes can help describe whether a primary finding is accompanied by changes in other measured domains. They may also help identify patterns that merit further study. However, when multiple outcomes are tested, some can appear notable by chance even if there is no corresponding effect. The registry record does not report whether a multiplicity strategy was specified or applied, and the secondary recalculated p-values are unadjusted. These results accordingly carry less confirmatory weight than a prespecified primary analysis with a clearly reported multiplicity plan.

The secondary outcomes are not independent simply because they have different labels: symptom, rescue-medication, and lung-function measures may capture related features of participants’ experience. The registry record does not report correlations among these outcomes or a method for combining them. They should be viewed as separate descriptive results, interpreted with their own intervals and measurement scales, rather than as a single composite conclusion.

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

• Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods Over the 12-week Treatment Period
• Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period
• Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-week Treatment Period
• Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Over the 12-week Treatment Period
• Number of Participants Who Withdrew Due to a Lack of Efficacy During the 12-week Treatment Period

9. Statistical Interpretation

10. Statistical Methods Explained

The registry describes the primary endpoint analysis as ANCOVA, with baseline, region, sex, age, and treatment as covariates. It also reports use of last observation carried forward to impute missing data: the last non-missing, pre-dose, post-baseline on-treatment measurement at a scheduled clinic visit was used for a missing value. These are the methods described for the primary endpoint; the registry record does not provide the full model specification or further detail about its implementation.

What does ANCOVA do?

In general, analysis of covariance models an outcome while adjusting for selected covariates. Including baseline can account statistically for differences in starting measurements and can improve the precision of a treatment comparison when baseline is related to the follow-up outcome. Region, sex, age, and treatment are also listed in the primary model. The adjusted result is conditional on the model and covariates, so it should not be confused with a simple subtraction of two group summaries.

The posted arm values for the primary endpoint are least-squares means, not raw participant-level observations. In general, a least-squares mean is a model-based group estimate adjusted for the covariates included in the analysis. The record does not report the fitted model’s coefficients, covariate distributions, or participant-level data, so the adjusted estimate cannot be independently reconstructed in full from the posted summaries.

How does the simple recalculation differ?

The recalculated primary comparison is an unadjusted mean difference based on the posted arm summaries. It is accompanied by an approximate standard error-based confidence interval and an unadjusted p-value. In general, a simple unadjusted comparison can provide a transparent summary-scale check, but it does not reproduce an adjusted ANCOVA unless the underlying data and analysis conditions support that equivalence. For this trial, the registry also labels its reported ANCOVA result as a median difference in final values, which further distinguishes it from the recalculated mean difference in change.

The recalculation estimates are based on summary statistics rather than individual participant records. The pooled standard deviation used for the standardized effect and planning illustration is approximate, as indicated in the record. In general, summary-statistic recalculations can be useful for describing scale and uncertainty, but they cannot check data cleaning, model diagnostics, covariate handling, or the consequences of individual missing observations.

What does a standard error describe?

The primary endpoint’s arm summaries report standard errors. In general, a standard error describes the sampling uncertainty of an estimate, rather than the spread of individual participant measurements. A smaller standard error indicates a more precise estimate under the analysis assumptions. It is not the same quantity as a standard deviation, which describes variability among observations. The recalculation uses the posted standard errors and group counts to approximate the comparison’s variability; it does not recover the original participant-level dispersion.

What is the role of imputation?

Last observation carried forward substitutes a participant’s last available qualifying measurement for a later missing measurement. In general, this approach makes an analysis possible when follow-up values are missing, but it assumes that the carried-forward value is a suitable stand-in for the unobserved value. That assumption may not hold for every participant or outcome. The registry record does not report the amount or pattern of missing primary endpoint data, or sensitivity analyses testing alternative missing-data assumptions. It also does not report whether the same imputation approach was used for secondary outcomes.

How should p-values be read?

In general, a p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of an estimate. The recalculated primary p-value is explicitly unadjusted. The sponsor’s reported primary p-value comes from the ANCOVA analysis. The record does not report a multiplicity adjustment for the set of outcomes.

The trial’s original statistical plan, including the intended primary model details beyond the listed covariates and imputation method, is not reported in the registry record. Interim analyses, stopping rules, the original sample-size justification, and whether any analyses were prespecified beyond the registry descriptions are also not reported in the registry record. The reported methods therefore support a description of the posted analysis, but not a complete audit of the trial’s analytic decisions.

11. Confidence Intervals and Precision

The recalculated primary mean difference is 0.119 liters, with a 95% confidence interval from 0.027 to 0.211. The interval expresses uncertainty around the estimated difference: under the assumptions of this unadjusted calculation, values across that range are compatible with the observed summary data. Its width also indicates that the true group difference is not pinned down to the reported point estimate alone. The registry’s ANCOVA result is 0.120 liters, with a 95% confidence interval from 0.026 to 0.213.

In general, a confidence interval is a range generated by a procedure that, over repeated applications under its assumptions, would cover the target quantity at the stated confidence level at the corresponding frequency. It is not a range containing a fixed proportion of participant measurements, and it is not a probability statement about this particular interval. Interpretation depends on the analysis model, the data, and the assumptions used to calculate it.

The arm-level standard errors for the primary endpoint are 0.033 liters for placebo and 0.033 liters for FF 50 µg OD. These summarize uncertainty around the arm estimates, not the spread of individual FEV1 changes. The confidence interval for the group comparison is more informative for the precision of the difference than comparing the arm standard errors by eye.

The lower bounds of both posted primary intervals are positive, but statistical separation from zero does not answer whether the difference is clinically important. The registry record gives no clinical-importance threshold for this endpoint. It also does not report sensitivity intervals under alternative missing-data assumptions or a confidence interval for a difference defined by a clinical response threshold. The interval should thus be read as precision for the statistical comparison as calculated, not as a complete account of uncertainty about clinical meaning.

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 participants per arm for 80% power and participants per arm for 90% power. They are planning illustrations based on the observed effect, not the trial’s own original design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each planning scenario targets the stated fraction of the observed effect. These figures are participants per arm, not total participants and not total events.

In plain terms, the 80% power column describes the illustrative number of participants per arm needed for an 80% chance of detecting the chosen effect under those assumptions if that effect is the true one. The 90% column uses a higher chance of detection and therefore requires more participants per arm under otherwise identical assumptions. These are prospective planning quantities; they are not observed power for this completed trial.

The scenarios consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller effect requires more participants per arm. The observed effect is an estimate from this trial and may itself be uncertain; using it as a planning target does not establish what effect should be expected in another study.

The figures are not a reconstruction of the trial’s actual sample-size calculation. The original sample-size justification, target effect, assumed variability, and any allowance for withdrawals are not reported in the registry record. The planning display should be read as an illustration of how sample requirements change with the selected effect and power target, not as evidence about the study’s original design or about the adequacy of its enrollment.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.119; pooled standard deviation σ = 0.343.
2. n = 2 × (1.96 + 0.842)² × 0.343² / 0.119² = 130.3, rounded up to 131 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.119                      # observed difference in means
sigma <- 0.342895754690701                     # 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(1436071)
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 = 131 (80% power), 175 (90% power)
 75% of observed effect: n per arm = 232 (80% power), 311 (90% power)
 50% of observed effect: n per arm = 522 (80% power), 698 (90% power)
power.t.test: 131.3 
Simulated power at n = 131 per arm: 0.800 (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 registry reports a sponsor analysis for the primary endpoint using ANCOVA. It is labelled “Median Difference (Final Values)” and gives an estimate of 0.120 liters, a 95% confidence interval from 0.026 to 0.213, and p = 0.012. This is the trial’s posted model-based result. The record identifies the covariates used in the ANCOVA and describes last observation carried forward for missing primary measurements.

The simple recalculation is a different summary: it compares the posted least-squares mean changes using an unadjusted mean difference. It gives 0.119 liters, a 95% confidence interval from 0.027 to 0.211, and an unadjusted p-value of 0.011. Although the numerical estimates are close, the recalculation should not be presented as a replication of the sponsor’s ANCOVA. The measures and adjustment differ, and the registry’s label for the sponsor estimate refers to final values rather than the unadjusted mean change.

The record does not flag a discrepancy between the sponsor analysis and the recalculation. The two results can be described side by side as related but not identical analyses. For interpretation of the study’s reported primary analysis, the sponsor’s ANCOVA result is the relevant registry result; the recalculation is a supplementary, unadjusted check based on posted summary statistics. Neither estimate alone supplies a threshold for clinical importance.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and several secondary outcomes, but it does not report a multiplicity adjustment or a hierarchy for testing the secondary outcomes. In general, examining multiple outcomes creates more opportunities for chance findings. A prespecified strategy may control how results are interpreted across a family of tests, but no such strategy is reported in the registry record. The unadjusted secondary p-values should therefore not be read as if each were the sole planned test.

The primary endpoint description specifies ANCOVA covariates and last observation carried forward for missing data. The registry does not report how many primary measurements were missing, why they were missing, or whether the missingness differed by treatment group. It also does not report sensitivity analyses using alternative assumptions. In general, imputation can affect estimates because substituted values are not observed follow-up measurements; the suitability of an approach depends on the missing-data process and assumptions.

The primary analysis population is described as randomized participants who received at least one dose, with participants associated with one investigator excluded after good clinical practice issues were identified during a site audit. The record’s population description then ends after stating that participants needed non-missing covariates. The remaining condition is not reported in the registry record. This incomplete description limits the ability to understand exactly who contributed to the analysis.

The record reports a total enrollment of 248, while the endpoint-specific group counts vary. It does not provide a complete participant flow or an explanation for each difference in analysis counts. The registry record also does not report interim analyses, stopping rules, the full original statistical analysis plan, or the original sample-size justification. These missing details matter when assessing prespecification, exclusions, and the robustness of the reported estimates; their absence does not itself establish that the analysis was inappropriate.

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: appendicitis perforated (0.8%), multiple injuries (0.8%).

The posted serious adverse event figures show 1 affected participant among 121 at risk in the placebo group and 1 among 121 at risk in the FF 50 µg OD group. The record lists appendicitis perforated and multiple injuries as top serious adverse event terms, each at 0.8%; it does not assign those terms to a particular arm in the information. The figures describe counts and recorded terms, not whether an event was caused by study treatment.

For other adverse events, 27 of 121 participants are listed as affected in the placebo group and 18 of 121 in the FF 50 µg OD group. These are descriptive counts in the registry record. They do not establish that a treatment caused or prevented an event, and they do not summarize its severity, duration, or clinical consequences.

Deaths are listed as null for both groups. That does not establish that there were no deaths; death counts are not reported in the registry record. Safety comparisons also require care because the counts alone do not describe exposure time, event timing, or the full clinical context. No medical conclusion should be drawn from these sparse figures alone.

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

The posted primary results describe a higher estimated mean change in evening clinic FEV1 in the FF 50 µg OD group than in the placebo group. The unadjusted recalculation estimates a difference of 0.119 liters, while the registry’s reported ANCOVA analysis gives a result of 0.120 liters under a different stated measure. The confidence intervals communicate uncertainty around these estimates. Together, the figures describe the statistical result recorded for the trial’s primary endpoint.

They do not, by themselves, determine how important the difference is to participants. The registry record does not give a threshold for clinical importance, nor does it connect the measured change to a defined change in symptoms or daily functioning. The result is a group-level estimate; it does not say what happened to every participant or predict an individual’s outcome.

The primary endpoint covers the stated baseline-to-Week 12 period. The posted results do not establish whether a change would persist beyond that period. Nor do these data answer questions about populations, settings, treatment patterns, or follow-up periods not described in the record. The study population is specifically described as adults and adolescents with persistent asthma who were not currently receiving inhaled corticosteroids.

The secondary outcomes offer additional measurements, but their unadjusted results require cautious interpretation because several outcomes were considered and the registry does not report a multiplicity plan. Results for symptom-free periods and withdrawals due to lack of efficacy are not posted. Safety counts are also descriptive and do not establish causation. Taken together, the registry record supports a careful account of the measured comparisons and their precision, not a broader medical recommendation or a conclusion about outcomes beyond those measured.

18. Why This Trial Matters Statistically

This trial illustrates why a reported treatment comparison should be read together with its endpoint definition, analysis method, and uncertainty. The primary endpoint is a change-from-baseline measure, and the registry describes an adjusted ANCOVA analysis with specified covariates. A separate unadjusted recalculation is available from the posted group summaries, but its estimate is not identical in meaning to the sponsor’s model-based result. Keeping those analyses distinct avoids treating a convenient summary calculation as though it reproduced the full analysis.

The confidence intervals are important because a point estimate alone can make a result seem more exact than it is. The primary interval gives a range of values compatible with the unadjusted calculation under its assumptions, while the registry also reports an interval for the adjusted analysis. Neither interval supplies a clinical-importance threshold, underscoring the distinction between statistical precision and clinical interpretation.

The record also shows how secondary outcomes add context without automatically strengthening a primary finding. Several related outcomes are named, only some have posted numerical results, and no multiplicity strategy is reported. That combination makes it important to distinguish a planned primary comparison from exploratory or unadjusted secondary evidence.

Finally, the population description, missing-data approach, and analysis counts matter for reproducibility. The registry gives useful details, including the LOCF approach and an investigator-related exclusion, but the population description is incomplete and several design and analysis details are not reported. Statistical interpretation depends not only on estimates, but also on understanding whom the estimates represent and which assumptions were used to obtain them.

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 posted primary result has two different statistical descriptions: the registry’s ANCOVA analysis is labelled as a median difference in final values, while the simple recalculation is an unadjusted mean difference in change. Their close numerical values do not remove the distinction between estimands and methods. The recalculation is based on summary statistics, not individual data, and cannot reproduce the sponsor’s adjusted model or assess its diagnostics.

The primary analysis description includes last observation carried forward, but the registry does not report the amount or pattern of missing data, alternative missing-data sensitivity analyses, or the complete analysis-population condition. The record’s description of participants with non-missing covariates ends before its final condition is specified. The participant counts in the endpoint summaries also differ from total enrollment and across outcomes, without a complete accounting in the posted record.

Only three secondary outcomes have numerical results included in the posted summaries, although additional outcomes are named. The record does not report whether secondary analyses were adjusted for multiplicity. The recalculated comparisons use approximate variability derived from posted standard errors, and the planning illustrations use the observed effects rather than the trial’s original assumptions.

The registry does not report the original sample-size justification, the full analysis plan, interim analyses, or stopping rules. It also gives no clinical-importance threshold for FEV1. The safety information is limited to group counts and listed event terms; deaths are not reported, and event attribution is not established by the counts. These limitations constrain interpretation of precision, generalizability, and clinical meaning.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Clinical Study Evaluating Safety and Efficacy of Fluticasone Furoate in People With Asthma — NCT01436071.
• Registry record last updated 2017-01-11; status last verified 2016-11.
• Results first posted 2014-09-03.
• 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.

23. Record Summary

NCT01436071 is a completed randomized, parallel-group, phase 3 trial of fluticasone furoate 50mcg versus placebo in adults and adolescents with persistent asthma who were not currently receiving inhaled corticosteroids. Enrollment was 248. The primary outcome was change from baseline in evening clinic FEV1 at Week 12.

The registry reports an ANCOVA result of 0.120 liters, with a 95% confidence interval from 0.026 to 0.213 and p = 0.012. An unadjusted recalculation gives a mean difference of 0.119 liters, with a 95% confidence interval from 0.027 to 0.211 and p = 0.011. These are related but methodologically distinct results. Secondary results are posted for three outcomes; results for other listed secondary outcomes are not reported in the registry record.

The record describes last observation carried forward for missing primary measurements, but does not report the original sample-size justification, a multiplicity strategy, or a complete analysis-population description. The posted estimates should be interpreted with those limitations and with the distinction between statistical difference and clinical importance in mind.