Advair HFA For Chronic Obstructive Pulmonary Disease(COPD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Advair HFA For Chronic Obstructive Pulmonary Disease(COPD) (NCT00633217), a randomized phase 4 study. The primary outcome is Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) 2 Hours Post-dose of Blinded Study Drug.

2. Clinical Question

3. Trial Design

This was a Phase 4 randomized, double-blind, double-dummy, parallel-group trial. The registry lists an enrollment of 247 and a 12-week comparison of two fluticasone propionate/salmeterol formulations in participants with COPD. The study is recorded as completed. Its start is listed as 2008-03, and primary completion as 2009-02.

The two regimens were HFA MDI 230/42 mcg twice daily and DISKUS 250/50 mcg twice daily. In addition to the assigned active formulation, each group received the matching placebo for the other inhaler type. This double-dummy arrangement is consistent with a design intended to maintain masking when the two delivery devices differ. The registry identifies masking as double; further details about who was masked are not reported in the registry record.

In a parallel-group design, participants are assigned to a group and followed in that group rather than crossing over between treatments. Random allocation can help balance both measured and unmeasured participant characteristics across groups, although the allocation method and any stratification factors are not reported in the registry record. The registry does not report the recruitment setting, locations, participant demographics, eligibility criteria, adherence, or treatment discontinuations.

The brief description says the study could last up to approximately 15 weeks, included five clinic visits, and involved breathing tests and daily peak expiratory flow diary measurements. That description gives context for the study procedures; the primary efficacy timeframe was baseline through Week 12, with FEV1 assessed two hours after study-drug administration. The original design assumptions and sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: all participants who had been randomized to study drug. The numbers analyzed do not match Baseline numbers due to missing data for some participants.

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 in Forced Expiratory Volume in One Second (FEV1) 2 Hours Post-dose of Blinded Study Drug, measured over 2 hours after administration of blinded study drug; Baseline through Week 12.

The primary endpoint was mean change from baseline in forced expiratory volume in one second (FEV1), measured two hours after administration of blinded study drug. FEV1 is the maximal amount of air a person can forcefully exhale in one second, assessed in this trial using spirometry. Change was defined as the endpoint value minus the baseline value, so a positive change represents an increase relative to baseline.

The endpoint time was not a single named visit for every participant in the registry description. Endpoint was defined as the last scheduled observation for two-hour post-dose FEV1 during the 12-week treatment period. The reported primary outcome therefore summarizes change at that endpoint, rather than the course of lung-function measurements at every visit.

FEV1 is a continuous lung-function measure, which allows the outcome to be expressed as a mean change and a between-group mean difference. Comparing changes from baseline focuses on how the measured value shifted during the treatment period, while the randomized groups provide the basis for a comparative estimate. As a general statistical point, a continuous outcome can retain information about the magnitude of individual measurements rather than reducing them to categories. The registry does not report a clinically meaningful threshold for interpreting a given difference in milliliters.

7. Results Posted in the Registry

• DISKUS 250/50 mcg and Matching HFA MDI Placebo: mean 150.00 versus 155.00 on control; difference -5.00 (95% CI -67.82 to 57.82), standardized effect d = -0.02; z-test p = 0.876.

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 AM Pre-dose FEV1

• 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:
  • DISKUS 250/50 mcg and Matching HFA MDI Placebo: mean 77.00 versus 74.00 on control; difference 3.00 (95% CI -53.96 to 59.96), standardized effect d = 0.01; z-test p = 0.918.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between DISKUS 250/50 mcg and Matching HFA MDI Placebo and the control. The interval gives the range of effects that remain compatible with the data.

Mean Change From Baseline in Peak Expiratory Flow

• 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:
  • DISKUS 250/50 mcg and Matching HFA MDI Placebo: mean 18.70 versus 21.80 on control; difference -3.10 (95% CI -10.23 to 4.03), standardized effect d = -0.11; z-test p = 0.394.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between DISKUS 250/50 mcg and Matching HFA MDI Placebo and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists two secondary lung-function outcomes: mean change in morning pre-dose FEV1 and mean change in peak expiratory flow. Across these outcomes, the recalculated contrasts are modest relative to the uncertainty represented by their intervals, which include zero. This overall pattern is broadly consistent with the primary unadjusted comparison in that none of the recalculated intervals clearly separates the group contrast from zero.

The secondary outcomes complement the primary endpoint by describing lung function at a different measurement time or with a different measure. Morning pre-dose FEV1 concerns a measurement before study-drug administration, while peak expiratory flow provides another measure of airflow. They do not replace the primary endpoint or resolve the difference between the simple unadjusted recalculation and the sponsor's reported ANCOVA analysis.

These secondary recalculations are unadjusted. The registry does not report corresponding sponsor analyses for them, and does not describe a multiplicity adjustment or a hierarchy governing how the outcomes were to be interpreted. General explanation: when several outcomes are tested, the chance of at least one apparently notable result can increase, even if none reflects a reliable underlying effect. Adjustments or prespecified outcome hierarchies can help manage that issue, but their use cannot be assumed when it is not described.

For these reasons, the secondary outcomes are best treated as supporting context rather than independent confirmation. Their estimates and uncertainty can inform the overall pattern, but the number of outcomes considered and the unreported multiplicity strategy make isolated secondary p-values less persuasive than a clearly specified primary analysis. The registry's missing protocol and analysis-plan details limit stronger conclusions about how the secondary results were intended to contribute to the main question.

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

• Mean Change From Baseline in AM Pre-dose FEV1
• Mean Change From Baseline in Peak Expiratory Flow

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a measured change in FEV1 expressed in milliliters. The registry reports group means and standard errors. The standard error describes the precision of an estimated group mean, rather than the spread of individual participant measurements. A standard deviation would describe participant-to-participant variability; it is not the dispersion reported for the primary group means in the registry.

What does the unadjusted comparison estimate?

The recalculated comparison is the difference between the posted group means, expressed as DISKUS minus HFA MDI. A negative estimate means the posted mean change was lower in the DISKUS group for this subtraction order; it does not by itself establish a meaningful treatment difference. The recalculation is simple and unadjusted: it does not account for baseline FEV1 or other covariates. It is based on the posted summary statistics and is distinct from the sponsor's analysis.

General explanation: random allocation supports a fair comparison by reducing systematic differences between groups on average. It does not guarantee identical groups, nor does it remove uncertainty from sampling or missing measurements. An unadjusted contrast and an adjusted analysis can differ because they use different statistical procedures and may handle baseline information differently.

What is ANCOVA?

ANCOVA, or analysis of covariance, compares outcome means while accounting for one or more covariates. General explanation: in a randomized trial, adjusting for a baseline measure can improve precision and account for chance differences in that measure. The registry reports ANCOVA for the sponsor's non-inferiority or equivalence analysis, but the covariates, model specification, adjusted estimate and confidence interval are not reported in the registry record. The reported p-value cannot substitute for those missing details.

How should the p-values be understood?

A p-value measures how incompatible the observed data are with a specified statistical hypothesis, under the assumptions of the analysis. It is not the probability that a treatment works, that the null hypothesis is true, or that the observed estimate is clinically important. The unadjusted recalculation has p = 0.876. Separately, the registry lists p = 0.021 for the sponsor's ANCOVA analysis designated as non-inferiority or equivalence. Those p-values arise from different analyses and should not be treated as interchangeable. The hypothesis, direction and margin for the sponsor's test are not available in the record.

General explanation: a conventional superiority test often asks whether the data are inconsistent with no difference. Non-inferiority asks whether an intervention is not worse than a comparator by more than a prespecified margin; equivalence asks whether the difference lies within prespecified bounds in both directions. A p-value without the margin, estimate and confidence interval is insufficient to judge the magnitude of the contrast or its relation to those bounds. The registry record does not report the trial's non-inferiority or equivalence margin.

Why do confidence intervals matter?

A confidence interval gives a range of values compatible with the data under the statistical method used. General explanation: it conveys both the direction and precision of an estimate, whereas a p-value alone does not. The recalculated primary interval extends on both sides of zero, so the posted unadjusted summary statistics do not pin down the direction of the mean difference. Its width also makes clear that the exact size of the contrast is uncertain. The interval is not a guarantee that the true value lies within its limits, nor is it a range of individual participant responses.

How do missing observations affect interpretation?

The registry defines the primary population as the Intent-to-Treat population, meaning participants randomized to study drug, and notes that numbers analyzed do not match baseline numbers because of missing data. This signals that not every randomized participant contributed to every reported outcome analysis. General explanation: if data are missing, the analysis may be affected depending on how much is missing and whether the reasons for missingness are related to outcomes or treatment. The record does not describe missing-data methods, reasons for missing measurements, or sensitivity analyses. It is therefore not possible to determine from the registry entry how missing observations influenced the estimates.

The record also does not report a detailed statistical analysis plan, the original sample-size calculation, interim analyses, or the prespecified approach to multiple outcomes. These gaps limit independent assessment of whether the posted analyses followed a planned strategy. The reported results remain interpretable as recorded, but the methods cannot be fully reconstructed from the available registry information.

11. Confidence Intervals and Precision

The recalculated primary mean difference is -5.0 mL, with a 95% confidence interval from -67.82 to 57.82. The estimate compares DISKUS with HFA MDI by subtracting the HFA MDI group mean change from the DISKUS group mean change. The interval includes zero and permits values on either side of zero, so the posted summary statistics are compatible with more than one direction for the unadjusted contrast.

General explanation: a confidence interval represents uncertainty in an estimated group contrast under the calculation method. It helps distinguish a precise estimate from one that leaves a wide range of plausible values. It does not describe the range of outcomes among individual participants, and it does not establish that every value inside the interval is equally likely. The interval also does not by itself establish equivalence or non-inferiority; those interpretations depend on prespecified margins and the analysis used.

The interval above comes from a simple recalculation of the posted group summaries, not from the sponsor's ANCOVA. The registry reports a 95% confidence level for the sponsor analysis but does not provide that analysis's confidence limits or adjusted estimate. Given the discrepancy flagged in the record, the sponsor's own analysis takes precedence. Its p-value is reported, but without the estimate, confidence interval and margin, the precision and direction of that adjusted result cannot be assessed from the record.

Standard errors accompany the group means, but they are not confidence intervals for the between-group difference. General explanation: each standard error describes uncertainty in its corresponding estimated mean, while the interval for a contrast depends on the uncertainty of both group estimates and the calculation method. The primary recalculated interval is therefore more informative about the precision of the unadjusted between-group contrast than either group standard error considered alone.

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 illustrations based on the observed effect in the posted results, not the trial's original design calculation. For these continuous outcomes, the figures are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set at the stated fraction of the observed effect. The original trial's design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives an illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect were the true effect and the model assumptions held. The 90% power column gives the corresponding planning figure for a 90% chance. Power is a design characteristic calculated for an assumed effect; it is not a probability that the observed finding is correct.

Rows that plan for 75% or 50% of the observed effect consider smaller target differences than the row using 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants for the same planned power. This is why the illustrative participant counts rise as the assumed effect becomes smaller. The values can be very large when the observed effect is close to zero, because basing planning on such a small contrast implies trying to detect an even smaller one.

These figures are not observed power. They are planning illustrations using the listed assumptions and effect sizes derived from the posted results; they do not establish that the trial was designed for those targets or that its original protocol used those methods. They should not be read as a retrospective judgment of whether the trial was adequately designed.

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 = -5.000; pooled standard deviation σ = 243.627.
2. n = 2 × (1.96 + 0.842)² × 243.627² / -5.000² = 37,269.2, rounded up to 37,270 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 <- -5                      # observed difference in means
sigma <- 243.627404507527                     # 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(633217)
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 = 37,270 (80% power), 49,893 (90% power)
 75% of observed effect: n per arm = 66,257 (80% power), 88,699 (90% power)
 50% of observed effect: n per arm = 149,077 (80% power), 199,572 (90% power)
power.t.test: 37270.1 
Simulated power at n = 37,270 per arm: 0.802 (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 an ANCOVA analysis for the primary comparison, classified as non-inferiority or equivalence, with p = 0.021. It does not give the adjusted effect estimate, confidence interval, analysis margin, covariates or detailed test specification. In contrast, the recalculated unadjusted comparison from the posted group summary statistics gives a mean difference of -5.0 mL, a 95% confidence interval from -67.82 to 57.82, and p = 0.876.

These results should not be treated as competing estimates from identical analyses. The recalculation is a simple unadjusted comparison; ANCOVA is an adjusted method, and the sponsor's reported analysis is specifically designated as a non-inferiority or equivalence analysis. The record flags a discrepancy, so the sponsor's own analysis takes precedence. The recalculated result is useful as a transparent check based on the posted summary values, but it does not replace the sponsor's planned analysis.

The reported p-value alone does not show the size or direction of the adjusted difference, nor whether it fell within a non-inferiority or equivalence margin. Without those details, it is not possible to independently evaluate the sponsor's conclusion from the registry entry. The registry record also does not report the original analysis plan or whether other prespecified analyses were conducted.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary efficacy outcome and two secondary outcomes. It does not report a multiplicity adjustment, a testing hierarchy, or a plan for interpreting several outcomes together. General explanation: testing more than one outcome can increase the chance of a nominally unusual result arising by chance. Methods such as adjustment procedures or a prespecified testing sequence can address this concern, but the registry record does not say whether such methods were planned or used. The secondary results should therefore be interpreted as exploratory or supportive rather than treated as independently confirmatory.

The primary population is defined as the Intent-to-Treat population, comprising all participants randomized to study drug. However, the registry notes that numbers analyzed do not match baseline numbers because of missing data. It does not specify the number with missing primary outcome data, reasons for missingness, how missing values were handled, or whether sensitivity analyses were performed. General explanation: the consequences of missing observations depend partly on why measurements are absent and on the assumptions used to analyze them. Those assumptions cannot be assessed from the registry entry.

The primary endpoint was defined using the last scheduled two-hour post-dose observation during the 12-week treatment period. The record does not describe how unscheduled measurements, incomplete follow-up, or other deviations were treated. It also does not report a per-protocol population or other analysis populations for the sponsor's non-inferiority or equivalence analysis.

Details needed to reproduce or fully evaluate the primary model are also unavailable. The registry does not report the non-inferiority or equivalence margin, covariates in the ANCOVA, model assumptions, interim analyses, or the original statistical analysis plan. These absences do not invalidate the posted estimates, but they limit assessment of prespecification, robustness to missing data, and the relation between the sponsor's p-value and the intended clinical criterion.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chronic obstructive pulmonary disease exacerbation (2.5%), urinary tract infection (1.7%), appendicitis (0.8%), gastritis (0.8%), contusion (0.8%).

The registry reports serious adverse events among participants at risk in each group. For HFA MDI with matching DISKUS placebo, 6 of 121 participants at risk had a serious adverse event. For DISKUS with matching HFA MDI placebo, 3 of 126 participants at risk had a serious adverse event. These are group-specific counts and denominators, not rates calculated for a new time period or adjusted for exposure.

The listed serious-event terms include COPD exacerbation at 2.5%, urinary tract infection at 1.7%, and appendicitis, gastritis, contusion and hypoglycaemia at 0.8% each. The registry does not specify in this listing which group each term occurred in. Death counts are not reported in the registry record.

General explanation: a serious adverse event is an event meeting a seriousness criterion; seriousness is not the same as severity, and a reported event does not by itself establish that study treatment caused it. These figures are descriptive. They do not establish comparative safety, particularly without further information on exposure, event timing, causality assessment, and the broader adverse-event profile.

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

The posted results address a specific comparison: mean change from baseline in two-hour post-dose FEV1 at the endpoint during a 12-week trial of two fluticasone propionate/salmeterol inhaler formulations in participants with COPD. For the simple unadjusted calculation, the group mean changes were close and the estimated difference was -5.0 mL. The interval around that estimate is wide enough to include differences in either direction.

The record also reports a sponsor ANCOVA analysis classified as non-inferiority or equivalence, with p = 0.021. Because the registry flags a discrepancy, the sponsor's own analysis takes precedence over the unadjusted recalculation. Yet the adjusted estimate, confidence limits and margin are not reported, so the registry entry alone does not allow an independent assessment of the magnitude of the sponsor's result or its relation to the intended non-inferiority or equivalence criterion.

Neither a small point estimate nor a p-value alone establishes that two treatments are equivalent, nor does a result that is not statistically distinguishable from zero establish no difference. General explanation: evidence about equivalence or non-inferiority depends on a prespecified margin and a compatible analysis, not simply on failing to detect a difference in a conventional superiority comparison. Those protocol details are absent from the record.

The findings also do not establish that the regimens would produce the same results in populations unlike those enrolled, over different durations, or on outcomes not measured in this trial. Participant characteristics, detailed eligibility criteria and broader clinical outcomes are not reported in the registry record. The safety counts are descriptive and do not determine causation or comparative risk.

Accordingly, the statistical meaning is bounded by the recorded outcomes, the available summary statistics, and the unreported analysis details. The results describe this trial's posted comparisons; they are not personal medical guidance and do not establish a general treatment recommendation.

18. Why This Trial Matters Statistically

This trial illustrates why the reported analysis and a transparent summary-statistic recalculation can answer related but different questions. The primary group means allow an unadjusted contrast and confidence interval to be reconstructed, while the registry separately records an ANCOVA analysis designated as non-inferiority or equivalence. The discrepancy makes it important to distinguish a descriptive recalculation from the sponsor's own analysis rather than treating one p-value as a replacement for the other.

It also demonstrates why the label attached to a statistical test matters. Non-inferiority and equivalence are not conclusions that follow merely from a small estimated difference or a nonsignificant superiority test. They depend on a prespecified margin, a suitable analysis and sufficient precision. Here, the sponsor analysis is identified by type and p-value, but the estimate, interval and margin are not reported in the registry record. That limits independent statistical interpretation.

The endpoint itself raises a useful interpretive point: the trial measured change in a continuous spirometric outcome at a defined post-dose time and endpoint visit. A mean difference gives a concise group-level summary, but uncertainty around it remains central. The recalculated interval shows why the point estimate should not be read in isolation.

Finally, the registry notes missing outcome data and lists multiple outcomes without detailing missing-data handling or multiplicity strategy. These are not minor presentation details: they affect how confidently readers can connect the reported numbers to the original analysis plan. The trial is therefore a practical example of the value of complete reporting for interpreting both estimates and the methods behind 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.

Several trial-specific details needed to assess applicability are not reported in the registry record, including participant demographics, detailed eligibility criteria, recruitment settings, and study locations. The record describes participants with COPD but does not permit evaluation of how closely the enrolled group reflects particular clinical subgroups.

The primary analysis is limited by unavailable information about missing outcomes. The registry says analyzed numbers do not match baseline numbers because some data are missing, but does not describe the extent, reasons, handling, or sensitivity analyses. The analyzed sample sizes also differ by outcome, so the estimates are based on the available outcome-specific data rather than necessarily on every randomized participant.

The sponsor's ANCOVA result is incompletely reported: the record provides p = 0.021 and identifies the analysis as non-inferiority or equivalence, but does not provide its adjusted effect, confidence interval, covariates, or margin. This prevents independent evaluation of the sponsor's analysis and its clinical threshold. The unadjusted recalculation is not a substitute, particularly because the record flags a discrepancy and the sponsor analysis takes precedence.

The registry does not report the original sample-size justification, detailed analysis plan, multiplicity approach, interim analyses, adherence, or treatment discontinuations. It also provides no death counts and limited detail about serious adverse events beyond counts and listed terms. These omissions constrain assessment of robustness, safety comparisons and generalizability, without changing the numerical results that are recorded.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Advair HFA For Chronic Obstructive Pulmonary Disease(COPD) — NCT00633217.
• Registry record last updated 2016-12-08; status last verified 2016-10.
• Results first posted 2009-11-26.
• 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 describes a completed Phase 4 randomized, double-blind, double-dummy, parallel-group trial comparing fluticasone propionate/salmeterol HFA MDI 230/42 mcg twice daily with DISKUS 250/50 mcg twice daily in participants with COPD. The primary outcome was mean change from baseline in FEV1 measured two hours after study-drug administration at the endpoint during the 12-week treatment period.

The posted group means were 155.0 mL for HFA MDI and 150.0 mL for DISKUS. The simple unadjusted recalculation gives a mean difference of -5.0 mL and a 95% confidence interval from -67.82 to 57.82. The registry also reports an ANCOVA analysis classified as non-inferiority or equivalence, with p = 0.021; its estimate, confidence limits and margin are not reported. Because the record flags a discrepancy, the sponsor's own analysis takes precedence.

Two secondary lung-function outcomes and descriptive serious adverse event counts are also recorded. Missing outcome handling, multiplicity methods and several details of the original analysis plan are not reported in the registry record.