Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT01529632), a randomized phase 3 study. The primary outcome is Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment.

2. Clinical Question

The study addressed whether the fixed combination and concurrent administration of the individual components produced different measured lung-function values at the end of the treatment period. The listed primary outcome is a continuous measure in liters, rather than a count or a time-to-event outcome. The registry record also lists measures of FEV1 over the first four hours after dosing, rescue-medication use, and daytime symptoms as secondary outcomes.

The comparison is between treatment strategies as assigned in the trial, not between people who chose one treatment or another. The registry record says patients were analyzed according to randomized treatment. For the primary outcome, however, it defines the analysis population more narrowly as a Per Protocol Set. These details matter when interpreting to whom the posted primary estimates apply: the record does not describe them as results for every enrolled patient.

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 3 study sponsored by Novartis Pharmaceuticals. The registry record lists 193 enrolled participants and the condition as chronic obstructive pulmonary disease. The study started in 2012-05, had primary completion in 2012-12, and is listed as completed.

One group received QVA149 plus placebo once daily for 28 days. The comparison group received QAB149 plus NVA237 once daily for 28 days. The record describes QAB149 as indacaterol maleate and NVA237 as glycopyrronium bromide. The primary endpoint was assessed on Day 29, after the stated 28-day treatment period.

Random allocation is intended to create groups that are comparable on average at the start of a trial, while masking is intended to reduce influences of treatment knowledge on trial conduct or assessment. Those are general features of randomized, masked designs; the registry record does not identify which four roles were masked or describe the allocation sequence or its concealment. It also does not report the original sample-size justification, the trial’s design assumptions, or interim analyses. These points should not be inferred from the planning illustrations calculated from the posted results.

The primary outcome population was the Per Protocol Set. It included Full Analysis Set patients with available data and without major protocol deviations or criteria causing exclusion, and patients were analyzed according to randomized treatment. The registry record does not provide a detailed account of how many participants were excluded from that set, why they were excluded, or how missing primary measurements were handled. The outcome-specific group counts are therefore more informative for the posted primary estimates than the overall enrollment figure alone.

The trial’s short treatment period and its listed lung-function outcomes frame the question as a comparison of measured responses during treatment. The record does not establish from these details what the results might mean for longer-term outcomes or for patients outside the study population.

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: Open-label, active QAB149 and NVA237 were administered during a 14-day period prior to randomization in order to stabilize patients and standardize baseline lung function. The patients were then randomized to either the fixed dose combination or free combination arms of blinded treatment in a 1:1 ratio and received study drug for 28 days.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Per Protocol Set includes the Full analysis Set patients with available data and without any major protocol deviations or criteria causing exclusion. Patients were analyzed according to the treatment to which they were randomized.

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 Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment, measured over Day 29.

The primary endpoint was trough forced expiratory volume in one second (FEV1) after 28 days of blinded treatment. FEV1 is the volume of air a person can forcibly exhale in the first second of a breathing maneuver. The registry record reports the endpoint in liters and defines trough FEV1 as the average of readings taken 23 hours 15 minutes and 23 hours 45 minutes after dosing on Day 29.

Measuring at these later post-dose times gives an estimate of lung function near the end of the once-daily dosing interval, rather than an estimate of the immediate response after dosing. That is a general description of why a trough measure can be useful for a once-daily treatment comparison; it does not imply any particular clinical threshold or benefit. The record says spirometry followed internationally accepted standards.

The primary outcome is reported as a least-squares mean, a model-based estimate that accounts for the covariates and structure specified in the analysis. The model included treatment, baseline FEV1, FEV1 reversibility components, baseline smoking status, baseline inhaled corticosteroid use, country, and center nested within country; center was included as a random effect. The registry record does not report a clinical threshold for interpreting the size of a difference in liters.

7. Results Posted in the Registry

• QAB149 + NVA237: mean 1.47 versus 1.46 on control; difference 0.01 (95% CI -0.05 to 0.06), standardized effect d = 0.03; z-test p = 0.822.

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.

Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 1

• 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:
  • QAB149 + NVA237: mean 1.57 versus 1.60 on control; difference -0.02 (95% CI -0.06 to 0.01), standardized effect d = -0.21; z-test p = 0.156.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between QAB149 + NVA237 and the control. The interval gives the range of effects that remain compatible with the data.

Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 28

• 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:
  • QAB149 + NVA237: mean 1.59 versus 1.57 on control; difference 0.01 (95% CI -0.04 to 0.07), standardized effect d = 0.07; z-test p = 0.659.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between QAB149 + NVA237 and the control. The interval gives the range of effects that remain compatible with the data.

The registry record lists secondary measures covering FEV1 over the first four hours after dosing on Day 1 and Day 28, peak FEV1, the Day 28 time course, rescue-medication use, and days without daytime symptoms. Numerical comparisons are posted for the AUC measures on Day 1 and Day 28. Numerical results for the other listed secondary measures are not reported in the registry record.

Across the two posted AUC comparisons, the recalculated mean differences point in opposite directions, and both reported intervals include zero. This mixed pattern does not provide a consistent secondary signal that changes the interpretation of the primary comparison. The AUC outcomes measure lung function over a period after dosing, whereas the primary endpoint measures trough FEV1 near the end of the dosing interval. They therefore address related but distinct aspects of the response. Their estimates should not be treated as replications of the primary endpoint.

The secondary comparisons are unadjusted recalculations from posted summary statistics. The registry record does not report whether a multiplicity strategy was prespecified or applied. In general, interpreting many outcomes without accounting for multiple testing increases the chance that one or more results may appear notable by chance. The unadjusted p-values should therefore be regarded as exploratory descriptions rather than definitive evidence. The record also does not provide a complete statistical analysis plan or numerical results for all listed secondary outcomes, limiting assessment of the overall secondary-outcome pattern.

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

• Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 1
• Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 28
• Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 28 Post-dose
• Time Course of Forced Expiratory Volume in One Second (FEV1) (Pre-dose to 4 Hours Post Dose) on Day 28
• Change From Baseline in the Mean Daily, (Daytime and Nighttime Combined) Number of Puffs of Rescue Medication Used Over 28 Days of Treatment
• Change From Baseline in Percentage of Days With 'no Daytime Symptoms' Over 28 Days of Treatment

9. Statistical Interpretation

10. Statistical Methods Explained

The primary analysis is described as a mixed model for trough FEV1. The record names treatment, baseline FEV1, FEV1 reversibility components, baseline smoking status, baseline inhaled corticosteroid use, and country as model terms. It also includes center nested within country, with center treated as a random effect. A mixed model can represent both measured covariate relationships and grouped data structure. In general, accounting for centers within countries can allow outcomes to vary across centers rather than treating every observation as independent of center membership.

The registry reports least-squares means with standard errors for each treatment group. In general, a least-squares mean is a model-based group estimate adjusted for the terms in the model, whereas a raw mean is calculated directly from observed values. The standard error describes uncertainty in an estimated mean; it is not the spread of individual participants’ measurements. The posted primary group estimates are 1.459 liters and 1.465 liters, with standard errors listed in the record. The standard errors are not repeated because they have more than three decimal places.

The comparison calculations accompanying the group estimates are labeled as unadjusted recalculations from posted summary statistics. They are not the same as a direct result from the mixed model described for the endpoint. The recalculated primary mean difference is 0.006 liters, with an unadjusted p-value of 0.822. The record gives no sponsor-reported model-based comparison or p-value for the primary endpoint. Because the listed discrepancy flag is false, there is no noted conflict requiring the sponsor’s own analysis to take precedence over the recalculation; nevertheless, the recalculation remains a simple unadjusted comparison and should not be presented as the specified model’s result.

In general, a confidence interval describes a range of estimates compatible with the data and the procedure used to form the interval. The intervals for the posted primary and secondary recalculated comparisons cross zero. For a difference between groups, zero represents no difference in the direction and scale defined for that comparison. An interval that includes zero therefore does not establish a difference, but it also does not prove that the true difference is exactly zero. The registry record does not state the confidence level for these intervals, so no confidence level should be assumed from the record.

The reported p-values for these recalculated comparisons are unadjusted. In general, a p-value evaluates the compatibility of data with a specified null model under the assumptions of the test; it is not the probability that the null hypothesis is true and it is not a measure of clinical importance. The registry record does not report a multiplicity procedure for the outcomes. When many outcomes or comparisons are examined, unadjusted results can be more likely to include apparently notable findings by chance. That general concern is relevant to secondary outcomes, which should be interpreted with particular care when no adjustment strategy is reported.

What does the model adjust for?

The listed terms include baseline FEV1 and other baseline characteristics, as well as country and center structure. In general, covariate adjustment can account for measured characteristics included in a model and may improve the precision of a group comparison. It cannot address unmeasured factors simply by being a mixed model. The record does not provide coefficient estimates for the covariates, diagnostics, model-fit assessments, or sensitivity analyses.

What is the role of the analysis population?

The primary endpoint population is the Per Protocol Set, defined as Full Analysis Set patients with available data and without major protocol deviations or specified exclusion criteria. The record says patients were analyzed according to randomized treatment. These are distinct pieces of information: treatment assignment determines the group label, while the Per Protocol definition determines who contributes to the primary analysis. The numbers used for the primary group estimates are 81.0 for QVA149 and 96.0 for QAB149 plus NVA237. The registry record does not give a fuller participant flow or explain the handling of every missing value.

Why can dispersion and sample size matter?

In general, an estimate is more precise when the data contain less unexplained variability and when more observations contribute, although the actual precision also depends on design and analysis. The registry reports standard errors for the least-squares means, and the recalculation uses an approximate pooled standard deviation. That pooled value is marked as approximate because it is derived from the posted standard errors and group sizes rather than directly reported as a standard deviation. Variability is important because a small observed mean difference can still be uncertain when the estimates are imprecise. The posted interval, rather than the difference alone, helps communicate that uncertainty.

The trial’s original statistical plan, sample-size justification, and interim-analysis arrangements are not reported in the registry record. The separate planning figures are illustrations based on the observed effect and stated planning assumptions, not evidence about what the original trial was designed to detect. They should not be confused with the observed group estimates or with the trial’s actual inferential analysis.

11. Confidence Intervals and Precision

The primary recalculated mean difference is 0.006 liters, and the reported interval extends to both negative and positive values. Because zero lies within that interval, the data are compatible with no difference as well as with differences in either direction under the unadjusted calculation. The interval’s width indicates that the posted comparison does not pin down a single precise value for the difference. The registry record does not state the confidence level associated with the interval, so it is described simply as the reported interval.

The primary least-squares means are based on 81.0 participants in the QVA149 group and 96.0 in the QAB149 plus NVA237 group. The group standard errors are reported in the registry record, but the recalculated comparison is based on posted summary statistics and is not the model-based uncertainty estimate from the specified mixed model. The record does not report the direct sponsor-model interval for the treatment contrast. That distinction limits the precision claims that can be made from these figures.

Precision is not the same as statistical significance or clinical importance. In general, a narrower interval gives a more precise estimate, while a wider interval leaves more uncertainty about the size and direction of a difference. Even a precise estimate would need to be interpreted against a clinically meaningful threshold; no such threshold is reported in the registry record. The primary interval crossing zero therefore should not be translated into proof of identical effects, nor should its endpoints be treated as a clinical boundary.

The secondary AUC comparisons also have reported intervals spanning zero. Their interpretation is further constrained because the record does not report a multiplicity adjustment or detailed analysis plan for those secondary results. The listed standard errors and recalculated intervals can describe sampling uncertainty under their respective calculations, but they do not address uncertainty caused by unreported analysis choices or missing-data handling.

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, not total participants and not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect used in each illustration is the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column means the illustrated number of participants per arm for a design with an 80% chance of detecting the chosen effect under those assumptions, if the effect and assumptions used for planning were true. The 90% power column has the same interpretation for a 90% chance. These are planning concepts, not guarantees for a future study; actual performance depends on whether the assumptions match the study conditions. This is not observed power.

The rows consider planning for 100%, 75%, and 50% of the observed effect. As the assumed effect becomes smaller, more participants per arm are needed to distinguish it from random variation under the same assumptions. For the primary comparison, the illustrative requirements rise across those smaller-effect scenarios: for 100% of the observed effect, the figures are 13,566 per arm for 80% power and 18,161 per arm for 90% power; for 75%, they are 24,117 and 32,285; and for 50%, they are 54,262 and 72,642. These figures are illustrations derived from the observed effect, not the design target or observed power of this completed study. The sample-size calculations for secondary outcomes are separate illustrations and should be read using their own effect estimates.

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 = 0.006; pooled standard deviation σ = 0.176.
2. n = 2 × (1.96 + 0.842)² × 0.176² / 0.006² = 13,565.4, rounded up to 13,566 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 <- 0.00600000000000001                      # observed difference in means
sigma <- 0.176380057181725                     # 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(1529632)
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 = 13,566 (80% power), 18,161 (90% power)
 75% of observed effect: n per arm = 24,117 (80% power), 32,285 (90% power)
 50% of observed effect: n per arm = 54,262 (80% power), 72,642 (90% power)
power.t.test: 13566.4 
Simulated power at n = 13,566 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. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes in addition to the primary endpoint, but it does not report a multiplicity adjustment or a hierarchy for testing them. Multiplicity matters because the more outcomes or comparisons assessed, the greater the opportunity for chance findings when each is interpreted separately. This is a general statistical concern, not evidence that any particular posted result is false. The recalculated p-values are unadjusted and should be interpreted accordingly.

The record also does not report the original sample-size justification, prespecified statistical analysis plan, interim analyses, or a stated confidence level for the posted intervals. It describes the mixed-model terms for the primary endpoint but does not provide model diagnostics, sensitivity analyses, or the direct sponsor-model treatment contrast. The simple recalculated comparison is not a substitute for those details.

For the primary outcome, the analysis population is the Per Protocol Set, defined by availability of data and absence of major protocol deviations or criteria causing exclusion. The registry record does not give a participant flow showing how many people met each criterion, nor does it describe how missing primary measurements were handled. It lists outcome-specific numbers for the primary estimates, but those counts do not explain why other enrolled participants are not represented in the primary analysis.

The record says patients were analyzed according to randomized treatment. That statement describes treatment assignment for analysis, but it does not remove the consequences of excluding people from a Per Protocol analysis or resolve missing data. In general, exclusions based on events after randomization can affect how well an estimate preserves the balance created by randomization. Without further information about exclusions and missingness, the direction or size of any resulting influence cannot be determined from the registry record.

15. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.2%), bronchial carcinoma (1.9%), chronic obstructive pulmonary disease (1.1%), pneumothorax (1.1%), aortic aneurysm (1.1%).

For serious adverse events, the registry lists 4 affected participants among 90 at risk in the QVA149 group and 6 among 103 at risk in the QAB149 plus NVA237 group. For other adverse events, it lists 20 of 90 and 12 of 103, respectively. These are counts of participants with at least one event as presented in the record; they do not describe event severity beyond the serious versus other grouping, duration, or whether events were considered related to treatment.

The registry also lists serious-event terms and percentages, including pneumonia at 2.2%, bronchial carcinoma at 1.9%, chronic obstructive pulmonary disease at 1.1%, pneumothorax at 1.1%, aortic aneurysm at 1.1%, and pericarditis at 1.0%. These terms and percentages describe the posted safety record, not a causal comparison between treatments. Death counts are not reported in the registry record.

Safety denominators differ from the primary outcome analysis counts, so the event figures should not be combined with or substituted for the Per Protocol Set results. The record does not provide enough information to assess event timing, exposure-adjusted rates, or comparative risk with a specified statistical method.

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

The primary outcome compares model-based mean trough FEV1 estimates after 28 days of treatment. The posted means are close, and the unadjusted recalculated difference is small in the reported units. The interval includes zero, and the unadjusted p-value is 0.822. Together, these values describe a comparison that does not establish a clear difference in this recalculation, while leaving uncertainty about the size and direction of the underlying difference.

Not detecting a difference is not the same as demonstrating that two treatments are equivalent. Equivalence and non-inferiority conclusions require an appropriate prespecified margin and an analysis designed to evaluate that question. Neither a margin nor a direct sponsor-model contrast is reported in the registry record. The figures also do not establish whether any difference would be clinically meaningful, because a clinical interpretation threshold is not reported.

The primary endpoint represents trough lung function at the end of the dosing interval on Day 29. It does not, on its own, describe long-term outcomes or every aspect of COPD. The secondary AUC measures address FEV1 during the hours after dosing, and other listed secondary outcomes concern rescue medication and daytime symptoms. Numerical results for some listed outcomes are not reported in the registry record. The available secondary comparisons have unadjusted intervals spanning zero and should be read cautiously in the context of multiple outcomes.

The findings are specific to the trial’s population, treatments, 28-day regimen, outcome definitions, and analysis population. The primary estimates use the Per Protocol Set, not necessarily every enrolled participant. The record does not fully describe missing-data handling, participant flow, or the consequences of exclusions. Accordingly, these results should be understood as a statistical description of the posted measurements, not as individualized medical guidance or a recommendation about treatment.

17. Why This Trial Matters Statistically

This trial illustrates why the estimated group means alone are not enough to interpret a clinical comparison. The primary estimates are least-squares means from a specified mixed model, while the difference, interval, and p-value posted for comparison are simple unadjusted recalculations. Keeping those analysis types distinct prevents an unadjusted calculation from being mistaken for the trial’s model-based treatment test.

It also shows why a non-significant p-value should not be translated into proof of equality. The primary recalculated interval spans zero, but the registry record does not provide a prespecified equivalence or non-inferiority margin. The size and precision of an estimate must be considered alongside the question the trial was designed to answer; the original design assumptions are not reported.

The population definition is another important statistical feature. Although the study was randomized, the primary result is described for the Per Protocol Set, whose definition requires available data and excludes major protocol deviations or other specified criteria. Understanding that distinction requires information about participant flow and missing-data handling, which is not reported in the registry record.

Finally, the record lists several secondary outcomes, but the numerical results and multiplicity approach are incomplete. Unadjusted secondary findings can be useful descriptively, yet they carry less confirmatory weight when the overall testing strategy is not reported. The case therefore demonstrates the value of reading estimates, uncertainty, analysis population, and reporting completeness together rather than relying on a single p-value.

18. 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 principal limitation of the posted primary comparison is that the registry record describes a mixed model but does not report a direct sponsor-model treatment contrast, its interval, or its p-value. The recalculated comparison is unadjusted and based on posted summary statistics. It should not be interpreted as if it were the mixed-model result.

The primary analysis uses the Per Protocol Set, which excludes patients without available data and those with major protocol deviations or other exclusion criteria. The record does not provide participant flow, reasons for exclusions, or a detailed missing-data method. This limits assessment of how well the posted primary estimate represents all randomized participants.

The registry record does not report the original sample-size justification, original design assumptions, interim analyses, or a complete statistical analysis plan. The planning illustrations based on observed effects cannot fill those gaps. The record also does not state a clinical interpretation threshold, equivalence margin, non-inferiority margin, or confidence level for the posted intervals.

Several secondary outcomes are listed, but numerical results are not reported for all of them, and no multiplicity approach is described. Safety information is presented as participant counts and selected event terms; death counts are not reported in the registry record, and detailed timing or exposure-adjusted comparisons are not given. Finally, the treatment period is 28 days, so the posted measurements do not provide a direct description of longer-term outcomes.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD) — NCT01529632.
• Registry record last updated 2014-02-12; status last verified 2014-01.
• Results first posted 2014-02-12.
• 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.

22. Record Summary

NCT01529632 is a completed randomized, quadruple-masked, parallel-group phase 3 study of QVA149 versus QAB149 plus NVA237 in patients with moderate to severe COPD. The record lists 193 enrolled participants and a 28-day once-daily treatment period.

The primary endpoint was trough FEV1 on Day 29, reported as least-squares means in liters for the Per Protocol Set. The posted group estimates are 1.459 for QVA149 and 1.465 for QAB149 plus NVA237. The simple unadjusted recalculation gives a mean difference of 0.006 liters, with an interval spanning zero and an unadjusted p-value of 0.822. A direct sponsor-model comparison is not reported in the registry record.

The record lists several secondary outcomes, but numerical results are not reported for all listed outcomes. Its safety counts describe serious and other adverse events, while death counts are not reported in the registry record. The registry record also does not report the original sample-size justification, multiplicity plan, or detailed handling of missing primary data.