Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) (NCT00794157), a randomized phase 3 study. The primary outcome is Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85).

2. Clinical Question

The study was designed to provide confirmatory efficacy and safety information for both doses. The registry record states that its data would be used for registration of indacaterol in Japan. The posted primary results are adjusted least-squares means for each group and unadjusted comparisons against placebo. The comparisons show the estimated mean differences and confidence intervals, allowing the size and precision of the observed differences to be considered alongside the statistical tests.

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group, placebo-controlled study sponsored by Novartis Pharmaceuticals. Its official title describes a 12-week, multicenter study. The registry record lists the study start as 2008-11, primary completion as 2009-10, and status as completed. Enrollment was 347.

The three assigned groups received indacaterol 150 μg, indacaterol 300 μg, or placebo. Each was administered once daily in the morning through a single dose dry powder inhaler. The arm descriptions specify that daily inhaled corticosteroid treatment, if applicable, was to remain stable. Salbutamol/albuterol was available, but the arm-description text is truncated, so its complete use instructions are not reported in the registry record.

The primary outcome was trough FEV1 in liters, assessed at the end of treatment at Week 12 + 1 Day (Day 85). The group results are least-squares means with standard errors. The primary population is described as the intent-to-treat population, defined in the record as all randomized patients who received at least 1 dose of study drug. The record also states that last observation carried forward was used for imputation.

The record reports secondary trough FEV1 outcomes at Week 2, Week 4, Week 8, and Week 12 (Day 84). Although the study title identifies a 12-week treatment period, the primary measurement is specified at the subsequent day. Details such as the randomization sequence, allocation concealment, the roles covered by quadruple masking, and the original sample-size rationale 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 randomized patients who received at least 1 dose of study drug. The imputation technique used as last observation carried forward (LOCF).

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) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85), measured over End of treatment (Week 12 + 1 day, Day 85).

Forced expiratory volume in 1 second (FEV1) is the volume of air a person can forcefully exhale during the first second of a breathing test. It is a continuous measure, recorded in liters. The endpoint is useful for comparing average lung-function measurements between assigned groups while retaining information about the scale of the measurement.

The primary measure was trough FEV1 at the end of treatment, specified as Week 12 + 1 Day (Day 85). Trough FEV1 was defined as the average of measurements taken 23 hours 10 minutes and 23 hours 45 minutes after dosing. Measuring near the end of the daily dosing interval focuses on lung function before the next scheduled dose rather than shortly after administration. The record says spirometry followed internationally accepted standards.

The reported group values are least-squares means, rather than unadjusted raw averages. The analysis description lists baseline FEV1 and screening measurements taken before and after salbutamol and ipratropium as covariates. Adjustment for these measurements estimates group means conditional on the specified covariates. Standard errors describe uncertainty around each estimated group mean; they are not standard deviations describing variation among individual measurements.

The endpoint measures lung function, not symptoms, daily functioning, exacerbations, or quality of life. Those outcomes should not be inferred from the FEV1 result. The registry record does not report a threshold for a clinically important difference, so statistical evidence about a difference does not by itself establish its clinical importance.

7. Results Posted in the Registry

• Indacaterol 150 μg: mean 1.34 versus 1.17 on control; difference 0.17 (95% CI 0.10 to 0.24), standardized effect d = 0.67; z-test p = <0.001.
• Indacaterol 300 μg: mean 1.37 versus 1.17 on control; difference 0.20 (95% CI 0.13 to 0.27), standardized effect d = 0.81; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2

• 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:
  • Indacaterol 150 μg: mean 1.33 versus 1.17 on control; difference 0.16 (95% CI 0.09 to 0.23), standardized effect d = 0.73; z-test p = <0.001.
  • Indacaterol 300 μg: mean 1.34 versus 1.17 on control; difference 0.17 (95% CI 0.10 to 0.24), standardized effect d = 0.79; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Indacaterol 150 μg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Indacaterol 300 μg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4

• 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:
  • Indacaterol 150 μg: mean 1.32 versus 1.18 on control; difference 0.14 (95% CI 0.07 to 0.21), standardized effect d = 0.65; z-test p = <0.001.
  • Indacaterol 300 μg: mean 1.33 versus 1.18 on control; difference 0.15 (95% CI 0.09 to 0.21), standardized effect d = 0.72; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Indacaterol 150 μg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Indacaterol 300 μg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8

• 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:
  • Indacaterol 150 μg: mean 1.30 versus 1.14 on control; difference 0.16 (95% CI 0.08 to 0.24), standardized effect d = 0.62; z-test p = <0.001.
  • Indacaterol 300 μg: mean 1.32 versus 1.14 on control; difference 0.18 (95% CI 0.10 to 0.26), standardized effect d = 0.73; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Indacaterol 150 μg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Indacaterol 300 μg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes measure trough FEV1 at Week 2, Week 4, Week 8, and Week 12 (Day 84). Across these assessments, the group estimates follow the same broad direction as the primary endpoint: both indacaterol groups have higher reported least-squares mean FEV1 than placebo. The unadjusted comparisons at these time points also report p-values of <0.001. This overall pattern is consistent with the primary end-of-treatment result, rather than pointing to a reversal in direction at the reported secondary assessments.

The secondary outcomes add information about measurements taken at different points in the treatment period, but they do not replace the primary comparison. Multiple time points and dose comparisons create opportunities for chance findings when each is considered separately. Because the registry record does not report a multiplicity adjustment, the secondary p-values should be treated as exploratory or supportive rather than as independent confirmation with the same evidential weight as the primary endpoint.

Availability also varies across the secondary assessments, and the posted group counts differ by time point. That means the set of participants contributing measurements may not be identical across outcomes. The record does not explain the pattern of unavailable measurements or give a missing-data analysis specific to the secondary outcomes. Consequently, apparent consistency across time points should be interpreted alongside possible changes in the analyzed data.

The secondary endpoint summaries are unadjusted re-calculations from posted group statistics, and their standard deviations are approximate. The registry record lists the outcome time points but does not provide separate reported analyses for them. The estimates can describe the observed pattern in trough FEV1, but they do not establish effects on outcomes that were not measured or reported in these summaries.

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

• Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2
• Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4
• Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8
• Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 (Day 84)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a least-squares mean represent?

A least-squares mean is an estimated group mean from a statistical model. Unlike a simple average, it accounts for covariates included in that model. The primary analysis description lists baseline FEV1, screening FEV1 before and after salbutamol, and screening FEV1 before and after ipratropium as covariates. This adjustment can help compare groups on a common modeled basis, but its interpretation depends on the model and the data available for the included measurements. Full model details beyond the listed covariates are not reported in the registry record.

The posted least-squares means are 1.34 liters for the 150 μg group, 1.37 liters for the 300 μg group, and 1.17 liters for placebo. Their standard errors are 0.024, 0.023, and 0.025, respectively. A standard error describes the estimated precision of a group mean, not the spread of individual participant values. It generally becomes smaller when an estimate is more precise, which can reflect both the amount of information and the variability in the data.

What does a mean difference tell the reader?

A mean difference expresses how far apart two group means are on the endpoint's original measurement scale. The primary comparisons are against placebo. The estimated difference is 0.17 liters for indacaterol 150 μg and 0.2 liters for indacaterol 300 μg. The sign and size describe the direction and magnitude of the estimated contrast; the associated interval communicates uncertainty about that estimate.

The comparisons are unadjusted re-calculations from the posted summary statistics. Their standard deviations are approximated from the group standard errors, and the record does not report a separate adjusted pairwise analysis. Such re-calculations are useful for an interpretable contrast, but they do not reproduce every feature of the trial's full statistical model.

How should the p-values be read?

Each primary unadjusted comparison has a p-value of <0.001. A p-value evaluates the compatibility of the observed data with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not quantify the probability that an observed difference is due to chance. It also does not indicate whether a difference is clinically meaningful. The p-values reported for these comparisons are unadjusted, so they do not account for the possible multiplicity arising from testing several doses and outcomes.

In general, an unadjusted test evaluates a comparison without correcting its significance threshold or p-value for other tests in a family of analyses. When many outcomes or contrasts are examined, the chance of finding at least one apparently small p-value can increase. The registry record does not report a multiplicity procedure for the posted results. This is one reason the primary endpoint is more central to interpretation than a collection of secondary comparisons.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the observed data under the calculation's assumptions and procedure. In repeated use, a confidence-interval method with a stated confidence level has a long-run coverage property: intervals constructed in that way contain the true parameter at the stated rate. An individual interval should not be read as a probability statement that the true effect lies within its endpoints.

For the primary comparisons, the interval for the 150 μg contrast extends from 0.102 to 0.238 liters, and the interval for the 300 μg contrast extends from 0.133 to 0.267 liters. Both intervals are above zero. Their widths also show that the effects are estimated with uncertainty, rather than known exactly. The displayed intervals are based on the unadjusted summary-statistic calculations, not on a reported adjusted pairwise model.

Why does the analysis population matter?

The record defines the intent-to-treat population as all randomized patients who received at least 1 dose of study drug. This definition retains participants according to their randomized assignment after meeting the stated dose condition, rather than restricting analysis only to people who completed treatment. The record states that last observation carried forward was used for imputation. This method fills a missing later value using an earlier observed value; it assumes that the carried-forward value is an adequate substitute for the unavailable value. Depending on why measurements are missing and how outcomes change over time, that assumption may be weak. The registry record does not report the amount or pattern of missing primary outcome data, or sensitivity analyses assessing the imputation assumption.

In general, the validity of a clinical-trial comparison depends not only on the statistical test but also on randomization, outcome measurement, missing-data handling, adherence to the analysis plan, and transparent reporting. Some of those details are not reported in the registry record. The posted results are therefore best read as estimates from the specified population and analysis, with the noted limits on the available methodological detail.

11. Confidence Intervals and Precision

The 95% confidence interval for the unadjusted mean difference between indacaterol 150 μg and placebo is 0.102 to 0.238 liters. For indacaterol 300 μg versus placebo, it is 0.133 to 0.267 liters. Both intervals are entirely above zero, matching the direction of the estimated contrasts and the reported unadjusted p-values of <0.001.

Confidence intervals are useful because they show a range of estimates compatible with the data and the calculation's assumptions, rather than presenting a point estimate alone. In general, a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The interval does not express the full range of possible individual responses, and it does not establish whether an effect meets a threshold of clinical importance.

These intervals accompany unadjusted comparisons recalculated from the posted summary statistics. Their pooled variability estimates are approximate, derived from the reported group standard errors. They are not reported adjusted pairwise intervals from the covariate model used to produce the least-squares means. The registry record does not report the sponsor's confidence intervals for adjusted contrasts or the exact model-based uncertainty for those contrasts.

The intervals should also be interpreted in the context of the analysis population and last-observation-carried-forward imputation. The record does not report the extent or reasons for missing primary outcome measurements, which limits assessment of how missingness may affect precision and potential bias. The confidence intervals describe statistical uncertainty under the calculation; they do not account for every limitation in study conduct or reporting.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm for 80% power and participants per arm for 90% power. They are not total sample sizes. The planning illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses a target effect equal to the stated fraction of the observed effect. For continuous outcomes, the figures are participants per arm; the note about total events applies to time-to-event calculations, not these FEV1 comparisons.

For each comparison, the planning rows consider 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The 80% power column gives the modeled number of participants per arm for an 80% chance of rejecting the null hypothesis if the assumed effect and other planning assumptions hold. The 90% power column gives the corresponding planning number for a 90% chance under those assumptions. These are design-planning quantities, not guarantees about a future study.

For example, planning for 75% of the observed effect in the primary 150 μg comparison gives 62 participants per arm for 80% power and 83 participants per arm for 90% power. In the primary 300 μg comparison, the corresponding figures are 43 and 58 participants per arm. These illustrations vary by comparison because they are anchored to the observed effects and variability estimates.

Smaller effects are harder to distinguish from random variation, so the planning illustration requires more participants per arm as the assumed effect gets smaller. These figures are based on the observed results and stated assumptions, not on the trial's original design rationale. The original design assumptions are not reported in the registry record. This is not observed power: it is a planning illustration, not a retrospective measure of whether the completed trial had adequate power.

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 = 0.170; pooled standard deviation σ = 0.253.
2. n = 2 × (1.96 + 0.842)² × 0.253² / 0.170² = 34.7, rounded up to 35 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 <- 0.17                      # observed difference in means
sigma <- 0.252716726941114                     # 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(794157)
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 = 35 (80% power), 47 (90% power)
 75% of observed effect: n per arm = 62 (80% power), 83 (90% power)
 50% of observed effect: n per arm = 139 (80% power), 186 (90% power)
power.t.test: 35.7 
Simulated power at n = 35 per arm: 0.793 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The trial includes a primary endpoint, two dose comparisons against placebo, and secondary FEV1 assessments at several time points. Testing multiple comparisons can increase the chance of at least one apparently strong result even when no adjustment is made. The posted comparison p-values are unadjusted. A multiplicity-control strategy, such as a prespecified hierarchy or another adjustment, is not reported in the registry record. The original statistical analysis plan and its handling of multiple outcomes are also not reported in the registry record.

The primary endpoint should therefore remain the main focus when interpreting the efficacy results. Secondary outcomes may support the overall pattern, but their unadjusted p-values should not be treated as if each were the sole confirmatory test. The record does not report whether any interim analyses were planned or conducted, so that information is not reported in the registry record.

The primary analysis population is described as the intent-to-treat population, consisting of all randomized patients who received at least 1 dose of study drug. The registry record says last observation carried forward was used for imputation. This approach uses a participant's earlier observation as a substitute for an unavailable later measurement. In general, such an assumption can be problematic if the outcome would have changed after the last observation or if missingness is related to outcome or treatment.

The number and reasons for missing primary endpoint observations, the timing of missingness, and sensitivity analyses are not reported in the registry record. The registry record also does not provide a detailed account of protocol deviations, adherence, or how such cases were handled. These omissions make it difficult to assess the robustness of the estimates to alternative missing-data assumptions. They do not by themselves establish that the analysis is biased; they identify questions that cannot be resolved from the registry information.

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 5% 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 (1.8%), upper respiratory tract infection (0.9%), osteonecrosis (0.9%), bladder cancer (0.9%), thrombocytopenia (0.9%).

The registry record reports serious adverse events for groups with 114 participants at risk in the indacaterol 150 μg group, 116 in the indacaterol 300 μg group, and 117 in the placebo group. The corresponding counts affected were 4, 2, and 6. These are counts, not estimates of treatment effect, and the record does not provide a comparative statistical analysis for them.

The listed serious-event terms include chronic obstructive pulmonary disease at 1.8%, and upper respiratory tract infection, osteonecrosis, bladder cancer, thrombocytopenia, and pneumonia at 0.9% each. The registry record does not give enough detail in the listed terms to determine how events were distributed across treatment groups. Death counts are not reported in the registry record.

Other adverse events are listed for 24 participants in the 150 μg group, 26 in the 300 μg group, and 26 in the placebo group, with 114, 116, and 117 at risk, respectively. These figures should be read as descriptive registry summaries. Without event definitions, timing, severity details, exposure information, and a comparative analysis, they do not establish whether observed differences are related to treatment.

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

The posted primary outcome results show higher estimated average trough FEV1 at the end of treatment in both indacaterol groups than in the placebo group. The unadjusted mean differences are 0.17 liters for 150 μg and 0.2 liters for 300 μg, and both reported unadjusted p-values are <0.001. The confidence intervals for both contrasts are above zero. These findings describe the estimated group differences in the posted summaries and the uncertainty represented by their intervals.

They do not mean that every participant experienced an increase, nor do group averages predict an individual participant's response. They also do not establish how the measured difference translates into symptoms, daily activity, exacerbation risk, or quality of life. Those interpretations require relevant outcomes and clinical context, and the registry record does not state a threshold for a clinically important FEV1 difference.

The comparison is between randomized groups, but the displayed contrasts are unadjusted re-calculations based on the posted summary statistics. The group means themselves are least-squares means from a covariate-adjusted analysis. The record does not include a full report of adjusted pairwise analyses, the complete statistical analysis plan, or all details needed to assess missingness and multiplicity. The primary analysis used last observation carried forward, an assumption that may affect the estimates if unavailable values differ from the carried-forward observations.

The safety summaries also require caution. Serious adverse event counts are reported, but the registry information does not provide a comparative statistical assessment or enough detail to attribute events to treatment. No death counts are reported in the registry record. Efficacy and safety should be considered separately; the FEV1 result alone cannot establish an overall balance of benefits and harms.

Overall, the posted data support a statistical difference in average trough FEV1 in the two indacaterol comparisons, under the reported analysis and the assumptions used for the re-calculated contrasts. The degree of clinical importance and the broader benefit-harm interpretation are not determined by these results alone.

17. Why This Trial Matters Statistically

This trial is statistically informative because it compares two active dose groups with placebo in a randomized, masked, parallel-group design and reports a continuous physiological endpoint at a defined end-of-treatment assessment. A continuous outcome such as FEV1 retains information about the scale of measured differences, and the reported group means, standard errors, comparisons, and confidence intervals allow readers to consider both the estimated contrast and its uncertainty.

The primary results also illustrate why different statistical summaries answer different questions. Least-squares means describe model-adjusted group estimates; mean differences express the contrast on the original liters scale; p-values address compatibility with a null hypothesis; and confidence intervals show a range of estimates compatible with the calculation. None of these alone indicates clinical importance. The record does not provide a clinical-importance threshold for the endpoint.

The secondary time-point results offer a view of whether the direction of the FEV1 estimates is broadly consistent during treatment. Their evidential role is limited by multiple comparisons, unadjusted testing, and incomplete reporting of missing-data details. Sample-size illustrations can also help show how planning requirements depend on the effect a future study aims to detect, but they are not the original rationale for this trial and are not observed power.

Finally, the registry record demonstrates the value of distinguishing trial-reported analyses from summary-statistic re-calculations. The primary group estimates are reported as least-squares means, while the pairwise comparisons are unadjusted re-calculations using approximate pooled variability. Keeping that distinction visible helps prevent a useful secondary calculation from being mistaken for the sponsor's full model-based analysis.

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 registry record does not report the original sample-size justification, randomization sequence generation, allocation concealment, or which parties were covered by quadruple masking. It identifies a 12-week study and a primary assessment at Week 12 + 1 Day (Day 85), but it does not provide a detailed account of visit windows or the handling of deviations from the planned assessment schedule.

The posted primary means are least-squares means, but full model specifications beyond the listed covariates are not reported. The pairwise estimates and confidence intervals are unadjusted re-calculations from posted summary statistics, using approximate pooled variability. They are not substitutes for adjusted comparisons from a complete model output. Multiplicity adjustment for dose comparisons and secondary time points is not reported.

The primary analysis used last observation carried forward. The amount and reasons for missing data, and sensitivity analyses using alternative assumptions, are not reported in the registry record. Secondary assessment group counts differ across time points, but the record does not explain the pattern of missing measurements. This limits assessment of whether the observed time-course pattern is influenced by changes in the available data.

The posted safety information is descriptive and does not include a comparative analysis or full detail on timing, severity, exposure, or event attribution. Death counts are not reported in the registry record. The record also does not provide a clinical-importance threshold for FEV1, limiting interpretation of the practical relevance of the numerical differences. These reporting limits constrain what can be concluded from the registry summaries; they do not establish that the study's underlying analyses were inadequate.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Confirmatory Study of Indacaterol in Patients With Chronic Obstructive Pulmonary Disease (COPD) — NCT00794157.
• Registry record last updated 2011-08-17; status last verified 2011-07.
• Results first posted 2011-08-17.
• 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

The registry record describes a completed, randomized, quadruple-masked, parallel-group, placebo-controlled Phase 3 study sponsored by Novartis Pharmaceuticals. Enrollment was 347. The study evaluated once-daily indacaterol 150 μg and 300 μg against placebo in patients with COPD.

The primary endpoint was trough FEV1 in liters at Week 12 + 1 Day (Day 85), reported as least-squares means with standard errors. The primary population was defined as randomized patients who received at least 1 dose, with last observation carried forward used for imputation. Secondary trough FEV1 outcomes were listed at Week 2, Week 4, Week 8, and Week 12 (Day 84).

The posted primary estimates were higher in both indacaterol groups than placebo, with unadjusted comparisons and confidence intervals above zero. The comparisons are re-calculations from summary statistics, and their pooled variability estimates are approximate. Details on multiplicity handling, missing-data patterns, and the original design assumptions are not reported in the registry record.