12-week Open-label Evaluation of Efficacy and Safety of Indacaterol: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 12-week Open-label Evaluation of Efficacy and Safety of Indacaterol (NCT01232894), a randomized phase 3 study. The primary outcome is Change From Baseline on Clinical COPD Questionnaire (CCQ) Score.

2. Clinical Question

In statistical terms, the question is whether the mean change in CCQ score differed between the randomized treatment groups over the stated follow-up. A complete answer would require the group-level changes, their variability, and an estimate of the between-group contrast with its precision. Those results are not reported in the registry record. The outcome description notes that the CCQ score was recalculated and that statistical significance remained the same, but it does not state the comparison’s estimate, test, or p-value. That statement alone does not show the magnitude or precision of the treatment-group contrast.

3. Trial Design

This was a phase 3, randomized, parallel-group, open-label study of treatment regimens that included indacaterol in patients with moderate to severe COPD. The registry record describes the study as multicenter and gives a 12-week duration. Enrollment was 90. The study status is recorded as completed.

Participants were randomized to either indacaterol or their current LABA bronchodilator therapy. The indacaterol regimen was 150 µg once daily through a single-dose dry powder inhaler. The comparator was not described as a common assigned product; it was participants’ existing LABA therapy. This distinction matters when interpreting the comparison: the record identifies the treatment strategy but does not name the individual comparator medicines or give details of their use.

The study was open-label, with no masking. Knowledge of assigned treatment can influence experiences, reporting, and assessment, particularly for outcomes that depend on participant responses. Randomization helps establish a comparison between assigned groups, but it does not remove every possible influence of open-label conduct.

The registered primary outcome was change from baseline in CCQ score, with baseline and 12 weeks specified as the timeframe. Efficacy and safety were assessed. The registry record lists one outcome measure and no analyses. It does not report the number randomized to each arm, the number contributing to the primary outcome by arm, or a numerical treatment effect. It also does not report details of the randomization procedure or a statistical analysis plan. These omissions limit how fully the conduct and analysis can be evaluated from the registry record alone.

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: Full analysis Set: all patients who received at least one dose of study drug and have evaluable data for analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline on Clinical COPD Questionnaire (CCQ) Score, measured over Baseline and 12 weeks.

The primary endpoint is change from baseline in the Clinical COPD Questionnaire (CCQ) score, expressed in units on a scale. The questionnaire is self-administered and contains ten questions covering symptoms, mental state, and functional state. Each question uses a 7-point scale, with 0 meaning no limitations and 6 meaning extreme or complete limitations. The final score is the mean of the responses to the ten questions.

A change score represents how the questionnaire score differs at follow-up from the participant’s baseline score. Comparing mean changes between randomized groups can describe whether the groups’ average reported COPD-related status changed differently during the study. The CCQ is used as a patient-reported measure spanning several aspects of the condition, rather than as a direct measurement of a single symptom or physiological function.

The registry record states that the CCQ score was recalculated according to a cited scoring approach and that statistical significance remained the same. It does not give baseline or follow-up means, mean changes, standard deviations, or a between-group estimate. The actual size and precision of the primary result therefore cannot be assessed from the record. The description also does not clarify how incomplete questionnaire responses were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change describe?

General statistical explanation. For a continuous measure such as CCQ score, a mean summarizes the average value in a group. A mean change summarizes the average within-person difference between a follow-up measurement and baseline. The mean change for each group describes its average trajectory, while the difference between group mean changes is the direct randomized comparison of interest. These are related but distinct quantities: observing change in one group alone does not establish how that change compares with the other group.

The registry record names the outcome as a mean and its dispersion as a standard deviation. A standard deviation describes how dispersed individual observations are around a group mean. It is not the same as a confidence interval: the standard deviation describes variability among observations, whereas a confidence interval describes uncertainty around an estimated quantity. The record does not report the outcome means, standard deviations, or confidence intervals, so none can be interpreted for this comparison.

Why is the between-group estimate important?

General statistical explanation. A treatment effect is commonly expressed as a contrast between groups, such as the difference in their mean changes. That contrast focuses on the randomized comparison rather than treating each group’s change as separate evidence. Its confidence interval communicates precision: a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. A p-value, when reported, addresses compatibility with a specified null hypothesis under the analysis assumptions. Neither a p-value nor statistical significance alone describes the size or practical importance of an effect.

For this trial, the registry record does not give the contrast, interval, or p-value. Its statement that statistical significance remained the same after the CCQ score was recalculated does not reveal any of those quantities. It also does not identify the original test or the analysis assumptions, so the statement cannot support a fuller reconstruction of the statistical result.

What does randomization contribute?

General statistical explanation. Random assignment is intended to make treatment groups comparable on average at the start of a study, including on factors that may not have been measured. It does not ensure identical group characteristics in a particular trial, and it does not remove the need to examine follow-up completeness and analysis choices. In this study, treatment allocation was randomized, but details of the sequence generation, concealment, and any stratification are not reported in the registry record.

The parallel-group design means each participant was assigned to a treatment group and the groups were compared over the study period. The record identifies the comparator as participants’ current LABA therapy. Because the specific medicines and regimens are not named, the comparison is between the indacaterol strategy and the existing-therapy strategy as described, not a clearly specified single comparator product.

How should the reported significance statement be read?

General statistical explanation. Statistical significance is a decision under a chosen analysis and threshold; it is not a measure of effect size, clinical importance, or certainty that a finding will recur. A result can be statistically significant while estimated imprecisely or be small in magnitude, and a result that does not meet a significance threshold can still be compatible with effects that matter. Interpretation therefore normally considers the estimate, its uncertainty, the analysis population, and the study context together.

The registry record does not report the threshold used for the primary comparison, its statistical test, or the estimated effect. The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. These are planning assumptions, not evidence of observed power, and the record does not give numerical planning results in the registry record for this analysis. The trial’s own sample-size justification is not reported in the registry record.

Why can variability and over-dispersion matter?

General statistical explanation. For continuous outcomes, variability affects the precision of a group mean and of a between-group contrast. Greater variability generally makes it harder to estimate a mean difference precisely when other aspects of the design are held constant. Over-dispersion is more often discussed for count outcomes: it means the observed variability exceeds what a basic model assumes. If ignored, uncertainty can be understated. The registered primary outcome is continuous, and the record does not identify an over-dispersion issue or a model used to address one.

Repeated measurement also raises analytic choices. A comparison might use change scores or model follow-up values while accounting for baseline values; the registry record does not say which approach was used. It does not describe how correlations between baseline and follow-up measurements were handled, or whether any covariates were included. No particular method should be inferred from the outcome description alone.

What can the safety counts establish?

General statistical explanation. Safety counts show how many participants in the reported at-risk groups were recorded as affected by an event category. Such counts can identify events observed during a trial, but they do not by themselves establish that treatment caused an event or provide a complete comparison of safety. Interpretation also depends on how events were defined, collected, coded, and followed over time. The registry record gives counts for serious and other adverse events, but those additional details are not reported in the registry record.

The record lists no analyses. It does not report an analysis plan, handling of missing data, multiplicity procedures, or whether the safety summaries were prespecified. These absences mean that the statistical methods cannot be independently reconstructed from the record. The numerical information should therefore be read as a partial registry account rather than a full statistical report.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no analyses. It does not report whether the primary outcome involved multiple statistical comparisons, whether additional outcomes were planned, or whether any multiplicity adjustment was used. Multiplicity is a general concern when many hypotheses are tested: the chance of at least one apparently unusual result can increase as the number of tests grows. Whether that issue applies, and how it was addressed, is not reported in the registry record.

The registered primary outcome specifies baseline and 12 weeks, and the study duration is 12 weeks. The record does not give separate outcome results by time point or describe any additional timing of CCQ assessments. It states that the primary outcome has several categories or time points and was not reduced to one comparison. Accordingly, there is no single numerical comparison available to interpret from the listed outcome details.

The analysis population is described as patients who received at least one dose and had evaluable data. This definition indicates that inclusion in the primary analysis depended on treatment exposure and evaluable outcome data. The number included by arm, the number excluded from that analysis, and reasons for missing or unevaluable data are not reported in the registry record. The approach to missing questionnaire items and missing follow-up measurements is also not reported.

It is therefore not possible to determine from the registry record whether the primary comparison followed an intention-to-treat approach, how missing data were handled, or whether sensitivity analyses assessed the impact of missingness. These omissions matter because estimates can depend on who contributes data and how incomplete observations are treated. They should be considered uncertainties in the available record, not evidence that any particular method was or was not used.

11. 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: cardiac failure congestive (1.7%), pericarditis (1.7%), ventricular fibrillation (1.7%), sinusitis (1.7%), brain stem haemorrhage (1.7%).

The registry record reports serious adverse events for the indacaterol group as 3 affected among 59 at risk, and for the long-acting beta2-agonist group as 0 affected among 28 at risk. For other adverse events, it reports 9 affected among 59 at risk in the indacaterol group and 4 among 28 at risk in the LABA group. These are counts in the reported groups; they should not be converted into a claim about causation.

The serious adverse-event terms listed include cardiac failure congestive, pericarditis, ventricular fibrillation, sinusitis, brain stem haemorrhage, and dizziness, each reported at 1.7%. The registry entries do not specify which group each term belongs to, or whether any participant could contribute to more than one term. These term percentages should therefore be read as registry listings, not as a basis for reconstructing group-specific risks.

Deaths are not reported in the registry record. The record also does not describe event definitions, follow-up rules, or statistical comparisons for safety. The counts are useful descriptive information, but they do not by themselves establish comparative risk or rule out uncommon harms.

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

The record supports a description of what the trial set out to compare: indacaterol 150 µg once daily versus participants’ current LABA therapy, with change in CCQ score from baseline to 12 weeks as the registered primary outcome. It also documents the broad study design and reports serious and other adverse-event counts. Those details clarify the clinical and statistical question being asked.

The record does not provide the arm-level CCQ results or a numerical estimate of the difference between groups. As a result, it cannot establish from the available figures whether the average score changed more in one group, how large any difference was, or how precisely it was estimated. The statement that statistical significance remained the same after score recalculation does not supply the missing effect estimate or uncertainty interval.

This limitation is distinct from evidence that there was no effect. Without the results, neither the presence nor absence of a difference can be concluded from the registry record. Nor does the completed status imply a particular efficacy finding. The reported safety counts describe events recorded in the study, but do not establish whether treatment caused them or provide a definitive comparative safety assessment.

General interpretation of a randomized trial normally weighs the estimated treatment contrast, its precision, the analysis population, missing data, and the design together. Here, the primary numerical comparison and many analysis details are not reported in the registry record. The appropriate reading is therefore bounded: the registry record describes the question and some observed safety data, but does not permit a quantitative conclusion about the primary CCQ comparison.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a clearly defined endpoint and a reportable treatment effect. The CCQ outcome is described in detail, including its domains, response scale, scoring, and assessment timeframe. Yet without arm-level values and a between-group estimate, readers cannot evaluate the size or precision of the comparison. Endpoint detail alone is not enough to interpret an efficacy result.

The design also illustrates why the comparator must be understood as a treatment strategy. Indacaterol was compared with participants’ current LABA therapy, rather than a single named comparator regimen. That reflects the registered question, but leaves the exact comparator treatment composition unspecified in the registry record. Statistical interpretation depends on identifying what the groups actually represent.

The open-label design is relevant because the primary endpoint is self-administered. General statistical reasoning recognizes that knowledge of treatment assignment can affect participant-reported outcomes. Randomization supports a fair group comparison, while masking and consistent outcome assessment can address other potential influences; masking was not used in this study.

Finally, the record makes clear that safety counts and efficacy results are different forms of evidence. Serious and other adverse-event counts are reported, but the primary efficacy comparison is not numerically available. Keeping those evidentiary limits separate is central to reading a trial record carefully: documented design features and event counts should not be mistaken for a complete report of treatment effects.

14. 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 most important trial-specific limitation for statistical interpretation is that the registry record does not report the numerical primary outcome results. There are no group-level CCQ changes, standard deviations, treatment contrast, confidence interval, or p-value in the record details. The statement about unchanged statistical significance after score recalculation does not resolve this gap.

The study was open-label, and the primary endpoint was based on a self-administered questionnaire. Participants’ awareness of treatment assignment may influence reported symptoms, mental state, or functional state. The record does not report procedures intended to reduce such influence or details about how questionnaires were collected.

The comparator is described as participants’ current LABA therapy, without naming the specific medicines or describing a common regimen. This limits the ability to characterize the control strategy more precisely. The record also gives no arm-level count for the primary analysis population, although it defines that population by receipt of at least one dose and evaluable data.

Details needed to assess the analysis are not reported in the registry record: the statistical model or test, covariate adjustment, handling of missing data, and multiplicity procedures. Safety interpretation is also limited by the absence of event definitions and group assignment for the listed serious adverse-event terms. These limitations concern the information available in the registry record; they do not establish what methods were used outside the reported record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: 12-week Open-label Evaluation of Efficacy and Safety of Indacaterol — NCT01232894.
• Registry record last updated 2013-11-19; status last verified 2013-11.
• Results first posted 2013-11-19.
• 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.

18. Record Summary

NCT01232894 is a completed phase 3, randomized, parallel-group, open-label, multicenter study in patients with moderate to severe COPD. Enrollment was 90, and the study duration was 12 weeks. The study compared indacaterol 150 µg once daily by single-dose dry powder inhaler with participants’ current LABA therapy.

The primary outcome was change from baseline in CCQ score at 12 weeks. Its description defines the questionnaire and scoring, but arm-level outcome results and a numerical comparison are not reported in the registry record. The outcome population is described as patients who received at least one dose and had evaluable data.

Serious and other adverse-event counts are reported by group; deaths are not reported in the registry record. No analyses are listed, and statistical methods, missing-data handling, and multiplicity procedures are not reported in the registry record. The available information establishes the study question and design, but does not allow quantitative interpretation of the primary efficacy comparison.