Safety of Indacaterol in Patients (≥ 12 Years) With Moderate to Severe Persistent Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety of Indacaterol in Patients (≥ 12 Years) With Moderate to Severe Persistent Asthma (NCT00529529), a randomized phase 3 study. The primary outcome is Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study.

2. Clinical Question

The clinical question is primarily about safety, not whether the treatments improve asthma symptoms or prevent exacerbations. The primary endpoint counts participants with at least one adverse event; it does not count the total number of events each participant experienced. Asthma exacerbations were included among adverse events, but the registry record defines an exacerbation specifically as clinically significant worsening judged by the physician and requiring rescue oral or intravenous corticosteroids.

The comparison is between each indacaterol dose and the active-control group. The posted endpoint results describe the share of participants with an adverse event in each group and unadjusted comparisons of those shares. The study also posted secondary results for trough forced expiratory volume in 1 second (FEV1) at a specified follow-up and the number of asthma exacerbations per patient. Those outcomes add context but do not change the safety focus of the primary question.

The trial record identifies 805 participants enrolled and describes a randomized, parallel-group study. The primary endpoint population is based on treatment received, rather than enrollment alone. This distinction matters when interpreting the group counts: the primary analysis concerns participants who took at least one dose of study drug.

3. Trial Design

The registry record describes a completed phase 3, randomized, multicenter, double-blind, double-dummy, parallel-group study. Its stated purpose was to assess the safety of indacaterol 300 μg and 600 μg once daily compared with salmeterol 50 μg twice daily in patients with moderate to severe persistent asthma. The planned treatment period was 26 weeks. The study enrolled 805 participants.

Three treatment groups appear in the posted primary results: indacaterol 300 μg, indacaterol 600 μg, and salmeterol 50 μg. The arm descriptions identify once-daily morning administration for indacaterol and twice-daily administration for salmeterol. The double-dummy design included placebo inhalations alongside the active study treatments. This design is intended to help maintain masking when treatment regimens differ, although details of the masking procedures are not reported in the registry record.

The primary endpoint is a safety outcome measured from baseline (Day 1) to the end of the study (Week 26). The registry record defines the safety population as all participants who received at least one dose of study drug. The group counts for the primary endpoint are 268 for indacaterol 300 μg, 268 for indacaterol 600 μg, and 269 for salmeterol 50 μg.

The record lists a study start of 2007-09 and a primary completion of 2008-08. These dates describe the study record and do not establish when any particular analysis was conducted. The registry record does not report the original sample-size justification, specific randomization procedures, planned interim analyses, or the detailed statistical analysis plan. It also does not report the number of participants assigned to each group before accounting for the safety-population definition.

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: Safety population: All patients who received at least one dose of study drug.

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 Percentage of Patients With at Least 1 Adverse Event During the 26 Weeks of the Study, measured over Baseline (Day 1) to end of study (Week 26).

The primary endpoint is the percentage of patients with at least one adverse event during the study, from baseline (Day 1) to the end of study (Week 26). It is a participant-level measure: a participant is counted if they experienced at least one event during that period, regardless of whether they experienced additional events. The endpoint therefore describes how common it was for participants to experience any recorded adverse event, not the total event burden or severity for each participant.

The registry record states that adverse events include asthma exacerbations. It defines an asthma exacerbation as worsening of asthma judged clinically significant by the physician and requiring treatment with rescue oral or intravenous corticosteroids. Worsening treated only with inhaled or nebulized short-acting β2-agonists, or only with an increase in inhaled corticosteroids, was not considered an asthma exacerbation under this definition.

A participant-level adverse-event endpoint is used to describe safety experience during treatment. It allows the observed proportions in the randomized groups to be compared, but it combines different kinds of events and does not, by itself, indicate their seriousness, duration, or relationship to study treatment. Those details require separate event information and clinical interpretation. The endpoint also does not measure asthma control or lung function directly; the registry record lists those as separate secondary outcomes.

7. Results Posted in the Registry

• Indacaterol 600 μg: 66.4% (178/268) versus 54.9% (147/268) on control; risk difference 11.6 percentage points (95% CI 3.4 to 19.8), risk ratio 1.21 (1.05–1.39); unadjusted two-proportion z-test p = 0.006.
• Salmeterol 50 μg: 67.3% (181/269) versus 54.9% (147/268) on control; risk difference 12.4 percentage points (95% CI 4.3 to 20.6), risk ratio 1.23 (1.07–1.41); unadjusted two-proportion z-test p = 0.003.

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) 24 Hours Post-dose at Week 12 + 1 Day, Day 85

• 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 600 μg: mean 2.62 versus 2.61 on control; difference 0.01 (95% CI -0.05 to 0.07), standardized effect d = 0.03; z-test p = 0.759.
  • Salmeterol 50 μg: mean 2.54 versus 2.61 on control; difference -0.07 (95% CI -0.13 to -0.01), standardized effect d = -0.19; z-test p = 0.031.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Indacaterol 600 μg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Salmeterol 50 μg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study

• 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 deviations.
• Result:
  • Indacaterol 600 μg: mean 0.19 versus 0.17 on control; difference 0.02 (95% CI -0.07 to 0.11), standardized effect d = 0.04; z-test p = 0.666.
  • Salmeterol 50 μg: mean 0.19 versus 0.17 on control; difference 0.02 (95% CI -0.07 to 0.11), standardized effect d = 0.04; z-test p = 0.661.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Indacaterol 600 μg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Salmeterol 50 μg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address two related but distinct aspects of asthma research: lung function at a specified follow-up and the number of asthma exacerbations per patient over the study period. The overall pattern is not a uniform separation across all measures. The posted FEV1 comparison between the two indacaterol doses is close to zero, while the comparison with salmeterol is negative relative to indacaterol 300 μg. The exacerbation-count comparisons have small positive estimates against the same reference group, with reported intervals spanning zero.

These outcomes add context to the primary safety result but do not directly explain it. The primary endpoint records whether a participant experienced any adverse event; FEV1 is a lung-function measure, and exacerbation count measures a particular clinical event over time. The definitions, scales, and statistical summaries differ. A pattern in one outcome should not be treated as confirmation of a pattern in another, and the secondary results do not establish why adverse events occurred.

The registry record lists 17 outcome measures, while the posted secondary results include two outcomes. The pairwise results are unadjusted, and no reported analyses are listed for these secondary endpoints. When several outcomes and comparisons are examined, some apparently notable results can arise by chance even if there is no underlying effect. A multiplicity adjustment or a clear prespecified hierarchy can help address that issue, but such procedures are not reported in the registry record.

For that reason, the secondary findings are best read as exploratory context rather than as independent proof of a treatment difference. Their meaning is further limited by the absence of a reported analysis plan, model details for FEV1, and inferential methods for exacerbation counts. The registry record does not report how missing measurements were handled. The secondary outcomes can help frame questions about lung function and exacerbations, but the posted summaries alone do not settle those questions.

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

• Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at Week 12 + 1 Day, Day 85
• Number of Asthma Exacerbations Per Patient (Without Imputation) During the 26 Weeks of the Study

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: each person either had at least one adverse event during the follow-up period or did not. The reported percentage is the proportion of participants meeting that definition in each group. A risk difference expresses the difference between two such proportions on the probability scale. A positive estimate means the proportion is higher in the comparison group than in the reference group, given the comparison direction used in the posted results.

What does the interval estimate describe?

A confidence interval is a range of values compatible with the observed data under the statistical method used. It communicates precision as well as direction: a narrower interval indicates a more precise estimate, while a wider interval leaves more uncertainty about the size of the difference. The posted intervals for the primary comparisons are presented with the risk-difference estimates. The registry record does not state the confidence level or describe the exact method used to form those intervals, so those details are not reported in the registry record.

How should the p-values be read?

A p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of a difference. The posted primary p-values are unadjusted. That means they are not presented as corrected for the multiple treatment comparisons or the range of outcomes in the registry record. The statistical analysis plan and any prespecified multiplicity procedure are not reported in the registry record.

Why does the endpoint definition matter?

The primary endpoint combines adverse events into a single participant-level indicator. This is useful for describing the proportion of participants who experienced at least one event, but it treats different events as part of the same broad outcome. The endpoint does not distinguish event frequency beyond the first event, duration, severity, or clinical consequences. Asthma exacerbations are included, but only when they meet the stated clinical and treatment definition. A broader worsening of asthma that received only specified inhaled treatment is not counted as an exacerbation by that definition.

Interpretation also depends on the population used. The primary result is based on the safety population, defined as participants who received at least one dose of study drug. This is not necessarily the same as every participant enrolled or randomized. The registry record does not report a separate intention-to-treat analysis for this outcome, nor does it give details of how participants with incomplete follow-up or missing endpoint data were handled.

What do the secondary outcome summaries represent?

The FEV1 endpoint is reported as a least-squares mean with a standard error. A least-squares mean is an adjusted mean from a statistical model; the registry record does not report the model specification or covariates used. A standard error describes the precision of an estimated mean, rather than the spread of individual measurements. The posted between-group estimate and interval are recalculated comparisons based on the available summary information; they are not listed as reported analyses in the registry record.

The asthma exacerbation endpoint is reported as a mean number per patient with a standard deviation. A standard deviation describes variation among participant-level values, whereas a standard error describes precision of an estimated mean. Exacerbation counts can be concentrated at low values while some participants have higher counts, a pattern that may create over-dispersion relative to a simple model. In general, over-dispersion means the variability is greater than a model’s assumptions allow; that can make standard errors and p-values from an unsuitable model unreliable. The registry record does not report the distributional assumptions, model, or inferential analysis used for this outcome.

The posted pairwise summaries for the secondary outcomes are unadjusted comparisons. They provide descriptive statistical context but are not a replacement for a prespecified analysis plan. The registry record lists 17 outcome measures and does not report multiplicity handling, so chance findings across a collection of analyses remain a concern. It also lists no reported analyses for the secondary endpoints. Accordingly, the comparisons in the posted summaries should not be mistaken for sponsor-reported adjusted results.

Sample-size illustrations use a normal approximation, equal allocation between two groups, and a two-sided significance level of 0.05. They are calculated from the observed effect and consider the stated fractions of that effect. Such calculations describe hypothetical planning requirements under those assumptions; they do not recover the trial’s original design calculation. The original sample-size assumptions are not reported in the registry record. A recalculated comparison is a simple unadjusted calculation from posted summary statistics, and it should be kept distinct from a sponsor’s own analysis when the two differ. The record does not indicate a discrepancy for the displayed analyses.

11. Confidence Intervals and Precision

The primary risk-difference estimates are 0.116 for indacaterol 600 μg versus indacaterol 300 μg and 0.124 for salmeterol 50 μg versus indacaterol 300 μg. Their reported intervals are 0.034 to 0.198 and 0.043 to 0.206, respectively. These intervals give a range for the estimated difference rather than a single exact value. Both are on the positive side of zero, consistent with the higher observed adverse-event proportions in the two comparison groups.

Precision is not the same as certainty about cause or clinical importance. The intervals reflect sampling uncertainty under the methods used, but the registry record does not report the interval construction method or confidence level. They do not account for every possible source of uncertainty, such as missing data, measurement choices, or the selection of analyses. The absence of a reported multiplicity procedure also matters when several outcomes and comparisons are considered together.

The group sizes for the primary endpoint are 268, 268, and 269. The associated estimates are therefore based on a finite set of safety-population participants, not every person who might meet the trial’s eligibility conditions. The intervals help show how much uncertainty remains about the population difference, but they cannot establish that the observed proportions will recur in another setting.

For the secondary FEV1 comparison of indacaterol 600 μg with indacaterol 300 μg, the mean-difference estimate is 0.01 and its reported interval ranges from -0.054 to 0.074. For exacerbations per patient, the corresponding estimate is 0.02 and its interval ranges from -0.071 to 0.111. These intervals include zero and are relatively broad compared with the small point estimates. The registry record does not report adjusted analyses for these outcomes, so their precision should be considered alongside the limitations of the posted summary comparisons.

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 sample-size illustrations express the number of participants per arm for the two-group comparisons in this trial. These are not total event counts: the listed outcomes are binary or continuous, and the planning figures are participants per arm. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect and the statistical model assumptions are correct. The 90% power column uses a higher probability of detection, and therefore generally calls for a larger planned sample. These columns describe hypothetical study planning, not the probability that the completed trial’s findings are true.

Each planning scenario is anchored to an observed effect, then considers planning for 100%, 75%, or 50% of that effect. Smaller effects are harder to distinguish from random variation, so the illustrated requirement rises as the target effect becomes smaller. For example, the listed per-arm requirements for the primary adverse-event comparison of indacaterol 600 μg with indacaterol 300 μg increase from 279 for planning for 100% of the observed effect to 1,144 for planning for 50% of it at 80% power. The figures are planning illustrations based on the observed results and assumptions, not observed power.

These illustrations are not the original trial’s sample-size justification. The registry record does not report the trial’s own design assumptions, target effect, or original power calculation. The calculations also do not establish whether a future study should use the same allocation, analysis, or endpoint definition. They show how changing the target effect and desired power affects a hypothetical participant requirement under the stated assumptions.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.549; treatment proportion p₁ = 0.664; average p̄ = 0.606.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6909 = 1.3542.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6861 = 0.5774.
4. n = (1.3542 + 0.5774)² / (0.1157)² = 278.9, rounded up to 279 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
p0 <- 0.548507462686567                          # control proportion
p1 <- 0.664179104477612                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(529529)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 279 (80% power), 373 (90% power)
 75% of observed effect: n per arm = 503 (80% power), 673 (90% power)
 50% of observed effect: n per arm = 1,144 (80% power), 1,531 (90% power)
power.prop.test: 278.9 
Simulated power at n = 279 per arm: 0.801 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 17 outcome measures and includes primary and secondary results, but it does not report a multiplicity strategy. Multiplicity arises when several outcomes, treatment comparisons, or analysis choices are examined: the more opportunities there are to find a small p-value, the greater the chance of at least one apparently notable result arising by chance. Methods such as prespecified testing hierarchies or statistical adjustments can control aspects of this problem, but whether any such method was planned or used is not reported in the registry record.

The posted p-values for the comparisons are unadjusted. They should therefore be read as individual comparison statistics, not as results corrected for the full set of outcomes or comparisons. The registry record does not provide a detailed statistical analysis plan, identify planned interim analyses, or state which secondary analyses were prespecified. The sponsor’s intended inferential framework and any distinctions between confirmatory and exploratory analyses are not reported in the registry record.

Missing-data handling is also not reported in the registry record. For the primary endpoint, the record identifies the safety population as participants who received at least one dose, but it does not explain how participants without a complete adverse-event record through the end of follow-up were treated. For FEV1, it does not report an imputation approach or the analysis population beyond the posted group counts. The exacerbation outcome is explicitly described as without imputation, but that label does not explain whether all participants had complete observation or how any incomplete follow-up affected the summaries.

The registry record does not report sensitivity analyses for missing data, exclusions, or alternative endpoint definitions. Without those details, it is not possible to assess whether the results would change under different assumptions about unavailable observations. The reported population definitions and summary statistics remain useful for describing what was posted, but they do not answer every question about participant flow or analysis choices.

For the secondary endpoints, the registry record lists no reported analyses. The summary comparisons should therefore not be interpreted as fully documented sponsor analyses. Clearer reporting of multiplicity, analysis populations, missing-data methods, and prespecified models would be needed to judge how the results fit within the trial’s intended statistical plan.

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: asthma (1.1%), fall (0.7%), pregnancy (0.7%), splenic cyst (0.4%), atrial fibrillation (0.4%).

The serious adverse-event summaries report participants at risk and participants affected in each group. The registry record lists 5 serious adverse events among 268 participants at risk in the indacaterol 300 μg group, 11 among 268 in the indacaterol 600 μg group, and 8 among 269 in the salmeterol 50 μg group. These counts are separate from the primary endpoint, which includes any adverse event and does not require an event to meet the serious-event category.

The listed serious-event terms include asthma, fall, pregnancy, splenic cyst, atrial fibrillation, and cardiac arrest, with percentages reported for each term in the registry record. These are event-term summaries, not evidence that each term occurred only once or that each was caused by study treatment. The registry record does not report deaths for these groups.

Counts of serious events should be interpreted in light of the group sizes and the kinds of events included. They describe what was recorded during the study, but by themselves do not establish comparative risk, causation, or a broader safety profile. The record does not provide adjusted comparisons for serious adverse events.

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

The posted primary results show that the proportion of participants with at least one adverse event was 54.9% with indacaterol 300 μg, 66.4% with indacaterol 600 μg, and 67.3% with salmeterol 50 μg. The unadjusted risk-difference estimates compare each of the latter groups with indacaterol 300 μg. These figures describe the participants and follow-up recorded in this trial, using the registry’s broad adverse-event definition.

They do not show that every event was caused by treatment, that the events had similar seriousness, or that each participant experienced only one event. The primary endpoint counts people with at least one event and combines different event types. Serious adverse events are reported separately, and asthma exacerbations have a specific definition in the record. The primary result is therefore not a direct measure of the severity or total burden of adverse events.

The results also do not, by themselves, establish the clinical importance of a difference. Statistical estimates and intervals describe the observed comparisons and their precision under the analysis assumptions. The p-values are unadjusted, and the record does not report the statistical analysis plan, multiplicity handling, or missing-data methods. Those omissions limit how confidently the posted comparisons can be connected to a prespecified inferential claim.

The secondary endpoints address lung function and exacerbations, not the same outcome as the primary safety measure. Their summaries do not demonstrate that changes in one measure explain the adverse-event pattern. The secondary analyses are unadjusted, and the registry record lists no reported analyses for them. They should be regarded as context rather than as definitive confirmation of a broader treatment effect.

Finally, the trial followed participants for 26 weeks and enrolled people with moderate to severe persistent asthma aged ≥ 12 years. The posted results do not establish what would occur beyond that follow-up, in populations not represented by the trial, or under different treatment conditions. The registry record does not report information that would support those wider conclusions. The findings should be understood as a description of this randomized study’s recorded outcomes, not as medical advice or a general treatment recommendation.

17. Why This Trial Matters Statistically

This trial illustrates why the statistical description of a safety endpoint matters. A percentage with at least one adverse event answers a specific question about how many participants experienced any event. It does not describe the number of events, their severity, or whether they were judged related to treatment. Keeping those concepts separate prevents a broad participant-level proportion from being mistaken for a complete account of safety.

The randomized, parallel-group design and active-control comparison allow the observed group proportions to be compared within the study. At the same time, the primary endpoint’s broad definition means that event composition and seriousness require separate scrutiny. The record’s separate serious-event counts make clear that an overall adverse-event percentage and serious adverse-event summaries are different statistical quantities.

The trial also demonstrates the role of uncertainty intervals alongside point estimates. A single estimate gives a concise description of the observed comparison; an interval communicates that the underlying difference is not known exactly. Unadjusted p-values and intervals should be considered with the fact that the registry record lists multiple outcomes and does not report multiplicity procedures or a detailed analysis plan.

Finally, planning illustrations based on observed effects are not substitutes for an original sample-size justification. Their requirements change with the effect size targeted and the desired probability of detecting it. Because the registry record does not report the trial’s original design assumptions, the illustrations are useful for understanding planning sensitivity, not for reconstructing the investigators’ initial rationale. Together, these considerations show how endpoint definitions, analysis transparency, precision, and multiplicity shape a careful reading of clinical trial results.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several trial-specific limitations affect interpretation. The primary endpoint combines different adverse events into a single indicator of whether a participant experienced at least one event. The registry definition includes asthma exacerbations, but only when they meet a specified clinical judgment and treatment threshold. This makes the result dependent on event classification and does not capture the full distribution of event types or repeated events.

The posted primary comparisons are unadjusted, and the registry record does not report multiplicity methods despite listing 17 outcome measures. It also does not report a detailed statistical analysis plan, the original sample-size justification, or interim-analysis procedures. These gaps make it difficult to determine how closely the posted analyses align with prespecified choices.

The registry record does not report missing-data methods for the primary endpoint or FEV1 outcome. It gives a safety-population definition, but not a full account of participant flow or how incomplete follow-up was handled. For exacerbations, the endpoint is labeled without imputation, but the record does not explain the extent or handling of any incomplete observation.

The follow-up period was 26 weeks, so the posted outcomes describe that study period rather than longer-term experience. The record also does not provide adjusted comparisons for serious adverse events. The listed serious-event counts and terms are descriptive and do not establish causation. Finally, the secondary outcome models and their assumptions are not reported, limiting interpretation of their unadjusted comparisons.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Safety of Indacaterol in Patients (≥ 12 Years) With Moderate to Severe Persistent Asthma — NCT00529529.
• Registry record last updated 2011-08-29; status last verified 2011-08.
• Results first posted 2011-08-19.
• 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.

22. Record Summary

NCT00529529 is a completed, randomized phase 3 parallel-group study of indacaterol 300 μg or 600 μg once daily compared with salmeterol 50 μg twice daily in people with moderate to severe persistent asthma. The double-blind, double-dummy study enrolled 805 participants and lasted 26 weeks.

The primary endpoint was the percentage of participants in the safety population with at least one adverse event. The posted percentages were 54.9% for indacaterol 300 μg, 66.4% for indacaterol 600 μg, and 67.3% for salmeterol 50 μg. The registry record also includes secondary summaries for FEV1 and asthma exacerbations per patient.

Primary comparisons are posted as unadjusted risk differences. The registry record does not report the original sample-size justification, detailed statistical analysis plan, multiplicity procedure, or missing-data methods. These limits matter when assessing the precision and scope of the posted results.