New Breath Actuated MDI Symbicort Compared to Symbicort pMDI and Budesonide pMDI for 12 Weeks Twice a Day: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for New Breath Actuated MDI Symbicort Compared to Symbicort pMDI and Budesonide pMDI for 12 Weeks Twice a Day (NCT01360021), a randomized phase 3 study. The primary outcome is Forced Expiratory Volume in 1 Second (FEV1) - Post Dose.

2. Clinical Question

The study is described as a comparison of the efficacy of breath-actuated Symbicort with pressurized Symbicort after twice-daily dosing for 12 weeks. Its primary endpoint is defined as a descriptive measure of FEV1 rather than a single stated between-arm contrast. The registry lists measurements at baseline and week 0, 3, 7, 12, and Trt Avg, where Trt Avg means the mean of all available valid values after randomization. The stated endpoint timing is 60 minutes post-dose in clinic visits.

Those definitions identify the measurement and comparison of interest, but do not establish what difference the investigators considered important or what clinical conclusion should follow from a particular value. Such an interpretation would require the actual arm-level results and an analysis that accounts for the study design. The registry record does not report a reduced single comparison for the primary outcome.

3. Trial Design

This was a phase 3, randomized, triple-masked, parallel-group study in asthma. The registry records enrollment of 214 and a completed status. The study compared three inhaler regimens: Symbicort BA MDI 2x160/4.5 μg twice daily, Symbicort AC pMDI 2x160/4.5 μg twice daily, and budesonide AC pMDI 2x160 μg twice daily. The planned treatment duration was 12 weeks.

The registry describes a 12-week, double-blind study in its official title and lists masking as triple. Those are the recorded descriptions; further detail about which parties were masked, how masking was maintained, or whether it was assessed is not reported in the registry record. Randomization is recorded, but the sequence-generation method, allocation concealment, and the allocation ratio are not reported in the registry record.

The study started in 2011-11, with primary completion in 2012-08. Its primary outcome was post-dose FEV1 in liters, described using a geometric mean and geometric coefficient of variation. The endpoint description identifies clinic assessments 60 minutes post-dose at baseline and week 0, 3, 7, 12, and Trt Avg. The registry also lists peak expiratory flow, total asthma symptoms score, night-time awakenings measured as the percentage of awakening-free nights, and total daily rescue medication use among secondary outcomes.

The registry records 6 outcome measures and 10 analyses, but these counts do not specify the complete analysis plan. Details such as the planned statistical model, covariate adjustment, handling of repeated measurements, and rules for analysis exclusions are not reported in the registry record. The enrollment figure alone does not establish how the trial’s sample size was selected or what effect it was designed to detect; the sample-size justification is 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: Full analysis set: It consist of all randomized patients who received at least one dose of study medication and contributed sufficient data for at least one efficacy endpoint (Primary variable).

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.

Population: All Randomized patients

6. Primary Endpoint

The registry lists the primary outcome as Forced Expiratory Volume in 1 Second (FEV1) - Post Dose, measured over 60 minutes post-dose in clinic visits at baseline, and week 0, 3, 7, 12 and Trt Avg.

Forced expiratory volume in 1 second, or FEV1, is the volume of air a person can forcefully exhale during the first second of an expiratory maneuver. The registry reports this endpoint in liters and specifies a measurement 60 minutes after dosing during clinic visits. FEV1 is used in respiratory studies as a measure of lung function. In this trial, it provides a way to describe post-dose lung function over the treatment period for the three inhaler regimens.

The registry specifies a geometric mean and geometric coefficient of variation for the primary endpoint. A geometric mean summarizes values on a multiplicative scale, rather than by adding values and dividing by their count as in an arithmetic mean. This can be useful when measurements vary proportionally or have a right-skewed distribution. The geometric coefficient of variation describes relative spread on a percentage-like scale, rather than spread in the original units. These are general interpretations of the statistics named in the registry; the record does not explain why this scale was selected for this analysis.

Baseline is defined as the last pre-dose value before the first dose of randomized therapy. Trt Avg is defined as the mean of all available valid values after randomization. The endpoint description lists assessments at baseline and week 0, 3, 7, 12, and Trt Avg. The primary outcome has multiple categories or time points and is not reduced in the registry record to one comparison. The record therefore identifies what was measured and when, but not a single summary contrast with an estimate and uncertainty interval.

FEV1 is an objective measurement, but it is only one aspect of asthma status. The registry also identifies symptom, awakening, rescue-medication, and peak-flow outcomes. Their listed presence does not show their results or establish how they were analyzed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel-group design with triple masking. In a randomized trial, assignment is determined using a chance-based process, which is intended to make treatment groups comparable in expectation. A parallel-group design means participants are assigned to a treatment group and the groups are followed alongside one another. Masking is intended to limit the influence of knowledge about assigned treatment on trial conduct or outcome assessment. These are general descriptions; the particular randomization and masking procedures are not reported in the registry record.

What does the endpoint summary describe?

The primary endpoint is post-dose FEV1 in liters, reported as a geometric mean with a geometric coefficient of variation. A mean describes a central value, while a measure of variation describes how dispersed observations are. With a geometric summary, the natural interpretation is proportional: variation is expressed relative to the scale of the values rather than as an absolute number of liters. This can be appropriate for measurements whose variability grows with their level, though the registry does not state the rationale for selecting it.

The record defines baseline as the last pre-dose measurement before the first dose of randomized treatment. It defines Trt Avg as the mean of all available valid post-randomization values. The time frame includes baseline, week 0, 3, 7, 12, and Trt Avg, with measurements taken 60 minutes after dosing during clinic visits. Multiple time points can describe the pattern over time, while a treatment average can summarize post-randomization measurements. These summaries answer different descriptive questions and should not be assumed to be interchangeable.

The primary outcome is not reduced to one comparison in the registry record because it has several categories or time points. A single treatment-effect estimate would require a specified contrast, such as a comparison between two named arms at a selected time or an overall repeated-measures contrast. The record does not report such a single estimate, its standard error, a confidence interval, or a p-value. It also does not report the model used to account for repeated observations or the exact contrast definitions.

Why do analysis populations matter?

The primary endpoint population is described as the full analysis set: randomized patients who received at least one dose and contributed sufficient data for at least one efficacy endpoint. The definition indicates that randomization alone was not the sole criterion for inclusion in that stated analysis population. It does not establish that every eligible participant contributed data to every endpoint or visit. The number analyzed for each outcome and time point, and the handling of participants who discontinued or lacked measurements, are not reported in the registry record.

Different analysis populations can yield different estimates because they include different participants or measurements. A population that follows randomized assignment as closely as possible can preserve the benefits of randomization, while restricting analysis to participants with sufficient measurements may change the composition of the analyzed groups. These are general methodological considerations, not claims about the trial’s actual analysis beyond its stated full analysis set definition.

What can the sample-size assumptions tell us?

The registry’s planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. Such a calculation is a planning illustration, not observed power and not proof that the study was adequately powered. It should not be read as the trial’s original sample-size justification: that justification is not reported in the registry record. The record’s general convention says that time-to-event calculations give total events and other calculations give participants per arm.

Planning calculations depend on their assumptions. A calculation based on an observed effect may be especially sensitive to how that effect was estimated, and it does not replace a prespecified design justification. The registry does not report the original target enrollment rationale, the effect size used in the original design, or whether any such assumptions were revised. No sample-size result should be interpreted as observed power.

What statistical detail is absent?

The record does not report the primary model, covariates, treatment contrast, variance assumptions, confidence intervals, or inferential results for FEV1. It also does not report whether analyses were adjusted for baseline values, how repeated measures were handled, or what diagnostics were used. Those omissions prevent reconstruction of the primary inference from the endpoint definition alone.

Over-dispersion is a general issue for count outcomes: observed variability can exceed what a simple count model assumes, which can make standard errors too small if the model does not account for it. It is not possible to tell from the registry record whether over-dispersion was relevant to any analysis or whether any specific model addressed it. The listed safety results are counts, but the record does not provide an inferential model or an adjusted safety comparison.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is recorded across multiple assessment times and includes a treatment-average summary. The registry also lists several secondary outcomes: peak expiratory flow, total asthma symptoms score, percentage of awakening-free nights, and total daily rescue medication use. Considering multiple endpoints, times, or pairwise comparisons can increase the chance of finding at least one apparently notable result by chance when many tests are performed. Statistical methods for controlling this issue include prespecifying a testing order or adjusting significance thresholds. These are general principles; the multiplicity strategy for this trial is not reported in the registry record.

The record lists 6 outcome measures and 10 analyses, but those totals do not explain which results were confirmatory, how outcomes were prioritized, or whether the analyses were adjusted for multiple testing. The planned analysis hierarchy and any multiplicity adjustment are not reported in the registry record. Without those details and the underlying estimates, the listed outcomes cannot be used to determine which findings, if any, were intended to support a primary claim.

Missing-data handling is also not reported in the registry record. Although the full analysis set definition requires sufficient data for at least one efficacy endpoint, it does not describe how missing values were handled within an endpoint, across visits, or after treatment discontinuation. The record does not report the number of missing values, reasons for missingness, or any imputation or sensitivity analyses. Missing observations can affect both the estimate and its uncertainty, especially if the chance of missing a measurement is related to health status or treatment experience.

The primary endpoint’s listed time points and the Trt Avg definition make the availability of repeated measurements relevant. However, the registry does not state whether a model used all available observations, required complete visits, or applied another rule. Those details are necessary to assess how much the reported analysis might depend on assumptions about missing data.

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: appendicitis (1.4%).

The registry reports serious adverse events by listed treatment group. It records 0 affected among 71 at risk for budesonide, 0 among 71 for Symbicort BA MDI, and 1 among 71 for Symbicort pMDI. The record also lists other affected counts of 3 for budesonide, 2 for Symbicort BA MDI, and 7 for Symbicort pMDI, with 71 at risk in each group. These are counts as recorded; the registry does not provide uncertainty intervals or a statistical comparison for them.

Counts describe what was reported in the study, but small or zero counts do not establish that an event cannot occur or that groups have equal safety profiles. A comparative interpretation would require attention to the event definitions, observation period, participant follow-up, and statistical uncertainty. Those details are not reported in the registry record in the registry record.

Appendicitis appears among the top serious adverse event terms at 1.4%. The registry information does not identify the treatment group associated with that term. The death fields are null, so deaths are not reported in the registry record. A null entry should not be interpreted as an affirmative statement that no deaths occurred. The safety counts are descriptive registry data, not a basis for individual treatment decisions.

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

The record establishes that a randomized, triple-masked, parallel-group phase 3 study compared three inhaler regimens over 12 weeks in asthma. It identifies the doses, the post-dose FEV1 endpoint, the measurement schedule, and a full analysis set definition. It also gives selected adverse-event counts. These registry entries describe the intended comparison and some reported safety observations.

The record does not provide the single primary treatment contrast needed to state the direction or size of an FEV1 difference. It does not give an estimate with a confidence interval or a primary-outcome p-value. Consequently, the information does not establish whether one regimen had higher or lower post-dose FEV1 than another, or how precise any such difference would be. The lack of a reported contrast is not evidence that treatments were the same.

Likewise, the safety counts do not establish that one inhaler is safer or less safe than another. They are descriptive figures without reported adjusted comparisons or uncertainty intervals. The group attribution for the listed appendicitis term is not reported in the registry record, and death results are not reported in the registry record.

More broadly, a trial result depends on the analyzed population, outcome definitions, missing-data handling, statistical model, and multiplicity approach, as well as on the observed estimates. Several of these details are not reported in the registry record. The posted information therefore supports a description of study design and outcome definitions, along with limited safety counts, but not a complete evaluation of efficacy, equivalence, or comparative safety.

These limits are about what can be inferred from the registry information, not about what the full trial might have found. The registry record does not report enough primary outcome results to draw a conclusion about the comparative FEV1 findings. No medical advice or treatment recommendation follows from these descriptive details alone.

13. Why This Trial Matters Statistically

This trial is statistically useful to examine because it compares two delivery devices for the same listed Symbicort dose as well as a budesonide regimen, and it defines an objective lung-function endpoint. The randomized, parallel-group design provides a clear framework for comparing assigned regimens. The triple-masking designation also signals an effort to limit knowledge of assignment, although the practical masking procedures are not reported in the registry record.

The endpoint description illustrates why a study’s measurement schedule and summary scale matter. FEV1 is measured 60 minutes after dosing at multiple visits, and the registry uses geometric rather than arithmetic summaries. Those choices affect how readers should understand the reported central value and variability. The definition of Trt Avg also makes clear that the summary draws on available valid post-randomization values rather than being described as a single visit measurement.

The record also illustrates a common interpretive boundary: an outcome definition is not a result. Without a reported treatment contrast and uncertainty interval, the primary endpoint cannot support a conclusion about the comparative effect or its precision. Reporting secondary endpoints and analysis counts does not fill that gap, particularly when the multiplicity plan and results are unavailable.

Finally, the adverse-event counts show why descriptive safety data need careful framing. Counts can help identify what the registry recorded, but they do not by themselves quantify uncertainty or establish a comparative safety difference. Registry completeness and analysis detail are therefore central to responsible statistical interpretation, alongside the trial design itself.

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 primary limitation for interpretation is that the registry information does not include a single reduced comparison for the primary outcome. Although it defines post-dose FEV1, its geometric summaries, and several assessment times, it does not report arm-level estimates, a treatment-effect estimate, a confidence interval, or a p-value. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed from the registry record.

The analysis methods are incompletely described. The record does not report the randomization procedure, allocation concealment, detailed masking procedures, primary statistical model, covariate adjustments, or repeated-measures method. It does not report missing-data handling, the number of observations analyzed at each time point, or sensitivity analyses. The multiplicity strategy for the several outcome measures and analyses is also not reported in the registry record.

The full analysis set definition indicates that participants had to be randomized, receive at least one dose, and contribute sufficient data for at least one efficacy endpoint. The record does not establish the number contributing to each individual endpoint or visit, or how exclusions and discontinuations were handled. The original sample-size justification is not reported in the registry record; an illustration based on an observed effect should not be mistaken for the original design rationale or observed power.

Safety information is limited to the listed counts, with no reported uncertainty intervals or inferential comparison. The group associated with the appendicitis term is not specified in the registry information available, and deaths are not reported in the registry record. These limitations restrict both efficacy and safety interpretation and should prevent stronger claims than the registry data support.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: New Breath Actuated MDI Symbicort Compared to Symbicort pMDI and Budesonide pMDI for 12 Weeks Twice a Day — NCT01360021.
• Registry record last updated 2014-03-11; status last verified 2014-01.
• Results first posted 2014-03-11.
• 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

The registry describes a completed, phase 3, randomized, triple-masked, parallel-group study of three inhaler regimens for asthma. It records enrollment of 214, a 12-week treatment period, a start in 2011-11, and primary completion in 2012-08. The regimens were Symbicort BA MDI, Symbicort AC pMDI, and budesonide AC pMDI, each with the dose and twice-daily schedule stated in the record.

The primary endpoint was post-dose FEV1 in liters, summarized using a geometric mean and geometric coefficient of variation at multiple visits and for Trt Avg. The endpoint is not reduced to one comparison in the registry record. Selected serious and other adverse-event counts are listed, but inferential safety comparisons are not reported. Important analysis details, including the primary model, missing-data approach, multiplicity plan, and sample-size justification, are not reported in the registry record. The available information defines the study and its outcomes but does not provide a complete primary efficacy result.