Trial on the Effect of Budesonide/Formoterol and Inhaled Budesonide Alone on Exercise-Induced Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial on the Effect of Budesonide/Formoterol and Inhaled Budesonide Alone on Exercise-Induced Asthma (NCT01070888), a randomized phase 4 study. The primary outcome is Mean Difference Between Maximal Percentage Decrease in FEV1 After the Exercise Challenge Compared to the Run in Period, Budesonide/Formoterol - Budesonide.

2. Clinical Question

The trial asked whether budesonide/formoterol and budesonide alone differed in their effect on exercise-related lung-function decline among people with persistent asthma and exercise-induced asthma. Its primary outcome concerned the maximal percentage decrease in FEV1 after an exercise challenge, considered relative to a run-in period. FEV1 is forced expiratory volume in one second; the endpoint therefore focuses on a change in lung-function measurement following exercise rather than on symptoms, exacerbations, or another clinical outcome.

The intended comparison was within a crossover design: participants were assigned to a treatment sequence, with one study period using budesonide/formoterol and another using budesonide. The registry’s arm descriptions say that one sequence began with budesonide/formoterol and the other began with budesonide. Both descriptions also mention a dummy inhaler, blinding, and twice-daily use. The registry record does not report the dose strength or the duration of each individual treatment period.

The primary contrast is described as budesonide/formoterol minus budesonide. It is based on how the maximal fall in FEV1 after the exercise challenge compares with the run-in value under each treatment. The question is therefore whether the recorded change on that scale differs between the two treatments. The registry reports summary values for the sequence groups, but it does not report an analysis estimating the treatment contrast across the crossover periods. As a result, the posted figures do not establish the size or precision of a direct treatment comparison.

The record identifies the study as phase 4 and randomized, with quadruple masking, and lists exercise-induced asthma as the condition. The registry summary describes the intended population as children and adults with asthma and exercise-induced asthma; the reported ages of participants are not reported in the registry record. The reason for termination is not reported in the registry record.

3. Trial Design

The registry identifies this as a randomized, phase 4 crossover trial of budesonide/formoterol and inhaled budesonide. In a crossover design, participants receive more than one treatment in sequence, so comparisons can in principle use measurements from the same participant under different treatments. This general feature can reduce the influence of stable differences between participants, but it does not remove the need to account for treatment period and sequence in the analysis.

The arm descriptions specify two sequences. Participants in the budesonide/formoterol-first sequence were described as receiving blinded budesonide/formoterol and a dummy inhaler in the first period, then budesonide and a dummy inhaler in the second period. The budesonide-first sequence reverses that order. Each description says participants were asked to take 2 inhalations of each inhaler, twice daily. The duration of the periods is not reported in the registry record. The primary outcome timeframe is listed as 8 weeks, but the relationship between that timeframe and the length or timing of individual treatment periods is not further described.

The trial title describes a double-blind, double-dummy crossover trial, while the registry classifies masking as quadruple. Both descriptions indicate masking, but details about who was masked and how masking was maintained are not reported in the registry record. The randomization method, sequence generation, allocation concealment, and any washout between periods are also not reported in the registry record.

The registry lists enrollment as 6 and status as terminated. The summary outcome entries are organized by treatment sequence and report group sizes of 1 and 2. Those entries do not explain why the reported outcome summaries include fewer observations than the enrollment figure. The reason for termination, the number completing each period, and the number included in the primary analysis are not reported in the registry record.

Although the planned crossover structure suggests measurements under both treatments, the posted result does not provide the period-specific observations or a treatment-effect analysis. Consequently, the sequence-group summaries cannot be read as a complete analysis of the within-participant contrast. The statistical model, if any, used for the crossover comparison 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.

Before assignment: excluded from failed run-in or not qualify by exercise challenge

First Intervention (14 Days)

Reasons for not completing this period:

Washout (14 Days)

Reasons for not completing this period:

Second Intervention (14 Days)

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 Mean Difference Between Maximal Percentage Decrease in FEV1 After the Exercise Challenge Compared to the Run in Period, Budesonide/Formoterol - Budesonide, measured over 8 weeks.

The primary endpoint measures a treatment contrast in the maximal percentage decrease in FEV1 after an exercise challenge, relative to a run-in period. FEV1 is a measure of how much air a person can forcefully exhale in one second. The outcome is continuous: it is expressed as a percentage of fall in FEV1, and the registry identifies the summary as a mean with standard deviation.

As described in the record, the contrast is budesonide/formoterol minus budesonide. For each treatment, the calculation compares the maximal fall at baseline with the maximal fall during that treatment; the two resulting changes are then contrasted. The stated timeframe is 8 weeks. The registry does not explain in greater detail when the exercise challenge occurred within that timeframe or how many challenges contributed to each participant’s endpoint.

A continuous lung-function endpoint can retain information about the magnitude of change rather than reducing outcomes to categories such as improved or not improved. In general, a treatment contrast on this scale describes the average difference in the measured change between treatments. Its interpretation depends on the precise direction and construction of the scale, as well as the estimate’s uncertainty.

Here, the registry reports values by treatment sequence, not an estimated mean difference with a confidence interval for the treatment contrast. The negative sequence-group values should therefore be read only as summaries on the scale recorded for those groups. They do not, by themselves, show how precisely the treatments differ. The clinical importance of a given difference is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Continuous outcomes are commonly summarized using a mean and a measure of spread. The registry identifies the primary outcome as a mean and lists standard deviation as the spread measure. The mean describes the central value of the observations included in a group; the standard deviation describes how dispersed those observations are around the mean. These summaries do not, on their own, quantify the uncertainty in a treatment comparison.

For a treatment contrast, a confidence interval would show a range of values compatible with the data and the specified statistical method. A narrow interval generally indicates greater precision than a wide interval. No confidence interval is reported for the primary treatment contrast in the registry record. No p-value or other test result is reported either, so the precision and inferential strength of that comparison cannot be assessed from the posted result.

What does a crossover design compare?

In general, a crossover trial assigns participants to treatment sequences and measures outcomes during more than one treatment period. A participant may therefore contribute information under both treatments. This allows a comparison that accounts for stable characteristics shared across that participant’s periods. However, a suitable analysis still needs to account for the repeated measurements and the trial’s sequence and period structure.

The registry lists two treatment sequences, one starting with budesonide/formoterol and the other starting with budesonide. It does not report period-specific outcome data or an analysis of within-participant differences. The sequence summaries alone cannot show whether the analysis accounted for repeated observations, treatment sequence, or period. The statistical model and any assumptions used for the crossover comparison are not reported in the registry record.

Why can period and sequence matter?

As a general statistical consideration, outcomes in a crossover trial can vary between periods for reasons other than the treatment under study. A treatment effect may also differ depending on the order in which treatments were received, and effects from an earlier period may potentially carry into a later period. These are considerations for interpreting crossover data, not reported findings about this trial. The registry does not report whether the study included a washout period, assessed carryover, or prespecified methods for period or sequence effects.

The trial is described as double-blind and double-dummy in its title, and the registry lists quadruple masking. Masking can reduce the influence of expectations on treatment delivery or outcome assessment, but the registry does not describe the masking procedures in enough detail to assess how they operated. The general methods explanation should not be mistaken for confirmation that any particular bias was prevented in this trial.

What do the posted summaries tell us?

The result entries report a mean value and standard deviation for each sequence group. The budesonide-first entry reports -3.1, standard deviation 0.0, and a group size of 1. The budesonide/formoterol-first entry reports -19.4, standard deviation 30.5, and a group size of 2. These are descriptive summaries as organized in the registry. They are not a treatment contrast with a confidence interval. The entry with one observation cannot provide a useful estimate of variation among participants, while the other entry is also based on a very small reported group.

A standard deviation should not be confused with a standard error or a confidence interval. A standard deviation describes the observed spread; a standard error concerns uncertainty in an estimated mean and depends on the information contributing to that estimate. Neither can be reconstructed as a valid treatment-effect uncertainty measure from these entries alone. The registry also does not report the underlying individual measurements, so further checks or a reanalysis are not possible from the posted summaries.

How should missing results be handled?

General statistical practice calls for clear reporting of which participants contributed to each outcome, how missing measurements were handled, and which population was analyzed. Those details matter in a crossover trial because participants may have data for one period but not another. The registry does not report an analysis population, missing-data method, or period-level completion information. It would therefore be inappropriate to assume that the summaries include all enrolled participants or that missing measurements were handled in a particular way.

The registry lists enrollment as 6, while the displayed sequence-group sizes are 1 and 2. This difference is not reconciled in the record. It is not possible to determine from the summaries whether the remaining enrollment reflects absent outcome data, exclusions, incomplete periods, or another explanation. Those possibilities are not established by the registry, and the reason is not reported in the registry record.

What do planning calculations mean?

Sample-size planning is distinct from analysis of observed trial results. In general, a planning calculation uses assumptions about the effect to detect, variability, significance level, allocation, and statistical method to estimate how many participants per arm might be needed for a target power. Such a calculation is not observed power and does not show what the trial achieved. The registry describes a planning illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of the observed effect. The resulting planning values are not reported in the registry record, and they do not replace an estimate and uncertainty interval for the trial’s treatment effect.

For this record, the key methodological distinction is between descriptive sequence-group summaries and an analyzed crossover treatment effect. The former are posted; the latter, including its uncertainty and model, is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 1 outcome measure and 0 analyses. It reports no secondary outcomes. The primary outcome is a continuous FEV1 measure, but no inferential analysis of the primary treatment contrast is posted. A multiple-testing adjustment is therefore not reported, and it is not possible to determine from the record whether any outcome or analysis choices were prespecified beyond the listed primary endpoint.

Multiplicity concerns arise when several outcomes, time points, subgroups, or statistical comparisons are tested. In general, repeated testing can increase the chance of a false-positive result unless the analysis plan accounts for it. This is a general statistical point; the registry record does not report multiple tests or a multiplicity strategy for this trial. Interim analyses, stopping rules, and any statistical analysis plan are not reported in the registry record.

The registry does not report an analysis population, such as all randomized participants or participants who completed both treatment periods. It also does not describe how missing outcome measurements were handled. These details are particularly relevant in a crossover study, where data may be available for one treatment period but not another. The reported enrollment is 6, while the two sequence summaries have group sizes of 1 and 2; the record does not explain which participants contributed to those summaries or why the reported sizes differ from enrollment.

The study is marked terminated, but the timing and reason for termination are not reported in the registry record. No conclusions can be drawn from that status alone about the timing of the decision, its relationship to enrollment, or whether it affected the analysis. The absence of these details limits assessment of selective reporting, missing data, and the connection between the planned design and the posted results.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events by intervention group. For budesonide/formoterol, the serious-adverse-event group lists 5 at risk and 0 affected. For budesonide, it lists 4 at risk and 0 affected. These are the posted serious-event counts; the registry does not list any serious adverse-event terms.

Zero reported serious adverse events means that none are recorded in these group summaries. It does not establish that an event is impossible or that the treatments have no safety risks. The size and scope of the reported experience are limited, and the registry does not provide a detailed narrative explaining the safety data or how event collection was conducted.

The record also lists other, non-serious adverse events: 1 affected among 5 at risk for budesonide/formoterol, and 0 affected among 4 at risk for budesonide. These counts should be read as the registry reports them, not converted into percentages or used to infer a comparative risk. The crossover design means treatment exposures occurred in sequence, but the adverse-event entries do not report participant-level timing or explain how events were attributed when a participant received both treatments.

Deaths are not reported in the registry record. The adverse-event summaries do not provide enough information to determine event severity beyond the serious versus other categories, duration, relationship to treatment, or whether the same person could contribute in more than one treatment group. The at-risk counts in these summaries should not be treated as a description of the full enrollment without further reporting.

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

The registry record establishes that a randomized crossover trial was registered to compare budesonide/formoterol with budesonide for an exercise-related FEV1 outcome. It also posts sequence-group summaries for the outcome and adverse-event counts by intervention group. The primary outcome was defined as a continuous contrast involving maximal percentage decrease in FEV1 after an exercise challenge relative to a run-in period.

What the posted outcome does not establish is a treatment-effect estimate with a measure of uncertainty. The reported outcome values, -3.1 for the budesonide-first sequence and -19.4 for the budesonide/formoterol-first sequence, are not presented as a direct within-participant comparison between treatments. No confidence interval, test result, or primary analysis is reported. The differences between sequence-group values cannot be used to substitute for a crossover treatment-effect analysis.

The sequence summaries are based on reported group sizes of 1 and 2, while enrollment is listed as 6. The record does not explain the relationship between those counts. Without participant flow, period-specific measurements, and information about missing data, it is not possible to assess how representative the posted outcome summaries are of the enrolled participants or how the planned design was implemented in the analysis.

Statistical interpretation also depends on the scale and the uncertainty around the estimate. The registry describes the treatment contrast direction but does not provide a precision interval or a threshold for clinical importance. The negative signs in the sequence summaries do not, on their own, establish which treatment had a more favorable effect. No conclusion about efficacy or comparative benefit follows from the entries alone.

The safety counts are similarly limited. The serious adverse-event summaries list zero affected in each intervention group, and other adverse events are reported as 1 affected for budesonide/formoterol and 0 for budesonide. These counts are descriptive and do not quantify comparative safety reliably. The record does not report deaths, which should not be interpreted as a confirmation that none occurred.

The most defensible conclusion is about the state of the evidence in the registry: the intended comparison and endpoint are described, but the direct treatment analysis and essential details about analysis populations and missing data are not reported. The result is inconclusive as a comparative statistical estimate in the registry record; that is different from evidence that the treatments are equivalent or different.

13. Why This Trial Matters Statistically

This trial is statistically notable because its design and its posted results call for different levels of interpretation. A crossover trial is intended to compare treatments across periods, often using within-participant information. That structure can be valuable when outcomes are measured repeatedly, but the analysis needs to reflect the repeated measurements and sequence. In this record, the posted values are grouped by which treatment came first, rather than reported as an analyzed treatment contrast.

The distinction between design and result is important for clinical researchers. A title that identifies a crossover comparison does not itself demonstrate that the reported summary uses the design efficiently or estimates the intended contrast. To evaluate that, readers need the period-level data or a stated model, an effect estimate, and uncertainty. Those elements are not reported in the registry record.

The result also illustrates why the number enrolled and the number contributing to a particular outcome should be reported together. Enrollment is listed as 6, while the sequence-group entries report sizes of 1 and 2. The record does not explain the relationship. Without such context, readers cannot determine whether the outcome summary represents all enrolled participants, participants with complete data, or another analysis population.

Finally, descriptive means and standard deviations should not be mistaken for evidence of a treatment difference. One sequence summary has a group size of 1, and neither entry includes a confidence interval for the treatment contrast. A numerical value can look precise when written with a decimal, but the relevant issue is how much information supports it and what comparison it represents. The registry’s lack of a direct analysis makes that distinction especially important.

These features make the record useful as an example of how to separate a planned clinical question, a trial design, descriptive result entries, and inferential evidence. The posted information describes the intended question, but does not provide the statistical result needed to quantify the comparison.

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 immediate limitation is that the registry does not report a direct analysis of the primary crossover treatment contrast. It provides sequence-group means and standard deviations, but not a within-participant estimate, confidence interval, or test result. The sequence summaries should not be used to infer the treatment difference.

The reported outcome group sizes are 1 and 2, while enrollment is listed as 6. The registry does not explain the relationship between these figures, report participant flow, or state how many participants completed each treatment period. The analysis population and handling of missing measurements are not reported in the registry record. This leaves uncertainty about who contributed to the outcome summaries and what data were available for each treatment.

The record does not describe the crossover analysis model, treatment-period effects, sequence effects, or any assessment of carryover. It also does not report whether there was a washout between periods. These details are relevant to a crossover design, but their absence does not establish that the study did or did not use particular procedures.

The primary endpoint is defined in terms of maximal percentage fall in FEV1 after exercise relative to a run-in period, but details about measurement timing, repeated challenges, and the clinical importance of a difference are not reported. The reason for the terminated status is not reported in the registry record. The record also lacks a reported statistical analysis plan, multiplicity strategy, and interim-analysis information.

Safety reporting is limited to group-level counts. The record does not provide event descriptions, timing, attribution, or deaths. The small reported outcome summaries and absence of inferential results mean that neither comparative efficacy nor comparative safety can be judged precisely from the registry entries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial on the Effect of Budesonide/Formoterol and Inhaled Budesonide Alone on Exercise-Induced Asthma — NCT01070888.
• Registry record last updated 2021-07-07; status last verified 2021-07.
• Results first posted 2014-12-30.
• 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 phase 4 randomized crossover trial of budesonide/formoterol and budesonide for exercise-induced asthma in people with persistent asthma. Its primary endpoint is the mean difference in maximal percentage decrease in FEV1 after an exercise challenge relative to a run-in period, expressed as budesonide/formoterol minus budesonide. The outcome timeframe is 8 weeks.

The registry lists enrollment as 6 and status as terminated. The posted outcome summaries are organized by treatment sequence, with group sizes of 1 and 2, and do not provide a direct treatment-effect estimate or confidence interval. The reason for termination, analysis population, missing-data handling, and crossover statistical model are not reported in the registry record.

Serious adverse-event summaries list 0 affected in each intervention group. The registry also reports 1 other adverse event for budesonide/formoterol and 0 for budesonide. These are descriptive counts and do not establish comparative safety. Overall, the record describes the intended clinical comparison but does not report the inferential analysis needed to quantify it.