This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for To Investigate the Relative Efficacy of Terbutaline Turbuhaler® and Salbutamol Pressurized Metered Dose Inhaler (pMDI) a Single Blind Study (NCT01096017), a randomized phase 3 study. The primary outcome is FEV1 (Forced Expiratory Volume in 1 Second) Area Under Curve (AUC) 0-4 Hours After Drug Inhalation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01096017 |
| Phase | Phase 3 |
| Condition | Asthma |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Single |
| Enrollment | 24 |
| Arms in the primary outcome | 2 |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Japanese patients with asthma who needed treatment with inhaled glucocorticosteroids (ICS) were eligible. The brief summary describes the population as patients aged 16 years or older. The registry record lists 24 participants enrolled, while the primary outcome results report 22 participants in each treatment group.
Intervention
Terbutaline Turbuhaler® at 0.4 mg was one of the inhaled treatments. The study was single dose and assessed lung-function measures after inhalation.
Comparator
The active comparator was salbutamol pressurized metered dose inhaler (pMDI) at 200 μg. Placebo devices were also used as part of the treatment sequences: pMDI placebo and placebo Turbuhaler®.
Primary question
The primary question was whether the treatments differed in FEV1 area under the curve from 0–4 hours after inhalation. FEV1 is forced expiratory volume in 1 second, a measure of how much air a person can exhale in the first second of a forceful breath. The registry record describes the primary outcome as a geometric mean in milliliters × minutes.
The crossover design means that participants were assigned to treatment sequences in which each active treatment was given, with the order varying between sequences. One sequence began with terbutaline and then used salbutamol; the other began with salbutamol and then used terbutaline. This allows a within-participant comparison, but the registry record does not report the statistical model used to account for that design.
The study also set out to assess safety through adverse events and vital signs, including blood pressure and pulse rate. The posted results include adverse-event counts, but do not provide results for the vital-sign measures.
3. Trial Design
This was a Phase III, randomized, single-blind, single-dose crossover study in Japanese adult asthma patients. The registry record reports 24 participants enrolled and a completed study. Its start is recorded as 2010-03, with primary completion in 2010-04.
Participants were assigned to one of two sequences. In one sequence, terbutaline Turbuhaler® 0.4 mg was paired with pMDI placebo, followed by salbutamol pMDI 200 μg paired with placebo Turbuhaler®. The other sequence received those treatments in the reverse order. The crossover structure permits measurements under both active treatments in the same participant, while randomization of sequence determines the order. The registry record does not describe the details of allocation concealment, washout procedures, or how the analysis accounted for treatment order or period.
Single blind indicates that masking was recorded as single, but the registry record does not state who was masked. It also does not describe how masking was maintained when the two inhaler devices were used.
The primary outcome was FEV1 area under the curve (AUC) from 0–4 hours after drug inhalation. The measurement schedule included FEV1 at 5, 15, 30, 60, 120, 180 and 240 minutes. The primary outcome timeframe was at two visits during a maximum of 15 days. Secondary outcomes included FEV1 at individual time points, maximum percentage change in FEV1, the number of participants with a change greater than 15% within 4 hours, and time to a change of at least 15%.
The registry record includes 12 outcome measures and 11 posted secondary outcomes, but reports no analyses in its analysis listing. This does not establish whether analyses were conducted outside the registry record; their details are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 37 participants enrolled; 13 excluded (9 due to eligibility criteria not fulfilled and 4 for other reasons)
Treatment Period 1
| Stage | Salbutamol First, Then Terbutaline | Terbutaline First, Then Salbutamol |
|---|---|---|
| STARTED | 12 | 12 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 0 | 0 |
Washout 1 - 14 Days
| Stage | Salbutamol First, Then Terbutaline | Terbutaline First, Then Salbutamol |
|---|---|---|
| STARTED | 12 | 12 |
| COMPLETED | 12 | 12 |
| NOT COMPLETED | 0 | 0 |
Treatment Period 2
| Stage | Salbutamol First, Then Terbutaline | Terbutaline First, Then Salbutamol |
|---|---|---|
| STARTED | 12 | 12 |
| COMPLETED | 11 | 11 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Salbutamol First, Then Terbutaline | Terbutaline First, Then Salbutamol |
|---|---|---|
| Eligibility criteria not fulfilled | 1 | 1 |
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.
| Characteristic | Unit | All Study Participants |
|---|---|---|
| Participants analysed | 24 | |
| Age Continuous | Years | 41.7 (SD 7.4) |
| Sex: Female, Male: Female | Participants | 17 |
| Sex: Female, Male: Male | Participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as FEV1 (Forced Expiratory Volume in 1 Second) Area Under Curve (AUC) 0-4 Hours After Drug Inhalation, measured over At two visits during a maximum of 15 days. FEV1 timepoints: all time points t=5, 15, 30, 60, 120, 180 and 240 minutes..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Full Range |
| Unit | milliLiters x minutes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was FEV1 area under the curve from 0–4 hours after drug inhalation, measured in milliliters × minutes. FEV1 is the volume of air forcibly exhaled in the first second. Repeated FEV1 measurements after inhalation describe the course of lung function over the assessment period; the area under that time course combines the measurements into an overall measure across the period.
AUC can be useful when a treatment may affect both the size and duration of a response. Rather than relying on a single measurement, it captures the accumulated level of FEV1 across the scheduled time points. A larger AUC indicates a larger integrated FEV1 measure over the assessment interval, but interpretation of a treatment comparison requires an estimate of the between-treatment difference and its uncertainty.
The registry record reports geometric means for the two treatments, with full ranges. It does not report a primary between-treatment estimate, confidence interval, or p-value. The stated endpoint timeframe was at two visits during a maximum of 15 days, with FEV1 scheduled at 5, 15, 30, 60, 120, 180 and 240 minutes. The record does not give further details about how the AUC was calculated, how the visits contributed to the primary analysis, or how missing measurements were handled.
Because this is a crossover study, measurements under the treatments are related within participants. A comparative analysis should reflect that relationship. The analysis method used for the primary endpoint is not reported in the registry record, so the posted treatment-specific summaries alone do not establish the result of a formal crossover comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome summaries are geometric means of 617.6 for salbutamol pMDI and 634.6 for terbutaline Turbuhaler®, with 22 participants reported for each treatment. The record gives full ranges for both groups. Those ranges overlap, but a range describes the observed spread of participant values; it is not a confidence interval for a treatment difference. The posted summaries therefore describe the observed treatment-specific values, not the precision of a comparative effect estimate.
No primary comparison estimate, confidence interval, or p-value is reported in the registry record. As a result, the posted primary outcome summaries do not show how precisely the treatments differed, nor whether a formal analysis accounted for the paired nature of the crossover measurements. A difference between the two listed geometric means is not, by itself, a treatment-effect estimate with an assessment of uncertainty.
The registry record reports 24 participants enrolled, whereas each primary outcome group lists 22. It does not explain the difference or state how many participants contributed paired primary measurements. The sample accounting and analysis population are therefore unclear from the registry record. That limits interpretation of both the primary estimates and their relationship to the randomized cohort.
Some secondary outcomes have unadjusted comparison estimates based on the posted group summaries. Their intervals are broad, and the intervals for the displayed comparisons include values on both sides of no difference. These estimates are exploratory in the absence of a reported analysis plan and a stated approach to multiple comparisons. The secondary outcomes also represent different aspects of response: whether a threshold was reached, how long it took to reach it, and changes at particular time points. They should not be treated as interchangeable confirmations of the primary endpoint.
The record lists zero serious adverse events and zero other adverse events for each treatment group among 23 participants at risk in each group. Those entries describe what was recorded for the stated groups, but they do not provide a detailed account of event ascertainment, duration of safety follow-up, or the relationship between each group count and the crossover exposure. Death counts are not reported in the registry record.
Overall, the registry record supports a descriptive account of the treatment-specific primary outcome and selected secondary and safety outcomes. It does not include enough detail to establish a formal primary treatment comparison or its uncertainty. The summaries should therefore be read as descriptive posted results rather than as a complete report of the statistical evidence.
9. Statistical Methods Explained
What does the primary outcome summary represent?
A geometric mean summarizes measurements on a multiplicative scale. It is commonly useful when values are positive and their distribution is skewed, because multiplicative variation can be more natural than variation measured by adding and subtracting a fixed amount. This is a general statistical explanation; the registry record does not explain why a geometric mean was selected for this endpoint or describe any transformation used in the analysis.
The primary outcome lists a full range alongside each geometric mean. A range reports the lowest and highest observed values in the group. It gives information about the extent of the observed values but does not show how much uncertainty there is about the difference between treatments. In particular, the endpoints of a range are not confidence limits. A confidence interval is a statistical interval intended to express uncertainty around an estimated quantity, such as a treatment contrast. No primary confidence interval is reported in the registry record.
Why does the crossover design matter?
In a crossover study, each participant receives more than one treatment, so measurements from the same person are correlated. A paired analysis can use the fact that each participant serves as their own comparison, often reducing the influence of stable differences between participants. That advantage depends on an analysis that respects the within-participant structure. Treatment order and period can also matter in crossover studies. The registry record identifies randomized treatment sequences but does not report the primary analysis model or how sequence, period, or within-participant correlation were handled.
The group summaries do not show the distribution of within-participant differences. Without those paired data or a reported crossover analysis, the treatment-specific geometric means cannot be used to recover the precision of a formal comparison. The record lists 22 participants for each primary treatment summary, but does not state whether those are the same participants with complete measurements under both treatments.
How should secondary comparisons be read?
For the threshold outcome, the comparison is expressed as a risk difference: the difference between the proportions meeting the stated response threshold in the two groups. A risk difference of zero corresponds to equal proportions. The associated interval conveys uncertainty in that difference, and an interval spanning zero is compatible with both a lower and a higher proportion under the treatment comparison. The posted secondary result also includes a p-value that is explicitly unadjusted. An unadjusted p-value does not account for the number of outcomes or comparisons examined.
For time to response, the registry record gives group means and standard deviations and a mean-difference estimate with an interval. A mean difference expresses the contrast on the outcome's original scale, minutes. The standard deviation describes participant-to-participant spread, whereas the confidence interval for a mean difference concerns uncertainty in the estimated contrast. They answer different questions. General statistical principle: a large standard deviation can coexist with a relatively precise mean estimate when there is substantial information, while a small standard deviation does not by itself guarantee a precise treatment comparison.
The secondary comparisons are described as unadjusted. They are not listed as reported analyses in the registry record. They should therefore be distinguished from a prespecified sponsor analysis, whose methods and results are not reported in the registry record. No discrepancy between a reported analysis and a recalculated comparison is flagged in the record, but the absence of a discrepancy flag does not supply a missing statistical plan.
What do the planning illustrations mean?
The registry record includes planning illustrations based on observed secondary effects. The assumptions stated are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect considered is a stated fraction of the observed effect. Such calculations illustrate how a hypothetical future study's required sample size can change under different effect assumptions. They are not the trial's reported design justification and are not observed power. The trial's own sample-size assumptions and justification are not reported in the registry record.
Sample-size planning is sensitive to assumptions about the effect worth detecting, variability, allocation, analysis, and missing data. An effect estimated from a small study may be unstable, so using it as the basis for planning can yield an uncertain illustration. The record does not provide a prospective target effect or explain whether the planning scenarios relate to a planned future study.
What cannot be inferred from these methods?
The registry record does not report a primary hypothesis test, a primary comparison interval, a statistical model, an analysis population, or a method for handling missing outcomes. It also does not report multiplicity procedures, interim analyses, or a fuller statistical analysis plan. General statistical principles can explain why these details matter, but they cannot identify which methods were actually used. Without them, the posted summaries do not establish the confirmatory interpretation, precision, or robustness of the treatment comparison.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists multiple outcomes, including the primary FEV1 AUC, FEV1 at several time points, maximum percentage change, a threshold-response count, and time to threshold response. It does not report whether the study used a multiplicity adjustment, which outcomes were treated as confirmatory, or whether any testing hierarchy was specified. The adjustment approach, if any, is not reported in the registry record.
This matters because multiple statistical tests can raise the chance of at least one apparently unusual result even when no treatment difference exists. General statistical methods for addressing multiplicity include controlling the overall false-positive rate or emphasizing estimation and uncertainty rather than isolated p-values. The record does not state whether either approach was used. The unadjusted secondary p-values should not be interpreted as accounting for the full set of outcomes.
The registry record also does not report how missing FEV1 measurements were handled, whether participants with incomplete treatment sequences were included, or how the analysis population was defined. Although 24 participants were enrolled and the primary outcome lists 22 participants per treatment, the record does not explain the sample accounting. It is therefore not possible to determine from the registry record whether the primary summaries reflect all randomized participants, a complete-case group, or another analysis population.
No details are reported about interim analyses, stopping rules, or a full statistical analysis plan. Nor are the procedures for handling missing data, protocol deviations, or the within-participant structure of the crossover analysis described. These omissions do not establish that such procedures were absent; they mean that they are not reported in the registry record. Interpretation of statistical significance, bias from missing observations, and the intended hierarchy of evidence is consequently limited.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Salbutamol pMDI | 0 | 23 | 0.0% |
| Terbutaline Turbuhaler® | 0 | 23 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Salbutamol pMDI | 0 of 23 |
| Terbutaline Turbuhaler® | 0 of 23 |
For each treatment group, the registry record reports 23 participants at risk, zero participants with a serious adverse event, and zero with another adverse event. These are the posted event counts for the listed groups. The death counts are not reported in the registry record.
The adverse-event entries should be read as counts, not as a complete safety profile. The record does not provide detailed event terms, exposure duration for each treatment, event severity beyond the serious-event category, or information about how events were collected and attributed. It also does not explain how the at-risk counts relate to the primary outcome groups, which list 22 participants per treatment, in this crossover study.
Zero recorded events in these categories does not establish that an event is impossible or that no events occurred outside the recorded categories or follow-up. It describes the registry entries, and the absence of further safety detail limits what can be concluded from them. The brief summary also names blood pressure and pulse rate as safety measures, but results for those measures are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted primary results describe geometric mean FEV1 AUC values for each treatment over 0–4 hours after inhalation. They show the observed group summaries and full ranges, but do not include a formal primary comparison estimate or its uncertainty. For that reason, the record does not establish the size or precision of a between-treatment effect on the primary endpoint.
A treatment-specific summary is not equivalent to a randomized comparison. In this crossover design, the same participants were assigned to receive both active treatments in a randomized sequence. A valid comparative interpretation should account for the paired measurements and potentially relevant order or period effects. The registry record does not describe the model used or report a primary contrast that would make those considerations assessable.
The secondary outcomes and adverse-event counts add descriptive information, but they do not repair missing details about the primary analysis. The secondary comparisons are unadjusted, and the record does not report whether multiple testing was addressed. The safety entries report no serious or other adverse events in the listed groups, but provide limited detail on follow-up and do not report death counts or vital-sign results.
These limitations do not mean that no analysis was performed or that the treatments are equivalent. They mean that the registry record does not report enough statistical information to support those conclusions. A lack of a reported primary p-value or confidence interval is not evidence of no difference; it leaves the comparative uncertainty unquantified in the registry record.
The trial therefore contributes a record of a randomized crossover comparison and treatment-specific outcome summaries in the described population. Its posted results should be interpreted as descriptive evidence with incomplete reporting of the comparative analysis. No medical conclusion about treatment choice follows from these summaries alone.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its crossover design and outcome summaries make the distinction between descriptive values and a treatment comparison especially important. Each participant received both active treatments in a randomized sequence, so a comparison should use the within-participant relationship rather than treating the treatment groups as if they were independent samples. The registry record does not report how the primary analysis addressed that feature.
The record also illustrates why a treatment-specific geometric mean and observed range do not answer the same question as a comparative estimate with uncertainty. The former describe the observed values under each treatment; the latter would quantify the estimated contrast and how precisely it is known. A primary contrast and interval are not reported, so readers cannot assess the precision of the comparison from the posted primary summaries alone.
Several secondary outcomes offer additional descriptions of response, but unadjusted results from multiple outcomes have a different evidential status from a prespecified primary analysis. Without a reported multiplicity approach or outcome hierarchy, isolated secondary comparisons should be interpreted cautiously. This is a general statistical issue that applies even when the outcomes are clinically related.
Finally, the enrollment count and outcome sample counts are not reconciled in the registry record, and key analysis details are absent. These gaps demonstrate how reporting of analysis populations, missing-data methods, and crossover models affects the ability to interpret a result. Complete statistical reporting is essential not only for reproducing an analysis but also for judging what its estimates can and cannot establish.
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.
Several limitations specific to this trial follow from the registry record. First, it reports 24 participants enrolled but 22 participants for each primary treatment summary and does not explain the difference. It is not possible to establish the number with complete paired primary measurements or the analysis population from these entries alone.
Second, the primary outcome is reported as treatment-specific geometric means and full ranges without a primary treatment contrast, confidence interval, or p-value. The analysis method for the crossover structure is also not reported. This leaves the comparative precision and the treatment-order handling unclear.
Third, the record gives limited detail about the endpoint calculation, including how the FEV1 time points were combined into AUC and how the two visits contributed to the analysis. It does not report missing-measurement procedures, period or sequence effects, or other model details. The stated outcome schedule and study design do not resolve those omissions.
Fourth, the posted secondary comparisons are unadjusted, while the registry record does not report a multiplicity strategy or analysis hierarchy. The safety results are also limited: death counts and results for the named vital-sign measures are not reported, and details about event follow-up and exposure are not given. These are reporting limitations; they do not establish that relevant procedures or analyses were not conducted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: To Investigate the Relative Efficacy of Terbutaline Turbuhaler® and Salbutamol Pressurized Metered Dose Inhaler (pMDI) a Single Blind Study — NCT01096017.
- Registry record last updated 2012-08-31; status last verified 2012-07.
- Results first posted 2012-08-31.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed, randomized, single-blind, single-dose, crossover Phase III study of terbutaline Turbuhaler® 0.4 mg and salbutamol pMDI 200 μg in Japanese patients with asthma who needed ICS treatment. It reports 24 participants enrolled and describes two treatment sequences using active inhalers and placebo devices.
The primary endpoint was FEV1 AUC from 0–4 hours after inhalation. Treatment-specific geometric means and full ranges are posted, with 22 participants listed per treatment, but a primary comparative estimate and its uncertainty are not reported in the registry record. Secondary outcomes cover FEV1 response over time and threshold response; the listed comparisons are unadjusted. Serious and other adverse-event counts are zero in each group among 23 participants at risk, while death counts and vital-sign results are not reported in the registry record.
Details of the primary statistical model, analysis population, missing-data handling, and multiplicity approach are not reported in the registry record.