Comparison of Single-Dose Efficacy of an Albuterol Breath-Actuated Inhaler (Albuterol-HFA-BAI) Versus an Albuterol Metered-Dose Inhaler (Albuterol-HFA-MDI) in Participants With Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of Single-Dose Efficacy of an Albuterol Breath-Actuated Inhaler (Albuterol-HFA-BAI) Versus an Albuterol Metered-Dose Inhaler (Albuterol-HFA-MDI) in Participants With Asthma (NCT00530062), a randomized phase 4 study. The primary outcome is Area-Under-the-Effect Curve of Percent Change in Test-Day Baseline Forced Expiratory Volume in 1 Second (FEV1) Versus Time (up to 2 Hours Postdose), %FEV1 AUEC0-2.

2. Clinical Question

The question concerns the response measured after a single dose, not longer-term asthma control. FEV1 is forced expiratory volume in 1 second, a measure of the volume of air forcibly exhaled in the first second of a breath. The primary outcome combines the change in this measure over time into an area-under-the-curve summary. It therefore reflects both the size and persistence of the measured response during the specified postdose period.

The clinical comparison is between delivery devices for the same stated albuterol dose. The study description focuses on participants with poor inhaler coordinating ability, making the delivery method central to the research question. The registry record does not report a treatment recommendation or a minimum difference considered clinically important. The results can describe the observed comparison and its statistical precision, but do not by themselves determine whether any difference would matter to patients.

3. Trial Design

The registry identifies this as a randomized, unmasked, phase 4 crossover trial in participants with asthma. Its stated purpose was to compare single-dose efficacy of albuterol-HFA-BAI with albuterol-HFA-MDI among asthmatics with poor inhaler coordinating ability. Enrollment is listed as 49. The study status is completed, with a start date of 2007-07-25 and a primary completion date of 2008-10-24.

In a crossover design, the treatment comparison is organized around treatment periods and sequences rather than a simple parallel assignment in which each participant receives only one treatment. The registry descriptions say participants received a single actuation of albuterol 90 mcg using either device in treatment period 1 or 2. The primary endpoint description also says that the adjusted analysis accounted for treatment sequence and study period. The registry record does not report the sequence details, a washout interval, or the timing between treatment periods.

Randomization is reported, while masking is listed as none. Thus, the record does not describe blinded treatment assignment. It reports the primary outcome for an ITT population defined as randomized participants who took at least one dose of the assigned study medication; the primary results list 49 participants for each treatment. The record does not report details of adherence, withdrawals, missing observations, or the handling of incomplete outcome measurements.

The primary endpoint was analyzed as a continuous measure. The registry describes the reported primary analysis as an analysis of covariance (ANCOVA) of adjusted means and identifies study center, treatment sequence, and study period as adjustment factors in the endpoint description. No additional details about the fitted model, assumptions, or analysis plan are 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: Eligible participants were randomized to receive the following 2 treatments on separate occasions 2-7 days apart: Albuterol-hydrofluoroalkane-breath-actuated inhaler (HFA-BAI) and Albuterol-HFA-metered-dose inhaler (MDI).

Overall Study

Analysis population for the primary outcome, as defined in the registry: ITT population included all randomized participants who took at least 1 dose of the assigned study medication.

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: Intent-to-treat (ITT) population included all randomized participants who took at least 1 dose of the assigned study medication.

6. Primary Endpoint

The registry lists the primary outcome as Area-Under-the-Effect Curve of Percent Change in Test-Day Baseline Forced Expiratory Volume in 1 Second (FEV1) Versus Time (up to 2 Hours Postdose), %FEV1 AUEC0-2, measured over Baseline, Up to 2 hours postdose.

The primary endpoint is the area-under-the-effect curve of percent change in test-day baseline FEV1 versus time, up to 2 hours after dosing. Its unit is percent change from baseline*hour. The baseline value was the average of the two predose FEV1 measurements. The record says the area was calculated using the linear trapezoidal rule, which approximates the area between measured time points by joining adjacent observations with straight lines.

An area-under-the-curve outcome is used to summarize a sequence of measurements in one value. In general, it can reflect both the magnitude of change and how that change evolves during the observation period; it is not simply a single measurement at the end of follow-up. Here, the endpoint focuses on the percent change in FEV1 and covers up to 2 hours postdose. Its interpretation is tied to that time window and to the measurements collected within it.

The registry reports treatment means and standard errors, and describes the primary analysis as a mixed-effect analysis of variance adjusted for study center, treatment sequence, and study period. This adjusted analysis addresses the crossover structure described in the record. The endpoint is a measure of short-term lung-function response after one dose; the registry does not report it as a measure of longer-term symptoms, exacerbations, or sustained asthma control.

7. Results Posted in the Registry

• Albuterol-HFA-MDI: mean 20.46 versus 21.40 on control; difference -0.95 (95% CI -7.20 to 5.31), standardized effect d = -0.06; z-test p = 0.767.

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.

Percent Change From Baseline in FEV1 Within 30 Minutes Postdose

• 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:
  • Albuterol-HFA-MDI: mean 10.11 versus 10.78 on control; difference -0.66 (95% CI -3.94 to 2.61), standardized effect d = -0.08; z-test p = 0.692.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Albuterol-HFA-MDI and the control. The interval gives the range of effects that remain compatible with the data.

Percent Change From Baseline in FEV1 up to 2 Hours Postdose

• 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:
  • Albuterol-HFA-MDI: mean 13.73 versus 14.32 on control; difference -0.59 (95% CI -4.16 to 2.98), standardized effect d = -0.07; z-test p = 0.747.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Albuterol-HFA-MDI and the control. The interval gives the range of effects that remain compatible with the data.

Area-Under-the-Effect Curve of Change in Test-Day Baseline FEV1 Versus Time (up to 2 Hours Postdose), FEV1 AUEC0-2

• 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:
  • Albuterol-HFA-MDI: mean 0.41 versus 0.44 on control; difference -0.04 (95% CI -0.16 to 0.09), standardized effect d = -0.12; z-test p = 0.563.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Albuterol-HFA-MDI and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary continuous outcomes cover percent change in FEV1 within 30 minutes, percent change in FEV1 up to 2 hours, and the area under the curve for change in FEV1 over up to 2 hours. Across these measures, the group means are close, and the unadjusted comparison intervals include zero. That broad pattern is consistent with the primary result in the limited sense that these posted comparisons do not establish a clear difference between devices.

These secondary outcomes provide different views of short-term response: a measurement within 30 minutes, a summary over the postdose period, and an area-under-the-curve measure in liters*hours rather than percent change. They are related to the primary endpoint because they concern FEV1 after dosing, but they are not identical outcomes. The primary measure uses percent change from baseline over time and is reported through an adjusted analysis; the recalculated secondary comparisons are unadjusted.

The registry lists additional secondary outcomes, including threshold responses and timing measures. Their numerical results are not reported in the registry record used for this interpretation. No conclusions about those outcomes can be drawn from the three continuous measures.

In general, when multiple outcomes or comparisons are tested, the chance of observing at least one apparently unusual result can increase. Unadjusted secondary p-values do not account for that multiplicity, and the registry does not report a correction or testing hierarchy. The secondary results therefore carry less confirmatory weight than the designated primary analysis. They are best read as supporting descriptive context, not as independent proof of a treatment difference or as evidence of equivalence.

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

• Percent Change From Baseline in FEV1 Within 30 Minutes Postdose
• Percent Change From Baseline in FEV1 up to 2 Hours Postdose
• Area-Under-the-Effect Curve of Change in Test-Day Baseline FEV1 Versus Time (up to 2 Hours Postdose), FEV1 AUEC0-2
• Percentage of Participants With a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose
• Percentage of Participants With a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose
• Time to a 12% Increase From Baseline in FEV1 Within 2 Hours Postdose
• Time to a 15% Increase From Baseline in FEV1 Within 2 Hours Postdose
• Time to Maximum Increase in FEV1

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant's outcome is a numerical area-under-the-effect curve. The registry reports group means and standard errors, alongside an adjusted comparison based on ANCOVA. In general, a mean summarizes the central value of a continuous measurement, while a standard error describes the uncertainty in an estimated mean. A standard error is not the same as the spread of individual participant measurements.

Why adjust the primary comparison?

The registry says the primary mean was obtained from a mixed-effect analysis of variance adjusted for study center, treatment sequence, and study period. In general, adjustment can account for features of the design that may be associated with the outcome. Sequence and period are especially relevant concepts in a crossover comparison: responses may vary with the order in which treatments are received or with the period in which they are measured. The record names these adjustment factors, but it does not report the model specification, covariance structure, or further assumptions. Those details are not reported in the registry record.

The treatment estimate from the adjusted analysis is the registry's reported comparison for the primary outcome. The sponsor reports a difference in adjusted mean of 0.946, a 95% confidence interval from -2.293 to 4.185, and p = 0.559. The interpretation of a difference's sign depends on the order used to subtract treatment means. The registry lists the groups but does not state the subtraction direction in the result description, so the estimate is best quoted as reported rather than assigned an unstated direction.

What is the recalculated comparison?

The unadjusted recalculation uses the posted group means and standard errors to estimate a simple difference, without fitting the trial's adjusted crossover model. It gives an MDI-minus-BAI mean difference of -0.946, with a 95% confidence interval from -7.205 to 5.313 and p = 0.767. This is useful as a transparent comparison derived from the summary values, but it does not replace the sponsor's analysis. It does not account for the study center, treatment sequence, or study period in the way the reported primary analysis does.

In general, a confidence interval describes a range of effect estimates compatible with the observed data under the method's assumptions. A p-value describes how unusual data at least as inconsistent with a null hypothesis would be if that null and the model assumptions held. Neither statistic states the probability that a treatment is effective, nor does a p-value quantify clinical importance. A confidence interval that includes zero means the data do not establish a nonzero difference at the corresponding confidence level; it does not prove equality.

Why does the crossover structure matter?

In a crossover design, participants receive treatments in different periods, so within-participant information may contribute to comparisons. In general, this can be useful because participants can serve as their own reference, but the analysis must account for the treatment order and period structure. The record confirms that the reported primary model adjusted for sequence and period, but does not provide enough detail to assess all modeling choices. The recalculation based on group summary statistics should therefore be read as an unadjusted illustration, not as a reconstruction of the trial's full analysis.

Why can over-dispersion matter in other analyses?

General statistical context: for count or binary outcomes, over-dispersion means that variation is greater than a simple model assumes. If it is ignored, standard errors may be too small and confidence intervals too narrow. The primary endpoint in this trial is continuous, and the registry describes it using means and standard errors; over-dispersion is not identified as a feature of the reported primary analysis. This concept is included as a general distinction, not as a finding about this trial.

The registry provides no detailed account of diagnostic checks, missing-data methods, sensitivity analyses, interim analyses, or the original statistical analysis plan. Those methods are not reported in the registry record, so their use cannot be inferred from the posted estimates.

11. Confidence Intervals and Precision

The primary sponsor-reported 95% confidence interval extends from -2.293 to 4.185 for the adjusted mean difference of 0.946. Because the interval crosses zero, the data are compatible with no difference under the reported model, as well as with values on either side of zero. The interval also makes clear that the estimate is not exact: there is uncertainty around the point estimate, and the range is broad enough that the result does not sharply distinguish among possible treatment differences.

The unadjusted recalculation has a 95% confidence interval from -7.205 to 5.313 for the MDI-minus-BAI difference. This interval also includes zero and is wider than the sponsor-reported adjusted interval. The two intervals arise from different analyses and should not be compared as if they were estimates from an identical model. The recalculated interval uses posted summary statistics, while the sponsor's primary result is adjusted for factors identified in the record.

In general, a confidence interval is a measure of statistical precision: narrower intervals indicate less uncertainty about the effect estimate under the method's assumptions, while wider intervals indicate more. It does not guarantee that the true effect lies in the interval for this particular trial, and it does not address whether the values in the interval are clinically important. The registry does not state a threshold for clinical importance.

The posted primary data include standard errors for each treatment mean, but no confidence limits for the individual means. The comparison interval is therefore the more direct guide to uncertainty about the treatment contrast. The findings support caution about drawing a firm conclusion on the size or direction of a difference. They do not establish that the treatments have equivalent effects, and they do not precisely exclude differences that could be relevant under a clinical threshold not reported in the registry record.

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 figures are planning illustrations based on the observed effect, not the trial's original design calculations. The listed 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 at the stated fraction of the observed effect. For these continuous outcomes, the figures are participants per arm, not total events. The event-count convention applies to time-to-event planning illustrations, and the endpoints discussed in these posted results are continuous.

The 80% power column describes the number of participants per arm in a hypothetical study designed to have an 80% chance of detecting the specified effect if that effect were present and the planning assumptions held. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations, not probabilities that the observed trial result is correct. The figures are not observed power.

Planning for 75% of the observed effect requires more participants per arm than planning for 100% of the observed effect, and planning for 50% requires more again. This reflects a general statistical relationship: smaller differences are harder to distinguish from random variation, so more information is needed to detect them at the same significance and power targets. The values therefore illustrate how strongly projected sample requirements depend on the effect size chosen for planning.

The observed comparison in this trial is based on the registry's listed treatment groups and its crossover analysis. The planning illustrations use assumptions that are explicitly stated for those calculations; they should not be mistaken for the protocol's sample-size justification. The trial's original design assumptions and sample-size justification are not reported in the registry record. The illustrations also do not account for design details beyond those listed, so they are not a substitute for planning a future crossover study using an appropriate model and its own 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.946; pooled standard deviation σ = 15.806.
2. n = 2 × (1.96 + 0.842)² × 15.806² / -0.946² = 4,382.3, rounded up to 4,383 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
delta <- -0.945999999999998                      # observed difference in means
sigma <- 15.8060387510597                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(530062)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 4,383 (80% power), 5,867 (90% power)
 75% of observed effect: n per arm = 7,791 (80% power), 10,430 (90% power)
 50% of observed effect: n per arm = 17,530 (80% power), 23,467 (90% power)
power.t.test: 4383.3 
Simulated power at n = 4,383 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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. Analyses Reported by the Sponsor

The registry reports the sponsor's primary analysis as ANCOVA, with a difference in adjusted mean of 0.946, a 95% confidence interval from -2.293 to 4.185, and p = 0.559. The endpoint description says the primary mean came from a mixed-effect analysis of variance adjusted for study center, treatment sequence, and study period. This adjusted comparison is the analysis reported for the trial's primary outcome.

The unadjusted recalculation gives an MDI-minus-BAI difference of -0.946, a 95% confidence interval from -7.205 to 5.313, and p = 0.767. It is computed from the posted summary statistics and does not reproduce the adjusted crossover model. The difference in the sign of the point estimates reflects the stated direction of the recalculated contrast versus the reported adjusted estimate; the registry result does not specify the subtraction direction for its adjusted contrast.

The sponsor-reported analysis should be read as the trial's own primary comparison, while the recalculation is a supplementary unadjusted check. Both intervals include zero and neither analysis provides strong evidence of a nonzero difference. Their estimates and precision should not be treated as interchangeable because their methods differ. The discrepancy flag is false in the registry record; this does not remove the methodological distinction between the adjusted result and the unadjusted recalculation.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary endpoint and lists secondary outcomes, but it does not report a multiplicity adjustment, a prespecified hierarchy for testing outcomes, or a detailed statistical analysis plan. Those features are not reported in the registry record. Without that information, the secondary comparisons should be treated as exploratory or supportive rather than as a set of independent confirmatory tests.

Multiplicity matters in general because repeated statistical testing can increase the likelihood of at least one chance finding. Adjustments or a prespecified testing order can address that concern, but no such approach is described in the registry record. The posted unadjusted secondary comparisons should therefore be interpreted with restraint, especially when considered alongside several outcomes and time windows.

The primary population is described as the ITT population including all randomized participants who took at least one dose of assigned study medication. This definition is reported, but the registry does not provide details on how many participants had missing measurements, how missing observations were handled, or whether any sensitivity analyses were conducted. The record lists 49 participants for each primary treatment group; that information alone does not establish that every scheduled measurement was available or explain how incomplete data were treated.

The reported primary analysis adjusted for study center, treatment sequence, and study period. Further details about model assumptions, the handling of within-participant correlations, or alternative analyses are not reported in the registry record. Interim analyses and stopping rules are also not reported. These omissions limit independent assessment of how fully the posted analysis plan addressed multiplicity and missing data. They do not demonstrate that a particular method was or was not used; they mean only that the registry record does not describe it.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The registry lists zero serious adverse events in the Albuterol-HFA-BAI group among 49 at risk and zero in the Albuterol-HFA-MDI group among 49 at risk. It also lists zero other adverse events and zero deaths for each treatment group. No serious adverse-event terms are listed.

These figures describe the adverse-event counts recorded during the study as presented in the registry. A zero count means that no event was recorded in that category for the listed group; it does not establish that an event is impossible, nor does it rule out less common or later events. The study involved a single-dose comparison and the record does not provide a detailed safety narrative, event definitions, follow-up duration for safety, or information about whether all events were systematically collected.

The listed at-risk figures are group-level registry entries. The record does not report a separate analysis of safety differences, confidence intervals, or a statistical comparison between devices. Thus, the figures support a descriptive account of the posted adverse-event data, not a conclusion that either device has no risk or that safety is equivalent.

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

The main statistical result is that the registry's adjusted primary comparison did not establish a difference in the area under the curve for percent change in FEV1 over up to 2 hours after a single dose. The adjusted estimate was 0.946, with a 95% confidence interval from -2.293 to 4.185 and p = 0.559. The interval includes zero, and the estimate is uncertain. The posted results therefore do not establish a statistically clear difference, but they also do not demonstrate that the devices have identical effects.

The unadjusted recalculation and the posted secondary continuous comparisons likewise have confidence intervals that include zero. They are useful context but do not replace the primary adjusted analysis. The recalculation uses a different approach, and the secondary comparisons are not reported as adjusted tests of the primary question. The registry does not identify a clinically important difference, so statistical uncertainty cannot be translated into a judgment about clinical importance.

The result applies to the study's stated population and setting: participants with asthma and poor inhaler coordinating ability, receiving a single 90 mcg actuation of albuterol by one of the two inhaler devices and assessed over the reported postdose period. It does not address longer-term treatment, repeated dosing, other outcomes not reported, or groups not described in the record.

The adverse-event entries record zero serious adverse events, zero other adverse events, and zero deaths for each listed treatment group. Those counts are descriptive and do not prove an absence of risk. The registry's outcome estimates also cannot support individual treatment decisions. In general, trial statistics characterize group-level data under a study's design and analysis; they do not determine what is appropriate for a particular person.

In short, the posted evidence is compatible with no clear difference in the measured short-term FEV1 response, while retaining uncertainty about the size and direction of any difference. It should not be read as proof of equivalence, as evidence about long-term control, or as a treatment recommendation.

18. Why This Trial Matters Statistically

This trial is statistically notable because it compares delivery devices in a crossover design, where treatment sequence and study period can matter to the analysis. The registry's primary analysis accounts for study center, treatment sequence, and study period. That distinction helps explain why the sponsor-reported adjusted comparison is more directly relevant to the stated primary question than a simple recalculation from group means.

The primary outcome also illustrates the value and limits of summarizing repeated measurements with an area-under-the-curve measure. In general, such a summary can represent response across a defined time window rather than at a single measurement time. At the same time, its meaning depends on how measurements were collected, how the area was calculated, and which postdose period was included. The registry reports the trapezoidal calculation and the up-to-2-hour window, giving the result a specific interpretation.

The contrast between a point estimate and its confidence interval is important. A reported mean difference alone can look definitive, but the interval indicates substantial uncertainty around that estimate. Here, the primary interval crosses zero, and the record does not define a clinical threshold. Statistical non-significance therefore cannot be turned into a claim of equivalence or clinical sameness.

The planning illustrations further demonstrate, in general, how projected sample requirements depend on the effect size selected for detection. They are not a retrospective measure of the trial's ability to find a difference and do not reveal the original design rationale. Keeping those planning assumptions distinct from the observed trial analysis helps prevent misleading claims about power.

19. 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 registry record gives limited detail on the crossover procedures. It identifies treatment periods and reports adjustment for sequence and period, but does not describe the sequences, washout interval, timing between treatments, or other procedural details. Those features can inform interpretation of a crossover study, but cannot be reconstructed from the reported results.

The study was unmasked. The record does not describe procedures to reduce the influence of knowledge of treatment assignment on measurement or reporting. The primary endpoint is based on FEV1 measurements, but the registry does not provide operational details about measurement quality or assessment procedures.

The primary outcome is a short-term, single-dose measure. It does not directly describe longer-term asthma outcomes. The registry's stated population is participants with asthma and poor inhaler coordinating ability, so the findings should not be generalized to populations or treatment circumstances not described in the record. The record does not report a clinically important difference, limiting interpretation of whether the interval's possible values would matter clinically.

The sponsor's adjusted result is reported, but detailed model specifications, diagnostics, missing-data methods, sensitivity analyses, multiplicity handling, and interim analyses are not reported in the registry record. The unadjusted recalculation cannot supply those missing details and should not be used in place of the sponsor's primary analysis. The sample-size illustrations use their stated assumptions and observed effect; the original sample-size rationale is not reported. Finally, the posted adverse-event counts are descriptive and do not establish comparative safety or rule out risks not observed during the recorded study.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Comparison of Single-Dose Efficacy of an Albuterol Breath-Actuated Inhaler (Albuterol-HFA-BAI) Versus an Albuterol Metered-Dose Inhaler (Albuterol-HFA-MDI) in Participants With Asthma — NCT00530062.
• Registry record last updated 2022-09-07; status last verified 2022-08.
• Results first posted 2022-08-31.
• 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.

23. Record Summary

The registry describes a completed, randomized, unmasked, phase 4 crossover trial comparing single-dose albuterol-HFA-BAI with albuterol-HFA-MDI in participants with asthma and poor inhaler coordinating ability. Each treatment description specifies a single actuation of albuterol 90 mcg, administered in treatment period 1 or 2. Enrollment is listed as 49.

The primary outcome was the area-under-the-effect curve for percent change in baseline FEV1 over up to 2 hours after dosing. The sponsor-reported adjusted analysis gave a difference in adjusted mean of 0.946, with a 95% confidence interval from -2.293 to 4.185 and p = 0.559. The interval includes zero and does not establish a clear treatment difference or equivalence.

The posted safety entries list zero serious adverse events, zero other adverse events, and zero deaths for each treatment group. Details about missing data, multiplicity, and several elements of the statistical plan are not reported in the registry record.