Aerosol Inhalation Treatment for Dyspnea - Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aerosol Inhalation Treatment for Dyspnea - Patients (NCT02524054), a randomized phase 1, phase 2 study. The primary outcome is Change in Subject Rating of Breathing Discomfort (Dyspnea) Before and After Treatment..

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-masked, crossover trial in Phase 1 and Phase 2. The listed enrollment is 24, and the record marks the study as completed. The start date is 2014-11-01 and the primary completion date is 2016-11-30. Beth Israel Deaconess Medical Center is listed as the sponsor.

The arm descriptions include a Study 2a group and two Study 2b sequences. Study 2a is described as a single administration of 40mg aerosol furosemide over 10-15 min, and that description calls the administration unblinded. In Study 2b, one sequence receives furosemide aerosol on one day and saline aerosol on another; the other sequence receives saline first and furosemide on another day. Both Study 2b descriptions specify a 15 min baseline measurement, inhalation over 10-15 min, a 15 min outcome measurement, and observation for adverse effects for 2 hours.

The overall record labels masking as double, while the Study 2a description explicitly calls its administration unblinded. The record does not explain how these descriptions relate to each other. Nor does it report a washout interval, how period or sequence effects were handled, or whether the Study 2a group was included in the randomized crossover comparison. These details matter when interpreting results from a crossover design, because measurements from the same participant across treatment periods are related and can depend on treatment order or timing.

The primary endpoint is a continuous measure: the mean change in subject rating of breathing discomfort before and after treatment. The registry lists the standard deviation as its measure of dispersion and gives a timeframe of 15 min. It also lists urine output in mL as a secondary outcome. The record does not provide participant characteristics or details of the allocation procedure.

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

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 Change in Subject Rating of Breathing Discomfort (Dyspnea) Before and After Treatment., measured over 15 min.

The primary endpoint is the change in a participant’s rating of breathing discomfort during an arm-exercise test. Participants rated dyspnea using a visual analog scale before and after drug or placebo intervention. The outcome is defined as the rating before treatment minus the rating after treatment, with measurements taken at equivalent work intensities. The registry describes the endpoint as a mean, with standard deviation as the measure of spread, and gives the timeframe as 15 min.

In general, a continuous symptom rating can retain information about the degree of reported discomfort rather than reducing the result to a category such as improved or not improved. Measuring before and after intervention also gives a within-person change for each assessment. But the meaning of a score depends on the scale’s range, anchors, and interpretation. The registry record does not report the visual analog scale’s range or anchors, or a threshold for a change that would be considered important to participants.

The endpoint’s sign follows its stated calculation. A negative value means the after-treatment rating was numerically higher than the before-treatment rating; a positive value means it was numerically lower. The record does not state whether higher values correspond to greater or lesser discomfort, so the direction of the numerical change alone cannot establish whether symptoms improved or worsened. The description also notes that the average interval between the end of inhalation and the post-intervention rating differed across the listed arms: 38.7 minutes for the Study 2a arm, 21.8 minutes for the Study 2b furosemide arm, and 21.3 minutes for the Study 2b saline arm. These timing details are relevant to interpreting what moment the endpoint represents.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Methods explanations below distinguish general statistical principles from what the registry record specifically reports. The record gives group means and standard deviations for the continuous primary outcome, and it identifies a two-sided t-test for the Study 2b comparison. It does not provide the full statistical analysis plan.

What does a mean change describe?

In general, a mean is an average that describes the center of a set of measured values. Here, each value is intended to represent a before-minus-after rating of breathing discomfort, and the arm-level results summarize those changes. A mean can be informative about the average direction and size of the measured changes, but it does not show how each participant responded. The standard deviation describes how spread out the observed values are around their mean. It is not the same as a confidence interval and does not, by itself, indicate how precisely the mean or a treatment contrast has been estimated.

The reported group summaries are -1.86 and standard deviation 2.31 for Study 2a furosemide, -0.61 and standard deviation 1.61 for Study 2b furosemide, and -0.15 and standard deviation 0.94 for Study 2b saline. They describe the observed groups, not a difference calculated between the Study 2b treatments. The record does not report the estimated treatment contrast or its uncertainty interval.

What does a t-test assess?

In general, a t-test evaluates evidence about a difference in means relative to the variability and amount of information in the data, under assumptions appropriate to its design. The reported test is two-sided, so it evaluates departures in either direction rather than prespecifying only one direction. The registry gives p = 0.35 for the Study 2b comparison. A p-value is not a measure of effect size, and it does not establish equivalence or prove that there is no treatment difference. A non-small p-value can reflect a small observed contrast, substantial variability, limited information, or some combination; the registry record does not permit those possibilities to be separated for this comparison.

In a crossover study, the same participant contributes measurements under more than one intervention. As a general matter, paired or otherwise repeated-measures methods can account for the relationship between those observations. A conventional comparison that treats observations as independent may not reflect that relationship. The registry record names a t-test but does not report whether the analysis used paired observations, how the treatment sequence was modeled, or whether period effects were assessed. The method cannot be fully evaluated from the abbreviated registry description alone.

Why do confidence intervals matter?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure. It helps readers judge precision and the sizes of effects that remain plausible, information that a p-value alone does not provide. No confidence interval for the Study 2b treatment contrast is reported in the registry record. The arm-level standard deviations are not substitutes for that interval, because they describe spread within groups rather than uncertainty around the between-treatment estimate.

How should the design and timing be considered?

In general, crossover designs can make within-participant comparisons useful by controlling for characteristics that remain stable within a participant. They also require attention to order, time period, and possible carryover from an earlier treatment period. The Study 2b descriptions list opposite treatment orders but do not report a washout interval or details of how order, period, or carryover were handled analytically. The record also does not explain the relationship between the overall double-masked designation and the Study 2a description of a single unblinded administration.

The primary endpoint description identifies a 15 min timeframe, while also reporting average intervals between the end of drug administration and post-intervention ratings: 38.7 minutes for Study 2a furosemide, 21.8 minutes for Study 2b furosemide, and 21.3 minutes for Study 2b saline. In general, differences in measurement timing can matter if an outcome changes over time. The record does not explain why these intervals differ or how timing was addressed in the analysis.

What do the planning illustrations mean?

In general, sample-size calculations estimate the amount of information a future study might need to detect a prespecified effect under stated assumptions. The planning illustrations associated with this record are described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect expressed as a stated fraction of the observed effect. They are planning illustrations, not evidence about the design chosen for this completed trial and not observed power. The registry record does not report the trial’s own sample-size justification or whether these planning assumptions were used when the trial was designed.

Sample-size planning depends on the target contrast, variability, design, and assumptions about how observations relate to one another. In a crossover setting, an illustration based on equal allocation between two arms may not capture the paired structure unless its method explicitly incorporates that structure; the record does not provide enough detail to determine whether it does. Planning values should therefore be understood only within their stated assumptions and should not be presented as a retrospective judgment about the trial’s success or as an observed result.

More generally, the record lists two outcome measures and two analyses, but it does not report a multiplicity strategy or enough detail to establish how the analysis population was defined. Those omissions limit conclusions about the confirmatory status and robustness of the reported test.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Aerosol Furosemide Study 2a", "Aerosol Furosemide Study 2b", "Aerosol Saline Study 2b")
n   <- c(7, 17, 17)
m   <- c(-1.86, -0.61, -0.15)
sp  <- c(2.31, 1.61, 0.94)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Aerosol Furosemide Study 2a  7  -1.860  2.310  -3.996  0.276
CARM  Aerosol Furosemide Study 2b  17  -0.610  1.610  -1.438  0.218
CARM  Aerosol Saline Study 2b  17  -0.150  0.940  -0.633  0.333

11. Analyses Reported by the Sponsor

The registry-reported Study 2b analysis is a two-sided t-test with p = 0.35. It does not report a treatment-effect estimate or a confidence interval. The arm summaries give means and standard deviations for each group, but they do not replace a reported between-treatment estimate or provide its precision.

The record does not flag a discrepancy between a sponsor analysis and a recalculation. No separate recalculated treatment contrast is reported in the record, so there is no numerical recalculation to set alongside the registry test. The sponsor’s analysis should therefore be read as the available inferential result, with its method and reporting limits in view. In particular, the registry does not clarify whether the t-test accounted for the paired nature of a crossover comparison or how sequence and period effects were handled.

The absence of a reported confidence interval means the p-value cannot show which treatment differences remain compatible with the data. It should not be restated as proof of no difference, equivalence, or a particular clinical effect. The record’s numerical group means describe the outcome as defined, but the scale anchors are not reported, so their direction cannot be assigned a clinical meaning from the numerical signs alone.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and two analyses. The primary outcome is change in breathing-discomfort rating, and the listed secondary outcome is urine output in mL. The record does not describe whether these outcomes were tested under a prespecified hierarchy, whether one or more analyses were considered primary, or whether any adjustment for multiple testing was used. Without that information, the reported p-value should be interpreted as the result of the stated comparison, not automatically as a multiplicity-adjusted confirmatory finding.

The registry record does not report missing-data counts or how missing outcome measurements were handled. It also does not specify the analysis population, such as whether the reported results include all randomized participants, only participants with complete measurements, or another defined group. The reported group sizes are 7 for Study 2a and 17 for each Study 2b arm. Because the design is crossover, the same people may contribute observations under both Study 2b treatments; the registry record does not give the number with complete paired outcomes or explain how incomplete pairs were treated.

These omissions affect interpretation in general statistical terms. Missingness can influence an estimate when the availability of measurements is related to participant characteristics, treatment, or outcome. A stated analysis population and missing-data method help readers judge which observations informed an estimate and how incomplete data were addressed. Likewise, an explicit multiplicity plan clarifies how to interpret findings when more than one outcome or analysis is examined.

The record does not report an interim-analysis plan, a missing-data sensitivity analysis, or details of prespecified analysis decisions. Their status is not reported in the registry record; their absence from this description should not be taken as evidence that any particular procedure was or was not performed.

13. 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 0% reporting threshold.

The registry’s adverse-event figures report zero serious events and zero deaths in each listed group. The recorded numbers at risk are 7 for Study 2a furosemide, 17 for Study 2b furosemide, and 17 for Study 2b saline. The record also reports zero participants affected by other adverse events in each group. No serious adverse-event terms are listed.

These figures describe what the registry reports, not proof that no adverse effects occurred outside the recorded reporting framework. They do not show whether events were actively solicited, how events were defined or attributed, or how complete follow-up was. The record does not report the methods used to collect adverse events. It also does not provide event-level descriptions for the zero affected counts.

Study 2b descriptions specify observation for adverse effects for 2 hours after inhalation. That planned observation window does not establish the duration or completeness of all safety follow-up, which is not reported in the registry record. The Study 2a description does not specify the same observation period. Finally, zero reported events in these groups cannot establish that a treatment has no safety risks; it means only that the registry lists zero affected participants for the reported categories in these groups.

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

The results describe breathing-discomfort ratings collected before and after inhalation during an exercise test. The arm-level mean changes are -1.86 for Study 2a furosemide, -0.61 for Study 2b furosemide, and -0.15 for Study 2b saline. The registry-reported comparison between the Study 2b groups is a two-sided t-test with p = 0.35. This describes the reported test result, but does not by itself indicate the size or precision of a treatment contrast.

The endpoint is defined as the before-treatment rating minus the after-treatment rating. Thus, negative mean values indicate numerically higher post-treatment ratings than pretreatment ratings. However, the record does not specify whether higher scale scores signify more or less discomfort. Without the scale anchors, the numerical direction cannot be translated into an improvement or worsening in symptoms. The scale’s range and a threshold for a meaningful change are also not reported.

The reported test does not establish that the treatments are equivalent, nor does it prove that there is no treatment difference. The registry does not report a confidence interval for the comparison, so readers cannot assess the range of effects compatible with the test. The record also does not explain whether the t-test accounted for repeated measurements within participants, despite the crossover design and the two Study 2b sequences.

The study record includes a distinct Study 2a description of a single, unblinded furosemide administration. Its results are not a randomized furosemide-versus-saline contrast and should not be interpreted as one. Likewise, the reported adverse-event counts are limited to the registry’s categories and do not establish absence of all possible harms.

Overall, the record offers outcome summaries and a reported test, but leaves important interpretive details unreported: scale direction, the treatment contrast and its confidence interval, crossover analysis details, missing-data handling, and the analysis population. The results should be understood within those limits rather than extended to conclusions the registry does not support.

15. Why This Trial Matters Statistically

This trial illustrates a statistical challenge that arises when a symptom is measured repeatedly and a participant receives more than one intervention. A crossover design can support within-person comparison, but its analysis needs to reflect the dependence between observations and account for treatment order and period. The registry identifies the trial as crossover and lists two Study 2b treatment sequences, yet it reports only that the comparison used a two-sided t-test. It does not say how the repeated measurements or sequence were handled.

The endpoint also highlights why a result’s definition matters. The outcome is explicitly calculated as the rating before treatment minus the rating after treatment. A negative value consequently means the post-treatment rating was numerically higher, but the registry does not state what higher values on the visual analog scale represent. Clear reporting of scale direction and anchors is essential for translating numerical changes into interpretable symptom changes.

Another statistical lesson is that a p-value is not a substitute for an effect estimate and its uncertainty. The record reports p = 0.35 for the Study 2b comparison, but no treatment contrast or confidence interval. Readers can therefore identify the reported test result, but cannot judge the precision or range of effect sizes consistent with that test using the registry record alone.

Finally, the record juxtaposes a general double-masked trial designation with a Study 2a description that calls the administration unblinded. The distinction between a controlled comparison and a single-arm summary is consequential: the latter cannot isolate treatment differences in the same way as a randomized comparator. Taken together, these features make the study useful for understanding how design, endpoint definition, analysis details, and transparent uncertainty reporting shape interpretation of clinical trial results.

16. 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 trial-specific reporting gaps constrain interpretation. The primary outcome is described as a visual analog scale rating, but its range, anchors, and direction are not reported. As a result, the signs of the mean changes cannot be mapped to more or less discomfort from the registry record alone. No threshold for a clinically meaningful change is provided.

The timing description warrants attention. The primary outcome lists a timeframe of 15 min, while the narrative gives average intervals between the end of drug administration and the post-intervention rating of 38.7 minutes for Study 2a furosemide, 21.8 minutes for Study 2b furosemide, and 21.3 minutes for Study 2b saline. The record does not explain these differences or how they were incorporated in the analysis. It also does not report a washout interval or how period, sequence, or carryover were addressed in the crossover comparison.

There is a reporting ambiguity between the overall double-masked designation and the Study 2a arm description, which calls the administration single and unblinded. The record does not explain the relationship between Study 2a and the Study 2b crossover groups. The reported t-test is not described in enough detail to establish whether it used paired observations. No treatment contrast or confidence interval is reported.

The record does not state the analysis population, missing-data method, multiplicity strategy, or sample-size justification. The listed enrollment is 24, while the arm summaries report group sizes of 7 and 17 for the listed groups; the record does not explain the relationship between enrollment and those arm summaries. These limitations concern what is reported in the registry record and do not establish that particular procedures were absent from the conduct of the trial.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Aerosol Inhalation Treatment for Dyspnea - Patients — NCT02524054.
• Registry record last updated 2018-01-23; status last verified 2017-12.
• Results first posted 2017-10-13.
• 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.

20. Record Summary

NCT02524054 is a completed randomized, double-masked crossover study listed in Phase 1 and Phase 2, sponsored by Beth Israel Deaconess Medical Center. The registry lists dyspnea as the condition, enrollment of 24, a start date of 2014-11-01, and primary completion on 2016-11-30. The interventions are furosemide and aerosolized saline.

The primary endpoint is the mean before-minus-after change in breathing-discomfort rating during an arm-exercise test, with standard deviation as the dispersion measure. The Study 2b group summaries are -0.61 with standard deviation 1.61 for furosemide and -0.15 with standard deviation 0.94 for saline. The registry reports a two-sided t-test with p = 0.35 for the Study 2b comparison. The record does not report its treatment-effect estimate or confidence interval. Urine output in mL is listed as a secondary outcome.

The record reports zero serious adverse events and zero deaths in the listed groups. Important details—including the scale’s direction, crossover analysis, missing-data handling, analysis population, and multiplicity strategy—are not reported in the registry record.