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 Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings (NCT00685035), a randomized phase 4 study. The primary outcome is Sputum Wet and Dry Weight.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00685035 |
| Phase | Phase 4 |
| Condition | Cystic Fibrosis |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 17 |
| Arms in the primary outcome | 4 |
| Lead sponsor | University of Minnesota |
| Results posted | Yes |
2. Clinical Question
Population
Participants with cystic fibrosis were enrolled in a completed Phase 4 trial sponsored by the University of Minnesota. The registry reports enrollment of 17, while the posted sputum outcome counts are 16 for each wet-weight setting and 16 and 15 for the two dry-weight settings. The record does not describe participant characteristics or explain the differences between these counts.
Intervention
One device protocol used higher inflation pressure with variable-frequency oscillations. The registry’s primary hypothesis describes a combination of low and high oscillator frequencies. The arm description contains some protocol detail, but it is incomplete; the full settings are not reported in the registry record.
Comparator
The comparison protocol used lower inflation pressure and mid-frequency oscillations. The same VEST therapy device was used for both protocols, so the intended contrast concerns settings rather than different devices.
Primary question
The registry asks whether the higher-pressure, variable-frequency protocol is associated with greater sputum production than the lower-pressure, mid-frequency protocol. Sputum wet and dry weight were collected during sessions on days 1 and 4, with treatment order randomized across participants. The posted summaries describe the observed measurements; they do not, by themselves, establish a causal explanation for any difference.
3. Trial Design
This was a randomized, triple-masked, crossover trial of two device-setting protocols in cystic fibrosis. In a crossover design, participants receive more than one condition in an assigned sequence, allowing comparisons to be made across conditions within the same participant. The record states that half the participants used the higher-pressure, variable-frequency protocol first on day 1 and the lower-pressure, mid-frequency protocol on day 4; the other half used the reverse order. This order allocation helps distinguish a setting contrast from a simple first-session versus later-session contrast, although the registry record does not describe any period or sequence adjustment in the analysis.
The study was listed as Phase 4, with enrollment of 17, and is marked completed. The registry lists the start as 2008-05 and primary completion as 2008-08. It identifies the University of Minnesota as sponsor. The masking label is triple, but which people or roles were masked is not reported in the registry record. The record does not describe how randomization was generated or concealed, whether participants completed both sessions, or how any incomplete crossover data were handled.
The primary outcome was sputum wet and dry weight. The registry also lists spirometry, sputum rheology and in vitro cough transportability, and perceived comfort as secondary outcomes. Numeric results are posted for spirometric changes and the primary sputum summaries, but numeric results for every listed secondary measure 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.
Period 1: First Intervention: 30 Minutes
| Stage | Higher Pressure/Variable-freq, Then Lower Pressure/Mid-freq | Lower Pressure/Mid-freq, Then Higher Pressure/Variable-freq |
|---|---|---|
| STARTED | 9 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Higher Pressure/Variable-freq, Then Lower Pressure/Mid-freq | Lower Pressure/Mid-freq, Then Higher Pressure/Variable-freq |
|---|---|---|
| Pulmonary lab plethysmography malfunctio | 1 | 0 |
Period 2: 2-day Washout
| Stage | Higher Pressure/Variable-freq, Then Lower Pressure/Mid-freq | Lower Pressure/Mid-freq, Then Higher Pressure/Variable-freq |
|---|---|---|
| STARTED | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 0 |
Period 3: 2nd Intervention
| Stage | Higher Pressure/Variable-freq, Then Lower Pressure/Mid-freq | Lower Pressure/Mid-freq, Then Higher Pressure/Variable-freq |
|---|---|---|
| STARTED | 8 | 8 |
| COMPLETED | 8 | 8 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: In a previous study with similar design,21 the standard deviation for the difference in the mean sputum wet weight between treatment arms was 4.6 g. Assuming the same standard deviation for the current study, enrollment of 16 subjects provided an 80% chance of detecting a 3.5-g difference in the sputum wet weights at a significance level of .05.
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 | 17 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 33.3 (SD 7.3) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 10 |
| Region of Enrollment: United States | participants | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Sputum Wet and Dry Weight, measured over Produced during each airway clearance therapy session on days 1 and 4.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | grams |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is sputum wet and dry weight, measured in grams from material expectorated during each airway-clearance session on days 1 and 4. The registry describes collection in pre-weighed containers, followed by centrifugation and removal of supernatant to reduce saliva. Wet weight was calculated by weighing the container with the sputum pellet. The material was then dried in an oven before the container was weighed again to obtain dry weight. Thus, wet weight reflects the collected pellet before drying, while dry weight reflects the residue after desiccation.
These measures were chosen to quantify sputum production during the airway-clearance sessions, matching the trial’s stated hypothesis about whether settings would yield greater sputum production. They are measurement outcomes, not direct measures of every aspect of airway clearance or of longer-term health. The registry specifies medians with full ranges for the arm summaries. The posted wet-weight medians were 6.4 grams with higher pressure/variable frequency and 4.8 grams with lower pressure/mid-frequency; their full ranges were 0.49 to 22.0 and 0.24 to 15.0 grams, respectively. For dry weight, the posted medians were 0.2 and 0.12 grams, with ranges of 0.009 to 0.62 and < 0.001 to 1.0 grams, respectively. The dry-weight counts were 16 and 15. These summaries describe the recorded distributions, but do not alone provide a paired treatment-effect estimate or its uncertainty.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The descriptive primary-outcome summaries place the median wet weight higher under the higher-pressure, variable-frequency settings than under the lower-pressure, mid-frequency settings. The same ordering appears in the dry-weight medians. These are descriptive comparisons: the registry reports medians and full ranges by setting, not a confidence interval for a paired median contrast. The ranges are broad, and the record does not give the individual paired measurements, so the summaries cannot show how consistently a participant’s sputum weight changed between settings.
The registry also posts an ANCOVA analysis with a mean difference of .23 and p = .02, with a 95% confidence level noted but no confidence-interval bounds. The analysis lists all four wet- and dry-weight outcome groups. The record does not specify which outcome contrast the .23 represents, the units for that estimate, or the detailed ANCOVA model. It would therefore be unsafe to assign the estimate to wet weight, dry weight, or a particular setting contrast. The reported p-value indicates that the sponsor’s analysis found evidence against its modeled null hypothesis under its analysis, but the missing contrast definition and interval prevent a clear account of its magnitude and precision.
For spirometry, the posted group means show changes in FEV1 of 70.0 ml after higher-pressure/variable-frequency therapy and 90.0 ml after lower-pressure/mid-frequency therapy, with standard deviations of 90.0 and 120.0 ml. The unadjusted recalculation gives a mean difference of 20.0 ml, with a 95% confidence interval from -53.5 to 93.5 and p = 0.594. For FVC, the means are 80.0 ml for each setting, with standard deviations of 160.0 and 230.0 ml. The recalculated mean difference is 10.0 ml, with a 95% confidence interval from -79.95 to 99.95 and p = 0.828. Both intervals include values on either side of no difference. These recalculations are imprecise and are not a substitute for an analysis that accounts for the crossover structure.
Overall, the posted results do not give a single, fully interpretable estimate of the primary setting contrast. The descriptive medians show an ordering, while the reported ANCOVA estimate lacks enough detail to identify its contrast. The spirometry recalculations are compatible with a range of differences. The small study enrollment and incomplete reporting of model details limit what can be inferred from these results.
9. Statistical Methods Explained
What do the descriptive summaries convey?
The primary outcome summaries use medians and full ranges. A median gives the midpoint of ordered observations, while the full range records the smallest and largest observed values. These summaries can be useful when measurements are skewed or include widely separated observations, because a median is less influenced by extreme values than a mean. A range, however, is strongly affected by the most extreme observations and does not express the uncertainty around a treatment contrast. The registry does not post a confidence interval for a paired wet- or dry-weight comparison.
In a crossover trial, each participant can contribute measurements under both settings. A comparison that uses the within-participant pairing can account for stable differences between participants. The registry describes a randomized order and sessions on days 1 and 4, but does not report whether its primary analysis used paired observations, adjusted for period or order, or addressed missing session data. These details matter because an analysis that treats the settings as unrelated groups may not represent the trial’s crossover design.
What does the ANCOVA result establish?
ANCOVA is a general statistical method that estimates a group contrast while adjusting for one or more covariates. The registry reports an ANCOVA mean difference of .23 and p = .02, and identifies a 95% confidence level, but gives no confidence-interval limits. It lists all four sputum groups as part of the analysis. Without the contrast definition, covariates, model specification, and outcome scale, the estimate cannot be clearly assigned to a particular endpoint or interpreted in grams. A p-value alone does not communicate the size or precision of an effect. The record does not state whether the reported analysis was prespecified or whether other analyses were conducted.
How should the spirometry recalculations be read?
The unadjusted recalculations compare the posted means using the posted standard deviations and group counts. They are simple comparisons of summary statistics and are not the sponsor’s reported ANCOVA. For FEV1, the recalculated mean difference is 20.0 ml, its 95% confidence interval is -53.5 to 93.5, and p = 0.594. For FVC, the recalculated mean difference is 10.0 ml, its 95% confidence interval is -79.95 to 99.95, and p = 0.828. A confidence interval describes the range of estimates reasonably compatible with the data and the assumptions of the calculation. Both intervals span zero and also allow differences in either direction. They are wide relative to the point estimates, indicating limited precision.
These recalculations use the arm-level summaries and do not incorporate the within-person covariance that may be available in a crossover trial. A paired analysis can have different uncertainty from an unpaired summary-based comparison, depending on how measurements within a participant are related. The registry does not post the paired covariance or a reported analysis for these secondary outcomes, so an adjusted crossover-specific estimate cannot be reconstructed from the listed summaries.
What do the planning illustrations mean?
The sample-size illustrations are planning calculations based on observed secondary effects, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They show participants per arm for 80% or 90% power under assumptions about the effect to detect. Rows based on 100%, 75%, or 50% of an observed effect are hypothetical planning scenarios, not trial findings. They are not observed power and do not establish what sample size the investigators originally planned. The registry record does not report the trial’s own sample-size justification.
Planning calculations based on an observed effect can be unstable, particularly when the study is small and the observed estimate is uncertain. Smaller assumed effects require larger sample sizes to distinguish them from random variation, all else being equal. These illustrations are not a substitute for a design-based calculation using a prespecified clinically relevant effect and a suitable model for the crossover structure. The registry does not report the original planning assumptions in sufficient detail to compare them with these illustrations.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANCOVA | Mean Difference (Final Values) .23 | not reported | 0.020 |
The sponsor’s posted analysis is an ANCOVA result: a mean difference of .23, p = .02, and a stated 95% confidence level. No confidence-interval bounds are posted. Because the analysis lists all four sputum groups and does not identify the specific contrast or the units for .23, its estimate cannot be confidently matched to the wet-weight or dry-weight setting comparison from the descriptive summaries.
The recalculated results concern the secondary spirometry summaries, not a reanalysis of the sponsor’s ANCOVA. They are unadjusted mean comparisons based on the posted group means, standard deviations, and counts. They do not reproduce the sponsor’s model and do not account for within-participant pairing in the crossover design. Their estimates and p-values therefore answer a different, limited statistical question.
The registry does not flag a discrepancy between the sponsor analysis and a recalculation. That does not resolve the interpretation issue: the sponsor result lacks enough detail to identify its contrast, and the recalculated spirometry comparisons are not a check of that result. The ANCOVA model specification, outcome contrast, and interval limits are not reported in the registry record.
11. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity strategy. It lists a primary sputum outcome, several secondary outcome areas, and four outcome measures, but does not say whether a formal testing hierarchy, adjustment for multiple comparisons, or designation of exploratory analyses was used. When many outcomes or contrasts are examined, some nominally small p-values may arise by chance even if no underlying effect exists. A prespecified approach helps clarify which analyses are confirmatory and how to interpret individual p-values. The posted record does not provide that context.
Missing-data handling and analysis populations are also not described. Enrollment is 17, while posted counts for sputum wet weight are 16 under each setting, and dry-weight counts are 16 and 15. Spirometry summaries list 16 observations for each setting and measure. The record does not explain why these counts differ, whether the same participants contributed to both conditions, or how incomplete measurements were handled. It does not identify an intention-to-treat, per-protocol, or other analysis population.
These omissions are especially relevant for a crossover study. The interpretation of a within-participant comparison depends on whether both measurements are available and how incomplete pairs are treated. The registry describes randomized treatment order but does not report an analysis of order or period effects, nor does it explain whether a participant’s sequence was included in the model. It also does not report interim analyses or stopping rules. Their absence from the registry record should not be taken to mean that none occurred.
Because the sponsor’s ANCOVA contrast and model are not described, it is not possible to determine whether its p-value reflects a single prespecified comparison or one of several analyses. The registry record does not report the details needed to judge multiplicity control, missing-data assumptions, or the relationship between the stated primary hypothesis and the posted model.
12. 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 |
|---|---|---|---|
| Lower Pressure/Mid-frequency | 0 | 17 | 0.0% |
| Higher Pressure/Variable Frequency | 0 | 16 | 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 |
|---|---|
| Lower Pressure/Mid-frequency | 0 of 17 |
| Higher Pressure/Variable Frequency | 0 of 16 |
The registry reports zero serious adverse events among 17 participants at risk for lower-pressure/mid-frequency settings and zero among 16 at risk for higher-pressure/variable-frequency settings. It also reports zero other adverse events in those listed groups. These are event counts in the registry’s safety summaries; they do not establish that no events of any kind occurred outside the recorded categories or reporting period.
The death fields are null rather than numeric, so deaths should not be interpreted as reported zero. The record does not provide serious-event terms, because no serious-event terms are listed, and it does not give further detail about how adverse events were collected, classified, or attributed to a setting. With a small enrolled group, zero reported events still leaves uncertainty about uncommon events. The figures describe what was recorded in this trial, not a definitive safety comparison between the protocols.
13. What the Result Does, and Does Not, Mean
The posted evidence describes a small randomized crossover comparison of two settings using the same device. The primary descriptive medians are higher for the higher-pressure, variable-frequency protocol for both wet and dry sputum weight. However, the record does not give a clear paired treatment-effect estimate or confidence interval for those median comparisons. The additional ANCOVA result is difficult to interpret because the specific contrast, outcome scale, and interval bounds are not reported.
The spirometry summaries and their unadjusted recalculations are imprecise. Their confidence intervals include zero and values on either side of zero, so the recalculations do not isolate a direction or magnitude with precision. They are not a substitute for a crossover analysis using participant-level paired information. The registry’s listing of secondary sputum and comfort outcomes without numeric results also means the posted record cannot support a broader account across all outcomes.
These data do not establish that one set of settings is superior, nor do they establish equivalence or absence of a meaningful difference. A non-small p-value in a secondary recalculation is not proof of no effect; a small p-value in the sponsor’s ANCOVA cannot be interpreted confidently without knowing which contrast it represents. Statistical significance, effect size, and precision are distinct considerations, and the registry’s incomplete model reporting limits all three.
The results are specific to the participants, device, protocols, sessions, and measurements recorded in this trial. The record does not provide enough information to generalize the findings to other settings, populations, or treatment schedules. Clinical decisions cannot be drawn from these statistics alone.
14. Why This Trial Matters Statistically
This trial raises several statistical issues that are common in small crossover studies. Randomized treatment order and within-participant comparisons can be valuable because each participant can serve as their own control. But the benefit depends on preserving the pairing in the analysis and accounting for possible period or sequence effects. Although the registry describes the order design, it does not report enough analytical detail to verify how the crossover structure was used.
The record also illustrates why descriptive summaries and inferential estimates serve different purposes. Medians and ranges help characterize the observed sputum measurements, while a treatment contrast with an uncertainty interval would help quantify how precisely the settings differ. The registry’s ANCOVA result includes a p-value but leaves its contrast and units unclear, illustrating why a p-value without a clearly defined estimand and confidence interval can be difficult to interpret.
Finally, a small enrollment and a range of outcomes make transparency about missing data, multiplicity, and analysis populations especially important. The spirometry recalculations are wide and unadjusted, while numeric results for some listed secondary outcomes are absent from the registry record. Planning illustrations based on observed effects can help readers understand how assumptions affect future sample-size requirements, but they cannot replace the original design rationale or turn an imprecise result into a definitive conclusion. The central lesson is to interpret each statistic in light of the design and the reporting detail available.
15. 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 record constrain interpretation. The sputum endpoint is summarized by arm-level medians and ranges, but no confidence interval or paired treatment contrast is posted. Since the design is crossover, individual paired measurements could materially affect uncertainty; those data are not reported. The ANCOVA result gives a mean difference of .23 and p = .02 but does not identify the outcome contrast, units, model covariates, or confidence-interval bounds. This prevents a clear translation of the reported result into the setting comparison.
The arm descriptions do not fully specify the device protocols. The higher-pressure description is incomplete, and the registry does not provide a complete account of frequencies and session procedures for both settings. Masking is labeled triple, but the masked roles are not identified. The record also does not explain differences among the enrollment and endpoint counts or describe missing-data methods, analysis populations, or adjustment for sequence and period.
Numeric results are not reported in the registry record for all listed secondary outcomes. The recalculated spirometry contrasts use posted summary statistics and are unadjusted; they cannot recreate a participant-level crossover analysis. The sample-size illustrations are based on observed secondary effects rather than the trial’s reported design assumptions, which are not described. Multiplicity handling, interim analyses, and the statistical analysis plan are not reported. These limitations do not show that the methods were inadequate, but they leave important questions unresolved for readers of the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Comparison of Airway Clearance Therapy in Cystic Fibrosis Using the Same VEST Therapy Device But With Different Settings — NCT00685035.
- Registry record last updated 2016-07-25; status last verified 2016-06.
- Results first posted 2016-07-25.
- 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.
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19. Record Summary
NCT00685035 is a completed Phase 4 randomized, triple-masked crossover trial sponsored by the University of Minnesota. It enrolled 17 participants with cystic fibrosis to compare higher-pressure, variable-frequency and lower-pressure, mid-frequency settings on the same VEST device. Treatment order was randomized across sessions on days 1 and 4.
The primary outcome was sputum wet and dry weight, reported as medians and full ranges. The registry also posts an ANCOVA mean difference of .23 with p = .02, but does not identify the specific contrast or provide confidence-interval limits. Spirometry summaries and unadjusted recalculations are also posted; their estimates are imprecise and do not account for participant-level pairing. Numeric results for some listed secondary outcomes are not reported in the registry record. Details on missing data, multiplicity, the analysis population, and the full statistical model are not reported.