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 A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis (NCT00680316), a randomized phase 4 study. The primary outcome is Change in Reactance at 8 Hz (Xrs8) From Visit 2 to Visit 3 (Change From Baseline at Visit 2 to Visit 3, After Study Drug Treatment)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00680316 |
| Phase | Phase 4 |
| Condition | Cystic Fibrosis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genentech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Children aged 3 to 5 years with cystic fibrosis. The registry summary says approximately 40 patients were planned for enrollment, but only 3 were eligible for random allocation and received treatment.
Intervention
Dornase alfa, identified in the trial title as Pulmozyme®.
Comparator
Placebo.
Primary question
What change in reactance at 8 Hz (Xrs8) occurred from Visit 2 to Visit 3 after study drug treatment? The intended measurement interval was 16 +/- 2 days. No efficacy analyses were performed because there were no patients with complete pre- or post-treatment pulmonary function test data, including forced oscillometry.
The central question was whether pulmonary function, health-related quality of life, and respiratory symptoms could be evaluated after treatment with dornase alfa in preschool-aged children with cystic fibrosis. The registered primary endpoint focused on Xrs8, a forced oscillometry measure. The study also listed changes in reactance at other frequencies, resistance at several frequencies, and respiratory symptom domain scores from the Cystic Fibrosis Questionnaire Revised (CFQ-R) for parents of preschoolers and for preschoolers.
The primary question cannot be answered with an estimated treatment effect from the posted results. The registry describes the intended endpoint and timeframe, but reports that children could not perform forced oscillometry or did not remain stable during the study. No complete pulmonary function test data were available for efficacy analysis. The record therefore documents the clinical question and the barriers to measuring its primary outcome, rather than a comparison of pulmonary function between treatment groups.
3. Trial Design
This was a Phase IV, multicenter, randomized, double-blind, placebo-controlled trial with a parallel-group design. The registry lists dornase alfa and placebo as the interventions. The study was intended for children aged 3 to 5 years with cystic fibrosis and was designed to evaluate pulmonary function, health-related quality of life, and respiratory symptoms.
The registry summary says approximately 40 patients were planned for enrollment. The trial was terminated, and only 3 patients were eligible for random allocation and received treatment: 1 in the dornase alfa group and 2 in the placebo group. All 3 completed the study assessments, but they did not have usable pulmonary function test data. The record lists a start date of 2008-06 and a primary completion date of 2009-05.
Randomization is intended to allocate participants to treatment groups by chance, helping reduce systematic differences between groups. Double blinding is intended to limit the influence of treatment knowledge on participant experience, care, or outcome assessment. A placebo group provides a comparison under the trial’s planned conditions. These design features describe the intended structure; they do not compensate for the absence of usable primary outcome data or create an estimable treatment comparison.
The registry record does not report the randomization procedure, allocation concealment details, or the specific operational procedures used to maintain blinding. It also does not report a statistical analysis plan or a sample-size justification. The summary describes the planned enrollment and the number who received treatment, but it does not explain why enrollment was limited or why the trial was terminated. Those reasons are not reported in the registry record.
The design was intended to support a randomized comparison, but the resulting record is primarily descriptive. With no complete pulmonary function test data for efficacy analysis, the design cannot yield the planned comparison for the primary endpoint. The small number treated also means that adverse-event counts should be read as descriptions of these participants, not as stable estimates of event frequency.
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
| Stage | Dornase Alfa | Placebo |
|---|---|---|
| STARTED | 1 | 2 |
| COMPLETED | 1 | 2 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Children were unable to perform forced oscillometry (FOT) or did not remain stable during the study. No efficacy analyses were performed because no patients had complete (pre- or post-treatment) data for pulmonary function tests, including FOT.
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 | Dornase Alfa | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 2 | 3 | |
| Age, Continuous | years | 5.6 | 4.6 (SD 1.5) | 4.9 (SD 1.2) |
| Gender: Female | Participants | 1 | 0 | 1 |
| Gender: Male | Participants | 0 | 2 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Reactance at 8 Hz (Xrs8) From Visit 2 to Visit 3 (Change From Baseline at Visit 2 to Visit 3, After Study Drug Treatment)., measured over from Visit 2 to Visit 3 (16 +/- 2 days).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was change in reactance at 8 Hz (Xrs8) from Visit 2 to Visit 3, described as change from baseline at Visit 2 after study drug treatment. The registered timeframe was 16 +/- 2 days. Forced oscillometry measures how pressure and flow respond to externally applied pressure at the airway opening. The registry describes reactance as a measure incorporating changes in pressure and volume and the rate of those changes in response to pressure oscillations at a specific frequency. It states that reactance is thought to reflect elastic properties of the lung.
As a general measurement principle, a defined endpoint makes the study question concrete: it specifies what is measured and the comparison period of interest. Forced oscillometry was selected for this primary measure because it assesses lung function through the response to pressure oscillations. The record specifies 8 Hz as the frequency used for the primary endpoint.
The endpoint’s intended role should be distinguished from whether it was successfully observed. The registry says children were unable to perform forced oscillometry or did not remain stable during the study. No efficacy analyses were performed because no patients had complete pre- or post-treatment pulmonary function test data, including forced oscillometry. Thus, the endpoint is described, but the registry record does not provide a usable estimate of change in Xrs8 or a treatment-group comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main statistical finding is the absence of an efficacy estimate, not evidence for or against a treatment effect. The registry identifies change in Xrs8 as the primary endpoint, but states that no efficacy analyses were performed because no patients had complete pre- or post-treatment pulmonary function test data. The record also says that children could not perform forced oscillometry or did not remain stable during the study. Consequently, the posted results do not establish the magnitude, direction, or precision of a treatment-group difference in the primary outcome.
The planned enrollment was approximately 40 patients, while only 3 patients were eligible for random allocation and received treatment. There was 1 patient in the dornase alfa group and 2 in the placebo group. All 3 completed study assessments, but completion of assessments did not yield usable pulmonary function test data. This distinction matters: completing study visits or other assessments does not mean that the primary endpoint was observed in a form suitable for analysis.
Because there is no efficacy estimate, a confidence interval for the primary treatment effect is not available in the registry record. In general, a confidence interval describes a range of values compatible with the data and the method used to calculate it. It communicates precision as well as the estimated effect. Without analyzed primary endpoint data, neither the estimated effect nor its uncertainty can be interpreted.
The registered secondary outcomes include changes in reactance at 4, 6, and 10 Hz; resistance at 4, 6, 8, and 10 Hz; and respiratory symptom domain scores from the CFQ-R for parents of preschoolers and for preschoolers. The record lists no analyses. It does not report efficacy estimates for these outcomes, so they cannot be used to fill the gap in the primary result or to support a treatment comparison.
The adverse-event information is descriptive. Serious adverse events were reported for 0 of 1 participant in the dornase alfa group and 0 of 2 participants in the placebo group. Other adverse events were reported for 1 of 1 and 2 of 2 participants, respectively. These observations apply to the small groups treated in this trial; they do not provide a precise estimate of how often events would occur in a broader population. The registry does not provide serious adverse event terms, and deaths are not reported in the registry record.
The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. However, no efficacy effect was estimated in this trial. The registry record therefore does not support a planning illustration anchored to a usable observed primary effect. Any sample-size figure based on an effect from another source would require information not reported in the registry record.
Overall, the posted results show that the intended primary pulmonary function comparison was not analyzed because the required data were unavailable. They do not show that the treatment groups were equivalent, and they do not quantify a treatment effect. The result is an incomplete efficacy record with descriptive safety information, rather than a conclusive randomized comparison.
9. Statistical Methods Explained
Statistical interpretation depends first on identifying what was intended to be measured, what data were obtained, and what analyses were performed. In this trial, the primary endpoint was change in Xrs8 from Visit 2 to Visit 3. The registry identifies the planned interval as 16 +/- 2 days and explains that the measure was to be collected using forced oscillometry. It also states that there were no complete pre- or post-treatment pulmonary function test data for any patient and that no efficacy analyses were performed. These registry entries define the limit of the available statistical interpretation.
What would a treatment comparison estimate?
As a general concept, a randomized parallel-group trial can estimate a contrast between outcomes in participants assigned to the intervention and those assigned to the comparator. The exact contrast depends on the endpoint and analysis method. For a change endpoint, an analysis might compare change over time between groups, but the registry record does not report the planned statistical model or test. It would be inappropriate to infer the intended method from the endpoint description alone.
Here, the obstacle precedes the choice of model: the required pulmonary function measurements were not complete. Without analyzable outcome values, a treatment contrast for Xrs8 cannot be calculated from the posted results. Random assignment does not itself produce an effect estimate; the outcome data and a specified analysis are also required.
Why does missing outcome information matter?
As a general statistical principle, missing outcome data reduce the information available for estimating a treatment effect. The implications depend on why measurements are missing and how missingness relates to participant characteristics, treatment, or unobserved outcomes. The registry notes difficulty performing forced oscillometry or remaining stable during the study. It does not provide participant-level reasons, a missing-data analysis, or an account of whether any method for handling incomplete measurements was considered. Those details are not reported in the registry record.
In this case, the issue is especially direct because the registry says no patient had complete pre- or post-treatment pulmonary function test data for efficacy analysis. There is therefore no reported primary endpoint dataset from which to estimate either group changes or a difference between groups. A statistical method cannot recover the observed primary outcome values when those values are not available in the record.
What do uncertainty measures communicate?
In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that spans a range of possible effects may leave substantial uncertainty about magnitude or direction. A p-value, when used, is a measure calculated under a statistical model and a specified null hypothesis; it is not a measure of clinical importance or the probability that a hypothesis is true.
The registry record reports no primary efficacy estimate, confidence interval, or efficacy p-value. It also lists no analyses. The absence of those statistics is not the same as a result showing no difference. It means the posted record does not contain an analyzed primary comparison to interpret.
How should the planning assumptions be read?
The record describes planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. Such calculations are general planning tools: they show how a hypothetical future study’s size could depend on a target effect and selected assumptions. They are not observed power, and they do not turn an unmeasured treatment effect into evidence.
The registry does not report a usable observed primary effect because it says no efficacy analyses were performed. Therefore, the assumptions alone do not establish a sample-size estimate that can be tied to this trial’s observed Xrs8 effect. The planned enrollment of approximately 40 patients is reported, but the sample-size justification is not reported in the registry record.
What can the safety counts tell us?
As a general principle, event counts and the number of participants at risk provide a descriptive account of what was recorded among those treated. They are not automatically precise estimates of event rates in a wider population, particularly when the groups are very small. The registry reports serious and other adverse-event counts by group, but does not give serious event terms. These figures can be described as trial observations without implying that they establish comparative safety.
The record also does not report the statistical analysis plan, interim analyses, or the method, if any, used to analyze safety outcomes. Those elements are not reported in the registry record. The statistical reading should remain anchored to the information documented: an intended randomized comparison, no efficacy analyses, and adverse-event counts that describe the participants treated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and several secondary outcomes. The secondary outcomes include changes in reactance at 4, 6, and 10 Hz; changes in resistance at 4, 6, 8, and 10 Hz; and respiratory symptom domain scores from the CFQ-R for parents of preschoolers and for preschoolers. The record lists no analyses. It does not report results for these outcomes or explain whether any multiplicity adjustment was planned.
As a general statistical concept, multiplicity arises when several outcomes, time points, or comparisons are tested. Considering many results can increase the chance of finding an apparently notable result by chance. A prespecified analysis plan can identify which outcome is primary and how secondary analyses should be interpreted. The statistical plan and any multiplicity procedure are not reported in the registry record, so no adjustment or testing hierarchy should be assumed.
Missing pulmonary function data are central to interpretation. The registry says children could not perform forced oscillometry or did not remain stable during the study, and that no patients had complete pre- or post-treatment pulmonary function test data. It reports that all 3 patients completed the study assessments, but this did not mean complete pulmonary function data were available. The record does not report a missing-data strategy, imputation method, or sensitivity analysis.
The analysis population is also not described in detail. The summary reports 3 patients eligible for random allocation who received treatment, with 1 in the dornase alfa group and 2 in the placebo group. It does not specify an intention-to-treat or per-protocol efficacy population, and no efficacy analyses were performed. Those population definitions are not reported in the registry record. Without complete primary outcome data and a reported analysis population, there is no basis for a treatment-effect estimate or for judging how incomplete observations might affect one.
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 |
|---|---|---|---|
| Dornase Alfa | 0 | 1 | 0.0% |
| Placebo | 0 | 2 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dornase Alfa | 1 of 1 |
| Placebo | 2 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dornase Alfa | Placebo |
|---|---|---|---|
| Increase in cough | Respiratory, thoracic and mediastinal disorders | 1 of 1 | 0 of 2 |
| Bad dreams | Psychiatric disorders | 0 of 1 | 1 of 2 |
| Flu symptoms | General disorders | 0 of 1 | 1 of 2 |
The registry reports serious adverse events for 0 of 1 participant in the dornase alfa group and 0 of 2 participants in the placebo group. These are counts among the participants at risk in each group. They describe what was recorded in this trial; they do not establish that serious adverse events cannot occur or support a precise comparison between treatments.
Other adverse events were reported for 1 of 1 participant in the dornase alfa group and 2 of 2 participants in the placebo group. The registry does not list the terms for these other events in the information available for this record, so their nature or severity beyond the reported category cannot be described. The top serious adverse event terms are not listed. Deaths are not reported in the registry record.
As a general principle, a count from a small trial is highly limited as a guide to event frequency beyond the participants observed. The groups in this study were very small, so the event counts should be read as descriptive observations rather than stable estimates of risk or evidence of a difference between groups. The registry record does not report a statistical comparison of adverse events.
12. What the Result Does, and Does Not, Mean
The trial record documents a planned randomized comparison of dornase alfa with placebo in children aged 3 to 5 years with cystic fibrosis. Its primary endpoint was change in Xrs8 after study drug treatment. The record also describes secondary measures involving reactance, resistance, and respiratory symptoms. These details clarify the study’s intended question and outcome measurements.
The results do not provide an answer to the primary efficacy question. Although 3 patients received treatment and completed study assessments, they did not have usable pulmonary function test data. The registry states that no patients had complete pre- or post-treatment pulmonary function test data, including forced oscillometry, and that no efficacy analyses were performed. No estimated treatment effect or uncertainty interval is reported.
This absence of an estimate should not be interpreted as a finding that the treatments had the same effect. It also should not be interpreted as evidence that one treatment changed pulmonary function more than the other. The record does not contain the analyzed outcome information needed to make either claim. In general, a study that cannot measure its primary outcome cannot establish the size or direction of a treatment effect on that outcome.
The safety information has a narrower descriptive meaning. It records serious and other adverse events among the participants treated, but the small group sizes and lack of serious event terms limit interpretation. The event counts do not establish comparative safety or provide a precise estimate for a broader group of patients.
The registry also reports that approximately 40 patients were planned for enrollment but only 3 were eligible for random allocation and received treatment. It does not explain the reason for the limited enrollment or the termination. These missing explanations prevent a more detailed account of why the study stopped or how the enrollment experience arose. The record supports a description of what was intended and what data were available, but not a conclusion about efficacy or a detailed explanation for the trial’s outcome.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the difference between a well-defined research question and an answerable analysis. The registry identifies a specific primary endpoint, Xrs8 change, and a specific measurement interval. It also describes the randomized, double-blind, placebo-controlled design. Yet the intended comparison depends on collecting usable pulmonary function measurements, and the record says those data were not available for efficacy analysis.
Randomization is an important design feature, but it cannot substitute for outcome information. Without complete measurements, the groups cannot be compared on the primary endpoint using the posted data. The trial therefore demonstrates that design quality and data availability are separate requirements for an interpretable treatment-effect estimate.
The enrollment record also matters for statistical interpretation. Approximately 40 patients were planned, but only 3 were eligible for random allocation and received treatment. That difference is relevant to the feasibility and completeness of the trial record, while the reason for the limited enrollment is not reported. The observed adverse-event counts should likewise be understood in the context of the small groups, rather than treated as precise evidence about event frequency.
Finally, the record distinguishes study completion from endpoint completion: all 3 patients completed the study assessments, but pulmonary function data were not usable. For researchers, this is a reminder that outcome measurement feasibility is part of a study’s evidentiary foundation. The posted information cannot quantify the primary effect, but it clearly identifies why a statistical comparison was not performed.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation is that no efficacy analyses were performed. The registry states that no patients had complete pre- or post-treatment pulmonary function test data, including forced oscillometry, so the primary endpoint has no reported estimate. Children were unable to perform forced oscillometry or did not remain stable during the study. The record does not provide additional participant-level detail about these measurement difficulties.
Only 3 patients were eligible for random allocation and received treatment, although approximately 40 were planned for enrollment. There was 1 patient in the dornase alfa group and 2 in the placebo group. Such a small treated group limits the amount of information available even for outcomes that were collected. The registry does not report why enrollment was limited or why the trial was terminated.
The registry does not report a statistical analysis plan, efficacy analysis population, missing-data method, or multiplicity procedure. It lists secondary outcomes but no analyses. The record also does not provide a sample-size justification. These omissions mean the analysis choices and rationale cannot be reconstructed from the registry record.
The safety results are also limited in scope. Serious adverse event terms are not listed, and deaths are not reported in the registry record. Other adverse event terms are not described in the record information available for this analysis. The small group sizes make the counts descriptive rather than precise estimates of event frequency.
These limitations do not change the registered design or endpoint, but they constrain what can be concluded from the posted results. The trial record cannot support an efficacy estimate for the primary pulmonary function outcome or a detailed explanation of the operational factors that led to the incomplete data.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Pulmozyme® (Dornase Alpha) in 3- to 5-Year-Old Patients With Cystic Fibrosis — NCT00680316.
- Registry record last updated 2017-01-12; status last verified 2016-11.
- Results first posted 2011-06-17.
- 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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18. Record Summary
The registry describes a Phase IV, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of dornase alfa versus placebo in children aged 3 to 5 years with cystic fibrosis. The primary endpoint was change in reactance at 8 Hz from Visit 2 to Visit 3, over 16 +/- 2 days.
Approximately 40 patients were planned for enrollment, but 3 were eligible for random allocation and received treatment: 1 in the dornase alfa group and 2 in the placebo group. All 3 completed study assessments, but no patients had complete pulmonary function test data for efficacy analysis. No efficacy analyses were performed. The registry lists the trial as terminated, with a start date of 2008-06 and a primary completion date of 2009-05.
Serious and other adverse-event counts are reported by treatment group, but the record does not provide a usable primary efficacy comparison. The reason for termination, sample-size justification, and statistical analysis plan are not reported in the registry record.