An Evaluation of Dupilumab in Patients With Nasal Polyposis And Chronic Symptoms Of Sinusitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Evaluation of Dupilumab in Patients With Nasal Polyposis And Chronic Symptoms Of Sinusitis (NCT01920893), a randomized phase 2 study. The primary outcome is Change From Baseline in Bilateral Endoscopic Nasal Polyp Score (NPS) at Week 16.

2. Clinical Question

This is a comparison of two treatment strategies, each including mometasone furoate nasal spray, rather than a comparison of dupilumab alone with no treatment. The primary endpoint concerns endoscopic polyp size. Separate secondary outcomes address participant-reported sinusitis symptoms, rhinosinusitis severity, nasal airflow, smell, sinus CT assessments, and time to first NPS response. The registry record lists an asthma subgroup outcome as well. It does not report a single primary-outcome result that would establish the size or precision of the treatment contrast.

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group, placebo-controlled phase 2 study with two arms. Enrollment was 60. One arm received dupilumab 300 mg weekly after a 600 mg loading dose on Day 1; the other received placebo for dupilumab. Both arms also received mometasone furoate nasal spray. The record does not report the allocation ratio, the parties included in the triple masking, or details of how randomization and masking were implemented.

The study began in 2013-08 and had a primary completion date of 2014-11. Its status is completed. The primary endpoint was change from baseline in bilateral endoscopic nasal polyp score at Week 16. Secondary outcomes included symptom scores, a visual analogue scale for rhinosinusitis symptom severity, nasal peak inspiratory flow, smell-test scores, sinus CT assessments, an NPS outcome in participants with asthma, and time to first NPS response. The record lists 11 outcome measures.

The stated primary population was the intent-to-treat population: randomized participants were analyzed according to their allocated group. For a particular time point, the number analyzed was defined as the number with available data. That definition describes which available observations contributed at a time point; it does not specify how missing observations were handled in a treatment-effect analysis.

The registry record does not report a detailed statistical analysis plan, the sample-size justification used to design the trial, or whether interim analyses were conducted. The planning illustration associated with the posted results is explicitly based on the observed effect and is not the trial's own design calculation. Its assumptions should not be mistaken for documented design features of the study.

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: Randomization was stratified according to medical history of asthma (with/without asthma) and by nasal biopsy (biopsy performed,Yes/No). Assignment was done centrally using Interactive Voice/Web Response System in 1:1 ratio (dupilumab:placebo)after 4-week run-in period on Mometasone furoate nasal spray (MFNS) and confirmation of selection criteria.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population included all randomized participants analyzed according to the treatment group allocated by randomization. Here, number analyzed = number of participants with available data for specified time points.

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: Baseline population included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Bilateral Endoscopic Nasal Polyp Score (NPS) at Week 16, measured over Baseline, Week 16.

The primary endpoint was change from baseline in bilateral endoscopic nasal polyp score at Week 16. Nasal endoscopy was used to score the right and left nostrils, and the two nostril scores were summed. Each nostril was scored from 0, meaning no polyp, to 4, meaning large polyps; the total score ranged from 0 to 8. A lower score indicates smaller-sized polyps.

This endpoint is used to quantify polyp burden through an endoscopic assessment rather than relying only on a participant's report of symptoms. Change from baseline expresses how the measured score at the specified follow-up differs from the starting score. Comparing change between randomized groups can describe the contrast between the assigned treatment strategies, subject to the analysis population, available data, and statistical methods used.

The score is a bounded scale, so its possible values are limited to the stated range. A mean change can provide a group-level summary, while variation among participants matters for judging how representative or precise that summary is. The registry record identifies the endpoint as a mean with standard deviation, but it does not report a single numerical primary comparison, its standard error, or a confidence interval. The record also does not provide a result that can be interpreted as the magnitude of a difference between treatment groups.

The endpoint is specific to endoscopic polyp size. It does not, by itself, represent every aspect of chronic sinusitis or establish how participants experienced symptoms. The listed secondary outcomes address some other dimensions, but their presence does not substitute for a reported primary endpoint estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary measure summarized as a mean and standard deviation. The endpoint is a change score, calculated from measurements at baseline and Week 16, and the intended comparison is between randomized treatment groups. No single primary comparison or numerical result is reported, so the statistical concepts below explain how such summaries are generally read rather than describing an unreported analysis.

What does a mean summarize?

In general, a mean represents the arithmetic average of participant measurements in a group. For a change-from-baseline endpoint, a group mean change summarizes the average movement in scores over the specified interval. An average can make a group-level pattern easier to describe, but it does not show whether every participant changed in the same way. Individual responses may vary around the mean.

The standard deviation describes the spread of individual observations around their group mean. It is not the same as the uncertainty in the mean: the standard deviation characterizes variation among observations, while a standard error or confidence interval concerns precision of an estimate. The registry record identifies standard deviation as the dispersion measure for the primary endpoint, but does not give its numerical value for either arm.

Why compare change between groups?

General statistical reasoning favors a between-group contrast when the question concerns assigned treatment. A change within one group alone cannot distinguish a treatment-related pattern from changes that may also occur under the comparator. Random assignment is intended to make the groups comparable on average at the start, though the registry record does not report baseline balance or allocation details. The relevant contrast would depend on the analysis actually used; that analysis is not reported as one numerical primary comparison in the record.

Change scores also need interpretation in light of the starting measurement and the available follow-up observations. The record defines the intent-to-treat population as randomized participants analyzed by assigned group, while also defining the number analyzed at a specified time point as those with available data. This means the stated population label does not, by itself, reveal whether every randomized participant contributed an observed Week 16 value or how missing values were treated.

What does a confidence interval convey?

In general, a confidence interval expresses uncertainty around an estimated effect under a particular statistical method and its assumptions. A narrow interval indicates greater precision than a wide interval, but the interval's interpretation depends on the analysis and the data. It is not a statement that all individual outcomes fall within its limits, nor does it state the probability that a fixed true effect is inside a particular calculated interval. No confidence interval for the single primary comparison is reported in the registry record.

A p-value is also conditional on a statistical model and a null hypothesis. In general, it describes how unusual data at least as extreme as those observed would be if that null model and its assumptions held. It does not measure effect size, clinical importance, or the probability that a treatment hypothesis is true. The registry record does not report a p-value for a single primary comparison.

Why can dispersion and model choice matter?

The primary outcome is a score bounded between 0 and 8. General methods should take account of the scale and the distribution of observed values. A mean and standard deviation can be informative summaries, but their adequacy as a full model depends on the data. If observations are unusually concentrated near a boundary, markedly skewed, or otherwise inconsistent with model assumptions, an analysis based only on normal-distribution assumptions may not describe uncertainty well. The registry record does not report distributional diagnostics or alternative-model checks.

Over-dispersion is a general concern when an analysis assumes less variability than is present in the data. If it occurs, uncertainty may be understated unless the method accounts for the extra variability. This is a general statistical issue, not a finding about this trial: the registry record does not report that over-dispersion was assessed or present.

How should the planning illustration be read?

The associated planning illustration uses the observed effect as its basis and describes assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. It considers detecting a stated fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the trial was designed with those assumptions. The registry record does not report the trial's own sample-size justification. Sample-size calculations depend on assumptions about the target effect, variability, allocation, and analysis; changing those assumptions can change the planned sample size. The illustration cannot replace a reported treatment-effect estimate and uncertainty interval.

For all of these methods, the distinction between what was planned, what was observed, and what was analyzed is essential. The record gives a design description and endpoint definition, but does not report the detailed statistical plan, numerical primary result, or enough analysis details to reconstruct the inferential comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple outcomes, including the primary NPS endpoint and secondary symptom, airflow, smell, CT, asthma-subgroup, and response-time measures. When several outcomes, time points, subgroups, or comparisons are examined, the chance of obtaining at least one apparently notable result can increase. General methods for addressing this include prespecifying a hierarchy, adjusting significance thresholds, or interpreting results as exploratory. The registry record does not report whether any such approach was used, so no multiplicity adjustment or testing hierarchy can be assumed.

The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. It therefore does not provide a single primary contrast for interpretation. The number of outcome measures is listed as 11, but this count alone does not establish how many hypotheses were tested, which results were confirmatory, or whether results were adjusted for multiple testing.

The stated intent-to-treat population includes randomized participants analyzed according to assigned group. For each specified time point, the number analyzed is defined as the number with available data. This definition clarifies that an observed-data count may vary by time point; it does not describe a missing-data method. Imputation, assumptions about the reason data were missing, sensitivity analyses, and handling of participants without Week 16 measurements are not reported in the registry record.

The detailed statistical analysis plan, interim analyses, and sample-size justification are also not reported in the registry record. These omissions limit the ability to establish which analyses were prespecified, how missing observations or multiple comparisons were handled, and how the analysis relates to the study's intended design.

11. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: herpes zoster (3.3%), uterine cancer (3.3%), hypoaesthesia (3.3%), mononeuropathy (3.3%), transient ischaemic attack (3.3%).

The registry record reports serious adverse events for participants at risk in each arm. In the placebo arm, 30 participants were at risk and 4 were affected by a serious adverse event. In the dupilumab 300 mg QW arm, 30 participants were at risk and 2 were affected. The record also reports other adverse events: 22 affected participants in the placebo arm and 27 in the dupilumab arm, with 30 at risk in each arm. Deaths were reported as 0 in both arms.

These counts are descriptive. They do not establish that treatment caused an event, and the registry record does not provide the timing, duration, severity grading, or participant-level overlap of events. The listed serious-event terms are herpes zoster, uterine cancer, hypoaesthesia, mononeuropathy, transient ischaemic attack, and arrhythmia, each shown as 3.3%. The term listing does not give arm-specific attribution, so these percentages should not be assigned to a particular treatment arm from the record.

Counts of participants affected are not the same as counts of all event occurrences if a participant can experience more than one event. The registry record does not report enough detail to determine that distinction for these figures. Nor do these summary counts establish comparative safety beyond the events and follow-up represented in the record.

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

This trial addresses a specific statistical question: whether change in endoscopic bilateral nasal polyp score at Week 16 differed between a dupilumab-plus-mometasone strategy and a placebo-plus-mometasone strategy in participants with bilateral nasal polyposis and chronic sinusitis symptoms. Its randomized, parallel, masked design provides the framework for that comparison, and the score has a defined range and direction.

However, the registry record does not report a single primary treatment comparison or its numerical result. It is therefore not possible from this record to describe the observed size or precision of the primary contrast, or to say whether the groups differed on that endpoint. The endpoint definition and planned comparison should not be mistaken for evidence of an outcome. Secondary outcomes are listed, but their numerical findings are not included in the registry record for this interpretation.

The safety counts provide a limited descriptive account of serious and other adverse events and deaths. They do not establish causality, and the listed serious-event terms are not attributed to arms in the term listing. A complete safety interpretation would require more detail about event definitions, timing, severity, exposure, and analysis.

More generally, statistical evidence from a trial is tied to its population, assigned treatment strategies, outcome definitions, and analysis methods. The record describes the population and regimens, but does not report the detailed statistical plan or key inferential output for the primary endpoint. It does not establish how the findings apply beyond the enrolled study population, nor does it provide a basis for broader claims about all symptoms or outcomes related to nasal polyposis and sinusitis.

The appropriate reading is therefore bounded: the registry record documents a completed randomized phase 2 comparison and its outcome framework, but it does not contain the single numerical primary result needed to quantify that comparison.

13. Why This Trial Matters Statistically

This trial is statistically notable for the way its clinical question is organized around a defined, bounded, continuous endpoint. The bilateral endoscopic NPS combines right and left nostril scores, with a stated range from 0 to 8 and a clear direction in which lower scores indicate smaller-sized polyps. That definition helps readers understand what the measure represents and what a change would mean on the scale.

The randomized, triple-masked, parallel-group design is also important to interpretation. Random assignment provides a basis for comparing assigned treatment strategies, while masking is intended generally to reduce the influence of expectations on conduct or assessment. The registry record does not describe the mechanics of randomization or identify who was masked, so those aspects cannot be evaluated from the record.

The comparator is clinically and statistically specific: both arms received mometasone furoate nasal spray, with dupilumab in one arm and placebo for dupilumab in the other. Consequently, the intended contrast concerns adding dupilumab to the shared nasal spray regimen, not dupilumab versus no treatment. Making the treatment contrast explicit prevents misreading the comparison.

The registry record also illustrates why a clearly defined endpoint is not enough for statistical interpretation. It identifies a primary measure and a Week 16 assessment, but notes that the primary outcome has several categories or time points and was not reduced to one comparison. Without a single estimate and its uncertainty, readers cannot quantify the primary contrast. The record's missing detail on multiplicity, missing data, and analysis methods further limits the assessment of how the reported outcomes should be interpreted.

These features make the study useful as a case in reading trial records: design, endpoint definition, and analysis reporting are distinct pieces of evidence, and each is needed to understand what a trial can establish.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

A central limitation of the registry record is that it does not report a single numerical primary-outcome comparison. Although it defines the endpoint, scale, assessment time, and summary type, it does not give the group-level changes, a treatment contrast, or uncertainty for that contrast. The primary result therefore cannot be quantitatively interpreted from the record.

The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. It does not explain which categories or time points were analyzed, how they were selected, or how multiple comparisons were handled. The number of outcome measures is listed, but a statistical hierarchy and multiplicity strategy are not reported.

Information on missing data is also limited. The intent-to-treat definition specifies analysis according to randomized assignment, while the number analyzed at a time point is defined by availability of data. The record does not report the count of missing observations at each time point, the reasons for missingness, imputation methods, or sensitivity analyses.

The detailed statistical analysis plan, the trial's sample-size justification, and interim analyses are not reported in the registry record. Neither the numerical results for secondary endpoints nor details needed to evaluate their analysis are included in the registry record. The safety summary lacks event timing, severity details, and arm-specific attribution for the listed serious-event terms. These limitations restrict both efficacy interpretation and a fuller assessment of safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Evaluation of Dupilumab in Patients With Nasal Polyposis And Chronic Symptoms Of Sinusitis — NCT01920893.
• Registry record last updated 2017-06-26; status last verified 2017-06.
• Results first posted 2017-06-02.
• 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.

18. Record Summary

The registry record describes a completed randomized, triple-masked, parallel, placebo-controlled phase 2 study of dupilumab in participants with bilateral nasal polyposis and chronic symptoms of sinusitis. Enrollment was 60. Both arms received mometasone furoate nasal spray; the study compared dupilumab with placebo for dupilumab.

The primary endpoint was change from baseline in bilateral endoscopic NPS at Week 16, on a scale from 0 to 8, with lower scores indicating smaller-sized polyps. Secondary outcomes covered symptoms, rhinosinusitis severity, airflow, smell, sinus CT measures, an asthma subgroup, and time to first NPS response. The record reports selected adverse-event counts and deaths of 0 in both arms.

The registry record does not report a single numerical primary comparison, detailed statistical analysis plan, multiplicity strategy, or missing-data method. Those gaps prevent quantitative interpretation of the primary treatment contrast from the record.