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 to Evaluate the Onset of Effect and Time Course of Change in Lung Function With Benralizumab in Severe, Uncontrolled Asthma Patients With Eosinophilic Inflammation (NCT02869438), a randomized phase 3 study. The primary outcome is Change From Baseline (Visit 4) to Day 28 (Visit 8), Day 56 (Visit 9), and Day 84 (Visit 10) in Pre-BD FEV1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02869438 |
| Phase | Phase 3 |
| Condition | Asthma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 233 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Patients with severe, uncontrolled asthma and eosinophilic inflammation. The primary endpoint identifies the full analysis set as its population. The registry record does not give further eligibility details in the registry record considered for this analysis.
Intervention
Benralizumab, administered subcutaneously. The safety groups are labeled Benra 30 mg, but further dosing and schedule details are not reported in the registry record.
Comparator
Placebo, also administered subcutaneously. The trial is described as placebo-controlled, randomized, double-blind, and parallel-group.
Primary question
How does change from baseline in pre-BD FEV1 differ between benralizumab and placebo at Day 28, Day 56, and Day 84, and when does the registry-defined statistical criterion for onset first occur? The registry entries do not include the endpoint estimates, p-values, or the actual time of onset.
Pre-BD FEV1 is the forced expiratory volume in one second measured before bronchodilator administration. The primary outcome concerns change from baseline at repeated post-baseline visits, rather than a single end-of-treatment measurement. The registry describes using an average over the mean differences between the groups to assess whether the study is positive and whether an effect is maintained. It separately defines onset as the first post-baseline time point at which the p-value for the mean difference is less than or equal to 0.05.
This framing makes the timing of measurement central to the question: the study was intended to assess both early change and its course through Day 84. The registry record does not report the group-specific changes, between-group mean differences, uncertainty intervals, p-values, or which visit, if any, met the stated onset criterion. Therefore, the clinical question can be described from the design and endpoint definition, but the record details do not establish the direction, size, or statistical precision of the observed result.
3. Trial Design
This was a randomized, double-blind, parallel-group, placebo-controlled Phase 3b study. It enrolled 233 participants and is recorded as completed. The registry lists asthma as the condition. Benralizumab and placebo were both administered subcutaneously. Details of the randomization procedure, allocation ratio, concealment, and the specific blinding arrangements are not reported in the registry record.
The listed study period began on 2016-11-09, with primary completion on 2018-08-01. The study description states that the purpose was to investigate the onset and maintenance of benralizumab’s effect on lung function, blood eosinophils, asthma control measures, and quality of life during 12-week treatment. A subset of patients was to take part in a body plethysmography substudy. Further operational details, including visit windows, treatment schedule, and the substudy’s selection process, are not reported in the registry record.
The primary endpoint is change from baseline in pre-BD FEV1 at Day 28, Day 56, and Day 84, assessed in the full analysis set. The registry describes the endpoint as a mean and identifies standard deviation as its dispersion measure. The study also lists secondary outcomes covering eosinophil counts, pre-BD lung-function measures, an FEV1 responder outcome, asthma control, quality of life, FeNO, and total lung capacity for substudy patients.
The record lists 23 outcome measures and 35 analyses. These counts indicate that the record contains multiple outcomes and analyses, but do not, by themselves, establish how hypotheses were grouped, whether multiplicity adjustments were used, or which analyses were confirmatory. Those details are not reported in the registry record. The sample-size assumptions described for planning illustrations are explicitly not the trial’s own design assumptions; the registry’s sample-size justification is 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.
Before assignment: 233 participants were randomized to receive treatment in study D3250C00038 (Solana) with benralizumab 30 mg or placebo. Of the 233 patients randomised, all (100.0%) received treatment with study drug. 118 (50.6%) patients received benralizumab 30 mg and 115 (49.4%) patients received placebo.
Overall Study
| Stage | Benra 30 mg | Placebo |
|---|---|---|
| STARTED | 118 | 115 |
| COMPLETED | 115 | 113 |
| NOT COMPLETED | 3 | 2 |
Reasons for not completing this period:
| Reason | Benra 30 mg | Placebo |
|---|---|---|
| Lost to Follow-up | 1 | 0 |
| Adverse Event | 1 | 0 |
| Withdrawal by Subject | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set
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 | Benra 30 mg | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 118 | 115 | 233 | |
| Age, Continuous | years | 51.9 (SD 13.62) | 50.9 (SD 12.34) | 51.4 (SD 12.99) |
| Sex: Female, Male: Female | Participants | 74 | 83 | 157 |
| Sex: Female, Male: Male | Participants | 44 | 32 | 76 |
| Race/Ethnicity, Customized: White | Participants | 69 | 67 | 136 |
| Race/Ethnicity, Customized: Black or African American | Participants | 3 | 4 | 7 |
| Race/Ethnicity, Customized: Asian | Participants | 39 | 40 | 79 |
| Race/Ethnicity, Customized: Other | Participants | 7 | 4 | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline (Visit 4) to Day 28 (Visit 8), Day 56 (Visit 9), and Day 84 (Visit 10) in Pre-BD FEV1, measured over From first IP dose to Day 84.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Liter |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures change from baseline in pre-bronchodilator forced expiratory volume in one second, or pre-BD FEV1. FEV1 is a continuous lung-function measure. The registry specifies assessments at Day 28, Day 56, and Day 84, with the timeframe described as extending from first investigational product dose to Day 84. The outcome is expressed as a mean, with standard deviation identified as the measure of dispersion.
Comparing change from baseline between randomized groups focuses the comparison on how the measured value changes over the study period, rather than on post-baseline values alone. The registry states that the average over the mean differences between benralizumab and placebo is used to determine whether the study is positive and to assess maintenance of effect. It also defines a separate onset criterion: the first post-baseline visit at which the p-value for the mean difference is less than or equal to 0.05.
These are related but distinct questions. The average across the specified visits concerns the overall group contrast and maintenance over time; the onset rule concerns when a visit-specific contrast first reaches the stated significance threshold. The primary endpoint definition does not itself report the observed changes or establish whether either criterion was met. Endpoint estimates, visit-specific p-values, confidence intervals, and the observed onset time are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the primary outcome and the rule intended to assess onset, but the endpoint results needed to interpret those questions are not reported in the registry record. In particular, the registry entries do not give mean changes from baseline by group, mean differences between groups, confidence intervals, p-values, or the first visit that met the stated onset rule. No conclusion about the direction or size of the lung-function contrast, its precision, or whether it met the registry’s criterion can be drawn from these registry entries alone.
The distinction between statistical significance and effect size is important. A p-value evaluates how compatible the observed data are with a specified null hypothesis under the analysis assumptions; it does not state the size or clinical importance of a difference. A mean difference describes the estimated contrast in the endpoint’s units, while an interval estimate, if reported, would convey its statistical uncertainty. The registry’s definition uses a p-value threshold for onset, but the actual p-values and effect estimates are not reported in the registry record.
The outcome is measured at multiple visits. The registry says that the average over mean differences is used to assess whether the study is positive and whether effect is maintained, while the onset rule identifies the first visit with a p-value at or below the stated threshold. Without the estimates at each visit and details of how the average was calculated, readers cannot determine how the overall contrast relates to the individual time-point contrasts. Nor can the onset definition reveal whether the effect persisted after its first qualifying visit; that requires the observed results across visits.
The study’s randomized, double-blind, placebo-controlled parallel design is relevant to how a treatment comparison is structured. Randomization can support comparability of groups on average, and blinding can reduce some forms of bias, but the registry entries do not describe implementation details or establish that all potential sources of bias were eliminated. The observed analysis results and their precision remain necessary for assessing the primary question.
The registry lists a range of secondary outcomes and reports 23 outcome measures and 35 analyses. Multiple outcomes and analyses raise questions about how the statistical error rate was managed and which results were designated primary or confirmatory. The multiplicity strategy is not reported in the registry record. Consequently, the primary endpoint definition should not be treated as evidence that every listed analysis was adjusted or interpreted under a single prespecified testing plan.
The record also reports serious and other adverse-event counts, but these are separate from the efficacy endpoint. Their interpretation depends on the event definitions, ascertainment, follow-up, and comparative context. The counts describe what was recorded for the named groups; they do not, without further information, establish causation or provide a complete account of benefit and harm.
9. Statistical Methods Explained
What does a mean change describe?
The primary endpoint is continuous and is reported using a mean. In general, a mean summarizes the central value of a set of measurements. A change-from-baseline outcome compares a participant’s post-baseline measurement with that participant’s baseline measurement, and a group mean summarizes those changes. The contrast between group means then describes the average difference in change between benralizumab and placebo. The endpoint’s unit is liter.
In general, a mean is informative about an average but does not show the full distribution of participant-level responses. The registry identifies standard deviation as the dispersion measure. In general, standard deviation describes how spread out individual observations are around their mean. It is not the same as the standard error, which describes the sampling uncertainty of an estimate. The record details do not include the actual means, standard deviations, or standard errors for the primary endpoint.
Why measure the outcome at repeated visits?
The primary outcome specifies measurements at Day 28, Day 56, and Day 84. Repeated measurements can describe how a group contrast develops over time, rather than limiting assessment to one visit. The registry’s stated purpose includes investigating onset and maintenance. Its onset rule uses the first post-baseline visit at which the p-value for the mean difference is less than or equal to 0.05. Its description of the overall assessment refers to an average over mean differences.
As a general statistical matter, repeated observations from the same participant may be related; they should not automatically be treated as independent measurements. A suitable analysis may need to account for that relationship. The statistical model, covariance structure, handling of visit-specific contrasts, and exact calculation of the average are not reported in the registry record. Those details matter for reproducing the analysis and understanding how the estimates and their uncertainty were obtained.
What does the onset rule mean?
In general, a p-value measures how unusual data at least as incompatible with a null hypothesis as the observed data would be, assuming the null hypothesis and the statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. Here, the registry uses a threshold of 0.05 to define the first visit qualifying as onset. The actual visit-specific p-values are not reported in the registry record, so the rule can be explained but its result cannot be identified.
Because the rule examines a sequence of visits, interpretation depends on whether and how the analyses account for multiple opportunities to meet the threshold. In general, repeated testing can increase the chance of a false-positive finding if each test is treated as an independent opportunity without an appropriate strategy. The registry entries do not state whether the onset assessments were adjusted, ordered under a formal testing procedure, or treated as descriptive. The multiplicity approach is not reported in the registry record.
What do the planning assumptions represent?
The sample-size assumptions are described as planning illustrations computed from the observed effect, not as the trial’s design. They specify a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. For time-to-event tables, the assumption text says the displayed quantity is a total number of events; for other cases, it describes participants per arm. The primary endpoint is continuous, not a time-to-event endpoint.
These assumptions describe a hypothetical planning exercise. In general, a sample-size calculation asks how much information would be needed under chosen assumptions to detect a specified effect with a selected error rate and power. Such a calculation is not evidence that the original trial was designed with those assumptions, and it is not observed power. The registry entries do not provide the numerical planning outputs, so they cannot support a statement about the implied sample size for any particular effect fraction. The trial’s own sample-size justification and design assumptions are not reported in the registry record.
What is unavailable for independent statistical review?
The registry entries identify the endpoint, population, visits, summary measure, and onset threshold, but do not report the primary estimates or the inferential details needed for a full review. In particular, the analysis model, covariates, missing-data methods, confidence intervals, exact test specification, and multiplicity strategy are not reported in the registry record. In general, these elements help determine how estimates should be interpreted, how uncertainty is represented, and whether the stated analysis can be reproduced.
The registry entries also do not say whether the primary endpoint analysis followed a prespecified statistical analysis plan or whether any changes were made. No interim analysis information is reported in the registry record. Without those details and the outcome estimates, the statistical description can clarify the intended questions and general concepts, but it cannot reconstruct the primary analysis or verify its findings.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 23 outcome measures and 35 analyses, in addition to a primary endpoint with measurements at Day 28, Day 56, and Day 84. These are reasons to ask how multiple outcomes, time points, and analyses were handled, but the counts alone do not indicate how many confirmatory hypotheses were tested or how the testing was organized.
In general, multiplicity arises when several statistical tests contribute to conclusions. Without an appropriate strategy, repeated testing can increase the chance of at least one false-positive result. Possible approaches in general include adjusting significance thresholds, specifying a testing order, or treating some analyses as exploratory. The registry record does not report which approach, if any, was used. It also does not describe whether the onset criterion was adjusted for its repeated visit assessments.
Missing-data handling is likewise important for repeated lung-function measurements. In general, missing observations can affect the analysis, particularly when the reasons for missingness relate to outcomes or treatment. The statistical method for missing primary outcome data, the amount of missing data, and the assumptions used to address it are not reported in the registry record.
The primary endpoint names the full analysis set as its population. Further details about the set’s definition, which randomized participants were included, and how protocol deviations or incomplete measurements were handled are not reported in the registry record. These omissions limit assessment of whether the analysis population and missing-data approach could influence the estimated group contrast.
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 |
|---|---|---|---|
| Benra 30 mg | 1 | 118 | 0.8% |
| Placebo | 7 | 115 | 6.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Benra 30 mg | 0 of 118 |
| Placebo | 0 of 115 |
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 |
|---|---|
| Benra 30 mg | 28 of 118 |
| Placebo | 30 of 115 |
Most frequent serious adverse event terms
| Event term | Organ system | Benra 30 mg | Placebo |
|---|---|---|---|
| Pneumonia | Infections and infestations | 0 of 118 | 2 of 115 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 0 of 118 | 2 of 115 |
| Coronary artery disease | Cardiac disorders | 0 of 118 | 1 of 115 |
| Drug hypersensitivity | Immune system disorders | 1 of 118 | 0 of 115 |
| Lower respiratory tract infection | Infections and infestations | 0 of 118 | 1 of 115 |
| Generalised tonic-clonic seizure | Nervous system disorders | 0 of 118 | 1 of 115 |
| Migraine | Nervous system disorders | 0 of 118 | 1 of 115 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Benra 30 mg | Placebo |
|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | 11 of 118 | 18 of 115 |
| Nasopharyngitis | Infections and infestations | 8 of 118 | 6 of 115 |
| Upper respiratory tract infection | Infections and infestations | 6 of 118 | 6 of 115 |
| Bronchitis | Infections and infestations | 6 of 118 | 3 of 115 |
Serious events with the highest arm-level rate: pneumonia (1.7%), asthma (1.7%), coronary artery disease (0.9%), lower respiratory tract infection (0.9%), generalised tonic-clonic seizure (0.9%).
The safety record gives serious adverse-event figures separately for the Benra 30 mg and placebo groups. In the Benra 30 mg group, 1 of 118 participants was reported with a serious adverse event; in the placebo group, 7 of 115 were reported with a serious adverse event. The record also reports other adverse events for 28 of 118 in the Benra 30 mg group and 30 of 115 in the placebo group. Deaths are recorded as 0 in each group.
These are counts with the corresponding at-risk denominators as listed in the record. They describe events recorded during the study, not necessarily events caused by study treatment. The registry entries do not provide event-level timing, duration, severity definitions, exposure-adjusted rates, or adjudication details. A comparison of these counts alone cannot establish a causal difference between groups.
The record lists pneumonia and asthma at 1.7% each, and coronary artery disease, lower respiratory tract infection, generalised tonic-clonic seizure, and migraine at 0.9% each among the top serious terms. Those percentages should be read as the registry’s reported figures; the registry entries do not provide further detail about how terms were selected or classified. Safety counts are distinct from the primary lung-function endpoint and should be interpreted alongside the trial’s design and the limitations of the posted record.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-blind, placebo-controlled study was conducted to investigate benralizumab’s onset and maintenance of effect on lung function and other outcomes in severe, uncontrolled asthma with eosinophilic inflammation. It specifies a primary measure, pre-BD FEV1 change from baseline at Day 28, Day 56, and Day 84, and states how the registry intended to assess an overall contrast and onset.
Those descriptions do not supply the primary endpoint results. The group means, between-group estimates, uncertainty intervals, visit-specific p-values, and observed onset time are not reported in the registry record. Accordingly, the registry entries do not show the magnitude or precision of the lung-function contrast, whether the stated statistical threshold was reached, or whether a contrast was maintained through the later visits. The endpoint definition alone is not a result.
In general, statistical significance and clinical importance are different considerations. A p-value does not convey the size of a difference, while an estimate in the endpoint’s units does not by itself establish whether a difference is meaningful to patients. Interpretation ordinarily considers the estimated effect, its uncertainty, the endpoint’s context, and the analysis plan. Those pieces are not all available in the registry entries.
The safety figures provide recorded serious and other adverse-event counts, along with deaths and selected serious-event terms. They are descriptive and do not by themselves establish whether events were caused by treatment or whether one group’s overall safety profile was preferable. The registry entries do not include enough detail to resolve those questions.
The appropriate conclusion is therefore limited: the record describes the design, endpoint framework, and selected safety counts, but does not report the primary efficacy results needed to answer the stated lung-function question. Any stronger conclusion about treatment effect or its timing would go beyond what is reported in the registry record.
13. Why This Trial Matters Statistically
Statistically, this study is notable for defining both an overall repeated-visit question and a time-to-onset rule using a continuous lung-function outcome. The primary endpoint concerns mean change in pre-BD FEV1 at Day 28, Day 56, and Day 84. Its description uses the average over the mean differences to assess whether the study is positive and whether effect is maintained, while onset is defined by the first visit where the group-comparison p-value is less than or equal to 0.05.
These definitions illustrate why a clinical-trial result is more than a single p-value. An overall contrast across visits and a first qualifying time point answer different statistical questions. Estimation at each visit, the uncertainty around those estimates, and a clear account of the repeated-measures model and multiplicity strategy are relevant to understanding whether the pattern is consistent and how much precision it has. Those results and methods are not reported in the registry record.
The study also lists outcomes spanning lung function, eosinophil counts, asthma control, quality of life, FeNO, and a body plethysmography substudy. The presence of multiple outcome measures makes clear why readers benefit from knowing which analyses were primary, how secondary analyses were interpreted, and how missing measurements were treated. The registry counts 23 outcome measures and 35 analyses, but does not provide the details needed to map each analysis to a testing strategy.
The record’s value for statistical interpretation is thus both specific and limited: it documents the intended endpoint and onset definition, but does not report the estimates needed to evaluate them. It also provides a reminder that planning illustrations based on an observed effect are separate from a trial’s original design assumptions and do not represent observed power.
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 main trial-specific limitation for interpreting the primary question is that the registry entries do not report the primary endpoint estimates or p-values. Without group-specific changes, mean differences, uncertainty intervals, and visit-specific results, readers cannot assess effect direction, magnitude, precision, or the time point meeting the stated onset criterion.
The registry specifies multiple primary visits and an onset threshold, but does not report the statistical model, the method used to form the average over mean differences, or whether repeated testing was addressed through a multiplicity strategy. These details are necessary to understand how the repeated measurements were analyzed and how the reported inferential statements, if any, should be interpreted.
The full analysis set is named, but its exact definition and the handling of missing or incomplete measurements are not reported in the registry record. Details of randomization implementation, allocation ratio, blinding procedures, protocol deviations, and analysis-plan changes are also not reported in the registry record. These gaps limit evaluation of potential analysis and conduct biases.
The study description refers to a subset participating in a body plethysmography substudy, but the selection process and substudy results are not reported in the registry record. The secondary outcomes are listed, yet their estimates and analysis details are not included in the registry entries. The reported adverse-event counts also lack further information about follow-up, event ascertainment, and causality assessment. These limitations constrain interpretation of both the primary question and the broader clinical context.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Onset of Effect and Time Course of Change in Lung Function With Benralizumab in Severe, Uncontrolled Asthma Patients With Eosinophilic Inflammation — NCT02869438.
- Registry record last updated 2019-10-29; status last verified 2019-10.
- Results first posted 2019-10-07.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed, randomized, double-blind, parallel-group, placebo-controlled Phase 3b study of benralizumab and placebo in patients with severe, uncontrolled asthma and eosinophilic inflammation. Enrollment was 233. The listed study period began on 2016-11-09, and primary completion was 2018-08-01.
The primary outcome is change from baseline in pre-BD FEV1 at Day 28, Day 56, and Day 84, in the full analysis set. The registry defines an average over mean differences for assessing the overall question and a first-visit p-value threshold for onset. The primary estimates, p-values, and observed onset time are not reported in the registry record.
The record lists 23 outcome measures and 35 analyses. It also reports serious and other adverse-event counts, selected serious-event terms, and no deaths in either listed group. The registry’s detailed statistical plan, missing-data methods, and multiplicity strategy are not reported in the registry record.