Study to Assess Functionality, Reliability, and Performance of a Single-Use Auto-Injector With Benralizumab Administered at Home: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Functionality, Reliability, and Performance of a Single-Use Auto-Injector With Benralizumab Administered at Home (NCT02918071), a na phase 3 study. The primary outcome is Number of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an AI Device at Home.

2. Clinical Question

GRECO was designed to assess the functionality, reliability, and performance of a single-use auto-injector used for at-home subcutaneous administration. Its stated purpose also included confirming safety and clinical benefit in patients with severe asthma. These aims should be distinguished: the primary endpoint concerns successful device-supported administration, while the registry lists separate secondary outcomes concerning asthma control, pharmacokinetics, pharmacodynamics, and immunogenicity.

Because the study had no control group, the central question is descriptive rather than comparative. The endpoint can characterize whether the specified administration criteria were met at the listed assessment times. It cannot, by itself, establish how administration would compare with another device or setting. No primary endpoint counts or success rates are reported in the registry record, so the outcome cannot be quantified from the record.

3. Trial Design

GRECO, registered as NCT02918071, is described as a Phase 3, multicenter, open-label, single-group study. The registry lists 121 participants enrolled and the study status as completed. The recorded study start date is 2016-11-10, and the primary completion date is 2017-08-21. The condition listed is asthma; the official title specifies adult patients with severe asthma.

Participants received benralizumab, a biological intervention, by subcutaneous injection. The arm description states that benralizumab was administered every 4 weeks. Administration was intended to occur at home using a single-use auto-injector. Patients or caregivers were involved in reporting the administration outcome. The record does not describe a control arm, random allocation, or masking; allocation is listed as not applicable and masking as none.

The primary outcome is a participant count based on successful administration at Week 12, Week 16, and across Week 12 and 16. The primary population is defined as patients who received at least one dose of benralizumab. The listed secondary outcomes concern change from baseline in mean Asthma Control Questionnaire-6 score, serum benralizumab concentration, peripheral blood eosinophil levels, and anti-drug antibodies.

The registry record lists 7 outcome measures and 13 analyses, but it does not provide a complete statistical analysis plan, sample-size justification, or explanation of how the analyses were organized. The study design can support description of the enrolled group's administration experience and measured outcomes. Without a comparison group, it cannot separate changes associated with treatment or device use from other explanations. No inference about comparative effectiveness should be drawn from this design alone.

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: 121 participants receive treatment with benralizumab 30 mg at every 4 weeks schedule.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set - all patients who were administered for at least one dose of Benralizumab.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients/Caregivers Who Successfully Administered Benralizumab 30 mg Subcutaneously (SC) by Injection With an AI Device at Home, measured over Week 12, Week 16, Week 12 and 16.

The primary endpoint counts patients or caregivers who successfully administered benralizumab 30 mg subcutaneously with the auto-injector at home. It is assessed at Week 12, Week 16, and across Week 12 and 16. The record defines a successful administration using several requirements: the injection had to be completed, every one of the 5 questionnaire questions had to receive a “Yes,” and visual inspection and function tests had to be passed adequately. A patient still in the study at a specified timepoint is defined as a patient who had been treated for that timepoint.

This endpoint is relevant to the study's stated focus on device functionality, reliability, and performance in a home setting. It combines completion of the injection with patient or caregiver responses and device checks rather than relying on injection completion alone. A count can describe how many participants met all stated criteria, while the assessment at different timepoints can describe whether criteria were met at each specified assessment.

The registry record does not report the endpoint counts, denominators by timepoint, or the number meeting the success definition. It therefore does not support a numerical conclusion about the proportion of participants who successfully administered treatment. The primary outcome also does not itself measure comparative device performance, because the study has no comparison arm.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants who meet a defined success criterion. For a count endpoint, interpretation begins with the number of participants meeting the definition and the number eligible for assessment. A count alone does not show the frequency in the population unless its denominator is also clear. Here, the registry record defines the primary population as patients who received at least one dose of benralizumab, but it does not report the endpoint counts or timepoint-specific denominators.

What the success definition captures

The definition requires several conditions to be met together: injection completion, “Yes” responses to all 5 questionnaire questions, and adequate passage of visual inspection and function tests. This makes the outcome a composite operational measure of administration success. In general, a composite endpoint can summarize multiple required components, but it may conceal differences among those components. Separate component results help show whether an overall outcome reflects injection completion, questionnaire responses, device inspection, or some combination. Those component results are not reported in the registry record.

The outcome is assessed at Week 12 and Week 16, as well as across Week 12 and 16. Repeated assessments can describe performance at different times, but their interpretation depends on the definitions used for each timepoint and for the combined assessment. The record gives the timepoints but does not explain the analysis details for the combined result, such as how participants with an assessment at only one timepoint were treated. That handling is not reported in the registry record.

How to read a count and its uncertainty

In general, an estimate of the number or proportion meeting an endpoint is subject to sampling variability: another group of similar participants could produce a different result. A confidence interval expresses the uncertainty around an estimate under specified statistical assumptions. Wider intervals indicate less precision, while narrower intervals indicate greater precision. The registry record does not report a primary endpoint estimate or confidence interval, so the precision of the administration-success result cannot be assessed.

For binary outcomes, an analysis commonly distinguishes participants who have the event from those who do not. That distinction is useful only when the event definition, analysis population, and handling of unavailable assessments are clear. In this study, success is defined, and the full analysis set is described, but the primary outcome results and missing-data procedures are not reported. It would be inappropriate to treat missing or unreported assessments as either successes or failures.

What the design permits

A single-group study can describe outcomes among participants receiving the study intervention. Since there is no control group, the design does not estimate a between-group treatment effect. In general, a randomized comparison helps distinguish differences associated with assigned interventions from other influences; that type of comparison is absent. The open-label design also means that masking is not listed, and the endpoint includes patient or caregiver reporting. This context matters when interpreting a self-reported component, although the record does not quantify any influence of open-label assessment.

The primary endpoint concerns use of the auto-injector at home, while separate secondary outcomes concern asthma control and biological measures. These outcomes address different questions and should not be treated as interchangeable. A device-administration count does not measure a change in asthma control, and a laboratory measure does not directly establish successful home administration. The listed outcomes include change from baseline in mean ACQ-6 score, serum concentration of benralizumab, peripheral blood eosinophil levels, and anti-drug antibodies. Their results are not reported in the registry record.

Planning illustrations are not trial results

Planning sample-size illustrations use assumptions about an effect to detect and a chosen statistical procedure. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it defines the effect in relation to a stated fraction of the observed effect. Such illustrations are hypothetical planning exercises, not observed trial outcomes and not evidence that the study had a particular probability of detecting an effect. The study itself is single-group, so a two-arm illustration does not describe its design. The registry record does not report the trial's own sample-size justification.

In general, over-dispersion occurs when count outcomes vary more than a model assumes, which can make standard errors too small if the model does not account for that extra variability. This concept may matter for some count analyses, but the primary endpoint is reported as a participant count and the registry record does not specify a model for it. No claim about over-dispersion or a particular modeling approach can therefore be made for this study.

What statistical significance would and would not mean

In general, a p-value assesses how compatible observed data are with a specified null model, given the model assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or practical importance of an effect. A confidence interval adds information about the range of values reasonably compatible with the data and analysis assumptions. Neither a p-value nor a confidence interval for the primary endpoint is reported in the registry record. Because the study lacks a comparator, a test of a between-arm difference is not applicable to the described design.

Finally, multiple outcomes and analyses create a multiplicity issue: when many statistical questions are examined, the chance of at least one apparently notable finding can increase. A prespecified hierarchy or adjustment can address some multiplicity concerns, but the registry record does not report whether such methods were planned or used. The count of listed outcome measures and analyses does not by itself establish which results were primary, how tests were ordered, or whether any adjustment was applied.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 7 outcome measures and 13 analyses. It identifies the administration-success count as the primary outcome and lists secondary outcomes for asthma control, benralizumab concentration, peripheral blood eosinophil levels, and anti-drug antibodies. The number of outcomes and analyses makes it important to know which comparisons were prespecified and whether any multiplicity strategy was used. The registry record does not report a testing hierarchy, adjustment method, or complete statistical analysis plan. It is not possible to determine whether reported secondary findings, if available, would have been adjusted for multiple testing.

The primary endpoint has assessments at Week 12, Week 16, and across Week 12 and 16. The record describes the timing and success criteria, but does not explain how these assessments relate analytically, whether one timepoint was designated as the key test, or how the combined assessment was constructed. Those details are not reported in the registry record.

The primary population is described as the full analysis set: patients who received at least one dose of benralizumab. The record does not provide the number contributing to each primary assessment, the extent of missing endpoint data, or the method used to address missing observations. It also does not explain whether exclusions occurred after enrollment. Because these details are absent, the enrolled total of 121 should not be assumed to be the denominator for every outcome.

Missing-data handling matters because an unavailable assessment is not necessarily equivalent to failure or success. Different assumptions about unavailable observations can alter an estimate. No missing-data assumption or imputation procedure is reported in the registry record, so no such procedure should be attributed to this study.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (0.8%).

The safety figures list 121 participants at risk for serious adverse events and 1 participant affected. For other adverse events, 121 participants were at risk and 45 were affected. The record lists 0 deaths. These are participant counts, not a description of the total number of event episodes, and they should be read separately from the primary endpoint concerning successful administration.

The most frequent serious adverse-event term listed is asthma, at 0.8%. This is the reported percentage for that term; it does not provide the full clinical context, timing, or course of the event. The registry record does not provide detailed event narratives, severity grades, or an assessment of relatedness in the information.

In general, an adverse event occurring during a study is not automatically caused by the study treatment or device. A single-group study also has no control-group rate for comparison. The listed counts therefore describe events among participants at risk but do not establish causation or comparative safety. The record does not report additional detail needed to interpret differences among types of events or their timing.

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

The record establishes that GRECO was a completed, open-label, single-group study of home administration of subcutaneous benralizumab using a single-use auto-injector in adults with severe asthma. It specifies a practical primary outcome: the number of patients or caregivers who met a multi-part definition of successful administration at Week 12, Week 16, and across Week 12 and 16. It also reports selected safety counts and identifies several secondary outcomes.

What the record does not establish is how many participants met the primary success definition. The primary endpoint result is not reported in the registry record. There is therefore no basis in the record for saying what proportion completed administration successfully, whether success was consistent across assessments, or which part of the definition was most often unmet. The description of an endpoint is not itself evidence that the endpoint was achieved.

The study design also limits the conclusions that could be drawn even if primary outcome counts were available. With no control group and no masking, the data can describe the experience of the enrolled group but cannot provide a like-for-like comparison with another device, setting, or treatment. The study's stated aim included safety and clinical benefit, but the available record does not report results for the listed asthma-control or biological outcomes.

The adverse-event counts indicate that serious and other adverse events were recorded among participants, with 0 deaths listed. These figures do not establish that benralizumab or the auto-injector caused any event, and they do not permit comparison with another group. A fuller interpretation would require outcome details, analysis denominators, and methods that are not reported in the registry record.

Accordingly, the record is informative about the trial's purpose, design, definitions, and selected event counts, but it is insufficient to quantify the primary administration outcome or draw a comparative conclusion. Absence of a reported result should not be mistaken for a result of zero or for evidence that the outcome was either met or not met.

13. Why This Trial Matters Statistically

GRECO addresses a statistical question that differs from a conventional comparison of treatment groups. Its primary endpoint is a defined count of successful home administrations, with success requiring injection completion, patient or caregiver questionnaire responses, and adequate visual and functional checks. This makes clarity about the endpoint definition, analysis population, and assessment timepoints especially important.

The endpoint illustrates how a composite definition can be useful and demanding at once. Requiring every component means the count represents complete success under the study's operational criteria. At the same time, an overall count alone would not reveal which component most often determined whether a participant met the definition. Component-level results and transparent denominators would help readers understand the measure, but those results are not reported in the registry record.

The study also highlights why design and question must be interpreted together. A single-group study can describe the experience of participants using an auto-injector at home. It does not provide a direct estimate of how that experience differs from another device or setting. The open-label design and patient or caregiver reporting are relevant context, while not proving that assessment was biased.

Finally, the record demonstrates the distinction between a planned or defined outcome and a reported finding. The study's enrollment, endpoint definition, and safety counts are available, but the primary administration result is not. Readers need the numerical result, timepoint-specific denominators, and methods for missing data and multiplicity to evaluate the estimate and its precision. Without those items, the most defensible statistical reading is descriptive and limited.

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 central limitation for interpreting the primary endpoint is that its results are not reported in the registry record. The endpoint is defined, but counts of participants meeting the success criteria are absent for Week 12, Week 16, and the combined assessment. No uncertainty estimates are reported either. The study's primary statistical finding therefore cannot be assessed from the record.

The enrolled total of 121 does not resolve this gap. The primary population is defined by having received at least one dose, and the registry record does not report how many participants contributed data at each assessment. Timepoint-specific denominators, withdrawals, and missing assessments are not described. The record also does not say how a missing questionnaire response or unavailable inspection result affected endpoint classification.

The study has no comparison arm and is open-label. Consequently, it cannot estimate a controlled contrast in device performance or distinguish outcomes from other factors through randomization. The patient or caregiver reports are part of the success definition, but the record does not give details about how those reports were collected beyond the stated questionnaire criterion.

Although the registry lists secondary outcomes and a total number of analyses, it does not report the full statistical plan, methods for multiplicity, or the results of those secondary outcomes. The sample-size justification and any interim analyses are not reported in the registry record. These omissions limit assessment of precision, analysis choices, and the relationship between planned questions and reported findings.

The safety information is also limited to selected counts and a serious-event term. It does not give detailed event descriptions, timing, severity grades, or comparative rates. These limitations mean that the registry entries support a description of design and selected recorded events, but not a complete evaluation of the study's efficacy, device performance, or safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess Functionality, Reliability, and Performance of a Single-Use Auto-Injector With Benralizumab Administered at Home — NCT02918071.
• Registry record last updated 2018-11-02; status last verified 2018-10.
• Results first posted 2018-11-02.
• 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

NCT02918071, GRECO, was a completed Phase 3, multicenter, open-label, single-group study with 121 participants enrolled. It evaluated a single-use auto-injector for at-home subcutaneous administration of benralizumab in adults with severe asthma. Benralizumab 30 mg was described as administered every 4 weeks.

The primary outcome was the count of patients or caregivers meeting a multi-part definition of successful administration at Week 12, Week 16, and across Week 12 and 16. The primary endpoint results are not reported in the registry record. Listed secondary outcomes concern asthma control, benralizumab concentration, peripheral blood eosinophil levels, and anti-drug antibodies.

The safety record lists 1 participant with a serious adverse event, 45 participants with other adverse events, and 0 deaths, among 121 at risk for each category. Asthma is listed as the most frequent serious adverse-event term, at 0.8%. The design has no comparator, and the registry record does not report the complete statistical plan, missing-data methods, or trial sample-size justification.