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 Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma (NCT01287039), a randomized phase 3 study. The primary outcome is Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01287039 |
| Phase | Phase 3 |
| Condition | Eosinophilic Asthma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 489 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Teva Branded Pharmaceutical Products R&D, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants were 12-75 years of age with eosinophilic asthma. The primary endpoint analysis used the randomized set. The registry record reports 489 participants enrolled and describes the primary outcome population as the randomized set.
Intervention
Reslizumab 3.0 mg/kg was administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses. The study evaluated efficacy, safety, and immunogenicity.
Comparator
The control group received placebo intravenously once every 4 weeks ( +-7 days) for a total of 13 doses. The study was placebo-controlled and used parallel groups.
Primary question
During Day 1 to Week 52, what was the frequency of clinical asthma exacerbations in each group, and how did the adjusted exacerbation rate for reslizumab compare with placebo? The registry reported adjusted means and a rate ratio with a confidence interval and p-value.
The clinical question concerns the frequency of clinically defined exacerbations over the treatment period, rather than a single measurement of lung function or symptoms. An event counted as a clinical asthma exacerbation when either or both specified treatment or urgent-care criteria were met and at least one other measurement corroborated worsening clinical signs and symptoms. A committee adjudicated exacerbations to support consistent event classification.
The primary result is a comparison between randomized groups, not a direct estimate of what would happen to every individual participant. The reported rate ratio describes the relative event rate under the registry's adjusted analysis. It should be read together with its confidence interval, which conveys uncertainty around that estimate, and with the outcome definition and analysis population.
3. Trial Design
This was a Phase 3, randomized, double-blind, placebo-controlled, parallel-group study. The registry identifies masking as quadruple. It was conducted at multiple centers, enrolled 489 participants, and is recorded as completed. The study start is listed as 2011-04, with primary completion in 2013-12.
Participants were assigned to reslizumab 3.0 mg/kg or placebo. Both interventions were administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses. The primary endpoint covered Day 1 to Week 52. The registry describes its primary analysis population as the randomized set and reports 244 participants in the placebo arm and 245 in the reslizumab arm for that outcome.
Randomization supports a comparison between assigned groups by helping balance measured and unmeasured characteristics on average. Masking is intended to limit the influence of knowledge about assigned treatment on participant experience, care, outcome assessment, or analysis. The registry identifies the design features but does not report further operational details about how randomization or masking was implemented.
The primary endpoint was the frequency of clinical asthma exacerbations during 12 months of treatment. Secondary measures included lung function, asthma-related questionnaires, time to first exacerbation, blood eosinophil count, short-acting beta-agonist use, and treatment-emergent adverse events. The registry lists 13 outcome measures and 11 analyses, while the posted secondary outcome results include a subset of the listed measures.
The record does not report the protocol's sample-size justification, planned recruitment assumptions, or whether interim analyses were planned. It also does not report enough detail to infer how the study handled all departures from assigned treatment, missing measurements, or analysis populations beyond the population label attached to the primary endpoint. These omissions limit what can be concluded about design decisions from the registry record 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: 997 of 1486 screened patients were not randomized: 888 were excluded on the basis of not meeting inclusion criteria, 23 withdrew consent, 17 had an adverse event during the screening period, 12 met an exclusion criterion, 7 were lost to follow-up and 50 were excluded for other reasons. One placebo patient was randomized but not treated.
Overall Study
| Stage | Placebo | Reslizumab 3.0 mg/kg |
|---|---|---|
| STARTED | 244 | 245 |
| COMPLETED | 215 | 218 |
| NOT COMPLETED | 29 | 27 |
Reasons for not completing this period:
| Reason | Placebo | Reslizumab 3.0 mg/kg |
|---|---|---|
| Noncompliance with study procedures | 0 | 1 |
| Change of location/residence | 0 | 3 |
| Elective surgery | 0 | 1 |
| Protocol Violation | 2 | 3 |
| Excluded medication taken | 1 | 0 |
| Noncompliance with study medication | 0 | 1 |
| Problem with travel | 0 | 1 |
| Death | 1 | 0 |
| Change of residence | 1 | 0 |
| Adverse Event | 7 | 4 |
| Withdrawal by Subject | 14 | 11 |
| Lost to Follow-up | 3 | 2 |
Analysis population for the primary outcome, as defined in the registry: Randomized 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.
Population: Randomized set
| Characteristic | Unit | Placebo | Reslizumab 3.0 mg/kg | Total |
|---|---|---|---|---|
| Participants analysed | 244 | 245 | 489 | |
| Age, Continuous | years | 46.7 (SD 14.83) | 46.6 (SD 13.82) | 46.6 (SD 14.32) |
| Sex: Female, Male: Female | Participants | 161 | 142 | 303 |
| Sex: Female, Male: Male | Participants | 83 | 103 | 186 |
| Race/Ethnicity, Customized: White | participants | 182 | 173 | 355 |
| Race/Ethnicity, Customized: Black | participants | 20 | 14 | 34 |
| Race/Ethnicity, Customized: Asian | participants | 33 | 50 | 83 |
| Race/Ethnicity, Customized: American Indian or Alaskan Native | participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Pacific Islander | participants | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Other | participants | 9 | 7 | 16 |
| Race/Ethnicity, Customized: Non-Hispanic and non-Latino | participants | 223 | 216 | 439 |
| Race/Ethnicity, Customized: Hispanic or Latino | participants | 21 | 28 | 49 |
| Race/Ethnicity, Customized: Unknown | participants | 0 | 1 | 1 |
| Weight | kg | 76.5 (SD 18.71) | 75.6 (SD 19.05) | 76.0 (SD 18.87) |
| Height | cm | 165.0 (SD 9.74) | 164.9 (SD 10.42) | 164.9 (SD 10.07) |
| Body Mass Index | kg/m^2 | 28.0 (SD 6.16) | 27.7 (SD 6.26) | 27.9 (SD 6.20) |
| Oral Glucocorticosteroid (OCS) Use at Baseline: OCS - Yes | participants | 46 | 46 | 92 |
| Oral Glucocorticosteroid (OCS) Use at Baseline: OCS - No | participants | 198 | 199 | 397 |
| Asthma Exacerbations In Previous 12 Months | exacerbations | 2.1 (SD 2.31) | 1.9 (SD 1.63) | 2.0 (SD 2.00) |
| Forced Expiratory Volume in 1 Second | liters | 1.928 (SD 0.7908) | 1.894 (SD 0.7258) | 1.911 (SD 0.7583) |
| Asthma Control Questionnaire (ACQ) Overall Score | units on a scale | 2.763 (SD 0.8782) | 2.657 (SD 0.8541) | 2.710 (SD 0.867) |
| Asthma Quality of Life Questionnaire (AQLQ) | units on a scale | 4.159 (SD 1.0883) | 4.303 (SD 1.1208) | 4.231 (SD 1.1059) |
| Asthma Symptom Utility Index (ASUI) | units on a scale | 0.613 (SD 0.2029) | 0.633 (SD 0.1938) | 0.623 (SD 0.1984) |
| Number of Short-Acting Beta-Agonist Puffs (SABA) Daily | puffs/day | 2.7 (SD 3.18) | 2.4 (SD 2.82) | 2.6 (SD 3.01) |
6. Primary Endpoint
The registry lists the primary outcome as Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment, measured over Day 1 to Week 52.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | CAEs in 52 weeks |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures the frequency of clinical asthma exacerbations from Day 1 to Week 52. The registry reports adjusted means in CAEs in 52 weeks. The event definition combines clinical worsening with specified treatment or urgent-care criteria, and requires corroboration by at least one other measurement indicating worsening signs and symptoms. Events were adjudicated by committee to promote consistency.
One criterion was use of systemic corticosteroids, an increase in inhaled corticosteroid use for 3 or more days, or a specified increase for participants already using corticosteroids. The other criterion was asthma-related emergency treatment, such as an unscheduled physician-office or emergency-room visit for nebulizer or other urgent treatment, or an asthma-related hospitalization. A qualifying event could meet either or both criteria.
Counting events over the treatment period captures repeated exacerbations, not just whether a participant experienced a first event. That makes an event-rate measure relevant to a question about overall exacerbation burden during follow-up. The registry used a negative binomial regression model adjusted for stratification factors and reported adjusted means, with a rate ratio comparing groups.
The endpoint depends on both the clinical definition and the quality and consistency of event ascertainment. Adjudication can support consistent classification, but the record does not give further details about adjudication procedures. Nor does it report event-level data or individual participant follow-up. The adjusted arm-level estimates therefore describe the trial's reported group comparison, not the precise event history of each participant.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports an adjusted CAE rate of 1.804 in the placebo group, with a 95% confidence interval from 1.372 to 2.372. For reslizumab 3.0 mg/kg, the adjusted rate was 0.904, with a 95% confidence interval from 0.678 to 1.205. These are adjusted means for CAEs in 52 weeks, based on the randomized set.
The reported rate ratio for reslizumab versus placebo was 0.501, with a 95% confidence interval from 0.373 to 0.674 and p < 0.001. The point estimate expresses the adjusted rate in the reslizumab group relative to the adjusted rate in the placebo group. The interval gives a range of values compatible with the observed data under the model and its assumptions. The interval does not include the value representing equal rates, and the reported p-value indicates that the observed comparison would be unusual under the null hypothesis of no rate difference, assuming the analysis model and test are appropriate.
That statistical description does not establish that the model is correct or that every relevant source of bias has been removed. It is also not a statement about the certainty of an individual participant's outcome. The estimate applies to the study's endpoint definition, analysis population, follow-up period, and reported adjusted analysis. The record identifies adjustment for stratification factors but does not name those factors.
The results use different summaries for the two arms and the between-group comparison. The adjusted means describe estimated rates for each group; the rate ratio summarizes their relative comparison. The confidence intervals around the arm-specific means and the interval for the rate ratio answer related but distinct questions. The rate ratio is the direct comparative statistic to use when interpreting the reported group contrast.
The posted data also include secondary outcomes, including lung function and questionnaire measures. They provide related information about other measured outcomes, but they do not replace the primary exacerbation-rate endpoint. Their interpretation depends on each outcome's scale, analysis model, and the broader issue of multiple testing. The record does not report whether a multiplicity strategy was prespecified, so secondary p-values should not be treated as if they necessarily control the chance of false-positive findings across all outcomes.
Overall, the primary analysis reports a lower adjusted exacerbation rate in the reslizumab group than in the placebo group, with a confidence interval and p-value indicating a statistically clear group difference under the reported analysis. The statistical finding is specific to this trial and does not, by itself, establish the broader clinical meaning of the difference or answer questions not studied in the registry record.
9. Statistical Methods Explained
The primary endpoint is an event rate: the number of clinical asthma exacerbations accrued over a defined period of follow-up. Unlike an endpoint that records only whether an event occurred, an event-rate outcome can reflect repeated events. Participants may contribute different numbers of observed events, and follow-up or event patterns may not behave like a continuous measurement with normally distributed errors.
Why use a negative binomial model?
General: A Poisson model is a familiar starting point for counts, but it assumes that the variability in counts follows a particular relationship to the mean. In many real datasets, counts vary more than that assumption allows. This is called over-dispersion. A negative binomial model allows extra variability and can therefore be more appropriate for event counts when the data are over-dispersed. The registry states that the adjusted CAE rate and confidence intervals were based on a negative binomial regression model adjusted for stratification factors. It does not report the diagnostics or model checks used to assess the fit.
A regression model can account for specified factors when estimating a group comparison. The registry says the primary model adjusted for stratification factors, but does not name them. The adjusted group estimates are therefore the reported results to interpret; the exact adjustment cannot be reconstructed from the record. The registry lists Chi-squared as the method for the reported rate-ratio analysis. It does not give further detail on the test statistic or how that label relates to the regression model used to estimate adjusted rates.
What does the rate ratio communicate?
General: A rate ratio compares the event rate in one group with the event rate in another. A value representing equal rates is the reference point. Values below that reference indicate a lower estimated rate in the numerator group, while values above it indicate a higher estimated rate. The registry's comparison is reslizumab versus placebo. Its point estimate is 0.501, and its 95% confidence interval is 0.373 to 0.674.
A confidence interval conveys uncertainty in an estimate under the statistical model. It is not a guarantee that the true value lies within the interval, nor does it account automatically for every possible source of bias, model misspecification, or selective reporting. The interval's interpretation depends on the analysis assumptions and the quality of the data. The registry reports a 95% confidence interval for the primary rate ratio and for each arm's adjusted mean.
How do the secondary continuous outcomes differ?
Several secondary outcomes are continuous measures, including change from baseline in FEV1, AQLQ, and ACQ. The registry reports least-squares means and standard errors for those outcomes, and specifies mixed models for repeated measures for FEV1 and ACQ. These models are designed for repeated observations on the same participants. General: A repeated-measures model can account for the fact that measurements from one participant over time are related rather than independent. Its estimates may also use information from multiple scheduled measurements, depending on the model and its assumptions.
The registry does not provide the full model specifications, covariance structures, or missing-data assumptions for those analyses. Accordingly, the reported model-based estimates cannot be fully reproduced from the registry record. The posted recalculations for continuous outcomes are simple unadjusted comparisons based on summary statistics; they are not replacements for the registry's repeated-measures analyses. Their confidence intervals and p-values can differ because they use a different approach and make different assumptions.
What do planning illustrations mean?
Planning illustrations translate an assumed effect into approximate participants per arm for 80% power or 90% power under the stated assumptions: two-sided significance level 0.05, equal allocation, and a normal approximation. Rows describe planning for 100%, 75%, or 50% of the observed effect. These are illustrations based on the observed estimate, not the trial's original design calculation and not observed power. If the true effect were smaller than the estimate used for planning, the required sample size would be larger under the same assumptions.
The record does not report the trial's own sample-size justification or the assumptions used when the trial was designed. The planning illustrations should therefore be understood as hypothetical scenarios for future-study planning, not as evidence that the trial was adequately powered for every endpoint. They also do not address recruitment feasibility, loss to follow-up, multiplicity, or features of the original analysis plan that are not reported.
How should unadjusted p-values be read?
General: A p-value measures how incompatible the observed data are with a specified null hypothesis under the test's assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. An unadjusted p-value does not account for the fact that many outcomes or comparisons may be examined. When several tests are performed, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity.
For the secondary outcomes, the registry reports model-based analyses, while the recalculated comparisons are unadjusted and use posted summary statistics. Differences between those results should be read as differences in analysis method, not as evidence that either calculation reproduces the other. The record does not report enough statistical detail to reproduce every model or determine how secondary testing was managed.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Chi-squared | CAE rate ratio (reslizumab vs placebo) 0.5010 | 0.3726 to 0.6737 | < 0.001 |
The primary result is reported as an adjusted negative binomial analysis: arm-specific adjusted means, a rate ratio, a 95% confidence interval, and p < 0.001. No competing recalculated primary estimate is presented in the posted results, so the registry's reported primary analysis is the basis for interpreting the endpoint.
For secondary continuous outcomes, the registry reports model-based analyses, including mixed model repeated measures for FEV1 and ACQ. The simple recalculations use posted arm-level summary statistics and produce unadjusted comparisons. They do not reproduce the repeated-measures model or all of its possible adjustments. As a result, their estimates, confidence intervals, or p-values may differ from the registry's reported analyses.
The difference is particularly visible for AQLQ: the unadjusted recalculation has a confidence interval that includes zero and p = 0.056, while the registry's reported model-based analysis has a 95% confidence interval from 0.048 to 0.428 and p = 0.014. For FEV1 and ACQ, the recalculated and reported estimates are closer, but their intervals and p-values are not identical. The registry does not provide enough model detail to attribute each difference to a specific modeling decision.
These recalculations are useful as transparent checks based on summary data, but they should not be substituted for the registry's own analyses. They are not adjusted versions of the sponsor's analyses, and they do not establish that the model-based results are incorrect. Interpretation should distinguish the registry's prespecified-looking model estimates from exploratory, unadjusted calculations without assuming details of the analysis plan that are not reported.
11. Multiplicity, Missing Data and Analysis Populations
Multiplicity concerns arise when an analysis considers many outcomes, time points, or comparisons. Even when each test uses a conventional significance threshold, a larger collection of tests increases the chance that at least one result will appear notable by chance. General: A prespecified strategy can control or organize that risk, for example by adjusting tests or by testing outcomes in a defined sequence. The appropriate approach depends on the trial's aims and design.
The registry lists 13 outcome measures and 11 analyses and includes several secondary outcomes. It does not report whether the secondary analyses were controlled for multiplicity, whether a hierarchy was planned, or which outcomes were intended to support confirmatory claims. Accordingly, the secondary p-values cannot be interpreted as if a family-wise testing strategy were known. This limitation does not change the reported primary result, but it affects how strongly the secondary findings can be treated as confirmatory.
Missing-data handling is also important, especially for repeated measurements over time. The registry identifies mixed models for repeated measures for FEV1 and ACQ, but does not report the full model specification, missing-data assumptions, or sensitivity analyses. It does not report how missing primary endpoint observations, incomplete follow-up, or other missing outcome information were handled. Differences in the number of participants contributing to different secondary outcomes are recorded, but the reasons for those differences are not reported in the registry record.
The primary outcome is labeled as using the randomized set, but the registry does not provide a fuller definition of that analysis population or state whether all randomized participants contributed to the analysis. It does not report a detailed intention-to-treat definition, per-protocol population, or alternative analysis populations for the primary result. The randomized arm counts for the primary endpoint are reported, but those counts alone do not explain the treatment of participants with incomplete follow-up or missing event data.
These gaps mean that the registry record supports interpretation of the reported estimates, but not a complete audit of the analysis plan or robustness to missing data and multiplicity. The trial protocol and statistical analysis plan are not reported in the registry record, so their details should not be inferred.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Placebo | 34 | 243 | 14.0% |
| Reslizumab 3.0 mg/kg | 24 | 245 | 9.8% |
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 |
|---|---|
| Placebo | 184 of 243 |
| Reslizumab 3.0 mg/kg | 165 of 245 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Reslizumab 3.0 mg/kg |
|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | 13 of 243 | 11 of 245 |
| Chest pain | General disorders | 0 of 243 | 2 of 245 |
| Bronchitis | Infections and infestations | 2 of 243 | 0 of 245 |
| Gastroenteritis | Infections and infestations | 1 of 243 | 1 of 245 |
| Pneumonia | Infections and infestations | 0 of 243 | 2 of 245 |
| Right ventricular failure | Cardiac disorders | 1 of 243 | 0 of 245 |
| Sinus tachycardia | Cardiac disorders | 1 of 243 | 0 of 245 |
| Diaphragmatic hernia | Gastrointestinal disorders | 0 of 243 | 1 of 245 |
| Diarrhoea | Gastrointestinal disorders | 1 of 243 | 0 of 245 |
| Oesophagitis | Gastrointestinal disorders | 0 of 243 | 1 of 245 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Reslizumab 3.0 mg/kg |
|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | 123 of 243 | 92 of 245 |
| Upper respiratory tract infection | Infections and infestations | 32 of 243 | 39 of 245 |
| Nasopharyngitis | Infections and infestations | 33 of 243 | 28 of 245 |
| Sinusitis | Infections and infestations | 28 of 243 | 21 of 245 |
| Headache | Nervous system disorders | 30 of 243 | 19 of 245 |
| Influenza | Infections and infestations | 23 of 243 | 17 of 245 |
| Bronchitis | Infections and infestations | 22 of 243 | 13 of 245 |
| Back pain | Musculoskeletal and connective tissue disorders | 13 of 243 | 13 of 245 |
| Cough | Respiratory, thoracic and mediastinal disorders | 13 of 243 | 11 of 245 |
| Pharyngitis | Infections and infestations | 13 of 243 | 10 of 245 |
Serious events with the highest arm-level rate: asthma (5.3%), bronchitis (0.8%), chest pain (0.8%), pneumonia (0.8%), right ventricular failure (0.4%).
The safety summary reports serious adverse events affecting 34 of 243 participants in the placebo group and 24 of 245 participants in the reslizumab 3.0 mg/kg group. It also reports other adverse events affecting 184 of 243 participants in the placebo group and 165 of 245 participants in the reslizumab group. These are participant counts in the posted safety groups, not estimates of treatment effect or evidence of a statistically tested difference.
The listed serious adverse-event terms include asthma at 5.3%, bronchitis at 0.8%, chest pain at 0.8%, pneumonia at 0.8%, right ventricular failure at 0.4%, and sinus tachycardia at 0.4%. The record does not provide arm-specific counts for these terms in the listed summary, so they should not be assigned to a particular group based on this information. The registry does not report death counts in this record.
Safety counts require careful context: participants may experience more than one event, and a term's frequency does not by itself describe severity, causality, duration, or whether the event was related to treatment. The record does not provide enough detail to assess those aspects for each event. The reported figures describe the safety data posted in the registry, rather than establishing a causal comparison between treatments.
13. What the Result Does, and Does Not, Mean
The primary result means that the registry's adjusted analysis estimated different CAE rates between the randomized groups during Day 1 to Week 52. The reslizumab group's adjusted rate ratio relative to placebo was 0.501, with a 95% confidence interval from 0.373 to 0.674 and p < 0.001. The interval is relatively informative about the range of rate ratios compatible with the model and observed data, but it does not remove uncertainty or answer every clinical question.
It does not mean that every participant in the reslizumab group had fewer exacerbations, or that a particular participant's future course can be predicted from the group average. It does not establish how the result would translate to populations or treatment settings not represented by this trial. The record describes participants 12-75 years of age with eosinophilic asthma, so the estimate is specific to that study population and its eligibility criteria.
The primary endpoint is a defined clinical event count, not a complete measure of asthma status. Lung function, questionnaires, symptoms, medication use, and safety events provide other kinds of information. Those measures can complement the exacerbation result, but a finding on one outcome does not automatically establish a result on another. Secondary analyses also require caution because the registry does not report a multiplicity plan.
Statistical evidence should not be confused with clinical importance. The registry provides estimated rates and uncertainty, but it does not state a threshold for a clinically meaningful rate difference. Nor does the primary p-value measure the probability that the treatment hypothesis is true. It summarizes compatibility with a null comparison under the test's assumptions.
The result also does not establish the reason for the observed difference, the biological mechanism, or the benefit-risk balance for a particular person. The safety summary reports events but does not provide a full causal evaluation. The registry record supports a description of this randomized comparison; conclusions beyond the outcomes, participants, follow-up, and analyses recorded require evidence not contained in this record.
14. Why This Trial Matters Statistically
This trial illustrates why the outcome definition matters as much as the statistical model. The primary endpoint counts clinical asthma exacerbations using specified corticosteroid-treatment or urgent-care criteria, with corroboration of worsening signs and symptoms and committee adjudication. That operational definition determines which events enter the analysis and gives the rate comparison a concrete clinical meaning.
It also shows the distinction between arm-level rates and a comparative effect estimate. Adjusted means describe estimated event rates in each group, while the rate ratio directly compares those rates. Confidence intervals add information about precision that a point estimate or p-value alone cannot provide. Reading all three—the arm estimates, the relative comparison, and its interval—gives a fuller statistical account than relying on a significance label.
The record also demonstrates that secondary analyses need to be read according to their methods. Repeated-measures models and simple unadjusted recalculations do not answer exactly the same statistical question. Their differences are especially important when an analysis depends on observations across time, adjustment, or assumptions about incomplete data. Without full model details, a summary-statistic recalculation is a useful check but not a substitute for the registry's reported model.
Finally, the trial highlights the limits of registry reporting. The record identifies the design, endpoint, adjusted primary analysis, and selected secondary results, but does not report the sample-size justification, full statistical plan, multiplicity strategy, or detailed missing-data handling. A careful statistical reading can describe the posted evidence while keeping those unknowns visible. That distinction helps prevent a well-defined primary comparison from being overextended into claims the record does not establish.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record does not report the sample-size justification or the assumptions used to plan enrollment. The planning illustrations based on observed secondary effects are not the trial's original design calculation, and cannot establish that the study was designed with a particular power for each endpoint.
The primary model is identified as negative binomial regression adjusted for stratification factors, but the factors themselves, model diagnostics, and further model specifications are not reported. The record also lists Chi-squared as the method for the reported rate-ratio analysis without further explanation. This leaves limited detail for independent reproduction of the primary analysis.
Details of event ascertainment beyond the endpoint definition and committee adjudication are not reported. The registry does not give individual event histories, adjudication procedures, or detailed follow-up data. It is therefore not possible to assess from the record alone how incomplete follow-up or missing event information may have affected estimates.
For secondary outcomes, full model specifications and missing-data assumptions are not reported. The recalculations use simple unadjusted comparisons of posted summary statistics, so they cannot reproduce every feature of the registry's repeated-measures analyses. Their differences from the reported analyses should not be interpreted as proof that either result is erroneous.
The record does not report a multiplicity strategy, a complete statistical analysis plan, or a fuller definition of all analysis populations. It also does not provide arm-specific counts for each listed serious adverse-event term, and death counts are not reported in the registry record. These limits constrain interpretation of secondary claims, safety details, and the reproducibility of some analyses.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma — NCT01287039.
- Registry record last updated 2021-11-09; status last verified 2021-11.
- Results first posted 2016-06-27.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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19. Record Summary
NCT01287039 was a completed Phase 3, randomized, quadruple-masked, placebo-controlled, parallel-group study of reslizumab 3.0 mg/kg in participants with eosinophilic asthma. The study enrolled 489 participants and evaluated intravenous dosing once every 4 weeks ( +-7 days) for a total of 13 doses. The primary endpoint was the adjusted frequency of clinical asthma exacerbations from Day 1 to Week 52 in the randomized set.
The registry reports an adjusted rate ratio of 0.501 for reslizumab versus placebo, with a 95% confidence interval from 0.373 to 0.674 and p < 0.001. The primary model was negative binomial regression adjusted for stratification factors. Secondary results cover other clinical, questionnaire, lung-function, and safety measures, but multiplicity handling, detailed missing-data methods, and the original sample-size justification are not reported in the registry record.