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 Assess the Immunogenicity and Safety of CSL's 2013/2014 Formulation of Enzira® Vaccine in Healthy Volunteers (NCT01857297), a non-randomized phase 4 study. The primary outcome is The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01857297 |
| Phase | Phase 4 |
| Condition | Influenza, Human |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 120 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Seqirus |
| Results posted | Yes |
2. Clinical Question
Population
Healthy volunteers aged 18 years or older, divided into an Adults group aged 18 to 59 years and an Older Adults group aged 60 years or older. The registry record lists enrollment as 120. The primary endpoint applies to an evaluable population: vaccinated participants with both pre- and post-vaccination antibody titre results, no prohibited medication use, and no exclusion under the stated elimination criteria.
Intervention
Enzira® vaccine, the 2013/2014 formulation. The arm descriptions identify the vaccine as a sterile, thiomersal-free suspension containing 45 mcg total haemagglutinin antigen per 0.5 mL dose, with 15 mcg for each of the three recommended influenza strains for the Northern Hemisphere 2013/2014 influenza season.
Comparator
There is no untreated, placebo, or alternative-vaccine comparator group in the registry record. Both age groups received the study vaccine. The study is listed as non-randomized, open-label, and parallel; the age groups therefore should not be treated as randomized, like-for-like control arms.
Primary question
Approximately 21 days after vaccination, what percentage of evaluable participants achieved seroconversion or a significant increase in antibody titre? The registry defines these responses using haemagglutination inhibition criteria for H1N1, H3N2, and B influenza virus strains. Numerical results for this primary endpoint are not reported in the registry record.
3. Trial Design
This is a Phase IV, single-centre, open-label, non-randomized, parallel-group study of the 2013/2014 formulation of Enzira® vaccine. Its stated purpose is to assess antibody response and safety in healthy volunteers. The registry divides participants into Adults aged 18 to 59 years and Older Adults aged 60 years or older. The listed enrollment is 120, and the registry status is completed.
The intervention is the same vaccine in both groups. The arm descriptions specify a sterile, thiomersal-free suspension with 45 mcg total haemagglutinin antigen per 0.5 mL dose, including 15 mcg for each of three recommended influenza strains for the Northern Hemisphere 2013/2014 season. The registry lists the study start as 2013-05 and primary completion as 2013-06. The primary endpoint timeframe is approximately 21 days after vaccination.
Because there is no separate comparator group and allocation was non-randomized, the two age groups do not provide a randomized treatment contrast. They are age-defined groups receiving the same intervention. Differences between their results, if reported, could not by themselves be attributed to age or to a treatment effect without accounting for other explanations; the registry record does not provide such an analysis.
The record names frequency of any solicited adverse events and frequency of any unsolicited adverse events as secondary outcomes. It lists five outcome measures but no registered analyses. Further detail on the statistical plan, recruitment procedures, allocation process, and 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: None relevant
Overall Study
| Stage | Adults (18 to 59 Years) | Older Adults (60 Years or Older) |
|---|---|---|
| STARTED | 60 | 60 |
| COMPLETED | 60 | 60 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The Evaluable Population included all participants who were vaccinated with the Influenza Vaccine, provided both pre- and post-vaccination antibody titer results, did not use a prohibited medication as per the protocol, and were not excluded from the analysis according to the elimination criteria.
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 | Adults (18 to 59 Years) | Older Adults (60 Years or Older) | Total |
|---|---|---|---|---|
| Participants analysed | 60 | 60 | 120 | |
| Age, Customized: Years | years | 34.5 (SD 11.17) | 69.4 (SD 6.02) | 51.9 (SD 19.65) |
| Sex: Female, Male: Female | Participants | 40 | 30 | 70 |
| Sex: Female, Male: Male | Participants | 20 | 30 | 50 |
6. Primary Endpoint
The registry lists the primary outcome as The Percentage of Evaluable Participants Achieving Seroconversion or Significant Increase in Antibody Titre., measured over Approximately 21 days after vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of evaluable participants who achieve seroconversion or a significant increase in antibody titre. It assesses an immune response after vaccination, rather than a clinical influenza outcome. The specified timeframe is approximately 21 days after vaccination, and the endpoint uses haemagglutination inhibition (HI) antibody titres for H1N1, H3N2, and B influenza virus strains.
The registry defines seroconversion for a participant whose pre-vaccination HI titre is below 10 as reaching a post-vaccination titre of at least 40. For a participant whose pre-vaccination titre is at least 10, a significant increase is defined as a four-fold or greater increase in titre. These rules distinguish a response from a low starting titre from a substantial rise when the starting titre is already higher.
In general, an endpoint based on a prespecified antibody-response rule gives a consistent way to classify immune responses across participants. The percentage describes how common the defined response was in the analyzed population; it does not, by itself, describe protection from illness or establish a causal treatment effect. The registry record gives a 95% confidence interval as the endpoint's dispersion measure, but numerical endpoint estimates and interval limits are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the question and response definitions, but it does not report numerical results for the primary immunogenicity endpoint. Consequently, the percentage achieving seroconversion or a significant increase, the corresponding 95% confidence interval, and any group-specific primary endpoint estimates are not reported in the registry record. The outcome cannot be characterized as high, low, precise, or different between age groups from the available record.
The absence of a reported estimate is not evidence that no antibody responses occurred. It means the registry record does not provide the numerical result needed to describe their frequency or uncertainty. Similarly, the existence of a defined response criterion does not establish how many participants met it. The analysis population is defined, but results for that population are not reported.
The design also limits what a comparison between age groups could establish. Both groups received Enzira® vaccine, and the record specifies non-randomized allocation with no masking. The groups are defined by age, not by assignment to vaccine versus a control. Even if group-specific values were available, an unadjusted difference would be descriptive and could reflect differences between groups other than age. There is no randomized comparator in the record from which to estimate the vaccine's effect relative to no vaccination or another intervention.
The safety information records no serious adverse events among the 60 participants at risk in each age group. For other adverse events, the record lists 40 affected participants among 60 at risk in the Adults group and 16 affected participants among 60 at risk in the Older Adults group. These are descriptive counts, not evidence of a causal difference between groups. The registry does not provide event-level descriptions for serious events, and death counts are not reported in the registry record.
In general, estimates are easier to interpret when outcome definitions, analysis populations, missing-data rules, and uncertainty measures are reported together. Here, the primary response definition and evaluable-population criteria are available, but numerical primary results and registered analyses are not. The record therefore supports a description of the study framework and the listed safety counts, not a conclusion about the magnitude or precision of the immune response.
9. Statistical Methods Explained
What does a percentage endpoint represent?
The primary outcome is a binary classification at the participant level: a participant either meets the specified antibody-response criterion or does not. The reported endpoint would express the number meeting the criterion as a percentage of the evaluable population. In general, this is a direct way to describe the frequency of a defined response. It does not retain the full detail of each titre value, because participants are classified according to the stated thresholds and fold-change rule.
The classification combines two cases. For a pre-vaccination HI titre below 10, seroconversion requires a post-vaccination titre of at least 40. For a pre-vaccination titre of at least 10, the criterion is a four-fold or greater rise. This distinction takes the starting titre into account when defining response. The registry attributes the criteria to the CPMP/BWP/214/96 Note for Guidance on Harmonisation of Requirements for Influenza Vaccines.
What does a confidence interval communicate?
The registry specifies a 95% confidence interval as the dispersion measure for the primary endpoint. In general, a confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the estimate itself describes the observed response frequency in the analyzed population. An interval does not account for every possible source of bias, such as selection into an analysis population or the absence of a suitable control group.
No interval limits or primary endpoint estimates are reported in the registry record. It is therefore not possible to assess the precision of the immune-response estimate or compare its uncertainty between age groups. The stated confidence level alone is not a result.
Why does the analysis population matter?
The endpoint is defined for the evaluable population, not automatically for every participant enrolled. The record describes this population as participants who were vaccinated, had both pre- and post-vaccination antibody titre results, did not use a prohibited medication under the protocol, and were not excluded according to the elimination criteria. In general, restricting an analysis to participants with the required measurements can make the endpoint calculable, but the resulting estimate applies to that defined population.
The number of participants meeting the evaluable-population definition, the reasons for exclusions, and the handling of missing titre results are not reported in the registry record. Without those details and the numerical endpoint results, readers cannot determine how the evaluable group relates to enrollment or assess the potential effect of missing measurements.
How should the two age groups be compared?
The study is listed as parallel, non-randomized, and open-label. Both age groups received the same vaccine, and the record identifies no control group. In general, randomization helps make treatment groups comparable on average, whereas a non-randomized age-group comparison may be affected by differences between the groups. The age categories themselves are not a randomized intervention.
Accordingly, a numerical contrast between the age groups, if reported, would describe the observed groups and would not isolate a causal effect of age or vaccination. The registry record lists no analyses, and it does not report adjusted comparisons or a statistical model. The analysis plan beyond the endpoint definition and confidence-interval measure is not reported in the registry record.
What does the sample-size illustration mean?
The record describes sample-size calculations as planning illustrations based on the observed effect, rather than as the study's original design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such calculations ask how many participants per arm might be needed under those assumptions to detect a specified effect with a chosen power.
These illustrations are not observed power, do not alter the reported study results, and do not show that the trial was designed around the effect used in the calculation. The record does not report the trial's sample-size justification, and numerical sample-size illustration results are not included in the registry record.
Why does over-dispersion matter?
In general, over-dispersion refers to greater variability in data than a statistical model expects. It can affect standard errors and confidence intervals when a model assumes less variability than is present. The primary endpoint is a participant-level percentage, and the registry record does not report a model or identify an over-dispersion adjustment. No claim about whether such an adjustment was used can be made from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and identifies the percentage achieving seroconversion or a significant increase in antibody titre as the primary endpoint. It also names the frequency of any solicited adverse events and the frequency of any unsolicited adverse events among the secondary outcomes. The record does not provide numerical primary endpoint results or results for those secondary outcomes as a complete set.
When a study evaluates several outcomes or makes several comparisons, multiplicity can matter because repeated statistical tests may increase the chance of at least one apparently unusual result. In general, a prespecified approach to multiplicity helps readers understand which conclusions are confirmatory and how uncertainty is handled across analyses. The registry record does not report a multiplicity adjustment, a hierarchy of tests, or other details of a statistical analysis plan. It lists no registered analyses.
The primary endpoint applies to the evaluable population, which requires vaccination, pre- and post-vaccination titre results, no prohibited medication use, and no exclusion under the elimination criteria. This definition makes clear that the endpoint does not necessarily include every enrolled participant. However, the counts excluded at each step, missing-data methods, and sensitivity analyses are not reported in the registry record. It is therefore not possible to assess how missing titre measurements or other exclusions affected the primary estimate.
The registry's description of eligibility for the evaluable population is not a complete account of how missing outcomes were handled. In general, excluding participants without required measurements can affect the interpretation of an estimate if those participants differ systematically from those with complete data. Whether that concern applies in this study cannot be determined from the record.
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 |
|---|---|---|---|
| Adults (18 to 59 Years) | 0 | 60 | 0.0% |
| Older Adults (60 Years or Older) | 0 | 60 | 0.0% |
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 |
|---|---|
| Adults (18 to 59 Years) | 40 of 60 |
| Older Adults (60 Years or Older) | 16 of 60 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Adults (18 to 59 Years) | Older Adults (60 Years or Older) |
|---|---|---|---|
| Injection site pain | General disorders | 35 of 60 | 8 of 60 |
| Headache | Nervous system disorders | 15 of 60 | 6 of 60 |
| Malaise | General disorders | 14 of 60 | 4 of 60 |
| Chills | General disorders | 6 of 60 | 4 of 60 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 6 of 60 | 1 of 60 |
| Pyrexia | General disorders | 4 of 60 | 0 of 60 |
The registry's serious-adverse-event figures list 0 affected participants among 60 at risk in the Adults group and 0 among 60 at risk in the Older Adults group. The record lists no serious adverse-event terms. These counts describe what the registry reports; they do not establish that serious events are impossible or that the vaccine has no serious risks. The death counts are not reported in the registry record.
For other adverse events, the registry lists 40 affected participants among 60 at risk in the Adults group and 16 among 60 at risk in the Older Adults group. The record names frequency of any solicited adverse events and frequency of any unsolicited adverse events as secondary outcomes, but the listed counts do not separate events by type in the information. They should not be interpreted as a comparison of causal risk: the study is non-randomized, has no control group, and the groups differ by age.
In general, adverse-event counts depend on the event definitions, observation period, and completeness of reporting. The record does not provide enough detail to reconstruct event timing, severity beyond the serious/non-serious distinction, or participant-level patterns. The counts should therefore be read as descriptive safety information in the registry record, not as a comparative estimate against an untreated or alternative-treatment group.
12. What the Result Does, and Does Not, Mean
The study record establishes that the investigation assessed antibody response and safety after the 2013/2014 Enzira® vaccine formulation in healthy adults in two age-defined groups. It specifies a primary immune-response measure, the HI titre criteria used to classify response, an approximate assessment timeframe, and the characteristics of the evaluable population. It also reports descriptive adverse-event counts for the two groups.
It does not report the numerical primary endpoint results. The percentage of evaluable participants who met the response definition and its 95% confidence interval are not reported in the registry record. Therefore, the record does not show the magnitude or precision of the antibody response, nor does it allow a comparison of that response across the age groups.
The listed safety figures are limited to counts among participants at risk. They are not a controlled comparison, and they do not establish whether events were caused by vaccination. The non-randomized, open-label design and lack of a separate control group also limit causal interpretation. The age groups should not be treated as randomized arms, and any observed differences would be descriptive rather than a clean estimate of an age effect.
In general, an antibody-response endpoint is not the same as a clinical outcome such as illness. The defined response can describe an immune measure, but the registry record does not report whether participants developed influenza or whether vaccination changed clinical outcomes. It also does not provide enough statistical detail to assess missing data, multiplicity, or adjusted analyses. The appropriate reading is therefore narrow: the record describes the study design and endpoint rules, but does not report the primary numerical result needed to characterize the measured immune response.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between an endpoint definition and an endpoint result. The registry specifies a measurable immune-response outcome, the threshold rules used to classify participants, and the population to which the endpoint applies. Those details make clear what a future numerical estimate would represent. However, without the estimate and its confidence interval, readers cannot assess either the observed response frequency or its precision.
The record also illustrates why study design affects interpretation. Both age groups received the vaccine, and the comparison is non-randomized. Thus, the age groups do not supply the kind of randomized control contrast that can separate intervention effects from other group differences. A statistical comparison, even if available, would need to be understood in light of this design rather than read as a causal result.
For safety, the registry reports counts of affected participants but does not provide a comparator group. Descriptive counts can communicate what was recorded among participants at risk, yet they cannot establish comparative risk on their own. The absence of serious events in the reported counts also needs to be interpreted as a feature of the observed record, not as proof that serious events cannot occur.
Finally, the distinction between enrollment and the evaluable population matters for percentage outcomes. The endpoint is restricted to participants with specified measurements and eligibility characteristics, while the number excluded and the handling of missing data are not reported. This limits assessment of how representative the analyzed population may be. Together, these features show why statistical interpretation depends not only on outcome definitions, but also on available estimates, uncertainty, analysis populations, and design.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation of the registry record for interpreting immunogenicity is that it does not report numerical results for the primary endpoint. No response percentage or confidence-interval limits are reported. The stated endpoint criteria therefore cannot be used to judge the observed magnitude or precision of the response.
The design is non-randomized, open-label, and lacks a separate comparator group. Both groups received the same vaccine and are distinguished by age. This limits causal interpretation and means the groups are not a like-for-like control comparison. The single-centre setting is also part of the study design described in the record.
The endpoint is restricted to an evaluable population, but the record does not report how many participants met that definition, how many were excluded, or why exclusions occurred. It does not describe missing-data handling or sensitivity analyses. The record also lists no registered analyses, and the statistical analysis plan, multiplicity approach, and adjusted comparisons are not reported.
Safety information is limited to the listed counts. Serious-event terms are not listed, and death counts are not reported in the registry record. The available information does not describe event timing or provide detailed breakdowns for the solicited and unsolicited adverse-event outcomes. These limitations constrain both the interpretation of safety and comparisons between the age groups.
Further details on recruitment, protocol implementation, and the study's sample-size justification are not reported in the registry record. The record's planning illustration is not a substitute for that justification or for the missing primary endpoint results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Immunogenicity and Safety of CSL's 2013/2014 Formulation of Enzira® Vaccine in Healthy Volunteers — NCT01857297.
- Registry record last updated 2018-06-27; status last verified 2018-04.
- Results first posted 2014-01-15.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry describes a completed Phase IV, single-centre, open-label, non-randomized study of the 2013/2014 Enzira® vaccine formulation in healthy adults. Participants were classified as Adults aged 18 to 59 years or Older Adults aged 60 years or older; the listed enrollment is 120.
The primary endpoint is the percentage of evaluable participants achieving seroconversion or a significant increase in HI antibody titre approximately 21 days after vaccination. The record defines the response criteria and specifies a 95% confidence interval, but numerical primary results are not reported in the registry record. The listed safety counts include no serious adverse events among 60 at risk in either group; other adverse-event counts are also recorded. Because there is no randomized comparator, the age groups do not provide a controlled treatment comparison.