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 Study to Evaluate Safety and Immunogenicity of Sub-unit Adjuvanted Influenza Vaccine Administered to Elderly Subjects, Formulation 2011-2012 (NCT01344057), a na phase 2 study. The primary outcome is Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01344057 |
| Phase | Phase 2 |
| Condition | Seasonal Influenza |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 63 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Vaccines |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled elderly participants. The primary endpoint population was the per-protocol analysis set: participants who correctly received the vaccine, provided evaluable serum samples before and after vaccination, and had no major protocol violations. The number in that analysis set is not reported in the registry record.
Intervention
Participants received one intramuscular dose of a trivalent, subunit, inactivated influenza vaccine adjuvanted with MF59C.1. The intervention is identified as seasonal influenza vaccine, with FLUAD named in the primary endpoint description.
Comparator
No comparator was administered. The study had a single group and no like-for-like control group, so the registry record does not support a randomized or controlled comparison.
Primary question
At day 22, what percentage of participants achieved seroconversion or a significant increase in single radial hemolysis area against each of the three vaccine strains, as measured by the SRH assay? The registry record specifies this question but does not report the percentages or confidence intervals.
This question concerns an immune-response measure after vaccination, rather than a comparison of clinical illness between treatment groups. For each strain, the endpoint combines participants meeting either of two stated response definitions: seroconversion or a significant increase in SRH area. The registry record says the European CHMP criterion is met if the percentage achieving either response is 30% for participants aged 65 years or older. That threshold gives context for interpreting the endpoint definition, but the registry record does not report whether the observed percentage reached it.
The study also listed solicited local and systemic reactions as a secondary outcome. Safety information is reported separately from the primary immunogenicity question; it does not establish a comparative safety effect because no comparator group was included.
3. Trial Design
This was a Phase II, open-label, uncontrolled, multicenter study of a seasonal influenza vaccine in elderly participants. The registry record describes a single-group model, no masking, and no comparator. Participants received one intramuscular single dose during the vaccination visit. The study was completed. Its recorded start was 2011-05 and its primary completion was 2011-06.
The registry record lists an enrollment of 63. That figure is not necessarily the denominator for the primary outcome: the endpoint was specified for a per-protocol population requiring correct vaccination, evaluable serum samples before and after vaccination, and no major protocol violations. The size of that analysis population is not reported in the registry record. The reported enrollment should therefore not be substituted for an endpoint-specific denominator.
The primary outcome was assessed at day 22 and expressed as the percentage of participants who achieved seroconversion or a significant increase in SRH area for each of the three vaccine strains. A 95% confidence interval was specified as the measure of dispersion. The registry record describes the endpoint definitions and assay but does not give the observed percentages, confidence intervals, or strain-specific denominators.
Because the design is uncontrolled, the recorded observations describe participants who received the vaccine; they do not estimate a contrast against an untreated or alternative-treatment group. Open-label status means the study was not masked, but the registry record does not give further details about who knew treatment assignment or how that knowledge was managed. The method of participant selection, details of recruitment, and the protocol’s statistical analysis plan are 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: Blood sample for immunogenicity assays were collected before vaccination (Day 1) and after 21 Days.
Overall Study
| Stage | FLUAD |
|---|---|
| STARTED | 63 |
| COMPLETED | 62 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | FLUAD |
|---|---|
| Premature Withdrawal | 1 |
Analysis population for the primary outcome, as defined in the registry: Per protocol (PP) analysis set included all enrolled participants who had correctly received the vaccine, provided evaluable serum samples before and after vaccination, and had no major protocol violations.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Baseline analysis population was defined as all participants who were enrolled into the study.
| Characteristic | Unit | FLUAD |
|---|---|---|
| Participants analysed | 63 | |
| Age, Continuous | Years | 73.2 (SD 5.2) |
| Sex: Female, Male: Female | Participants | 31 |
| Sex: Female, Male: Male | Participants | 32 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD, measured over day 22.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint measures the percentage of participants with a specified SRH response against each of the three vaccine strains at day 22. Seroconversion was defined as a negative pre-vaccination serum result followed by a post-vaccination serum area of at least 25 mm2. A significant increase was defined as at least a 50% increase in area from a positive pre-vaccination serum result. The combined endpoint counts a participant who meets either definition.
SRH is the assay named in the registry record for evaluating this immune response. Reporting a percentage makes the endpoint a binary-response summary: participants either meet the stated response definition for a strain or do not. The accompanying 95% confidence interval is intended to convey uncertainty around the estimated percentage, rather than to describe the range of individual participant measurements.
The endpoint is useful for describing the proportion meeting a prespecified laboratory response definition. The registry record also names a CHMP criterion: the percentage achieving seroconversion or a significant increase should be 30% for participants aged 65 years or older. This criterion supplies a benchmark for interpreting the measure, but it is not itself an observed result. The registry record does not include the percentages, confidence intervals, or an indication of whether the criterion was met.
Results were intended for the per-protocol population, which excluded participants who did not meet the stated receipt, serum-evaluation, and protocol-compliance conditions. The number included in that population is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes what the primary endpoint was intended to measure, but it does not provide the result needed to judge the observed immune response. It names a percentage for each of the three vaccine strains, an assessment at day 22, and a 95% confidence interval. The observed percentages and intervals are not reported in the registry record. Consequently, the primary endpoint cannot be described as high, low, precise, or imprecise from this record.
The CHMP criterion of 30% for participants aged 65 years or older is a stated benchmark, not an outcome. Without the strain-specific observed percentages, there is no basis in the registry record for saying whether any strain met that criterion. The endpoint definitions do allow a reader to understand what would count as a response: either a specified change from a negative baseline result or a specified increase from a positive baseline result. They do not reveal how many participants met either condition.
The 95% confidence interval, if reported, would help convey the precision of an estimated percentage. In general, a confidence interval reflects the uncertainty associated with sampling and the analysis assumptions; it is not a range that contains a fixed proportion of individual outcomes. Since no confidence limits are reported, the statistical precision of the estimates is unknown. The per-protocol denominator is also not reported, which further prevents assessment of how much information contributed to each estimate.
The design limits interpretation in a separate way. This was a single-group, uncontrolled, open-label study. Its observations can describe responses and recorded safety events among vaccinated participants, but they cannot establish how those observations compare with a control group. The study does not provide a controlled estimate of a difference attributable to vaccination. No causal comparison should be inferred from the single-group results.
The registry record lists enrollment of 63 and reports safety counts for the FLUAD group: 0 participants with serious adverse events and 6 with other adverse events, each with 63 at risk. These are descriptive counts. The record does not provide a comparator, and it does not state in the posted outcome information whether the reported events were attributed to vaccination. Deaths are not reported in the registry record. The adverse-event counts do not fill the gap in the missing primary immunogenicity results.
The record lists no analysis entries. It does not report an analysis method for the primary endpoint, any adjustment strategy, or a statistical plan. In particular, no multiplicity procedure is reported for evaluating responses across the three strains. A reader should therefore distinguish the endpoint’s stated definitions from statistical conclusions that would require results and analysis details. The principal conclusion supported by the registry record is about the planned measurement and the design, not the magnitude or precision of the immune response.
9. Statistical Methods Explained
The primary endpoint is a binary-response percentage. For each strain, the endpoint classifies each participant according to whether the participant meets the combined response definition. A participant qualifies by meeting either the seroconversion definition or the significant-increase definition. The percentage is a summary of the share of the relevant analysis population that qualifies. The registry record does not report the actual percentages or the denominators used for the strain-specific estimates.
What does a confidence interval add?
A confidence interval expresses uncertainty around an estimate under the statistical method used. For a percentage, it helps show how much precision the data provide about the underlying response proportion. A narrow interval generally indicates greater precision than a wide interval, while the interval’s position indicates which values are compatible with the data and method. These are general interpretations; the specific interval method used in this study is not reported in the registry record. Although a 95% confidence interval is named as the dispersion measure, neither the limits nor the method for calculating them appears in the record.
Confidence intervals should not be read as a range containing most individual participants’ measurements. The endpoint is based on a classification of each participant, and its interval concerns uncertainty in the group percentage. It also does not by itself establish that an endpoint is clinically important or that a benchmark has been met. For this trial, the registry record gives a CHMP benchmark but no observed percentage or interval with which to assess it.
Why does the analysis population matter?
The primary outcome was specified for the per-protocol analysis set. Membership required correct receipt of the vaccine, evaluable serum samples before and after vaccination, and absence of major protocol violations. This definition means the analysis set may differ from the enrollment count. The registry record does not report its size, the number excluded, or the reasons for any exclusions. It is therefore not possible to determine the endpoint’s actual denominator or evaluate how exclusions affected the estimate.
In general, a per-protocol analysis describes outcomes among participants meeting the protocol conditions used to define that set. It may answer a different question from an analysis that includes everyone enrolled or assigned to a group. Which analysis is appropriate depends on the study question and design. The registry record does not report an alternative population analysis for this endpoint, and the single-group design does not include treatment assignment to compare.
What does the endpoint definition imply?
The combined endpoint joins two routes to qualifying as a response. The first route starts with a negative pre-vaccination serum result and requires a post-vaccination area of at least 25 mm2. The second starts with a positive pre-vaccination result and requires at least a 50% increase in area. This structure accounts for different baseline states within the stated endpoint definition. It also means the combined percentage cannot be reconstructed from a single threshold without knowing each participant’s baseline category and follow-up result.
Each vaccine strain is evaluated separately. In general, multiple strain-specific outcomes can raise a multiplicity question: when several outcomes are assessed, the chance of at least one apparently noteworthy result may differ from the chance associated with a single prespecified test. The registry record does not report whether formal hypothesis tests were used or whether any multiplicity adjustment was planned. It is not appropriate to assume either that adjustment occurred or that it was unnecessary.
What can the study design estimate?
An uncontrolled single-group study can summarize outcomes observed after the intervention in that group. It does not directly estimate a difference between the intervention and a comparator. General statistical reasoning distinguishes a within-group response percentage from a treatment contrast: the former describes the observed group, while the latter requires a comparison and an analysis that accounts for the study design. There was no comparator in this study.
Open-label status indicates that the study was not masked. In general, lack of masking can affect how subjective events are reported or assessed, depending on the outcome and procedures. The primary outcome uses an SRH assay, but the registry record does not report the assay procedures, laboratory masking, or quality-control details. It also does not report how solicited reactions were elicited or assessed. These missing details limit appraisal of measurement procedures; they do not establish that measurement bias occurred.
What analysis details are absent?
The registry record does not report the statistical method used to calculate the endpoint percentage or its confidence interval. It does not report a statistical analysis plan, hypothesis tests, adjustment methods, interim analyses, or a sample-size justification. The record lists no analysis entries. General methods for binary outcomes can differ in how they calculate interval limits and handle sparse data, so the method matters when interpreting precision. No particular method can be attributed to this study from the available record.
The record’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not match the described single-group, uncontrolled design. No sample-size illustration or observed-power conclusion can be interpreted as a study result. The record does not report that these assumptions formed part of the trial’s original design or statistical plan.
In general, over-dispersion is a concern when variability in observed outcomes exceeds what a chosen model assumes. It can make standard errors too small if the model fails to allow for the extra variability. The registry record does not specify a model for this endpoint or report evidence of over-dispersion, so that issue cannot be evaluated for this study. More broadly, the absence of reported analysis details means the reader can describe the intended outcome and design, but cannot independently reproduce or verify the statistical analysis.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint covers responses against each of the three vaccine strains. Evaluating multiple strain-specific outcomes raises a general multiplicity consideration: the interpretation of several estimates or tests can differ from that of a single outcome, particularly when selecting or emphasizing results after seeing the data. The registry record does not report a multiplicity adjustment, a hierarchy among the strain outcomes, or whether formal hypothesis tests were conducted. No adjustment strategy should be assumed.
The primary outcome was defined for the per-protocol population. That population required correct vaccine receipt, evaluable serum samples before and after vaccination, and no major protocol violations. The number meeting those conditions is not reported in the registry record. The record also does not state how missing serum results, withdrawals, or other missing endpoint data were handled, or whether any participants were excluded from a particular strain analysis. These details matter because the denominator determines the meaning of a reported percentage and because missingness can affect interpretation.
The enrollment count is 63, but it should not be treated as the denominator for the primary outcome without confirmation that every enrolled participant met the per-protocol criteria and had evaluable data. Such confirmation is not reported. The registry record does not provide an intention-to-treat analysis or another analysis population for comparison with the per-protocol set.
More generally, a missing-data method should be judged in relation to the outcome and reasons data are absent. The record does not report imputation, sensitivity analyses, or assumptions about missing outcomes. It also does not report a statistical analysis plan, interim analyses, or the sample-size justification. These omissions limit assessment of the planned analysis and robustness; they do not establish that any particular handling method was used.
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 |
|---|---|---|---|
| FLUAD | 0 | 63 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| FLUAD | 6 of 63 |
Most frequent non-serious adverse event terms
| Event term | Organ system | FLUAD |
|---|---|---|
| Injection site erythema | General disorders | 3 of 63 |
| Injection site haemorrhage | General disorders | 2 of 63 |
| Injection site induration | General disorders | 2 of 63 |
| Injection site pain | General disorders | 2 of 63 |
| Injection site swelling | General disorders | 2 of 63 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 2 of 63 |
| Myalgia | Musculoskeletal and connective tissue disorders | 2 of 63 |
| Mastoiditis | Infections and infestations | 1 of 63 |
The registry record lists the FLUAD group with 63 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 63 at risk and 6 affected. These are counts recorded for the study group, not a comparison with another treatment or control group. The record does not report deaths.
A count of 0 serious adverse events means that the registry record reports no affected participants in that category for this group. It should be read as an observed study count, not as proof that a serious event is impossible or that no risk exists outside the observed participants and follow-up. The registry record does not provide the event definitions, event-specific details, follow-up completeness, or a comparator that would support a relative safety estimate.
The record lists no serious adverse event terms. It does not state in the safety figures whether other events were judged related to the vaccine. Therefore, the count of 6 should be read as a recorded count of participants with other adverse events, without inferring causality. These safety summaries are distinct from the solicited local and systemic reactions listed as a secondary outcome; detailed results for that outcome are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record describes a study designed to measure immunogenicity after one dose of an adjuvanted influenza vaccine in elderly participants. It defines a response using the SRH assay, specifies assessment at day 22, and names a 95% confidence interval. Those details make the intended endpoint understandable, but the observed percentages and intervals are not reported. The record therefore does not establish the size or precision of the measured response, or whether the stated CHMP criterion was met.
The record also supports a limited description of safety observations: it lists 0 participants with serious adverse events and 6 with other adverse events among 63 at risk in the FLUAD group. Those counts are not comparative estimates. The record does not report deaths, and does not establish whether the other adverse events were attributed to vaccination. A registry count alone cannot be used to compare risks with another intervention when no comparator group is present.
The design was open-label and uncontrolled, with a single group and no comparator. In general, an uncontrolled study can describe what was observed among participants receiving the intervention, but it cannot separate intervention effects from other influences through a concurrent group comparison. It therefore does not answer how outcomes would differ under another treatment or no treatment. No causal effect estimate is reported.
The endpoint population was per protocol, and its membership count is not reported. The enrollment count of 63 does not establish how many participants contributed evaluable samples to each strain-specific outcome. The record does not report missing-data handling, a statistical analysis plan, or the method used to calculate confidence intervals. These limitations make it impossible to assess independently the precision, completeness, or robustness of the primary outcome analysis.
The appropriate interpretation is consequently narrow: the registry record specifies the intended immune-response measure and gives limited group-level adverse-event counts, but it does not report the primary outcome results needed to characterize immunogenicity. It should not be read as evidence that a clinical illness outcome changed, nor as a controlled estimate of benefit or harm.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between an outcome definition and an outcome result. The registry record describes in detail how the primary immune-response endpoint was classified, including separate baseline-dependent definitions for seroconversion and significant increase. It also specifies the assessment time, the per-protocol population, and a confidence-interval level. Yet the actual strain-specific percentages and intervals are not reported. A well-defined endpoint does not, by itself, show what the study observed.
The design also illustrates why a single-group study answers a narrower statistical question than a controlled comparison. The study can describe the proportion meeting a response definition among eligible participants, but it cannot estimate a difference against an unexposed or alternative-treatment group. That distinction matters when interpreting any recorded post-vaccination outcome: description of a group is not the same as estimation of a comparative effect.
The case also highlights the role of analysis-population reporting. Although enrollment is listed, the primary endpoint uses a per-protocol set with eligibility conditions tied to vaccination, evaluable samples, and protocol compliance. Without the size of that set and strain-specific denominators, readers cannot judge how many observations underlie the percentages or how exclusions may have shaped them.
Finally, the record names three strain-specific outcomes and a benchmark, while leaving the analysis method and multiplicity approach unreported. That combination underscores the importance of reporting estimates, uncertainty, analysis populations, and methods together. Without them, readers can understand the intended statistical question but cannot assess the magnitude, precision, or robustness of its answer.
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 most consequential limitation of the registry record is that it does not report the primary endpoint results. The outcome is defined for each of the three vaccine strains at day 22, but no observed percentages or 95% confidence intervals are given. It is therefore not possible to assess the response magnitude, its precision, or whether the stated CHMP criterion was reached.
The trial was a single-group, uncontrolled study with no comparator. Its design does not support a direct treatment contrast, and the open-label status means masking was absent. The record does not provide details about laboratory masking or procedures for assessing the listed solicited reactions. These are limits on what can be assessed from the record; they are not evidence that bias necessarily occurred.
The endpoint was specified for a per-protocol population, but the size of that population and the endpoint-specific denominators are not reported. Handling of missing serum results, exclusions, and incomplete outcome data is also not reported. Enrollment of 63 cannot be assumed to equal the number analyzed.
The record does not report the statistical method for the percentage or confidence interval, the statistical analysis plan, a multiplicity procedure, or a sample-size justification. It also does not give detailed results for the secondary outcome of solicited local and systemic reactions. Safety reporting is limited to the listed counts; deaths are not reported, and attribution of other adverse events is not stated. These omissions constrain statistical and clinical interpretation of the study record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate Safety and Immunogenicity of Sub-unit Adjuvanted Influenza Vaccine Administered to Elderly Subjects, Formulation 2011-2012 — NCT01344057.
- Registry record last updated 2023-04-28; status last verified 2023-04.
- Results first posted 2016-01-28.
- 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 record describes a completed Phase II, open-label, uncontrolled, multicenter study of a subunit, inactivated influenza vaccine adjuvanted with MF59C.1 in elderly participants. Enrollment was 63. The intervention was one intramuscular single dose, and no comparator was administered.
The primary endpoint was the percentage achieving seroconversion or a significant increase in SRH area against each of the three vaccine strains at day 22. The specified population was per protocol, and a 95% confidence interval was named. The observed percentages, confidence intervals, and per-protocol population size are not reported in the registry record.
The safety record lists 0 participants with serious adverse events and 6 with other adverse events among 63 at risk in the FLUAD group. Deaths are not reported. Analysis methods, multiplicity handling, and missing-data methods are not reported in the registry record.