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 Safety and Immunogenicity of One Dose of Seasonal Trivalent Influenza Virus Vaccine (TIVf, Purified Surface Antigen, Inactivated, Egg Derived) in Adults, Aged 18 Years and Above (NCT01885117), a non-randomized phase 3 study. The primary outcome is Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVf.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01885117 |
| Phase | Phase 3 |
| Condition | Human Influenza |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 125 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Vaccines |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy adults aged 18 years and above, with separate age cohorts of 18 to ≤60 years and ≥61 years. The primary immunogenicity analysis was specified for a per-protocol population: participants who received vaccination and had immunogenicity data at baseline and after vaccination, subject to the listed consent and influenza-related conditions. The registry record's description of those conditions ends mid-word, so its complete population definition is not reported in the registry record.
Intervention
Participants received one dose of TIVf, a trivalent, surface-antigen, inactivated subunit influenza vaccine. The formulation was based on the 2013/2014 Northern Hemisphere composition. The official study title identifies the vaccine as Fluvirin®. The study was designed to assess safety and immunogenicity, including antibody response against each of the three vaccine strains.
Comparator
There was no separate control group. This was a non-randomized, single-group study, with results reported for the two age cohorts that received the vaccine. The cohorts are not a like-for-like treatment comparison: age defines group membership, and the study does not describe random assignment between them. Consequently, the design does not estimate a vaccine-versus-control effect.
Primary question
The primary question was what percentage of participants in each age cohort had a Single Radial Hemolysis area of ≥25mm2 against each vaccine strain at baseline and Day 22 after vaccination. The registry also describes the related European CHMP immunogenicity criterion: postvaccination percentages above >70% for adults aged 18 to ≤60 years and >60% for participants aged ≥61 years. The registry record does not report the resulting percentages or confidence intervals.
3. Trial Design
This was a Phase III, open-label, non-randomized, single-group, multicenter study of a trivalent, surface-antigen, inactivated subunit influenza vaccine. The registry lists an enrollment of 125 and a completed status. The study began in 2013-08, with primary completion in 2013-09. Novartis Vaccines is listed as sponsor.
Adults aged 18 years and above were assigned to age cohorts, not randomized treatment arms. One cohort comprised adults aged 18 to ≤60 years, and the other comprised adults aged ≥61 years. Both cohorts received one dose of TIVf, formulated for the 2013/2014 Northern Hemisphere season. The study summary states that its purpose was to confirm safety and immunogenicity in the two cohorts and assess antibody response to each vaccine antigen around 21 days after immunization.
The primary endpoint description uses Day 1 as baseline and Day 22 as the postvaccination assessment. The per-protocol population was described as participants who received vaccination and contributed immunogenicity data at both time points, with additional conditions concerning consent and RT-PCR-confirmed influenza. The final part of that population description is truncated in the registry record, so the complete criteria are not reported in the registry record.
Because all participants received TIVf and there was no randomized control group, differences between the age cohorts cannot be interpreted as treatment effects. Cohort results can describe the recorded outcomes for each age group, but this design does not isolate the effect of vaccination from other influences or establish what outcomes would have occurred without vaccination. Details of allocation procedures beyond the non-randomized, single-group classification 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.
Overall Study
| Stage | TIVf (18 to ≤ 60 Years) | TIVf (≥ 61 Years) |
|---|---|---|
| STARTED | 61 | 64 |
| COMPLETED | 61 | 64 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Analysis was done on the per-protocol population i.e all subjects who have received study vaccination and provided immunogenicity data both at baseline and after vaccination; did not withdraw informed consent and did not have Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) confirmed influenza during the study.
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 | TIVf (18 to ≤ 60 Years) | TIVf (≥ 61 Years) | Total |
|---|---|---|---|---|
| Participants analysed | 61 | 64 | 125 | |
| Age, Continuous | years | 39.2 (SD 11.2) | 68.2 (SD 4.7) | 54.1 (SD 16.9) |
| Sex: Female, Male: Female | Participants | 29 | 34 | 63 |
| Sex: Female, Male: Male | Participants | 32 | 30 | 62 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Subjects With Single Radial Hemolysis (SRH) Areas ≥25mm2, Against Each of Three Vaccine Strains After Receiving One Dose of TIVf, measured over Day 1 (baseline) and Day 22 (postvaccination).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentages of subjects |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of participants whose Single Radial Hemolysis (SRH) area was ≥25mm2 against each of the three vaccine strains. It is assessed at Day 1, before vaccination, and Day 22, after vaccination. The study summary describes the postvaccination assessment as approximately 21 days after immunization, or three weeks after vaccination.
This endpoint is an antibody-response measure. SRH is one of the named laboratory methods used to assess response to influenza vaccine antigens; the registry summary also mentions Hemagglutination Inhibition (HI) as a method for measuring antibody response. The primary outcome specifically describes percentages meeting the SRH area threshold. The registry record does not report how use of SRH versus HI was determined, or any resulting percentages for the strains or age cohorts.
A threshold-based percentage makes the outcome interpretable as the share of the analyzed cohort reaching a stated laboratory response level. It does not show the full distribution of antibody measurements, and it does not by itself establish clinical protection. The registry describes a related European CHMP criterion, with postvaccination percentages above >70% for adults aged 18 to ≤60 years and >60% for participants aged ≥61 years. These are criteria described in the record, not reported outcomes. Whether the observed response met them is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the intended primary immunogenicity measure but does not include its numerical results. It gives no postvaccination percentages for the age cohorts or individual vaccine strains, and no confidence interval values. It therefore does not allow a reader to judge the magnitude or precision of the reported primary endpoint from the registry record alone. The description of a confidence interval as the measure of dispersion does not supply the interval itself.
The study's primary outcome is defined as the percentage of participants with SRH areas ≥25mm2 against each strain. The record also states age-specific CHMP thresholds: above >70% for adults aged 18 to ≤60 years and above >60% for participants aged ≥61 years. These thresholds are interpretive criteria, not evidence that either cohort reached them. Without the outcome estimates, there is no basis in the registry record to state whether a criterion was met, how far the observed estimate lay from it, or how uncertain that estimate was.
The available safety entries report zero participants affected by serious adverse events in each age cohort, and report 41 and 24 participants affected by other adverse events in the respective cohorts. The record does not include the specific terms for serious events, and its death entries are not reported. The meaning and level of detail for the category labelled other adverse events are not explained in the available record. These counts should be read as registry-reported safety entries, not as a complete account of event timing, severity, or causal attribution.
Since the study had no separate control group, the safety and immunogenicity records are descriptive. They do not estimate how these outcomes compare with no vaccination or with another vaccine. Nor can differences between the age cohorts be attributed solely to age or vaccination: the study was not randomized and does not report a comparative analysis. The trial's stated purpose and endpoint definitions describe what it set out to assess, but they are not substitutes for its missing outcome estimates.
Enrollment is listed as 125, while the safety entries use cohort-specific at-risk denominators of 61 and 64. Those entries give a useful description of the recorded safety populations, but the registry record does not explain how the safety denominators relate to enrollment or to the per-protocol immunogenicity population. The endpoint population is defined separately and the complete eligibility or exclusion text is truncated. Interpretation should therefore keep the endpoint population, safety population, and enrollment figure distinct.
Overall, the posted registry information supports a description of the design, endpoint definition, and selected safety counts. It does not support a quantitative conclusion about the primary antibody-response findings, because the results and their confidence intervals are not reported in the registry record. It also does not support causal comparisons or claims about clinical outcomes.
9. Statistical Methods Explained
The primary endpoint is a percentage: the share of the analyzed population meeting the SRH area threshold for each vaccine strain. For a percentage, a confidence interval describes uncertainty around an estimated proportion. In general, an interval is informative about precision: a narrower interval indicates greater precision under the assumptions of the method, while a wider interval indicates greater uncertainty. The registry identifies 95% confidence intervals as the dispersion measure, but does not report the endpoint estimates or the intervals themselves.
What does the threshold capture?
Each participant is classified according to whether the recorded SRH area reaches ≥25mm2 for a given strain. The primary outcome then summarizes the share meeting that threshold in each age cohort. This turns laboratory response measurements into an interpretable percentage, but it does not preserve all information in the original measurements. Participants just below and well below the threshold fall into the same category, as do participants just above and well above it. The registry record does not report continuous SRH values or distributions, so those features cannot be assessed.
The record describes antibody response assessment by SRH or HI, while the primary endpoint specifically names SRH areas. It does not explain which assay was used for each antigen, whether both methods were used, or how assay selection was handled in the analysis. Those operational details are not reported in the registry record. The endpoint timing is described as Day 1 and Day 22, with the summary also referring to approximately 21 days after immunization.
How should the confidence interval be understood?
In general, a confidence interval is a range of values compatible with the observed data under a statistical procedure and its assumptions. It is not a range containing a fixed proportion of individual participants, and it does not remove uncertainty about selection, measurement, or study design. Here, a confidence interval could help assess the precision of each cohort's percentage against each strain. Because no numerical intervals are included in the registry results described, precision cannot be evaluated for those outcomes.
The CHMP thresholds give a reference for interpreting the postvaccination percentages: above >70% for the 18 to ≤60 years cohort and >60% for the ≥61 years cohort. A point estimate near a threshold may be less definitive than an estimate clearly separated from it, and its uncertainty matters. In general, confidence intervals help show whether an estimate is precise enough to distinguish from a benchmark. The registry record gives neither estimates nor intervals, so the relationship between the observed responses and the stated criteria is not reported.
What can a single-group design establish?
In general, a single-group study can describe measurements observed after an intervention, but it lacks a concurrent untreated or alternative-treatment group for estimating a comparative effect. This study is classified as non-randomized and single-group, with two age cohorts receiving the same vaccine. Age-cohort results can be described separately, but they do not provide randomized evidence that any difference is caused by age, vaccine response, or another factor. Potential influences that are not controlled by a comparator remain mixed with the observed outcomes.
The open-label design means the study is not described as masked. The registry does not report masking of laboratory personnel or other safeguards against measurement awareness. It also does not report an inferential model or adjusted comparison between the age cohorts. The stated per-protocol analysis population focuses on participants with vaccination and immunogenicity data at baseline and after vaccination, but the registry text is truncated before the population criteria are complete. How missing measurements were handled is not reported in the registry record.
What do the planning illustrations represent?
The planning illustrations are described as recalculations based on an observed effect, rather than as the original trial design justification. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. For time-to-event illustrations, the stated output is a total event count; for other illustrations, it is participants per arm. These assumptions describe hypothetical planning exercises, not outcomes observed in this study.
That hypothetical setup does not match the study's single-group, non-randomized design with age cohorts. In particular, equal allocation between two arms is a planning assumption, not a description of how participants were assigned in this trial. A sample-size calculation based on an observed effect is not observed power and does not establish that the trial was adequately powered. The registry record does not report an original sample-size justification, target power, or statistical plan. No planning result should be treated as a trial finding.
In general, over-dispersion occurs when outcome variability is greater than a model assumes. It can make standard errors too small if not accommodated, leading to intervals that are too narrow and tests that are too optimistic. The registry information does not identify an over-dispersion model or describe the use of one for this endpoint. This general issue is relevant to analyses of proportions or clustered data when their assumptions warrant it, but the record does not give enough detail to determine whether it applies to the reported analyses.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint concerns three vaccine strains and two age cohorts, with assessments at baseline and Day 22. This creates multiple related summaries even though the registry lists a primary outcome measure. The record does not report whether the analyses across strains, age cohorts, or time points were treated as separate inferential tests, nor whether any adjustment for multiple comparisons was planned. A multiplicity strategy is not reported in the registry record.
Multiplicity matters when several statistical claims are evaluated: the chance of at least one false positive can increase as the number of tests grows, depending on the testing plan and the relationship among tests. In general, a prespecified strategy can clarify which comparisons are confirmatory and how uncertainty should be interpreted. The registry provides no statistical analysis plan or details on how multiplicity was addressed, so conclusions about formal error control cannot be made.
The primary analysis population is described as per-protocol and requires immunogenicity data at baseline and after vaccination. The registry text then ends partway through the influenza-related condition, leaving the complete criteria unreported in the registry record. The number excluded from this population, the number with missing outcome measurements, and the handling of missing data are not reported. It is also not stated whether any sensitivity analyses assessed the effect of missingness or deviations from protocol.
The safety entries identify at-risk groups separately from the immunogenicity analysis population. The registry does not explain whether the safety and per-protocol populations differ, or how participants with incomplete follow-up were handled for safety summaries. The outcome analyses count is listed as zero, and numerical primary endpoint results are not included in the record described. The analysis methods, prespecified hypotheses, interim analyses, and statistical plan are not reported in the registry record. These gaps limit assessment of both the analysis population and the robustness of the reported findings.
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 |
|---|---|---|---|
| TIVf (18 to ≤ 60 Years) | 0 | 61 | 0.0% |
| TIVf (≥ 61 Years) | 0 | 64 | 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 |
|---|---|
| TIVf (18 to ≤ 60 Years) | 41 of 61 |
| TIVf (≥ 61 Years) | 24 of 64 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TIVf (18 to ≤ 60 Years) | TIVf (≥ 61 Years) |
|---|---|---|---|
| Injection site pain | General disorders | 33 of 61 | 19 of 64 |
| Fatigue | General disorders | 14 of 61 | 6 of 64 |
| Headache | Musculoskeletal and connective tissue disorders | 14 of 61 | 5 of 64 |
| Malaise | General disorders | 9 of 61 | 1 of 64 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 5 of 61 | 1 of 64 |
The registry lists serious adverse event figures by age cohort. For the 18 to ≤60 years cohort, 0 participants are recorded as affected among 61 at risk. For the ≥61 years cohort, 0 participants are recorded as affected among 64 at risk. These are registry entries for the recorded serious adverse event category; they do not establish that no event occurred outside the captured reporting period or population.
The record also lists 41 participants affected by other adverse events among 61 at risk in the younger cohort, and 24 among 64 at risk in the older cohort. The registry does not define the specific scope of the category labelled other adverse events in the available information. These are counts, not descriptions of event severity, duration, relatedness to vaccination, or clinical consequences. Specific serious adverse event terms are not listed. Death figures are not reported in the registry record.
Because there is no control group, these entries cannot estimate excess risk attributable to vaccination. The record does not provide event-level narratives, timing, or a comparative safety analysis. The counts should therefore be read as descriptive registry results, with the limits of the recorded categories and denominators kept in view.
12. What the Result Does, and Does Not, Mean
The study was designed to describe safety and antibody response after one dose of TIVf in two adult age cohorts. Its primary endpoint was a threshold-based SRH percentage for each of the three vaccine strains, assessed at baseline and Day 22. The registry also identifies CHMP response criteria for the two age groups. Those design details explain the intended question and how a response was to be summarized.
They do not reveal the numerical immunogenicity outcome. The registry record does not report percentages of participants reaching the SRH threshold, confidence intervals, or whether either cohort met its stated criterion. Without those results, the magnitude of the response and its statistical precision cannot be evaluated from the registry record. It would be inappropriate to infer the outcome from the study objective, vaccine formulation, or completion status.
The safety record reports zero affected participants for serious adverse events in both cohorts and gives counts for other adverse events. Those data are descriptive, and the registry does not provide enough detail to characterize the events fully. In particular, specific serious event terms and death figures are not reported in the registry record. The safety counts do not establish whether the vaccine caused an event, because causal attribution and comparative evidence are not reported.
The two age cohorts are not randomized treatment groups. As both received the vaccine, differences between them cannot be interpreted as a comparison of vaccination against a control. The study therefore does not establish the causal effect of TIVf, its comparative performance against another product, or its effect on clinical influenza outcomes. Antibody measurements are immunogenicity outcomes and should not be treated as direct evidence of clinical protection.
The record is useful for identifying the trial's structure, its intended endpoint and timing, the response thresholds, and selected safety counts. The absence of endpoint results, complete population criteria, and detailed statistical methods leaves important uncertainty about the analyses and their interpretation. No claim that the vaccine did or did not work follows from these registry entries alone.
13. Why This Trial Matters Statistically
This study raises several important statistical interpretation issues. Its primary question is expressed through percentages meeting an antibody threshold, rather than a direct comparison of clinical outcomes. Such a measure can be useful for summarizing immunogenicity, and the registry links it to age-specific CHMP criteria. However, the endpoint percentages and confidence intervals are not reported in the registry record, so readers cannot assess how the observed findings relate to those criteria.
The design also illustrates the distinction between describing cohorts and making causal comparisons. Two age cohorts received the same intervention, but there was no randomized control group. A difference between age-cohort summaries would not, by itself, establish an age effect or a treatment effect. Study design determines which questions can be answered; a statistical analysis cannot create a missing comparator.
Population definitions are equally important. The endpoint is specified for a per-protocol population requiring vaccination and immunogenicity data at baseline and after vaccination. The remainder of the recorded criteria is truncated, and missing-data handling is not reported. Without full eligibility details and information about exclusions, it is difficult to judge exactly whom the endpoint results would represent or how incomplete observations might affect them.
Finally, the record includes safety counts and describes planning illustrations based on an observed effect. These should not be conflated: safety counts describe recorded events, while planning calculations are hypothetical and depend on assumptions. The planning assumptions describe two-arm equal allocation, unlike the single-group trial design. This distinction helps prevent an illustrative sample-size calculation from being mistaken for evidence of observed power or a feature of the trial's original 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 most consequential limitation of the registry information is that it defines the primary endpoint but does not report its numerical results. Percentages, confidence intervals, and the relationship of the observed responses to the CHMP criteria are not reported in the registry record. Consequently, the primary immunogenicity findings cannot be evaluated for magnitude or precision using the available entry.
The single-group, non-randomized design has no concurrent control group. Its outcomes can be described, but comparisons with no vaccination or another treatment are not available from this design. The age cohorts are descriptive groups, not randomized arms. The open-label classification is recorded, while details about laboratory masking or other measures to limit measurement bias are not reported.
The per-protocol population description is incomplete: it ends partway through a condition concerning RT-PCR-confirmed influenza. The full analysis population criteria, participant flow into that population, and missing-data handling are not reported in the registry record. The record also does not explain whether the safety populations and immunogenicity population were aligned.
For safety, the record gives counts in serious and other adverse event categories, but specific serious event terms are absent, the other-event category is not fully defined, and death figures are not reported. Event timing, severity, relatedness, and follow-up details are not reported in the registry record. The available counts therefore have limited clinical detail.
The statistical plan, multiplicity approach, interim analyses, and original sample-size justification are not reported. The separate planning assumptions are illustrations based on an observed effect and do not describe the trial's original design or establish observed power. These omissions limit assessment of the analyses, but should not be filled in by assumptions about common practice.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Immunogenicity of One Dose of Seasonal Trivalent Influenza Virus Vaccine (TIVf, Purified Surface Antigen, Inactivated, Egg Derived) in Adults, Aged 18 Years and Above — NCT01885117.
- Registry record last updated 2014-03-12; status last verified 2014-02.
- Results first posted 2014-03-12.
- 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
NCT01885117 is a completed Phase III, open-label, non-randomized, single-group, multicenter study sponsored by Novartis Vaccines. It enrolled adults aged 18 years and above and assessed one dose of TIVf, a trivalent, surface-antigen, inactivated vaccine formulated for the 2013/2014 Northern Hemisphere season. The two age cohorts were 18 to ≤60 years and ≥61 years.
The primary outcome was the percentage with SRH areas ≥25mm2 against each of the three vaccine strains at baseline and Day 22. The registry describes age-specific CHMP criteria but does not report the primary outcome estimates or confidence intervals. Safety entries record 0 serious adverse event cases in each cohort and 41 and 24 participants affected by other adverse events, respectively; death figures are not reported. The complete per-protocol definition and statistical plan are not reported in the registry record.