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 of Quadrivalent Influenza Vaccine Among Children (NCT01240746), a randomized phase 3 study. The primary outcome is Geometric Mean Titers Against Influenza A Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01240746 |
| Phase | Phase 3 |
| Condition | Influenza |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 4363 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi Pasteur, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
Population
Children aged 6 months to less than 9 years of age. The primary outcome description identifies randomized and vaccinated participants in the per-protocol population; it does not give the number analyzed for that outcome.
Intervention
The investigational quadrivalent influenza vaccine (QIV), described as containing four influenza strains.
Comparator
Two trivalent influenza vaccine (TIV) groups: the licensed 2010-2011 TIV containing the primary B strain, and an investigational TIV containing the alternate B strain.
Primary question
Whether antibody responses after QIV were non-inferior to responses after each TIV, assessed using geometric mean titer ratios for each of four virus strains separately. The secondary objective asked whether responses to each B strain were superior with QIV to responses after the TIV lacking that B strain.
The study also had an observational safety objective. It planned to describe solicited injection-site and systemic adverse events collected for 7 days after vaccination, unsolicited adverse events collected from 21 days after vaccination, and adverse events of special interest and serious adverse events from Visit 1 to Visit 2. These are stated collection periods and objectives; the record does not give safety results for every category or describe how each category was analyzed.
The posted primary outcome is titled as geometric mean titers against influenza A strains after vaccination with QIV or TIV. Its description says that the A/Victoria/210/2009 and A/California/07/2009 data for TIV participants were pooled. Thus, the primary outcome description is narrower than the study-level objective, which refers to antibody responses for all four strains. The actual titer values and comparative estimates are not reported in the registry record, so the stated question can be described, but its answer cannot be determined from these details.
3. Trial Design
This was a phase 3, randomized, quadruple-masked, parallel-group study of vaccine formulations in children. The registry record lists enrollment of 4363 and identifies influenza as the condition. The study status is completed. Its recorded start was 2010-11, and its primary completion was 2011-12.
Participants were assigned to one of three vaccine groups: licensed 2010-2011 TIV containing the primary B strain, investigational TIV containing the alternate B strain, or investigational QIV. The record describes all three as vaccines without preservative. The parallel-group structure means that the trial compared groups receiving different formulations rather than describing a crossover between formulations. Random allocation supports a comparative design, while masking is intended to reduce the influence of knowledge of assignment on trial conduct or outcome assessment. The registry record does not describe who was masked or how masking was maintained.
Enrollment is the number recorded for the study overall, not necessarily the number included in any particular endpoint analysis. The primary outcome description specifies randomized and vaccinated participants in a per-protocol population, but the number in that population is not reported in the registry record. Nor does the record detail the allocation ratio, randomization procedure, concealment method, or exclusions from the per-protocol analysis.
The primary objective was to demonstrate non-inferiority of antibody responses to QIV compared with each of the two TIV formulations. A secondary objective concerned superiority of responses to each B strain when QIV was compared with the TIV that did not contain the corresponding strain. Safety was an observational objective. Although these objectives establish the broad comparison structure, the statistical plan, non-inferiority margins, and prespecified analysis procedures are not reported in the registry record.
These features describe how the study was organized, not the magnitude or certainty of any vaccine difference. No primary outcome estimates or hypothesis-test results are included in the record details available for this analysis.
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: A total of 4363 participants who met all the inclusion criteria and none of the exclusion criteria were enrolled, randomized and vaccinated in the study.
Overall Study
| Stage | Study Group 1 (2010-2011 Trivalent Influenza Vaccine) | Study Group 2 (Investigational Trivalent Influenza Vaccine) | Study Group 3 (Investigational Quadrivalent Influenza Vaccine) |
|---|---|---|---|
| STARTED | 736 | 725 | 2902 |
| COMPLETED | 677 | 677 | 2659 |
| NOT COMPLETED | 59 | 48 | 243 |
Reasons for not completing this period:
| Reason | Study Group 1 (2010-2011 Trivalent Influenza Vaccine) | Study Group 2 (Investigational Trivalent Influenza Vaccine) | Study Group 3 (Investigational Quadrivalent Influenza Vaccine) |
|---|---|---|---|
| Adverse Event | 2 | 0 | 10 |
| Lost to Follow-up | 23 | 20 | 102 |
| Protocol Violation | 24 | 15 | 72 |
| Withdrawal by Subject | 10 | 13 | 59 |
Analysis population for the primary outcome, as defined in the registry: Geometric mean titers (GMT) to influenza vaccine A antigens were determined in randomized and vaccinated participants, per-protocol population. The GMT data for antigen A/Victoria/210/2009 and A/California/07/2009 were pooled for participants vaccinated with either 2010-2011 TIV or the investigational TIV. Data presented in column for Group 1.
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 | Study Group 1 (Trivalent Influenza Vaccine) | Study Group 2 (Investigational Trivalent Influenza Vaccine) | Study Group 3 (Investigational Quadrivalent Influenza Vaccine) | Total |
|---|---|---|---|---|---|
| Participants analysed | 736 | 725 | 2902 | 4363 | |
| Age, Categorical: <=18 years | Participants | 736 | 725 | 2902 | 4363 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | Months | 49.6 (SD 29.0) | 49.6 (SD 28.7) | 49.8 (SD 29.7) | 49.8 (SD 29.4) |
| Sex: Female, Male: Female | Participants | 367 | 359 | 1427 | 2153 |
| Sex: Female, Male: Male | Participants | 369 | 366 | 1475 | 2210 |
| Region of Enrollment: United States | Participants | 736 | 725 | 2902 | 4363 |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Mean Titers Against Influenza A Strains After Vaccination With Fluzone® Quadrivalent Influenza Vaccine or Trivalent Influenza Vaccines in All Participants, measured over Day 28 post final vaccination.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Titers |
| Endpoint classification | not reduced to a single comparison |
The posted primary outcome is geometric mean titer (GMT) against influenza A strains, measured at Day 28 post final vaccination. The assay was hemagglutination inhibition (HAI), using serum samples. A titer is a measure of the antibody response detected by the assay; the GMT summarizes titers using a geometric rather than arithmetic average. Geometric summaries are often used for antibody measurements because titers can be strongly right-skewed and are commonly interpreted on a multiplicative scale.
The record specifies a 95% confidence interval as the measure of dispersion. A confidence interval expresses uncertainty around an estimated quantity: narrower intervals indicate greater precision, while wider intervals indicate less precision. The interval does not by itself establish whether a prespecified non-inferiority or superiority criterion was met; interpretation requires the relevant estimate, the interval, and the prespecified decision rule.
The assay’s lower limit of quantitation was the lowest dilution used, 1/10. Titers below that level were reported as <10. Such values are below the assay’s quantifiable range, not necessarily evidence of a literal zero antibody response. The registry description does not explain how below-limit values were handled in the GMT calculation.
The outcome description identifies the per-protocol population and states that two influenza A antigen GMT datasets for TIV participants were pooled. The actual GMTs, confidence intervals, group sizes, and comparative ratios are not reported in the registry record. The title refers to influenza A strains, while the study-level primary objective describes four strains, including both B strains. This difference in scope should be kept in mind when interpreting the stated objective alongside the specific posted outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of QIV with two TIV formulations, with antibody response as the principal efficacy-related focus and safety as an observational objective. It states that the primary objective was non-inferiority for antibody responses across four strains, evaluated through GMT ratios, and that the secondary objective concerned superiority for B-strain responses in comparisons with a TIV that lacked the corresponding strain.
Those objectives are not themselves results. The primary outcome title and description identify GMTs against influenza A strains at Day 28 post final vaccination, but no GMT values, confidence intervals, GMT ratios, or hypothesis-test results are reported in the registry record. Accordingly, the posted information does not establish whether non-inferiority or superiority criteria were met, nor does it show the size or precision of any antibody-response difference. A conclusion about those questions would require the relevant estimates and the decision thresholds specified in the statistical plan. The non-inferiority margins and that plan are not reported in the registry record.
The primary outcome description also names a per-protocol analysis population and says that the two A-strain GMT datasets for participants in the TIV groups were pooled. It does not state the number analyzed, how protocol deviations were handled, or whether other analysis populations were used for the comparisons. The study objective covers four strains, whereas the posted primary outcome title specifies influenza A strains. The record therefore gives a broad objective and a more specific outcome description without reporting the numerical analyses needed to assess either.
The safety figures describe affected participants in three groups. Serious adverse events were reported for 7 of 734 participants in the licensed TIV group, 14 of 721 in the investigational TIV group, and 41 of 2892 in the QIV group. The record also gives counts of participants with other adverse events: 333, 329, and 1358, respectively, in those same groups. These counts should be read with their group denominators and the limits of the recorded safety information; they do not, on their own, establish comparative safety or causation.
Serious adverse event terms listed in the record include drowning, febrile convulsion, gastroenteritis, asthma, appendicitis, and mycoplasma infection, with percentages attached to the terms. The record does not assign those term percentages to specific treatment groups in the information. Death counts are not reported in the registry record. Details on event timing, severity, relatedness, and the handling of participants with incomplete safety follow-up are also not reported.
Overall, the registry record supports describing the study’s design, objectives, endpoint definition, and selected safety counts. It does not provide enough outcome information to quantify antibody differences, assess their precision, apply the planned inferential criteria, or make a comparative safety inference.
9. Statistical Methods Explained
The statistical concepts below are general explanations of the methods named in the registry record. They are not a reconstruction of an analysis plan. The statistical plan and key decision thresholds are not reported in the registry record.
What does a geometric mean titer describe?
A geometric mean is calculated on a transformed scale: measurements are transformed, averaged, and then expressed back on the original scale. This approach can be useful for antibody titers, which often vary multiplicatively rather than by equal additive increments. A GMT provides a group-level summary, but it does not show the full distribution of individual responses. Two groups can have similar GMTs while differing in the spread or shape of their individual titer distributions.
When a comparison is expressed as a GMT ratio, the estimate communicates relative antibody levels on a ratio scale. The direction and magnitude of a ratio require an explicit group ordering and a stated interpretation rule. For a non-inferiority question, the estimate is considered against a prespecified margin; a confidence interval is typically used to judge whether values inconsistent with the margin can be excluded. The margin and exact inferential rule for this study are not reported in the registry record, so the decision rule cannot be applied from the posted information.
What does non-inferiority ask?
Non-inferiority is not the same as showing that two treatments have identical effects. It asks whether the response with one treatment is not worse than the comparator by more than a prespecified acceptable amount. That amount must be chosen before interpreting the comparison and should be justified in the trial’s protocol or statistical plan. Neither the margin nor its justification is reported in the registry record. Without them, a reader cannot determine the threshold against which any GMT ratio would need to be assessed.
A non-significant test of difference would not, by itself, demonstrate non-inferiority. The relevant estimate and confidence interval must be evaluated against the margin. Because the record does not report those estimates or the margin, it is not possible to infer a non-inferiority conclusion from the objectives or study completion status.
How is superiority different?
Superiority asks whether the response in one group is greater than in its comparator under a stated statistical criterion. The secondary objective specifies comparisons for each B strain with the TIV that did not contain that strain, using GMT ratios and seroconversion rates. Seroconversion is a defined change in antibody status or level, but the exact definition used in this study is not reported in the registry record. The estimates, confidence intervals, and test results for these comparisons are also not reported.
Testing multiple strains and more than one outcome can raise multiplicity concerns. If many hypotheses are tested, the chance of at least one false-positive finding can increase unless the analysis plan accounts for the testing structure. The registry record does not report whether the trial used a hierarchy, adjusted significance levels, or another multiplicity strategy. No particular method should be assumed.
What does a confidence interval add?
A confidence interval gives a range of values compatible with the observed data under the statistical model and procedure used. It conveys precision as well as the location of an estimate. It is not a guarantee that the true value lies within a particular interval, and it does not replace clinical or design-based thresholds. For a GMT ratio, a confidence interval helps show how precisely the relative response was estimated; for a non-inferiority question, its relation to the prespecified margin is central. The record names a 95% confidence interval for the GMT outcome but does not provide interval values.
Precision depends partly on the amount and variability of information in the analyzed population. Overall enrollment is not enough to establish endpoint precision because the per-protocol analysis size, missing specimens, and variability of the measurements are not stated in the record. No precision estimate can be recreated from the available details.
How should below-quantitation titers be understood?
The assay reports titers below its lower limit of quantitation as <10. This is a censored measurement: the assay identifies that the titer is below its quantifiable threshold but does not provide an exact value within that range. Statistical handling of these observations can affect group summaries, especially if the frequency of below-limit values differs between groups. The registry record does not state the method used for handling such values, so no assumption about substitution or another approach is warranted.
Why do analysis populations matter?
The primary outcome description names randomized and vaccinated participants in a per-protocol population. A per-protocol analysis generally focuses on participants who met specified requirements for treatment and assessment, but the eligibility rules are specific to the protocol. The record does not say which deviations led to exclusion, how many participants were excluded, or whether analyses in other populations were also conducted. In non-inferiority trials, results can be sensitive to the choice of population; examining appropriate populations and explaining their roles is therefore important. The record does not provide enough detail to assess this issue for the present study.
The record’s sample-size assumptions describe a separate 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. Such illustrations are not observed trial results or observed power, and they do not establish the original trial’s design rationale. The original sample-size justification is not reported in the registry record. No numerical planning results are stated in the record details used for this explanation.
10. Multiplicity, Missing Data and Analysis Populations
The study objective involves several related comparisons: QIV against each of two TIV formulations, responses across four virus strains, and secondary comparisons for each B strain using both GMT ratios and seroconversion rates. This creates a multiplicity question. In general, when many hypotheses are tested, the probability of at least one false-positive result can rise. A prespecified testing hierarchy or adjustment procedure can control how the results are interpreted, but the registry record does not report whether either was used. It also does not state which tests, if any, were designated as confirmatory or how the primary and secondary objectives were linked statistically.
Missing data and analysis populations are also important for antibody outcomes. The primary outcome description identifies randomized and vaccinated participants in a per-protocol population, but the record does not report how many participants contributed samples, how missing samples were handled, or the reasons for missingness. It does not describe exclusions from the per-protocol population, rules for protocol deviations, or whether an intention-to-treat or other analysis was performed. These details matter because estimates can depend on who is included and on how unavailable measurements are handled.
The assay classified titers below its quantitation limit as <10. The registry record does not describe the statistical treatment of those values. It also does not report whether missingness or below-limit measurements differed between groups. No assumptions about imputation, censoring, or sensitivity analyses should therefore be made.
The sample-size justification, interim analyses, and full statistical analysis plan are not reported in the registry record. The planning illustration described in the record is not evidence of the original trial’s design assumptions, and its assumptions should not be mistaken for a reported trial analysis plan. These omissions limit assessment of prespecification, control of false-positive findings, robustness to missing data, and the intended interpretation of the multiple antibody comparisons.
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 |
|---|---|---|---|
| Study Group 1 (Trivalent Influenza Vaccine) | 7 | 734 | 1.0% |
| Study Group 2 (Investigational Trivalent Influenza Vaccine) | 14 | 721 | 1.9% |
| Study Group 3 (Investigational Quadrivalent Influenza Vaccine) | 41 | 2892 | 1.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5.00% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Study Group 1 (Trivalent Influenza Vaccine) | 333 of 734 |
| Study Group 2 (Investigational Trivalent Influenza Vaccine) | 329 of 721 |
| Study Group 3 (Investigational Quadrivalent Influenza Vaccine) | 1358 of 2892 |
Most frequent serious adverse event terms
| Event term | Organ system | Study Group 1 (Trivalent Influenza Vaccine) | Study Group 2 (Investigational Trivalent Influenza Vaccine) | Study Group 3 (Investigational Quadrivalent Influenza Vaccine) |
|---|---|---|---|---|
| Febrile convulsion | Nervous system disorders | 2 of 734 | 3 of 721 | 8 of 2892 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 0 of 734 | 0 of 721 | 8 of 2892 |
| Gastroenteritis | Infections and infestations | 0 of 734 | 2 of 721 | 2 of 2892 |
| Respiratory syncytial vrus bronchiolitis | Infections and infestations | 1 of 734 | 1 of 721 | 2 of 2892 |
| Pneumonia | Infections and infestations | 1 of 734 | 1 of 721 | 1 of 2892 |
| Kawasaki's disease | Vascular disorders | 0 of 734 | 0 of 721 | 3 of 2892 |
| Viral upper respiratory tract infection | Infections and infestations | 0 of 734 | 1 of 721 | 1 of 2892 |
| Femur fracture | Injury, poisoning and procedural complications | 0 of 734 | 0 of 721 | 2 of 2892 |
| Bronchial hrperreactivity | Respiratory, thoracic and mediastinal disorders | 0 of 734 | 1 of 721 | 1 of 2892 |
| Bradycardia | Cardiac disorders | 0 of 734 | 0 of 721 | 1 of 2892 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Study Group 1 (Trivalent Influenza Vaccine) | Study Group 2 (Investigational Trivalent Influenza Vaccine) | Study Group 3 (Investigational Quadrivalent Influenza Vaccine) |
|---|---|---|---|---|
| Injection site pain | General disorders | 333 of 540 | 329 of 547 | 1358 of 2113 |
| Injection site erythema | General disorders | 246 of 699 | 238 of 692 | 972 of 2742 |
| Myalgia | Musculoskeletal and connective tissue disorders | 174 of 539 | 190 of 546 | 753 of 2110 |
| Malaise | General disorders | 180 of 539 | 181 of 546 | 705 of 2110 |
| Injection site Swelling | General disorders | 161 of 734 | 154 of 692 | 643 of 2742 |
| Headache | Nervous system disorders | 99 of 539 | 115 of 546 | 414 of 2110 |
| Cough | Respiratory, thoracic and mediastinal disorders | 95 of 734 | 89 of 721 | 341 of 2892 |
| Irritability | Psychiatric disorders | 84 of 159 | 77 of 144 | 339 of 628 |
| Injection site tenderness | General disorders | 77 of 159 | 72 of 145 | 340 of 628 |
| Fever | General disorders | 75 of 695 | 68 of 689 | 276 of 2739 |
Serious events with the highest arm-level rate: drowning (0.4%), febrile convulsion (0.4%), gastroenteritis (0.3%), asthma (0.3%), appendicitis (0.1%).
The registry record reports serious adverse event counts by study group. In the licensed 2010-2011 TIV group, 7 of 734 participants were recorded as affected; in the investigational TIV group, 14 of 721 were recorded as affected; and in the QIV group, 41 of 2892 were recorded as affected. These are counts with their recorded group denominators, not adjusted comparisons. The record does not provide confidence intervals or a comparative statistical analysis for these figures.
Other adverse events were recorded for 333 of 734 participants in the licensed TIV group, 329 of 721 in the investigational TIV group, and 1358 of 2892 in the QIV group. These broader counts are distinct from the serious adverse event counts and should not be interpreted as though every event had the same clinical importance. The registry record does not give the full event definitions, severity distributions, or group-specific details for all listed events.
The record lists drowning and febrile convulsion at 0.4%, gastroenteritis and asthma at 0.3%, and appendicitis and mycoplasma infection at 0.1% among the top serious adverse event terms. The information does not identify the treatment group associated with each percentage. Death counts are not reported in the registry record. The stated safety collection windows include solicited events for 7 days after vaccination, unsolicited events from 21 days after vaccination, and serious adverse events from Visit 1 to Visit 2; actual completeness of follow-up is not reported.
12. What the Result Does, and Does Not, Mean
This trial’s registry record establishes that a randomized, quadruple-masked, parallel-group study compared an investigational QIV with two TIV formulations in children. It states a non-inferiority objective for antibody responses and a secondary superiority objective for B-strain responses. It also describes a safety objective and reports selected adverse event counts. These details explain what the trial was designed to investigate, but they do not establish the results of the antibody comparisons.
The primary outcome is described as GMTs against influenza A strains at Day 28 post final vaccination, with 95% confidence intervals. The record gives no corresponding GMT estimates, intervals, ratios, or test results. Consequently, it does not show how large or precise the measured antibody responses were, whether the comparison met a non-inferiority margin, or whether the secondary superiority objective was met. The relevant margin, seroconversion definition, and statistical decision procedures are not reported in the registry record.
The safety counts provide descriptive information about participants recorded as having serious and other adverse events in each group. They do not demonstrate that an event was caused by a vaccine, and without a reported comparative analysis they do not quantify a statistically supported difference between groups. The term percentages are not tied to specific groups in the recorded details, and deaths are not reported in the registry record. The stated event-collection windows describe the intended observation periods, not necessarily the completeness of follow-up.
The record also does not report enough detail to assess multiplicity, missing outcome data, analysis-population sensitivity, or the original sample-size justification. These are relevant to how confidently results can be interpreted, but no specific handling method should be assumed. Overall, the registry information supports a description of the design, questions, endpoint, and selected safety summaries. It does not support a conclusion about comparative antibody performance or a causal safety conclusion.
13. Why This Trial Matters Statistically
Several statistical features make this study a useful example of why objectives and results must be distinguished. The primary aim was framed as non-inferiority, a question that requires a prespecified margin and an interval-based interpretation rather than simply a test for any difference. The registry record names GMT ratios but does not report the margin or the resulting estimates. A study’s objective alone cannot show whether its criterion was satisfied.
The design also involved multiple formulations and multiple viral strains. The study-level objective refers to four strains, while the specific posted primary outcome is titled as a GMT outcome against influenza A strains. Secondary objectives add comparisons for B strains and seroconversion rates. Such a structure makes the prespecified testing hierarchy and multiplicity approach important to understanding the strength of any positive findings. Those procedures are not reported in the registry record.
The endpoint illustrates common measurement issues in immunogenicity research. GMTs summarize titers on a geometric scale, confidence intervals describe uncertainty, and the assay’s lower quantitation limit creates below-threshold values that require a defined analytical treatment. The registry record specifies the assay and threshold but does not describe how below-limit results entered the calculations. These details can influence interpretation even when the overall design is clear.
Finally, analysis-population definitions matter. The primary outcome description specifies a per-protocol population, but the record does not state its size or the rules for inclusion. In a non-inferiority setting, transparent reporting of populations and sensitivity analyses is particularly relevant. The study therefore highlights the difference between a recognizable randomized design and a fully interpretable statistical result: the latter also depends on estimates, uncertainty, decision thresholds, and analysis details.
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 main limitation of the registry information is that it does not report numerical results for the primary antibody outcome. Although the outcome definition specifies GMTs, a confidence interval, an assay, and an assessment time, it gives no group estimates or comparative ratios. There is therefore no basis in the record to describe the magnitude or precision of the antibody responses or to determine whether the stated non-inferiority objective was met.
The registry record’s primary outcome description focuses on influenza A strains, while the study-level primary objective refers to four virus strains. The relationship between these descriptions is not explained in the recorded details. Results for the B-strain comparisons and seroconversion outcomes are not reported in the record information used.
Several details needed to assess inferential validity are also absent: the non-inferiority margin, multiplicity procedure, statistical analysis plan, sample-size justification, analysis-population counts, and methods for missing data and below-quantitation titers. The per-protocol population is named, but its eligibility criteria and size are not stated. Interim analyses are not reported in the registry record.
For safety, the record gives group counts and denominators but not confidence intervals, adjusted comparisons, detailed event timing, or full information on event severity and relatedness. The listed serious adverse event term percentages are not attributed to specific groups in the recorded details, and death counts are not reported in the registry record. The planned event-collection windows do not establish that all participants had complete follow-up. These limitations restrict interpretation to a description of the recorded design and selected summaries rather than a comprehensive evaluation of efficacy or safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Quadrivalent Influenza Vaccine Among Children — NCT01240746.
- Registry record last updated 2015-07-14; status last verified 2015-06.
- Results first posted 2014-01-14.
- 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 3, randomized, quadruple-masked, parallel-group study enrolling 4363 children. The three groups received licensed 2010-2011 TIV containing the primary B strain, investigational TIV containing the alternate B strain, or investigational QIV.
The primary objective was non-inferiority of antibody responses to QIV compared with the two TIV formulations. The posted primary outcome describes GMTs against influenza A strains at Day 28 post final vaccination, measured by HAI assay, with 95% confidence intervals. The study also had B-strain superiority and safety objectives. Numerical antibody comparisons and the statistical decision thresholds are not reported in the registry record.
Recorded serious adverse event counts were 7 of 734, 14 of 721, and 41 of 2892 in the three groups, respectively. The record also reports other adverse event counts, but the information does not establish comparative effects or causation. Important analysis details, including multiplicity handling, missing-data methods, and the original sample-size justification, are not reported.