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 on a High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age (NCT04544267), a randomized phase 3 study. The primary outcome is Number of Participants With Laboratory-Confirmed Influenza Illness Caused by Any Influenza Viral Types/Subtypes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04544267 |
| Phase | Phase 3 |
| Condition | Influenza |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 100 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi Pasteur, a Sanofi Company |
| Results posted | Yes |
2. Clinical Question
The trial was designed to compare high-dose quadrivalent influenza vaccine (QIV-HD) with standard-dose quadrivalent influenza vaccine (QIV-SD) in children 6 months through 35 months of age. Its primary question concerned prevention of laboratory-confirmed influenza illness caused by any influenza A or B type. The registry record also describes secondary questions about influenza illness under a more stringent threshold, illness caused by strains similar to those in the vaccine, and HAI immune response.
Population
Children 6 months through 35 months of age. A secondary efficacy question concerned participants 6 months through 23 months of age. The main efficacy cohort was not conducted.
Intervention
QIV-HD, administered as an injection on Day 0. A second dose on Day 28 was administered for participants for whom 2 doses of influenza vaccine were recommended.
Comparator
QIV-SD, administered using the same stated schedule: an injection on Day 0 and a second dose on Day 28 when 2 doses were recommended.
Primary question
Would QIV-HD differ from QIV-SD in the number of participants with laboratory-confirmed influenza illness caused by any influenza viral types or subtypes during the stated follow-up period?
That question is the intended comparison, not a conclusion supported by an efficacy result in the registry record. The record says the main efficacy cohort was not conducted because of a shift in global influenza vaccine guidelines, and that no analysis was performed. It therefore does not report an estimate comparing the vaccines for the primary endpoint.
3. Trial Design
This was a randomized, quadruple-masked, parallel Phase 3 study sponsored by Sanofi Pasteur, a Sanofi Company. The registry lists enrollment of 100 and describes two biological interventions: QIV-HD and QIV-SD. It does not report how participants were allocated between arms, the randomization procedure, or which roles were masked.
Each arm's schedule began with an injection on Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28. The primary endpoint timeframe began 14 days after the first vaccine administration and extended up to 6 months after the last administration, approximately 196 days. The registry does not give further details about the operational conduct of follow-up.
The study started on 2020-09-15, had a primary completion date of 2021-06-02, and is listed as terminated. The record attributes the absence of the main efficacy cohort to a shift in global influenza vaccine guidelines. It does not report another reason for termination. Although the trial was designed to assess efficacy, immune responses, and safety, no primary efficacy analysis was performed. The registry lists 35 outcome measures but no analyses.
The available safety figures are for a high-dose vaccine group. A corresponding standard-dose safety result is not reported in the registry record. The record also does not report participant flow by arm, the number randomized to each intervention, or how many participants completed follow-up. These gaps limit interpretation of the study's conduct and any comparison between its intended groups.
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: The sentinel safety cohort of 100 participants were enrolled in the study. This study was prematurely terminated following a global shift in the influenza vaccine composition from quadrivalent to trivalent formulation for 2024-2025 season. Hence, main efficacy cohort was not conducted, and the safety analysis of the sentinel cohort was presented.
Overall Study
| Stage | Quadrivalent Influenza Vaccine (Split Virion, Inactivated) High-Dose |
|---|---|
| STARTED | 100 |
| COMPLETED | 100 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The main efficacy cohort was not conducted due to shift in the global influenza vaccine guidelines. Hence, no analysis was performed.
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: Expanded safety analysis set included participants who received at least 1 dose of the study vaccine in the sentinel safety cohort.
| Characteristic | Unit | Quadrivalent Influenza Vaccine (Split Virion, Inactivated) High-Dose |
|---|---|---|
| Participants analysed | 100 | |
| Age, Continuous | years | 1.7 (SD 0.43) |
| Sex: Female, Male: Female | Participants | 54 |
| Sex: Female, Male: Male | Participants | 46 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 1 |
| Race/Ethnicity, Customized: Black or African American | Participants | 20 |
| Race/Ethnicity, Customized: White | Participants | 71 |
| Race/Ethnicity, Customized: Mixed Origin | Participants | 6 |
| Race/Ethnicity, Customized: Not Reported | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Laboratory-Confirmed Influenza Illness Caused by Any Influenza Viral Types/Subtypes, measured over From 14 days after the first vaccine administration up to 6 months after the last vaccine administration (vaccines administered at Days 0 and 28), approximately 196 days.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the number of participants with laboratory-confirmed influenza illness caused by any influenza viral types or subtypes. A positive influenza result on either polymerase chain reaction (PCR) or viral culture counted as laboratory confirmation. Testing was tied to an influenza-like illness, defined in the registry as fever occurring concurrently with at least one specified symptom. Those symptoms included respiratory symptoms such as cough, wheezing, difficulty breathing, nasal congestion, rhinorrhea, or sore throat, as well as otitis, vomiting, diarrhea, chills, tiredness, headache, or muscle aches.
The endpoint combines a clinical presentation with laboratory evidence. This distinction matters: a symptom episode alone does not satisfy the stated laboratory-confirmed endpoint, and a positive test is considered within the registry's described illness definition. Counting affected participants provides a clinical event measure for the intended comparison of vaccine groups. The endpoint timeframe was from 14 days after the first vaccine administration up to 6 months after the last vaccine administration, approximately 196 days.
The registry does not report endpoint counts by arm, an effect estimate, or an analysis. The main efficacy cohort was not conducted, so the intended endpoint cannot be used from this record to quantify a comparative vaccine effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The key interpretive fact is that the planned primary efficacy question has no reported analysis. The registry states that the main efficacy cohort was not conducted because of a shift in global influenza vaccine guidelines, and explicitly says that no analysis was performed. Consequently, there is no registry-reported comparison of QIV-HD with QIV-SD for laboratory-confirmed influenza illness.
This absence should not be read as evidence that the vaccines had the same outcome, nor as evidence that one had a better outcome. The registry record supplies no primary endpoint event counts, relative or absolute effect estimate, confidence interval, or p-value. Precision cannot be assessed for the intended efficacy contrast because no estimate and uncertainty interval are reported. In particular, the record does not establish whether an observed difference was large, small, or compatible with a range of effects.
The registry lists enrollment of 100, but that figure alone cannot describe the number analyzed for efficacy or the distribution of participants between arms. The record does not provide arm-specific enrollment or participant flow. It also lists 35 outcome measures and no analyses. The presence of outcome descriptions is not equivalent to reported outcome results.
Safety information is available for a high-dose group: the registry lists 100 at risk, 1 participant affected by a serious adverse event, 65 affected by other adverse events, and 0 deaths. Acute otitis media is listed among the top serious terms at 1.0%. These figures describe the entries in that reported group; they do not supply a randomized comparison with standard dose. A standard-dose safety result is not reported in the registry record, and the record does not establish that an event was caused by vaccination.
Immune-response objectives and additional illness outcomes are described, including HAI response and outcomes related to illness caused by vaccine-similar strains. But the registry does not provide analyses for them. The appropriate reading is therefore descriptive: the record documents the intended design and certain safety entries, while leaving the central comparative efficacy question unanswered.
9. Statistical Methods Explained
The methods described in the registry establish what the investigators intended to compare, but they do not provide a completed efficacy analysis. The study was randomized, quadruple-masked, and parallel, with QIV-HD and QIV-SD as the interventions. Randomization can help balance prognostic characteristics across groups on average, while masking can reduce the influence of expectations on care, reporting, or assessment. Those are general statistical purposes of these design features; the registry does not describe the randomization implementation or identify the people whose roles were masked.
What would an endpoint comparison estimate?
In general, a comparative efficacy analysis would contrast the frequency of participants meeting the endpoint in the two assigned groups over the specified follow-up. The primary endpoint is a participant count based on laboratory-confirmed influenza illness, with the registry's stated illness definition and test criteria. The record does not report the arm-specific counts or a comparison estimate. Because the main efficacy cohort was not conducted and no analysis was performed, no efficacy contrast can be interpreted from this record.
How should uncertainty be understood?
In general, an estimate describes the observed contrast in a study, while a confidence interval describes the statistical uncertainty around that estimate under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, but the interval's interpretation also depends on how the analysis was conducted. The registry record does not report an efficacy estimate, confidence interval, or p-value. It is therefore not possible to assess either the direction or precision of a primary efficacy contrast from the reported record.
What does the sample-size illustration represent?
The record describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are planning assumptions for an illustration, not a report of the trial's own design justification. The record does not report a sample-size justification or the numerical outputs of any illustration. Such planning figures, when used, are not observed power and do not substitute for an analysis of trial outcomes.
In general, power is a design concept describing the chance that a specified analysis would detect an effect of a prespecified size under its assumptions. It is not a measure of whether an effect occurred in a completed study. Because the primary analysis was not performed, an observed efficacy result or its precision cannot be recovered from the enrollment figure or from planning assumptions.
Why might event counts need special treatment?
In general, counts of events can have variability that exceeds the assumptions of a simple Poisson model, a property often called over-dispersion. If present, ignoring that extra variability can make uncertainty appear smaller than it is. Suitable count models may account for over-dispersion, but the registry does not report an analysis model, a dispersion assumption, or an over-dispersion assessment for the primary endpoint. The endpoint is described as a number of participants with illness, and no event-count model is stated.
Other methods may be relevant depending on the endpoint and data structure. For example, time-to-event methods concern the timing of an event and may account for different follow-up durations; a participant-count endpoint does not by itself establish that such a method was used. The registry does not report a time-to-event analysis for the primary outcome. The sample-size assumptions mention a separate approach for time-to-event illustrations, but this does not establish that the trial's efficacy endpoint was analyzed that way.
What can the reported safety summaries establish?
Descriptive safety counts can show how many participants in a reported group were recorded as affected within the registry's stated categories. They do not, by themselves, estimate a causal effect or a between-group difference. A comparative safety interpretation would require suitable information for both groups and clarity about the populations, follow-up, and event definitions. The record gives safety figures for the high-dose group but does not report corresponding standard-dose figures or a comparative safety analysis.
Overall, the methodological record supports a description of the planned trial structure and endpoint definitions. It does not support a statistical conclusion about comparative efficacy, because the planned main efficacy cohort and analysis are absent. Details such as the analysis population definitions, missing-data approach, model specification, and multiplicity procedure are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 35 outcome measures. It describes a primary efficacy endpoint and several secondary objectives, including illness caused by strains similar to those contained in the vaccine, illness in participants 6 months through 23 months of age, HAI immune response, other immune-response measures, revaccination response, and safety. Multiple outcomes can create a multiplicity issue when many hypotheses are tested: without an appropriate strategy, the chance of at least one apparently unusual result can increase. This is a general statistical concern, not a claim about an analysis in this study.
A method for controlling or otherwise addressing multiplicity is not reported in the registry record. No outcome analyses are listed. Since the main efficacy cohort was not conducted and no analysis was performed, the record gives no basis for evaluating how any planned testing hierarchy or multiplicity adjustment was applied.
The registry does not report how missing outcome data were handled, whether participants were excluded from any analysis, or what analysis populations were defined. It states that the main efficacy cohort was not conducted; it does not provide an alternative analyzed efficacy population. The number randomized by arm, participant disposition, and outcome availability are not reported in the registry record. These omissions prevent assessment of attrition, adherence to an intention-to-treat approach, or the potential influence of missing observations.
These limitations concern the ability to interpret reported results, rather than evidence that a particular bias occurred. In this case, the more fundamental issue is that no primary efficacy analysis is reported at all.
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 |
|---|---|---|---|
| Quadrivalent Influenza Vaccine (Split Virion, Inactivated) High-Dose | 1 | 100 | 1.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Quadrivalent Influenza Vaccine (Split Virion, Inactivated) High-Dose | 0 of 100 |
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 |
|---|---|
| Quadrivalent Influenza Vaccine (Split Virion, Inactivated) High-Dose | 65 of 100 |
Most frequent serious adverse event terms
| Event term | Organ system | Quadrivalent Influenza Vaccine (Split Virion, Inactivated) High-Dose |
|---|---|---|
| Otitis Media Acute | Infections and infestations | 1 of 100 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Quadrivalent Influenza Vaccine (Split Virion, Inactivated) High-Dose |
|---|---|---|
| Injection Site Pain | General disorders | 44 of 100 |
| Irritability | Psychiatric disorders | 38 of 100 |
| Crying | General disorders | 28 of 100 |
| Somnolence | Nervous system disorders | 25 of 100 |
| Injection Site Erythema | General disorders | 25 of 100 |
| Decreased Appetite | Metabolism and nutrition disorders | 22 of 100 |
| Injection Site Induration | General disorders | 12 of 100 |
| Injection Site Swelling | General disorders | 12 of 100 |
| Injection Site Bruising | General disorders | 9 of 100 |
| Pyrexia | General disorders | 9 of 100 |
Serious events with the highest arm-level rate: otitis media acute (1.0%).
The registry reports safety figures for a high-dose quadrivalent influenza vaccine group. It lists 100 participants at risk, 1 participant affected by a serious adverse event, 65 affected by other adverse events, and 0 deaths. Acute otitis media is listed as a top serious adverse event term at 1.0%. These are descriptive registry entries, not a comparison between QIV-HD and QIV-SD.
The serious-event count and the broader other-adverse-event count refer to different registry categories; they should not be added together or treated as interchangeable measures. The record does not provide the corresponding standard-dose safety figures, nor does it report a comparative safety analysis. It also does not state whether the listed events were judged related to vaccination. An adverse event recorded after vaccination is not, on that fact alone, established as caused by vaccination.
The figures should therefore be read as safety information recorded for the high-dose group, with the scope and limitations described in the registry. They do not establish comparative risk or support a causal conclusion.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized, quadruple-masked, parallel Phase 3 comparison intended to assess QIV-HD against QIV-SD in children 6 months through 35 months of age. It gives the primary endpoint definition and follow-up timeframe, describes the vaccine schedules, and records some safety information for a high-dose group. These details help explain what the study was designed to investigate.
However, the main efficacy cohort was not conducted because of a shift in global influenza vaccine guidelines, and the registry states that no analysis was performed. There is consequently no primary efficacy estimate to interpret. The record cannot show whether the two groups differed in laboratory-confirmed influenza illness, how large any difference might have been, or how precise an estimate would be. The absence of an analysis is not evidence of equivalence, benefit, or lack of benefit.
The safety entries also have limited scope. They describe the reported high-dose group and do not include a standard-dose comparison in the registry record. They should not be treated as proof that a vaccine caused an event, or as a comparative measure of safety.
Enrollment of 100 does not resolve these uncertainties. Without arm-specific participant flow, outcome counts, and analysis details, the enrollment figure cannot establish how much information was available for the intended efficacy comparison. The record's outcome and objective descriptions show the range of questions the study aimed to address, but descriptions alone are not findings. The sound interpretation is that the intended primary comparison remains unanswered in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between a study's design and its evidence. A randomized, masked comparison can be planned to answer a clinical question, but that design does not itself generate an interpretable efficacy result. The registry documents a direct comparison of high-dose and standard-dose quadrivalent influenza vaccines in young children, yet also states that the main efficacy cohort was not conducted and that no analysis was performed.
For biostatistical interpretation, this makes the status of the analysis as important as the endpoint definition. A carefully specified laboratory-confirmed outcome and follow-up period do not permit an effect estimate when the relevant cohort and analysis are absent. Nor can enrollment alone supply the missing group-specific event data or uncertainty estimates. The distinction prevents a reader from mistaking an intended comparison for a demonstrated finding.
The study also shows why outcome lists and safety summaries need to be read within their scope. The registry describes multiple efficacy and immune-response objectives, but lists no analyses. It reports safety entries for a high-dose group, but no corresponding standard-dose safety result. Those details can be reported accurately without turning them into unsupported comparative conclusions.
Statistically, the record is useful as an example of how incomplete outcome reporting limits inference. It documents design features and planned questions, while leaving the primary comparison unresolved. That boundary is central to a precise reading of clinical trial evidence.
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 is the absence of the planned primary efficacy analysis. The registry says the main efficacy cohort was not conducted because of a shift in global influenza vaccine guidelines, and that no analysis was performed. As a result, there are no primary endpoint counts or comparative efficacy estimates to assess.
Although enrollment is listed as 100, arm-specific enrollment and participant flow are not reported in the registry record. The record does not say how many participants were analyzed, completed follow-up, or had outcome data available. It also does not report a missing-data strategy, analysis populations, or the statistical model intended for the primary outcome. These gaps prevent evaluation of the consequences of attrition or analytic choices.
The registry lists 35 outcome measures and no analyses. A multiplicity strategy is not reported in the registry record, and no secondary efficacy or immune-response results are available in the record. Safety reporting is also incomplete for comparative interpretation: the listed figures concern a high-dose group, with no standard-dose safety figures or comparative analysis reported.
The registry does not provide a sample-size justification, detailed randomization methods, masking roles, or an explanation of termination beyond the stated guideline shift connected to the absent main efficacy cohort. These limitations do not establish that the trial was biased or that any unreported result favored either intervention. They define what can and cannot be inferred from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study on a High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age — NCT04544267.
- Registry record last updated 2025-12-24; status last verified 2025-12.
- Results first posted 2025-12-24.
- 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
This randomized, quadruple-masked, parallel Phase 3 study was designed to compare QIV-HD with QIV-SD in children 6 months through 35 months of age. It lists enrollment of 100, a start date of 2020-09-15, a primary completion date of 2021-06-02, and terminated status.
The primary endpoint was laboratory-confirmed influenza illness caused by any influenza viral types or subtypes. The registry states that the main efficacy cohort was not conducted because of a shift in global influenza vaccine guidelines and that no analysis was performed. It lists 35 outcome measures and no analyses. Safety figures are reported for a high-dose group, but a standard-dose safety comparison is not reported in the registry record. Thus, the record describes the intended study and selected safety information, but does not provide a comparative primary efficacy result.