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 Efficacy & Safety of Nasal Influenza Immunisation in Children (NCT02549365), a non-randomized phase 4 study. The primary outcome is Vaccine Efficacy.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02549365 |
| Phase | Phase 4 |
| Condition | Influenza Vaccines Efficacy and Safety |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 276 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
Children receiving live attenuated influenza vaccine (LAIV) and sibling controls of children in the intervention group. The registry summary describes an intended study population that included many children with a history of asthma or recurrent wheezing, but participant characteristics are not reported in the registry record.
Intervention
Administration of LAIV as per national guidance, followed by surveillance using nasal swabs if influenza-like illness occurred.
Comparator
Siblings of children in the intervention group, monitored with nasal swabs if influenza-like illness occurred. The arm description says this surveillance applied irrespective of the siblings’ vaccination status, so the comparator is not necessarily limited to unvaccinated children.
Primary question
How did the incidence of laboratory-confirmed influenza and other respiratory viruses compare between children receiving LAIV and sibling controls during the 2015/2016 influenza season? The registry names the primary outcome Vaccine Efficacy, but does not report an estimated effect or the exact calculation used to derive it.
The study focused on vaccine efficacy and safety in children, including children with atopic conditions, and on immune responses to LAIV. Its summary describes limited data on efficacy and immune correlates in UK children, particularly atopic children, as the motivation for the work. It also states that the study would assess whether outcomes varied with prior administration of pandemic influenza vaccine and/or LAIV. Whether those subgroup questions were evaluated, and what they showed, are not reported in the registry record.
The comparison is observational rather than randomized. Children were assigned to the intervention and sibling-control groups without random allocation, and the registry marks the study as unmasked. The comparison can therefore describe the observed groups, but group differences cannot automatically be attributed to vaccination. Vaccination status among controls is also described as unrestricted in the arm description, which matters when interpreting the contrast.
3. Trial Design
SNIFFLE-3 is a Phase 4, parallel, non-randomized study sponsored by Imperial College London. The registry lists an enrollment of 276 and a status of completed. The recorded study start is 2015-10, and primary completion is 2016-04. The registry summary describes an intended enrollment of 200 children and at least 200 unvaccinated household sibling controls; it does not explain how that planned description relates to the recorded enrollment.
The intervention was LAIV administered according to national guidance. Participants in the intervention arm were monitored during the influenza season, with nasal swabbing in the event of influenza-like illness. Siblings of intervention-arm participants formed the control arm and were also monitored by nasal swabbing if influenza-like illness occurred. The registry says sibling surveillance applied irrespective of vaccination status, while the primary outcome description refers to unvaccinated sibling controls. This leaves the precise vaccination composition of the analyzed control group unclear.
Allocation is recorded as non-randomized and masking as none. These features are important when reading comparisons: groups may differ for reasons related to vaccination choice, health, household circumstances, or other factors, and outcome assessment was not masked according to the registry. The registry does not report whether any statistical adjustment was used to address these possibilities.
The primary outcome is titled Vaccine Efficacy and is described through incidence of laboratory-confirmed influenza and other respiratory viruses in children receiving LAIV compared with sibling controls. The stated timeframe is the 2015/2016 influenza season, with exact dates to be set by Public Health England and an approximate duration of 3 months. Secondary outcomes concern immune response to LAIV and incidence of adverse events and serious adverse events in those receiving LAIV. The statistical analysis plan, including how outcomes were defined and compared, is not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Intervention | Controls |
|---|---|---|
| STARTED | 164 | 112 |
| COMPLETED | 164 | 112 |
| NOT COMPLETED | 0 | 0 |
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 | Intervention | Controls | Total |
|---|---|---|---|---|
| Participants analysed | 164 | 112 | 276 | |
| Age, Categorical: <=18 years | Participants | 164 | 112 | 276 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 65 | 48 | 113 |
| Sex: Female, Male: Male | Participants | 99 | 64 | 163 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: United Kingdom | Participants | 164 | 112 | 276 |
6. Primary Endpoint
The registry lists the primary outcome as Vaccine Efficacy, measured over During 2015/2016 influenza season - precise dates to be set by Public Health England as this varies annually. Approximate duration of 3 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled Vaccine Efficacy. Its description says efficacy would be assessed through documentation of laboratory-confirmed influenza and other respiratory viruses in children receiving LAIV compared with sibling controls during the 2015/2016 influenza season. The measure is specified as a count of participants. The registry does not state the exact case definition, whether influenza and other respiratory viruses were analyzed separately, or how a count of participants was converted into an efficacy estimate.
Counting participants with an event is a way to summarize how many people in a group experienced a defined outcome. For a clinical comparison, the underlying event definition and the period during which participants are observed are essential: a count alone does not indicate the probability of an event unless the number observed and the relevant follow-up are also clear. The registry gives the season as the timeframe and describes illness-triggered nasal swabbing, but detailed follow-up rules and testing criteria are not reported.
Laboratory confirmation can distinguish infections identified by testing from illness identified only by symptoms. The use of surveillance and nasal swabbing is part of the endpoint approach described in the record. However, the registry does not report how many participants were swabbed, how many tests were positive, or what proportion had complete follow-up. No efficacy estimate, confidence interval, or hypothesis-test result is reported in the registry record, so the endpoint’s observed magnitude and precision cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the intended primary comparison, but it does not report the results needed to quantify vaccine efficacy. There is no reported count of laboratory-confirmed infections by group, no estimated contrast, and no confidence interval or p-value. Consequently, the magnitude, direction, and statistical precision of the primary comparison are not reported in the registry record. The title Vaccine Efficacy should not be mistaken for a reported efficacy finding.
The design also affects what any comparison could establish. Since allocation was non-randomized, intervention and control participants may have differed before surveillance began. Such differences can affect observed infection counts even if the study measures outcomes consistently. The registry does not report baseline characteristics by group or an adjusted analysis that would help assess or account for differences. The sibling-control design links controls to intervention participants through households, but the analysis does not state whether this relationship was addressed statistically.
Control vaccination status is another point requiring care. The primary outcome description refers to unvaccinated sibling controls, while the control-arm description says surveillance was conducted irrespective of vaccination status. The registry does not report how many controls were vaccinated or whether the analysis excluded vaccinated siblings. Without that information, the exact comparison underlying the primary outcome is unclear.
The registry describes nasal swabbing when influenza-like illness occurred. This is a surveillance approach triggered by symptoms, rather than a statement that every participant was tested on a fixed schedule. The record does not report swabbing completion, the number of illness episodes, or whether testing practices were comparable across groups. These details matter because differences in illness recognition or testing can affect the number of laboratory-confirmed cases recorded.
Safety information is limited to the intervention group figures recorded for adverse events: 0 serious adverse events among 164 at risk, and 43 other adverse events among 164 at risk. The registry does not provide a control-group safety comparison, event descriptions for the serious-adverse-event category, or a complete account of follow-up. These counts describe the posted safety fields; they do not establish the absence of unrecorded events.
Overall, the record allows a description of the planned question, design, and selected safety counts, but not a conclusion about the observed primary efficacy result. The registry does not report the analysis methods, missing-data handling, or statistical uncertainty needed for a fuller interpretation.
9. Statistical Methods Explained
What does a participant count describe?
The primary outcome is specified as a count of participants. In general, a count records how many people met an outcome definition during the stated observation period. To interpret such a count in a comparison, readers also need to know how many people were observed in each group, how the outcome was defined, and whether participants had comparable opportunities for the outcome to be detected. The registry gives an enrollment of 276 overall but does not report the primary outcome counts or the analyzed group sizes.
The record describes laboratory-confirmed influenza and other respiratory viruses as the basis for assessing efficacy. In general, a binary outcome classifies each participant according to whether a defined event occurred or did not occur during follow-up. A group-level count can be used to describe event occurrence, while an efficacy analysis may compare event occurrence between groups. The registry does not specify the exact effect measure, the handling of multiple infections in one participant, or whether influenza and other respiratory-virus outcomes were combined or considered separately.
Why does the non-randomized design matter?
Random allocation is one way to balance measured and unmeasured characteristics between study groups on average. This study is recorded as non-randomized, so such balance cannot be assumed. In general, a difference between groups can reflect the intervention, differences in participant characteristics, or both. For example, factors associated with vaccination decisions or illness risk could also relate to the outcome. These are general concerns for non-randomized comparisons, not claims that any particular imbalance occurred in this study.
The comparator consists of siblings of intervention-arm participants, which defines a household-based relationship between groups. In general, people from the same household may share exposures or other characteristics. That relationship can be relevant to both the interpretation and analysis of outcomes. The registry does not report whether household pairing or clustering was included in the analysis. It also says that controls were surveilled irrespective of vaccination status, although the primary outcome description refers to unvaccinated siblings. How this was resolved analytically is not reported.
How should precision be understood?
A confidence interval is a statistical range intended to convey uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision; a wider interval indicates less precision. A confidence interval does not remove bias from a non-randomized design, and it does not correct problems caused by incomplete outcome ascertainment. No confidence interval or other precision estimate for the primary outcome is reported in the registry record.
A p-value, when used, measures how compatible the observed data are with a specified statistical model under a null hypothesis. It does not measure the size or clinical importance of an effect, and it does not demonstrate that the design is free from bias. The registry records one analysis but does not report its method, hypothesis, p-value, or whether any adjustment was made. No inferential result should therefore be inferred from the outcome title or from the existence of an analysis record.
What does symptom-triggered swabbing imply?
The registry describes nasal swabbing in the event of influenza-like illness. In general, this means laboratory confirmation depends on illness being recognized and a swab being collected and processed. Differences in symptom reporting, access to swabbing, timing, or specimen quality could affect detection. The record does not report the detailed surveillance protocol, test performance, adherence, or whether ascertainment was blinded. Because masking is recorded as none, readers should also note that outcome assessment was not described as masked.
What statistical plan is available?
The record lists three outcome measures and one analysis. Those counts do not reveal which outcomes were included in that analysis, what model was used, or whether the analysis followed a prespecified plan. The statistical analysis plan, including covariate selection, handling of repeated observations, subgroup methods, and sensitivity analyses, is not reported in the registry record.
In general, a model should reflect the type of outcome and the study design. For counts or binary participant outcomes, an analysis may compare event occurrence between groups, but the appropriate method depends on the outcome definition, follow-up, and dependence among observations. No particular model can be attributed to this study based on the registry entries. Where the posted results include recalculated estimates, those should be understood as simple unadjusted recalculations from posted summary statistics; the sponsor's own analysis takes precedence if a discrepancy is identified.
How should planning illustrations be read?
Any sample-size values displayed with the results are planning illustrations based on the observed effect, not the trial's own design justification and not observed power. Such illustrations depend on assumptions, including the stated significance level, allocation, approximation, and the fraction of the observed effect selected for detection. They describe hypothetical planning under those assumptions; they do not show that the study had a particular probability of finding an effect. The registry does not report the trial's own sample-size justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and one analysis. It does not report whether the outcomes were designated as primary or secondary in the statistical analysis plan beyond the primary and secondary outcome descriptions, nor whether any adjustment for multiple comparisons was planned or applied. When several outcomes or subgroup comparisons are examined, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can address that issue, but the registry record does not identify any such procedure.
The summary describes interest in whether efficacy, safety, and immune correlates varied with prior administration of pandemic influenza vaccine and/or LAIV. Whether these subgroup comparisons were conducted, how groups were defined, or whether they were prespecified is not reported. No subgroup findings should be inferred from the stated research aims.
Missing-data handling is not reported in the registry record. The record does not state how participants with no follow-up, missing swabs, incomplete illness reports, or unavailable laboratory results were treated. This matters because the primary outcome depends on illness surveillance and laboratory confirmation; participants without complete ascertainment may not have the same outcome status as participants with completed testing.
Analysis populations are also not reported. The record does not say whether results were based on all enrolled participants, those who received LAIV, participants with complete surveillance, or another defined group. The control-arm description allows surveillance regardless of vaccination status, while the primary endpoint description refers to unvaccinated sibling controls. The number of controls in each vaccination category and how they were handled in analysis are not reported. Without these details, the precise population represented by any efficacy comparison cannot be established from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Intervention | 0 | 164 | 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 |
|---|---|
| Intervention | 43 of 164 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Intervention |
|---|---|---|
| Rhinitis | Respiratory, thoracic and mediastinal disorders | 27 of 164 |
| Viral upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | 16 of 164 |
The registry safety fields list 0 serious adverse events among 164 participants at risk in the intervention group. They also list 43 other adverse events among 164 at risk. These are counts, not rates calculated here, and the registry does not report a control-group safety count in the posted fields. The serious adverse event terms are not listed, and deaths are not reported in the registry record.
A count of zero recorded serious adverse events does not by itself establish that no serious events occurred beyond the recorded surveillance, nor does it rule out uncommon risks. Interpretation depends on how events were defined, how actively they were sought, how long participants were followed, and whether reporting was complete. Those details are not reported in the registry record. The registry describes a secondary outcome concerning adverse events and serious adverse events in those who received LAIV, but the available figures do not give event types, timing, severity grading, or participant-level overlap.
The 43 other adverse events are not characterized by type or seriousness in the posted fields. They should not be treated as 43 distinct diagnoses or as evidence of a causal relationship with vaccination. The record does not describe how investigators assessed whether events were related to LAIV. The figures are therefore descriptive safety counts with limited context, not a complete comparative safety analysis.
12. What the Result Does, and Does Not, Mean
The record establishes that SNIFFLE-3 was designed to examine LAIV efficacy and safety in children using surveillance during the 2015/2016 influenza season. It identifies the intended primary comparison as laboratory-confirmed influenza and other respiratory viruses in children receiving LAIV versus sibling controls. It also records secondary interests in immune response and adverse events. These details describe the research question and study structure.
The record does not report the primary outcome results. It contains no group-specific laboratory-confirmed case counts, efficacy estimate, confidence interval, or p-value. Thus, the posted information cannot establish how the groups compared, how large any difference was, or how precise an estimate might be. It also cannot support a claim that vaccination did or did not change infection risk.
The design limits causal interpretation even if an observed comparison is available elsewhere. Participants were not randomly allocated, and the record does not report an adjusted analysis or baseline characteristics that would show how comparable the groups were. The sibling controls may share household context with intervention participants, but the record does not state whether this relationship was incorporated into the analysis. Control vaccination status is also uncertain because the endpoint description and arm description do not specify the same restriction.
The safety fields provide selected counts in the intervention group: 0 serious adverse events and 43 other adverse events among 164 at risk. They do not provide detailed event descriptions or a control comparison. These figures describe what is recorded, but they do not establish a complete safety profile.
In general, interpreting a clinical comparison requires both an estimate and its uncertainty, alongside attention to design, outcome measurement, and missing data. The registry record does not report enough statistical detail to make those assessments for the primary endpoint. The findings should therefore be understood as unreported in this registry record, rather than as evidence for either a positive or a null efficacy result.
13. Why This Trial Matters Statistically
This trial is statistically notable because it uses a non-randomized, sibling-control comparison to study a seasonal infection outcome. Such designs can be useful for studying outcomes in a real-world setting, but interpretation depends on understanding how participants entered each group and how differences between groups were handled. The registry confirms non-random allocation and no masking, while leaving the analysis methods and baseline group characteristics unreported.
The use of illness-triggered nasal swabbing also makes outcome ascertainment central to interpretation. Laboratory confirmation can provide a more specific outcome than symptoms alone, but detection depends on illness recognition, swab collection, and testing. The registry describes this surveillance approach without reporting its completeness or detailed procedures. Those features shape how confidently observed counts could represent infection occurrence across groups.
The household sibling comparison raises a further design consideration. Siblings may share aspects of their environment, while also differing in age, health, vaccination, or other characteristics. The registry does not state whether the analysis accounted for shared household context, nor does it clarify the vaccination status of controls used in analysis. Those are important elements for understanding the statistical contrast.
The record also illustrates the distinction between a stated research aim and a reported result. It describes efficacy, immune response, and adverse-event outcomes, but does not report an efficacy estimate or its precision. Statistical interpretation needs more than an outcome label: it requires group-specific data, a defined analysis, and information about uncertainty and missing observations. The available safety counts are similarly limited without event details or a comparator.
These considerations make the trial relevant for understanding how registry design details guide critical reading. The record supports a careful description of the question and methods, but not a quantitative conclusion about efficacy.
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.
Several limitations specific to this trial are apparent from the registry record. First, the study was non-randomized and unmasked. The record does not report baseline characteristics or an adjusted analysis, so it is not possible to assess whether the intervention and control groups were comparable or how measured differences were handled.
Second, the control-group definition is not fully consistent across descriptions. The primary outcome description refers to unvaccinated sibling controls, but the control-arm description says siblings were surveilled irrespective of vaccination status. The registry does not state the number of vaccinated controls, whether they were included in the efficacy analysis, or how vaccination status was handled.
Third, the primary outcome depends on laboratory confirmation following influenza-like illness. Detailed case definitions, swabbing procedures, testing methods, surveillance completeness, and outcome counts are not reported. The record also does not state how multiple respiratory viruses or repeated illness episodes were treated.
Fourth, key statistical details are unavailable: the analysis method, any covariate adjustment, handling of household dependence, missing-data procedures, analysis population, and multiplicity approach are not reported in the registry record. The enrollment field lists 276, while the brief summary describes an intended 200 children and at least 200 sibling controls; the record does not explain this difference in descriptions.
Finally, no primary efficacy estimate or uncertainty interval is reported. Safety reporting is limited to intervention-group counts without event terms or a control comparison. These omissions restrict assessment of effect magnitude, precision, and completeness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy & Safety of Nasal Influenza Immunisation in Children — NCT02549365.
- Registry record last updated 2019-12-11; status last verified 2019-12.
- Results first posted 2019-11-27.
- 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
NCT02549365, titled Efficacy & Safety of Nasal Influenza Immunisation in Children, is the Phase 4 SNIFFLE-3 study sponsored by Imperial College London. It is recorded as completed, non-randomized, unmasked, and parallel, with an enrollment of 276. The recorded start is 2015-10 and primary completion is 2016-04.
The intervention was LAIV according to national guidance, followed by symptom-triggered nasal swabbing. Sibling controls were monitored in the same way, with the control-arm description stating that surveillance applied irrespective of vaccination status. The primary outcome concerned laboratory-confirmed influenza and other respiratory viruses during the 2015/2016 influenza season. Secondary outcomes concerned immune response and adverse events.
The registry does not report an efficacy estimate, group-specific infection counts, confidence interval, p-value, or statistical analysis method. The posted intervention safety figures record 0 serious adverse events and 43 other adverse events among 164 at risk. Further detail on event types, missing data, analysis populations, and multiplicity is not reported in the registry record.