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 A/H1N1-SOIV (Swine Flu) Vaccine With and Without Adjuvant in Non-Elderly and Elderly Adults (NCT00973349), a randomized phase 2, phase 3 study. The primary outcome is Immunogenicity Results After Each Vaccination by Vaccine Group, in Participants 18 to 64 Years of Age.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00973349 |
| Phase | Phase 2, Phase 3 |
| Condition | Influenza |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 2719 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adults 18 or more years of age were eligible. The study evaluated non-elderly and elderly participants, with the primary immunogenicity outcome specified for participants 18 to 64 years of age. Other registry outcomes use age groupings of 18 to 60 years and ≥61 years, or ≥65 years, so the age boundaries vary across the listed outcomes.
Intervention
The study evaluated egg-derived, inactivated A/H1N1 vaccine formulations with different antigen doses and MF59 content. The listed formulations include antigen doses of 3.75 µg, 7.5 µg, 15 µg or 30 µg, with MF59 absent or present at 50% or 100% for the formulations described in the registry record.
Comparator
Participants were randomized among vaccine groups. The comparison is therefore among formulations with different antigen and adjuvant content, rather than between vaccination and no vaccination. The registry record does not report a placebo group.
Primary question
For participants 18 to 64 years of age, the primary outcome assessed seroconversion and seroprotection after each vaccination, at 21 days after each vaccination. The registry record does not report the group-specific primary outcome results, so the extent to which these outcomes differed among formulations cannot be determined from the recorded information.
The clinical question is about the immune response and safety profile associated with alternative vaccine formulations. Seroconversion captures a specified change in HI antibody titer from before vaccination to after vaccination; seroprotection uses an HI titer threshold. These are measures of immune response, not direct measurements of whether participants subsequently became ill.
The design includes separate formulations for comparing antigen amounts and MF59 content, and the record lists outcomes in both younger and older age groups. However, it does not provide a single reported contrast that isolates the effect of changing only antigen dose or only adjuvant content. Without the group-level endpoint results and a stated primary comparison, the clinical question cannot be reduced to a particular pairwise difference or a ranking of formulations.
3. Trial Design
This was a randomized, single-blind, parallel-group study listed as Phase 2 and Phase 3. Its official title describes a dose-finding study of adjuvanted and non-adjuvanted, egg-derived, inactivated A/H1N1 vaccine formulations in healthy adults 18 or more years of age. The registry record lists enrollment of 2719 participants and a completed status. Novartis is identified as the sponsor.
The vaccine groups varied in antigen dose and MF59 content. Listed formulations include 3.75 µg antigen with 50% MF59; 7.5 µg with no MF59, 50% MF59 or 100% MF59; 15 µg with no MF59, 50% MF59 or 100% MF59; and 30 µg with no MF59. The outcome listings distinguish younger and older participants. The primary immunogenicity outcome is for participants 18 to 64 years of age, while other outcomes use 18 to 60 years, ≥61 years, or ≥65 years. The reason for these differing age boundaries is not reported in the registry record.
The primary outcome timeframe is 21 days after each vaccination. Secondary outcomes include geometric mean HI titers, seroconversion, HI titers meeting the ≥1:40 threshold, geometric mean ratios from baseline, and solicited local and systemic reactions after the first and second vaccinations. These outcome descriptions indicate that immune response and short-term reactions were assessed after vaccination, but the registry record does not describe the full visit schedule or the duration of safety follow-up.
Although the study is randomized and single-blind, further details about the randomization procedure, allocation concealment, and who was blinded are not reported in the registry record. The protocol’s sample-size justification, planned interim analyses, and detailed statistical analysis plan are also not reported in the registry record. Enrollment is the number recorded for the study; it should not be treated as the analysis denominator for every outcome. For the primary outcome, the stated analysis population is the per protocol population.
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.
Only the first 6 of 16 groups are shown.
Overall Study
| Stage | 3.75_(50)MF59 (18-64 Years) | 7.5 w/o MF59 (18-64 Years) | 7.5_(50)MF59 (18-64 Years) | 7.5_(100)MF59 (18-64 Years) | 15 w/o MF59 (18-64 Years) | 15_(50)MF59 (18-64 Years) |
|---|---|---|---|---|---|---|
| STARTED | 170 | 168 | 171 | 168 | 170 | 169 |
| COMPLETED | 166 | 165 | 166 | 163 | 165 | 165 |
| NOT COMPLETED | 4 | 3 | 5 | 5 | 5 | 4 |
Reasons for not completing this period:
| Reason | 3.75_(50)MF59 (18-64 Years) | 7.5 w/o MF59 (18-64 Years) | 7.5_(50)MF59 (18-64 Years) | 7.5_(100)MF59 (18-64 Years) | 15 w/o MF59 (18-64 Years) | 15_(50)MF59 (18-64 Years) |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 |
| Withdrawal by Subject | 1 | 2 | 2 | 3 | 2 | 0 |
| Lost to Follow-up | 3 | 1 | 2 | 2 | 1 | 3 |
| Inappropriate enrolment | 0 | 0 | 1 | 0 | 0 | 0 |
| Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 |
| Unable to classify | 0 | 0 | 0 | 0 | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was based on the per protocol population.
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: ITT population for immunology assessments. Participants from one center excluded for GCP issues.
Only the first 6 of 17 groups are shown.
| Characteristic | Unit | 3.75_(50)MF59 (18 to 64) | 7.5 w/o MF59 (18 to 64) | 7.5_(50)MF59 (18 to 64) | 7.5_(100)MF59 (18 to 64) | 15 w/o MF59 (18 to 64) | 15_(50)MF59 (18 to 64) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 155 | 153 | 157 | 153 | 155 | 154 | |
| Age, Continuous | years | 40.3 (SD 12.8) | 39.8 (SD 12.9) | 39.1 (SD 13.5) | 40.6 (SD 12.2) | 41.8 (SD 12.9) | 39.7 (SD 13.1) |
| Sex/Gender, Customized: Male(18 to 64 or ≥65 years) | participants | 61 | 62 | 57 | 59 | 57 | 69 |
| Sex/Gender, Customized: Female(18 to 64 or ≥65 yrs) | participants | 94 | 91 | 100 | 94 | 98 | 85 |
6. Primary Endpoint
The registry lists the primary outcome as Immunogenicity Results After Each Vaccination by Vaccine Group, in Participants 18 to 64 Years of Age, measured over 21 days after each vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is described as immunogenicity results after each vaccination by vaccine group in participants 18 to 64 years of age. It is expressed as a number of participants, and the timeframe is 21 days after each vaccination. The endpoint description includes two related classifications based on HI antibody titers: seroconversion and seroprotection.
Seroconversion follows the definition attributed in the registry record to CBER. It includes participants whose prevaccination HI titer was <1:10 and whose post-vaccination titer was >40, or participants whose prevaccination titer was >10 and whose post-vaccination titer rose at least four-fold. Seroprotection is defined as having an HI antibody titer ≥1:40. These definitions distinguish a change from an individual’s baseline from reaching a specified post-vaccination titer threshold.
General statistical explanation: immune-response endpoints are used to describe whether participants meet prespecified antibody-based criteria after vaccination. They can compare measured responses among groups, but they do not by themselves establish how often a clinical illness occurs or how well a vaccine prevents illness. The relationship between an antibody measure and clinical protection is not quantified in the registry record.
The registry record does not report the number of participants meeting either criterion in each group, nor the corresponding uncertainty estimates. It therefore identifies what the endpoint was intended to measure without allowing the size or precision of any group difference to be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of eight vaccine formulations and lists immunogenicity and safety outcomes across age groups. It does not include the group-specific primary immunogenicity results in the registry record for this analysis. Accordingly, no conclusion about which formulation had a larger or smaller seroconversion or seroprotection result can be drawn from these recorded details. The endpoint definition and timing are stated, but the observed values and their uncertainty are not reported in the registry record.
The primary analysis is identified as based on the per protocol population. This means the endpoint was not described as an analysis of every participant enrolled, although the criteria used to determine inclusion in that population are not reported in the registry record. The enrolled total of 2719 does not supply the denominator for the primary outcome in each group. Denominators for that analysis are not reported in the registry record.
The registry lists a range of secondary outcomes: geometric mean HI titers, seroconversion and the HI ≥1:40 threshold in age-specific groups, geometric mean ratios from baseline, and solicited local and systemic reactions after the first and second vaccinations. The number of outcome measures is listed as 10 and the number of analyses as 28. These counts indicate that the record contains multiple outcome and analysis entries, but they do not establish which comparisons were considered confirmatory or how interpretation was adjusted for the number of tests.
General statistical explanation: an estimate describes the observed result in a group or contrast, while a confidence interval describes the range of values reasonably compatible with the data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, but neither an estimate nor its interval resolves design limitations or establishes clinical importance by itself. No confidence intervals, p-values, or group-level immunogenicity estimates are reported in the registry record, so statistical significance and precision cannot be evaluated.
Safety entries list serious adverse event counts and the number at risk for each vaccine group, as well as frequently listed serious event terms. These descriptive counts are not a substitute for a prespecified comparative safety analysis. The registry record does not provide a statistical comparison of serious adverse events between formulations, and the context needed to interpret the listed event-term percentages is not fully described. The counts should therefore be read as recorded observations, not as proof that one formulation is safer or less safe than another.
Overall, the record supports a description of the study design, intended immune-response measures, and some safety counts. It does not support a quantitative assessment of the primary outcome, a claim about the size of any formulation effect, or a judgment about the statistical certainty of such an effect.
9. Statistical Methods Explained
The study used a randomized, parallel-group design, with participants assigned among vaccine formulations. Randomization is intended, in general, to reduce systematic differences between groups at the start of a study. It does not guarantee that groups are identical, and it does not eliminate uncertainty caused by limited sample sizes, missing observations, or the way outcomes are measured. The registry record does not describe the randomization sequence or allocation concealment, so those implementation details cannot be assessed.
What does single-blind mean in this record?
The registry labels the study single-blind. In general, masking can reduce the risk that expectations affect treatment delivery, reporting, or assessment. The record does not identify which study participants or staff were blinded, how masking was maintained, or whether it could have been compromised by differences among formulations. Those details are not reported in the registry record, so the practical effect of blinding cannot be judged from the design label alone.
What do the immune-response measures represent?
The primary outcome uses participant counts for seroconversion and seroprotection after each vaccination, with assessment 21 days after each vaccination. Seroconversion is defined using both the baseline and post-vaccination HI antibody titers. The definition allows either a transition from a prevaccination titer <1:10 to a post-vaccination titer >40, or a minimum four-fold rise when the prevaccination titer was >10. Seroprotection is defined using a post-vaccination HI titer ≥1:40. These criteria produce binary classifications for individual participants: each person either meets a stated criterion or does not, based on the recorded titers and definition.
General statistical explanation: a count of participants meeting a binary endpoint can be compared across groups, but the count alone is not enough to determine the size or precision of a difference. The number assessed in each group is needed to interpret the count as a rate, and an uncertainty estimate is needed to assess precision. Neither the group-level primary outcome counts nor their analysis denominators are reported in the registry record.
Why are geometric means included as secondary outcomes?
The secondary outcomes include geometric mean HI titers and geometric mean ratios from baseline. General statistical explanation: antibody titers often have a multiplicative scale, so geometric summaries can be useful when values are skewed and changes are naturally expressed as fold differences. A geometric mean is calculated on a transformed scale and then returned to the original scale; it is not the same summary as an arithmetic average. The registry record lists these outcomes but does not report their values, the specific analysis method, or uncertainty estimates.
How should the age-group analyses be understood?
The primary outcome is specified for participants 18 to 64 years of age. Secondary outcomes include age groupings of 18 to 60 years and ≥61 years, as well as outcomes in 18 to 64 years and ≥65 years. These are not interchangeable definitions. Comparisons across results must take account of the age boundaries actually used for each outcome. The registry record does not explain why the boundaries differ, and it does not provide detailed age-stratified outcome estimates for assessing whether responses varied by age.
What does the safety counting approach show?
The safety information records numbers at risk and numbers affected by serious adverse events and other adverse events for each listed group. General statistical explanation: these counts provide descriptive information about events observed during the recorded safety assessment. Comparing counts without considering denominators, follow-up time, event definitions, and uncertainty can be misleading. Even when denominators are available, an unadjusted difference in event counts is not necessarily evidence of a causal difference between formulations. The registry record does not provide the full follow-up time, detailed event-collection rules, or comparative statistical analysis needed for a fuller interpretation.
What can be inferred from the analysis labels?
The primary outcome analysis is described as per protocol. In general, a per protocol analysis considers participants who meet specified requirements for study participation and outcome assessment. It may help describe outcomes among participants who followed the study procedures, but the exclusions used to define it can affect the groups being compared. A separate intention-to-treat analysis would generally retain participants according to randomized assignment, but such an analysis is not described in the record. The specific per protocol criteria and the handling of participants with missing measurements are not reported in the registry record.
The record lists 10 outcome measures and 28 analyses. General statistical explanation: when many outcomes, time points, age groups, or pairwise comparisons are examined, the chance of at least one apparently unusual result can increase if each is interpreted as an independent test. Approaches such as prespecifying a primary comparison or adjusting for multiplicity can help control that issue, but the choice depends on the study’s aims and analysis plan. The registry record does not report whether or how multiplicity was addressed.
The posted material includes no primary outcome estimates or inferential statistics in the registry record analyzed for this narrative. As a result, there is no basis for describing a recalculated effect, evaluating the agreement of a recalculation with a sponsor analysis, or discussing planning illustrations based on an observed effect. Any sample-size justification for the actual study, including assumptions about effect size and statistical power, is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 10 outcome measures and 28 analyses. The outcomes cover immune-response measures, age-specific groups, assessments after each vaccination, and solicited local and systemic reactions. When several outcomes or comparisons are analyzed, multiplicity is a concern: in general, conducting many tests can increase the chance of observing at least one result that appears statistically unusual even when there is no underlying difference. Interpretation therefore depends on which outcomes and contrasts were prespecified as primary, whether secondary analyses were exploratory, and whether any adjustment strategy was planned.
The record identifies a primary outcome for participants 18 to 64 years of age, but the detailed statistical analysis plan and the hierarchy of comparisons are not reported in the registry record. It does not state whether multiplicity was controlled, how the 28 analyses were organized, or how any subgroup and repeated-time assessments were handled. The existence of multiple analyses alone does not show that a particular result is biased; it does mean that results need to be interpreted in the context of a prespecified plan, which is unavailable.
The primary outcome is described as analyzed in the per protocol population. The criteria for that population, the number included in each group, and the treatment of participants with missing or unusable HI titer measurements are not reported in the registry record. No imputation method or sensitivity analysis for missing outcome data is described. Missingness can affect interpretation if the likelihood of having an observed measurement differs across groups or is related to participants’ outcomes. Without details on the amount, reasons, and handling of missingness, the potential impact cannot be assessed.
The record does not describe an intention-to-treat analysis, interim analyses, or a sample-size justification. These items should not be inferred from the randomized design or enrollment total. The absence of a reported detail is not evidence that a method was or was not used; it means that the registry record does not document it.
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 |
|---|---|---|---|
| 3.75_(50)MF59 | 5 | 170 | 2.9% |
| 7.5 w/o MF59 | 5 | 168 | 3.0% |
| 7.5_(50)MF59 | 5 | 171 | 2.9% |
| 7.5_(100)MF59 | 5 | 165 | 3.0% |
| 15 w/o MF59 | 6 | 170 | 3.5% |
| 15_(50)MF59 | 6 | 169 | 3.6% |
| 15_(100)MF59 | 5 | 174 | 2.9% |
| 30 w/o MF59 | 7 | 168 | 4.2% |
| 3.75_(50)MF59 (Above 65 Yrs) | 9 | 170 | 5.3% |
| 7.5 w/o MF59 (≥65 Yrs) | 16 | 166 | 9.6% |
| 7.5_(50)MF59 (≥65 Yrs) | 18 | 173 | 10.4% |
| 7.5_(100)MF59 (≥65 Yrs) | 11 | 169 | 6.5% |
| 15 w/o MF59 (≥ 65 Yrs) | 12 | 169 | 7.1% |
| 15_(50)MF59 (≥65 Yrs) | 20 | 171 | 11.7% |
| 15_(100)MF59 (≥65 Yrs) | 14 | 169 | 8.3% |
| 30 w/o MF59 (≥65 Yrs) | 10 | 167 | 6.0% |
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 |
|---|---|
| 3.75_(50)MF59 | 125 of 170 |
| 7.5 w/o MF59 | 108 of 168 |
| 7.5_(50)MF59 | 121 of 171 |
| 7.5_(100)MF59 | 128 of 165 |
| 15 w/o MF59 | 113 of 170 |
| 15_(50)MF59 | 122 of 169 |
Most frequent serious adverse event terms
| Event term | Organ system | 3.75_(50)MF59 | 7.5 w/o MF59 | 7.5_(50)MF59 | 7.5_(100)MF59 | 15 w/o MF59 | 15_(50)MF59 |
|---|---|---|---|---|---|---|---|
| Abortion Spontaneous | Pregnancy, puerperium and perinatal conditions | 0 of 170 | 1 of 168 | 1 of 171 | 0 of 165 | 1 of 170 | 1 of 169 |
| Road Traffic Accident | Injury, poisoning and procedural complications | 1 of 170 | 0 of 168 | 2 of 171 | 0 of 165 | 0 of 170 | 0 of 169 |
| Myocardial Infarction | Cardiac disorders | 1 of 170 | 0 of 168 | 0 of 171 | 1 of 165 | 0 of 170 | 1 of 169 |
| Cellulitis | Infections and infestations | 0 of 170 | 0 of 168 | 1 of 171 | 0 of 165 | 1 of 170 | 0 of 169 |
| Viith Nerve Paralysis | Nervous system disorders | 0 of 170 | 0 of 168 | 0 of 171 | 1 of 165 | 0 of 170 | 1 of 169 |
| Cerebral Infarction | Nervous system disorders | 0 of 170 | 0 of 168 | 0 of 171 | 0 of 165 | 0 of 170 | 1 of 169 |
| Dehydration | General disorders | 0 of 170 | 0 of 168 | 0 of 171 | 0 of 165 | 0 of 170 | 1 of 169 |
| Depression | Psychiatric disorders | 0 of 170 | 1 of 168 | 0 of 171 | 0 of 165 | 0 of 170 | 0 of 169 |
| Pneumonia | Infections and infestations | 0 of 170 | 0 of 168 | 0 of 171 | 0 of 165 | 1 of 170 | 0 of 169 |
| Retinal Detachment | Eye disorders | 1 of 170 | 0 of 168 | 0 of 171 | 0 of 165 | 0 of 170 | 0 of 169 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 3.75_(50)MF59 | 7.5 w/o MF59 | 7.5_(50)MF59 | 7.5_(100)MF59 | 15 w/o MF59 | 15_(50)MF59 |
|---|---|---|---|---|---|---|---|
| Injection site pain | General disorders | 97 of 170 | 68 of 168 | 90 of 171 | 109 of 165 | 72 of 170 | 102 of 169 |
| Headache | Nervous system disorders | 56 of 170 | 49 of 168 | 51 of 171 | 42 of 165 | 60 of 170 | 55 of 169 |
| Myalgia | Musculoskeletal and connective tissue disorders | 40 of 170 | 34 of 168 | 32 of 171 | 43 of 165 | 32 of 170 | 39 of 169 |
| Fatigue | General disorders | 33 of 170 | 33 of 168 | 35 of 171 | 31 of 165 | 31 of 170 | 37 of 169 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 20 of 170 | 17 of 168 | 22 of 171 | 22 of 165 | 22 of 170 | 16 of 169 |
| Nausea | Gastrointestinal disorders | 20 of 170 | 18 of 168 | 25 of 171 | 15 of 165 | 16 of 170 | 18 of 169 |
| Diarrhoea | Gastrointestinal disorders | 17 of 170 | 18 of 168 | 24 of 171 | 13 of 165 | 21 of 170 | 18 of 169 |
| Injection site erythema | General disorders | 23 of 170 | 15 of 168 | 21 of 171 | 14 of 165 | 15 of 170 | 11 of 169 |
| Chills | General disorders | 15 of 170 | 13 of 168 | 15 of 171 | 12 of 165 | 13 of 170 | 15 of 169 |
| Injection site induration | General disorders | 15 of 170 | 9 of 168 | 15 of 171 | 13 of 165 | 12 of 170 | 14 of 169 |
Serious events with the highest arm-level rate: osteoarthritis (2.3%), prostate cancer (1.8%), influenza (1.2%), pneumonia (1.2%), coronary artery disease (1.2%).
For each vaccine group, the registry lists the number at risk and the number affected by serious adverse events. For example, the 3.75_(50)MF59 group among the younger participants is listed with 170 at risk and 5 affected; the 7.5 w/o MF59 group is listed with 168 at risk and 5 affected. In the groups identified as ≥65 years, the 3.75_(50)MF59 group is listed with 170 at risk and 9 affected, while the 15_(50)MF59 group is listed with 171 at risk and 20 affected. These are recorded counts, not adjusted comparisons.
The registry also lists serious event terms and percentages: Osteoarthritis at 2.3%, Prostate Cancer at 1.8%, and Influenza, Pneumonia, Coronary artery disease, and Spinal Column Stenosis at 1.2% each. The denominator and the precise context for these term percentages are not reported in the registry record, so they should not be interpreted as group-specific rates.
General statistical explanation: safety counts are influenced by the number of participants assessed, the duration and completeness of follow-up, and the definitions used to classify events. A group count by itself does not establish that an event was caused by vaccination or that risk differs between groups. The record does not report deaths for these groups; death counts are not reported in the registry record. It also does not provide comparative estimates or uncertainty intervals for serious adverse events.
12. What the Result Does, and Does Not, Mean
The study was designed to assess immunogenicity, safety and tolerability across A/H1N1 vaccine formulations differing in antigen dose and MF59 content. The registry record specifies how the primary immune-response outcome was defined and when it was assessed: 21 days after each vaccination. It also lists secondary immune-response and safety outcomes, including measurements in older participants and reaction assessments after the first and second vaccinations.
Those design details explain what the study set out to measure, but they do not show the resulting immune responses. Group-specific seroconversion counts, seroprotection counts, HI titers, geometric mean ratios, and corresponding uncertainty estimates are not reported in the registry record. Consequently, the posted information does not establish the direction, size, precision, or statistical significance of a difference among the vaccine formulations.
The safety entries are descriptive counts of serious adverse events and other adverse events in the listed groups. They do not by themselves establish a causal relationship to a vaccine formulation or a comparative safety effect. The record’s serious event terms and percentages also lack enough denominator context to interpret them as group-specific risks.
General statistical explanation: a statistically detectable difference, if reported, would not automatically establish that the difference is clinically important. Conversely, an imprecise estimate would not establish that groups are equivalent. Assessing these questions requires the observed estimates, their uncertainty, the clinical context, and an analysis plan that identifies the intended comparisons. Those results and details are not reported in the registry record used for this account.
The conclusions that can be drawn are therefore limited to the design and outcome definitions: this was a randomized, single-blind, parallel-group study of multiple formulations in healthy adults, with immunogenicity assessments and safety monitoring. No claim that a particular formulation performed better, worse, or similarly to another is supported by the recorded outcome information.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it compares multiple formulations rather than a single vaccine with a no-vaccine control. Antigen dose and MF59 content vary across the listed groups, while outcomes are also considered across age categories. This creates a structured set of comparisons, but it also makes the interpretation dependent on knowing which contrasts were planned and how the multiple outcomes and analyses were handled.
The primary endpoint combines two antibody-based classifications, seroconversion and seroprotection. They answer related but different questions: one concerns change from baseline under defined criteria, while the other concerns reaching the HI ≥1:40 threshold. Treating these measures as interchangeable could obscure what each represents. The registry record defines them, but does not report the group-level results needed to compare them.
The age boundaries are another important statistical detail. Outcomes are listed for participants 18 to 64 years of age, 18 to 60 years of age, ≥61 years of age, and ≥65 years of age. Differences in age definitions can complicate comparisons across outcomes and analyses. The reasons for using those boundaries are not reported in the registry record.
Finally, the record illustrates the distinction between describing a trial’s design and interpreting its results. Randomization and masking are relevant design features, and the enrollment total gives context for the study’s scale. Neither feature substitutes for outcome estimates, denominators, uncertainty intervals, missing-data information, and a prespecified analysis plan. Because the primary immunogenicity results are not reported in the registry record, the main statistical contribution of the record is to define the questions and measures rather than to resolve a comparison among formulations.
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 important limitation for interpreting outcomes is that group-specific primary immunogenicity results are not reported in the registry record. The endpoint definitions and timeframe are available, but no seroconversion or seroprotection counts, group denominators for the primary analysis, effect estimates, confidence intervals, or p-values are included in the registry record analyzed. The size and precision of any contrast therefore cannot be evaluated.
The primary outcome is based on the per protocol population, but the criteria for that population and its group-specific size are not reported in the registry record. The record also does not describe missing-data handling, the number of participants with unavailable titer measurements, or sensitivity analyses. These omissions limit assessment of how exclusions or missing measurements might influence the comparison.
The study lists multiple outcomes and analyses and uses different age boundaries across outcome descriptions. The statistical plan, primary comparison hierarchy, and multiplicity approach are not reported in the registry record. The reason for the age-group differences is also not reported. These details matter when deciding how to interpret any isolated outcome or subgroup result, but no such result values are available.
Further design details are not reported in the registry record, including the randomization procedure, allocation concealment, the identities of those blinded, and the full follow-up schedule. The safety counts are not accompanied by a comparative analysis or complete denominator context for the listed serious event terms. These are limitations of the recorded information and do not establish that the study failed to use methods that are not documented.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Immunogenicity of A/H1N1-SOIV (Swine Flu) Vaccine With and Without Adjuvant in Non-Elderly and Elderly Adults — NCT00973349.
- Registry record last updated 2015-12-07; status last verified 2015-10.
- Results first posted 2011-05-25.
- 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
NCT00973349 is a completed randomized, single-blind, parallel-group Phase 2 and Phase 3 study sponsored by Novartis. The registry lists enrollment of 2719 healthy adults 18 or more years of age and describes eight A/H1N1 vaccine formulations with differing antigen doses and MF59 content.
The primary outcome assessed seroconversion and seroprotection in participants 18 to 64 years of age, 21 days after each vaccination, using specified HI antibody criteria. Secondary outcomes include geometric mean HI titers, geometric mean ratios, age-group-specific immune-response measures, and solicited local and systemic reactions after the first and second vaccinations. The primary analysis population is described as per protocol.
Serious adverse event counts and selected event terms are listed, but comparative safety estimates are not reported. Group-specific primary immunogenicity results, uncertainty estimates, detailed missing-data methods, and the statistical plan are not reported in the registry record. The record therefore describes the trial’s questions and methods more fully than its comparative outcome results.