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 to Evaluate Immunological Equivalence Between Two Investigational Influenza Vaccines in Adults (H1N1) (NCT00979407), a randomized phase 3 study. The primary outcome is Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00979407 |
| Phase | Phase 3 |
| Condition | Influenza |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 336 |
| Arms in the primary outcome | 2 |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy male or female adults aged 18 to 60 years with influenza as the condition under study. The registry reports an enrollment of 336. The primary immunogenicity analysis was described as using the According-to-Protocol cohort at Day 21, comprising evaluable participants who received 1 vaccine dose and had assay results available for H1N1 antibodies from the specified blood sample.
Intervention
Two doses of investigational influenza vaccine GSK2340272A, administered intramuscularly in the deltoid region: the non-dominant arm at Day 0 and the dominant arm at Day 21.
Comparator
Two doses of investigational influenza vaccine GSK2340274A, administered by the same stated route, location, and schedule: the non-dominant arm at Day 0 and the dominant arm at Day 21.
Primary question
How did serum hemagglutination inhibition antibody titers against the Flu A/CAL/7/09 strain compare between the two vaccine groups at Day 21? The study’s stated purpose was to assess equivalence of the immune responses. The registry reports a geometric mean titer and 95% confidence interval for each group, but does not report an equivalence margin or a formal equivalence-test result.
3. Trial Design
This was a Phase 3, randomized, double-masked, parallel-group study sponsored by GlaxoSmithKline. It is listed as completed. The registry gives a start date of 2009-10-12 and a primary completion date of 2009-11-09. Enrollment was 336. The two groups received different investigational influenza vaccines, with both groups following the same two-dose schedule and administration procedure described in the registry.
The primary outcome was serum hemagglutination inhibition antibody titer against Flu A/CAL/7/09 at Day 21. The analysis is described as using the According-to-Protocol cohort for immunogenicity at Day 21. The registry reports 155 participants in each group for the primary outcome, whereas the adverse-event record gives 167 participants at risk in each group. Those counts relate to different reported analyses and should not be treated as interchangeable.
The brief study description also identifies safety and reactogenicity as a purpose. Secondary outcomes include seroconversion, seroprotection, antibody titers, and geometric mean fold rise, as well as a count of participants with potential immune-mediated diseases. Although the registry lists 18 outcome measures and reports 17 secondary outcomes, the available record does not give detailed estimates for every listed outcome. A statistical analysis plan, the method of sequence generation, allocation concealment details, and masking procedures are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Out of 336 subjects enrolled in the study, 2 subjects did not receive any vaccination.
Overall Study
| Stage | GSK2340272A GROUP | GSK2340274A GROUP |
|---|---|---|
| STARTED | 167 | 167 |
| COMPLETED | 161 | 160 |
| NOT COMPLETED | 6 | 7 |
Reasons for not completing this period:
| Reason | GSK2340272A GROUP | GSK2340274A GROUP |
|---|---|---|
| Withdrawal by Subject | 3 | 4 |
| Lost to Follow-up | 3 | 3 |
Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity at Day 21, which included all evaluable subjects who received 1 vaccine dose and for whom assay results were available for antibodies against H1N1 antigen for the blood sample taken 21 days after the first vaccine dose.
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 | GSK2340272A GROUP | GSK2340274A GROUP | Total |
|---|---|---|---|---|
| Participants analysed | 167 | 167 | 334 | |
| Age, Continuous | Years | 40.1 (SD 11.65) | 39.7 (SD 11.98) | 39.90 (SD 11.80) |
| Sex: Female, Male: Female | Participants | 87 | 77 | 164 |
| Sex: Female, Male: Male | Participants | 80 | 90 | 170 |
| Race/Ethnicity, Customized: Geographic ancestry – African heritage / african american | Participants | 2 | 3 | 5 |
| Race/Ethnicity, Customized: Geographic ancestry – White - arabic / north african heritage | Participants | 0 | 3 | 3 |
| Race/Ethnicity, Customized: Geographic ancestry – White - caucasian / european heritage | Participants | 165 | 161 | 326 |
6. Primary Endpoint
The registry lists the primary outcome as Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against Flu A/CAL/7/09 Strain of Influenza Disease, measured over At Day 21.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Titers |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the geometric mean titer (GMT) of serum hemagglutination inhibition (HI) antibodies against the Flu A/CAL/7/09 influenza strain, assessed at Day 21. HI titers are measurements of antibody activity in a laboratory assay. The registry identifies 1:10 as the reference seropositivity cutoff. A GMT summarizes titers on a multiplicative scale: conceptually, it is suited to measurements that can vary across orders of magnitude, rather than being an ordinary arithmetic average.
The reported GMTs describe the average antibody response on that scale in the analyzed participants. The 95% confidence intervals communicate uncertainty around each group estimate; they do not show the range of individual participants’ titers. The endpoint is relevant to the stated immunogenicity question because it measures antibody response to the specified strain at a specified time after vaccination. It is not, by itself, a clinical measure of influenza illness, prevention, or duration of protection.
The registry reports this endpoint for the According-to-Protocol immunogenicity cohort at Day 21. It describes eligible participants as evaluable, having received 1 vaccine dose, and having assay results available for the specified blood sample. The registry record does not state how missing assay results were handled beyond that cohort description.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At Day 21, the reported GMT was 383.6 for GSK2340272A, with a 95% confidence interval from 327.2 to 449.7. For GSK2340274A, the GMT was 339.1, with a 95% confidence interval from 285.4 to 403.0. Each estimate is a group summary for the analyzed participants, not a prediction of the response for an individual participant. The intervals express uncertainty in the estimated group means.
The interval ranges overlap, but overlap alone is not an equivalence test. The study’s stated aim was to assess immunological equivalence, yet an equivalence conclusion requires a prespecified margin and an analysis that evaluates the difference against that margin. Neither the margin nor a formal equivalence-test result is reported in the registry record. The posted GMTs and confidence intervals therefore describe the observed group responses but do not, on their own, establish that the responses met a defined equivalence criterion.
The primary outcome is reported for 155 participants in each group. The overall enrollment and the adverse-event analysis counts are not the denominators for this primary immunogenicity estimate. The registry describes the primary analysis population as an According-to-Protocol cohort and states that it included evaluable participants with assay results after 1 vaccine dose. The outcome is measured at Day 21, so this result addresses the antibody response at that assessment time; it does not describe later antibody levels.
No formal primary comparison estimate or primary p-value is reported in the registry record. The registry also does not report a confidence interval for the difference between the two GMTs. As a result, the precision of the contrast between groups cannot be read directly from separate group confidence intervals. A formal equivalence analysis would ordinarily focus on an estimated contrast and its uncertainty relative to a prespecified margin, rather than relying on whether separate intervals overlap.
In general, a confidence interval is a way to express the uncertainty associated with an estimate under the statistical model used. It is not a statement that a fixed percentage of individual titers lies inside the interval, and it does not establish equivalence merely because two intervals overlap. For this trial, the available registry result supports a descriptive account of the two Day 21 GMTs. The key inferential information needed to judge equivalence is not reported in the registry record.
9. Statistical Methods Explained
The primary outcome is a geometric mean, so its interpretation differs from that of an ordinary mean of raw measurements. In general, geometric means are useful when values are positive and their variation is naturally multiplicative. A common approach is to work with logarithms of the measurements, calculate a mean on that scale, and then transform the result back. This can make a distribution with a long upper tail more amenable to summary, but it does not remove the need to examine the underlying data and assumptions. The exact computational procedure for the reported GMT is not reported in the registry record.
What does the confidence interval describe?
The registry gives a 95% confidence interval for each group GMT. In general, a confidence interval describes the uncertainty in an estimate under the analysis assumptions. It is not an interval containing 95% of participant values, and it does not mean there is a 95% probability that a fixed, already-calculated parameter lies within that particular interval. Its width reflects the estimate’s precision under the method used. The registry does not describe the specific interval calculation, transformations, or variance estimator.
Separate group intervals are not the same as an interval for a between-group contrast. In general, a comparison is most directly assessed using an estimated difference or ratio and its confidence interval, together with the criterion relevant to the research question. That distinction matters for an equivalence objective: the aim is not merely to find similar-looking point estimates, but to determine whether plausible differences are bounded within a clinically or scientifically specified margin. The registry record does not report that margin or a formal contrast analysis.
What is special about an equivalence question?
In general, equivalence testing uses a prespecified range of differences considered acceptably small for the purpose of the study. Evidence for equivalence depends on whether the uncertainty around the between-group contrast lies within that range, using the test and confidence level specified in the analysis plan. A conventional test for a difference answers a different question: failure to detect a difference does not establish equivalence. Here, the stated objective is equivalence, but the registry does not report the decision rule, margin, or test outcome. Consequently, the posted group GMTs cannot be treated as a substitute for those missing elements.
How should the analysis population be understood?
The registry identifies the primary analysis population as the According-to-Protocol cohort for immunogenicity at Day 21. Its description refers to evaluable participants who received 1 vaccine dose and had assay results available for antibodies against the H1N1 antigen from the blood sample taken 21 days after the first vaccination. The reported primary counts are 155 in each group. This population definition makes clear that the estimate is not described as an analysis of every enrolled participant. The registry does not report a complementary intention-to-treat estimate, the detailed exclusions from the cohort, or reasons that participants were not evaluable.
In general, analysis-population choices can affect interpretation. A protocol-adherent population can focus on participants with sufficient data and adherence for the planned measurement, while an analysis including all randomized participants can preserve the original randomized comparison but may require explicit methods for unavailable outcomes. Different populations can answer related but not identical questions. Because the registry does not report additional primary analyses or detailed missing-data handling, robustness across populations cannot be assessed from this record.
Why does over-dispersion matter in general?
Over-dispersion occurs when observed variability is greater than a statistical model expects. In general, it can make standard errors too small if the model does not account for the extra variation, which can make confidence intervals appear more precise than warranted. It is a consideration for count or binary outcomes when their variability does not fit a simple model. The primary endpoint is a GMT, and the registry does not state that over-dispersion was assessed or that a particular model was used. It would therefore be inappropriate to claim that this issue affected the primary estimate.
What can planning calculations tell us?
In general, a sample-size calculation describes what a design might be expected to detect under specified assumptions; it does not show the probability that the completed study found a true effect. Planning illustrations based on an observed effect are especially dependent on that effect estimate and should not be interpreted as observed power. The registry’s sample-size assumptions describe an illustration using equal allocation, a two-sided significance level of 0.05, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These are planning assumptions, not a report of the trial’s original design justification. The trial’s own sample-size justification is not reported in the registry record.
Overall, the record supplies group-level GMTs and confidence intervals, but not the detailed primary statistical plan. In general, readers would need the prespecified equivalence margin, the contrast estimate and its uncertainty, the analysis method, and the handling of missing measurements to fully evaluate an equivalence analysis. Those details are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 18 outcome measures and reports 17 secondary outcomes, alongside the primary endpoint. The secondary outcomes include repeated or closely related descriptions of seroconversion, HI antibody titers, seroprotection, and geometric mean fold rise. The registry record does not explain whether these entries represent distinct assessments, different time points, or duplicated labels. The time frame is stated for the primary Day 21 endpoint and for the potential immune-mediated disease outcome, but a complete mapping of time points and analyses for every secondary outcome is not reported.
A multiplicity plan describes how interpretation or error rates are handled when several outcomes or comparisons are evaluated. In general, testing many outcomes without adjustment raises the chance that at least one result may appear unusual by chance. This does not make secondary results useless, but it affects how much confirmatory weight to give them. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a prespecified testing sequence. The available secondary p-value is identified as unadjusted.
The registry describes the primary analysis as using an According-to-Protocol immunogenicity cohort, and the primary outcome counts are 155 in each group. It does not report detailed participant flow into that cohort, the number and reasons for exclusions, or how missing assay results were handled. It also does not report a corresponding analysis of all randomized participants. These omissions limit assessment of whether the primary result is sensitive to the analysis population or missing measurements.
For the secondary potential immune-mediated disease outcome, the registry reports 167 participants at risk in each group. The difference between these denominators and the primary analysis counts reflects the distinct reported populations for those outcomes; the record does not provide a full reconciliation. The timing and completeness of surveillance for all other secondary outcomes are not reported in the registry record. Without a published analysis plan or further participant-level detail, it is not possible to determine whether every planned outcome and analysis is represented in the posted 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 |
|---|---|---|---|
| GSK2340272A GROUP | 9 | 167 | 5.4% |
| GSK2340274A GROUP | 11 | 167 | 6.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| GSK2340272A GROUP | 0 of 167 |
| GSK2340274A GROUP | 0 of 167 |
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 |
|---|---|
| GSK2340272A GROUP | 157 of 167 |
| GSK2340274A GROUP | 159 of 167 |
Most frequent serious adverse event terms
| Event term | Organ system | GSK2340272A GROUP | GSK2340274A GROUP |
|---|---|---|---|
| Nephrolithiasis | Renal and urinary disorders | 1 of 167 | 1 of 167 |
| Acute coronary syndrome | Cardiac disorders | 1 of 167 | 0 of 167 |
| Thyroid mass | Endocrine disorders | 1 of 167 | 0 of 167 |
| Anal fissure | Gastrointestinal disorders | 0 of 167 | 1 of 167 |
| Gastritis | Gastrointestinal disorders | 0 of 167 | 1 of 167 |
| Inguinal hernia | Gastrointestinal disorders | 1 of 167 | 0 of 167 |
| Appendicitis | Infections and infestations | 0 of 167 | 1 of 167 |
| Perirectal abscess | Infections and infestations | 0 of 167 | 1 of 167 |
| Pyelonephritis | Infections and infestations | 0 of 167 | 1 of 167 |
| Foot fracture | Injury, poisoning and procedural complications | 0 of 167 | 1 of 167 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GSK2340272A GROUP | GSK2340274A GROUP |
|---|---|---|---|
| Pain | General disorders | 153 of 167 | 151 of 167 |
| Myalgia | Musculoskeletal and connective tissue disorders | 85 of 167 | 104 of 167 |
| Fatigue | General disorders | 92 of 167 | 79 of 167 |
| Headache | Nervous system disorders | 83 of 167 | 80 of 167 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 53 of 167 | 66 of 167 |
| Chills | General disorders | 57 of 167 | 47 of 167 |
| Swelling | General disorders | 36 of 167 | 36 of 167 |
| Erythema | Skin and subcutaneous tissue disorders | 35 of 167 | 28 of 167 |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | 28 of 167 | 28 of 167 |
| Nasopharyngitis | Infections and infestations | 13 of 167 | 9 of 167 |
Serious events with the highest arm-level rate: acute coronary syndrome (0.6%), thyroid mass (0.6%), anal fissure (0.6%), gastritis (0.6%), inguinal hernia (0.6%).
The adverse-event record lists 9 serious adverse events among 167 participants at risk in the GSK2340272A group and 11 among 167 at risk in the GSK2340274A group. It reports 0 deaths in each group. These are counts for the safety population described in the record, not the primary immunogenicity analysis population. The counts alone do not establish whether an event was caused by vaccination.
The registry lists six serious-event terms—acute coronary syndrome, thyroid mass, anal fissure, gastritis, inguinal hernia, and appendicitis—each with a reported frequency of 0.6%. It does not specify how these terms were distributed between the vaccine groups in the available record. The nature, severity, timing, and relatedness assessments for the listed events are not reported in detail.
The record also reports other adverse events in 157 participants in the GSK2340272A group and 159 in the GSK2340274A group. These totals do not describe the types or seriousness of those events. In general, safety counts are interpreted alongside definitions, follow-up, event severity, and attribution procedures. Those details are not reported in the registry record, so the figures are descriptive and should not be treated as a complete account of comparative safety.
12. What the Result Does, and Does Not, Mean
The posted primary results show Day 21 GMT estimates of 383.6 for GSK2340272A and 339.1 for GSK2340274A, each with a 95% confidence interval. They describe the measured antibody responses in the reported According-to-Protocol immunogenicity cohort. They do not describe antibody levels for every enrolled participant, individual response distributions, clinical influenza outcomes, or antibody persistence beyond the stated assessment.
The trial’s objective was immunological equivalence, but the registry record does not report the equivalence margin or a formal equivalence-test result. Accordingly, the two group summaries should not be interpreted as proof that the vaccines are equivalent. Nor does the record establish that they are different: the reported estimates and separate intervals are not a complete test of either proposition. A formal conclusion requires the prespecified comparison and decision criterion, which are not reported in the registry record.
The study also included safety and reactogenicity as purposes, and the record gives adverse-event counts and deaths. These figures are descriptive. The registry information available does not provide enough detail about event relatedness, severity, timing, or the full pattern of events to support a broad comparative safety conclusion. Similarly, the limited detailed secondary results do not allow a complete account of all listed immunogenicity outcomes.
In general, a trial result answers a question defined by its population, intervention, comparator, outcome, and assessment time. This record addresses antibody titers against a specified strain at Day 21 in a described analysis population. It does not, on its own, establish clinical protection, comparative effectiveness against influenza illness, long-term response, or equivalence under a particular margin. Such conclusions would require evidence and analyses beyond the reported primary summaries.
13. Why This Trial Matters Statistically
This trial raises a central statistical distinction: showing that two estimates are not obviously far apart is not the same as demonstrating equivalence. Equivalence is a positive inferential claim, dependent on a prespecified acceptable range and a comparison whose uncertainty is evaluated against that range. The registry states an equivalence objective, while reporting group GMTs and confidence intervals; the margin and formal equivalence result are not reported. That gap illustrates why the design question and the displayed estimates must be interpreted together.
The choice of analysis population also matters. The primary immunogenicity result is reported for an According-to-Protocol cohort, while the adverse-event counts use a different set of denominators. Each population is tied to a particular outcome and should be interpreted in that context. Without detailed participant flow or complementary primary analyses, readers cannot assess how exclusions or unavailable assay results might affect the estimate.
The record also illustrates the distinction between a primary endpoint and a broad collection of secondary outcomes. Immunogenicity can be described through titers, seroconversion, seroprotection, and fold rise, but multiple measures do not automatically provide multiple independent confirmations. A clear testing hierarchy and multiplicity approach help distinguish confirmatory evidence from exploratory patterns; those details are not reported in the registry record.
Finally, confidence intervals are essential to interpreting precision, but separate intervals are not a substitute for an interval around the comparison of interest. The primary summaries communicate uncertainty in each group’s GMT, while the registry does not report a contrast interval. The case is a useful reminder that clear statistical interpretation depends not only on estimates, but also on the estimand, analysis population, decision rule, and reporting of uncertainty.
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 trial-specific limitations of interpretation follow from the registry record. The primary outcome is measured at Day 21, and the reported summaries do not describe later antibody responses. The record does not report a clinical influenza endpoint, so the GMT result cannot be used to characterize influenza illness or clinical protection. The primary analysis is described as According-to-Protocol, but detailed exclusions, participant flow, and a complementary analysis are not reported.
The study’s stated purpose was to assess immunological equivalence, but the equivalence margin and formal test result are not reported. A between-group primary contrast and its confidence interval are also not reported. Without those elements, the posted group summaries cannot establish whether a prespecified equivalence criterion was met. The exact method used to calculate the GMT confidence intervals is not reported either.
The registry lists many secondary outcomes but does not give detailed results for all of them. It does not report a multiplicity strategy or a hierarchy for secondary testing. The potential immune-mediated disease outcome is available, but the available record does not give the same level of detail for every listed immunogenicity endpoint. These gaps constrain an overall assessment of consistency across outcomes.
Safety reporting is also limited: counts are available, but details about event timing, severity, causality, and group allocation for the listed serious-event terms are not reported in the registry record. The statistical analysis plan, sample-size justification, allocation concealment, and full missing-data procedures are not reported. These are limitations of what can be concluded from the registry record, rather than proof that the procedures were or were not performed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate Immunological Equivalence Between Two Investigational Influenza Vaccines in Adults (H1N1) — NCT00979407.
- Registry record last updated 2018-08-06; status last verified 2017-05.
- Results first posted 2018-08-06.
- 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 describes a completed, randomized, double-masked, parallel Phase 3 study sponsored by GlaxoSmithKline, with enrollment of 336 adults aged 18 to 60 years. It compared two investigational adjuvanted influenza vaccines administered in two doses at Day 0 and Day 21. The primary endpoint was the Day 21 GMT of HI antibodies against Flu A/CAL/7/09, reported for an According-to-Protocol immunogenicity cohort.
The posted GMTs were 383.6 for GSK2340272A and 339.1 for GSK2340274A, with a 95% confidence interval for each group. The registry does not report an equivalence margin or formal equivalence-test result. Secondary and safety information is available in part, but detailed results and analysis methods are not reported for every outcome. The record therefore supports description of the reported antibody summaries, not a definitive equivalence or broad clinical conclusion.