Sanofi H1N1 Influenza Vaccine Administered at Two Dose Levels in Adult and Elderly Populations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sanofi H1N1 Influenza Vaccine Administered at Two Dose Levels in Adult and Elderly Populations (NCT00943631), a randomized phase 2 study. The primary outcome is Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs).

2. Clinical Question

3. Trial Design

The registry identifies this as a randomized, triple-masked, parallel-group phase II study of an unadjuvanted Sanofi Pasteur H1N1 influenza vaccine. The sponsor is the National Institute of Allergy and Infectious Diseases (NIAID). The condition is influenza. The record lists enrollment as 406, status as completed, a start date of 2009-08, and primary completion in 2010-03. The study summary describes a planned enrollment of up to 450 healthy adults; the posted enrollment figure is 406.

Participants were assigned to one of two vaccine dose groups. The 15 mcg group received vaccine on Days 0 and 21, as did the 30 mcg group. The arm descriptions specify planned age-stratum allocations within each group, while the posted outcome denominators vary by endpoint. Those denominators should be read as the participants contributing to each reported outcome, not assumed to be identical across analyses.

The primary endpoint counted participants reporting vaccine-associated serious adverse events over the period from Day 0 through Day 180 after the last vaccination. A study clinician licensed to make medical diagnoses determined whether an event was associated with vaccination. The registry defines serious events by consequences such as death, life-threatening illness, persistent or significant disability, inpatient hospitalization or its prolongation, congenital anomaly or birth defect, or an event that might have jeopardized the participant or required intervention to prevent one of those outcomes.

Secondary outcomes focus on HAI antibody titers in age strata and at follow-up points after vaccination. They include four-fold or greater increases from baseline and titers of 1:40 or greater. The registry record does not report the full analysis plan, sample-size justification, or details of the masking procedures. These details should not be inferred from the design labels.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Vaccine-associated Serious Adverse Events (SAEs), measured over Day 0 through Day 180 after last vaccination.

The primary endpoint is the number of participants reporting vaccine-associated serious adverse events from Day 0 through Day 180 after the last vaccination. It is a participant-count endpoint: a person is counted if a qualifying serious event was reported and judged by a study clinician to be associated with vaccination. The registry definition covers serious medical consequences, including death, a life-threatening event, persistent or significant disability, inpatient hospitalization or prolongation of hospitalization, a congenital anomaly or birth defect, and events requiring intervention to prevent such outcomes.

This kind of endpoint is used to capture serious safety events over a defined observation period. It is distinct from a count of all symptoms or all adverse events, because the outcome is restricted to events meeting the record's seriousness criteria and additionally judged vaccine-associated. The registry reports zero participants with this primary outcome in the 15 mcg group and zero in the 30 mcg group. Separately, it reports other adverse events, which are not interchangeable with the primary endpoint.

A zero count is an observed result, not proof that the underlying risk is zero. Rare events may not occur in a study even when a risk exists, and the record's primary result does not establish the absence of every possible safety concern. The registry record does not report a detailed statistical analysis plan for this endpoint. Interpretation should therefore remain tied to the reported counts, their follow-up definition, and the study population.

7. Results Posted in the Registry

• H1N1 Vaccine 30 Mcg: 0.0% (0/204) versus 0.0% (0/202) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants in the 65 Years and Older Age Stratum With 4-fold or Greater HAI Antibody Titer Increases Against Influenza H1N1 2009 Virus at 8-10 Days Following 2 Doses of H1N1 Vaccine

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • H1N1 Vaccine 30 Mcg: 84.0% (84/100) versus 72.3% (68/94) on control; risk difference 11.7 percentage points (95% CI 0.1 to 23.2), risk ratio 1.16 (1.00–1.35); unadjusted two-proportion z-test p = 0.049.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for H1N1 Vaccine 30 Mcg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants in the 65 Years and Older Age Stratum With 4-fold or Greater HAI Antibody Titer Increases Against Influenza H1N1 2009 Virus at 21 Days Following 2 Doses of H1N1 Vaccine

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • H1N1 Vaccine 30 Mcg: 81.2% (82/101) versus 73.7% (70/95) on control; risk difference 7.5 percentage points (95% CI -4.2 to 19.2), risk ratio 1.10 (0.95–1.28); unadjusted two-proportion z-test p = 0.208.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between H1N1 Vaccine 30 Mcg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants in the 65 Years and Older Age Stratum With a Serum Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater Against Influenza H1N1 2009 Virus at 8-10 Days Following 2 Doses of H1N1 Vaccine

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • H1N1 Vaccine 30 Mcg: 92.0% (92/100) versus 85.1% (80/94) on control; risk difference 6.9 percentage points (95% CI -2.1 to 15.8), risk ratio 1.08 (0.98–1.20); unadjusted two-proportion z-test p = 0.130.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between H1N1 Vaccine 30 Mcg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes examine antibody responses rather than serious adverse events. Across the reported older-adult results, the observed response proportions are higher in the 30 mcg group for the listed outcomes. The estimated between-group differences are not equally precise: one earlier four-fold-rise comparison has a confidence interval just above zero, while the later four-fold-rise and the earlier HAI-threshold comparisons have intervals that include zero. These patterns should be considered together with the endpoint definitions, time points, and denominators rather than as a single uniform dose effect.

These immune outcomes are related to the study's immunogenicity aim, but they do not determine the primary safety result. The primary endpoint counted vaccine-associated serious adverse events through Day 180 after the last vaccination; the secondary outcomes measured antibody responses at specific follow-up times. A difference in an antibody measure is not itself evidence of a difference in serious adverse events, and the primary zero counts do not determine the size of an immune response.

The registry lists six secondary outcome measures, while only three numerical secondary results appear in the record. The remaining secondary results are not reported in the registry record. This incomplete outcome picture makes it difficult to assess the full pattern across all planned or registered measures.

The secondary comparisons are unadjusted, and the registry record does not report a multiplicity strategy. General explanation: when several outcomes or time points are tested, the chance of obtaining at least one apparently unusual result can increase, even if there is no real effect across the family of outcomes. Adjustment methods or a clearly prespecified hierarchy can address that issue, but neither is reported. Consequently, an isolated unadjusted p-value should be treated as exploratory rather than as conclusive evidence. The secondary data are useful for describing the reported immune-response pattern, but they carry less inferential weight than a fully specified and multiplicity-aware analysis would.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants in the 18-64 Year Age Stratum With 4-fold or Greater HAI Antibody Titer Increases Against Influenza H1N1 2009 Virus at 8-10 and 21 Days Following 2 Doses of H1N1 Vaccine
• Number of Participants in the 65 Years and Older Age Stratum With 4-fold or Greater HAI Antibody Titer Increases Against Influenza H1N1 2009 Virus at 8-10 Days Following 2 Doses of H1N1 Vaccine
• Number of Participants in the 65 Years and Older Age Stratum With 4-fold or Greater HAI Antibody Titer Increases Against Influenza H1N1 2009 Virus at 21 Days Following 2 Doses of H1N1 Vaccine
• Number of Participants in the 18-64 Year Age Stratum With a Serum Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater Against Influenza H1N1 2009 Virus at 8-10 and 21 Days Following 2 Doses of H1N1 Vaccine
• Number of Participants in the 65 Years and Older Age Stratum With a Serum Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater Against Influenza H1N1 2009 Virus at 8-10 Days Following 2 Doses of H1N1 Vaccine
• Number of Participants in the 65 Years and Older Age Stratum With a Serum Hemagglutination Inhibition (HAI) Antibody Titer of 1:40 or Greater Against Influenza H1N1 2009 Virus at 21 Days Following 2 Doses of H1N1 Vaccine

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary comparison estimate?

The primary outcome is reported as a participant count in each randomized dose group. The posted comparison expresses the difference between groups as a risk difference, with the 30 mcg group compared with the 15 mcg group. A risk difference is the difference in the proportions experiencing the defined event. General explanation: this measure is expressed on an absolute scale, so it describes how far apart the event proportions are, rather than how many times one proportion is the other. In the primary result, both observed counts are zero and the reported risk difference is 0.0.

For binary outcomes, a participant either meets the outcome definition or does not. This makes clear why the denominator matters: the count is interpreted relative to the number of participants at risk or contributing to that specific outcome. The posted denominators can vary by endpoint. They should not be replaced with the enrollment figure or with an arm size from a different outcome.

How should the immune-response comparisons be read?

The secondary comparisons use counts and proportions for binary immune-response outcomes. The risk difference compares the proportion meeting the outcome in the 30 mcg group with the proportion in the 15 mcg group. The confidence interval describes a range of values compatible with the observed data under the statistical method used. General explanation: an interval that includes zero is compatible with no difference on the risk-difference scale, as well as with differences in either direction. An interval that does not include zero indicates that zero is outside the interval under that method, but does not by itself address multiplicity, clinical importance, or bias.

For the older-stratum four-fold response at the earlier assessment, the reported risk difference is 0.117, with a 95% confidence interval from 0.001 to 0.232 and an unadjusted p-value of 0.049. The point estimate favors the 30 mcg group on this outcome, but the lower endpoint is close to zero. At the later assessment, the risk difference is 0.075, with a confidence interval from -0.042 to 0.192 and an unadjusted p-value of 0.208. For the earlier HAI threshold outcome, the risk difference is 0.069, with a confidence interval from -0.021 to 0.158 and an unadjusted p-value of 0.13. These are separate outcomes at specified times, not repeated versions of the primary safety endpoint.

The registry also lists relative risk and odds ratio estimates for these secondary comparisons. General explanation: a relative risk compares probabilities as a ratio, while an odds ratio compares odds. These ratio measures can convey a contrast differently from an absolute risk difference. They are not substitutes for the observed counts, and their interpretation can be less intuitive when outcomes are common. The registry record does not report a formal model or adjustment strategy for these comparisons, so they should be treated as descriptive, unadjusted contrasts.

What do the p-values say?

A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the test assumptions were true. General explanation: it is not the probability that the null hypothesis is true, nor a measure of the size or importance of an effect. The reported p-values for the secondary outcomes are explicitly unadjusted. Since the registry lists multiple secondary outcomes and assessment times, a p-value close to a conventional threshold should not be interpreted as definitive evidence without considering the full family of tests and the analysis plan. That plan is not reported in the registry record.

How should the planning illustrations be understood?

The sample-size illustrations use the observed effect as their starting point and show planning for 100%, 75%, and 50% of that observed effect, at 80% and 90% power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning illustrations, not the trial's original sample-size justification and not observed power. General explanation: power is a design property calculated for a specified effect and assumptions; after a study is completed, the observed data do not establish the probability that the study “had power.” The registry record does not report the trial's own sample-size justification, and the illustrations should not be read as a reconstruction of the original design.

The registry reports no secondary analyses in the posted analysis listings. It also does not report model specifications, covariate adjustment, handling of missing observations, or analysis-population definitions. Those omissions limit reproducibility and make it inappropriate to attribute methods that are not described in the registry record.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimated effect. For the primary safety comparison, the registry reports a risk difference of 0.0 and a confidence interval from 0.0 to 0.0 because neither group had an observed primary event. This interval reflects the posted comparison; it should not be read as evidence that the true risk difference must be exactly zero. With no observed events, the result cannot rule out risks that were not observed during the study.

The immune-response intervals show differing degrees of statistical compatibility with zero difference. For the earlier four-fold response outcome in participants aged 65 years and older, the risk-difference interval runs from 0.001 to 0.232. It excludes zero, but its lower endpoint is close to zero and the unadjusted p-value is 0.049. At the later assessment, the interval runs from -0.042 to 0.192, so values on either side of zero are compatible with the data under the stated interval method. The interval for the earlier HAI threshold outcome, -0.021 to 0.158, also includes zero.

General explanation: a confidence interval is not a guarantee that the true effect lies within its endpoints. It is a procedure that, under its assumptions, produces intervals that cover the true parameter at a stated long-run rate. A wider interval indicates less precision than a narrower interval on the same scale. Interpretation also depends on the outcome definition and analysis method, neither of which can be fully evaluated when the statistical plan is not reported.

The secondary estimates are based on the endpoint-specific denominators stated in the registry. They are not all based on the same number of participants, and the record does not explain why denominators differ. The reported intervals quantify sampling uncertainty under their methods; they do not account for all possible uncertainty from missing data, selection, measurement, or multiple testing. No confidence interval should be treated as a direct measure of clinical importance.

12. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary immune outcomes spanning age strata, antibody-response definitions, and follow-up assessments. It does not report a multiplicity adjustment, a hierarchy of outcomes, or a strategy identifying which secondary comparisons were confirmatory. The p-values attached to the posted secondary comparisons are unadjusted. General explanation: multiplicity matters because repeated testing creates more opportunities for a result to cross a nominal significance threshold by chance. Without a stated plan, the result with an unadjusted p-value of 0.049 should not be treated as if it were the only test performed.

The record includes six secondary outcome measures, but numerical results are not reported for all of them. It does not explain whether unreported results were not collected, not analyzed, or omitted from the registry entry. The registry record also does not report the protocol's missing-data rules, the handling of participants who did not complete follow-up, or reasons for differences in outcome-specific denominators. Therefore, the effect of missing observations on the reported proportions cannot be assessed from this record.

Analysis-population definitions are not reported in the registry record. In particular, the record does not specify whether outcomes were analyzed according to randomized assignment, vaccination received, availability of a post-vaccination measurement, or another population definition. The arm-level denominators indicate who contributed to each reported outcome, but they do not establish the criteria used to include or exclude participants.

The registry lists no reported secondary analyses, and it does not describe the statistical plan for the primary endpoint. It is therefore not possible to determine from the record whether any adjustments, sensitivity analyses, interim analyses, or prespecified subgroup methods were used. These omissions do not change the posted counts, but they limit the ability to judge whether the reported comparisons fully reflect the planned analyses or how robust they are to alternative assumptions.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lipoma (0.5%), renal cyst (0.5%), osteoarthritis (0.5%), ischaemic cardiomyopathy (0.5%), post procedural complication (0.5%).

The primary safety endpoint counted participants with vaccine-associated serious adverse events from Day 0 through Day 180 after the last vaccination. The posted count is zero in the 15 mcg group and zero in the 30 mcg group. The clinician's judgment of association to vaccination was part of the endpoint definition, so the primary count is not a count of every serious medical event occurring during follow-up.

The registry separately reports other adverse events in 149 of 202 participants at risk in the 15 mcg group and 150 of 204 participants at risk in the 30 mcg group. These figures should not be conflated with the serious-event endpoint. The listed serious-event terms each have a frequency of 0.5%; the registry record does not establish from those term listings that each event was judged vaccine-associated. No death counts are reported for the safety groups.

General explanation: an observed zero does not prove that the risk is absent. A study can observe no cases while leaving uncertainty about uncommon events, particularly when the outcome is rare. These safety findings describe the reported follow-up and population; they do not establish comparative safety beyond that scope.

14. What the Result Does, and Does Not, Mean

The results answer a limited set of questions about two H1N1 vaccine dose levels in healthy adult and older-adult populations. For the primary endpoint, the registry reports no participants with vaccine-associated serious adverse events in either dose group during the specified period. This is the observed safety result, and the posted risk-difference estimate is 0.0. The result is not proof that the true risk is zero, nor does it establish that the doses are equivalent or that no serious event could occur outside the study's observed experience.

The secondary results describe HAI antibody responses at specified times. In the reported older-adult comparisons, observed response proportions are higher in the 30 mcg group for the measures listed, but the intervals and unadjusted p-values differ across outcomes. These findings do not establish clinical protection from influenza, prevention of infection, or a benefit in health outcomes. HAI titers are immune-response measures in this record, not direct counts of influenza illness avoided.

The conclusions are also bounded by the registry's reporting. Numerical results for only three of the six listed secondary measures are present. Analysis populations, missing-data procedures, and the multiplicity plan are not reported in the registry record. Therefore, the immune-response comparisons should be treated as descriptive and interpreted cautiously, especially where results are unadjusted.

General explanation: statistical evidence is specific to the question, outcome, population, and follow-up period studied. A safety endpoint and an antibody endpoint capture different aspects of a trial, and neither alone establishes every aspect of a vaccine's effects. The registry supports statements about the posted counts and estimates; it does not support claims about unreported outcomes or broader populations. No medical advice follows from these registry results.

15. Why This Trial Matters Statistically

This trial illustrates why endpoint definition is central to clinical-trial interpretation. “Serious adverse events” is not simply a synonym for all adverse events: the primary outcome is restricted by seriousness criteria and by clinician-assessed association with vaccination. The registry also reports a separate count of other adverse events. Keeping those categories distinct prevents a frequent interpretive error: treating different safety measures as though they count the same events.

The study also demonstrates the difference between an observed zero and a precise claim of no risk. Both dose groups had zero observed primary events, producing a reported risk difference of 0.0. That is a clear description of the trial observation, but the absence of observed events cannot establish that the underlying risk is exactly zero. In safety research, the observation window, event definition, group size, and precision all matter.

The immune-response outcomes show why effect estimates should be read with their uncertainty and testing context. One unadjusted comparison has an interval that excludes zero by a small margin, while other reported intervals include zero. Considering several outcomes and time points without a reported multiplicity plan makes isolated threshold-based interpretation less secure. The statistical lesson is not to discard secondary endpoints, but to distinguish exploratory signals from confirmatory evidence.

Finally, the registry record illustrates the importance of transparent reporting. Without the full analysis plan, missing-data rules, and analysis-population definitions, readers cannot fully reconstruct how every comparison was produced. Reporting these elements would help assess reproducibility and the robustness of conclusions. The available record still supports useful description, provided that the conclusions remain within the scope of its reported outcomes and methods.

16. 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 registry record has important reporting limitations for interpreting this trial. It lists six secondary outcome measures, but numerical results are reported for only three. The remaining secondary results are not reported in the registry record, so the complete pattern across registered immune-response measures cannot be evaluated. The record does not clarify why those results are absent.

The statistical analysis plan is not reported in the registry record. In particular, the record does not describe the planned multiplicity approach, analysis populations, missing-data methods, covariate adjustments, or sensitivity analyses. The posted secondary p-values are unadjusted, and without the analysis plan it is not possible to determine whether the results were prespecified as confirmatory or exploratory.

Outcome-specific denominators vary across the reported immune outcomes. The registry gives the contributing counts, but does not explain the denominator differences or the reasons participants may not have contributed to each measure. This limits assessment of possible selection effects or the impact of missing measurements.

The primary safety result is based on observed events during the specified follow-up and in the reported trial groups. Zero vaccine-associated serious adverse events in both groups does not rule out rare events or establish safety equivalence. The registry does not report the number of deaths for the safety groups. The serious-event term list should also be interpreted cautiously, because the record does not establish that each listed term was judged associated with vaccination.

Lastly, the sample-size illustrations are calculated from observed effects under stated assumptions, not a report of the trial's original design justification. The registry record does not report that original justification. These reporting limitations do not invalidate the posted data, but they constrain how strongly and broadly the results can be interpreted.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Sanofi H1N1 Influenza Vaccine Administered at Two Dose Levels in Adult and Elderly Populations — NCT00943631.
• Registry record last updated 2012-10-31; status last verified 2010-03.
• Results first posted 2011-04-13.
• 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.

20. Record Summary

The registry describes a completed, randomized, triple-masked, parallel-group phase II study of an unadjuvanted H1N1 influenza vaccine in healthy adult and elderly populations. Participants received either 15 mcg or 30 mcg on Days 0 and 21. The primary endpoint was the number of participants reporting vaccine-associated serious adverse events from Day 0 through Day 180 after the last vaccination.

The posted primary result is zero participants in each dose group, with a risk difference of 0.0 and confidence interval from 0.0 to 0.0. The record also reports other adverse-event counts and selected older-adult immune-response results. Those secondary comparisons are unadjusted, and numerical results for three of the six listed secondary measures are not reported in the registry record. The analysis plan, missing-data methods, and analysis populations are not reported. The results therefore describe the posted outcomes but do not establish absence of risk, dose equivalence, or clinical protection.