Influenza Vaccine in Pregnant Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Influenza Vaccine in Pregnant Women (NCT00905125), a randomized phase 2 study. The primary outcome is Number of Participants With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer Greater Than or Equal to 40 Against Each Antigen Included in the 2008-2009 Seasonal Inactivated Trivalent Influenza Vaccine (TIV).

2. Clinical Question

In statistical terms, the primary question concerns antibody responses at a specified threshold, assessed separately for the influenza B, H1N1, and H3N2 antigens. It is not a single reported overall response measure: the registry describes counts for each antigen and two time points. The analysis population is described as participants with blood collected at both time points, with one participant excluded because the baseline blood draw occurred after vaccination.

The record also lists secondary outcomes based on microneutralization antibody titers, including threshold attainment, four-fold or greater rises, and geometric mean titers. These outcomes address different features of antibody response and should not be treated as interchangeable with the primary HAI outcome. The registry record does not report results for these secondary outcomes, either.

3. Trial Design

This was a Phase 2, randomized, parallel-group trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It compared two inactivated trivalent influenza vaccines: Fluzone® and Fluarix®. The registry record reports enrollment of 102 participants and a completed status. The study summary describes the trial as US-based.

Participants were assigned by chance to one of the two vaccine groups. Each arm description specifies a single 0.5 mL intramuscular injection. The record classifies the masking as triple, while the official title calls the study double-blind. It does not explain this difference or identify which parties were masked, so the precise masking arrangements are not reported in the registry record.

The trial used a parallel-group structure: each participant was assigned to one vaccine group rather than receiving both vaccines in sequence. The listed study dates are a start in 2009-06 and primary completion in 2010-03. The summary describes participation lasting about 8 months, with blood collection on Day 0 and 28 days after vaccination. The primary outcome description also specifies blood collection before vaccination and at Day 28.

The study summary describes an intended enrollment of about 200 women aged 18-39 years, inclusive, in their second or third trimester, from 14 weeks of gestation to term, inclusive. The registry record's actual enrollment field is 102. The reason for the difference between the intended and recorded enrollment is not reported in the registry record. Nor is the sample-size justification, including its assumptions or target precision, reported in the registry record.

The registry record lists 14 outcome measures. It does not report the detailed statistical analysis plan, the randomization method, allocation concealment procedures, or an interim-analysis plan. Those design details should not be inferred from the randomized and masked labels alone.

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

Analysis population for the primary outcome, as defined in the registry: Participants are included in this ITT analysis if blood was collected at both timepoints. One participant was excluded because the baseline blood draw was done after vaccination.

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 With a Serum Hemagglutination Inhibition Assay (HAI) Antibody Titer Greater Than or Equal to 40 Against Each Antigen Included in the 2008-2009 Seasonal Inactivated Trivalent Influenza Vaccine (TIV), measured over Day 0 prior to and Day 28 after receiving single dose..

The primary endpoint counts participants with a serum hemagglutination inhibition assay (HAI) antibody titer of at least 40 against each antigen included in the 2008-2009 seasonal inactivated trivalent influenza vaccine. The specified antigens are influenza B, H1N1, and H3N2. Blood was collected before vaccination and again 28 days after the single dose.

HAI is an assay used to measure antibodies that inhibit influenza-virus hemagglutination. A threshold-based outcome turns a continuous or graded assay result into a count of participants who meet a stated criterion. That can make a result easier to interpret as the proportion of the analyzed group reaching the threshold, but it also discards information about how far titers lie above or below that cutoff. This is a general feature of threshold outcomes, not a finding about this trial.

The registry specifies a count for each antigen rather than one combined endpoint. Responses can differ across antigens, so a count for one antigen cannot stand in for the counts for the others. The registry record does not state a rule for combining the antigen-specific outcomes into a single measure.

The outcome population is described as an intention-to-treat analysis of participants with blood collected at both time points. One participant was excluded because the baseline sample was collected after vaccination. The registry record defines the measurement and population but does not report the antigen-specific counts, uncertainty estimates, or comparisons between vaccine groups. Consequently, the size and precision of any observed difference are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be described from the registry record are limited. It identifies randomized allocation, a parallel-group comparison, a primary outcome based on counts, and an analysis population requiring blood samples at both stated time points. A detailed statistical analysis plan is not reported in the registry record. The following explanations describe general statistical concepts relevant to this outcome; they are not claims about methods used in this trial unless the record explicitly states them.

What does the threshold outcome count?

The primary outcome counts participants whose HAI antibody titer is at least 40 for each antigen. A threshold outcome classifies each participant as either meeting or not meeting the criterion for an antigen. Researchers can compare the fraction meeting that criterion between groups, but a fraction is not the same as the underlying distribution of titers. Participants with values just below the threshold and participants with much lower values are both counted as not meeting it; participants above the threshold are counted together regardless of how high their values are.

For this trial, the registry describes separate antigens and both pre-vaccination and post-vaccination sample times. Those dimensions matter when interpreting an analysis: a result for one antigen or time point does not automatically describe the others. The record does not state a single summary rule that combines all antigen-specific findings.

How should uncertainty be understood?

A confidence interval is a general statistical tool for expressing uncertainty around an estimated quantity. For a group difference, it can show a range of values compatible with the data under the model and method used. A narrow interval indicates greater precision than a wide interval, while an interval spanning values on either side of no difference may indicate that the data do not distinguish clearly between those possibilities. These are general explanations, not interpretations of this trial: no confidence intervals or primary group estimates are reported in the registry record.

A p-value is also a general measure, calculated under a specified statistical model and null hypothesis. It does not measure the probability that a treatment works, nor does it describe the size or importance of an effect. The registry record does not report a p-value for the primary endpoint. The analysis method, whether adjusted or unadjusted, is also not reported in the registry record.

Why do allocation and masking matter?

Randomized allocation is intended, in general, to make assigned groups comparable on average with respect to measured and unmeasured characteristics. Masking can reduce the influence of expectations on care, assessment, or reporting, depending on who is masked and how the procedures are implemented. The registry record labels the study randomized and classifies its masking as triple. Its official title uses the term double-blind, and the record does not clarify the difference or specify who was masked. The randomization sequence and concealment procedures are not reported in the registry record.

What does the stated analysis population imply?

The primary outcome description calls the analysis intention-to-treat, but defines inclusion as having blood collected at both time points. One participant was excluded because the baseline draw took place after vaccination. In general, intention-to-treat refers to analyzing participants according to their randomized groups, regardless of treatment received or adherence. Requiring measurements at both time points can mean that some randomized participants are not included in a particular outcome analysis if measurements are unavailable or ineligible. The record does not provide further details about missing samples, exclusions beyond the stated participant, or how missing data were handled.

Missing-data methods can affect estimates when participants with unavailable measurements differ from those with complete measurements. General approaches include analyzing complete cases or using statistical models or imputation, each relying on assumptions. Which approach, if any beyond the stated inclusion rule, was used is not reported in the registry record. It also does not report the numbers randomized to each arm for the primary analysis or the outcome-specific denominators.

How should multiple outcomes be considered?

The record lists 14 outcome measures, including several antigen-specific HAI and microneutralization measures. In general, testing multiple outcomes raises a multiplicity issue because the chance of at least one result appearing unusual can increase as more comparisons are made. Methods to address this can include designating a primary comparison in advance or adjusting statistical thresholds across a family of tests. Whether such methods were specified or applied in this trial is not reported in the registry record.

The trial record describes the primary endpoint in terms of several antigens and time points, and the analysis is not reduced to one comparison. That structure makes it important to identify which comparison is being interpreted and whether it was planned as primary. The detailed hierarchy of tests and any multiplicity strategy are not reported in the registry record.

What do planning illustrations mean?

In general, sample-size planning uses assumptions about the effect to detect, the significance level, allocation, and statistical model. The planning assumptions associated with this trial describe a two-sided significance level of 0.05, equal allocation, and a normal approximation; the illustrations are based on stated fractions of an observed effect. Such illustrations are planning exercises, not observed power and not evidence that the trial achieved a particular level of precision. The sample-size justification used when the trial was designed is not reported in the registry record. The registry record does not report the primary outcome estimates needed to assess the observed effect directly.

The choice of statistical model also depends on the outcome. For counts or proportions, the analysis must reflect the data structure and the comparison being estimated. General methods may yield different estimates or uncertainty depending on assumptions such as independence and the handling of repeated measurements. The registry record does not report the model, covariate adjustments, or analysis details used for the primary endpoint. No specific statistical method should therefore be attributed to the trial beyond the elements explicitly described in its record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures. The primary HAI endpoint itself concerns three antigens and measurements before vaccination and at Day 28. The record does not report a multiplicity strategy, such as an adjustment across antigen-specific comparisons or a prespecified hierarchy for interpreting multiple outcomes. Whether any adjustment was planned or used is not reported in the registry record.

The primary outcome description defines the analysis population as participants with blood collected at both time points. It notes that one participant was excluded because the baseline blood draw occurred after vaccination. It does not report the total number of participants with missing samples, reasons for any other exclusions, or the distribution of missing measurements by assigned group. It also does not describe imputation, sensitivity analyses, or other missing-data procedures; these methods are not reported in the registry record.

The description uses the term intention-to-treat but also specifies a requirement for blood at both time points. In general, those details should be considered together: an analysis restricted to participants with complete, eligible measurements may differ from an analysis retaining every randomized participant. The record does not provide sufficient detail to determine how this population was operationalized beyond the stated inclusion rule and the one exclusion.

The registry record does not report an interim-analysis plan, stopping rules, or a full statistical analysis plan. It also does not report primary outcome results, so it is not possible to assess the impact of missing data or multiplicity on the reported estimates.

11. 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: postpartum haemorrhage (3.6%), caesarean section (3.6%), retained products of conception (2.2%), hellp syndrome (2.2%), premature labour (2.2%).

The registry reports serious adverse events for 8 of 46 participants in the Fluzone® group and 13 of 56 participants in the Fluarix® group. For other adverse events, it reports 42 of 46 participants in the Fluzone® group and 50 of 56 participants in the Fluarix® group. These are participant counts, not counts of every individual event, and the record does not provide a statistical comparison of the groups.

The listed serious-event terms include Postpartum haemorrhage (3.6%), Caesarean section (3.6%), Retained products of conception (2.2%), HELLP syndrome (2.2%), Premature labour (2.2%), and Polydactyly (2.2%). The record does not assign these terms to a vaccine group in the information, nor does it provide the event-level context needed to interpret their relationship to vaccination. The percentages should therefore be read as reported, without assuming a denominator or group-specific rate that is not stated.

Adverse-event counts are descriptive safety information. They do not establish that a vaccine caused an event or that two groups differ beyond what could occur by chance. The deaths field has no reported value, so deaths are not reported in the registry record. Detailed definitions, timing, severity grading, relatedness assessments, and comparative safety analyses are also not reported in the registry record.

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

The trial record documents a randomized comparison of two influenza vaccines in pregnant women and defines antibody outcomes assessed before vaccination and 28 days afterward. It also reports participant counts for serious and other adverse events. These details describe the structure of the study and the kinds of outcomes collected.

The primary outcome results are not reported in the registry record. There are no reported counts of participants meeting the HAI threshold for the influenza B, H1N1, or H3N2 antigen, and no estimates comparing the groups. The record therefore does not establish the size or direction of any difference in antibody response, or the precision with which such a difference could be estimated.

The threshold endpoint captures whether each participant reached the stated titer criterion. In general, it does not convey the full pattern of antibody titers, and separate antigen-specific results may not have the same pattern. The registry also lists microneutralization outcomes, but their results are not reported in the registry record. No conclusion about those measures can be drawn from their definitions alone.

The safety counts show the number of participants recorded with serious and other adverse events in each group. They do not, by themselves, establish causation, comparative risk, or the clinical meaning of individual events. The registry does not report a statistical safety comparison or sufficient event-level details to support those interpretations.

Accordingly, the record supports describing how the trial was organized, what it intended to measure, and which adverse-event counts were recorded. It does not support a conclusion about comparative vaccine effectiveness, antibody response, or safety. Absence of reported outcome results should not be interpreted as evidence that groups were the same or different; the relevant estimates and uncertainty are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an outcome result are distinct parts of a clinical-trial record. The registry specifies a threshold-based HAI measure, the antigens assessed, and the collection times. Those details make the intended measurement understandable, but they do not reveal the observed counts or the comparison between vaccine groups. Without results and uncertainty estimates, the statistical question cannot be answered from the registry record.

The design also highlights the importance of distinguishing intended enrollment from recorded enrollment. The study summary describes an intended enrollment of about 200, while the registry reports enrollment of 102. Enrollment affects the information available for estimating group differences, but the reason for the difference and the planned precision are not reported in the registry record. A reader cannot infer the trial's original sample-size justification from enrollment alone.

Multiple antigen-specific endpoints raise a further statistical issue. Separate outcomes can provide detail about responses to particular antigens, but they also require clarity about which comparisons were primary and how multiple testing was handled. The registry lists 14 outcomes, yet a multiplicity plan is not reported in the registry record.

Finally, the record's description of an intention-to-treat analysis alongside a requirement for measurements at both time points illustrates why analysis-population definitions matter. The stated exclusion is explicit, but other missing-data details are not. Clear reporting of who was analyzed, how missing measurements were addressed, and how uncertainty was quantified is essential for assessing what trial results mean. These results and methods are not reported in the registry record.

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 this trial from its registry record is the absence of primary outcome results. The record defines the HAI endpoint but does not report the antigen-specific counts, estimates comparing the groups, confidence intervals, or p-values. The secondary antibody outcomes are listed without results as well.

The enrollment field reports 102 participants, while the study summary describes an intended enrollment of about 200. The reason for this difference is not reported in the registry record. A sample-size justification and the assumptions behind the original design are also not reported, so the intended precision of the primary comparison cannot be assessed.

The analysis population is described as participants with blood collected at both time points, and one participant was excluded because the baseline draw occurred after vaccination. The record does not provide further information about missing samples, the number of participants analyzed for each antigen, or methods used to address missing data. It also does not give the detailed statistical analysis plan.

The registry lists multiple outcomes and antigen-specific measurements but does not report whether multiplicity was addressed. It does not describe an interim-analysis plan, the randomization procedure, or the allocation-concealment process. Masking is classified as triple, while the official title says double-blind; the reason for the different labels and the masked parties are not reported in the registry record.

The safety information is limited to participant counts and a list of serious-event terms with percentages. The record does not provide the event-level timing, group attribution for the listed terms, causality assessments, or comparative statistical analyses. These omissions limit interpretation of both efficacy-related outcomes and safety; they do not, on their own, establish that the trial's results favored either vaccine.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Influenza Vaccine in Pregnant Women — NCT00905125.
• Registry record last updated 2012-06-13; status last verified 2010-03.
• Results first posted 2011-04-06.
• 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.

18. Record Summary

NCT00905125 is a completed Phase 2, randomized, parallel-group trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It compared a single 0.5 mL intramuscular injection of Fluzone® with a single 0.5 mL intramuscular injection of Fluarix® in pregnant women. The registry reports enrollment of 102 and lists study start in 2009-06 and primary completion in 2010-03.

The primary endpoint counted participants with an HAI antibody titer of at least 40 against each of three seasonal influenza vaccine antigens, with blood collected before vaccination and at Day 28. The analysis population was described as requiring blood at both time points; one participant was excluded because the baseline draw followed vaccination. The registry record does not report primary or secondary antibody outcome results or a detailed statistical analysis plan.

Serious and other adverse-event participant counts are reported by group. The record does not report deaths, detailed comparative safety analyses, or a multiplicity plan.