Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women (NCT00992017), a na phase 2 study. The primary outcome is The Number of Participants Who Had at Least One Adverse Event (AE).

2. Clinical Question

This is a safety and immunogenicity question in a defined clinical population, not a randomized comparison of vaccination with another intervention or no vaccination. The record also lists secondary immune-response outcomes, including maternal and infant antibody measures, maternal cell-mediated immune responses, and response to seasonal trivalent influenza vaccine. Those outcomes broaden the study’s objectives, but the posted record does not give their numerical results in the registry record described for this analysis.

The clinical question is therefore best read as a descriptive assessment of adverse events and immune-response measures among vaccinated pregnant women with HIV. Without a concurrent comparison group, the record cannot by itself separate events occurring after vaccination from events that would have occurred in the same population without vaccination. The reported counts describe events in the study population; they do not establish a causal effect.

3. Trial Design

This was a phase II, single-group study of an inactivated monovalent influenza A (H1N1) vaccine in pregnant women infected with HIV-1. The registry lists enrollment as 130 and the study as completed. The record gives a start of 2009-10 and primary completion of 2010-11. It does not describe a randomized allocation: allocation is listed as not applicable, and masking is listed as none.

Participants in the vaccine group received two doses 21 days apart. The primary safety population was defined as all 128 pregnant women who received at least one vaccination. The primary endpoint concerned participants with at least one adverse event, with measurement extending up to 6 months after delivery. The event description includes abnormal laboratory values, signs and symptoms, diagnoses, and solicited local and systemic adverse events. Severity was graded using the DAIDS scale, from mild through death.

The registry also lists immune-response outcomes for pregnant women and infants, as well as response to seasonal trivalent influenza vaccine. These objectives are consistent with a study assessing both safety and immunogenicity, but their numerical results are not reported in the registry record.

A single-group design can describe outcomes observed among those enrolled and vaccinated. It does not provide a concurrent control group for estimating what would have happened to a comparable population without vaccination. Consequently, observed events cannot be attributed to the vaccine solely on the basis of this design. The record does not report the protocol’s sample-size justification, a detailed statistical analysis plan, or the methods used to handle missing outcome data.

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: Two study participants were enrolled but left the clinic before receiving any vaccination and they were taken off study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All 128 pregnant women who received at least one vaccination are included in this analysis.

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 The Number of Participants Who Had at Least One Adverse Event (AE), measured over Measured up to 6 months after delivery.

The primary endpoint is the number of participants who had at least one adverse event. It is a participant-level count: a participant is counted as having an event if one or more events meet the endpoint definition. The registry describes several event categories, including abnormal laboratory values, signs and symptoms, diagnoses, and solicited local or systemic adverse events. It also states that event severity was graded using the DAIDS scale: grade 1 is mild, grade 2 moderate, grade 3 severe, grade 4 life threatening or disabling, and grade 5 death.

A safety endpoint of this kind is used to describe the occurrence and severity of harms during a defined follow-up period. It can help readers understand what events were observed in the population receiving the intervention. The endpoint’s timeframe is measured up to 6 months after delivery, so it concerns events recorded across that specified follow-up period rather than only events immediately after a dose.

Counts need careful interpretation. A participant-level count does not convey how many episodes an affected participant experienced, when each event began, or whether an investigator judged it related to vaccination. The registry record does not report those details in the endpoint information. Nor does a count alone provide a comparison with the event experience that would have occurred without vaccination. The reported figures are descriptive safety information, not a controlled estimate of treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design determines which statistical interpretations are available. This study is listed as single-group, with allocation not applicable and masking none. The available safety results therefore describe events in the vaccinated group; they are not estimates of a randomized contrast. Statistical methods cannot compensate for the absence of a concurrent control group when the question is whether vaccination caused an event or changed its frequency.

What does a participant count represent?

The primary outcome is a count of participants who had at least one adverse event. This differs from a count of all event episodes: a participant with multiple events can still be represented once in a participant-level count. The endpoint description covers laboratory abnormalities, signs and symptoms, diagnoses, and solicited local or systemic events. The registry also provides separate serious and other event counts. It does not state in the record that these categories are mutually exclusive, so they should not be added together or treated as independent groups.

A count is most informative when read with its population at risk and outcome definition. The primary safety population is all 128 women who received at least one vaccination. For the adverse-event listing, 128 are recorded at risk for serious events and 128 at risk for other events. These are denominators for descriptive reporting, not evidence that every participant completed every follow-up assessment. Completion and missingness by outcome are not reported in the registry record.

Why are uncertainty estimates useful?

In general, a confidence interval expresses the range of values compatible with observed data under a specified statistical model and procedure. It can show the precision of an estimate: a wider interval generally indicates greater uncertainty, while a narrower interval indicates more precision. A count without an interval gives no direct measure of sampling uncertainty. No confidence intervals for the safety outcomes are reported in the registry record, so precision cannot be assessed from interval estimates.

In general, a hypothesis test evaluates data against a specified null hypothesis and analysis plan. A p-value is not a measure of the size or clinical importance of an effect, and it cannot establish causation. No test result or p-value for the primary endpoint is reported. The registry lists zero analyses, and it does not report the statistical analysis plan in the record.

What does a single-group design allow?

In general, a single-group study can estimate or describe outcomes within the observed group, subject to the quality of outcome ascertainment and completeness of follow-up. It cannot directly estimate a between-group difference without a comparator. Historical or external comparisons would require additional data and assumptions, neither of which are reported in the registry record. The figures should therefore be read as counts observed in the vaccinated group, rather than as a comparative effect.

Masking is listed as none. In general, knowledge of treatment assignment can affect reporting, assessment, or recording of outcomes, particularly for events requiring judgment. The registry record does not describe specific safeguards or adjudication procedures, so their presence or absence cannot be inferred.

How should planning calculations be read?

In general, sample-size calculations estimate the amount of information a future study may need under specified assumptions about an effect, variability, significance level, and design. The record’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of an observed effect. Those are planning assumptions, not a description of this single-group study’s allocation. The illustration is not observed power and should not be read as a result from the completed trial. The record does not report the trial’s own sample-size justification.

Over-dispersion is a general concern when count data vary more than a chosen model expects; ignoring it can make uncertainty look too small. That issue is relevant only if an appropriate count model and analysis are used. The registry record does not report a count-model analysis or an over-dispersion assessment, so none should be attributed to this study.

In general, results also depend on outcome definitions, follow-up completeness, and how repeated events are handled. The endpoint specifies a follow-up period measured up to 6 months after delivery, but the record does not report event-level timing, repeated-event methods, or missing-data procedures. These details limit what can be inferred about the underlying statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes alongside the primary safety endpoint. They include maternal and infant HAI antibody measures, maternal cell-mediated immune responses measured by B-cell and T-cell ELISPOT assay values, and response to seasonal trivalent influenza vaccine. Multiple outcomes create a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses this. Whether adjustment is appropriate depends on the study objectives and analysis plan.

The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or an inferential analysis plan. The number of analyses is listed as zero. No adjustment method, prespecified testing order, or interpretation rule should therefore be assumed. The secondary outcomes are listed as study measures, but numerical results for them are not reported in the registry record.

Missing data can also affect interpretation. In general, an analysis may be biased if participants with missing measurements differ systematically from those with observed measurements, or if missingness is related to the outcome. The record identifies 128 vaccinated women in the primary safety population, but it does not describe completeness of follow-up for each measure, reasons for missing data, or an imputation or sensitivity-analysis method. It is therefore not possible to determine from this record how missing measurements were handled.

The primary safety population is explicitly described as all 128 pregnant women who received at least one vaccination. No additional analysis populations, such as a per-protocol or immunogenicity-evaluable population, are specified in the registry record. Their definitions and use are not reported in the registry record.

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: pre-eclampsia (3.9%), premature labour (2.3%), vomiting (0.8%), influenza like illness (0.8%), pneumonia (0.8%).

The serious adverse-event listing records 21 participants affected among 128 at risk in the H1N1 vaccine group. For other adverse events, it records 118 affected among 128 at risk. These categories describe the posted safety counts; they should not be added because the registry record does not say whether participants can appear in both categories.

The listed serious-event terms include pre-eclampsia (3.9%), premature labour (2.3%), vomiting (0.8%), influenza like illness (0.8%), pneumonia (0.8%), and wound infection (0.8%). The percentages are registry entries for the named terms. The record does not provide further detail about event timing, recurrence, attribution, or the denominator used for each listed percentage. They should not be interpreted as proof that vaccination caused an event.

The endpoint description uses DAIDS severity grades, from grade 1, mild, through grade 5, death. The adverse-event summary does not provide a death count; it is not reported in the registry record. A missing death entry should not be interpreted as a reported count of zero. Overall, these figures describe safety events recorded in one vaccinated group and do not provide a controlled comparison.

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

The results establish a limited descriptive point: adverse events were recorded among pregnant women with HIV who received H1N1 vaccine, and the registry reports counts for serious and other adverse events. The primary safety population included all 128 participants who received at least one vaccination. Serious-event terms and their listed percentages give additional detail about events recorded in the study.

The record does not establish that the vaccine caused any particular event. Pregnancy and HIV infection define the studied population, and the study has no concurrent comparison group. Without such a group, the observed event counts cannot be contrasted with event experience under another intervention or without vaccination. The counts are also not a forecast for every pregnant person with HIV, because the record does not establish that this study population represents all such people.

The record does not report confidence intervals or inferential tests for these safety results, so their statistical precision is not quantified. It also does not report numerical results for the listed immune-response outcomes in the registry record. The study’s title and listed objectives indicate that immunogenicity was assessed, but they are not themselves evidence of a particular immune response.

These results do not answer whether vaccination is appropriate for an individual, and they should not be used as medical advice. Statistically, the central distinction is between describing what was observed and estimating a causal effect. This registry record supports the former, within the defined study population and follow-up description; it does not support the latter. Further details about outcome ascertainment, missing data, and the analysis plan are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a safety description and a comparative treatment-effect estimate. The study addressed a defined population—pregnant women infected with HIV-1—and recorded adverse events after an H1N1 vaccination schedule. Such descriptive evidence can document the types and counts of events observed in a study, which is a distinct purpose from testing whether an intervention changes risk relative to a control.

The single-group design is central to interpretation. Because allocation is listed as not applicable and there is no comparator, the data cannot provide a randomized contrast. A count can be reported accurately while still leaving causal attribution unresolved. This distinction matters whenever readers encounter event counts without a control group: the figures characterize the study experience but do not show what would have happened in the absence of the intervention.

The registry also illustrates why outcome definitions matter. The primary endpoint concerns participants with at least one adverse event, while the record separately lists serious and other events and gives selected serious-event terms. The categories and terms should not be combined without knowing their overlap and construction. Participant-level counts, event-level counts, severity grades, and event attribution each answer different questions.

Finally, the absence of reported inferential analyses, confidence intervals, multiplicity procedures, and missing-data methods places limits on precision and reproducibility. These are not reasons to discard descriptive findings; they define the level of conclusion the record can support. For statistical readers, separating observed counts, uncertainty, and causal claims is particularly important when a registry record presents safety information from a single group.

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 main trial-specific limitation is the absence of a concurrent comparison group. The design is single-group, allocation is not applicable, and masking is listed as none. Consequently, the observed adverse-event counts cannot estimate a between-group difference or establish that vaccination caused an event. The record does not provide an external comparator or explain a method for constructing one.

The primary safety population includes 128 women who received at least one vaccination, while enrollment is listed as 130. The record does not explain the difference between these entries, and no explanation should be inferred. It also does not report the number completing each follow-up assessment, outcome-specific missingness, or reasons for missing data. The specified safety timeframe extends up to 6 months after delivery, but the timing and recurrence of individual events are not given in the registry record.

The registry describes event categories and severity grading, but does not report event-attribution procedures or adjudication details. The serious and other event counts may overlap; the record does not say otherwise. Selected serious-event terms are listed, but the listing does not provide a complete event-level account. The death count is not reported in the registry record.

The record lists secondary immune-response outcomes but does not give their numerical results in the registry record. It also does not report a detailed statistical analysis plan, multiplicity handling, confidence intervals, or missing-data methods. The protocol’s sample-size justification is not reported in the registry record. These gaps limit assessment of precision, outcome completeness, and how the study’s multiple objectives were analyzed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety of and Immune Response to an H1N1 Influenza Vaccine in HIV Infected Pregnant Women — NCT00992017.
• Registry record last updated 2021-11-05; status last verified 2014-12.
• Results first posted 2012-03-13.
• 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.

18. Record Summary

The registry describes a completed phase II, single-group study of an inactivated monovalent H1N1 vaccine in pregnant women infected with HIV-1. Enrollment is listed as 130; the primary safety population comprises all 128 women who received at least one vaccination. Participants received two doses 21 days apart, and safety measurement extended up to 6 months after delivery.

The primary endpoint was the number of participants with at least one adverse event. The adverse-event listing records 21 participants with serious events and 118 with other events, each among 128 at risk. Selected serious-event terms and percentages are also listed. The study had no comparator, and the registry lists no analyses. Numerical results for the listed immune-response outcomes, inferential estimates, and details of missing-data handling are not reported in the registry record.