Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age. (NCT00829010), a non-randomized phase 3 study. The primary outcome is Number of Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL)..

2. Clinical Question

3. Trial Design

This was a Phase 3, parallel-group, non-randomized study with no masking. The registry records enrollment of 489 and a completed study. It evaluated pneumococcal vaccine GSK1024850A in infants classified by HIV infection and exposure status, as well as in HIV-unexposed uninfected infants receiving different vaccine schedules. The stated objectives included immunogenicity, safety, reactogenicity, and nasopharyngeal carriage of S. pneumoniae and H. influenzae through 24 months of age.

The arm descriptions distinguish HIV-infected infants, HIV-exposed uninfected infants, and HIV-unexposed uninfected infants. The schedule groups include a 3-dose primary course with a booster, a 3-dose course without a booster, and a 2-dose primary course followed by a booster. The descriptions also mention other vaccines, including Tritanrix-HepB/Hib, measles, Rotarix, and Local OPV. The registry excerpts do not give complete descriptions of all co-administered vaccine schedules.

Non-randomized allocation matters for interpretation. Group membership was not assigned by random allocation according to the registry. The groups also represent different HIV exposure or infection categories and different vaccine schedules. Consequently, contrasts between groups cannot be interpreted as if they arose from a randomized comparison in otherwise exchangeable groups. The registry record does not report methods used to address differences between groups.

The primary endpoint was assessed one month after primary immunization. The stated timing was post-Dose 3 at Month 3 for the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, and HIV- (3+0) Group, and post-Dose 2 at Month 3 for the HIV- (2+1) Group. The registry record does not report a statistical analysis plan, sample-size justification, or interim analysis methods.

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: The study included 3 populations defined based on the human immunodeficiency virus status of the mother and the infant. Infant born from: * a HIV positive mother and HIV infected at Month 0 = HIV+/+. * a HIV positive mother and HIV exposed uninfected at screening = HIV+/-. * a HIV negative mother and HIV unexposed uninfected at Month 0 = HIV-

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The According-To-Protocol cohort for immunogenicity included evaluable subjects for whom data concerning immunogenicity outcome measures were available. This included subjects for whom assay results were available for antibodies against at least 1 study vaccine antigen component post dose II or III, as applicable, or after booster 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 Subjects With Anti-pneumococcal Vaccine Serotype Antibody Concentrations Equal to or Above 0.20 Microgram Per Millilitre (µg/mL)., measured over 1 month following primary immunization (post-Dose 3 at Month 3 for the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, HIV- (3+0) Group and post-Dose 2 at Month 3 for the HIV- (2+1) Group).

The primary endpoint is the number of subjects whose antibody concentration reached or exceeded 0.20 microgram per millilitre for pneumococcal vaccine serotypes. The listed serotypes are 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. Measurement was scheduled one month after primary immunization, with the relevant dose depending on the group’s schedule.

This is a binary response endpoint at the participant level for each serotype: a concentration either meets the stated threshold or does not. Counting participants above a threshold can make an immune-response summary easier to interpret than reporting concentration values alone. However, it discards information about how far an individual value lies above or below the threshold. It also does not directly measure whether participants developed pneumococcal disease or whether carriage changed.

The endpoint description does not include the number meeting the threshold in any group, the number assessed for each serotype, or an estimated difference between groups. Those results are not reported in the registry record. The primary endpoint’s definition therefore supports an explanation of what was intended to be measured, but not a conclusion about the observed response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a participant count based on whether an antibody concentration meets a specified threshold. In general, a binary endpoint converts a measurement into categories, such as meeting or not meeting a criterion. This can simplify summaries, but it removes detail about the actual distribution of measurements. The registry defines the threshold and serotypes but does not report the observed counts or the number evaluated for each serotype.

What does a confidence interval describe?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis method. A narrow interval indicates greater precision than a wide interval, while the interval’s location shows which values are compatible with the estimate and method. The registry record does not report confidence intervals for the primary endpoint or for comparisons between groups, so precision cannot be assessed from the recorded results.

What would a group comparison require?

For a binary response, a comparison could be expressed using counts and proportions or a contrast between groups. The appropriate interpretation depends on the comparison being made, the analyzed population, and how missing observations are handled. In this study, the groups were non-randomized and differed by HIV exposure or infection status and by schedule. General statistical reasoning therefore cautions against treating an unadjusted contrast as a causal treatment effect. The registry record does not report a model, covariate adjustment, or a prespecified contrast.

Why does non-randomized allocation matter?

Random assignment is generally used to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. With non-randomized allocation, group membership may be associated with other differences that influence an outcome. Here, the groups are defined in part by HIV status or exposure and include different vaccination schedules. Any numerical contrast could reflect these group differences as well as schedule differences. The registry record does not report an approach for separating those influences.

How should the schedule timing be read?

The primary endpoint timeframe is one month after primary immunization. For the HIV+/+ Group, HIV+/- Group, HIV- (3+1) Group, and HIV- (3+0) Group, the record specifies post-Dose 3 at Month 3. For the HIV- (2+1) Group, it specifies post-Dose 2 at Month 3. This describes when the endpoint was measured; it does not make the number of primary doses identical across groups. The registry record does not report analyses that account for this difference in exposure history.

What can the analysis entries establish?

The registry lists 31 outcome measures and 0 analyses. These entries identify the breadth of outcomes and the absence of analyses recorded in the registry, respectively. They do not establish that no analysis occurred outside the record. Statistical methods, including the handling of repeated serotype measurements, any adjustment for multiple outcomes, and the treatment of missing data, are not reported in the registry record.

How should planning illustrations be interpreted?

General sample-size calculations estimate how many participants may be needed under specified assumptions to detect a target effect with a chosen statistical approach. The planning assumptions associated with this study use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is expressed as a stated fraction of an observed effect. These are planning illustrations, not observed results or observed power. The registry record does not report the trial’s own sample-size justification, and the specific illustration values are not reported in the registry record. No planning illustration can substitute for the actual outcome estimates or their uncertainty.

For endpoints that count participants with events, the number assessed in each group is important alongside the event count. Missing observations can change the analyzed population and the meaning of a proportion. The record describes an According-To-Protocol cohort for immunogenicity as evaluable subjects with relevant data available, including subjects with assay results for at least one study vaccine antigen component post dose II or III. It does not provide complete missing-data methods or all analysis-population details.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 31 outcome measures, including repeated categories of antibody concentrations and opsonophagocytic titers for vaccine and cross-reactive pneumococcal serotypes. Testing or interpreting many outcomes raises a general multiplicity issue: the more comparisons considered, the greater the chance that some results may appear notable by chance. A prespecified approach can clarify which outcomes are primary and how secondary findings should be interpreted. The registry record does not report a multiplicity adjustment, a hierarchy of statistical tests, or a complete statistical analysis plan.

The record identifies one primary endpoint: the number of subjects with antibody concentrations at or above 0.20 microgram per millilitre. It specifies the serotypes and assessment timing, but does not provide the group-specific results, uncertainty estimates, or analysis methods. The registry records 0 analyses. This describes the registry entry, not necessarily all work performed outside it.

The immunogenicity population is described as the According-To-Protocol cohort, consisting of evaluable subjects with immunogenicity data available. The description further refers to subjects with assay results for at least one study vaccine antigen component post dose II or III. Complete criteria for inclusion, exclusions from the analysis, and the handling of missing measurements are not reported in the registry record. No imputation or sensitivity-analysis methods are reported.

These omissions limit assessment of whether the analyzed participants differed from those enrolled or whether missing outcome measurements could affect interpretation. The record also does not describe how repeated results across serotypes were handled in statistical analyses.

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: bronchopneumonia (15.7%), pulmonary tuberculosis (13.3%), gastroenteritis (9.6%), pneumocystis jirovecii pneumonia (4.8%), bronchiolitis (4.0%).

The registry reports serious adverse event figures for five groups. The numbers at risk for serious events and the numbers with serious events are listed separately by group. For other adverse events, the record also gives numbers at risk and affected. These are descriptive group figures; the registry excerpt does not report a statistical comparison between groups or an assessment of whether events were caused by vaccination.

The listed serious-event terms and percentages include bronchopneumonia at 15.7%, pulmonary tuberculosis at 13.3%, gastroenteritis at 9.6%, Pneumocystis jirovecii pneumonia at 4.8%, bronchiolitis at 4.0%, and pneumonia at 3.0%. The record does not explain in this excerpt the precise denominator or counting method for each listed percentage. They should therefore be read as reported safety summaries, not as comparative risks calculated from the group figures.

Deaths are not reported in the registry record for these groups. The safety information does not establish a causal relationship between vaccination and any listed event, and the non-randomized group structure limits like-for-like comparisons.

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

The record establishes that a Phase 3, non-randomized study evaluated pneumococcal vaccine GSK1024850A in infant groups defined by HIV infection and exposure status and by vaccination schedule. It defines a primary immunogenicity endpoint based on whether serotype-specific antibody concentration met or exceeded 0.20 microgram per millilitre at the stated assessment time. It also describes objectives concerning safety, reactogenicity, and carriage.

The registry record does not report the primary endpoint counts or comparative estimates. It therefore does not show how many participants met the antibody threshold, how responses varied among serotypes, or how precisely any group difference was estimated. No result about the antibody endpoint can be inferred from its definition alone.

The study’s non-randomized allocation is a central limitation for comparative interpretation. The groups differ in HIV exposure or infection status, and some differ in vaccination schedule. Even if group results were available, differences would not automatically be attributable to vaccination schedule. The record does not report statistical adjustment intended to address group differences.

The serious adverse event figures and listed event terms describe safety information recorded for the groups. They do not establish that vaccination caused an event, and the registry does not report deaths for the groups in this record. The record also does not report statistical methods for comparing safety outcomes.

Overall, the registry describes the study question, design, endpoint definition, and selected safety summaries, but does not provide the primary outcome results or statistical analyses needed to judge the size or precision of immunogenicity differences. Its contents support a description of what was studied and how the endpoint was defined, not a conclusion about clinical protection or comparative treatment effects.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined immunogenicity endpoint is not the same as a reported result. The endpoint specifies a threshold, serotypes, and assessment timing, allowing readers to understand what outcome was intended. But without group counts, denominators, or uncertainty estimates, readers cannot assess the magnitude or precision of the observed responses from the registry record.

It also highlights the importance of design when interpreting group differences. Non-randomized allocation and groups defined by HIV status or exposure mean that comparisons are not equivalent to randomized contrasts. Schedule differences add another layer: some groups received different numbers of primary doses before endpoint assessment. Those features affect the questions a statistical contrast could answer and the assumptions needed to interpret it.

The record lists numerous outcomes, making transparent reporting of the analysis plan especially relevant. Details about primary and secondary analyses, multiplicity, missing data, and analysis populations would help readers judge how results should be interpreted. Those methods are not reported in the registry record, which also records 0 analyses.

Finally, the safety summaries demonstrate the distinction between describing events and making causal claims. Counts and listed event terms are useful context, but without a randomized comparison or reported comparative analysis they do not establish whether vaccination caused an event. The record is statistically informative about the study’s structure and intended measurements while leaving key result and method questions unresolved.

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 primary limitation for interpreting the immunogenicity objective is that the registry record does not report the endpoint results. It gives no group-specific counts meeting the antibody threshold, no denominators for those counts, and no estimates of contrasts or uncertainty. The primary outcome can therefore be described but not quantitatively interpreted.

Allocation was non-randomized, and the study groups differed by HIV status or exposure and by schedule. The registry record does not report adjustment methods that might address these differences. Comparisons between groups would not provide a like-for-like randomized control comparison.

The record identifies the immunogenicity analysis population as an According-To-Protocol cohort, but does not give complete eligibility criteria, participant flow, or missing-data procedures. It does not report whether results were assessed in additional analysis populations or how incomplete serotype measurements were handled.

Although the registry lists 31 outcome measures, it records 0 analyses. It does not report a statistical analysis plan, multiplicity handling, interim analyses, or the trial’s sample-size justification. The planning assumptions associated with illustrations are not a substitute for those design details or for observed estimates.

Some arm descriptions are incomplete in the registry excerpt. The primary endpoint timeframe refers to the HIV- (3+0) Group, while the arm descriptions identify an HIV- (EPI) Group. The record does not explain that label relationship. The safety summaries also do not describe causal attribution or a comparative safety analysis. These limitations restrict what can be concluded from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Primary and Booster Vaccination Study With a Pneumococcal Vaccine in HIV Infected, HIV Exposed Uninfected and HIV Uninfected Children 6 to 10 Weeks of Age. — NCT00829010.
• Registry record last updated 2018-08-17; status last verified 2017-10.
• Results first posted 2012-07-06.
• 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

This completed Phase 3 study enrolled 489 infants and used a parallel, non-randomized, unmasked design. It evaluated pneumococcal vaccine GSK1024850A in groups defined by HIV infection or exposure status and by vaccination schedule. The study objectives included immunogenicity, safety, reactogenicity, and nasopharyngeal carriage.

The primary endpoint counted subjects with antibody concentrations at or above 0.20 microgram per millilitre for specified pneumococcal vaccine serotypes, assessed one month after primary immunization. The registry record does not report the primary endpoint results or statistical analyses. It lists 31 outcome measures and 0 analyses.

Safety figures are reported by group, along with selected serious adverse event terms and percentages. The record does not report deaths for the groups. Non-randomized allocation, missing analytical details, and absent primary outcome results limit comparative interpretation.