Primary Vaccination Course in Children Receiving Pneumococcal Conjugate Vaccine GSK 1024850A or Prevenar™ and Hiberix™: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Primary Vaccination Course in Children Receiving Pneumococcal Conjugate Vaccine GSK 1024850A or Prevenar™ and Hiberix™ (NCT00680914), a randomized phase 3 study. The primary outcome is Number of Subjects With Vaccine Pneumococcal Serotypes Antibody Concentrations Above the Cut-Off Value.

2. Clinical Question

The study also set out to evaluate vaccine antibody responses and safety or reactogenicity. Its stated purpose was to assess immunogenicity after primary vaccination and to evaluate solicited and unsolicited symptoms and serious adverse events. The primary outcome is a threshold-based measure: it counts subjects whose antibody concentrations exceeded the specified cut-off. It is not a direct measure of clinical protection, disease incidence, or the magnitude of each subject’s antibody concentration.

The registry identifies antibody measures for vaccine pneumococcal serotypes as the primary outcome and lists other immunogenicity outcomes, including antibody concentrations, responses to cross-reactive serotypes, and opsonophagocytic activity. These outcomes address different aspects of immune response and should not be treated as interchangeable. The primary question is therefore specific: it concerns the proportion of assessed subjects crossing an antibody threshold, at the stated assessment time. Because the registry record does not report the primary results, it does not establish how many subjects crossed that threshold in either group or how the groups compared.

3. Trial Design

The registry describes a randomized, single-masked, parallel-group phase 3 study. It lists an enrollment of 503 and a completed status. The study start date is 2008-06-10, and the primary completion date is 2009-05-08. The condition is listed as streptococcal infections, and GlaxoSmithKline is identified as the sponsor. The registry record does not report the method used to generate the random allocation sequence, how allocation was concealed, or which participants or study personnel were masked.

The two groups received different pneumococcal conjugate vaccines, with Hiberix co-administered in both groups. The Synflorix group received three doses at Study Months 0, 2 and 4; the Prevenar group received three doses on the same schedule. This parallel design assigns subjects to a group and compares outcomes between groups rather than having each subject receive both pneumococcal vaccines. The record does not report further details about the vaccination setting or how adherence to the schedule was assessed.

The primary immunogenicity assessment was scheduled one month after administration of the third pneumococcal conjugate vaccine dose. The analysis population named for immunogenicity is the According-to-Protocol cohort. The registry record does not describe the cohort’s detailed eligibility rules, exclusions, or handling of protocol deviations. It also does not report a separate enrollment count for each group in the primary analysis.

Although the study is marked completed, completion status alone does not provide the outcome findings. The record contains an endpoint definition and safety counts, but it does not report the primary immunogenicity results or an inferential comparison between groups. A random assignment design can support a comparative interpretation when the corresponding analysis and results are reported; the design label by itself does not supply those results.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity.

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 Vaccine Pneumococcal Serotypes Antibody Concentrations Above the Cut-Off Value, measured over One month after administration of 3rd dose of the pneumococcal conjugate vaccine.

The primary endpoint counts subjects with antibody concentrations above the cut-off value for vaccine pneumococcal serotypes. The stated cut-off is 0.20 microgram per milliliter (ug/mL), and assessment was planned one month after administration of the third pneumococcal conjugate vaccine dose. The vaccine serotypes listed are 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F. The analysis population is described as the According-to-Protocol cohort for analysis of immunogenicity.

This threshold-based endpoint is used to summarize whether antibody concentrations reached a defined level. As a general statistical point, turning a continuous measurement into a threshold count can make a response easy to describe, but it also discards information about how far an individual measurement lies above or below the cut-off. Two groups could have similar counts above the threshold while differing in the distribution of antibody concentrations; conversely, a small shift around the cut-off could change the count without describing the full concentration pattern.

The registry record does not report the number or proportion of subjects above the cut-off for any listed serotype, nor does it report a combined summary or a comparison between groups. It lists antibody concentration measures separately among secondary outcomes. The primary definition therefore tells readers what was to be counted, but the record does not provide the observed values needed to interpret the endpoint’s result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a threshold endpoint count?

As a general explanation, a threshold endpoint classifies each assessed subject according to whether a measurement falls above a prespecified cut-off. The result can be expressed as a count or proportion meeting that criterion. In this trial, the defined threshold is an antibody concentration of 0.20 microgram per milliliter (ug/mL), assessed for the listed vaccine pneumococcal serotypes one month after the third dose. The registry record specifies the criterion but does not report the resulting counts.

A threshold is a simplification of the underlying continuous measurement. It can be useful when the scientific question concerns reaching a defined antibody level, but it does not show the spread of concentrations or how close measurements were to the cut-off. It also does not show whether concentrations were substantially higher in one group. The separate secondary outcome for antibody concentrations could address some of that information, but its results are not reported in the registry record.

What does randomization contribute?

As a general statistical principle, random assignment aims to make treatment groups comparable, on average, with respect to both measured and unmeasured characteristics before treatment. This supports a causal interpretation of a group comparison when allocation is implemented appropriately and the analysis follows the design. The registry labels the study randomized, but does not report the sequence-generation method or allocation concealment. More importantly for interpretation, the registry record does not report the primary group comparison. The design label cannot replace the missing outcome estimate.

The study is described as parallel-group: subjects received either Synflorix or Prevenar, with Hiberix co-administered in both groups. The two schedules were aligned at Study Months 0, 2 and 4. A parallel design makes the between-group comparison the natural basis for assessing the primary question. It does not mean the groups are identical in size, and the registry does not report the primary analysis group sizes.

How should the analysis population be understood?

The immunogenicity analysis is identified as using the According-to-Protocol cohort. As a general explanation, an according-to-protocol analysis focuses on subjects meeting defined protocol requirements, but the exact rules can differ across studies. The registry record does not report the detailed inclusion criteria for this cohort, the protocol deviations considered relevant, or how missing antibody measurements were handled. Therefore, the label alone is not enough to reconstruct who contributed to each endpoint result.

Analysis populations matter because excluding subjects after randomization can affect the comparability created by random assignment. This does not mean that such exclusions necessarily caused bias in this trial; the relevant details and results are not reported in the registry record. Readers would need the cohort definition, numbers assessed by group, reasons for exclusion, and the analysis method to evaluate the population used for each reported estimate.

What can a confidence interval tell a reader?

As a general explanation, a confidence interval communicates the precision of an estimated effect under a specified statistical procedure. A narrower interval generally represents greater precision than a wider interval, while the interval’s location indicates which effect values are compatible with the observed data and method. Statistical compatibility is not the same as clinical importance, and a confidence interval does not eliminate uncertainty about measurement, design, or analysis choices.

No primary effect estimate or confidence interval is reported in the registry record. The size and precision of the primary group difference therefore cannot be assessed. No p-value for the primary comparison is reported either. Without those results, it would be inappropriate to characterize the primary comparison as statistically significant, nonsignificant, or equivalent.

What do the planning assumptions mean?

As a general explanation, a sample-size calculation estimates how much information a planned study might need under specified assumptions. The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It is framed around detecting a stated fraction of the observed effect. Such an illustration is a planning exercise; it is not observed power and does not show that the trial achieved a particular precision or detected an effect.

The registry explicitly distinguishes these illustrations from the trial’s own design. The record does not report the protocol’s sample-size justification, the effect assumed during original planning, or the statistical plan used for the completed trial. In addition, the primary outcome is not reduced to a single comparison in the registry’s analysis listing because it has several categories or time points. The planning framework should therefore not be mistaken for a reported primary analysis.

General sample-size calculations depend on assumptions about the target effect, variability or event rate, error rate, allocation, and analysis method. If those assumptions differ from the study’s actual circumstances, the planning result may not describe the precision achieved. A sample-size figure does not itself establish a treatment effect, and it should not be presented as evidence that a trial was adequately powered after the fact. The registry record does not provide enough detail to assess the original design calculation.

Why can over-dispersion matter in other outcome types?

As a general explanation, over-dispersion occurs when count data vary more than a model’s assumed distribution allows. If a model ignores that extra variability, its uncertainty estimates may be too small and its statistical conclusions may appear more precise than warranted. The primary endpoint in this record is described as subjects meeting a threshold, not as a rate of recurrent events. The registry does not report an over-dispersion model or a count-data analysis for the primary outcome, so no such method should be attributed to this trial.

For a binary threshold outcome, analysis choices can include comparing group proportions or modeling the outcome while accounting for specified covariates. These are general possibilities, not methods identified in the registry record. The record does not report a test, model, adjustment set, confidence interval method, or multiplicity procedure for the primary immunogenicity analysis. It therefore cannot support a reconstruction of the sponsor’s inferential method.

The record lists 14 outcome measures and no analysis entries. Outcome definitions alone do not reveal which comparisons were prespecified, how multiple serotypes or endpoints were handled, or whether any interim analysis was conducted. Those methods are not reported in the registry record. The available information supports explanation of the endpoint and design, but not a detailed account of the completed statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including antibody responses to vaccine and cross-reactive pneumococcal serotypes, anti-protein D and anti-PRP antibody measures, and opsonophagocytic activity. The primary outcome description itself covers several serotypes. Considering multiple outcomes or serotype-specific comparisons can raise multiplicity concerns: as a general statistical point, conducting many tests may increase the chance of at least one apparently unusual result if no adjustment or interpretation strategy is specified. The registry record does not report a multiplicity plan, adjustment method, or hierarchy of confirmatory and exploratory outcomes.

The registry lists no analysis entries. It does not report whether results were analyzed by individual serotype, combined across serotypes, or summarized in another way. It also does not report interim analyses or a statistical analysis plan. These details are not reported in the registry record and should not be inferred from the outcome list.

The stated immunogenicity population is the According-to-Protocol cohort. The registry record does not provide group-specific analysis counts, reasons for missing measurements, missing-data assumptions, imputation methods, or sensitivity analyses. These omissions limit assessment of how the analysis population relates to the randomized groups and how incomplete observations may have affected the findings.

As a general principle, missing data can affect interpretation when the likelihood of missingness is related to treatment, measured outcomes, or participant characteristics. Different assumptions about missing outcomes can lead to different estimates. The record does not provide information needed to assess whether missingness occurred or how it was handled. No specific missing-data method can therefore be attributed to this trial.

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: bronchiolitis (5.9%), urinary tract infection (2.4%), gastroenteritis (2.3%), pneumonia (1.1%), pharyngitis (0.8%).

The registry records serious adverse event counts for both groups. In the Synflorix group, 56 subjects with serious adverse events are listed among 374 at risk. In the Prevenar group, 9 are listed among 129 at risk. These are descriptive registry counts. They do not, on their own, establish a causal difference between the vaccines or indicate whether the difference is statistically precise.

The registry also lists bronchiolitis at 5.9%, urinary tract infection at 2.4%, gastroenteritis at 2.3%, pneumonia at 1.1%, pharyngitis at 0.8%, and croup infections at 0.8% among the top serious terms. The denominator, arm attribution, and detailed event-count basis for these percentages are not reported in the registry record. They should not be treated as group-specific rates or compared between groups without that information.

Deaths are recorded as null rather than as a numeric count. A null entry is not the same as a reported zero, so the registry record does not establish a death count. It also does not report enough detail about serious event definitions, follow-up, timing, or adjudication to support a fuller safety comparison. These limitations apply to interpretation of the recorded counts and do not change the separate fact that the primary immunogenicity results are not reported.

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

The registry record establishes that this was a randomized, single-masked, parallel-group phase 3 study of primary pneumococcal vaccination in Korean infants. It identifies the two vaccine groups, the shared Hiberix co-administration, the vaccination schedule, and a threshold-based primary immunogenicity endpoint. It also identifies the assessment time and the serotypes included in that endpoint. These details describe what the study set out to compare.

The record does not report the primary outcome values, a group difference, a confidence interval, or a statistical test. It therefore does not show how many subjects in either group exceeded the antibody cut-off, how close the group results were, or how precise any comparison might be. A completed study status does not fill this gap. Nor can the enrollment figure be used as a substitute for the immunogenicity analysis population, whose group-specific size is not reported.

The endpoint concerns antibody concentrations crossing a defined threshold. As a general interpretation point, antibody response measures are not the same as observed disease outcomes. The primary endpoint definition does not itself establish the level of clinical protection associated with a response, and the registry record does not report disease incidence comparisons. The listed secondary outcomes involve other immune measures, but their results are also not reported.

The safety counts offer descriptive information about serious adverse events recorded in the groups, but do not by themselves demonstrate whether any event pattern was caused by a vaccine or whether groups differed reliably. The record lacks the details required for a full comparative safety assessment, and its null death entries should not be read as a reported zero.

Thus, the registry record supports an account of the trial question and design, not a conclusion that either vaccine produced higher, lower, equivalent, or more precisely estimated antibody responses. It also does not establish that one vaccine is safer or less safe. Those conclusions require reported outcome estimates and methods that are not present in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly defined endpoint and a reported result. The registry specifies a measurable question: whether subjects crossed an antibody concentration threshold after a defined vaccination schedule. It identifies the analysis population and the time of assessment. Those details help readers understand the intended estimand, but they do not reveal the observed response.

The outcome is also a useful example of how threshold measures trade detail for interpretability. A count above a cut-off is straightforward to describe, but it does not preserve the full distribution of antibody concentrations. The registry separately lists concentration outcomes, illustrating that immune response can be described through more than one statistical lens. Without results, however, no comparison across these measures is possible.

The record highlights why analysis populations and reporting of uncertainty matter. The According-to-Protocol label is given, but detailed cohort rules and group-specific analysis numbers are not. The study is labeled randomized, but the primary comparison and its precision are not reported. Readers need both the design information and the outcome estimates to judge what the study found and how much uncertainty remains.

Finally, a completed registry entry and a detailed endpoint definition are not substitutes for transparent results reporting. Statistical interpretation depends on knowing the observed values, comparison method, and uncertainty. This record documents the question and design while leaving those key inferential elements unreported.

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 this trial from the registry record is that it does not report the primary immunogenicity results. No group-specific counts above the antibody cut-off, effect estimate, confidence interval, or primary comparison test is available. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed.

The endpoint includes several vaccine pneumococcal serotypes, and the registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison. The record does not explain how serotype-specific findings were intended to be combined or how multiplicity was addressed. It lists 14 outcome measures but no analysis entries. The statistical plan, including any interim analyses, is not reported in the registry record.

The analysis population is identified as the According-to-Protocol cohort for immunogenicity, but cohort criteria, group-specific analysis sizes, reasons for exclusions, and missing-data handling are not reported. These details are needed to evaluate how the analyzed population relates to randomized assignment and how incomplete measurements may have been handled. The registry also does not report the randomization procedure or allocation concealment, or specify who was masked under the single-masked design.

Safety information is limited to recorded counts and listed serious-event terms. The record does not provide the denominator and arm attribution for the listed percentages, detailed follow-up information, or enough context to assess event timing and ascertainment. Death entries are null, not numeric counts. These reporting limitations prevent a complete comparative safety interpretation.

The registry includes planning assumptions for sample-size illustrations but does not report the trial’s own sample-size justification or full statistical plan. The illustrations are not observed power. Taken together, these limitations mean the record supports a description of the trial design and endpoint but not a complete appraisal of its comparative efficacy or safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Primary Vaccination Course in Children Receiving Pneumococcal Conjugate Vaccine GSK 1024850A or Prevenar™ and Hiberix™ — NCT00680914.
• Registry record last updated 2018-06-08; status last verified 2018-05.
• Results first posted 2010-06-14.
• 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

NCT00680914 is a completed randomized, single-masked, parallel-group phase 3 study sponsored by GlaxoSmithKline. It compared three doses of Synflorix with three doses of Prevenar, with Hiberix co-administered in both groups at Study Months 0, 2 and 4. The registry lists enrollment of 503 and describes Korean infants receiving primary vaccination.

The primary endpoint counts subjects above an antibody concentration cut-off of 0.20 microgram per milliliter (ug/mL), assessed one month after the third pneumococcal vaccine dose. The immunogenicity population is identified as the According-to-Protocol cohort. Although the registry record defines this outcome and includes safety counts, it does not report the primary immunogenicity results or a statistical comparison between groups. Important details about the analysis plan, missing data, and multiplicity are also not reported in the registry record.