This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Zilbrix™ Hib and Polio Sabin™ (NCT00678301), a randomized phase 3 study. The primary outcome is Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00678301 |
| Phase | Phase 3 |
| Condition | Infections, Streptococcal |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 365 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Infants in sub-Saharan Africa receiving a primary vaccination course during the first 4 months of life. The trial enrolled 365 participants. The immunogenicity population was the According-To-Protocol cohort, defined as evaluable participants with available immunogenicity data; the record further describes eligibility in terms of assay results after vaccination.
Intervention
Three doses of Synflorix™, the pneumococcal conjugate vaccine, co-administered with Zilbrix™ Hib and oral Polio Sabin™. The described schedule was at 6-10-14 weeks of age.
Comparator
Zilbrix™ Hib and Polio Sabin™ without Synflorix™, on the same described 6-10-14-week schedule. The comparison therefore concerns adding the pneumococcal vaccine to the other vaccines in this course.
Primary question
What antibody concentrations against the vaccine pneumococcal serotypes were measured one month after the third Synflorix™ dose, and how did those concentrations compare between the vaccination groups? The outcome definition is recorded, but a group-level primary-outcome comparison is not reported in the registry record.
3. Trial Design
This was a randomized, parallel-group Phase 3 trial sponsored by GlaxoSmithKline. The record lists no masking. It enrolled 365 participants and is marked completed. The recorded study start was 2008-06-18, and primary completion was 2009-11-09.
The two groups differed in whether Synflorix™ was included. One group received three doses of Synflorix™ with three doses each of Zilbrix™ Hib and Polio Sabin™. The comparator group received the Zilbrix™ Hib and Polio Sabin™ vaccines without Synflorix™. Both descriptions specify a 6-10-14-week schedule. The trial summary places the vaccination course during the first 4 months of life.
Random allocation is a design feature intended to make the groups comparable on average at the time of assignment. In general, a parallel-group design assigns participants to one group and follows the outcomes within that group, rather than having each participant receive both regimens. The registry record does not report the allocation method, any stratification, or the procedures used to conceal assignments.
The trial assessed antibody responses and safety or reactogenicity, including solicited and unsolicited symptoms and serious adverse events. The primary outcome was geometric mean antibody concentration against vaccine pneumococcal serotypes at Month 3, described as one month after the third Synflorix™ dose. The registry lists additional antibody and seroprotection outcomes, as well as safety outcomes. Its stated primary outcome spans multiple serotypes, and the registry data do not reduce those measurements to one reported comparison.
Details of the sample-size justification, the recruitment target rationale, and any interim analyses are not reported in the registry record. The record also does not report a statistical analysis plan or additional details of randomization and masking beyond 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.
Before assignment: Among 365 enrolled participants, 8 were not administered any study vaccine and hence were not considered as starting the study.
Overall Study
| Stage | Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Zilbrix™ Hib + Polio Sabin™ |
|---|---|---|
| STARTED | 239 | 118 |
| COMPLETED | 231 | 116 |
| NOT COMPLETED | 8 | 2 |
Reasons for not completing this period:
| Reason | Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Zilbrix™ Hib + Polio Sabin™ |
|---|---|---|
| Non-compliance with study procedures | 0 | 1 |
| Adverse Event | 1 | 0 |
| Withdrawal by Subject | 4 | 0 |
| Lost to Follow-up | 3 | 1 |
Analysis population for the primary outcome, as defined in the registry: The According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects with available immunogenicity data. The ATP cohort for immunogenicity included subjects for whom assay results were available for antibodies against at least one study vaccine antigen component 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.
| Characteristic | Unit | Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Zilbrix™ Hib + Polio Sabin™ | Total |
|---|---|---|---|---|
| Participants analysed | 239 | 118 | 357 | |
| Age, Continuous | Weeks | 7.1 (SD 1.15) | 7 (SD 1.18) | 7.07 (SD 1.16) |
| Sex: Female, Male: Female | Participants | 119 | 62 | 181 |
| Sex: Female, Male: Male | Participants | 120 | 56 | 176 |
| Race/Ethnicity, Customized: African heritage/African American | Participants | 239 | 118 | 357 |
6. Primary Endpoint
The registry lists the primary outcome as Concentrations of Antibodies Against Vaccine Pneumococcal Serotypes, measured over At Month 3, one month after the administration of the third dose of Synflorix vaccine.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | μg/mL |
| Endpoint classification | not reduced to a single comparison |
The primary outcome measures concentrations of antibodies against the vaccine pneumococcal serotypes. The assessed serotypes were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Concentrations are expressed in μg/mL, and the outcome is summarized using a geometric mean with a 95% confidence interval. Measurements were scheduled at Month 3, one month after the third Synflorix™ dose.
The outcome definition also gives an assay seropositivity cut-off: antibody concentrations of at least 0.05 μg/mL. That threshold defines a classification of seropositivity; it is distinct from the continuous antibody concentration summarized by the geometric mean. Other listed outcomes address seropositivity, seroprotection, cross-reactive serotypes, and opsonophagocytic activity.
In general, antibody concentration is used as an immunogenicity measure because it describes the level of the measured immune response rather than only whether a participant crosses a threshold. A geometric mean is useful for measurements that are commonly analyzed on a multiplicative scale. A confidence interval conveys uncertainty around the estimated group quantity. The registry record gives the endpoint definition but does not report the primary-outcome estimates or their confidence intervals, so the magnitude and precision of the measured response cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of a vaccination course that included Synflorix™ against a course of Zilbrix™ Hib and Polio Sabin™ without Synflorix™. Its primary immunogenicity outcome is antibody concentration against vaccine pneumococcal serotypes, assessed one month after the third Synflorix™ dose. This establishes what the trial was designed to measure, but does not establish what the comparison found.
No group-level primary-outcome estimates, confidence intervals, or statistical tests are reported in the registry record. The primary outcome covers several serotypes, and the record indicates that it has not been reduced to one comparison. Consequently, there is no single reported effect estimate to interpret across the groups. The registry's listing of the outcome definition should not be mistaken for a result.
The absence of an estimate also means that precision cannot be evaluated. A confidence interval would indicate the range of values compatible with the data under the analysis assumptions; without a reported interval, the uncertainty around any group contrast is unknown. The record does not provide enough information to describe the direction or magnitude of an antibody difference, or to assess whether individual serotypes showed similar patterns.
The safety summary records serious adverse events in the group receiving all three vaccines and none in the comparator group. It also records other adverse events in both groups and reports zero deaths in each. These are descriptive counts in the registry summary. They do not, by themselves, establish whether an event was caused by a vaccine or whether an apparent difference reflects a treatment effect. The record does not supply a detailed comparative safety analysis.
Several secondary immunogenicity outcomes are listed, including antibody concentrations against cross-reactive serotypes 6A and 19A, opsonophagocytic activity, and seropositivity or seroprotection measures. The registry record lists 26 outcome measures, but reports zero analyses. Without results for those outcomes, they cannot fill the gap in the primary comparison or be used to characterize the consistency of immune responses.
Overall, the posted information supports a description of the trial design, endpoint definitions, and selected safety counts. It does not support a conclusion about the size, direction, or statistical precision of the primary immunogenicity comparison. No inference about clinical protection can be drawn from the endpoint definition alone.
9. Statistical Methods Explained
The registry record identifies a randomized, parallel-group Phase 3 design and defines a geometric mean antibody concentration as the primary outcome. It does not report a statistical analysis plan or primary-outcome estimates. The methods concepts below explain how such measures are generally interpreted; they are not claims about analyses performed in this trial.
What does a geometric mean describe?
In general, a geometric mean summarizes measurements after taking logarithms, averaging on that transformed scale, and returning to the original scale. This approach is often useful for antibody concentrations, which may vary multiplicatively and can be skewed on their original scale. A geometric mean is not the same as an arithmetic average. It is best understood alongside its confidence interval and the analysis population used to calculate it.
Here the endpoint definition names antibody concentration in μg/mL and gives a 95% confidence interval as the dispersion measure. The registry record does not report the geometric means or confidence intervals by group. It also does not report whether the primary comparison used transformed concentrations, a model-based contrast, or another procedure. Those details are not reported in the registry record.
How should a confidence interval be read?
In general, a confidence interval expresses the uncertainty associated with an estimate under the chosen statistical method. It is not a guarantee that the true value lies in that particular interval, and it does not by itself show whether a difference is important. For a comparison, the interval for the contrast is especially relevant: its width indicates precision, while its location describes the plausible direction and magnitude under the model. The registry record specifies 95% confidence intervals for the primary outcome but does not post the estimates or intervals needed to make that assessment.
Why do the serotypes matter?
The primary outcome includes ten vaccine serotypes: 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. These are separate antibody measurements, rather than a single antibody concentration for one organism type. In general, multiple endpoints or categories can produce a set of comparisons that may differ in direction and precision. A single overall statement would need a clearly defined summary method. No such reduction to one comparison is reported in the registry record.
The record also defines seropositivity using an assay threshold of at least 0.05 μg/mL. In general, a threshold-based outcome turns a continuous measurement into a category. This can make the result easier to describe as a proportion above a cutoff, but it discards information about differences among values on either side of the threshold. The threshold-based outcomes are conceptually distinct from the primary geometric mean concentration.
What does randomization contribute?
In general, random assignment reduces the risk that measured and unmeasured participant characteristics systematically determine which intervention is received. It supports a causal comparison when allocation is implemented appropriately and when follow-up, outcome measurement, and analysis are handled in a way that preserves the randomized comparison. Randomization does not ensure identical groups, and it does not eliminate bias from missing outcomes, deviations from assigned treatment, or selective reporting.
The registry labels the allocation randomized, but does not report the sequence-generation procedure, concealment process, or details of any stratification. Masking is listed as none. Without further information, the effect of the open-label design on outcome measurement or reporting cannot be assessed. Antibody concentrations are laboratory measurements, but the registry record does not describe who collected, processed, or interpreted the assays.
How should planning illustrations be interpreted?
In general, sample-size calculations estimate the number of participants needed to detect a specified effect under stated assumptions. They are planning tools, not evidence that a study achieved a particular probability of detecting its observed result. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation; they also describe effects scaled as fractions of an observed effect. The stated convention is participants per arm for non-time-to-event calculations. These assumptions are not evidence of the trial's own sample-size justification.
A planning calculation based on an observed effect is meaningful only when the effect and comparison are clearly defined. Here, the primary outcome spans multiple serotypes and is not reduced to one comparison in the registry record. The actual planning values are not reported in the registry record. Any such illustration should therefore be read as hypothetical rather than as an observed property of the trial, and never as observed power.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome includes antibody concentrations across multiple vaccine serotypes, and the registry lists a range of additional immunogenicity outcomes. In general, assessing many outcomes creates a multiplicity issue: the more comparisons made, the more opportunities there are for a result to appear noteworthy by chance. Common approaches include defining a hierarchy of outcomes, adjusting statistical tests, or identifying analyses as exploratory. The registry record does not report whether any multiplicity strategy was planned or used.
The primary outcome has not been reduced to one comparison in the registry record. There is no reported primary-outcome analysis, and the record lists 26 outcome measures but zero analyses. It is therefore not possible to determine which comparisons were tested, whether outcomes were prioritized, or whether any adjustment was applied. The results needed to assess multiplicity are not reported in the registry record.
The immunogenicity population is described as the According-To-Protocol cohort for immunogenicity, consisting of evaluable participants with available immunogenicity data. The record further notes that assay results had to be available for antibodies against at least one study vaccine antigen component after vaccination. In general, an according-to-protocol analysis can exclude participants who did not meet specified protocol requirements. Such exclusions can affect comparability if they differ across groups or relate to outcomes. The criteria and counts of exclusions are not reported in the registry record.
Details about missing antibody measurements, how missing values were handled, and the number of participants contributing to each serotype analysis are not reported in the registry record. The record also does not report an intention-to-treat analysis or a comparison of results across analysis populations. Without those details, the influence of missing data and post-randomization exclusions cannot be evaluated.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | 5 | 239 | 2.1% |
| Zilbrix™ Hib + Polio Sabin™ | 0 | 118 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | 0 of 239 |
| Zilbrix™ Hib + Polio Sabin™ | 0 of 118 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | 238 of 239 |
| Zilbrix™ Hib + Polio Sabin™ | 117 of 118 |
Most frequent serious adverse event terms
| Event term | Organ system | Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Zilbrix™ Hib + Polio Sabin™ |
|---|---|---|---|
| Bronchopneumonia | Vascular disorders | 4 of 239 | 0 of 118 |
| Haematoma | Vascular disorders | 1 of 239 | 0 of 118 |
| Febrile convulsion | Nervous system disorders | 1 of 239 | 0 of 118 |
| Malaria | Infections and infestations | 1 of 239 | 0 of 118 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Synflorix™ + Zilbrix™ Hib + Polio Sabin™ | Zilbrix™ Hib + Polio Sabin™ |
|---|---|---|---|
| Pain | General disorders | 234 of 239 | 112 of 118 |
| Fever (rectal temperature ≥ 38.5°C) | General disorders | 207 of 239 | 105 of 118 |
| Irritability | General disorders | 192 of 239 | 88 of 118 |
| Swelling | General disorders | 173 of 239 | 83 of 118 |
| Allergic bronchitis | Respiratory, thoracic and mediastinal disorders | 83 of 239 | 46 of 118 |
| Rhinitis | Infections and infestations | 85 of 239 | 42 of 118 |
| Gastroenteritis | Infections and infestations | 61 of 239 | 32 of 118 |
| Redness | General disorders | 57 of 239 | 30 of 118 |
| Abdominal distension | Gastrointestinal disorders | 43 of 239 | 22 of 118 |
| Ear infection | Infections and infestations | 42 of 239 | 21 of 118 |
Serious events with the highest arm-level rate: bronchopneumonia (1.7%), haematoma (0.4%), febrile convulsion (0.4%), malaria (0.4%).
The registry safety summary lists 239 participants at risk in the Synflorix™ plus Zilbrix™ Hib plus Polio Sabin™ group and 118 in the Zilbrix™ Hib plus Polio Sabin™ group. Serious adverse events were recorded for 5 participants in the first group and 0 in the comparator group. Other adverse events were recorded for 238 and 117 participants, respectively. The recorded death count was 0 in each group.
The registry also lists the following serious adverse event terms and percentages: Bronchopneumonia, 1.7%; Haematoma, 0.4%; Febrile convulsion, 0.4%; and Malaria, 0.4%. These terms are descriptive entries, not proof that an event was caused by a study vaccine. The record does not provide enough detail to connect each term to an individual group or to assess event timing, severity beyond the registry classification, or attribution.
In general, safety counts should be read with their denominators and definitions. The figures describe recorded events among participants at risk; they do not establish a causal contrast or account for differences in follow-up. The registry record does not report a detailed statistical comparison of serious adverse events or other adverse events. These summaries are therefore descriptive and should not be interpreted as a complete assessment of comparative risk.
12. What the Result Does, and Does Not, Mean
The trial record is useful for identifying the intended immunogenicity question: whether antibody concentrations against vaccine pneumococcal serotypes were assessed after a primary course that included Synflorix™ alongside Zilbrix™ Hib and Polio Sabin™. It also identifies a comparator receiving the latter vaccines without Synflorix™. The randomized design gives the comparison a structure intended to support assessment of differences between groups, subject to the conduct and analysis of the trial.
What the record does not establish is the result of that comparison. No primary-outcome estimates, confidence intervals, or tests are reported. The endpoint definition, assay cutoff, and list of serotypes are not evidence of a particular antibody response. Without reported group estimates, the direction, size, and precision of any primary difference are unknown. The secondary outcomes likewise appear as outcome definitions rather than reported analyses.
The safety summary provides descriptive information: serious adverse events were recorded in one group and not the other, other adverse events were recorded in both groups, and no deaths were recorded. Those counts alone cannot determine causation, comparative risk, or whether the observed pattern is compatible with chance. More detailed event-level data and an analysis plan are not reported in the registry record.
In general, antibody measurements are immunogenicity outcomes. They should not be treated as direct measurements of clinical protection unless that relationship is established and the trial reports relevant clinical outcomes. The registry record does not report clinical efficacy results. It therefore cannot establish whether vaccination prevented infection or disease, nor can it support a treatment recommendation.
The appropriate reading is bounded: the record describes a completed randomized trial, its groups, its intended antibody endpoint, and selected safety counts. It does not provide the primary comparison required to judge the immunogenicity result or its statistical uncertainty. The absence of reported analyses is a limitation of what can be interpreted from the registry record, not evidence that the trial had no results outside the registry.
13. Why This Trial Matters Statistically
This trial illustrates why an outcome definition and an outcome result are different things. The registry specifies a biologically relevant measurement, its unit, summary statistic, time point, serotypes, and assay threshold. Those details allow readers to understand what the investigators intended to measure. They do not reveal the group estimates or the uncertainty around them.
It also highlights the challenge of interpreting a multi-component immunogenicity endpoint. Antibody concentrations are assessed for ten vaccine serotypes, while the registry separately lists cross-reactive serotypes, opsonophagocytic activity, and threshold-based classifications. In general, a collection of related outcomes needs a transparent analysis strategy so readers can distinguish a prespecified primary comparison from secondary or exploratory findings. The registry record does not report such a strategy or any analyses.
The open-label, randomized, parallel-group design also shows how different design features address different concerns. Randomization is intended to limit systematic differences at assignment, whereas masking concerns awareness of group assignment. The record lists no masking. In general, the implications of this combination depend on outcome measurement and conduct, details that are not reported in the registry record.
Finally, the safety summary underscores the importance of distinguishing event counts from causal conclusions. Counts and percentages can describe what was recorded, but comparative interpretation requires clear denominators, definitions, follow-up, and an analysis approach. Overall, this trial matters statistically as an example of how complete outcome definitions can coexist with insufficient posted results for estimating an effect.
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 trial-specific limitation for interpretation is that the registry record does not report the primary antibody concentration results. It defines a geometric mean outcome and a 95% confidence interval, but supplies no group estimates or interval limits. The primary outcome spans several serotypes and is not reduced to one comparison, leaving no single effect estimate to interpret.
The record reports zero analyses despite listing 26 outcome measures. It therefore does not provide results for the listed primary and secondary immunogenicity outcomes. The multiplicity approach, analysis plan, model specification, handling of assay values, and criteria for the according-to-protocol population are not reported in the registry record. The number of participants contributing to each outcome is also not reported.
The summary describes an open-label trial, but does not explain how laboratory personnel, outcome assessors, or participants were handled with respect to group awareness. The allocation sequence and concealment procedures are not reported. These omissions limit assessment of potential design and measurement biases, although they do not establish that bias occurred.
The safety data are limited to summary counts and selected serious adverse event terms. Detailed event timing, group-specific term counts, attribution, duration of follow-up, and comparative analyses are not reported in the registry record. Accordingly, the safety information should be treated as descriptive rather than as a complete comparative assessment.
The record also does not report the rationale for the enrollment target, the trial's own sample-size calculation, interim analyses, or a clinical efficacy outcome. These missing details constrain assessment of planning, precision, and clinical relevance. They do not negate the stated design, but they prevent a fuller appraisal of how the trial was planned and what its results indicate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Primary Vaccination Course in Children Receiving the Pneumococcal Vaccine GSK 1024850A, Zilbrix™ Hib and Polio Sabin™ — NCT00678301.
- Registry record last updated 2019-11-15; status last verified 2019-10.
- Results first posted 2017-10-27.
- 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.
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18. Record Summary
This completed Phase 3 randomized, parallel-group trial, sponsored by GlaxoSmithKline, enrolled 365 infants in sub-Saharan Africa. One group received Synflorix™ with Zilbrix™ Hib and Polio Sabin™; the comparator group received Zilbrix™ Hib and Polio Sabin™ without Synflorix™. The listed schedule was 6-10-14 weeks of age, and masking was listed as none.
The primary outcome was geometric mean antibody concentration against vaccine pneumococcal serotypes at Month 3, one month after the third Synflorix™ dose. The registry lists 26 outcome measures and zero analyses. Primary group estimates and confidence intervals are not reported in the registry record.
The safety summary records serious adverse events in 5 participants in the Synflorix™ group and 0 in the comparator group, other adverse events in 238 and 117 participants, and 0 deaths in both groups. These are descriptive registry figures; a detailed comparative safety analysis is not reported.