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 Safety & Immunogenicity Study of 10-Valent Pneumococcal Conjugate Vaccine When Administered as a 2-Dose Schedule (NCT00307034), a randomized phase 3 study. The primary outcome is Number of Seroprotected Subjects Against Pneumococcal Serotypes.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00307034 |
| Phase | Phase 3 |
| Condition | Infections, Streptococcal |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 351 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Infants enrolled in a phase III study of a 10-valent pneumococcal conjugate vaccine. The primary immunogenicity analysis used the according-to-protocol cohort, defined as evaluable subjects with immunogenicity data.
Intervention
GSK Biologicals' 10-valent pneumococcal conjugate vaccine on the 2-4-11 months schedule, co-administered with a DTPa-combined vaccine at 2-4-11 months.
Comparator
The same pneumococcal vaccine on the 2-3-4-11 months schedule, co-administered with a DTPa-combined vaccine at 2-4-11 months.
Primary question
What number of subjects met the antibody threshold for seroprotection against the assessed pneumococcal serotypes one month after dose 2, at Month 3?
The clinical question concerns immunogenicity after the early doses of the pneumococcal vaccine schedules. Both groups also received a DTPa-combined vaccine, described as Infanrix hexa or Infanrix-IPV/Hib. The registry record states that these co-administered vaccines were used according to national recommendations.
The registry labels one arm “2-dose group,” although its arm description gives a 2-4-11 months schedule. The comparator arm is described as receiving the pneumococcal vaccine at 2-3-4-11 months. The primary assessment is one month after dose 2, not after completion of the full schedule. Thus, the stated endpoint addresses the response at that specified early time point; it does not, by itself, describe the result after the final scheduled dose.
The registry lists a primary outcome definition and the analysis population, but it does not report the number of seroprotected subjects by arm or a statistical comparison. The magnitude and precision of any difference between schedules are therefore not reported in the registry record.
3. Trial Design
This was a randomized, open-label, parallel-group phase III study sponsored by GlaxoSmithKline. The registry lists enrollment of 351 and a completed status. The official title describes the study as phase IIIa and identifies an intramuscular 10-valent pneumococcal conjugate vaccine schedule. Start and primary completion dates are listed as 2006-01-01 and 2007-01-01.
The two arm descriptions distinguish the pneumococcal vaccine schedules: 2-4-11 months in the arm labelled “2-dose group” and 2-3-4-11 months in the comparator arm. Both descriptions specify co-administration of DTPa-combined vaccine at 2-4-11 months. The named co-administered vaccines were Infanrix hexa or Infanrix-IPV/Hib. The registry does not give the number of participants assigned to each randomized arm in its general design information; the adverse-event listings give safety denominators of 175 and 176 for the two named Synflorix groups.
Randomization is intended, in general, to balance participant characteristics across groups on average. Open-label means the study was not masked; the registry lists masking as none. Knowledge of the assigned schedule can matter for outcomes involving subjective assessment, although the primary endpoint is based on measured antibody concentrations. The registry does not report further details about allocation procedures or concealment.
The primary outcome was assessed in the according-to-protocol cohort for immunogenicity, rather than being described as an analysis of every enrolled participant. The registry defines that cohort as evaluable subjects for whom immunogenicity data were available. It does not report the cohort size by arm, exclusions, or reasons participants may not have been evaluable. The record also lists secondary immune outcomes covering pneumococcal and other vaccine-related antibodies and opsonophagocytic activity.
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
| Stage | Synflorix I Group | Synflorix II Group |
|---|---|---|
| STARTED | 175 | 176 |
| COMPLETED | 173 | 169 |
| NOT COMPLETED | 2 | 7 |
Reasons for not completing this period:
| Reason | Synflorix I Group | Synflorix II Group |
|---|---|---|
| Adverse Event | 1 | 2 |
| Withdrawal by Subject | 1 | 2 |
| Lost to Follow-up | 0 | 3 |
Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity concerning data were available.
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 I Group | Synflorix II Group | Total |
|---|---|---|---|---|
| Participants analysed | 175 | 176 | 351 | |
| Age, Continuous | Weeks | 12 (SD 1.94) | 12.1 (SD 1.9) | 12.05 (SD 1.92) |
| Sex: Female, Male: Female | Participants | 86 | 82 | 168 |
| Sex: Female, Male: Male | Participants | 89 | 94 | 183 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Seroprotected Subjects Against Pneumococcal Serotypes, measured over One month post-dose 2 (Month 3) administration of Synflorix™ vaccine.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Subjects |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of subjects classified as seroprotected against pneumococcal serotypes one month after dose 2, at Month 3. Seroprotection was defined as an antibody concentration at least 0.20 micrograms per milliliter. The serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.
This is a binary classification for each subject and serotype: the measured concentration either meets the stated threshold or it does not. Counting subjects who meet a threshold gives a clinically interpretable summary of how many participants reached the prespecified antibody level. It does not retain the full range of antibody concentrations, so it is different from reporting a geometric mean concentration. The registry describes antibody measurement by 22F enzyme-linked immunosorbent assay and says concentrations were expressed as geometric mean concentrations as well.
Seroprotection is an immunogenicity measure, not a direct count of infections or a demonstration of clinical protection. The record does not report the arm-specific primary outcome counts, the proportion of subjects meeting the threshold, or a comparison estimate and confidence interval. Consequently, the result’s size and statistical precision cannot be described from the registry record.
The primary analysis population was the according-to-protocol immunogenicity cohort: evaluable subjects with immunogenicity data. This population definition matters because the reported endpoint is not necessarily based on every enrolled participant. Cohort counts and details of missing antibody measurements are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question, the schedules compared and the definition of the primary immunogenicity outcome. It does not provide the actual primary outcome values by arm. No estimate of the between-group contrast, confidence interval, or test result for the primary endpoint is reported in the registry record. It is therefore not possible to state from this record how many subjects reached the threshold in either arm or how precisely the schedules differed on that measure.
The primary endpoint is a threshold-based antibody outcome assessed one month after dose 2. Its interpretation is specific to the listed serotypes and time point. The record also describes antibody concentrations as geometric mean concentrations, but does not report numerical concentrations in the registry record for this analysis. The secondary outcomes include seroprotection and antibody concentrations for pneumococcal serotypes, opsonophagocytic activity, and antibody concentrations for several co-administered vaccine antigens. Their results are not reported in the registry record.
The event listings identify 175 subjects at risk in the Synflorix I Group and 176 in the Synflorix II Group for serious adverse events. The listed serious adverse event counts are 5 and 7, respectively. These are descriptive counts and should not be treated as a formal comparison: the record does not provide a confidence interval or statistical test for them. The group labels do not, in the information available, explicitly map to the schedule descriptions, so the safety counts should not be assigned to a particular schedule without further record detail.
The registry lists several serious event terms with a frequency of 0.6% each. These include events in the primary and booster phases. The record does not provide event-specific denominators or further context in the listed details, so those frequencies should be read as reported rather than combined or compared. Death counts are not reported in the registry record.
Enrollment was 351, and the study is marked completed. Completion and enrollment do not establish that the primary analysis included all enrolled subjects: the defined analysis population was the evaluable according-to-protocol immunogenicity cohort. Its size is not reported in the registry record. Overall, the posted information permits a description of the design and outcome definitions but not a conclusion about the direction, magnitude, or precision of the primary immunogenicity comparison.
9. Statistical Methods Explained
What does the primary outcome count?
The endpoint is a binary subject-level classification based on antibody concentration. For each assessed pneumococcal serotype, a subject qualifies as seroprotected if the concentration meets the stated threshold of 0.20 micrograms per milliliter. A binary outcome can be summarized by counting subjects in each category. In a randomized comparison, the usual statistical question is whether the frequency of the qualifying outcome differs between groups, with an estimate of the difference and its uncertainty.
The registry defines the primary outcome as the number of seroprotected subjects, but does not report those counts by arm or an inferential comparison. Without the arm-specific values, no effect estimate can be interpreted. A confidence interval, in general, describes a range of values compatible with the data and the estimation method; it communicates precision as well as the direction and size of an estimated contrast. No primary-outcome confidence interval is reported in the registry record.
Why keep the antibody threshold distinct from antibody concentration?
A threshold outcome answers how many subjects reached a specified concentration. It discards information about how far a measured value lies above or below the cutoff. A continuous concentration summary retains more detail about the distribution of measurements, although antibody concentrations are often summarized with geometric means when values are skewed. The registry describes 22F enzyme-linked immunosorbent assay measurement and geometric mean concentrations, but provides no numerical concentration results in the record details.
What does randomization contribute?
In general, random assignment is used to reduce systematic differences between comparison groups at baseline. It does not guarantee identical groups, and the quality of the comparison also depends on how assignments were generated and concealed. The registry identifies the study as randomized but does not report the sequence-generation method or allocation concealment. It lists the study as open-label with no masking. Laboratory measurement is the basis of the primary endpoint, but the record does not describe whether laboratory personnel were masked to assignment.
Why does the analysis population matter?
The primary analysis was specified for the according-to-protocol immunogenicity cohort, defined in the registry as evaluable subjects with immunogenicity data. This is narrower in description than all enrolled participants. An analysis based on evaluable participants can be affected if missing measurements or exclusions are related to assignment or outcome. That is a general concern, not evidence that such a pattern occurred in this trial. Cohort counts by arm, exclusions, and reasons for missing data are not reported in the registry record.
How should planning calculations be understood?
General sample-size planning asks how many participants would be needed to detect an assumed effect under specified statistical assumptions. The registry’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These assumptions describe an illustrative planning exercise, not the trial’s original design justification. The trial’s own sample-size justification is not reported in the registry record. Specific planning participant counts and the underlying observed effect are not reported in the registry record, so no such values can be interpreted.
A planned sample size is not “observed power.” Power is a design concept tied to an assumed effect and analysis procedure; calculating it after observing data does not resolve uncertainty about the estimated effect. Planning illustrations that scale an observed effect are hypothetical design scenarios. They do not change the evidence from the enrolled participants, and they should not be read as additional trial results.
What about multiple outcomes and time points?
The primary outcome concerns multiple pneumococcal serotypes, and the registry lists numerous secondary immunogenicity outcomes. When many hypotheses are tested, the chance of at least one apparently unusual result can increase if no multiplicity strategy is used. Methods such as prespecifying a primary comparison or adjusting inference across tests can address that issue, depending on the scientific question. The registry record does not report a multiplicity strategy, hierarchy of testing, or adjustment method. It also does not report interim analyses or a detailed statistical analysis plan.
The endpoint description sets a specific time point, one month after dose 2 at Month 3. The registry also notes that the primary outcome has several categories or time points and is not reduced to one comparison. In the absence of a single posted comparison result, the endpoint definition should not be mistaken for a numerical result. The reported details do not support reconstructing an analysis from summary statistics.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary immunogenicity outcome and several secondary outcomes. The primary endpoint itself assesses seroprotection across 10 pneumococcal serotypes, while secondary outcomes cover additional pneumococcal and co-administered vaccine immune measures. Testing multiple serotypes, outcomes, or time points can raise multiplicity concerns. In general, multiplicity methods control or describe the increased chance of false-positive findings across a family of tests. The registry does not report a testing hierarchy, adjustment procedure, or other multiplicity strategy.
The registry’s primary analysis population is the according-to-protocol cohort for immunogenicity. It includes evaluable subjects for whom immunogenicity data were available. The record does not report how many participants were included in that cohort in each arm, how many were excluded, or why any participant lacked evaluable data. It also does not describe an imputation approach or other missing-data method. Missing-data handling is therefore not reported in the registry record.
These details affect interpretation. An according-to-protocol analysis describes results among participants meeting the analysis criteria; it is not automatically equivalent to an analysis of every randomized participant. If inclusion or availability of measurements relates to treatment assignment or response, the analyzed groups may differ from the groups created by randomization. That is a general methodological consideration, not a claim about what happened in this study.
The registry reports an enrollment of 351, but does not provide the participant flow or the primary analysis counts by arm in the registry record for this description. A statistical analysis plan, interim analysis details, and the sample-size justification are not reported in the registry record.
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 I Group | 5 | 175 | 2.9% |
| Synflorix II Group | 7 | 176 | 4.0% |
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 I Group | 173 of 175 |
| Synflorix II Group | 175 of 176 |
Most frequent serious adverse event terms
| Event term | Organ system | Synflorix I Group | Synflorix II Group |
|---|---|---|---|
| Respiratory syncytial virus infection (Primary phase) | Infections and infestations | 1 of 175 | 1 of 176 |
| Asthma (Primary phase) | Respiratory, thoracic and mediastinal disorders | 0 of 175 | 1 of 176 |
| Febrile convulsion (Booster phase) | Nervous system disorders | 1 of 174 | 0 of 171 |
| Dyspepsia (Primary phase) | Gastrointestinal disorders | 0 of 175 | 1 of 176 |
| Dermatitis allergic (Primary phase) | Skin and subcutaneous tissue disorders | 1 of 175 | 0 of 176 |
| Bronchopneumonia (Primary phase) | Infections and infestations | 0 of 175 | 1 of 176 |
| Gastroenteritis (Primary phase) | Infections and infestations | 0 of 175 | 1 of 176 |
| Gastroenteritis viral (Primary phase) | Infections and infestations | 1 of 175 | 0 of 176 |
| Lower respiratory tract infection (Primary phase) | Infections and infestations | 0 of 175 | 1 of 176 |
| Salmonellosis (Primary phase) | Infections and infestations | 1 of 175 | 0 of 176 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Synflorix I Group | Synflorix II Group |
|---|---|---|---|
| Irritability (Primary phase) | General disorders | 149 of 175 | 158 of 176 |
| Redness (Primary phase) | General disorders | 137 of 175 | 135 of 176 |
| Drowsiness (Primary phase) | General disorders | 130 of 175 | 130 of 176 |
| Redness (Booster phase) | General disorders | 118 of 174 | 115 of 169 |
| Fever- rectal (Primary phase) | General disorders | 108 of 175 | 116 of 176 |
| Irritability (Booster phase) | General disorders | 113 of 174 | 104 of 169 |
| Swelling (Primary phase) | General disorders | 111 of 175 | 105 of 176 |
| Pain (Primary phase) | General disorders | 92 of 175 | 110 of 176 |
| Pain (Booster phase) | General disorders | 103 of 174 | 93 of 169 |
| Swelling (Booster phase) | General disorders | 97 of 174 | 99 of 169 |
Serious events with the highest arm-level rate: otitis media (booster phase) (0.6%), febrile convulsion (booster phase) (0.6%), pneumonia (booster phase) (0.6%), urinary tract infection (booster phase) (0.6%), dermatitis allergic (primary phase) (0.6%).
The serious adverse event listings give denominators of 175 subjects in the Synflorix I Group and 176 in the Synflorix II Group. The corresponding serious adverse event counts are 5 and 7. These are counts of subjects affected as listed in the registry, not a statistical estimate of the difference in risk. No confidence interval or formal between-group test for these figures is reported in the registry record.
The registry also lists serious event terms with a reported frequency of 0.6% each: otitis media, febrile convulsion, pneumonia and urinary tract infection during the booster phase, and dermatitis allergic and respiratory syncytial virus infection during the primary phase. The record details do not give further event-specific denominators or details about whether a subject could contribute to more than one term. The listed frequencies should therefore be read individually, not added together.
The groups are named Synflorix I and Synflorix II in the safety listing. The registry entries do not explicitly connect those labels to the schedule descriptions, so the event counts should not be attributed to a particular schedule. Deaths are not reported in the registry record; a blank death entry does not establish that there were no deaths. The safety listings are descriptive and do not, on their own, establish a causal relationship between vaccination and an event.
12. What the Result Does, and Does Not, Mean
The posted information describes a randomized comparison of two pneumococcal vaccine schedules given alongside DTPa-combined vaccines. It identifies the primary immune outcome as the number of subjects meeting an antibody threshold for the assessed pneumococcal serotypes one month after dose 2. It also identifies the according-to-protocol immunogenicity cohort as the analysis population.
The registry record does not report the primary outcome counts by arm, a comparison estimate, or its precision. It therefore does not establish from the reported details which schedule had more subjects meeting the antibody threshold, how large any difference was, or whether an estimated difference was compatible with a range of values that would matter statistically. The listed endpoint definition is not itself evidence of a particular result.
Even if numerical antibody results were available, seroprotection would remain an immunogenicity measure. It records whether antibody concentration crosses a specified cutoff; it does not directly measure pneumococcal disease or establish the degree of clinical protection. Likewise, the listed secondary immune outcomes would address additional laboratory measures, not automatically clinical outcomes.
The serious adverse event counts and listed event terms provide descriptive safety information. They do not establish that an event was caused by vaccination, nor do they by themselves provide a precise comparative safety estimate. The record does not report a formal statistical comparison for the serious adverse event counts, event-specific denominators for the listed terms, or death counts.
Accordingly, the registry entries support a clear account of the study design, endpoint definition, analysis population and reported serious-event listings. They do not support a conclusion about the primary result or the relative performance of the schedules. The study is marked completed, but completion does not replace the missing numerical results and analysis details needed to judge the magnitude and precision of the immunogenicity comparison.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between a vaccination schedule and the time point at which an immune response is assessed. The primary outcome is measured one month after dose 2, at Month 3, while the arm descriptions include schedules that continue through Month 11. The endpoint therefore addresses a specified stage of the schedules, rather than summarizing the complete course.
It also illustrates how an immune response can be represented in different ways. A threshold-based count is easy to interpret as the number of subjects who meet a defined antibody level, while a concentration summary retains information about the magnitude of measured antibody responses. The registry lists both seroprotection and geometric mean concentration-related outcomes, but does not give numerical results for the primary outcome in the record details.
Randomized, parallel-group studies can support comparisons between assigned schedules, while an open-label design and an according-to-protocol analysis population remain important context. The primary outcome is laboratory-based, but the registry does not say whether laboratory assessment was masked. The defined analysis cohort also means that participant inclusion and missing measurements matter to interpretation; those counts and handling details are not reported.
Finally, the record demonstrates why design details and results must be distinguished. Enrollment, outcome definitions and adverse event counts describe aspects of the study, but they do not substitute for an arm-specific primary estimate with a measure of precision. With no primary comparison result reported, statistical interpretation must remain focused on what was measured and what information is absent.
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 limitation for interpreting efficacy-related findings is that the registry record does not report numerical results for the primary seroprotection outcome. There are no arm-specific primary counts, comparison estimate, confidence interval, or test result in the registry record. The magnitude and precision of the primary immunogenicity comparison cannot therefore be assessed.
The analysis population is defined as the according-to-protocol immunogenicity cohort, but cohort sizes, participant flow, exclusions and reasons for missing measurements are not reported in the registry record. The record also does not describe missing-data handling. This limits assessment of how the analyzed participants relate to the full enrolled population.
The study is described as randomized and open-label, but randomization methods, allocation concealment and masking of laboratory personnel are not reported. The record lists many secondary immune outcomes, but a multiplicity plan and statistical analysis plan are not reported. The trial’s own sample-size justification, interim analyses and detailed analysis methods are also not reported in the registry record.
For safety, serious event counts are listed by Synflorix group, but their mapping to the schedule descriptions is not explicit in the registry entries. The listed event-term frequencies have no further event-specific context, and death counts are not reported. These limitations constrain interpretation of both the immune outcomes and the safety listings without implying that an unreported result was favorable or unfavorable.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety & Immunogenicity Study of 10-Valent Pneumococcal Conjugate Vaccine When Administered as a 2-Dose Schedule — NCT00307034.
- Registry record last updated 2018-06-08; status last verified 2017-02.
- Results first posted 2017-04-04.
- 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
NCT00307034 is a completed, randomized, open-label, parallel-group phase III study sponsored by GlaxoSmithKline, with enrollment of 351. It compared a 10-valent pneumococcal conjugate vaccine given on 2-4-11 months and 2-3-4-11 months schedules, alongside DTPa-combined vaccines administered at 2-4-11 months.
The primary outcome was the number of subjects meeting the antibody threshold for seroprotection against 10 pneumococcal serotypes one month after dose 2, at Month 3. The primary analysis population was the evaluable according-to-protocol immunogenicity cohort. The registry record does not report primary outcome counts or a between-group estimate.
Safety listings give serious adverse event counts of 5 among 175 subjects and 7 among 176 subjects in the Synflorix I and Synflorix II groups. Several serious event terms are listed at 0.6% each. The schedule mapping for these group labels and death counts are not reported in the registry record.