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 Immunization of Children Previously Primed With GSK Pneumococcal Vaccine GSK1024850A and of Unprimed Children in Nigeria (NCT01153893), a non-randomized phase 3 study. The primary outcome is Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited)..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01153893 |
| Phase | Phase 3 |
| Condition | Infections, Streptococcal |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 105 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy Nigerian children previously enrolled in the primary vaccination study NCT00678301. The registry record distinguishes children previously primed with Synflorix from unprimed children who had not previously received a pneumococcal vaccine. Overall enrollment was 105.
Intervention
The study evaluated pneumococcal vaccine GSK1024850A, identified in the arm descriptions as Synflorix. Previously primed children received a booster dose. Unprimed children received a two-dose catch-up course in the second year of life. The record also describes co-administration with a booster dose of Infanrix.
Comparator
The two groups followed different vaccination histories and schedules. The allocation was non-randomized, so the groups are not a like-for-like control comparison. The unprimed group should not be treated as a randomized comparator for the primed group.
Primary question
Among the primed group, how many participants reported Grade 3 solicited or unsolicited symptoms within 31 days (Day 0 to Day 30) after the Synflorix booster? Grade 3 was defined as severe symptoms that prevented normal activity. The registry record does not report the primary endpoint result.
The broader study objective was to assess safety, reactogenicity and immunogenicity when the vaccine was given as a booster or as a two-dose catch-up vaccination. The primary endpoint focuses on severe symptoms after the booster in the primed group; it does not directly answer whether the groups differed, because they were not randomized and received different schedules. Other listed outcomes cover antibody concentrations, opsonophagocytic activity and additional adverse-event categories. The registry record identifies those outcomes but does not report their results.
3. Trial Design
NCT01153893 is recorded as a completed Phase 3 study with a parallel-group model and non-randomized allocation. The registry lists enrollment of 105. The study began on 2010-10-04, and primary completion was recorded as 2011-02-16. Masking was listed as none. GlaxoSmithKline was the sponsor.
The study included a Synflorix/Infanrix primed group and a Synflorix/Infanrix unprimed group. Previously primed participants had received Synflorix in the primary study NCT00678301. They received a Synflorix booster co-administered with an Infanrix booster at 15-21 months of age. Participants in the unprimed group had not previously received a pneumococcal vaccine. They received a two-dose Synflorix catch-up course at 15-21 and 17-23 months of age, with an Infanrix booster co-administered with the first Synflorix dose.
These groups differ in prior vaccination and in the pneumococcal vaccination schedule. Non-randomized allocation means that group membership was not assigned randomly, and the groups should not be interpreted as equivalent treatment arms. Differences in outcomes, if reported, could reflect differences between the groups beyond the vaccine schedules. The registry record does not report a randomized comparison or an adjustment strategy for such differences.
The record describes the booster-phase objectives and outcomes. It states that objectives and outcomes for the primary vaccination phase are in a separate protocol posting, NCT00678301. Thus, this record concerns the later booster and catch-up phase rather than the primary vaccination phase itself.
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: Because of an issue with the informed consent of a child, the data of the child, who had a non-related to study medication serious adverse event, are not detailed in this analysis. Data were reanalyzed for the 104 subjects with data available.
Overall Study
| Stage | Synflorix/Infanrix Primed Group | Synflorix/Infanrix Unprimed Group |
|---|---|---|
| STARTED | 68 | 36 |
| COMPLETED | 67 | 36 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Synflorix/Infanrix Primed Group | Synflorix/Infanrix Unprimed Group |
|---|---|---|
| Adverse Event | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The Total Vaccinated cohort included all vaccinated subjects.
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/Infanrix Primed Group | Synflorix/Infanrix Unprimed Group | Total |
|---|---|---|---|---|
| Participants analysed | 68 | 36 | 104 | |
| Age, Continuous | Months | 16.7 (SD 1.00) | 16.4 (SD 0.91) | 16.55 (SD 0.955) |
| Sex: Female, Male: Female | Participants | 29 | 17 | 46 |
| Sex: Female, Male: Male | Participants | 39 | 19 | 58 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited)., measured over Within 31 days (Day 0 to Day 30) after administration of a booster dose of Synflorix vaccine in the Synflorix/Infanrix primed Group..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants reporting Grade 3 solicited or unsolicited symptoms within 31 days (Day 0 to Day 30) after the Synflorix booster in the primed group. Grade 3 means a severe symptom that prevented normal activity. Solicited local symptoms were pain, redness and swelling; solicited general symptoms were drowsiness, fever, irritability and loss of appetite. An unsolicited adverse event was an event reported in addition to the solicited symptoms, including a solicited symptom beginning outside its specified follow-up period.
The endpoint is a participant count, so it is intended to describe how many vaccinated participants experienced a severe symptom in the defined period. Severity and timing make the endpoint relevant to short-term reactogenicity and tolerability. It combines solicited and unsolicited symptoms, however, and therefore includes events collected through different reporting routes. Interpretation depends on the stated follow-up window and Grade 3 definition.
The primary endpoint applies specifically to the primed group after a booster dose. It is not a direct comparison of the booster schedule with the unprimed catch-up schedule. Although the registry identifies the endpoint and its definition, the primary endpoint count is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and design, but does not report the primary endpoint result. It therefore does not support a numerical conclusion about the number of primed participants who experienced Grade 3 solicited or unsolicited symptoms during the specified follow-up period. The endpoint definition is detailed, but its count and any associated estimate of uncertainty are not reported in the registry record.
The posted adverse-event summary includes 1 serious adverse event among 68 participants at risk in the primed group and 0 among 36 participants at risk in the unprimed group. It also reports other adverse events in 46 of 68 participants in the primed group and 25 of 36 participants in the unprimed group. These are descriptive counts in groups with different vaccination histories and schedules. Because allocation was non-randomized, these figures do not constitute a randomized comparative estimate and should not be read as evidence that one schedule caused a difference in event frequency.
The serious-event listing identifies Drowning at 1.5%. The record does not establish from this listing alone whether the event was caused by vaccination. A serious adverse event is a safety classification, not a statement of causation. The registry record gives no deaths for either group. It does not report further detail in the registry record for interpreting the circumstances or relationship of the listed serious event.
The study also lists antibody concentrations, opsonophagocytic activity and other safety outcomes. These outcome titles show the planned scope of assessment, but their outcome values are not reported in the registry record. The record lists 10 outcome measures and 0 analyses. Consequently, there are no posted analysis estimates, confidence intervals or hypothesis-test results in the analysis record from which to judge precision or statistical evidence for these outcomes.
Even when an outcome count is available, a count alone has limited comparative meaning without a clear denominator, outcome definition, follow-up context and appropriate analysis. The posted adverse-event counts include at-risk denominators, but the study design remains non-randomized. Confidence intervals, when reported, describe the range of values compatible with the data under an analysis model; they do not remove design limitations or establish causation. No confidence intervals are reported for the outcomes.
Overall, the record supports a description of the study design, planned endpoints and a small set of adverse-event counts. It does not provide the primary Grade 3 symptom result or the immunogenicity results. Claims about comparative efficacy, safety differences, or the size and precision of treatment effects would go beyond the reported results.
9. Statistical Methods Explained
The registry describes a parallel study with non-randomized allocation and no masking. These design features matter when interpreting any observed differences. A parallel design follows participants in separate groups, while non-randomized allocation means group membership is not assigned by chance. As a result, the primed and unprimed groups are not interchangeable control groups: they entered with different pneumococcal vaccination histories and received different schedules.
What does a participant count describe?
The primary endpoint is a count of participants with Grade 3 symptoms, rather than a continuous measurement such as an antibody concentration. For a count to be interpretable, it needs its population, event definition and observation period. The registry gives these elements: the Total Vaccinated cohort includes all vaccinated subjects; Grade 3 symptoms are severe symptoms preventing normal activity; and the primary window is within 31 days (Day 0 to Day 30) after the booster in the primed group. The record does not give the primary count itself.
For adverse-event counts, the denominator identifies the number of participants at risk in each group. The posted serious-event figures are 1 among 68 in the primed group and 0 among 36 in the unprimed group. A count does not by itself quantify uncertainty. Statistical uncertainty depends on the amount of information and the analysis used. No confidence intervals or formal comparisons are reported in the registry record.
Why does the allocation matter?
Random allocation can, in expectation, balance measured and unmeasured baseline characteristics across groups. That feature is absent in a non-randomized study. Here, prior pneumococcal vaccination is explicitly different between the groups, and the dosing schedules differ as well. A direct numerical contrast could therefore mix effects of schedule with differences in prior vaccination or other group characteristics. The registry record does not report a statistical adjustment plan, so an adjusted comparison should not be assumed.
Descriptive results can still characterize the observed participants and events. They do not, without an appropriate design and analysis, isolate a causal effect. This distinction is especially important for the adverse-event counts: reporting the values by group is not equivalent to testing whether the schedules differ or attributing an event to vaccination.
What would an interval or test add?
In general, a confidence interval expresses uncertainty around an estimate under the chosen statistical model. A narrower interval indicates greater precision under that model, while a wider interval indicates less precision. A hypothesis test evaluates compatibility between data and a specified null hypothesis under its assumptions. Neither tool corrects non-random allocation, missing outcome information or an unsuitable comparison. No interval estimates or hypothesis-test results are reported for the outcomes in this registry record.
The primary outcome is a binary event at the participant level: a participant either met the Grade 3 symptom definition during the window or did not. For binary outcomes, analyses may describe event counts and denominators or compare event probabilities. The registry record supplies the endpoint type and some safety counts, but no primary endpoint result or comparative effect estimate. No new effect estimate can be inferred from the outcome descriptions alone.
What is the role of the planning assumptions?
The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not the trial's own design justification, and they do not establish that the trial had a particular probability of detecting an effect. The registry record does not report the trial's sample-size justification or the numerical planning outputs. Such illustrations are not observed power and should not be interpreted as evidence about the study's results.
When a planning calculation uses a fraction of an observed effect, the result depends on the chosen target effect and the model assumptions. A planning sample size is a prospective illustration, not a summary of what the completed trial demonstrated. The record does not report the fractions or the numerical sample-size values needed to discuss individual scenarios.
What analyses are documented?
The record lists 10 outcome measures and 0 analyses. The primary outcome definition and secondary outcome titles are available, but the statistical analysis procedures and numerical results are not reported in the registry record. It is therefore not possible to establish whether analyses were adjusted, how uncertainty was quantified, or whether any prespecified statistical model was used. The absence of reported analysis details should not be filled in with assumptions based on common practice.
The secondary outcomes include antibody concentrations against vaccine and cross-reactive pneumococcal serotypes, opsonophagocytic activity against those serotype categories, antibodies against Protein D, and several adverse-event summaries. These outcome types do not all have the same statistical form. Concentration outcomes summarize quantitative measurements, while event outcomes summarize participants reporting events. Their analysis may require different descriptive summaries and models, but the registry record does not state which methods were used.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes alongside the primary Grade 3 symptom endpoint. These cover antibody concentrations, opsonophagocytic activity, Protein D antibodies and several adverse-event categories. When several outcomes are assessed, the chance of at least one apparently notable result can increase if each is tested separately. General approaches to multiplicity include defining a hierarchy, adjusting test thresholds or treating secondary findings as descriptive. The registry record does not report whether multiplicity was addressed or how outcomes were prioritized beyond identifying the primary endpoint.
Missing-data methods are not reported in the registry record. The primary population is described as the Total Vaccinated cohort, defined as all vaccinated subjects, but this alone does not explain how missing symptom reports or incomplete follow-up were handled. The record does not report missingness counts, imputation procedures, sensitivity analyses or rules for including participants with incomplete observations. Without those details, the effect of missing information on the endpoint cannot be assessed.
The record gives group-specific numbers at risk for the adverse-event summary: 68 in the primed group and 36 in the unprimed group. Overall enrollment was 105. The registry record does not explain the relation between overall enrollment and the group-specific at-risk populations, so no reason for the difference should be inferred.
The study is non-randomized, and the two groups differ in prior vaccination and schedule. The record does not report a method for adjusting comparisons for these differences. It also does not report a protocol-level statistical analysis plan, interim analyses, or a sample-size justification. These omissions limit assessment of prespecification, missing-data handling and the interpretation of multiple outcome findings.
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/Infanrix Primed Group | 1 | 68 | 1.5% |
| Synflorix/Infanrix Unprimed Group | 0 | 36 | 0.0% |
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/Infanrix Primed Group | 46 of 68 |
| Synflorix/Infanrix Unprimed Group | 25 of 36 |
Most frequent serious adverse event terms
| Event term | Organ system | Synflorix/Infanrix Primed Group | Synflorix/Infanrix Unprimed Group |
|---|---|---|---|
| Drowning | General disorders | 1 of 68 | 0 of 36 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Synflorix/Infanrix Primed Group | Synflorix/Infanrix Unprimed Group |
|---|---|---|---|
| Pain | General disorders | 27 of 68 | 13 of 36 |
| Respiratory tract infection | Infections and infestations | 13 of 68 | 7 of 36 |
| Malaria | Infections and infestations | 8 of 68 | 10 of 36 |
| Fever | General disorders | 8 of 68 | 3 of 36 |
| Swelling | General disorders | 4 of 68 | 2 of 36 |
| Conjunctivitis | Eye disorders | 3 of 68 | 2 of 36 |
| Furuncle | Infections and infestations | 4 of 68 | 1 of 36 |
| Upper respiratory tract infection | Infections and infestations | 3 of 68 | 2 of 36 |
| Enteritis | Gastrointestinal disorders | 0 of 68 | 2 of 36 |
Serious events with the highest arm-level rate: drowning (1.5%).
The serious adverse-event summary reports 1 event among 68 participants at risk in the Synflorix/Infanrix primed group and 0 among 36 at risk in the unprimed group. The record lists Drowning at 1.5% among the top serious terms. It reports no deaths for either group. These figures describe the registry's safety summary; they do not establish that an event was caused by vaccination.
The summary also reports other adverse events in 46 of 68 participants in the primed group and 25 of 36 participants in the unprimed group. These counts are distinct from the serious-event counts. They should be read with their group denominators and in light of the different vaccination histories and schedules. The groups were not randomized, so a difference in counts would not by itself establish a difference caused by the treatment schedule.
A serious adverse event is a regulatory safety category and is not synonymous with a Grade 3 solicited symptom. The primary endpoint concerns severe symptoms that prevented normal activity within the defined post-booster period. The posted serious-event summary does not replace that endpoint, and its count does not supply the missing primary symptom result.
12. What the Result Does, and Does Not, Mean
The record documents a completed Phase 3 study examining a booster schedule in previously primed children and a catch-up schedule in unprimed children. It defines a primary short-term symptom endpoint and lists immunogenicity and additional safety outcomes. It also provides some group-specific adverse-event counts. These details allow readers to understand what the study set out to assess and the context of the reported safety figures.
The record does not report the primary Grade 3 symptom count, numerical results for the listed immunogenicity outcomes, confidence intervals or formal analysis results. The listed adverse-event counts are descriptive. Because allocation was non-randomized and the groups differed in prior vaccination and schedule, those counts do not establish a causal difference between schedules. The serious-event listing also does not on its own identify whether the event was related to vaccination.
The study's outcomes have distinct meanings. Antibody concentration and opsonophagocytic activity are immunogenicity measures; symptom counts and adverse-event summaries concern safety and reactogenicity. A planned outcome is not a result, and the inclusion of an outcome in the registry does not demonstrate a favorable or unfavorable finding. The absent numerical results prevent assessment of the magnitude and precision of the primary and immunogenicity outcomes.
Accordingly, the record supports a description of the trial question, design and a limited set of observed safety counts, but not a conclusion about comparative vaccine effects. It cannot establish that either schedule was better or worse, nor can it establish the absence of events beyond those reported. The findings should be interpreted within the specific populations and follow-up described, and not generalized beyond what the registry record reports.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it places two different vaccination histories and schedules in separate, non-randomized groups. A reader might be tempted to treat one group as the control for the other, but the groups are not like-for-like comparators. That distinction is essential: an observed numerical difference would not isolate the effect of the vaccine schedule when group membership and prior vaccination differ.
The record also separates a clearly defined primary endpoint from a wider set of secondary safety and immunogenicity outcomes. This illustrates why endpoint definitions, follow-up windows and populations matter. The primary endpoint concerns Grade 3 solicited or unsolicited symptoms during a specified period after the booster in the primed group; it is not interchangeable with the broader serious adverse-event summary or with antibody outcomes.
Another statistical lesson is the difference between outcome registration and outcome reporting. The registry names 10 outcome measures but lists 0 analyses. Without numerical primary and immunogenicity results or uncertainty estimates, readers cannot evaluate effect size or precision for those outcomes. A detailed endpoint definition does not fill that reporting gap.
Finally, the adverse-event counts show why denominators and design context should accompany counts. The figures are reported by group, but group sizes and prior schedules differ, and no randomized comparative analysis is documented. Reading the counts descriptively is possible; interpreting them as causal evidence is not supported by the record. These issues are broadly relevant when evaluating registry entries with multiple outcomes and non-randomized groups.
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 direct limitation is incomplete outcome reporting in the registry record. The primary endpoint is defined but its result is not reported. The listed secondary outcomes include immunogenicity and additional safety measures, but their numerical results are not reported. The record lists 0 analyses, so there are no reported estimates, confidence intervals or hypothesis tests with which to assess magnitude or precision.
The non-randomized design limits comparative interpretation. The primed and unprimed groups differ by prior pneumococcal vaccination and received different schedules. The registry record does not report methods for adjusting comparisons for these differences. Any group contrast would therefore need particular caution and cannot be treated as a randomized estimate.
The record does not report the statistical analysis plan, missing-data procedures, multiplicity handling, interim analyses or the trial's sample-size justification. These details would help readers assess prespecification and the robustness of the analyses. The listed planning assumptions are an illustration and are not evidence of observed power or a substitute for the trial's design rationale.
Follow-up and endpoint scope also constrain interpretation. The primary symptom endpoint covers the defined post-booster period in the primed group and does not summarize all possible safety outcomes or establish longer-term effects. The serious-event summary is limited to the events and denominators reported. The record does not provide additional context for the Drowning term or establish its relationship to vaccination.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immunization of Children Previously Primed With GSK Pneumococcal Vaccine GSK1024850A and of Unprimed Children in Nigeria — NCT01153893.
- Registry record last updated 2018-09-20; status last verified 2016-09.
- Results first posted 2012-03-15.
- 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
NCT01153893 is a completed, non-randomized Phase 3 parallel-group study sponsored by GlaxoSmithKline. It enrolled 105 participants and evaluated Synflorix as a booster in previously primed children and as a two-dose catch-up course in unprimed children, with Infanrix co-administration described in both groups. The primary outcome was the number of primed participants reporting Grade 3 solicited or unsolicited symptoms within 31 days (Day 0 to Day 30) after the booster.
The registry record reports serious adverse events in 1 of 68 at-risk primed participants and 0 of 36 at-risk unprimed participants, with other adverse events in 46 of 68 and 25 of 36, respectively. Drowning is listed at 1.5% among top serious terms. The primary endpoint result, immunogenicity results and analysis estimates are not reported in the registry record. Non-randomized allocation and the different group histories and schedules limit direct comparison.