Immunization of Children Previously Primed With GSK Pneumococcal Vaccine GSK1024850A and of Unprimed Children in Mali: Complete Statistical Analysis

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 Mali (NCT00985465), a non-randomized phase 3 study. The primary outcome is Number of Subjects With Grade 3 Adverse Events (Solicited and Unsolicited).

2. Clinical Question

The study addresses safety, reactogenicity and immunogenicity in children receiving different schedules according to prior vaccination. The Pn-Pn group consisted of children previously vaccinated with GSK1024850A in the Malian centre of NCT00678301 and receiving a booster. The Zil-Pn group consisted of children from the unprimed group at that centre, with no previous pneumococcal vaccination, receiving two doses of GSK1024850A. These histories are central to interpreting the groups: the contrast is not simply between two randomly assigned schedules in otherwise comparable children.

The record also lists outcomes for solicited local and general symptoms, unsolicited adverse events, serious adverse events, antibody concentrations against vaccine serotypes, and opsonophagocytic activity. These outcomes broaden the stated objectives, but numerical results for them are not reported in the registry record apart from the adverse-event counts described separately. The primary question is specifically about participants with Grade 3 events during the stated 31-day period, not about all possible effects, longer-term safety, or a causal difference between schedules.

3. Trial Design

This was a Phase 3, parallel-group, non-randomized study sponsored by GlaxoSmithKline. It enrolled 218 participants and is listed as completed. The study start date was 2009-11-12, and the primary completion date was 2010-06-26. Masking is listed as none. These design features describe how the trial was conducted, but do not establish how participants entered each group beyond the prior-vaccination histories stated in the record.

Both groups received the same pneumococcal conjugate vaccine, GSK1024850A, but in different circumstances. The Pn-Pn group had previously received that vaccine in the Malian centre of NCT00678301 and received a booster dose in this study. The Zil-Pn group had not previously received any pneumococcal vaccine and received two doses as catch-up immunization. The brief description places the catch-up vaccination in the second year of life. The posted outcome description focuses on the booster phase; objectives and outcomes for the primary phase are described as belonging to the separate record NCT00678301.

Because allocation was non-randomized, group membership is connected to earlier vaccination history. Thus, any crude difference between groups could reflect prior immunization and other group differences as well as the schedule being assessed. The record does not describe a randomized assignment process, masking, or a parallel untreated control group. It also does not report the protocol’s rationale for the enrollment target, detailed eligibility criteria, or any adjustment strategy for between-group comparisons.

The registry lists 12 outcome measures and 0 analyses. That distinction matters: outcome measures identify what was intended to be assessed, while analyses and numerical estimates would show how results were evaluated and what was observed. The record includes adverse-event counts for the two groups, but does not report a numerical result for the named primary endpoint or an inferential comparison. Consequently, the design and available counts support a description of the posted record, not a claim that one schedule is safer or more effective than the other.

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: A total of 218 subjects were enrolled (147 subjects in the Synflorix Primed Group and 71 subjects in the Synflorix Unprimed Group). A total of 210 subjects were vaccinated in the booster vaccination study (141 out of 160 from the Synflorix Primed Group and 69 out of 78 from the Synflorix Unprimed Group).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one vaccine dose administration documented.

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 Grade 3 Adverse Events (Solicited and Unsolicited), measured over Within 31 days (Day 0-Day 30) after booster vaccination.

The primary endpoint is the number of participants with Grade 3 adverse events, solicited or unsolicited, within 31 days (Day 0-Day 30) after booster vaccination. The endpoint description says that the incidence and nature of Grade 3 symptoms reported during this period are presented. The unit is participants, so the focus is on how many people experienced an event meeting the stated severity category, rather than simply counting event episodes.

Solicited events are symptoms specifically sought during safety follow-up; unsolicited events are also included in the primary endpoint, according to the registry wording. The record does not specify the symptom list, the criteria used to classify an event as Grade 3, or the method used to combine multiple events for a participant. Those details are not reported in the registry record, so the endpoint can be described by its stated category and observation window but not independently reconstructed.

As a general statistical rationale, a participant-level safety endpoint can provide a direct description of the proportion of an assessed group experiencing a defined event category during a defined period. The severity threshold and time window help make the outcome more focused than a count of every symptom at any time. However, the registry does not report the primary endpoint count or an uncertainty interval. The adverse-event counts listed elsewhere do not identify how many participants had Grade 3 events, so they cannot substitute for the primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a participant count, not a continuous measurement. It concerns Grade 3 solicited and unsolicited adverse events within 31 days (Day 0-Day 30) after booster vaccination. A count endpoint of this kind is usually interpreted alongside the number of participants assessed, because the count alone does not communicate how much of the group it represents. In this record, the primary outcome count itself is not reported, so an event frequency for that endpoint cannot be described.

The stated primary analysis population is the Total Vaccinated cohort, defined as participants with at least one vaccine dose administration documented. This definition uses vaccine receipt rather than simply enrollment as its inclusion condition. The record does not give the number in that cohort for the primary analysis, nor does it report how missing safety observations were handled. The denominators in the adverse-event summary are listed separately by group and should be understood as the participants at risk for those entries, not assumed to be the primary endpoint analysis denominator without further information.

In general, binary event outcomes can be summarized as the number of participants with an event and the number assessed. A comparison may then be expressed using an absolute difference, a relative measure, or a model-based estimate. Each approach answers a somewhat different question and relies on analysis choices. No comparison estimate or model is reported in the registry record, so there is no posted effect measure to interpret or reproduce. No adjusted analysis is reported either.

Allocation was non-randomized, and the groups have different vaccination histories. As a general statistical principle, random assignment can help balance both measured and unmeasured characteristics on average, while non-randomized group membership may be associated with other differences. Here, the contrast joins prior immunization status to the current schedule: previously primed children received a booster, while unprimed children received two catch-up doses. A simple group contrast would therefore not isolate the effect of schedule alone. The record does not state that a causal comparison was planned or that confounding was addressed using covariate adjustment.

The posted sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, the assumptions describe participants per arm. This is a planning framework, not observed power and not evidence that the trial was designed around those inputs. The registry does not report the trial’s own sample-size justification, and the primary effect needed to interpret such an illustration is not reported in the registry record. No planning result should be treated as a trial outcome.

As a general explanation, a significance level is a threshold used in a specified testing procedure to control the probability of a particular type of false-positive conclusion under its assumptions. A normal approximation is a mathematical method for estimating a sampling distribution; its suitability depends on the data and the endpoint. The posted assumptions do not establish that this method was used for the trial’s actual analysis. Since the record lists 0 analyses and does not specify a primary inferential procedure, the assumptions should be read only as the stated framework for planning illustrations.

Safety outcomes can overlap: a participant might have more than one symptom or adverse event, and a participant-level measure may differ from an event-level count. This is a general distinction, not a description of unreported trial results. The primary endpoint is worded as a number of participants, while the secondary outcome titles also refer to numbers of subjects with specified symptoms or events. The registry does not explain deduplication, repeated-event handling, exposure adjustment, or how events were assigned to severity categories. These methods are not reported in the registry record.

The study also lists antibody concentrations against vaccine pneumococcal serotypes and opsonophagocytic activity against the same listed serotypes. These are distinct types of immune measurements from adverse-event counts. General statistical methods for such outcomes may involve summaries of distributions or comparisons across time and groups, but the registry record does not specify transformations, estimands, time points, or analysis models. The record’s outcome titles alone do not establish which methods were used. Without reported estimates and their uncertainty, no quantitative immune response interpretation can be made from those titles.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including multiple safety outcomes and immune outcomes involving antibody concentrations and opsonophagocytic activity. The number of listed outcomes does not by itself show how many statistical hypotheses were tested, since the registry also lists 0 analyses. A multiplicity plan—such as a hierarchy of endpoints, adjustment procedure, or designation of exploratory outcomes—is not reported in the registry record. No adjustment for multiple comparisons should therefore be assumed.

The record identifies the Total Vaccinated cohort for the primary analysis and defines it as participants with at least one documented vaccine dose. It does not describe analysis populations for each secondary outcome, or explain how participants with incomplete follow-up or unavailable measurements were treated. Missing-data methods, imputation, censoring rules, and sensitivity analyses are not reported in the registry record.

As a general statistical consideration, missing outcomes can affect both the estimate and its interpretation, particularly if the likelihood of missingness is related to safety symptoms, vaccination history, or other participant characteristics. The record does not provide enough information to assess whether missingness occurred or whether it could have influenced the reported counts. The adverse-event entries give participants at risk and affected counts, but do not provide a fuller account of follow-up completeness.

The registry also does not report an analysis plan specifying primary and secondary testing procedures, handling of repeated observations, or control of false-positive findings across outcomes. These omissions limit reconstruction of the intended statistical analysis. They do not demonstrate that no such methods were used outside the registry record; they mean that they are not reported in the registry record.

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 non-serious adverse event terms

The adverse-event summary lists 0 serious adverse events among 141 participants at risk in the Synflorix Primed Group and 0 among 69 participants at risk in the Synflorix Unprimed Group. It also lists 125 participants with other adverse events among 141 at risk in the primed group, and 64 among 69 at risk in the unprimed group. These are the counts recorded for the named categories. The record does not report death counts.

These figures should not be confused with the primary endpoint. The primary endpoint is the number of participants with Grade 3 solicited or unsolicited adverse events during 31 days (Day 0-Day 30) after booster vaccination, and its numerical result is not reported in the registry record. The other-event category is not further defined in the adverse summary, so it cannot be assumed to mean Grade 3 events or a specific type of symptom.

As a general statistical point, a zero observed count is not proof of zero underlying risk. It describes the observations in the stated group and period. The record does not provide event-term details for serious adverse events, since no serious terms are listed, and does not report a comparative analysis. Non-randomized allocation and differing prior vaccination histories also mean the group counts are descriptive, not a controlled estimate of the effect of one dosing schedule versus another.

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

The record documents a completed Phase 3 study of GSK1024850A in Malian children, with a booster schedule for children previously primed with the vaccine and a two-dose catch-up schedule for children not previously vaccinated against pneumococcus. It gives the intended primary safety outcome and a specified 31-day observation window. The posted adverse-event summary also gives serious and other event counts by group.

Those details do not answer the primary question quantitatively: the number of participants with Grade 3 solicited or unsolicited adverse events is not reported in the registry record. The counts for serious and other adverse events are not substitutes for that endpoint. The registry lists no analyses, and it does not report inferential comparisons or uncertainty estimates for the primary endpoint. Thus, the record does not establish the size or precision of a difference between groups.

The results should also not be read as a randomized comparison. The groups were formed around different previous vaccination histories and received different current schedules. A group contrast could reflect those histories and other differences, as well as the schedules themselves. The record does not report an adjustment strategy that would separate these influences.

The outcome list indicates that immune responses were also of interest, including antibody concentrations and opsonophagocytic activity across vaccine serotypes. Their numerical results are not reported in the registry record. Therefore, the outcome titles do not establish the magnitude, durability, or comparative pattern of immune responses.

As a general interpretation principle, absence of a reported estimate is not evidence of no effect, and a small or zero event count does not establish equivalence or absence of risk. The posted information supports a description of the design and the adverse-event counts that are recorded. It does not support a conclusion about comparative benefit, comparative safety, or clinical effectiveness.

13. Why This Trial Matters Statistically

This study illustrates why vaccination history is part of the statistical question rather than background detail. Previously primed children received a booster, while children with no prior pneumococcal vaccination received two catch-up doses. The groups therefore represent different immunization pathways. Treating them as though they were exchangeable comparison arms would ignore a defining feature of the design.

It also highlights the difference between an endpoint definition and an endpoint result. The registry clearly describes a participant-level Grade 3 adverse-event outcome, including its observation period and the inclusion of solicited and unsolicited events. Yet the corresponding numerical result is not reported in the registry record. Careful reporting needs both a prespecified question and an estimate with enough context to judge its precision.

The adverse-event summary shows how descriptive safety counts can be informative while remaining limited. It records zero serious adverse events in the listed groups and gives counts for other events. But the record does not provide event terms for serious events, a Grade 3 endpoint count, or inferential comparisons. A reader must keep those categories distinct and avoid treating one as a proxy for another.

Finally, the registry lists safety and immunogenicity outcomes, but does not report their numerical analyses. Statistical interpretation depends on estimates, denominators, follow-up, and methods, not outcome titles alone. The record’s limitations make transparent reporting especially important: group structure, analysis population, outcome definition, missingness, and uncertainty all shape what conclusions can reasonably be drawn.

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 study is non-randomized and compares groups with different prior vaccination histories and different current schedules. This limits direct causal interpretation of any group contrast. The registry does not report a strategy for adjustment for confounding, and the groups should not be treated as like-for-like controls.

The principal limitation for interpreting the stated primary question is that its numerical result is not reported in the registry record. The record defines Grade 3 solicited and unsolicited adverse events within 31 days (Day 0-Day 30), but does not state how many participants experienced them or provide an uncertainty estimate. The serious and other adverse-event counts cannot fill that gap because they describe different categories.

Although 12 outcome measures are listed, the registry lists 0 analyses. A statistical analysis plan, multiplicity approach, detailed missing-data methods, and outcome-specific analysis populations are not reported in the registry record. The criteria for Grade 3 classification, solicited symptom definitions, and handling of multiple events per participant are also not reported in the registry record.

The adverse summary uses the group titles Synflorix Primed Group and Synflorix Unprimed Group, whereas the arm descriptions use Pn-Pn and Zil-Pn. The record does not explain this difference in labels. Death counts are not reported in the registry record, and serious-event terms are not listed. Numerical immune outcomes are also not reported in the registry record, limiting interpretation of the stated immunogenicity objectives.

Finally, enrollment of 218 is reported, but the record does not provide a detailed account of participant flow, follow-up completeness, or the relation between enrolled participants and each endpoint-specific analysis population. Without those details, the completeness and representativeness of the outcome counts cannot be fully assessed from the registry record.

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 Mali — NCT00985465.
• Registry record last updated 2018-12-14; status last verified 2018-07.
• Results first posted 2018-12-14.
• 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

NCT00985465 is a completed Phase 3, non-randomized, unmasked, parallel-group study sponsored by GlaxoSmithKline. It enrolled 218 participants, began on 2009-11-12, and had a primary completion date of 2010-06-26. The study assessed pneumococcal vaccine GSK1024850A in Malian children previously enrolled in NCT00678301.

Previously primed participants received a booster dose; unprimed participants received two catch-up doses. The primary endpoint was the number of participants with Grade 3 solicited or unsolicited adverse events within 31 days (Day 0-Day 30) after booster vaccination. The registry defines the primary analysis population as the Total Vaccinated cohort, participants with at least one documented vaccine dose.

The registry lists 12 outcome measures and 0 analyses. It reports serious and other adverse-event counts by group, but the primary endpoint result, inferential comparisons, uncertainty estimates, and numerical immune outcomes are not reported in the registry record. The non-randomized design and different prior vaccination histories constrain comparative interpretation.