Safety & Immunogenicity of Pneumococcal Vaccine 2189242A Co-administered With DTPa-HBV-IPV/Hib in Healthy Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety & Immunogenicity of Pneumococcal Vaccine 2189242A Co-administered With DTPa-HBV-IPV/Hib in Healthy Infants (NCT01204658), a randomized phase 2 study. The primary outcome is Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms Related to Vaccination - Primary Phase of the Study.

2. Clinical Question

Statistically, the question is whether the recorded short-term symptom experience differs across the vaccine regimens. The registry describes a randomized, double-blind, parallel-group phase 2 study, but it does not provide the primary symptom counts, effect estimates, confidence intervals, or a reported test of between-group differences. The listed aims also include antibody concentrations and opsonophagocytic activity during the primary and booster phases. Those immunogenicity outcomes broaden the study’s assessment, but numerical results for them are not included in the record details.

3. Trial Design

This was a randomized, double-blind, parallel-group phase 2 trial sponsored by GlaxoSmithKline. The registry lists an enrollment of 576 and a status of completed. The recorded study start date is 2010-09-27, and the primary completion date is 2011-11-03. The population is described as healthy infants; group descriptions specify infants aged 6–14 weeks at primary vaccination.

The listed regimens include GSK 2189242A with low doses of pneumococcal pneumolysin toxoid proteins (dPly) and pneumococcal histidine protein D (PhtD), and GSK 2189242A with high doses of those proteins. The other listed groups received Synflorix or Prevnar 13. Each regimen was co-administered with Infanrix Hexa. Group descriptions state that the primary vaccination course involved 3 doses, with a booster phase also described. The brief summary places the booster at 12-15 months of age; the registry’s group descriptions also refer to booster vaccination at a later study month but do not give a complete account for every group in the record excerpt.

Randomization is intended, in general, to reduce systematic differences between groups at assignment, while double masking is intended to limit influences from knowledge of assigned treatment. The registry does not state who was masked, how allocation was generated or concealed, or whether masking was maintained. It also does not report a detailed protocol for visits, adherence, or deviations. Those details should not be inferred from the design labels alone.

The four named regimens allow the registry to record outcomes across the experimental formulations and the two comparator vaccines. However, the record does not specify a hierarchy of pairwise contrasts or identify one comparator as the sole reference for the primary endpoint. The sample-size justification, the planned statistical analysis, and any interim-analysis procedure are not reported in the registry record. The listed enrollment is a study-level figure and should not be treated as the number analyzed for every endpoint.

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: The study duration is approximately 10 to 14 months depending on age at recruitment and age at booster vaccination. 2 Phases in the study: Primary Phase when subjects received a 3-dose of pneumococcal vaccine co-administered with Infanrix hexa™ (Months 0, 1, 2), and Booster Phase when subjects received one dose of the same vaccines (Month 10).

Primary Phase

Reasons for not completing this period:

Booster Phase

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Total Vaccinated cohort for the Primary Phase, which included all subjects who received at least one of the 3 vaccine doses against pneumococcal diseases, with analysis done solely on subjects with post-vaccination solicited symptoms results 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Any and Grade 3 Solicited General Symptoms and With Solicited General Symptoms Related to Vaccination - Primary Phase of the Study, measured over Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course.

The primary outcome is titled as the number of participants with any and Grade 3 solicited general symptoms and with symptoms considered related to vaccination during the primary phase. The monitored symptoms were drowsiness, irritability, loss of appetite, and fever. Any symptom means that the symptom occurred regardless of intensity or assessed relationship to vaccination. Related symptoms were those investigators assessed as causally related to vaccination.

Grade 3 definitions describe substantial symptom severity: drowsiness that prevented normal activity, crying that could not be comforted or that prevented normal activity, not eating at all, and rectal temperature higher than 40.0°C. Fever of at least 38°C was the threshold for recording fever as a solicited symptom. The registry states that the primary results correspond specifically to related Grade 3 fever, even though the outcome title covers several symptom categories.

Recording solicited symptoms during the 7-day (Days 0-6) periods after each dose provides a defined window for capturing short-term reactogenicity. Counts can describe how many participants experienced an event under the registry’s definitions. For a comparative interpretation, counts alone would not establish the size or precision of a difference between regimens; group-specific estimates and uncertainty would also be needed. The primary numerical results and their statistical uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary outcome, the basic observation is whether a participant did or did not meet the event definition within the specified assessment period. Here, the primary endpoint is based on counts of participants experiencing solicited symptoms, with separate concepts of any symptom, Grade 3 severity, and investigator-assessed relationship to vaccination. The registry identifies related Grade 3 fever as the primary result of interest. A count is clinically interpretable in relation to its group and the number assessed, but a count alone does not quantify a contrast between groups.

What would a group comparison show?

In general, a comparative analysis might report each group’s event frequency and an effect measure contrasting groups. Different effect measures answer different questions: an absolute difference describes separation in event frequency, while a relative measure describes the event frequency in one group in relation to another. These measures should not be reconstructed without the necessary group-specific outcome data and the prespecified analysis. The registry record does not report the primary endpoint counts or a designated primary pairwise contrast, so such a comparison cannot be described from the record.

Why does uncertainty matter?

In general, an estimate based on observed participants is subject to sampling variability. A confidence interval communicates uncertainty around an estimate under the assumptions of its statistical method. A wide interval indicates less precision than a narrow interval, though interpretation also depends on the outcome and the question being asked. The primary endpoint’s estimate and confidence interval are not reported in the registry record. No p-value for that endpoint is reported either. It is therefore not possible to assess statistical evidence for a group difference or how precisely any difference was estimated.

How should event counts be read?

Counts should be read with their event definition, analysis population, assessment window, and group denominator. In this study, solicited symptoms were assessed in the 7-day (Days 0-6) periods after each dose of the 3-dose primary course. The primary analysis population included participants who had received at least one pneumococcal vaccine dose and had post-vaccination solicited-symptom results available. The record does not give the primary symptom counts by group, so the reported study enrollment should not be substituted for an endpoint-specific denominator.

General statistical practice distinguishes a participant count from a count of repeated events. The primary outcome is expressed as the number of participants with symptoms. The record does not state whether a participant with the same symptom after more than one dose was counted once or separately in every dose-specific analysis. Since the outcome is described across several categories and dose windows, dose-specific and participant-level summaries should not be assumed to be interchangeable.

What do the planning calculations mean?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. In general, a planning calculation asks what sample size might be needed under chosen assumptions to detect a specified effect with a chosen power. It is not a measure of power actually achieved in the completed trial. These illustrations are not a record of the trial’s own design justification, and the registry does not report that justification. The record also indicates that the primary outcome spans several categories or time points and is not reduced to one comparison for this calculation approach.

The planning assumption that the effect to detect is a stated fraction of the observed effect makes the illustration dependent on the observed effect used as its starting point. In general, planning from an observed effect can be sensitive to uncertainty in that estimate. The numerical planning outputs and the observed primary effect are not included in the record details, so no particular planning value or underlying effect can be interpreted.

Why can over-dispersion matter?

For count outcomes in general, a statistical model may assume a particular relationship between the mean and variability. Over-dispersion means the observed variation is greater than the model expects; if not addressed, uncertainty can be understated. That issue is not established for this primary endpoint, which is described as participant counts for binary symptom events. The registry does not report a count model, a dispersion estimate, or an analysis plan that would justify attributing over-dispersion to this trial.

The record lists 29 outcome measures and 8 analyses. In general, testing many outcomes or contrasts raises a multiplicity question: a statistical plan may specify which comparisons are primary and whether adjustment is used to control the risk of misleading positive findings across tests. The registry information does not report an adjustment method or a complete testing hierarchy. The presence of multiple listed outcomes does not itself indicate that an adjustment was or was not performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures and 8 analyses. The outcomes include symptoms, adverse events, antibody concentrations against several pneumococcal proteins and serotypes, and opsonophagocytic activity. The primary outcome title itself covers multiple symptom categories and dose-related time points, while the registry identifies related Grade 3 fever as the primary result. This makes the precise definition of the primary contrast important when interpreting any future numerical result.

In general, multiplicity arises when several outcomes, time points, or pairwise comparisons are evaluated. A statistical analysis plan may specify a testing hierarchy or adjustment to address the chance of false-positive findings across repeated tests. The registry record does not report the plan for multiplicity, any adjustment method, or a complete hierarchy of comparisons. It is therefore not possible to determine from the record whether the reported analyses were adjusted or how confirmatory claims were intended to be controlled.

The primary safety analysis population is defined as the Total Vaccinated cohort for the Primary Phase: participants who received at least one of the pneumococcal vaccine doses and had post-vaccination solicited-symptom results available. This definition clarifies that the primary symptom analysis was not simply described as all enrolled participants. The record does not report how many participants had outcome data available for each dose or symptom, how missing symptom assessments were handled, or whether any sensitivity analyses were conducted.

In general, missing outcome data can affect both the denominator and the interpretation of an event frequency, especially if availability is related to symptom occurrence or assigned regimen. The record does not describe the reasons for missing assessments or a missing-data method. A complete statistical analysis plan, including analysis populations for the other outcomes, is not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchitis (2.1%), concussion (2.1%), otitis media (2.1%), laryngitis (1.4%), febrile convulsion (1.4%).

The registry lists serious adverse event counts by group. In the 10PP-LD/Infanrix Hexa Group, 13 participants with serious events are listed among 146 at risk; the count for other adverse events is 141 among 146 at risk. In the 10PP-HD/Infanrix Hexa Group, the corresponding figures are 9 among 142 for serious events and 137 among 142 for other adverse events. In the Synflorix/Infanrix Hexa Group, they are 21 among 145 and 139 among 145. In the Prevnar 13/Infanrix Hexa Group, they are 17 among 142 and 134 among 142. The registry lists zero deaths in each group.

These are descriptive counts. They do not establish that an event was caused by a vaccine, and the record does not report a statistical comparison of the groups for these outcomes. The serious-event terms listed with percentages are bronchitis, 2.1%; concussion, 2.1%; otitis media, 2.1%; laryngitis, 1.4%; febrile convulsion, 1.4%; and pneumonia, 1.4%. The record does not report group attribution or denominators for these term-specific percentages. The counts should therefore be read as registry safety summaries, not as adjusted comparisons or causal estimates.

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

The record documents a randomized, double-blind, parallel phase 2 study of pneumococcal vaccine regimens co-administered with DTPa-HBV-IPV/Hib in healthy infants. It identifies the primary safety question, the symptom definitions, the assessment window, the study groups, and selected adverse-event counts. These details help define what the trial set out to assess and how its primary symptom outcome was framed.

It does not report numerical results for the primary endpoint. Without related Grade 3 fever counts by group or an estimated contrast with uncertainty, the registry record cannot establish the direction or size of a difference between regimens. It also cannot show how precise such a difference would be. The endpoint description and the study design are not substitutes for outcome results.

The serious adverse event counts and listed event terms provide descriptive safety information, but they do not establish causation or show whether differences between groups are statistically meaningful. Zero deaths are recorded in each group; this should not be expanded into a claim that no safety concerns occurred, since other adverse events and serious events are also listed. The record does not provide an analysis accounting for differences in follow-up or other factors.

The listed secondary outcomes indicate that immunogenicity was also assessed during the primary and booster phases. Their presence does not demonstrate a particular antibody response or functional activity. Numerical results for those outcomes are not reported in the registry record. Likewise, planning illustrations based on an observed effect are calculations under stated assumptions, not evidence of the trial’s observed power or proof of an outcome.

Overall, the registry supports a description of the design, outcome definitions, and posted safety counts. It does not support a conclusion that one regimen had a greater or lesser primary symptom burden, nor does it establish comparative immunogenicity. Those interpretations would require the corresponding numerical results, analysis details, and measures of uncertainty.

13. Why This Trial Matters Statistically

This trial illustrates why registry descriptions and numerical results answer different statistical questions. A detailed endpoint definition tells readers what was counted, the severity threshold, who assessed relatedness, and the time window. It does not reveal how often the event occurred or whether groups differed. For the primary outcome, the record specifies related Grade 3 fever as the primary result, yet does not report the group-specific counts or a comparative estimate.

The trial also contains several dimensions of analysis: multiple vaccine regimens, symptom categories, dose-related observation windows, safety outcomes, and immunogenicity measures across primary and booster phases. In general, that breadth makes a prespecified outcome hierarchy and transparent multiplicity handling important. The registry lists 29 outcome measures and 8 analyses but does not report a complete statistical plan or a method for multiplicity. Readers therefore cannot determine how the various outcomes were prioritized for inference.

The stated analysis population is another important part of interpretation. The primary symptom analysis includes vaccinated participants with post-vaccination solicited-symptom results available, rather than simply being described as all enrolled participants. That definition helps explain which observations could contribute, while the absence of endpoint-specific denominators and missing-data methods limits assessment of completeness.

Finally, the record distinguishes what was assessed from what was found. It identifies antibody and functional activity outcomes and reports selected adverse-event counts, but the primary and immunogenicity results are not numerically reported. Keeping design, outcome measurement, descriptive safety counts, and comparative inference separate prevents a study’s aims from being mistaken for evidence about its results.

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 statistical interpretation is that numerical results for the primary endpoint are not reported in the registry record. Group-specific counts for related Grade 3 fever, effect estimates, confidence intervals, and p-values are not included. Without these values, the magnitude and precision of a primary comparison cannot be assessed.

The primary outcome title spans any symptoms, Grade 3 symptoms, and symptoms considered related to vaccination, and the registry says that primary results correspond to related Grade 3 fever. The record does not provide a full presentation of results across all symptom categories and dose windows. It also does not identify a single designated pairwise comparison among the listed regimens. This limits reconstruction of the precise inferential question.

The primary analysis population requires at least one pneumococcal vaccine dose and available post-vaccination solicited-symptom results. Endpoint-specific denominators, missing-assessment reasons, and methods for handling missing data are not reported. The statistical analysis plan, sample-size justification, and multiplicity approach are also not reported in the registry record.

The group descriptions in the record are incomplete in places, and the registry does not state who was masked or how randomization and allocation concealment were conducted. Numerical immunogenicity results are not included. The posted serious and other adverse-event counts are descriptive, with no reported comparative analysis; term-specific serious-event percentages lack group attribution and denominators in the record. These limitations constrain interpretation to the design, outcome definitions, and the safety counts that are explicitly listed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety & Immunogenicity of Pneumococcal Vaccine 2189242A Co-administered With DTPa-HBV-IPV/Hib in Healthy Infants — NCT01204658.
• Registry record last updated 2019-05-29; status last verified 2019-05.
• Results first posted 2016-09-28.
• 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

NCT01204658 is a completed, randomized, double-blind, parallel phase 2 study sponsored by GlaxoSmithKline, with enrollment listed as 576. The study assessed GSK 2189242A pneumococcal vaccine formulations co-administered with DTPa-HBV-IPV/Hib, alongside groups receiving Synflorix or Prevnar 13 with Infanrix Hexa. The primary outcome concerned solicited general symptoms after each dose of the primary vaccination course; the registry identifies related Grade 3 fever as the primary result.

The registry provides group-level serious and other adverse-event counts and lists serious-event terms with percentages. It also lists antibody and opsonophagocytic activity outcomes. Numerical primary-endpoint and immunogenicity results, the full statistical analysis plan, and the trial’s sample-size justification are not reported in the registry record. Accordingly, the posted information describes the study and selected safety summaries but does not quantify the primary comparative result.