Study Evaluating Antibody Response Of 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) 24 Months After Toddler Dose.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating Antibody Response Of 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) 24 Months After Toddler Dose. (NCT01026038), a non-randomized phase 3 study. The primary outcome is Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) 1 Month After Single Dose of 13 Valent Pneumococcal Conjugate (13vPnC) Vaccine.

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label, nonrandomized, single-group study. Participants and clinicians knew which vaccine was administered. The study focused on healthy children who had received a 4-dose pneumococcal conjugate vaccine series during infancy in an earlier study, then received an additional dose of 13vPnC at least 24 months after their last toddler dose. The intervention is described as one dose of 0.5 mL given intramuscularly.

The study had two related aims: to assess persistence of pneumococcal antibodies since the prior study and to evaluate safety and immunogenicity after the additional 13vPnC dose. The primary outcome was serotype-specific IgG geometric mean concentration one month after vaccination. Secondary outcomes included pre-dose IgG GMCs, IgG GMCs at 4 to 7 days after vaccination, pre-dose and post-dose opsonophagocytic activity geometric mean titers, and specified post-dose OPA thresholds.

Enrollment was 263. This is the registry enrollment figure, not necessarily the number included in each outcome analysis. The primary outcome description specifies use of participants with available data for the relevant blood draw and an evaluable immunogenicity population. Outcome-specific participant counts are not reported in the registry record.

The safety record separates participants into categories labelled by prior vaccine sequences: 13vPnC/13vPnC/13vPnC, 7vPnC/7vPnC/13vPnC, and 7vPnC/13vPnC/13vPnC. These categories describe sequences, not a randomized comparison. The registry record does not explain the allocation process for these categories or establish that their participants were comparable. It also does not report a statistical analysis plan, a sample-size justification, or details of interim analyses.

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 263 participants who had received a 4-dose vaccination series of pneumococcal conjugate vaccine as part of study 6096A1-008 (NCT00366678) were enrolled for this study. Out of those 1 participant was a screen failure and was not included in results.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable immunogenicity population: eligible participants, randomized, blood drawn within required timeframes, at least 1 valid and determinate assay result for proposed analysis, received no prohibited vaccines, no major protocol violations. N= number of participants with determinate IgG antibody concentration to serotype.

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 Serotype-specific Pneumococcal Immunoglobulin G (IgG) Geometric Mean Concentration (GMC) 1 Month After Single Dose of 13 Valent Pneumococcal Conjugate (13vPnC) Vaccine, measured over One month after vaccination.

The primary endpoint was serotype-specific pneumococcal immunoglobulin G geometric mean concentration, measured one month after a single dose of 13vPnC. The assay results were expressed in mcg/mL. The endpoint covered 7 common pneumococcal serotypes and 6 additional serotypes specific to 13vPnC.

A geometric mean summarizes measurements that are often analyzed on a multiplicative rather than additive scale. In general, it is calculated after transforming measurements to a logarithmic scale, averaging on that scale, and transforming back. This can be useful for antibody concentrations, which may span a wide range and have a right-skewed distribution. The geometric mean describes the central level of measured antibody; it does not show how many participants crossed a particular threshold or how much individual responses varied.

The registry describes corresponding two-sided 95% confidence intervals. In general, a confidence interval represents uncertainty around an estimated population quantity under the analysis assumptions. A narrower interval indicates greater precision than a wider interval, but the interval does not itself describe individual-level variation. The GMC estimates and their confidence intervals are not reported in the registry record. Therefore, the endpoint's observed levels, serotype-to-serotype patterns, and precision cannot be assessed from the registry record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be described are those named in the registry record. The primary endpoint is a geometric mean concentration, with corresponding two-sided 95% confidence intervals. The record states that geometric means were calculated from participants with available data for the specified blood draw. It does not report the specific calculation procedure, any transformation details, the handling of measurements below or above assay limits, or a model used to estimate the GMCs.

What does a geometric mean represent?

In general, a geometric mean is a measure of central tendency suited to positive measurements that vary multiplicatively. The calculation typically uses a logarithmic scale because proportional differences can be more meaningful than equal absolute differences for measurements spread across a broad range. The mean on the transformed scale is then returned to the original units. This produces a summary that can be less influenced by very high values than an arithmetic mean, although it remains a summary and does not describe every participant's result.

For this study, the endpoint is measured in mcg/mL and is reported separately by serotype. A GMC for a serotype would summarize measured concentrations in the analyzed participants, rather than count participants above a threshold. The registry record does not give the serotype-specific GMC values or the number contributing to each estimate, so these features cannot be evaluated.

How should a confidence interval be read?

In general, a confidence interval expresses uncertainty in an estimate under the assumptions of the statistical procedure. Its width is informative about precision: a narrow interval indicates a more precise estimate than a wide interval. The interval is not a range containing most individual participant values, and it does not convey the full distribution of responses. The primary outcome description specifies two-sided 95% confidence intervals, but their endpoints are not reported in the registry record. The method used to construct them is also not reported in the registry record.

What can the design establish?

The study is described as open-label, nonrandomized, and single-group. In general, random assignment can help balance known and unknown participant characteristics between comparison groups. That protection is not available for a nonrandomized comparison. Open-label status means participants and clinicians knew the administered vaccine, though the registry record does not describe whether laboratory personnel were masked. Because there is no randomized concurrent comparator, the primary endpoint is best interpreted as a post-dose description of antibody concentrations in the analyzed group, not as an estimate of a randomized treatment contrast.

The categories in the safety record are named according to vaccine sequences. Those labels do not turn the design into a randomized multi-arm trial, and the registry record does not establish exchangeability among those categories. No comparative primary-endpoint analysis is described. The record also does not report covariate adjustment or another method intended to address differences between categories.

What do the planning assumptions mean?

The registry includes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not observed power and not evidence that the original study was designed with those assumptions. The record does not report a trial-specific sample-size justification. It also does not report numerical planning results in the registry record describing this study, so no participant requirement can be stated.

In general, a planning calculation estimates how much information a future study might need under specified assumptions. Its result depends on the assumed effect, variability, allocation, and statistical procedure. An illustration based on an observed effect is especially dependent on that estimate, which may itself be uncertain. It should not be read as a property of the completed study or as proof that its analyses had adequate precision.

What is not documented?

The registry record does not report a detailed statistical analysis plan, an approach to multiplicity across serotypes and outcomes, a method for missing assay results, a protocol for handling outliers, or interim analyses. These omissions do not establish that such procedures were not used; they mean they cannot be evaluated from the registry record. The record identifies 10 outcome measures and 302 analyses, but does not explain the relationship between those counts or how inferential error across analyses was addressed. No p-values or primary outcome estimates are available to interpret.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome covers multiple serotypes, and the registry also lists secondary outcomes involving antibody concentrations, OPA titers, and specified response thresholds. When many outcomes or serotypes are examined, the chance of obtaining at least one apparently unusual result can increase if each result is interpreted independently. In general, multiplicity procedures may control that risk, but the appropriate approach depends on which outcomes are confirmatory and how the analyses are organized. The registry record does not report whether multiplicity was addressed, which results were designated for formal hypothesis testing, or a hierarchy among outcomes.

The record reports 10 outcome measures and 302 analyses, but does not explain how these analysis counts relate to each other or whether every analysis was inferential. The primary endpoint description gives the outcome definition and confidence-interval level, but does not report a testing strategy or adjustment across serotypes. Without that information, the strength of any collection of positive or negative findings cannot be assessed. In this case, the primary GMC estimates and intervals are not reported in the registry record, so the multiplicity issue cannot be evaluated alongside the actual findings.

For the primary endpoint, the registry says the geometric means used participants with available data for the specified blood draw. It defines an evaluable immunogenicity population using eligibility, timing of blood collection, valid and determinate assay results, prohibited-vaccine exposure, and major protocol violations. The registry record does not report how many participants were excluded under each criterion, outcome-specific denominators, missing-data reasons, or any imputation method. It therefore does not allow assessment of whether missing measurements could have altered the estimates.

The population description also uses the term “randomized,” despite the trial being classified as nonrandomized and single-group. The registry record does not explain this inconsistency. It does not report a protocol deviation summary or a comparison of included and excluded participants. As a result, the effect of the evaluability criteria on the analyzed population remains uncertain.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse events for three vaccine-sequence categories. The category labelled 13vPnC/13vPnC/13vPnC has 130 participants at risk and 0 affected by a serious adverse event. The category labelled 7vPnC/7vPnC/13vPnC has 64 at risk and 0 affected. The category labelled 7vPnC/13vPnC/13vPnC has 64 at risk and 0 affected. These are the serious-event figures recorded for the categories.

The registry also lists counts for other adverse events: 82, 36, and 39 in the respective categories. These are not the serious adverse-event counts and should not be combined with them. The deaths fields are null, so deaths are not reported in the registry record; a null entry should not be interpreted as a confirmed count of zero.

At-risk counts are the denominators associated with the safety reporting categories, not necessarily the denominator for every immunogenicity analysis. The record does not provide event descriptions for the serious-event figures or additional detail on timing, duration, or attribution. These figures describe reported counts in the registry, not a comparison that establishes differences among vaccine histories. The nonrandomized design and the absence of a like-for-like control comparison limit comparative interpretation.

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

The record defines a study of antibody persistence and post-dose immunogenicity in children previously vaccinated during infancy. Its primary outcome was serotype-specific IgG GMC one month after a single 13vPnC dose. However, the numerical GMCs and confidence intervals are not reported in the registry record. The record therefore does not allow readers to characterize the measured concentration levels, compare serotype patterns, or assess the precision of the estimates.

The study also cannot be read as a randomized comparison of vaccine schedules. It is classified as nonrandomized and single-group, and no concurrent randomized comparator is described. Vaccine-sequence categories in the safety information do not provide a causal comparison for the primary antibody endpoint. Any differences between such categories could reflect participant characteristics or prior histories as well as other factors; the record does not provide an analysis that resolves those possibilities.

The serious adverse-event counts are recorded as zero affected in each of the three safety categories, with the corresponding at-risk counts specified in the safety information. This is a description of the registry entries, not proof that no unrecorded events occurred or that risks are equivalent across categories. The deaths fields are null rather than reported as zero. Counts for other adverse events are separately recorded and should not be mistaken for serious events.

In general, an antibody concentration is a laboratory measurement and not, by itself, a direct measure of clinical protection. The registry record does not provide a clinical endpoint linking the reported assay results to disease outcomes. Since the actual antibody estimates are also absent, the record cannot support conclusions about the magnitude or clinical significance of the measured response. It does establish the study question, the timing and type of measurement, and the broad design; it does not provide enough outcome detail for a full assessment of the primary findings.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a well-defined endpoint and a reported result. The primary outcome is described with a biological measure, units, timing, serotype coverage, and a confidence-interval approach. Those details tell readers what the investigators intended to summarize. They do not reveal the observed antibody levels when the estimates and intervals are not reported in the registry record.

The design also matters for interpretation. A single-group, nonrandomized study can describe measurements after vaccination in its analyzed participants. It cannot, on its own, separate the effect of the new dose from other explanations through a randomized concurrent comparison. The prior vaccine-sequence labels in the safety categories do not remove this limitation. Distinguishing descriptive evidence from comparative evidence is essential when reading immunogenicity studies.

The endpoint is serotype-specific, so a single overall summary would not capture the full structure of the question. Multiple serotypes and secondary outcomes can create a multiplicity challenge, while separate estimates may have different precision and participant counts. The registry record does not report the analysis strategy for these issues, nor does it provide the estimates needed to inspect the pattern across serotypes.

Finally, the record illustrates why enrollment, analysis populations, and safety denominators should not be treated as interchangeable. Enrollment is reported as 263, while safety counts are categorized by prior vaccine sequence and the primary endpoint uses an evaluable immunogenicity population. The record does not supply the endpoint-specific counts needed to reconcile these populations. Keeping these distinctions clear prevents an enrollment figure from being mistaken for the number contributing to every result.

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 consequential limitation for interpreting the primary outcome is that numerical serotype-specific GMC estimates and confidence intervals are not reported in the registry record. Without them, the antibody levels, precision, and pattern across serotypes cannot be assessed. The registry record also does not give outcome-specific denominators, so the number of participants contributing to each estimate is unknown.

The design is nonrandomized, open-label, and single-group. There is no randomized concurrent comparator for the primary endpoint, and the registry does not report a comparative analysis that could support a causal contrast. The safety categories are labelled by vaccine history, but the record does not establish that these categories are comparable or explain how participants entered them.

The registry's evaluable-population description includes the word “randomized,” which does not align plainly with its nonrandomized classification. The record does not clarify this wording. It also does not describe missing-data handling, the number excluded under each evaluability criterion, or the implications of missing assay measurements.

Other unreported details include the statistical analysis plan, the rationale for sample size, the approach to multiplicity, interim analyses, and the method used to construct confidence intervals. The registry identifies a planning illustration based on an observed effect, but that does not establish the design assumptions used for this trial. Safety information is limited to categorized counts; deaths are not reported in the registry record, and event-level descriptions are not available in the registry record. These limitations constrain interpretation but do not demonstrate that procedures or results were absent from the underlying study documentation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Evaluating Antibody Response Of 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) 24 Months After Toddler Dose. — NCT01026038.
• Registry record last updated 2012-02-08; status last verified 2012-01.
• Results first posted 2012-02-08.
• 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

NCT01026038 was a completed Phase 3, open-label, nonrandomized, single-group study sponsored by Pfizer. Enrollment was 263. It evaluated a single intramuscular dose of 13vPnC in healthy children previously given a 4-dose pneumococcal conjugate vaccine series during infancy, with the additional dose administered at least 24 months after the last toddler dose.

The primary endpoint was serotype-specific pneumococcal IgG GMC one month after vaccination, covering 7 common serotypes and 6 additional serotypes specific to 13vPnC. The record describes use of two-sided 95% confidence intervals and an evaluable immunogenicity population. Primary outcome values and outcome-specific participant counts are not reported in the registry record.

Safety information is organized by prior vaccine sequence. Serious adverse-event counts are recorded as 0 affected in each category; deaths are not reported in the registry record. The nonrandomized design, missing primary outcome estimates, and unreported analysis details limit statistical interpretation.