Study Evaluating the Impact of the 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Alaskan Native Children.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating the Impact of the 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Alaskan Native Children. (NCT00743652), a non-randomized phase 3 study. The primary outcome is Percentage of Participants Achieving Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 Micrograms Per Milliliter (Mcg/mL) 1 Month After the Infant Series.

2. Clinical Question

This question concerns an immunogenicity measure: whether participants reached a prespecified antibody threshold for each of the listed pneumococcal serotypes. It is distinct from a direct comparison of clinical disease outcomes. The registry's overall study description also names safety and impact as aims, but the primary endpoint is the proportion meeting the antibody threshold. The record describes five groups and an enrollment of 373; it does not report group-specific enrollment for the primary endpoint. Because allocation was non-randomized and the groups reflect different ages and prior-dose histories, outcome differences between groups could not by themselves be interpreted as effects of a randomized treatment contrast.

3. Trial Design

This was a Phase 3, open-label, non-randomized, parallel-group trial of 13-valent Pneumococcal Conjugate Vaccine in Alaskan Native children. The registry lists Pfizer as the sponsor, an enrollment of 373, and a completed study. The recorded start was 2009-01 and primary completion was 2010-09. Masking was none.

The five groups were defined by age and prior Prevnar exposure. Group 1 comprised subjects 6 weeks to younger than 10 months of age with no prior dose. Group 2 comprised subjects younger than 12 months with one prior dose, and Group 3 subjects younger than 12 months with two prior doses. Group 4 included subjects at least 12 months to younger than 2 years; Group 5 included subjects at least 2 years to younger than 5 years. The record describes catch-up dosing for the older groups in its outcome descriptions.

These groups are not described as randomized arms. Their different ages and prior-dose histories mean that they are not interchangeable comparison groups: those characteristics may relate to antibody responses and to which vaccination schedule was relevant. The registry specifically cautions that the arms are not a like-for-like control comparison. The record does not describe a randomized allocation process, a separate control vaccine, or a masked assessment.

The study description names safety, immunogenicity, and impact as aims. The primary outcome is an antibody-threshold measure, while secondary outcomes include additional antibody thresholds and reports of specified local reactions and systemic events. The record lists 27 outcome measures and zero analyses. A detailed statistical analysis plan, sample-size justification, and description of any interim analyses are not reported in the registry record. The recorded enrollment is not necessarily the number with evaluable results for every outcome.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable immunogenicity population: received treatments as randomized at all expected doses, blood drawn within specified timeframes, at least 1 valid and determinate assay result for proposed analysis, and no major protocol violations. N=number of participants with a determinate IgG antibody concentration to the given 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 Percentage of Participants Achieving Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 Micrograms Per Milliliter (Mcg/mL) 1 Month After the Infant Series, measured over 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3..

The primary endpoint is the percentage of participants who achieved a serotype-specific pneumococcal IgG antibody level of at least 0.35 mcg/mL after the infant series. It covers the seven common pneumococcal serotypes—4, 6B, 9V, 14, 18C, 19F, and 23F—and the six additional serotypes specific to 13vPnC—1, 3, 5, 6A, 7F, and 19A. The assessment was planned 28 to 56 days after the relevant dose: vaccination 3 for Group 1, vaccination 2 for Group 2, and vaccination 1 for Group 3.

This is a binary-threshold endpoint: each participant's measured antibody level is classified according to whether it meets the stated cutoff, and the endpoint expresses the proportion meeting it. In general, such a measure makes the response criterion explicit and allows the result to be described as a percentage, though it does not preserve all the detail of the underlying antibody measurements. The registry says exact two-sided confidence intervals were to be based on the observed proportion. It does not report the observed proportions or interval limits, so the size and precision of the endpoint results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a percentage, which is a binary-outcome summary: each evaluated participant either meets the stated antibody cutoff or does not. The registry specifies the cutoff as at least 0.35 mcg/mL and calls for results by serotype. In general, a percentage is easy to interpret as the share of evaluated participants satisfying a criterion, but it depends on defining who is included in the denominator and how missing measurements are handled. The record defines an evaluable immunogenicity population, but does not report the number evaluated for each serotype.

What does the confidence interval convey?

The primary endpoint description calls for an exact two-sided confidence interval based on the observed proportion. In general, a confidence interval expresses statistical uncertainty around an estimate under the assumptions of the method. It is not a guarantee that the interval contains the underlying value, nor does it describe the range of individual participants' antibody measurements. Here, the intended interval would accompany each observed percentage, but neither percentages nor interval limits are reported in the registry record. The record also does not state how any multiplicity across serotypes was handled.

Why does the assessment window matter?

The endpoint timing differs by infant group: the assessment is 28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3. These windows define when the blood measurement is considered relevant to the primary outcome. In general, measurements taken at different points in a dosing sequence are not automatically directly comparable, because dose history and timing form part of the outcome context. The registry record does not report whether participants were assessed at the same specific day within each window.

What does the study design allow?

In general, random allocation helps balance measured and unmeasured participant characteristics between treatment groups, while masking can reduce some forms of assessment or reporting bias. This study is recorded as non-randomized and open-label, with no masking. Its groups also differ by age and prior vaccination. The registry warns that the arms are not a like-for-like control comparison. Thus, group contrasts would be descriptive unless supported by suitable methods and assumptions; such adjusted analyses are not reported in the registry record. The parallel-group label means the groups are distinct study groups, not evidence that their baseline characteristics were balanced.

How should the planning calculations be read?

The recorded sample-size illustration is based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes detecting a stated fraction of the observed effect. In general, these are planning assumptions used to illustrate sample sizes under a chosen effect and model; they are not evidence that a trial had a particular probability of detecting its true effect. Such calculations are not observed power. Since the registry record does not report the observed primary effect or the sample-size justification for the trial's original design, the illustration should not be mistaken for a description of how enrollment was chosen.

For binary outcomes, in general, the precision of a percentage depends on the number of evaluable participants and the observed proportion. A reported confidence interval helps show that precision. Enrollment alone is not a substitute for the endpoint denominator: participants may not have a determinate assay result in the relevant window or may fail the stated evaluability criteria. The record's primary population definition requires receipt of expected treatments as randomized, blood drawn within specified timeframes, at least one valid and determinate assay result for the proposed analysis, and no major protocol violations. The registry wording uses “as randomized” even though allocation is recorded as non-randomized; the record does not explain this wording.

The endpoint description states that exact two-sided intervals would be used, while the sample-size illustration uses a normal approximation. These refer to different purposes: an interval method for describing uncertainty in the observed proportion and an approximation used in planning calculations. In general, the choice of method should be understood from the analysis being performed, not inferred from the study phase. The detailed statistical analysis plan, treatment of missing assay results, and any inferential procedures beyond the endpoint description are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 27 outcome measures, including multiple antibody endpoints and specified local reactions and systemic events. The primary endpoint itself concerns 13 serotypes. Whenever several outcomes or serotypes are examined, in general, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for multiplicity. Methods such as adjustment or a prespecified hierarchy can address that issue, but the registry record does not report whether any such approach was planned or used. It does not give a detailed statistical analysis plan.

The record lists zero analyses. It therefore does not provide analysis-level results, estimates, or uncertainty measures for the outcomes in this information. The primary outcome's description specifies an exact two-sided confidence interval based on the observed proportion; it does not explain how conclusions across serotypes were to be drawn or how secondary outcomes related to the primary analysis.

The primary evaluable immunogenicity population is described as participants who received treatments as randomized at all expected doses, had blood drawn within specified timeframes, had at least one valid and determinate assay result for the proposed analysis, and had no major protocol violations. The registry does not provide counts excluded for each reason, endpoint-specific denominators, or a comparison of included and excluded participants. Although enrollment is listed as 373, that number should not be treated as the denominator for every endpoint.

Missing-data methods, including any imputation or sensitivity analyses, are not reported in the registry record. The record also does not report how protocol deviations were assessed beyond the stated evaluability criterion, or whether analyses outside the evaluable population were planned. The primary population description's use of “as randomized” sits alongside the record's non-randomized allocation designation; the registry does not clarify the wording. These omissions limit assessment of how representative the analyzed participants would be of everyone enrolled.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: laryngomalacia (6.2%), respiratory distress (6.2%), gastrooesophageal reflux disease (6.2%), herpangina (6.2%), dehydration (6.2%).

The safety entries give group-specific numbers at risk and numbers affected by serious and other adverse events. For the infant series, Group 1 lists 151 at risk and 21 affected by serious events, with 11 affected by other events; Group 2 lists 51 at risk, 2 serious, and 4 other; Group 3 lists 25 at risk, 1 serious, and 1 other. For toddler dosing, Groups 1, 2, and 3 list 15, 23, and 16 at risk, respectively. The serious-event counts are 0, 0, and 2, and the other-event counts are 0, 0, and 0. Group 4, listed for 2 catch-up doses, has 66 at risk, 3 serious, and 1 other; Group 5, listed for 1 catch-up dose, has 79 at risk and zero in both affected counts.

The serious-event terms listed as most frequent are Laryngomalacia, Respiratory distress, Gastrooesophageal reflux disease, Herpangina, Dehydration, and Breath holding, each reported as 6.2%. These figures are descriptive; the record does not supply enough context to infer that the vaccine caused an event or to compare risk causally between groups. Death counts are not reported in the registry record. Definitions, follow-up details, and event-level denominators for the listed terms are not reported in the registry record.

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

The registry record's primary endpoint asks whether participants reached a defined serotype-specific IgG threshold after an infant-series dose. This is an immunogenicity outcome, not a direct measure of pneumococcal disease incidence. The record provides the threshold, serotypes, timing, and intended confidence-interval method, but does not report observed primary percentages or confidence intervals. Therefore, it cannot establish from the posted results whether, or how often, participants met the threshold.

The record also describes safety and other antibody outcomes. Its adverse-event counts can be read as descriptive counts within the listed risk sets, but they do not establish that the vaccine caused or prevented any event. No randomized control comparison is identified, and the record explicitly cautions that the groups are not like-for-like. Differences between groups would need to be interpreted in light of their different ages and prior-dose histories.

In general, a registry entry is useful for understanding a study's intended question, design, and stated outcome definitions. It is not a substitute for complete outcome reporting. Here, the absence of analysis results means readers cannot assess the estimated response proportions, their precision, or a comparative effect. The listed enrollment of 373 also does not reveal the number with an evaluable result for any particular serotype.

The record consequently supports a bounded reading: a Phase 3, non-randomized, open-label study evaluated 13vPnC in Alaskan Native children across groups defined by age and previous doses, with antibody thresholds and adverse events among its recorded outcomes. It does not support a conclusion about clinical efficacy, the magnitude of antibody responses, or causal safety effects. Those interpretations require outcome estimates and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and a result are different things. The registry precisely identifies a serotype-specific antibody threshold, the relevant infant-series dose for each group, and an assessment window. Those details define what a primary result would mean. Yet the registry record lists zero analyses and does not report the primary percentages or their confidence intervals. A clearly specified measure cannot by itself establish what was observed.

It also demonstrates the importance of design when reading group contrasts. The study is non-randomized and open-label, and its groups differ in age and prior vaccination history. The registry explicitly says the arms are not a like-for-like control comparison. A numerical difference between such groups, if available, would not automatically be a treatment effect. Recognizing this distinction prevents descriptive group data from being read as if they came from a randomized controlled comparison.

Finally, the study connects several statistical issues common in clinical research: defining an evaluable analysis population, interpreting confidence intervals for percentages, accounting for multiple serotypes and outcomes, and separating planning calculations from observed evidence. The record's population criteria and endpoint method offer some methodological detail, while key information on missing data, multiplicity, and the analysis plan is not reported. Together, these features show why readers need both an outcome estimate and enough information about its denominator and analysis to judge how precisely and credibly it addresses the research question.

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 principal limitation for interpreting outcomes is that the registry record does not report primary endpoint estimates or confidence intervals. Although the primary measure is defined for each of 13 serotypes, no observed percentages are available in the record. It also lists zero analyses, so there are no analysis-level results to evaluate. The enrollment of 373 does not identify how many participants contributed to each endpoint.

The non-randomized, open-label design limits the meaning of comparisons across groups. Groups were distinguished by age and prior Prevnar doses, and the registry states that they are not a like-for-like control comparison. The record does not describe a separate control intervention or a method for adjusting comparisons for those group differences. The registration information therefore does not establish a causal contrast.

Other specific details are incomplete. The record does not report the original sample-size justification, a detailed statistical analysis plan, handling of missing assay results, multiplicity procedures, or interim analyses. It describes an evaluable immunogenicity population but does not give counts excluded or endpoint-specific denominators. It also uses “as randomized” in that population definition despite recording allocation as non-randomized, without explaining the wording.

Safety entries provide group risk sets and affected counts, but fuller event definitions, follow-up context, and cause assessments are not reported in the registry record. Death counts are also not reported. The serious-event terms are presented with 6.2% figures, but the record does not provide further context for interpreting those term-specific percentages. These gaps restrict conclusions about both the precision of the findings and the comparability of outcomes across groups.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Evaluating the Impact of the 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Alaskan Native Children. — NCT00743652.
• Registry record last updated 2012-03-15; status last verified 2012-03.
• Results first posted 2012-02-10.
• 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

NCT00743652 is a completed Phase 3, open-label, non-randomized, parallel-group study of 13-valent Pneumococcal Conjugate Vaccine in Alaskan Native children. Pfizer is listed as sponsor; enrollment was 373, with a recorded start of 2009-01 and primary completion of 2010-09. Five groups were defined by age and prior Prevnar doses, from infants with differing prior-dose histories to children younger than 5 years.

The primary endpoint was the percentage reaching a serotype-specific IgG level of at least 0.35 mcg/mL after the relevant infant-series dose, assessed 28 to 56 days later. The record describes an evaluable immunogenicity population and exact two-sided confidence intervals, but does not report the primary estimates or interval limits. It lists 27 outcome measures and zero analyses. Safety counts are recorded by group, while deaths are not reported in the registry record. The registry cautions that the non-randomized groups are not a like-for-like control comparison.