Study Evaluating The Safety, Tolerability And Immunogenicity Of A 13-Valent Pneumococcal Conjugate Vaccine (13vPnC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating The Safety, Tolerability And Immunogenicity Of A 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) (NCT00546572), a randomized phase 3 study. The primary outcome is Pneumococcal OPA Geometric Mean Titers (GMTs) for the 12 Common Serotypes for 13vPnC Relative to 23vPS (Vax 1 / Year 0).

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, active-controlled, modified double-blind, parallel trial. Enrollment was 938. The population was ambulatory older adults aged 70 years and older, with a prior dose of 23vPS at least 5 years before enrollment. The registry describes the study as evaluating safety, tolerability, and immunogenicity.

At the first vaccination, one group received 13vPnC and the other received 23vPS. At year 1, the planned second vaccination was 13vPnC in both groups. Thus, the sequence comparison combines the different first vaccinations with a common planned vaccine at the later vaccination. Outcomes listed include antibody responses after the first vaccination and comparisons involving the second vaccination. The primary endpoint was assessed 1 month after the first vaccination; additional outcomes included response measures at year 1 and follow-up periods.

The registry lists the study start as 2007-11, primary completion as 2010-07, and status as completed. Wyeth is identified as the sponsor, with the record noting that Wyeth is now a wholly owned subsidiary of Pfizer.

The primary immunogenicity analysis was defined for an evaluable population rather than all enrolled participants. Eligibility for that analysis required adherence to randomized treatment at all expected doses, blood collection within specified timeframes, a valid and determinate assay result for the proposed analysis, and no major protocol violations. The record does not report the number of participants included in the primary analysis or provide a full participant flow description. Details of allocation procedures, the blinding procedures, and the reasons for any exclusions are not reported in the registry record.

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.

Vax 1 / Year 0

Reasons for not completing this period:

Vax 2 / Year 1

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable Immunogenicity population: 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 OPA antibody titer 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 Pneumococcal OPA Geometric Mean Titers (GMTs) for the 12 Common Serotypes for 13vPnC Relative to 23vPS (Vax 1 / Year 0), measured over 1 month after Vax 1 / Year 0.

The primary endpoint was the geometric mean titer (GMT) of antibodies measured by opsonophagocytic activity (OPA) assays. It covered the 12 serotypes common to 13vPnC and 23vPS: serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. The assessment was made 1 month after the first study vaccination and compared the 13vPnC group with the 23vPS group.

General statistical context: an OPA assay measures functional antibody activity in a laboratory setting. A GMT summarizes titers on a multiplicative scale and is commonly used when measurements are analyzed on the logarithmic scale. A GMT is not the same quantity as an arithmetic average of the original titers.

The registry specifies 95% confidence intervals for GMTs, back-transformed from intervals based on the Student t distribution for the mean logarithm of titers. Such an interval expresses uncertainty around an estimated GMT. Its width reflects the precision of the estimate under the analysis used; the interval alone does not describe every source of uncertainty in the study.

The endpoint is an antibody-response measure, not a direct measure of pneumococcal illness. The registry record does not report the GMT estimates or their confidence limits, so the magnitude and precision of the primary antibody response comparison cannot be described from the posted result information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary endpoint as a geometric mean titer measured by an OPA assay, with 95% confidence intervals. It states that the confidence intervals for GMTs are back transformations of intervals based on the Student t distribution for the mean logarithm of titers. The underlying numerical estimates, confidence limits, and any hypothesis-test results are not reported in the registry record.

Why use geometric mean titers?

General statistical context: antibody titers are often analyzed on a logarithmic scale because the scale of their variation can be multiplicative rather than additive. Taking logarithms converts multiplicative relationships into additive ones, making methods for means more appropriate to the transformed measurements. The mean is calculated on the log scale and then transformed back to the original titer scale. That back-transformed value is the geometric mean.

A geometric mean describes a central level on a multiplicative scale. It should not be interpreted as the arithmetic mean of the raw titers. Because the log transformation changes the scale, interpretation should stay aligned with the reported estimand: in this trial, the endpoint is GMT, not a difference in arithmetic average titers. The registry record identifies the endpoint but does not give the numerical estimates needed to describe the observed level in either group.

What does the confidence interval represent?

General statistical context: a confidence interval gives a range of values compatible with an estimate under the statistical procedure and its assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry specifies 95% confidence intervals for the GMTs and says they are obtained by calculating intervals for mean log titers using the Student t distribution, then back-transforming those limits.

Back-transformation returns the interval to the original titer scale. Because the scale is multiplicative, the resulting interval need not be symmetric around the GMT in the way an interval on the log scale is centered around its mean. The confidence interval is a measure of sampling uncertainty under the stated method; it does not address every potential source of bias, such as missing observations or protocol deviations.

What is the analysis population?

The primary endpoint population is described as the evaluable immunogenicity population. Participants had to receive treatment as randomized at all expected doses, have blood drawn within specified timeframes, have at least 1 valid and determinate assay result for the proposed analysis, and have no major protocol violations. This definition focuses the analysis on participants with data judged suitable for the immunogenicity assessment. It differs conceptually from simply analyzing every person enrolled.

General statistical context: restricting analysis to evaluable participants can make the endpoint measurement more complete for those included, but exclusions may affect how well results represent all randomized participants. Interpreting such an analysis requires knowing how many participants were excluded, why they were excluded, and whether exclusions differed between groups. The number analyzed for the primary endpoint and a detailed account of exclusions are not reported in the registry record.

What do the planning illustrations mean?

General statistical context: sample-size illustrations based on an observed effect are planning calculations, not a measure of the trial's observed power. The stated assumptions for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event calculations, the stated quantity is the total number of events, using the Schoenfeld method; other calculations are expressed as participants per arm.

These assumptions describe the illustrations, not a reported design justification for the original trial. The registry record does not report the trial's sample-size justification, the effect size used in its original planning, or an original power calculation. The illustrations cannot replace those missing design details and should not be interpreted as observed power.

What cannot be evaluated from the reported statistics?

The registry record does not report the primary GMT estimates or confidence intervals, the numerical contrasts for the listed analyses, or a single primary comparison result. It also does not report the hypothesis-testing procedure for the primary endpoint, whether the comparison was adjusted for any covariates, or the handling of multiplicity across analyses. Without those details, the endpoint definition and confidence-interval method can be described, but the statistical evidence for a between-group difference cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures and 58 analyses. Several outcomes address different serotypes, vaccination times, or comparisons between vaccination sequences. The primary endpoint itself covers 12 common serotypes, and the registry indicates that the primary outcome has several categories or time points and was not reduced to one comparison.

General statistical context: when many outcomes or comparisons are examined, the chance of finding at least one apparently notable result can increase if each is assessed separately without accounting for the number of tests. Common approaches include defining a hierarchy of hypotheses or adjusting inference across a family of comparisons. The appropriate approach depends on the scientific questions and the prespecified analysis plan. The multiplicity strategy is not reported in the registry record. It is also not reported whether the listed analyses were prespecified, exploratory, or subject to any adjustment.

The record defines an evaluable immunogenicity population using randomized treatment at all expected doses, blood collection within specified timeframes, at least 1 valid and determinate assay result, and no major protocol violations. This gives some information about eligibility for the primary analysis, but the number included and the handling of missing or indeterminate assay results are not reported. The record does not describe imputation, sensitivity analyses, or other missing-data procedures. Nor does it report a complete flow from the 938 enrolled participants to each endpoint-specific analysis population.

These omissions limit assessment of whether participants with available measurements differed from those without them, and whether conclusions are robust to analysis choices. A registry population definition does not by itself establish how missingness affected estimates. The posted endpoint information is therefore insufficient to assess multiplicity control or the sensitivity of the primary analysis to missing data.

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: basal cell carcinoma (0.8%), atrial fibrillation (0.7%), angina pectoris (0.6%), bradycardia (0.5%), pneumonia (0.5%).

The registry reports serious adverse-event counts by vaccination period, with the number at risk shown for each group. One month after vaccination at year 0, the serious adverse-event count was 3 among 463 participants in the 13vPnC group and 8 among 473 participants in the 23vPS group. In the 6-M FU period after the year-0 vaccination, the counts were 27 among 463 and 26 among 473, respectively.

After the year-1 vaccination, the serious adverse-event count was 4 among 391 participants in the 13vPnC / 13vPnC sequence and 7 among 404 in the 23vPS / 13vPnC sequence during the 1-month period. During the associated 6-M FU periods, the counts were 17 among 391 and 21 among 404. The year-1 groups are sequence groups, so their labels retain the vaccination received at year 0 as well as the year-1 vaccination.

General statistical context: these are counts within specified periods, not adjusted estimates of comparative risk. The record does not provide a statistical comparison or confidence intervals for these safety counts. Death counts are not reported in the registry record. The listed serious-event terms include basal cell carcinoma, atrial fibrillation, angina pectoris, bradycardia, pneumonia, and squamous cell carcinoma of skin, with percentages ranging from 0.5% to 0.8% as individually reported. The denominator and period for those term percentages are not stated alongside the list in the registry record.

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

The registry establishes the trial's clinical question and the intended primary measurement: OPA GMTs for 12 common serotypes, comparing 13vPnC with 23vPS 1 month after the first vaccination. It also describes how confidence intervals for GMTs were constructed. Those details clarify what the study set out to measure, but they do not provide the numerical primary result.

Without primary GMT estimates, confidence limits, and a reported comparison, the posted record cannot show the magnitude or precision of the antibody response contrast. It cannot support a conclusion that the groups had equal responses, nor can it support a conclusion that one group's response was greater. The absence of a reported result is distinct from a result showing no difference.

The safety counts describe serious adverse events during specified periods after each vaccination. They are useful descriptive information, but counts alone do not establish why events occurred or whether any observed difference was attributable to a vaccine. The registry does not report comparative uncertainty intervals or a statistical test for those counts. The serious-event term percentages are listed, but the record does not state their denominator and period in the same summary.

General statistical context: an antibody endpoint and a clinical disease endpoint answer different questions. A laboratory measure of functional antibody activity is not itself a count of infections or other clinical outcomes. The registry record identifies pneumococcal infections as the condition, but the primary endpoint described is immunogenicity. The reported information therefore does not establish an effect on clinical disease. It also does not supply enough results to assess whether the primary immunogenicity objective was met under any prespecified criterion, because that criterion and the numerical endpoint comparison are not reported.

13. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an endpoint result need to be read separately. The registry gives a specific immunogenicity measure: OPA GMTs for 12 serotypes common to the vaccines, assessed 1 month after the first vaccination. It also identifies the confidence-interval method. Yet the registry record does not report the GMT estimates or their confidence limits. A precise endpoint definition does not, by itself, reveal the findings.

The sequence design also matters statistically. The year-0 comparison is between 13vPnC and 23vPS, while both groups were scheduled to receive 13vPnC at year 1. Later outcomes therefore concern sequences that differ in their first vaccination but share the planned second vaccine. Keeping those time points and treatment sequences distinct avoids treating all observations as if they arose from the same comparison.

The evaluable immunogenicity population has explicit requirements, including valid assay data, vaccination as randomized, and no major protocol violations. That definition helps identify who could contribute to the primary analysis, but the registry does not report the analysis count or participant flow. This illustrates why an analysis population definition and information about actual inclusion are both needed for appraisal.

Finally, the record lists many outcome measures and analyses, while not reporting how multiplicity was handled. General statistical context: interpretation across multiple endpoints depends on which comparisons were planned and how inference was controlled. Together, the missing endpoint estimates, analysis counts, and multiplicity details restrict what can be concluded statistically, even though the trial design and intended measures are described.

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 interpreting the primary endpoint is that the registry record does not report the numerical GMT estimates, their 95% confidence intervals, or a single reduced comparison. It is therefore not possible to describe the observed antibody levels or the precision of the between-group contrast from the posted results. The record also does not provide a prespecified success criterion or a reported primary hypothesis test.

The primary outcome includes multiple serotype categories or time points and was not reduced to one comparison. Although the record lists 16 outcome measures and 58 analyses, it does not explain the multiplicity strategy or identify which analyses were confirmatory. The statistical plan, including any covariate adjustment or sensitivity analysis, is not reported in the registry record.

The primary population is described as evaluable, with requirements for receiving randomized treatment at all expected doses, timely blood collection, valid and determinate assay results, and no major protocol violations. The number of participants analyzed, endpoint-specific denominators, reasons for exclusion, and methods for handling missing or indeterminate results are not reported. These omissions make it difficult to assess selection into the analysis or the influence of missing data.

Safety data are presented as counts by period and group, but the record does not provide comparative confidence intervals or tests, and death counts are not reported. Serious-event term percentages are listed without their denominator and period in the summary. The registry also does not report a detailed allocation method, the procedures used to maintain blinding, or the original sample-size justification. These are limits on interpretation of the registry record, not claims about what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Evaluating The Safety, Tolerability And Immunogenicity Of A 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) — NCT00546572.
• Registry record last updated 2011-07-14; status last verified 2011-07.
• Results first posted 2011-05-30.
• 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

This completed phase 3 randomized, active-controlled, modified double-blind, parallel trial enrolled 938 ambulatory adults aged 70 years and older who had received a prior 23vPS dose at least 5 years before enrollment. The year-0 groups received 13vPnC or 23vPS; both were scheduled to receive 13vPnC at year 1.

The primary endpoint was OPA GMT for 12 common serotypes 1 month after the first vaccination, with 95% confidence intervals based on the mean logarithm of titers and back-transformed to the GMT scale. The record describes the endpoint and evaluable population but does not report the primary numerical estimates or a single comparison result. It lists 16 outcome measures and 58 analyses. Serious adverse-event counts are reported by group and follow-up period, but comparative uncertainty estimates are not reported. The trial start is listed as 2007-11, primary completion as 2010-07, and the registry status is completed.