Streptococcus Pneumonia: Effects of PCV13 on Pneumococcal Carriage: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Streptococcus Pneumonia: Effects of PCV13 on Pneumococcal Carriage (NCT01109108), a registered phase not stated study. The primary outcome is Nasopharngeal Colonization With PCV13 S. Pneumoniae.

2. Clinical Question

The central statistical question concerns the composition of pneumococcal carriage, not the overall proportion of all children who become colonized. The registry describes a proportion of PCV13 serotypes among n=1851 children already colonized with any S. pneumoniae. That denominator condition matters: the endpoint describes serotypes within the colonized group, and does not by itself quantify carriage prevalence in the full clinic population.

The record presents the work as an assessment of PCV13 impact in a clinical setting, with surveillance extended to examine serotype distribution over time. It does not report an estimated change in carriage, a comparison of vaccinated and unvaccinated children, or a numerical answer to the coverage question. The age groups therefore provide context for the population studied, but should not be interpreted as randomized treatment and control groups.

3. Trial Design

The registry lists an enrollment of 9000 and a COMPLETED status. The recorded study start is 2010-04 and primary completion is 2015-03. The brief description says surveillance was extended to complete 5 years and to assess the serotype distribution at a time when a new equilibrium was presumed to have been reached. That wording describes the study rationale; it does not establish that an equilibrium was demonstrated.

The study aim was to evaluate the impact of PCV13 as administered in the pediatric primary care clinic at Boston Medical Center on serotype-specific carriage of S. pneumoniae in children younger than 5 years. The registry lists two age groups: children younger than 2 years and children aged 2 to younger than 5 years. Both group descriptions include children with and without respiratory tract infection. These descriptions identify populations, not randomized interventions.

The registry explicitly cautions that this is not a randomized comparison, that allocation is not stated, and that the arms are not a like-for-like control comparison. The record does not provide a fuller design classification, a vaccination allocation procedure, or a description of a concurrent control group. It is therefore not possible to treat the age-group contrast as an estimate of the causal effect of PCV13.

The stated endpoint covers study years 1-5 and concerns PCV13 serotypes among children colonized with any S. pneumoniae. The brief summary also describes aims involving vaccine-serotype decline, the vaccination proportion associated with a 50% decline, and the relationship between immunogenicity and carriage decline. Numerical results for those aims are not reported in the registry record. Details of visit schedules, sampling procedures, participant follow-up, and how changes over time were analyzed 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Children colonized with any S. pneumoniae (PCV and non-PCV serotypes)

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 Nasopharngeal Colonization With PCV13 S. Pneumoniae, measured over Study years 1-5.

The primary endpoint is described as the proportion of PCV13 serotypes among n=1851 children colonized with any S. pneumoniae. Its stated timeframe is study years 1-5. The population includes children colonized with either PCV or non-PCV serotypes, so the endpoint asks what share of the recorded pneumococcal serotypes in this colonized group belong to the PCV13 serotypes.

This measure is useful for studying serotype distribution because it focuses on the composition of carriage, rather than treating every colonized child as having the same type of pneumococcus. Tracking the share of vaccine serotypes can address the study's stated interest in changes in vaccine-serotype carriage and the emergence or distribution of other serotypes. As a proportion, it also gives a common scale for describing the serotype mix within the endpoint population.

Interpretation depends on the denominator. The endpoint is conditional on colonization with any S. pneumoniae; it is not a measure of the proportion of all enrolled children who were colonized. Nor does the endpoint description alone establish that the same children were followed across the study period, how repeated samples were handled, or whether a child could contribute more than one observation. Those details are not reported in the registry record.

The registry gives the endpoint definition and denominator size, but not the numerator, the observed proportion, a confidence interval, or a comparison estimate. The numerical primary result is therefore not reported in the registry record, and the direction or precision of any change cannot be determined from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a proportion, a type of binary-outcome summary. For each observation classified as a PCV13 serotype or not, the proportion represents the share assigned to the PCV13-serotype category within the stated denominator. The registry describes that denominator as children colonized with any S. pneumoniae and gives its size as n=1851. The numerator and observed proportion are not reported in the registry record, so the endpoint cannot be reconstructed from the posted information.

What does the denominator mean?

Conditioning the analysis on colonization answers a specific question about serotype composition among colonized children. It differs from estimating carriage among all enrolled children, because children without pneumococcal colonization are outside the endpoint population. This distinction is important when interpreting a proportion: the outcome describes the mix of serotypes within a selected group, not the overall likelihood of colonization. General statistical principle: changing the denominator changes the question being answered, even when the numerator category is unchanged.

The endpoint description does not make clear whether each child contributes a single observation, whether specimens were collected repeatedly, or how multiple serotypes in a specimen were classified. Those design and analysis details are not reported in the registry record. If observations from the same child were included more than once, statistical methods might need to account for within-child dependence; this is a general consideration, not a method documented for this study.

How should uncertainty be understood?

A confidence interval is a range of estimates compatible with the observed data under a specified statistical procedure. In general, it conveys precision: a wider interval indicates less precision than a narrower interval. No confidence interval or other uncertainty measure for the primary endpoint is reported in the registry record. Without an estimate and its uncertainty, readers cannot assess how precisely the serotype proportion was determined or distinguish a stable pattern from one that might be sensitive to sampling variation.

The record also does not identify a statistical model, covariate adjustment, or hypothesis-testing procedure for the primary outcome. It gives one listed outcome measure and one listed analysis, but those counts do not describe the full analytic plan. The method used to handle changes across study years, clustering, or differences between age groups is not reported in the registry record.

What do the planning assumptions represent?

The registry material describes a planning illustration computed from an observed effect, rather than the trial's own design calculation. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These assumptions describe a hypothetical planning exercise. They do not establish the original study's sample-size justification, and the registry record does not report that justification.

A planning illustration asks what sample size might be needed under specified assumptions to detect a chosen effect. It is not an observed result, and it does not show the probability that the completed study detected an effect. In particular, sample-size planning based on an observed effect is conditional on that effect estimate and the illustration's assumptions. The registry record does not report the illustration's resulting sample sizes in the registry record described for this analysis. No sample-size figure should be inferred from the enrollment or endpoint denominator.

The equal-allocation assumption also does not match a documented randomized allocation scheme in this record: allocation is not stated, and the age groups are explicitly not a like-for-like control comparison. Thus, the illustration's two-arm planning assumptions should not be mistaken for evidence that participants were assigned equally to treatment and control arms. General statistical principle: sample-size calculations are meaningful only in relation to a specified outcome, effect, design, and analysis, and assumptions that differ from the actual study can make a planning result inapplicable.

Why can over-dispersion matter?

Over-dispersion occurs when the observed variability in data exceeds what a statistical model assumes. In general, ignoring it can make standard errors too small and uncertainty appear less than it is. The registry does not report a dispersion estimate or identify a model for the primary endpoint, so it is not possible to determine whether over-dispersion was assessed or relevant to the analysis. For a proportion based on correlated or clustered observations, dependence and heterogeneity can also affect uncertainty; whether such features were present or modeled is not reported in the registry record.

Overall, the available methods description is insufficient to reproduce the primary analysis. The endpoint definition and broad planning assumptions are stated, but the estimator, model, uncertainty calculation, handling of repeated observations, and any adjustment strategy are not reported in the registry record. These absences limit assessment of both precision and comparability across groups or study years.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and one analysis. This is a description of the entries recorded, not enough to establish that the study tested only one hypothesis or that no multiplicity issue arose. The brief summary describes several scientific aims, including vaccine-serotype decline, a vaccination proportion associated with a 50% reduction, and a relationship between immunogenicity and carriage decline. The statistical relationship among those aims and any prespecified hierarchy are not reported in the registry record.

Any multiplicity adjustment, family of hypotheses, primary-versus-secondary outcome hierarchy, or approach to selecting results is not reported in the registry record. Without those details, the degree to which multiple comparisons were planned or controlled cannot be assessed. General statistical principle: when many outcomes, groups, or time points are examined, the chance of finding an apparently unusual result can increase unless the analysis plan accounts for the set of comparisons. This is a general issue, not evidence that such a procedure was or was not used in this study.

Missing-data handling is not reported in the registry record. The record does not describe missing specimens, incomplete follow-up, exclusions, or imputation. It also does not specify an analysis population beyond describing the primary endpoint population as children colonized with any S. pneumoniae. Whether the primary analysis included all enrolled participants, only participants with usable specimens, or another defined population is not reported.

The record gives an enrollment of 9000 and an endpoint denominator of n=1851, but does not explain the participant flow between these quantities. The reasons for being outside the endpoint population, including whether participants were not colonized or lacked outcome data, are not detailed. No intention-to-treat population or alternative analysis population is identified 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 1% reporting threshold.

The registry lists serious adverse event counts separately for children younger than 2 years and children aged 2 to younger than 5 years. For the younger group, 4035 participants are listed as at risk and 0 as affected. For the older group, 4755 are listed as at risk and 0 as affected. The record also lists 0 other adverse events in each group and 0 deaths in each group. No serious adverse event terms are listed.

These are the safety counts recorded in the registry, not evidence that every participant was monitored in the same way or for the same duration; the safety collection and attribution methods are not reported in the registry record. Zero recorded events should be read as a count in this record, not as proof that an event is impossible or that a treatment caused no harm. The registry does not describe how adverse events were defined, assessed, or related to PCV13.

The age-group counts are not randomized comparison groups, and the record cautions that the arms are not like-for-like controls. The safety figures therefore do not support a causal comparison between age groups or a treatment-safety conclusion. They should be interpreted only as the posted event counts and listed at-risk counts.

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

The record establishes that the study focused on PCV13 serotype carriage among children younger than 5 years in a pediatric primary care setting and that surveillance covered study years 1-5. It also defines a primary endpoint: the proportion of PCV13 serotypes among n=1851 children colonized with any S. pneumoniae. These details clarify the population and the type of outcome the investigators intended to describe.

The record does not provide the numerical primary endpoint result. It therefore cannot show the observed proportion, whether the share of PCV13 serotypes declined, or how precisely any estimate was measured. The aims described in the brief summary, including a 50% reduction question and an immunogenicity-carriage relationship, are not numerical findings. No conclusion about the magnitude or direction of these effects can be drawn from the posted endpoint definition alone.

The endpoint is about the composition of serotypes among colonized children. It does not, by itself, determine the overall frequency of pneumococcal colonization, the number of children protected from infection, or the clinical consequences of carriage. A change in serotype mix is not equivalent to a change in all carriage, and the registry does not report broader clinical outcomes that would support those interpretations.

The study is not described as a randomized comparison, and the registry says allocation is not stated and the age groups are not like-for-like controls. Accordingly, the record does not support attributing a difference to PCV13 through a direct randomized contrast. The interpretation should remain descriptive and tied to the endpoint as registered. The safety counts likewise describe events recorded in the age groups; they do not establish comparative safety or causation.

In practical statistical terms, the record provides a question, a timeframe, and a denominator description, but not the estimate and uncertainty needed to judge the primary result. The result does not establish that PCV13 did or did not change carriage, and the absence of a reported estimate should not be treated as evidence of no effect.

13. Why This Trial Matters Statistically

This study raises a statistically important distinction between changes in serotype composition and changes in overall carriage. Its endpoint focuses on the proportion of PCV13 serotypes among children already colonized with any S. pneumoniae. That framing can be informative for surveillance of serotype distribution, but it does not answer every question about pneumococcal carriage or clinical outcomes. The denominator determines the scope of the conclusion.

The work also highlights the value and limits of surveillance over time. The brief summary describes interest in a changing serotype distribution and a possible new equilibrium after extended surveillance. Longitudinal observation can help describe patterns as they evolve, but interpretation depends on how samples, repeated observations, and changes in the population are handled. Those analytic details are not reported in the registry record, and the numerical time pattern is not reported either.

Study design matters when considering whether an observed difference can be attributed to an intervention. The registry explicitly notes that the age groups are not a randomized, like-for-like comparison. This is a useful reminder that describing groups side by side does not by itself create a causal contrast. Differences between age groups may reflect factors other than vaccination, and the record does not provide an adjusted comparison to address that concern.

The endpoint also illustrates why reporting an estimate together with its uncertainty is essential. A defined outcome and denominator make the question understandable, but without the observed proportion and precision measure, readers cannot assess the evidence for a pattern. The registry record documents the study's purpose and endpoint structure; it does not provide the numerical result needed to evaluate the primary statistical 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 most consequential limitation for interpretation is that the registry record does not report the numerical primary outcome estimate, its uncertainty, or group-specific results. It is therefore not possible to assess the magnitude or precision of the primary endpoint from this record. The brief summary states several aims, but numerical findings for those aims are not reported in the registry record.

The study's comparison structure is also limited in the information recorded. The registry states that this is not a randomized comparison, allocation is not stated, and the arms are not a like-for-like control comparison. The listed age groups do not provide a direct randomized contrast for estimating the effect of PCV13. Vaccination status, exposure definition, and a control-group definition are not reported in the registry record.

The endpoint applies to children colonized with any S. pneumoniae, rather than all enrolled children. The registry gives n=1851 for this endpoint population and lists enrollment of 9000, but does not describe participant flow or explain how the endpoint population was assembled. It is not clear from the record how non-colonized children, missing specimens, or repeated samples were treated.

Important analysis details are not reported in the registry record, including the statistical model, covariate adjustment, confidence intervals, missing-data methods, and handling of observations over time. The endpoint description does not say whether observations are independent or how potential within-child dependence was addressed. Multiplicity procedures and the analysis population are also not specified.

Finally, the stated surveillance objective refers to a presumed new equilibrium, but the record does not report an analysis demonstrating that equilibrium or a numerical serotype trend. These gaps mean that the registry entry supports description of the intended question and recorded population, but not a firm assessment of the result or its causal interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Streptococcus Pneumonia: Effects of PCV13 on Pneumococcal Carriage — NCT01109108.
• Registry record last updated 2017-03-14; status last verified 2017-01.
• Results first posted 2017-03-14.
• 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

The record concerns NCT01109108, sponsored by Boston Medical Center, with COMPLETED status. It lists enrollment of 9000, a start date of 2010-04, and primary completion at 2015-03. The study aimed to assess PCV13 impact on serotype-specific S. pneumoniae carriage in children younger than 5 years, with surveillance over study years 1-5.

The primary endpoint is described as the proportion of PCV13 serotypes among n=1851 children colonized with any S. pneumoniae. The registry also describes age groups of children younger than 2 years and children aged 2 to younger than 5 years, with and without respiratory tract infection. It cautions that the comparison is not randomized, allocation is not stated, and the groups are not like-for-like controls.

The numerical primary outcome, uncertainty measure, and results for the additional study aims are not reported in the registry record. Safety listings record 0 serious adverse events, 0 other adverse events, and 0 deaths in each age group. The available information supports understanding the study question and endpoint definition, but not estimating an intervention effect.