PCV13 Effectiveness Study Against Hospitalised VT Pneumococcal CAP in Adults 60 Years and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PCV13 Effectiveness Study Against Hospitalised VT Pneumococcal CAP in Adults 60 Years and Older (NCT04613375), a registered phase not stated study. The primary outcome is Number of Participants Categorized as Cases and Controls to Determine Vaccine Effectiveness (VE) of PCV13 Against Hospitalized VT CAP: Overall.

2. Clinical Question

The question is about the association between vaccination and case status within a hospitalized CAP population, rather than a comparison of randomized groups. The case and control definitions depend on valid UAD results and identification of PCV13 serotypes. The primary outcome is described over approximately 30 months. The registry lists enrollment of 1821 participants and identifies CAP as the condition under study. It does not report how many enrolled participants met the primary-outcome population definition or how many were ultimately classified as cases and controls.

3. Trial Design

The registry describes a low-intervention, prospective, multicentre, hospital-based study of adults aged 60 years and older hospitalized with CAP. The official title identifies the setting as a well-defined area in the south of the Madrid region. The study is completed, with a listed enrollment of 1821. The registry dates the start as 2021-03-12 and primary completion as 2023-10-25.

The design uses a test-negative approach. Participants with CAP and a valid UAD result are classified as cases when PCV13 serotypes are identified by any method. Participants with a valid UAD result and no identified PCV13 serotype are classified as controls. The stated effectiveness measure compares the odds of having received PCV13 for cases and controls. This structure differs from a randomized trial: the registry does not describe randomized allocation, and it does not present the groups as assigned treatment arms.

Urine sample collection and saliva collection are listed as diagnostic-test interventions. They support identification of pneumococcal infection or serotypes; the record does not describe them as vaccine interventions. The primary-outcome timeframe is approximately 30 months. Secondary outcomes include case and control classification by time since vaccination, the distribution of pneumococcal serotypes, saliva-based detection, underlying risk conditions, and antibiotic resistance among Streptococcus pneumoniae isolates.

The registry names Pfizer as sponsor. It does not report the number or identity of participating hospitals, detailed eligibility criteria, the vaccination ascertainment procedure, or the full operational protocol. It also does not report the statistical adjustment strategy or the results for the primary and secondary outcomes. Those omissions limit how much can be concluded from the design description alone.

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 1821 participants were enrolled in this study and 51 participants did not meet inclusion/exclusion of the study. In this study, a) pandemic period included data from 12 March 2021 to 31 July 2022 when last relevant coronavirus disease 2019 (COVID-19) wave in target population (aged \>=60 years) ended in Madrid; b) post-pandemic period included data from 01 August 2022 to 13 September 2023.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: CAP UAD population included all enrolled population who met all inclusion/exclusion criteria and who had a final diagnosis consistent with CAP with a valid UAD result.

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.

Population: The per-protocol population included all participants in all enrolled population who met all inclusion/exclusion criteria.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Categorized as Cases and Controls to Determine Vaccine Effectiveness (VE) of PCV13 Against Hospitalized VT CAP: Overall, measured over Approximately 30 months.

The primary outcome concerns the number of participants categorized as cases and controls for estimating PCV13 vaccine effectiveness against hospitalized vaccine-type CAP. A case is a participant with CAP, a valid UAD result, and PCV13 serotypes identified by any method. A control is a participant with CAP and a valid UAD result, but without a PCV13 serotype identified. The analysis population is defined as enrolled participants who meet the inclusion and exclusion criteria, have a final diagnosis consistent with CAP, and have a valid UAD result.

The endpoint is useful because it establishes the groups whose vaccination histories are compared. The registry defines effectiveness as one minus the odds ratio comparing the odds of having received PCV13 among cases and controls, multiplied by 100%. In general, an odds ratio expresses the relative odds of an exposure across outcome groups. Here, it is used to quantify the association between vaccination history and case classification within the hospitalized CAP population.

The outcome is listed over approximately 30 months. Although the endpoint description explains the intended calculation, the registry record does not report the case count, control count, odds ratio, vaccine-effectiveness estimate, confidence interval, or p-value. The definition therefore describes what the study sought to estimate, not the magnitude or precision of the result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

How does the test-negative comparison work?

In general, a test-negative design compares people who seek care for a similar clinical syndrome and are classified by testing as having or not having the target infection or serotype. The registry applies this structure among participants hospitalized with CAP: cases have a valid UAD result and PCV13 serotypes identified by any method, while controls have a valid UAD result without a PCV13 serotype. Comparing vaccination histories within this clinical population is intended to reduce some differences that can arise when cases are compared with people who did not seek similar care. It does not make the groups randomized or guarantee that they are otherwise comparable.

The registry record defines the primary analysis population as enrolled participants who satisfy eligibility criteria, have a final diagnosis consistent with CAP, and have a valid UAD result. This definition matters because the estimate pertains to that population, not automatically to every person enrolled or every adult with CAP. The record does not state how many participants met this definition or how many had complete vaccination information.

What does the odds ratio represent?

The odds ratio compares the odds of prior PCV13 vaccination among cases with the odds among controls. The registry defines vaccine effectiveness as one minus that odds ratio, multiplied by 100%. In general, an odds ratio is a relative measure of association. Its interpretation depends on how cases and controls are defined, how exposure is measured, and which analysis is used. The effectiveness formula is a definition; without the observed odds ratio, it yields no numerical effectiveness estimate.

The registry does not report whether the primary comparison was adjusted for other participant characteristics. In general, adjustment can account for measured differences between groups, but it cannot remove bias from unmeasured factors and depends on the selected model and variables. The adjustment approach and any adjusted estimate are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval describes the statistical uncertainty around an estimate under the model and assumptions used. A narrow interval indicates greater precision than a wide interval, while an interval spanning values compatible with different directions or magnitudes of association may leave substantial uncertainty. A p-value addresses compatibility of the observed data with a specified null model; it is not a measure of clinical importance and does not express the probability that a hypothesis is true. The registry record does not report a confidence interval or p-value for the primary outcome, so neither precision nor statistical evidence can be evaluated from the endpoint description.

Over-dispersion is a general issue for count outcomes when variability exceeds what a model assumes. The primary outcome is described as a count of participants, but the record does not identify a count model or report a dispersion parameter. It would therefore be inappropriate to claim that over-dispersion was present or that a particular correction was applied. More broadly, model choice should reflect the data structure, but the statistical model is not reported in the registry record.

What information is missing about the analysis?

The registry lists 9 outcome measures and 8 analyses. The primary outcome is defined, and several secondary outcomes are named, but the record does not give the analysis specifications, model covariates, handling of repeated or stratified comparisons, or result estimates. It does not report whether interim analyses were planned or performed, or how the sample size was justified. These details should not be inferred from the completed status or enrollment count.

General planning illustrations based on an observed effect are not the same as the trial’s original sample-size justification and are not observed power. A sample-size calculation estimates the number of participants needed under stated assumptions; it cannot establish that an effect was detected or that an estimate is precise. The registry record does not report the trial’s own design assumptions for sample size.

The listed primary timeframe is approximately 30 months. This describes the outcome timeframe, but the record does not explain participant-level follow-up, the timing of vaccination ascertainment, or whether all participants had the same observation period. These details can affect interpretation of exposure and outcome classification. Without the analysis plan and numerical results, the appropriate reading is limited to the design and endpoint definitions that are explicitly recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures and 8 analyses. The primary outcome is the overall case and control classification used to determine PCV13 vaccine effectiveness against hospitalized vaccine-type CAP. Named secondary outcomes address classification by time since vaccination, pneumococcal serotypes, saliva-based identification, underlying risk conditions, high-risk conditions, and antibiotic resistance. The registry record does not report how the analyses map to the listed outcomes or identify a prespecified hierarchy among them.

When a study examines multiple outcomes or performs multiple comparisons, general statistical practice recognizes that the chance of at least one apparently noteworthy result can increase. Prespecifying a primary outcome and an analysis strategy can help readers distinguish the main question from exploratory findings. The record identifies a primary outcome, but does not report a multiplicity adjustment, a testing hierarchy, or a plan for interpreting multiple secondary analyses. It is not possible to determine whether any such procedures were used.

The primary analysis population requires eligibility, a final diagnosis consistent with CAP, and a valid UAD result. The registry record does not report the number of participants excluded from this population or the reasons for any missing or invalid results. It does not describe missing-data methods, whether analyses used complete records, or any sensitivity analyses. Consequently, the effect of missing information on case and control classification cannot be evaluated from this record.

The registry also does not report all analysis populations, such as whether the primary comparison included every eligible participant or a subset with complete vaccination information. These omissions are relevant to reproducibility and to judging whether the analyzed population matches the stated target population. They do not establish that the study handled multiplicity or missingness poorly; they mean those procedures are 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 0% reporting threshold.

The registry lists one group, All Participants, with 1680 participants at risk for serious adverse events and 0 participants affected. It also lists 1680 participants at risk for other adverse events and 0 affected. The recorded number of deaths is 198. No top serious adverse-event terms are listed.

These counts should be read as registry-reported safety figures, not as a complete account of causes, timing, or relationships to study procedures. The record does not report whether the deaths were related to the study, whether they occurred during a particular follow-up interval, or their causes. It also does not provide event narratives or explain how the at-risk group was defined. A recorded count of 0 affected for the listed adverse-event categories does not explain the separate death count.

The study is described as low intervention, with urine and saliva collection listed as diagnostic tests. That description does not establish whether any event was caused by a procedure or whether all events were captured. The registry record does not report additional safety detail that would resolve these questions. The figures therefore describe what is listed in the record, without establishing causation or a broader safety conclusion.

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

The record establishes that a prospective, multicentre, hospital-based study was conducted to examine PCV13 effectiveness against hospitalized vaccine-type CAP in adults aged 60 years and older. It defines a test-negative case and control population and describes how effectiveness was intended to be calculated from the odds ratio for prior vaccination. It also records enrollment of 1821 and marks the study completed.

Those details do not establish the size or direction of the estimated association. The registry record does not report case and control counts, the odds ratio, the vaccine-effectiveness estimate, or a confidence interval. Without those results, the record cannot show how strongly vaccination history was associated with case classification or how precisely that association was estimated. The endpoint definition is not a numerical result.

The design is observational rather than randomized. In general, estimates from an observational comparison can be influenced by differences between cases and controls, how vaccination and infection are measured, and selection into the analysis population. The registry describes eligibility and the need for a valid UAD result, but does not report enough detail to assess adjustment, missingness, or possible sources of bias.

The listed safety counts are also limited. The record reports 0 participants affected in the serious and other adverse-event categories, alongside 198 deaths, but does not give causes, timing, or relationship to study procedures. These figures should not be interpreted beyond their recorded categories.

Accordingly, the record supports a description of the research question, design, endpoint, and selected safety counts. It does not support a conclusion about the magnitude or precision of vaccine effectiveness, nor a causal interpretation of any association. The absence of an estimate from the registry record is not evidence that the estimate was zero or that no association existed; the result itself is not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how a test-negative design can frame an effectiveness question within a hospitalized population. Rather than comparing randomized treatment groups, it defines cases and controls by CAP status and identification of PCV13 serotypes, then compares their odds of prior vaccination. That makes clear that the estimand is tied to a specific clinical setting and case definition.

The validity of such an estimate depends on more than the formula. In general, classification accuracy, comparable vaccination ascertainment, and differences between cases and controls can affect the result. The registry identifies the need for a valid UAD result and specifies that cases may have serotypes identified by any method. Those definitions are central to interpreting the intended comparison. The record does not, however, report enough analytical detail to evaluate how classification, confounding, or missing data were addressed.

The endpoint also illustrates why estimates should be read with their uncertainty. An odds ratio transformed into vaccine effectiveness is still an estimate; its precision depends on the amount and pattern of information in the analyzed population. The registry record does not report the estimate or its confidence interval, so the central inferential result cannot be judged.

Finally, this record distinguishes study completion from complete results reporting. It lists enrollment, study status, the outcome framework, secondary questions, and selected safety counts, yet does not provide numerical effectiveness results. For biostatisticians and clinical researchers, that separation is important: a clear endpoint definition can explain what was intended to be estimated, but only the results and analysis details can show what the study found and how uncertain the finding is.

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 primary limitation for interpreting this record is that the numerical primary outcome is not reported. Case and control counts, the odds ratio, the vaccine-effectiveness estimate, and its uncertainty are absent. The completed status and enrollment figure do not substitute for these results.

The comparison is observational and not randomized. The registry does not report an adjustment strategy, so the degree to which measured participant differences were considered cannot be assessed. It also does not report how vaccination history was established, how serotype identification was performed across methods, or how consistency of classification was assured.

The primary analysis population requires a valid UAD result and a final CAP diagnosis. The record does not report the number of enrolled participants who met these criteria, how many had missing or invalid test results, or how exclusions were handled. It does not describe sensitivity analyses for missingness or alternative case definitions. These gaps prevent assessment of how participant selection might affect the comparison.

The registry names several secondary outcomes and lists 9 outcome measures and 8 analyses, but does not report a multiplicity strategy or detailed analysis plan. The sample-size justification, interim-analysis plan, and model specifications are not reported in the registry record. The record also does not provide detailed site information or explain participant-level follow-up within the approximately 30-month outcome timeframe.

These are limitations of the information recorded, not evidence that the underlying study necessarily lacked procedures to address them. They constrain independent evaluation of the analysis and results from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: PCV13 Effectiveness Study Against Hospitalised VT Pneumococcal CAP in Adults 60 Years and Older — NCT04613375.
• Registry record last updated 2025-06-11; status last verified 2025-06.
• Results first posted 2025-01-27.
• 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

NCT04613375 is a completed, low-intervention, prospective, multicentre, hospital-based study of PCV13 effectiveness against hospitalized vaccine-type CAP in adults aged 60 years and older. The registry lists enrollment of 1821 and a setting in the south of the Madrid region. Urine and saliva collection are listed as diagnostic-test interventions.

The primary outcome defines cases by CAP, a valid UAD result, and identification of PCV13 serotypes; controls have CAP and a valid UAD result without an identified PCV13 serotype. Vaccine effectiveness is defined using the odds ratio for prior vaccination among cases and controls. The primary timeframe is approximately 30 months.

The record lists secondary outcomes on serotypes, saliva detection, risk conditions, and antibiotic resistance. It reports 0 participants affected in the listed serious and other adverse-event categories and 198 deaths, without further detail on causes or relationships. Numerical primary effectiveness results and their uncertainty are not reported in the registry record.