Safety and Immunogenicity of V114 in Healthy Adults (V114-019/PNEU-AGE): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of V114 in Healthy Adults (V114-019/PNEU-AGE) (NCT03950622), a randomized phase 3 study. The primary outcome is Percentage of Participants With a Solicited Injection-site Adverse Event.

2. Clinical Question

These questions concern different kinds of outcomes. The primary outcome named in the registry record is a short-term safety measure, covering solicited injection-site events: redness or erythema, swelling, and tenderness or pain. The immune-response hypotheses concern OPA geometric mean titers (GMTs), a measure of antibody activity, and use a specified postvaccination assessment time. The registry record lists additional immune-response outcomes, including serotype-specific IgG measures and fold rises. It does not report a single comparative result for the primary safety endpoint, so the endpoint description alone cannot establish how often such events occurred in either group or how the groups compared.

3. Trial Design

This was a phase 3, randomized, double-blind, parallel-group, active comparator-controlled study. It enrolled healthy adults aged 50 years or older and compared V114 with Prevnar 13™. The registry record reports enrollment of 1205 participants. Both groups were assigned a single intramuscular dose of 0.5 mL at Visit 1 (Day 1). The record lists pneumococcal infections as the condition of interest and identifies Merck Sharp & Dohme LLC as the sponsor.

The study start date was 2019-06-13, and the primary completion date was 2020-03-30. Its status is completed. These dates describe the trial’s registry timeline; they do not, by themselves, describe the duration of participant follow-up. The primary safety outcome has a stated timeframe of up to Day 5 postvaccination, while the principal immune-response hypotheses specify assessment at 30 days postvaccination.

Randomization assigns participants to study groups by chance, which is intended to make the groups comparable at the outset. Double masking means that the study is described as blinded for two parties, but the registry record does not identify which parties. A parallel-group design means the assigned groups are followed as separate groups rather than participants switching between interventions. The active comparator is another vaccine, rather than an inactive control.

The registry record describes the study’s aims as evaluating safety and tolerability and comparing immune responses. It states noninferiority as the hypothesis for the 13 serotypes shared by the vaccines and superiority for the 2 serotypes unique to V114. The noninferiority margin, detailed allocation procedures, and specific masking procedures are not reported in the registry record. The record also does not report the protocol’s sample-size justification or interim-analysis plan.

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: The analysis population included all randomized participants who received study vaccination and were included in the intervention group according to the intervention they received.

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 With a Solicited Injection-site Adverse Event, measured over Up to Day 5 postvaccination.

The primary endpoint is the percentage of participants with a solicited injection-site adverse event up to Day 5 postvaccination. The specified events are redness or erythema, swelling, and tenderness or pain at the injection site. The endpoint is a binary participant-level outcome: a participant is counted according to whether an event meeting the definition was recorded during the stated timeframe. The registry record defines an adverse event as an untoward medical occurrence temporally associated with study intervention, whether or not it is considered related to the intervention.

In general, reporting a percentage helps describe how common an event was in a study group, while the accompanying group denominator indicates how many participants were considered in that measure. Comparing groups can help describe whether event frequencies differed in the trial. Such a comparison needs the event definition, follow-up window, analysis population, and uncertainty around the estimates to be interpreted properly.

Solicited events are actively specified for collection rather than limited to events participants or investigators happen to report without prompting. This makes the endpoint useful for describing short-term local reactions under a consistent set of definitions. It does not capture every possible safety outcome, and the short stated timeframe does not address events outside that window. The registry record does not report a single comparative result for this endpoint, so the event percentages and their precision cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record gives the study design and outcome definitions, but does not report a complete statistical analysis plan. The explanations below distinguish general statistical concepts from the specific methods documented in the registry record. The planned analysis details that are absent should not be inferred from the trial’s design or from the stated hypotheses.

What does randomization contribute?

In general, randomization assigns participants to groups by chance. Its purpose is to reduce systematic differences between groups at enrollment, including differences that may be difficult to measure. It does not guarantee that groups will be identical, and it does not by itself address missing observations, measurement errors, or differences in how outcomes are analyzed. The record identifies the study as randomized, but the specific randomization procedure and allocation concealment details are not reported in the registry record.

What does double masking mean?

In general, masking is intended to limit the influence of knowledge about assigned treatment on participant experience, clinical management, outcome assessment, or reporting. The record labels the study double-blind but does not identify the parties who were masked or describe how masking was maintained. Therefore, the label alone does not establish the exact masking procedures.

How should the primary endpoint be understood?

The primary endpoint is a percentage of participants with at least one specified solicited injection-site adverse event during the stated period, up to Day 5 postvaccination. In general, a percentage for a binary outcome is calculated from the number of participants meeting the event definition and the relevant analysis denominator. The registry record describes the event types and identifies the analysis population as randomized participants who received study vaccination, classified according to the intervention received. It does not report the primary endpoint’s group percentages or a single comparative result.

For a group comparison, an estimate describes the observed contrast between groups, and a confidence interval describes the range of values compatible with the data under the analysis assumptions. A confidence interval is not a guarantee that the true value lies within its limits. The record does not provide a confidence interval for the primary endpoint, so its precision cannot be assessed from the registry record.

What do noninferiority and superiority mean?

In general, a noninferiority analysis asks whether an intervention’s effect is not worse than the comparator by more than a prespecified margin. That margin is essential to interpreting the conclusion: a noninferiority result depends on the margin, the analysis, and the uncertainty around the estimate. The registry record states the noninferiority question for OPA GMTs for the 13 shared serotypes at 30 days postvaccination, but the margin and the analysis details are not reported in the registry record.

In general, a superiority analysis asks whether the evidence supports a better result on the defined outcome in one group than in the comparator group. The trial description states this question for OPA GMTs for the 2 serotypes unique to V114. No superiority result or uncertainty estimate for these comparisons is reported in the registry record.

Why use geometric means for immune measures?

OPA GMTs and geometric mean concentrations summarize antibody measurements on a multiplicative scale. In general, geometric means are useful when measurements are positive and vary over a wide range, because the log scale can make relative differences easier to analyze. A geometric mean fold rise summarizes change relative to baseline on a multiplicative scale. These are general properties of the measures; the registry record does not report the transformations, estimation procedures, or model details used for these outcomes.

The listed secondary outcomes include serotype-specific OPA and IgG measures, geometric mean fold rises, and percentages of participants meeting fourfold-rise criteria. A threshold-based percentage answers a different question from a group mean: it describes how many participants crossed a defined response threshold, while a geometric mean summarizes the distribution on a multiplicative scale. The record lists these outcome types but does not provide the complete analysis methods or comparative results for them.

Why does over-dispersion matter?

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too narrow and its tests can be misleading. The primary endpoint is a percentage outcome, for which suitable methods depend on the analysis question and data structure. The registry record does not identify a model for the primary outcome or report an over-dispersion assessment. No particular model should be attributed to this trial from the available record.

Likewise, sample-size calculations depend on assumptions about the outcome, target effect, variability, allocation, significance level, and desired power. Any planning illustration based on observed effects is not the trial’s design justification and is not observed power. The registry record does not report the protocol’s sample-size justification. It also does not report an interim-analysis plan, the handling of missing data, or the complete statistical analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and 42 analyses. The study description includes multiple immune-response questions across serotypes, as well as several safety and immunogenicity outcomes. When many outcomes or comparisons are examined, the chance of obtaining at least one apparently notable result by chance can increase. In general, multiplicity procedures may control that risk by adjusting inference or by specifying an order or hierarchy for testing. The appropriate approach depends on the study questions and the analysis plan.

The registry record does not report a multiplicity adjustment, a testing hierarchy, or which comparisons were designated for confirmatory inference. It also does not provide a complete statistical analysis plan. The stated noninferiority and superiority hypotheses identify intended questions, but do not supply the margin, testing details, or rules for interpreting the collection of analyses. Therefore, the record does not support a judgment about how multiplicity was handled.

Missing-data methods also matter because participants may not have outcome measurements at every assessment. In general, the analysis population and the way missing observations are handled can affect estimates, especially when missingness differs between groups or is related to outcomes. The primary endpoint description says that the analysis population included randomized participants who received study vaccination, classified according to the intervention received. The specific missing-data rules, exclusions, and sensitivity analyses are not reported in the registry record.

The registry record also does not report whether all randomized participants contributed to each immune-response analysis, or how any unavailable measurements were treated. These details are particularly relevant when interpreting noninferiority questions, because different analysis populations or missing-data assumptions can influence the conclusion. The available description is not enough to reconstruct those choices.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (0.2%), acute myocardial infarction (0.2%), angina unstable (0.2%), arrhythmia (0.2%), oesophagitis ulcerative (0.2%).

The safety entries list serious adverse events for each group using a stated number at risk and a number affected. For V114, 9 participants are listed as affected among 602 at risk; for PCV13, 13 are listed as affected among 600 at risk. The record lists 1 death in each group. These figures are descriptive counts as recorded. They are not, on their own, evidence that vaccination caused an event or that the groups differ statistically.

The record lists Anaemia, Acute myocardial infarction, Angina unstable, Arrhythmia, Oesophagitis ulcerative, and Viral infection among the serious-event terms, each with a reported percentage of 0.2%. These terms and percentages describe registry entries; the record does not provide further comparative analysis for them. It is not appropriate to infer that the entries are exhaustive of all safety events or to attribute them to a study intervention from these data alone.

Other adverse-event entries list 395 participants affected among 602 at risk for V114, and 336 among 600 at risk for PCV13. These entries should be kept distinct from serious adverse events and from the primary endpoint. The primary endpoint specifically concerns solicited injection-site events up to Day 5, whereas the safety counts are not presented as that same endpoint. The registry record does not report a single comparative result for the primary safety endpoint.

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

This trial record describes a randomized, double-blind comparison of V114 and Prevnar 13™ in healthy adults aged 50 years or older. It specifies a short-term primary safety outcome and immune-response hypotheses focused on OPA GMTs at 30 days postvaccination. These descriptions establish what the study set out to assess; they are not evidence that either hypothesis was met.

The posted safety entries give counts of participants affected by serious and other adverse events, along with deaths and selected serious-event terms. Those counts can describe what was recorded in each group, but they do not establish cause, comparative risk, or statistical significance. The registry record does not report the estimates and uncertainty needed for a complete comparison of the primary endpoint. The serious-event counts also do not answer the specific question about solicited injection-site events through Day 5.

The immune-response statements are hypotheses, not reported findings. The record does not report the OPA GMT estimates, confidence intervals, or test results for the shared or unique serotypes. Without those results and the noninferiority margin, the immune-response conclusions cannot be assessed from the registry record.

More generally, the trial’s results would apply most directly to the studied population and conditions, not automatically to groups or settings outside them. The design description alone cannot establish how well the interventions compare for outcomes that were not reported, or for events beyond the specified follow-up windows. The registry record also does not report enough detail to evaluate all analysis choices, including multiplicity and missing-data handling.

Accordingly, the available record supports a description of the trial’s design, endpoints, stated hypotheses, and selected safety counts. It does not support a treatment recommendation or a conclusion that one intervention is safer, less safe, or more immunogenic than the other. Such conclusions would require the relevant comparative results, their precision, and the analysis context.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining safety and immunogenicity questions in a randomized active-comparator design. Its primary endpoint is a participant-level safety measure, while the stated principal immune-response hypotheses use serotype-specific OPA GMTs. These outcomes use different scales and answer different questions: an event percentage describes how often a defined event occurred, while a geometric mean summarizes antibody activity on a multiplicative scale.

The stated immune-response hypotheses also distinguish shared serotypes from serotypes unique to V114. Noninferiority and superiority are not interchangeable claims. In general, noninferiority requires a prespecified margin and careful interpretation of the uncertainty around the comparison; superiority asks whether evidence supports a better outcome on the stated measure. The registry record states both types of question but does not report the results or the noninferiority margin, leaving their inferential interpretation unresolved.

The record lists 12 outcome measures and 42 analyses. That breadth makes clear why prespecified analysis choices matter: readers need to know which outcomes and comparisons are central, how multiplicity was addressed, and how missing measurements were handled. Those details are not reported in the registry record. The study therefore illustrates the distinction between a study’s stated aims and a complete statistical account of its findings.

Finally, descriptive safety counts should not be mistaken for comparative inference. Counts and denominators convey what was recorded, but confidence intervals and analysis details are needed to describe precision and support a group comparison. Since a single comparative result for the primary safety endpoint is not reported, the record is informative about design and outcome definitions without resolving that 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 registry record gives the trial design, selected outcome definitions, safety counts, and stated immune-response hypotheses, but it does not report a single comparative result for the primary safety endpoint. It therefore does not provide the primary endpoint estimates or their precision. The absence of those results limits interpretation of the central safety question.

For the immune-response hypotheses, the record does not report comparative OPA GMT estimates, confidence intervals, or test results. The noninferiority margin is not reported in the registry record. Without that margin and the relevant estimates, the noninferiority question cannot be evaluated from the record. The superiority hypothesis for the unique serotypes likewise cannot be assessed without comparative results and uncertainty measures.

The record lists 12 outcome measures and 42 analyses, but does not report a multiplicity strategy or a complete statistical analysis plan. It also does not report the specific missing-data rules, sensitivity analyses, interim-analysis plan, or protocol sample-size justification. These omissions prevent a full assessment of how analysis choices may have affected inference.

The primary safety outcome is limited to solicited injection-site events up to Day 5 postvaccination. It does not, by definition, describe every safety outcome or events outside that timeframe. The safety counts listed elsewhere in the record have different scopes and should not be treated as a substitute for the primary endpoint. Finally, the record’s description of healthy adults 50 years of age or older does not establish how findings would apply to other populations or settings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of V114 in Healthy Adults (V114-019/PNEU-AGE) — NCT03950622.
• Registry record last updated 2021-04-26; status last verified 2021-03.
• Results first posted 2021-03-18.
• 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

NCT03950622 is a completed phase 3, randomized, double-blind, parallel-group, active comparator-controlled study of V114 and Prevnar 13™ in healthy adults 50 years of age or older. The registry record reports enrollment of 1205 participants and single 0.5 mL intramuscular doses at Visit 1 (Day 1). The study start date was 2019-06-13, and the primary completion date was 2020-03-30.

The primary endpoint is the percentage of participants with a solicited injection-site adverse event up to Day 5 postvaccination. The study description also states immune-response hypotheses based on OPA GMTs at 30 days postvaccination. Safety counts and selected serious-event terms are listed, but a single comparative result for the primary endpoint and the immune-response estimates are not reported in the registry record. The record lists 12 outcome measures and 42 analyses, while detailed multiplicity, missing-data, and analysis-plan information is not reported.