This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13™ in Healthy Infants (V114-031/PNEU-LINK) (NCT03692871), a randomized phase 3 study. The primary outcome is Percentage of Participants With a Solicited Injection-site Adverse Event.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03692871 |
| Phase | Phase 3 |
| Condition | Pneumococcal Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 2409 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy infants, including full-term infants and premature infants. The registry describes full-term infants as those born at or after 37 weeks gestational age and premature infants as those born before 37 weeks. The primary endpoint population was randomized participants who received at least one dose of study vaccination. A premature infant immunogenicity substudy assessed immune-response measures and safety in that subgroup.
Intervention
The intervention was V114, given as a single 0.5 mL intramuscular injection at approximately 2 months, 4 months, 6 months, and 12-15 months of age. The trial assessed safety and tolerability, with the primary endpoint focusing on specified injection-site adverse events after vaccination. The registry also lists serotype-specific IgG measures for premature infants as secondary outcomes.
Comparator
The active comparator was Prevnar 13™, administered on the same described schedule and by the same route, with a single 0.5 mL injection at each vaccination. Because both groups received an active vaccine, the primary safety question concerns the observed injection-site event percentages between the randomized groups, rather than comparison with no vaccination or placebo.
Primary question
The primary question was what percentage of participants experienced a solicited injection-site adverse event up to Day 14 after each study vaccination. The specified events were redness, a hard lump, tenderness, and swelling at the injection site. Although the endpoint and its population are described, the registry record does not report the group percentages or an estimated between-group comparison. The posted record therefore does not establish the size or precision of any difference for this endpoint.
3. Trial Design
This was a Phase 3, multicenter, randomized, double-blind, active-comparator-controlled study with a parallel-group design. The registry lists an enrollment of 2409 and identifies Merck Sharp & Dohme LLC as the sponsor. The study began on 2018-12-14, reached primary completion on 2021-03-26, and is listed as completed. These details describe the trial’s design and administrative status; they do not supply the results of its primary comparison.
Participants were assigned to V114 or Prevnar 13™. The registry describes both groups as receiving four intramuscular vaccinations: at approximately 2 months, 4 months, 6 months, and 12-15 months of age. Each injection was described as 0.5 mL. The record identifies triple masking, but does not report the specific roles masked or the procedures used to maintain masking. It also does not report the randomization procedure or allocation-concealment method.
The main study included healthy full-term and premature infants. Premature infants were also included in an immunogenicity substudy. The listed secondary measures for that subgroup concern serotype-specific IgG concentrations at several points in the vaccination schedule and the percentage meeting a stated IgG threshold after Vaccination 3. These are separate from the primary injection-site safety endpoint. The record does not provide results for those secondary measures in the information available for this analysis.
Enrollment and analysis denominators need not describe the same population. The primary endpoint population is defined as randomized participants who received at least one dose, while the posted safety figures give their own at-risk counts. The registry record does not explain the relationship between these counts or the reasons for any difference.
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: This study enrolled healthy infants. Other inclusion criteria applied.
Overall Study
| Stage | V114 | Prevnar 13™ |
|---|---|---|
| STARTED | 1972 | 437 |
| COMPLETED | 1847 | 400 |
| NOT COMPLETED | 125 | 37 |
Reasons for not completing this period:
| Reason | V114 | Prevnar 13™ |
|---|---|---|
| Death | 1 | 1 |
| Lost to Follow-up | 24 | 9 |
| Physician Decision | 22 | 7 |
| Protocol Deviation | 1 | 0 |
| Withdrawal by Parent/Guardian | 77 | 20 |
Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least 1 dose of study vaccination
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.
| Characteristic | Unit | V114 | Prevnar 13™ | Total |
|---|---|---|---|---|
| Participants analysed | 1972 | 437 | 2409 | |
| Age, Continuous | weeks | 8.7 (SD 1.5) | 8.8 (SD 1.5) | 8.7 (SD 1.5) |
| Sex: Female, Male: Female | Participants | 948 | 227 | 1175 |
| Sex: Female, Male: Male | Participants | 1024 | 210 | 1234 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 293 | 74 | 367 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1678 | 362 | 2040 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 64 | 20 | 84 |
| Race (NIH/OMB): Asian | Participants | 730 | 152 | 882 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): Black or African American | Participants | 54 | 19 | 73 |
| Race (NIH/OMB): White | Participants | 966 | 214 | 1180 |
| Race (NIH/OMB): More than one race | Participants | 154 | 31 | 185 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 | 0 | 2 |
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 14 after each study vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint measures the percentage of participants with a solicited injection-site adverse event up to Day 14 after each study vaccination. The listed events are injection-site erythema (redness), induration (a hard lump), pain (tenderness), and swelling. An adverse event is defined in the registry as an untoward medical occurrence temporally associated with study treatment, whether or not considered related to treatment.
In general, solicited events are specified in advance and actively assessed, rather than being limited to symptoms that participants choose to report without prompting. This approach can make safety observations more consistent across treatment groups, provided the same procedures and observation windows are applied. The registry describes the endpoint and timeframe, but does not report how participants were prompted, how events were graded, or how overlapping symptoms were handled.
A percentage is a binary-outcome summary: each participant is classified according to whether the event criterion was met, and the result is expressed relative to an analysis denominator. In general, this makes the measure straightforward to interpret, but it does not convey event intensity, duration, or clinical importance. No primary endpoint percentages, confidence intervals, or between-group estimate are reported in the registry record, so the magnitude and precision of the comparison cannot be assessed from it.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary safety endpoint and defines its population, events, and observation window. It does not report the endpoint results. In particular, it gives no group-specific percentage for solicited injection-site adverse events, no estimated difference between V114 and Prevnar 13™, and no confidence interval or test result for that comparison. There is therefore no basis in the record for describing the direction, size, or statistical precision of the primary comparison.
The record lists 7 outcome measures and 9 analyses. Those counts indicate that multiple outcomes or analyses were registered, but do not by themselves reveal how results were analyzed, which comparisons were prespecified as confirmatory, or how multiplicity was handled. The primary endpoint is described as involving several categories or time points and is not reduced to one comparison in the available result information. Its actual category- and time-specific results are not reported in the registry record.
The posted safety figures include serious-event counts of 192 among 1965 at risk in the V114 group and 45 among 433 at risk in the Prevnar 13™ group. The registry also lists other adverse-event counts of 1807 among 1965 at risk and 395 among 433 at risk, respectively, and one death in each group. These are descriptive counts, not an adjusted comparison. The record does not report a causal assessment for the deaths or explain the relation between these broad safety counts and the primary solicited injection-site endpoint. The serious-event term percentages listed in the record are also not a substitute for the primary endpoint results.
In general, an estimate is more informative when accompanied by a confidence interval. The interval communicates the range of values compatible with the data under the stated statistical model; it is not a guarantee that the true value lies within that range. Without an endpoint estimate and its uncertainty, readers cannot judge whether the observed comparison is precise or whether a range of materially different values remains plausible. A missing result should not be interpreted as evidence of no difference.
The trial’s randomized, blinded, active-comparator design describes how the comparison was intended to be conducted. Design features alone do not establish what the results were. Interpretation must remain limited to the registered design and the safety counts that are actually posted, without inferring an unreported treatment effect.
9. Statistical Methods Explained
The primary outcome is a binary participant-level measure: a participant either met the endpoint definition or did not, within the stated observation period. For a binary percentage, the numerator is the number of participants meeting the event definition and the denominator is the number included in that analysis. The registry identifies the primary population as randomized participants who received at least one dose, but does not report the numerator, denominator, or percentage for the primary endpoint by group. The at-risk counts in the safety information should not be assumed to be the endpoint denominators.
In general, a comparison of binary outcomes can be reported using group percentages and an absolute difference in percentages, or another prespecified effect measure. Each measure answers a somewhat different question. A difference describes separation between group event frequencies, while a ratio describes their relative scale. Neither should be reconstructed without the relevant endpoint counts and the analysis definition. The registry record does not report a primary endpoint effect estimate, so no such comparison can be described.
Confidence intervals express uncertainty around an estimate under the assumptions of the statistical method used. In general, a narrower interval indicates greater statistical precision, while a wider interval indicates less precision. The interval’s interpretation depends on the analysis population, endpoint definition, and method. A confidence interval is not a measure of clinical importance, and it does not eliminate uncertainty about bias, missing observations, or the suitability of the model. No confidence interval for the primary endpoint is reported in the registry record.
In general, a hypothesis test evaluates how compatible the observed data are with a specified null hypothesis under the test’s assumptions. A p-value does not measure the probability that the null hypothesis is true, nor does it quantify the size or importance of an effect. A small p-value alone cannot establish a meaningful safety difference; a larger p-value cannot establish equivalence or absence of an effect. The registry record does not report a primary endpoint p-value or the test used, so there is no reported test result to interpret.
The study is randomized, parallel-group, and double-blind, and the record identifies triple masking. In general, randomization is intended to make treatment groups comparable with respect to measured and unmeasured baseline characteristics, on average. Blinding can reduce the influence of treatment knowledge on care or outcome assessment. These design properties do not guarantee that bias is absent: implementation, adherence, missing data, and outcome ascertainment also matter. The registry record does not report the randomization method, concealment procedures, masking roles, or adherence to masking.
The registry describes an endpoint assessed up to Day 14 after each vaccination. Repeated observation windows can generate multiple summaries, such as results by vaccination or event type. In general, analysis choices should specify whether the endpoint counts participants with at least one event across windows, reports each window separately, or uses another rule. These choices affect the estimand and interpretation. The record does not report the primary endpoint’s detailed aggregation rule or results for its multiple categories or time points.
The record lists 7 outcome measures and 9 analyses. These counts do not identify how many tests were confirmatory or whether any adjustment was made for multiple comparisons. In general, evaluating many outcomes can increase the chance of at least one chance finding if each is tested independently at a conventional threshold. Prespecified hierarchy, adjusted testing, or clear separation of confirmatory and exploratory analyses can address this issue, but the statistical plan for this trial is not reported in the registry record.
Sample-size calculations are planning tools, not observed evidence about the treatment effect. In general, such calculations depend on assumptions about the effect to detect, outcome frequency, allocation, significance level, and power. Planning illustrations associated with the posted analysis use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect framed as a fraction of the observed effect. They are illustrations rather than the trial’s original design justification, and they are not observed power. The registry record does not report the trial’s own sample-size justification or its underlying assumptions.
For safety endpoints, raw counts are informative but can be difficult to compare when denominators differ. In general, a fair comparison requires a clearly defined endpoint, compatible observation periods, and denominators matching the population at risk. It may also require accounting for follow-up duration or other features of the data, depending on the endpoint. The registry’s listed safety counts are descriptive; the record does not provide an adjusted analysis of them or explain all denominator choices.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 7 outcome measures and 9 analyses, including the primary solicited injection-site adverse-event endpoint and secondary immunogenicity measures for premature infants. The primary endpoint description spans several event categories and vaccination time points. The available information does not reduce those elements to one reported comparison, and it does not give group-specific primary endpoint results.
When several outcomes, time points, or contrasts are analyzed, the chance of a chance finding can increase if each is tested separately without an appropriate plan. In general, a statistical plan may define a hierarchy, adjust significance thresholds, or identify some analyses as exploratory. The registry record does not report whether any such multiplicity strategy was used. The outcome and analysis counts alone cannot establish that an adjustment was or was not applied.
The record defines the primary analysis population as randomized participants who received at least one dose. It does not report how missing endpoint observations were handled, whether participants with incomplete follow-up were excluded or otherwise included, or what sensitivity analyses were performed. It also does not report the analysis population for every secondary outcome or whether analyses followed assignment regardless of vaccination received.
In general, missing-data methods can influence estimates when the probability of missingness is related to treatment, outcome, or participant characteristics. Sensitivity analyses can assess how conclusions depend on assumptions about unobserved outcomes. Without a reported method and results, the effect of missing data on the trial’s estimates cannot be assessed. The registry record does not report the statistical analysis plan, so these 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.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| V114 | 192 | 1965 | 9.8% |
| Prevnar 13™ | 45 | 433 | 10.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| V114 | 1 of 1972 |
| Prevnar 13™ | 1 of 437 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| V114 | 1807 of 1965 |
| Prevnar 13™ | 395 of 433 |
Most frequent serious adverse event terms
| Event term | Organ system | V114 | Prevnar 13™ |
|---|---|---|---|
| Bronchiolitis | Infections and infestations | 27 of 1965 | 7 of 433 |
| Pneumonia | Infections and infestations | 12 of 1965 | 4 of 433 |
| Gastroenteritis | Infections and infestations | 15 of 1965 | 0 of 433 |
| Respiratory syncytial virus bronchiolitis | Infections and infestations | 9 of 1965 | 4 of 433 |
| Bronchitis | Infections and infestations | 8 of 1965 | 2 of 433 |
| Pyrexia | General disorders | 8 of 1965 | 1 of 433 |
| Escherichia pyelonephritis | Infections and infestations | 8 of 1965 | 1 of 433 |
| Exanthema subitum | Infections and infestations | 7 of 1965 | 1 of 433 |
| Escherichia urinary tract infection | Infections and infestations | 6 of 1965 | 1 of 433 |
| Influenza | Infections and infestations | 4 of 1965 | 3 of 433 |
Most frequent non-serious adverse event terms
| Event term | Organ system | V114 | Prevnar 13™ |
|---|---|---|---|
| Irritability | Psychiatric disorders | 1472 of 1965 | 300 of 433 |
| Somnolence | Nervous system disorders | 1088 of 1965 | 238 of 433 |
| Injection site erythema | General disorders | 863 of 1965 | 156 of 433 |
| Injection site pain | General disorders | 843 of 1965 | 158 of 433 |
| Decreased appetite | Metabolism and nutrition disorders | 817 of 1965 | 156 of 433 |
| Pyrexia | General disorders | 775 of 1965 | 176 of 433 |
| Injection site swelling | General disorders | 549 of 1965 | 101 of 433 |
| Injection site induration | General disorders | 497 of 1965 | 111 of 433 |
| Diarrhoea | Gastrointestinal disorders | 188 of 1965 | 40 of 433 |
| Nasopharyngitis | Infections and infestations | 158 of 1965 | 37 of 433 |
Serious events with the highest arm-level rate: bronchiolitis (1.6%), pneumonia (0.9%), respiratory syncytial virus bronchiolitis (0.9%), gastroenteritis (0.8%), influenza (0.7%).
The registry lists serious-event figures of 192 among 1965 at risk for V114 and 45 among 433 at risk for Prevnar 13™. It also lists other adverse-event figures of 1807 among 1965 at risk and 395 among 433 at risk, respectively. These counts should be read with their stated group denominators; they are not the primary solicited injection-site endpoint results. The record does not explain all details of how these safety categories were defined or how the at-risk populations relate to the primary endpoint population.
The listed serious-event terms include bronchiolitis at 1.6%, pneumonia at 0.9%, respiratory syncytial virus bronchiolitis at 0.9%, gastroenteritis at 0.8%, influenza at 0.7%, and bronchitis at 0.5%. These term-specific percentages are descriptive registry entries. The record does not provide a comparative analysis for each term or establish whether an event was caused by vaccination. One death is listed in each group; the record does not report a causal attribution for either death.
In general, safety counts are best interpreted alongside definitions, follow-up, exposure, and uncertainty estimates. The posted figures alone do not establish a treatment-related risk difference or support a causal conclusion.
12. What the Result Does, and Does Not, Mean
The record establishes that NCT03692871 was designed as a randomized, blinded, active-comparator study of V114 and Prevnar 13™ in healthy infants. It specifies the vaccination schedules, the primary safety question, and the inclusion of a premature infant immunogenicity substudy. It also posts selected safety counts and serious-event terms. These details describe the study and the information available, but they do not provide the primary endpoint comparison.
The primary outcome concerns the percentage of participants with specified injection-site events up to Day 14 after each vaccination. Because the registry record does not report the group percentages, an effect estimate, or its uncertainty, it does not show how the groups compared for that endpoint. The omission should not be interpreted as either a finding of no difference or a finding of a difference. The secondary immunogenicity outcome results are also not reported in the record.
The safety counts and term percentages are not equivalent to a complete benefit-risk assessment. They do not, on their own, indicate whether events were treatment-related, how long they lasted, how severe they were, or how groups compared after accounting for the analysis populations and follow-up. The death count in each group likewise does not establish cause or association.
In general, evidence from a randomized comparison is interpreted using the prespecified outcomes, analysis methods, effect estimates, and their uncertainty, together with the quality and completeness of follow-up. The registry’s design features are relevant context, but cannot replace unreported results. No medical conclusion about the relative safety or immunogenicity of the vaccines can be drawn from the missing primary and secondary estimates in this record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the difference between a clearly defined endpoint and a reported result. The registry specifies the primary safety outcome, its event categories, its observation window, and the population for analysis. Those definitions are necessary to interpret a comparison, but they are not enough to determine its size or precision when group results are absent.
The active-comparator design also makes the estimand important. The study asks about safety under two vaccination schedules, not against an untreated or placebo group. In general, an active-comparator trial’s interpretation depends on the endpoint, population, follow-up, and comparison method being clearly specified. The record does not supply the primary endpoint estimates needed to characterize that comparison.
There is a second useful statistical lesson in the premature infant substudy. The registry distinguishes safety from immunogenicity and lists IgG outcomes for a subgroup. These outcomes address different questions and use different measurements. In general, a safety endpoint based on whether an event occurred should not be conflated with a continuous antibody concentration or the percentage meeting a threshold.
Finally, posted serious-event counts, outcome totals, and analysis counts need context. Counts do not substitute for adjusted comparisons, uncertainty intervals, or the prespecified analysis plan. The record’s missing primary results and unreported methods limit what can be concluded, despite the detailed design description. This distinction helps readers separate trial conduct and registration information from evidence about comparative outcomes.
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 central limitation is that the registry record does not report the primary endpoint results. It gives neither group percentages for solicited injection-site adverse events nor an estimated comparison with a confidence interval. Without those values, the size and precision of the primary safety comparison cannot be assessed.
The record also does not report the full statistical analysis plan, including the method for handling multiple event categories or vaccination time points. Missing-data methods, sensitivity analyses, and the analysis populations for all outcomes are not reported in the registry record. These omissions restrict assessment of robustness and possible bias.
Although safety counts and selected serious-event term percentages are listed, the record does not provide a complete account of endpoint definitions and analysis procedures for those figures. It does not report causal attribution for the deaths, or an adjusted comparative analysis of the safety counts. The difference between the posted at-risk counts and the primary endpoint population definition is not explained.
The record identifies triple masking but does not report which study roles were masked or how masking was maintained. It also does not report the randomization procedure, allocation concealment, or the details of event ascertainment. These are relevant to evaluating implementation, but their absence from the registry information does not establish that the procedures were inadequate.
Finally, the registered secondary immunogenicity outcomes for premature infants are listed without results in the information available for this analysis. Conclusions are therefore limited to the trial’s design and the safety figures actually posted; unreported endpoints and methods cannot be inferred.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Safety and Tolerability of V114 and Prevnar 13™ in Healthy Infants (V114-031/PNEU-LINK) — NCT03692871.
- Registry record last updated 2023-07-28; status last verified 2023-07.
- Results first posted 2022-05-10.
- 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.
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18. Record Summary
NCT03692871 is listed as a completed Phase 3, multicenter, randomized, double-blind, active-comparator, parallel-group study in healthy infants. It compared V114 with Prevnar 13™ on a four-vaccination schedule and included full-term and premature infants. Premature infants were included in an immunogenicity substudy.
The primary outcome was the percentage of participants with a solicited injection-site adverse event up to Day 14 after each vaccination. The record defines the events and the primary population but does not report the primary group results or their statistical uncertainty. It lists 7 outcome measures and 9 analyses, along with selected safety counts and serious-event terms. The statistical plan, multiplicity handling, missing-data methods, and results for the listed secondary immunogenicity measures are not reported in the registry record. Accordingly, the available record describes the trial design and selected safety information but does not permit a quantitative interpretation of the primary comparison.