The Safety, Tolerability, and Immunogenicity Profiles of a Single Dose of V114, PNEUMOVAX® 23, or PREVNAR 13® in Adults 50 Years of Age or Older (V114-002): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Safety, Tolerability, and Immunogenicity Profiles of a Single Dose of V114, PNEUMOVAX® 23, or PREVNAR 13® in Adults 50 Years of Age or Older (V114-002) (NCT01513551), a randomized phase 2 study. The primary outcome is Percentage of Participants With an Adverse Event.

2. Clinical Question

The registry describes a randomized, triple-masked, parallel-group Phase 2 study in adults 50 years of age or older. Its stated purpose was to assess the safety, tolerability, and immunogenicity of V114 in comparison with the two licensed pneumococcal vaccines. For the primary hypothesis, it specifies serotype-specific immunoglobulin G geometric mean concentrations measured by the pneumococcal electrochemiluminescence assay at one month after vaccination, with noninferiority of V114 to PNEUMOVAX® 23 as the question of interest.

The posted primary endpoint instead reports the percentage of participants with an adverse event. Those results are descriptive of the observed safety follow-up and do not answer the stated antibody noninferiority hypothesis. A secondary outcome concerns geometric mean titers of pneumococcal serotype-specific opsonophagocytic activity antibodies. Further antibody results are not described in the outcome data used for this analysis, so the safety comparisons should not be read as a summary of immunogenicity.

3. Trial Design

This was a randomized, triple-masked, parallel-group Phase 2 study sponsored by Merck Sharp & Dohme LLC. It is listed as completed, with enrollment of 692 participants. Participants were assigned to receive one of three vaccines: V114, PNEUMOVAX® 23, or PREVNAR 13®. Each arm description specifies one 0.5 mL intramuscular injection on Day 1; the V114 formulation is described as aluminum-adjuvanted.

The registry lists 229 participants in the V114 group, 230 in the PNEUMOVAX® 23 group, and 230 in the PREVNAR 13® group for the posted primary outcome. The primary safety analysis population consisted of participants who received study vaccination and had safety follow-up. This population definition is important: the reported percentages describe participants in that safety population, rather than necessarily every person enrolled.

The registry’s study purpose includes safety, tolerability, and antibody response. It states a primary immunogenicity hypothesis about serotype-specific IgG geometric mean concentrations one month after vaccination, comparing V114 with PNEUMOVAX® 23 for noninferiority. The primary outcome posted for the analysis is instead the percentage of participants with an adverse event. The registry also lists a secondary outcome for geometric mean titers of serotype-specific OPA antibodies.

The randomization method in detail, allocation concealment procedures, and the identities of the masked parties are not reported in the registry record. Nor is the original sample-size justification or a detailed protocol for statistical analysis reported in the registry record. The planning illustrations are based on the observed safety comparisons and should not be mistaken for the study’s original design rationale.

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 consisted of those participants who received study vaccination and had safety follow-up.

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 baseline analysis population consisted of all randomized participants who received study vaccine.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With an Adverse Event, measured over All AEs: up to 14 days after vaccination; Serious Adverse Events (SAEs): up to 6 months after vaccination.

The primary outcome is the percentage of participants with an adverse event. The registry defines an adverse experience as an unfavorable and unintended change in body structure, function, or chemistry that occurs in temporal association with use of the sponsor’s product, whether or not considered related to that product. Worsening of a pre-existing condition is also included when it is temporally associated with product use.

The stated observation period distinguishes the broader adverse-event outcome from serious adverse events: all adverse events were followed for up to 14 days after vaccination, while serious adverse events were followed for up to 6 months. The analysis population consisted of participants who received vaccination and had safety follow-up. The percentages therefore describe the frequency of participants with an event under the registry’s definition and follow-up windows; they do not establish that vaccination caused an event or that an event was related to a vaccine.

Counting participants with at least one event is a straightforward way to describe how often an event was recorded in each group. It does not convey how many events an individual experienced, how severe each non-serious event was, or the timing and duration of all events. Those details are not reported in the registry record for this primary outcome. The endpoint also does not measure antibody response, the study’s stated primary hypothesis, so safety percentages should be interpreted separately from immunogenicity questions.

7. Results Posted in the Registry

• PNEUMOVAX® 23: 68.3% (157/230) versus 75.1% (172/229) on control; risk difference -6.8 percentage points (95% CI -15.1 to 1.4), risk ratio 0.91 (0.81–1.02); unadjusted two-proportion z-test p = 0.103.
• PREVNAR 13®: 65.7% (151/230) versus 75.1% (172/229) on control; risk difference -9.5 percentage points (95% CI -17.8 to -1.1), risk ratio 0.87 (0.78–0.99); unadjusted two-proportion z-test p = 0.027.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either had at least one adverse event during the defined follow-up or did not. A percentage describes the share of the analysis population with an event. Comparing those percentages focuses on the difference in observed event frequency between groups, rather than on the total number of events each participant experienced.

What does a risk difference describe?

A risk difference is the event percentage in one group minus the event percentage in another group, expressed on the percentage-point scale when the percentages are reported that way. A value of zero corresponds to equal event percentages. Positive and negative values depend on the order of subtraction, so the direction must be read with the named groups. In the sponsor’s reported comparisons, the risk differences are V114 minus the comparator: 6.8 for PNEUMOVAX® 23 and 9.5 for PREVNAR 13®. The recalculated estimates use the reverse order, so they appear negative. Reversing the comparison order changes the sign, not the underlying contrast.

Why are there confidence intervals?

A confidence interval conveys uncertainty around an estimated difference. Its endpoints indicate a range of values compatible with the observed data and the method used to form the interval. A narrower interval indicates greater precision than a wider one, while an interval that includes zero does not rule out no difference at the interval’s stated confidence level. The reported intervals are 95% confidence intervals calculated with the Miettinen & Nurminen method. They are not guarantees that the true difference lies within the interval, and they do not measure clinical importance.

How should the p-values be read?

The recalculated p-values are unadjusted comparisons based on the posted summary statistics. A p-value describes how unusual data at least as discrepant as the observed data would be under a specified null model of no difference, assuming that model and the calculation are appropriate. It is not the probability that the null hypothesis is true, nor does it quantify the size or importance of a difference. The registry’s reported Miettinen & Nurminen analyses list no p-value. The recalculated p-values should not be mistaken for sponsor-reported values.

The registry’s reported method is Miettinen & Nurminen for risk differences. This method is used to estimate a difference between two binomial proportions and construct an interval for that contrast. The registry results give the risk difference and its confidence limits but do not report additional method details. The recalculated comparisons use simple unadjusted calculations from the posted arm summaries; they are not a replacement for the sponsor’s reported analysis.

What does masking and randomization contribute?

Random allocation is intended to make treatment groups comparable on average with respect to measured and unmeasured participant characteristics. Masking is intended to reduce the potential for expectations or knowledge of assignment to influence participant reports, clinical assessments, or study conduct. The registry identifies the study as randomized and triple-masked, but details of the randomization procedure and which parties were masked are not reported in the registry record. These design labels do not remove all potential sources of bias, and they do not determine the precision of the comparisons on their own.

What information is not available?

The registry record does not report the trial’s original sample-size justification, the planned statistical analysis details beyond the stated hypothesis and posted method, or whether interim analyses were conducted. Multiplicity procedures, missing-data rules, and the handling of participants without complete follow-up are not reported in the registry record. The safety analysis population is described as vaccinated participants with safety follow-up, but further details about missing outcomes or exclusions are not stated.

The registry lists a primary immunogenicity hypothesis and a posted primary safety outcome. These represent distinct statistical questions: noninferiority of antibody concentrations is not the same as a comparison of adverse-event percentages. The methods and interpretation for one outcome cannot be assumed to apply to the other. The available adverse-event analysis therefore supports description of the posted safety comparison, not conclusions about unreported antibody analyses or the broader study protocol.

10. Confidence Intervals and Precision

The sponsor-reported 95% confidence interval for the V114 versus PNEUMOVAX® 23 risk difference is -1.4 to 15.0, with the difference expressed as V114 minus PNEUMOVAX® 23. Because the interval includes zero, it allows for no difference as well as for differences in either direction. Its width also shows that the estimated contrast is not pinned down to a very narrow range.

For V114 versus PREVNAR 13®, the sponsor-reported risk difference is 9.5, with a 95% confidence interval from 1.1 to 17.7. This interval does not include zero in the sponsor’s stated orientation. It still spans a range of possible effect sizes, so the point estimate should not be treated as an exact value. The interval concerns the difference in recorded adverse-event percentages; it does not quantify causation or clinical importance.

Confidence intervals are useful because a point estimate alone conceals sampling uncertainty. They do not account automatically for every design or analysis issue, such as unreported multiplicity procedures or missing-data handling. The registry reports the Miettinen & Nurminen method for these risk differences. Recalculated intervals are simple unadjusted estimates from the posted summaries and use the opposite group order; the registry’s own intervals are the reported analyses.

Precision is also limited by the size of the analyzed groups and the variability inherent in a binary outcome. The registry lists 229, 230, and 230 participants in the respective groups. The confidence intervals describe uncertainty for the comparisons, while the arm percentages describe the observed event frequency. Neither type of result should be substituted for the other.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations express the estimated number of participants per arm for 80% power and for 90% power. They are not total event counts. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The illustrations are based on the observed effect, not on the original design assumptions for this trial; those original assumptions are not reported in the registry record.

The 80% power column gives the planned participants per arm under the calculation assumptions for a design with an 80% chance of detecting the chosen effect if that effect were the true one and the assumptions held. The 90% power column uses a higher target probability of detection under the same stated framework. These are planning quantities, not descriptions of how many participants were analyzed in the trial. This is not observed power.

Each comparison has planning rows for 100%, 75%, and 50% of the observed effect. A smaller effect is harder to distinguish from random variation and therefore requires more participants per arm to meet the same target power, under the stated assumptions. The illustrations can help show how planning requirements change when the effect of interest is smaller than the observed estimate. They do not establish that the observed effect will recur in another study, and they do not indicate the power of this completed trial.

The curve should be read as a visual representation of the same planning relationship: the required sample size changes with the effect size being targeted. It is a planning aid for the specified two-arm comparison, not a forecast of outcomes or a record of the original enrollment calculation. The registry does not report the trial’s own sample-size justification, so the illustrations should remain separate from any claim about why the trial enrolled its participants.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.751; treatment proportion p₁ = 0.683; average p̄ = 0.717.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6371 = 1.2488.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6353 = 0.5347.
4. n = (1.2488 + 0.5347)² / (-0.0685)² = 678.2, rounded up to 679 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.751091703056769                          # control proportion
p1 <- 0.682608695652174                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1513551)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 679 (80% power), 908 (90% power)
 75% of observed effect: n per arm = 1,185 (80% power), 1,585 (90% power)
 50% of observed effect: n per arm = 2,614 (80% power), 3,498 (90% power)
power.prop.test: 678.2 
Simulated power at n = 679 per arm: 0.798 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Analyses Reported by the Sponsor

The registry reports risk differences using the Miettinen & Nurminen method. For V114 versus PNEUMOVAX® 23, the sponsor-reported difference is 6.8, with a 95% confidence interval from -1.4 to 15.0. For V114 versus PREVNAR 13®, the sponsor-reported difference is 9.5, with a 95% confidence interval from 1.1 to 17.7. The sponsor’s comparisons are oriented as V114 minus the comparator.

The simple unadjusted recalculations use the opposite ordering: comparator minus V114. This accounts for the reversed signs of the recalculated point estimates and interval limits. The recalculated p-values are 0.103 for PNEUMOVAX® 23 versus V114 and 0.027 for PREVNAR 13® versus V114. The registry does not list p-values for its own reported analyses, so these recalculated values should not be attributed to the sponsor.

The recalculations are not a correction of the registry’s results. They provide an unadjusted comparison from the posted summary statistics, whereas the registry identifies a specific method for its reported risk differences. The trial’s detailed analysis plan and any adjustments beyond the reported method are not reported in the registry record. Interpretation should therefore distinguish the sponsor’s reported estimates and intervals from the recalculated comparisons.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists seven outcome measures and two analyses, including the primary safety outcome and a secondary antibody-titer outcome. It also describes a primary hypothesis about noninferiority of serotype-specific IgG geometric mean concentrations. The available record does not explain how statistical testing across outcomes, groups, or serotypes was handled, or whether any multiplicity adjustment was planned or applied. Multiplicity procedures are not reported in the registry record.

This matters because repeated statistical comparisons can increase the chance of obtaining apparently notable results by chance if all are interpreted as independent confirmatory tests. Without a stated testing hierarchy or adjustment approach, the recalculated p-values should be treated as unadjusted descriptive inferential results, not as proof that an overall family of hypotheses was controlled. The reported confidence intervals also do not, on the available information, account for any unreported multiplicity procedure.

The primary analysis population is described as participants who received study vaccination and had safety follow-up. The registry does not report how participants with missing safety information were handled, what amount of follow-up was required, or whether any imputation or sensitivity analyses were used. Missing-data procedures and sensitivity analyses are not reported in the registry record. The listed arm sizes therefore describe the posted analysis groups, but the record does not provide enough detail to assess whether missingness could have influenced the comparisons.

The registry describes a primary immunogenicity hypothesis while the posted primary outcome analyzed is adverse events. How those outcomes relate to a formal testing hierarchy is not reported. Nor are interim analyses, subgroup plans, or a complete statistical analysis plan reported in the registry record. These gaps limit assessment of whether the posted comparisons were prespecified, how all planned analyses were interpreted together, and how robust the results are to alternative analysis choices.

These omissions do not invalidate the reported percentages or intervals. They define the boundary of what can be inferred from the registry record: the posted safety results can be described and compared using the stated information, but the broader confirmatory analysis strategy cannot be reconstructed.

15. 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: coronary artery occlusion (0.4%), appendicitis (0.4%), anal cancer (0.4%), anxiety (0.4%), cardiac failure (0.4%).

The serious adverse-event figures are reported separately from the overall adverse-event percentages. There were 4 participants with a serious adverse event in the V114 group, 7 in the PNEUMOVAX® 23 group, and 5 in the PREVNAR 13® group. The corresponding groups at risk were 229, 230, and 230. The registry specifies follow-up for serious adverse events through 6 months after vaccination.

These counts are small, and the registry does not provide confidence intervals or statistical comparisons for the serious-event counts in the registry record used for this analysis. They should be read as the numbers recorded in the respective groups, not as precise estimates of comparative risk. The registry also lists several serious-event terms at 0.4% each, including coronary artery occlusion, appendicitis, anal cancer, anxiety, cardiac failure, and myocardial infarction. The listed terms do not by themselves establish causation or a vaccine relationship.

All adverse events were followed for up to 14 days, whereas serious adverse events were followed for up to 6 months. The different observation periods matter when interpreting the categories. The serious-event figures should not be merged with the overall adverse-event percentages, and the registry’s definition does not imply that every event was considered related to vaccination.

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

The results describe the proportion of participants with a recorded adverse event in each study group during the stated follow-up. The observed percentages were 75.1% with V114, 68.3% with PNEUMOVAX® 23, and 65.7% with PREVNAR 13®. The sponsor-reported comparisons indicate that the V114 percentage was higher than the comparator percentage in each contrast, with different levels of uncertainty across the two confidence intervals.

For the comparison with PNEUMOVAX® 23, the 95% confidence interval includes zero, so the data do not exclude no difference under that interval. For the comparison with PREVNAR 13®, the sponsor’s 95% confidence interval is above zero in the stated direction. Neither interval identifies the cause of the events, their importance to participants, or whether the observed contrast would persist in another population or setting.

The outcome counts participants with an adverse event, not the number of events per participant. The broad definition includes events whether or not they were considered related to the sponsor’s product, and worsening of a pre-existing condition is also included under the stated definition. The overall percentage therefore should not be equated with the percentage experiencing a vaccine-caused event. The registry’s serious-event counts are a separate safety description with a longer follow-up period.

The trial’s stated primary hypothesis concerns antibody concentrations and noninferiority, not the adverse-event percentage. The safety results cannot establish whether that immunogenicity hypothesis was met. The registry also lists an OPA antibody outcome, but these safety comparisons do not summarize that outcome. Results for the antibody analyses relevant to the stated hypotheses are not reported in the registry record in the registry record used for this analysis.

These findings apply to the study groups of healthy adults 50 years of age or older who received a single vaccination and had safety follow-up. The record does not support extrapolation to other populations, vaccination schedules, or follow-up periods. The percentages and intervals are evidence about the posted observations, with uncertainty; they are not medical advice or a treatment recommendation.

17. Why This Trial Matters Statistically

This study illustrates why a statistical comparison needs both an effect estimate and an uncertainty interval. The observed percentages alone show the event frequency in each group, but do not indicate how precisely the groups differ. The reported risk differences and confidence intervals make the contrast and its uncertainty more explicit. Their interpretation also depends on the direction in which the groups are subtracted, as demonstrated by the opposite signs in the sponsor results and the unadjusted recalculations.

The endpoint highlights a common distinction in clinical safety analysis: whether a participant experienced at least one event is not the same as how many events occurred, how severe they were, or whether they were judged related to the intervention. A single percentage can be useful for comparing the occurrence of events, but it cannot substitute for detailed event descriptions or for separately reported serious-event results.

The registry also makes clear that a trial can have more than one scientific question. Its stated primary hypothesis concerns antibody response, while the posted primary safety endpoint concerns adverse events. Statistical findings for one outcome should not be used as evidence that a different outcome met its hypothesis. Keeping these questions distinct is essential when interpreting a multi-outcome clinical trial.

Finally, planning illustrations based on observed effects are not the same as the original sample-size justification or the trial’s achieved ability to detect an effect. Separating planning assumptions from the study’s own design record helps prevent retrospective calculations from being mistaken for prespecified decisions. Together, these considerations show how endpoint definition, comparison direction, precision, and reporting completeness shape interpretation.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the trial’s original sample-size justification, detailed randomization procedures, allocation concealment, or which parties were masked under the triple-masking designation. A full statistical analysis plan, multiplicity strategy, missing-data procedures, and interim-analysis information are also not reported in the registry record. These omissions constrain evaluation of prespecification, potential bias, and the relationship among the trial’s multiple outcomes.

The posted primary safety outcome is a percentage of participants with an adverse event, but the reported comparison does not provide event severity, duration, recurrence, or causal attribution for each participant. The endpoint’s definition includes events whether or not considered related to the sponsor’s product. Serious-event counts are available, but the registry does not report inferential comparisons for those counts in the registry record used.

The safety analysis population includes vaccinated participants with safety follow-up. Further detail about participants who did not contribute follow-up, any exclusions, and the handling of missing outcomes is not reported in the registry record. Without those details, the potential influence of missingness cannot be assessed from the posted information.

The study is identified as Phase 2 and enrolled healthy adults 50 years of age or older, with a single vaccination and defined safety observation periods. The record does not establish that these results apply to different populations or regimens. The stated primary hypothesis concerns antibody concentrations, but the safety comparison alone does not address that hypothesis. No further immunogenicity result should be inferred from the adverse-event percentages.

The recalculated comparisons are unadjusted calculations from the posted summary statistics. They do not reproduce unreported protocol procedures or account for any analysis choices that are absent from the registry record. The sponsor’s reported Miettinen & Nurminen estimates and intervals should remain distinct from those recalculations.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: The Safety, Tolerability, and Immunogenicity Profiles of a Single Dose of V114, PNEUMOVAX® 23, or PREVNAR 13® in Adults 50 Years of Age or Older (V114-002) — NCT01513551.
• Registry record last updated 2018-12-13; status last verified 2018-11.
• Results first posted 2018-12-13.
• 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.

22. Record Summary

NCT01513551 is a completed, randomized, triple-masked, parallel-group Phase 2 study sponsored by Merck Sharp & Dohme LLC. It enrolled 692 healthy adults 50 years of age or older and compared a single dose of V114 with PNEUMOVAX® 23 and PREVNAR 13®.

The posted primary safety outcome is the percentage of participants with an adverse event. The reported percentages were 75.1% for V114, 68.3% for PNEUMOVAX® 23, and 65.7% for PREVNAR 13®. Sponsor-reported risk differences were 6.8 and 9.5, respectively, with 95% confidence intervals of -1.4 to 15.0 and 1.1 to 17.7.

The registry’s stated primary hypothesis concerns antibody concentrations and noninferiority. The safety findings address a separate outcome. Detailed multiplicity procedures, missing-data methods, and the original sample-size justification are not reported in the registry record.