Safety, Tolerability, and Immunogenicity of a Single Dose of Merck 0657nI Staphylococcus Aureus Vaccine With or Without Merck Aluminum Adjuvant (V710-002): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, and Immunogenicity of a Single Dose of Merck 0657nI Staphylococcus Aureus Vaccine With or Without Merck Aluminum Adjuvant (V710-002) (NCT01324440), a randomized phase 1 study. The primary outcome is Number of Participants With a Positive Immune Response, Defined as a Change in Antibody Level Greater Than or Equal to a 2-fold-rise at Day 14 Compared to Baseline.

2. Clinical Question

3. Trial Design

This was a phase 1, randomized, double-blind, parallel-group study of a single dose of Merck 0657nI Staphylococcus Aureus vaccine, also called V710. Participants received V710 with Merck Aluminum Adjuvant or V710 without the adjuvant. The official study title describes the study as multicenter, and the registry lists healthy adults 18 to 70 years of age as the population.

The registry reports enrollment of 64 participants. The primary outcome results list 32 participants in each group. The study began in 2006-09, had primary completion in 2007-10, and is marked completed. The sponsor listed in the record is Merck Sharp & Dohme LLC.

The study was designed to evaluate safety, tolerability, and immunogenicity. Its posted primary endpoint concerns the proportion of participants meeting a specified antibody-rise definition at Day 14 compared with baseline. The comparison is between the two vaccine formulations, not between vaccination and no vaccination. No placebo group is listed in the interventions.

The registry does not report the original sample-size justification, the intended power for the trial, or detailed randomization procedures. It also does not report the number of study sites, the method used to maintain masking, or whether any interim analyses were planned. Those details should not be inferred from the phase, study title, or observed group sizes.

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 per-protocol analysis excluded patients who had missing baseline and/or postvaccination (Day 14) serology data and patients who developed a S. aureus infection during the 14 days postvaccination.

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 Number of Participants With a Positive Immune Response, Defined as a Change in Antibody Level Greater Than or Equal to a 2-fold-rise at Day 14 Compared to Baseline, measured over Baseline and Day 14 postvaccination.

The primary endpoint counts participants whose IgG antibody level at Day 14 was at least 2-fold higher than the baseline level. Antibodies were measured using a LUMINEX(TM) assay. The timeframe is baseline and Day 14 postvaccination. The endpoint turns a measured antibody change into a binary outcome: each participant either met the stated response definition or did not.

A binary endpoint can be useful for presenting how frequently participants cross a prespecified response threshold. It makes the outcome easy to express as participant counts and permits a direct comparison of response frequencies between groups. The result remains dependent on the specific threshold and measurement method used; it does not describe the size of each participant’s antibody change beyond whether it reached the threshold.

The registry defines the primary analysis population as per protocol. It excludes participants with missing baseline or postvaccination Day 14 serology data and participants who developed a S. aureus infection during the 14 days after vaccination. The registry does not report the number of exclusions or further details about handling missing measurements. The endpoint is an immunogenicity measure, not a clinical endpoint such as occurrence of infection.

7. Results Posted in the Registry

• V710 Without MAA: 71.9% (23/32) versus 84.4% (27/32) on control; risk difference -12.5 percentage points (95% CI -32.5 to 7.5), risk ratio 0.85 (0.65–1.11); unadjusted two-proportion z-test p = 0.226.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: a participant either had a positive immune response by the registry definition or did not. The response definition is an antibody level at Day 14 that is at least 2-fold higher than baseline. For this kind of endpoint, a natural first summary is the number meeting the definition in each group, alongside the number assessed. The registry lists 27 of 32 participants for V710 with MAA and 23 of 32 for V710 without MAA.

What the risk difference describes

The risk difference subtracts the response frequency in the comparison group from the response frequency in the reference group, according to the direction specified for the contrast. In the posted comparison, the contrast is V710 without MAA relative to V710 with MAA, and the estimated risk difference is -0.125. This is an absolute-scale estimate. It conveys how far apart the response frequencies are on the probability scale, rather than expressing the difference as a ratio.

A risk difference near zero would indicate similar observed response frequencies. A negative value in this contrast indicates a lower observed response frequency in the group without MAA. The estimate is not a guarantee that the same difference would be observed in another study. Sampling variability means that the underlying group difference could plausibly be different from the point estimate.

What the confidence interval adds

A confidence interval describes uncertainty around an estimate under the statistical method used. In repeated studies, intervals constructed by the same procedure would capture the underlying parameter at the stated confidence level at the corresponding long-run frequency, assuming the model and sampling conditions are appropriate. It is not a range containing a known proportion of individual participant outcomes, nor is it a probability statement about the fixed parameter after observing one interval.

For the risk difference, the posted 95% confidence interval is -0.325 to 0.075. Because it includes zero, the data do not rule out no difference on the risk-difference scale at the corresponding conventional two-sided testing threshold. It also spans differences in either direction. That breadth signals that the point estimate should not be read as precise evidence of a particular underlying effect.

Relative measures

The risk ratio compares the response frequencies as a ratio, while the odds ratio compares the odds of response. Their posted estimates are 0.852 and 0.473, respectively. The corresponding 95% confidence intervals are 0.655 to 1.108 for the risk ratio and 0.139 to 1.614 for the odds ratio. For both measures, the null value is 1; the intervals include that value. The odds ratio and risk ratio are not interchangeable, and the odds ratio can be farther from 1 than the risk ratio. Relative measures should be interpreted alongside the absolute response counts and risk difference.

What the p-value says

The unadjusted p-value is 0.226. General statistical interpretation: a p-value measures how incompatible the observed data, or data more extreme under the test, are with a specified null model. It is not a measure of the probability that the result occurred by chance, and it does not quantify the probability that one formulation is better. The registry does not report a detailed test specification or adjusted analysis. The posted p-value should therefore be read as an unadjusted comparison, not as evidence that uncertainty has been eliminated.

Why over-dispersion matters in other settings

General statistical context: over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors too small and intervals too narrow if the model does not account for the extra variability. The primary outcome is a binary participant count, and the registry does not report an over-dispersion assessment or a model-based adjustment. There is no basis in the registry record to claim that over-dispersion was evaluated for this comparison.

Analysis population and limitations of the summaries

The primary endpoint is described for a per-protocol population. Participants with missing baseline or Day 14 serology data, and those who developed a S. aureus infection during the 14 days after vaccination, were excluded from that population. The registry does not report how many participants were excluded, whether other protocol deviations were considered, or how missing values were handled beyond the stated exclusions. The published group counts alone cannot resolve these questions.

The registry reports zero analyses and does not provide details of the statistical methods used by the sponsor. The available comparison statistics can be interpreted as posted estimates, but the record does not establish the complete analysis plan, covariate adjustment, or any sensitivity analyses. In particular, no adjustment for multiple comparisons is reported. The study’s original design assumptions, including its planned power and sample-size rationale, are also not reported. These gaps limit how much can be inferred about the prespecification and robustness of the analysis.

10. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate. The risk difference for V710 without MAA compared with V710 with MAA is -0.125, and its 95% confidence interval runs from -0.325 to 0.075. This interval is wide enough to include no difference and differences in either direction. The data therefore do not pin down a single value with high precision.

The relative measures tell a similar uncertainty story. The risk ratio is 0.852, with a 95% confidence interval from 0.655 to 1.108. The odds ratio is 0.473, with a 95% confidence interval from 0.139 to 1.614. Each interval contains its respective null value, so the results are compatible with no relative difference as well as with effects in either direction on that scale.

Confidence intervals are not limits on the possible results of future studies. They express uncertainty about the estimated contrast under the method used and its assumptions. In a small study, a modest number of participants can materially affect the observed response counts, and the estimated difference may be sensitive to such variation. The registry lists 32 participants in each outcome group, which is important context for interpreting the interval width.

Precision is also distinct from whether a result is statistically significant. The p-value is 0.226, but the interval conveys more detail about the range of contrasts reasonably compatible with the data. Neither measure addresses whether an antibody response threshold corresponds to a clinically important outcome. That relationship is not reported in the registry record.

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 estimates are expressed as participants per arm, not as total events. They are illustrations based on the observed effect, rather than the original sample-size plan for this trial. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

The 80% power column gives the estimated participants per arm for a design that would have an 80% probability of detecting the specified effect under those assumptions, if that effect were the true one and the statistical model were appropriate. The 90% power column gives the corresponding participants per arm for a design with a 90% probability under the same general conditions. Power is a planning property for a hypothetical study design, not a description of the certainty in the observed result.

The planning rows consider 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The listed requirements rise as the assumed effect becomes smaller: for example, planning for 75% of the observed effect requires more participants per arm than planning for 100% of the observed effect, and planning for 50% requires more still. This is expected because smaller differences are harder to distinguish from random variation.

These figures are not observed power. They should not be used to claim that the completed trial had a particular probability of detecting an effect, nor do they explain the trial’s original design. The registry does not report the original sample-size justification or the assumptions used when the trial was planned.

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 = 0.844; treatment proportion p₁ = 0.719; average p̄ = 0.781.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5846 = 1.1459.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5779 = 0.4864.
4. n = (1.1459 + 0.4864)² / (-0.1250)² = 170.5, rounded up to 171 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 <- 0.84375                          # control proportion
p1 <- 0.71875                          # 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(1324440)
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 = 171 (80% power), 228 (90% power)
 75% of observed effect: n per arm = 288 (80% power), 385 (90% power)
 50% of observed effect: n per arm = 612 (80% power), 818 (90% power)
power.prop.test: 170.5 
Simulated power at n = 171 per arm: 0.801 (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. Multiplicity, Missing Data and Analysis Populations

The primary outcome is identified as the number of participants with a positive immune response at Day 14 by the stated antibody-rise definition. The registry lists four outcome measures, but it reports no secondary outcome results. It also lists zero analyses. The record does not provide a complete statistical analysis plan or describe which outcomes were designated primary or secondary beyond the posted primary endpoint.

Multiplicity arises when several outcomes, time points, groups, or statistical tests are examined. As the number of analyses grows, the chance of obtaining at least one apparently notable result by random variation can increase. Statistical plans sometimes address this through a prespecified hierarchy or adjustments to inference. The registry does not report whether multiplicity was considered, whether any adjustment was applied, or whether analyses beyond the posted comparison were performed. No such procedures should be assumed.

The primary outcome is described for a per-protocol population. The registry says this population excluded participants with missing baseline or Day 14 serology and those who developed a S. aureus infection during the 14 days after vaccination. It does not report the number excluded for either reason, the number assessed for each outcome, or the handling of missing data beyond these stated exclusions. The group counts listed for the outcome are 32 in each arm, but the record does not provide a participant flow that would explain the relation between enrollment, exclusions, and analysis populations.

The registry also does not report an intention-to-treat analysis, sensitivity analyses for missing measurements, or an analysis population for safety results beyond the group counts. These omissions limit assessment of how sensitive the results may be to population definitions and missing data. They do not establish that such analyses were not conducted; those details are simply not reported in the registry record.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 32 participants at risk for serious adverse events in each group and zero participants with a serious adverse event in each group. It does not list any serious adverse event terms. These are the posted serious-event counts; they do not provide detail about event timing, severity grading, or follow-up duration.

For other adverse events, the registry lists 21 affected participants among 32 at risk in the V710 with MAA group and 17 affected participants among 32 at risk in the V710 without MAA group. The record does not provide specific event terms in these results, so the counts cannot show which events occurred or their severity. Death counts are not reported in the record.

Zero observed serious adverse events in these groups does not establish that serious events cannot occur. A study with a limited number of participants may not characterize uncommon events reliably. The adverse-event results should be read as counts during the study’s recorded observation, not as a complete account of safety in other populations or longer-term use.

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

The primary result describes short-term IgG antibody responses after a single dose of V710 with or without MAA. The registry reports 27 positive responses among 32 participants in the with-MAA group and 23 among 32 in the without-MAA group. The estimated risk difference for without MAA relative to with MAA is -0.125, with a 95% confidence interval from -0.325 to 0.075. The interval includes no difference and values in either direction, so the result is uncertain about the underlying contrast.

The endpoint is an immunogenicity measure defined by a threshold in antibody change from baseline to Day 14. It does not measure whether participants developed an infection after the endpoint timeframe, and the registry does not report a clinical efficacy outcome. It therefore cannot establish whether either formulation prevents Staphylococcus aureus infection or changes the course of disease.

The posted safety counts show zero participants with serious adverse events in either group, alongside other adverse events in 21 of 32 participants with MAA and 17 of 32 participants without MAA. The record does not provide event terms for the other adverse events, and it does not report death counts. These data describe the events recorded in this study; they cannot rule out uncommon or later events.

The trial was a phase 1 study with 64 participants enrolled. Its limited size and short-term primary endpoint restrict the conclusions that can be drawn from the comparison. The registry does not report the original sample-size rationale, a full statistical analysis plan, or secondary outcome results. Accordingly, the evidence is best understood as a small study’s observed antibody-response and adverse-event counts, not as a definitive comparison of clinical outcomes.

16. Why This Trial Matters Statistically

This trial illustrates the distinction between an immunogenicity endpoint and a clinical outcome. A threshold-based antibody response is a measurable laboratory result, but it does not automatically establish protection against infection. Statistical interpretation must stay tied to the endpoint that was actually recorded: positive IgG response at Day 14 relative to baseline.

It also shows why absolute counts and uncertainty should be considered together. The response counts are 27 of 32 with MAA and 23 of 32 without MAA, while the risk-difference interval extends from -0.325 to 0.075. The point estimate gives one concise comparison, but the interval indicates that the underlying difference is not precisely determined. A result that appears numerically different between groups is not necessarily strong evidence of a stable difference.

The study is also a reminder that phase 1 findings and later clinical claims answer different questions. This study’s stated aims include safety, tolerability, and immunogenicity, and the primary result concerns antibody response. The registry does not report an infection-prevention outcome or secondary results. A reader should not treat an antibody response as a substitute for a clinical endpoint without evidence connecting the two.

Finally, analysis transparency affects interpretation. The registry gives a per-protocol population definition, but not the number excluded, the original sample-size justification, or a detailed statistical plan. Those omissions make it harder to evaluate prespecification and assess how participant exclusions might affect the result. Recognizing what is and is not documented is part of sound statistical reading.

17. 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 study enrolled 64 participants, with 32 listed in each primary outcome group. This is a limited basis for estimating response differences, and the confidence interval around the risk difference is broad, extending from -0.325 to 0.075. The result does not precisely identify the underlying difference between the formulations.

The endpoint is specific to antibody response at Day 14 and uses a threshold of at least a 2-fold rise from baseline. The registry does not report longer-term antibody measurements or clinical infection outcomes. The trial therefore cannot address durability of the measured response or establish whether it corresponds to a clinical benefit.

The primary analysis population excludes participants with missing serology data and those who developed a S. aureus infection during the 14 days after vaccination. The number of participants excluded for these reasons is not reported in the registry record. Without a participant flow or additional analyses, it is not possible to assess how exclusions may have influenced the observed comparison.

The registry does not report the original sample-size justification, detailed analysis methods, multiplicity procedures, or secondary outcome results. It also does not report specific terms for the other adverse events or death counts. These limitations restrict interpretation of the study’s design rationale, robustness, and safety detail. They should be treated as gaps in what is documented, rather than evidence that additional procedures or information did not exist.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Safety, Tolerability, and Immunogenicity of a Single Dose of Merck 0657nI Staphylococcus Aureus Vaccine With or Without Merck Aluminum Adjuvant (V710-002) — NCT01324440.
• Registry record last updated 2015-04-10; status last verified 2015-03.
• Results first posted 2011-10-17.
• 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.

21. Record Summary

The registry record describes NCT01324440, a completed randomized, double-blind, parallel-group phase 1 study of a single 30 µg dose of V710 with or without Merck Aluminum Adjuvant. It lists 64 participants enrolled and healthy adults 18 to 70 years of age as the population.

The primary endpoint was the number of participants with at least a 2-fold rise in IgG antibody level at Day 14 compared with baseline. The posted counts were 27 of 32 with MAA and 23 of 32 without MAA. The risk difference for without MAA relative to with MAA was -0.125, with a 95% confidence interval from -0.325 to 0.075 and an unadjusted p-value of 0.226.

The record also reports zero participants with serious adverse events in each group and other adverse events in 21 of 32 participants with MAA and 17 of 32 without MAA. Secondary outcome results and further adverse-event details are not reported.