A Study About Modified RNA Vaccines Against Influenza in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study About Modified RNA Vaccines Against Influenza in Healthy Adults (NCT06436703), a randomized phase 1, phase 2 study. The primary outcome is SSA: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination.

2. Clinical Question

The registry describes the broader purpose as evaluating safety, tolerability, and immune response for modified RNA influenza vaccines in healthy adults. The posted primary outcome is narrower: it counts participants reporting at least one local reaction, rather than measuring the severity or duration of each reaction. Local reactions were defined as pain at the injection site, redness, or swelling. The listed grading system ranges from Grade 1 (Mild) through Grade 4 (potentially life-threatening), but the primary outcome combines any grade into one percentage.

The primary result applies to Substudy A (SSA), not to all three substudy groups collectively. Substudy B and Substudy C are also described in the registry, with their own vaccine arms. The available primary outcome comparisons are for SSA vaccine groups against SSA: QIV 1. Numerical results for the listed antibody outcomes are not reported in the registry record. Consequently, the primary question addressed by the posted comparison is about short-term local reactions in SSA, not the full range of safety or immune-response questions in the study.

3. Trial Design

The registry identifies this as a randomized, quadruple-masked, parallel-group Phase 1 and Phase 2 study. The recorded enrollment is 1202, and the study status is completed. The registry lists a start date of 2024-05-23 and a primary completion date of 2025-02-05. Pfizer is named as sponsor.

The study is divided into three substudies: SSA, SSB, and SSC. Participants received one dose on Day 1, either of a modified RNA influenza vaccine under study or of an approved influenza vaccine for their age group. The listed intervention categories are Influenza ModRNA Vaccine and Quadrivalent Influenza Vaccine (QIV). Several vaccine groups appear within each substudy, with group labels distinguishing formulations and substudy assignment. The registry record does not report the details of how participants were assigned among those groups.

Randomization means that assignment to study groups is intended to use chance; masking means that specified groups involved in the study are kept unaware of assigned treatment. The registry labels masking as quadruple, but the identities of the masked parties are not reported in the registry record. A parallel design means participants are assigned to a group and followed in that group rather than crossing over between the interventions.

The enrollment figure is for the study record as a whole, whereas the primary outcome results are presented for SSA groups. The group-specific numbers analyzed for that outcome range from 94.0 to 97.0 in the listed arms. The registry’s brief description says eligible participants were generally healthy, at least 18 years old, and had not received an influenza vaccine within the last 6 months. Further eligibility details and the study’s original sample-size justification are not reported in the registry record.

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: Dose levels for nucleoside-modified ribonucleic acid (modRNA) vaccines are in numerical order from lowest to highest total modRNA dose, i.e., dose level 1 represents the lowest total modRNA dose and dose level 7 represents the highest total modRNA dose. Trivalent modRNA vaccines identified as formulation 3 encode for additional influenza strain-specific antigens.

Only the first 6 of 19 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who received the study intervention. Here "Overall Number of Participants Analyzed" signifies number of participants reporting at least 1 response (yes or no) in the e-diary or CRF after 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.

Population: Safety population included all participants who received the study intervention.

Only the first 6 of 20 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as SSA: Percentage of Participants With Local Reactions for up to 7 Days Following Vaccination, measured over From Day 1 through Day 7 after study vaccination [Vaccination on Day 1].

The primary endpoint is the percentage of participants with any local reaction during the period from Day 1 through Day 7 after study vaccination. The reactions counted were pain at the injection site, redness, and swelling. Participants recorded reactions in an electronic diary, or investigators recorded them in a case report form. The registry states that reactions were graded using CBER toxicity guidelines, but this endpoint combines all grades rather than reporting separate percentages by grade.

This is a binary participant-level outcome: each participant is classified according to whether at least one local reaction was reported during the defined period. The registry defines the analyzed safety population as participants who received the study intervention. For this outcome, the analyzed number means participants reporting at least one response, yes or no, in the diary or case report form after vaccination. That denominator definition matters because it is not simply a count of every participant initially assigned to a group.

In general, a percentage with an event offers a direct description of how often the recorded outcome occurred in each group over the stated observation period. It does not by itself describe the number of reactions per person, reaction duration, or severity. Those distinctions are important because a participant with multiple local reactions still contributes as a participant with an event for this endpoint. The registry lists other safety and immune-response outcomes, but this primary measure addresses only short-term local reactions.

7. Results Posted in the Registry

• SSA: Influenza ModRNA Vaccine 3A: 84.0% (79/94) versus 83.3% (80/96) on control; risk difference 0.7 percentage points (95% CI -9.8 to 11.2), risk ratio 1.01 (0.89–1.14); unadjusted two-proportion z-test p = 0.895.
• SSA: Influenza ModRNA Vaccine 4A: 80.2% (77/96) versus 83.3% (80/96) on control; risk difference -3.1 percentage points (95% CI -14.0 to 7.8), risk ratio 0.96 (0.84–1.10); unadjusted two-proportion z-test p = 0.575.
• SSA: Influenza ModRNA Vaccine 5A: 73.2% (71/97) versus 83.3% (80/96) on control; risk difference -10.1 percentage points (95% CI -21.7 to 1.4), risk ratio 0.88 (0.76–1.02); unadjusted two-proportion z-test p = 0.088.
• SSA: QIV 1: 42.6% (40/94) versus 83.3% (80/96) on control; risk difference -40.8 percentage points (95% CI -53.2 to -28.3), risk ratio 0.51 (0.40–0.66); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a percentage of participants with an event. In general, a binary outcome records whether each participant experienced the defined event or did not. For this study, the event is at least one reported local reaction of any grade in the specified post-vaccination period. The registry’s denominator description requires at least one yes-or-no response in the electronic diary or case report form. A percentage based on that denominator summarizes reported participant-level occurrence; it does not count the total number of individual reactions.

The arm-level results include a percentage and a 95% confidence interval. In general, a confidence interval gives a range of values reasonably compatible with the data and the method used to calculate it. It is not a range containing 95% of participant outcomes, and it does not mean there is a 95% probability that the true value lies within the particular calculated interval. Wider intervals indicate less precision than narrower intervals, all else being equal. The intervals for the five SSA groups are reported alongside their percentages so readers can assess uncertainty as well as the observed values.

The pairwise comparisons report risk differences, confidence intervals, and unadjusted p-values. In general, a risk difference expresses the difference between two event proportions on the proportion scale. A value of zero represents no difference on that scale; an interval that includes zero is compatible with no difference as well as values in either direction. The reported estimates and limits are retained on the scale used in the registry calculations, rather than converted into another unit. The reference for the listed comparisons is SSA: Influenza ModRNA Vaccine 2A.

The comparison p-values are explicitly unadjusted. In general, an unadjusted p-value evaluates one comparison without accounting for the fact that several comparisons may be examined. When many comparisons are made, the chance of at least one result appearing statistically unusual can increase. Whether this occurred as a concern in the study, and whether an adjustment or prespecified testing hierarchy was used, is not reported in the registry record. The posted p-values should not be treated as multiplicity-adjusted evidence.

The study is recorded as randomized and parallel-group. In general, random allocation can help balance measured and unmeasured participant characteristics across groups, while masking can reduce the influence of expectations on care or outcome assessment. These are design features, not guarantees that all sources of bias are removed. The registry identifies quadruple masking but does not specify the masked parties, and the detailed assignment process is not reported in the registry record. The recorded primary outcome uses diary or investigator reporting, so completeness and consistency of outcome recording are relevant considerations.

The registry reports a safety population consisting of participants who received the study intervention. For the primary outcome, the analyzed number specifically reflects participants with at least one response after vaccination. In general, analysis populations and missing outcome handling can affect interpretation because participants without recorded responses may not contribute in the same way as participants with complete records. The registry record does not report the method for handling missing primary outcome data or whether any alternative analysis population was used.

Eight secondary outcomes are listed, covering strain-specific hemagglutination inhibition (HAI) antibody titers at baseline and 4 weeks after vaccination, geometric mean fold rise, seroconversion, and the percentage with HAI titers at least 1:40 for SSA and SSB. These describe immune-response measures distinct from local reactions. Their numerical results are not reported in the registry record. The record lists 26 outcome measures and 0 analyses, but does not explain the meaning of the analysis count or provide a statistical analysis plan. Details such as model specifications, covariate adjustment, treatment of repeated measurements, and the trial’s original design assumptions are not reported in the registry record.

General note on over-dispersion: for count outcomes, over-dispersion occurs when observed variation exceeds what a simple model assumes. It can lead to overly narrow intervals or small p-values if ignored. The primary endpoint is a participant-level binary percentage, not a count rate, and the registry record does not report an over-dispersion assessment or a model-based analysis for this outcome.

10. Confidence Intervals and Precision

The primary arm estimates have 95% confidence intervals that show meaningful uncertainty around each reported percentage. For vaccine 2A, the interval is 74.4 to 90.2 around 83.3%. For vaccine 3A, it is 75.0 to 90.8 around 84.0%; for vaccine 4A, 70.8 to 87.6 around 80.2%; for vaccine 5A, 63.2 to 81.7 around 73.2%; and for QIV 1, 32.4 to 53.2 around 42.6%. These intervals give context for interpreting the differences between the group percentages.

For the three modified RNA comparisons against vaccine 2A, the risk-difference intervals include zero: -0.098 to 0.112 for vaccine 3A, -0.140 to 0.078 for vaccine 4A, and -0.217 to 0.014 for vaccine 5A. The QIV 1 comparison interval, -0.532 to -0.283, lies below zero. In general, this pattern means the posted estimates differ in precision and in how their intervals relate to the no-difference value. An interval excluding zero is not, by itself, a complete assessment of clinical importance or study-wide evidence, particularly when multiple comparisons are reported.

The group analyzed sizes for this endpoint are 96.0, 94.0, 96.0, 97.0, and 94.0 across the five listed arms. Group size and the observed event proportion both affect precision; intervals can remain broad even when a percentage is based on many participants, especially when the estimate is uncertain. No formal target precision or acceptable interval width is reported in the registry record. The intervals describe uncertainty under their calculation method and do not account for unreported sources of bias, missing data, or multiplicity.

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 are based on the observed effect, not the trial’s original design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses an effect equal to the stated fraction of the observed effect. For these binary comparisons, the displayed planning figures are participants per arm, not total events. The separate sample-size convention for time-to-event outcomes does not apply to this primary endpoint.

The 80% power column means the planned number of participants per arm under the stated assumptions for an 80% chance of detecting the modeled effect if that effect is real. The 90% power column uses the same idea but targets a 90% chance. These are planning quantities: they describe the sample size a hypothetical study would need under assumptions, not a result measured in the completed trial. This is not observed power.

Each comparison has its own observed estimate and therefore its own planning illustration. For example, planning for 75% of the observed effect in the comparison of vaccine 5A with vaccine 2A gives 441 participants per arm for 80% power and 590 participants per arm for 90% power. Planning for 50% of that observed effect gives 947 and 1,267 participants per arm, respectively. Smaller effects are harder to distinguish from random variation, so the planning calculations require more participants per arm as the effect to detect becomes smaller.

These figures should not be interpreted as the study’s actual enrollment target or as proof that the study was adequately or inadequately powered. The original sample-size justification, the trial’s own power assumptions, and whether its design accounted for multiple comparisons are not reported in the registry record. Because the calculations are tied to observed effects, they are also sensitive to how precisely those effects were estimated in the trial.

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 = 0.833; treatment proportion p₁ = 0.840; average p̄ = 0.837.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5225 = 1.0241.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5225 = 0.4397.
4. n = (1.0241 + 0.4397)² / (0.0071)² = 42,602.5, rounded up to 42,603 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 <- 0.833333333333333                          # control proportion
p1 <- 0.840425531914894                          # 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(6436703)
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 = 42,603 (80% power), 57,033 (90% power)
 75% of observed effect: n per arm = 76,070 (80% power), 101,836 (90% power)
 50% of observed effect: n per arm = 171,902 (80% power), 230,127 (90% power)
power.prop.test: 42602.5 
Simulated power at n = 42,603 per arm: 0.804 (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 registry lists 26 outcome measures and reports 0 analyses in the record. Eight secondary outcomes are specified for SSA and SSB. They concern HAI geometric mean titers at baseline and 4 weeks after vaccination, geometric mean fold rise from before vaccination to 4 weeks after vaccination, seroconversion at 4 weeks, and the percentage with HAI titers at least 1:40 at baseline and 4 weeks. Numerical results for these secondary outcomes are not reported in the registry record.

Four pairwise comparisons are posted for the primary SSA local-reaction outcome, each comparing a vaccine group with vaccine 2A. The p-values are described as unadjusted. In general, testing several hypotheses increases the chance that at least one result will appear statistically significant by chance if all null hypotheses are true. A multiplicity strategy might address that issue through adjusted thresholds, an ordered testing plan, or a distinction between confirmatory and exploratory outcomes. The planned strategy, if any, is not reported in the registry record. The p-values should therefore be interpreted as unadjusted comparisons, not as evidence that a family of tests was controlled at a specified overall error rate.

The primary outcome population is described as participants who received study intervention, with the analyzed number defined as those reporting at least one yes-or-no response after vaccination. The registry does not report how participants with no response were handled, whether missingness differed by group, or whether sensitivity analyses were conducted. It also does not report an intention-to-treat analysis for this outcome or any other analysis-population definitions beyond the stated safety population.

The detail needed to evaluate the full analysis process—including a statistical analysis plan, prespecified hypotheses, model specifications, and the relationship between listed outcomes and reported analyses—is not reported in the registry record. In general, absence of these details limits assessment of whether the posted analyses followed prespecified procedures. It does not establish that such procedures were absent; it means their content cannot be assessed from this record.

14. 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: pelvic fracture (3.3%), hypoglycaemia (3.3%), deep vein thrombosis (3.3%), hip fracture (3.2%), gastrointestinal ulcer haemorrhage (1.1%).

The serious adverse event entries report, by group, the number at risk and the number affected. For example, the registry lists 2 serious adverse events among 96 participants at risk in SSA: Influenza ModRNA Vaccine 2A, and 0 among 96 at risk in vaccine 3A and 0 among 96 at risk in vaccine 4A. In SSB, it lists 4 among 87 at risk in vaccine 4B and 4 among 90 at risk in vaccine 5B. These are group-specific counts; they should not be added together to create a study-wide count because the record does not establish whether participants or events overlap across entries.

The registry reports 0 deaths in each listed group. It also names serious-event terms with percentages, including Pelvic fracture and Hypoglycaemia at 3.3%, Deep vein thrombosis at 3.3%, Hip fracture at 3.2%, and Gastrointestinal ulcer haemorrhage and Hiatus hernia at 1.1%. The record does not connect these terms to specific study arms in the listed information, so they should not be assigned to a particular vaccine group. Serious adverse event counts are distinct from the primary local-reaction outcome and do not, alone, establish a causal relationship with vaccination.

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

The posted primary results describe how often participants in each SSA group reported at least one local reaction during the 7 days after vaccination. The percentages were higher in the four modified RNA groups than in QIV 1, while the comparisons among the modified RNA groups and vaccine 2A had confidence intervals that included zero. The QIV 1 comparison with vaccine 2A had a risk-difference interval below zero and an unadjusted p-value of <0.001. These observations apply to the recorded local-reaction endpoint, the stated groups, and the specified follow-up period.

They do not establish the overall safety profile of any vaccine, because one primary endpoint does not capture every type, severity, duration, or timing of adverse event. The primary outcome combines reactions of any grade, and the registry also reports separate serious adverse event counts. Those are different safety summaries and should not be merged into one conclusion. A zero count for deaths in the listed groups is a description of this record, not a guarantee about risk outside the observed study.

The registry describes the broader goal of assessing immune response, but numerical results for the listed HAI outcomes are not reported in the registry record. The local-reaction outcome therefore cannot answer whether the vaccines produced a particular immune response. Nor does this endpoint measure prevention of influenza illness. The listed study conditions include human influenza, but no clinical influenza outcome result is reported in the registry record for this analysis.

In general, statistical significance and clinical importance are different questions. A p-value describes compatibility with a statistical model, while an estimate and its interval show the direction and uncertainty of an observed difference. The record does not report a threshold for a clinically important difference. The comparisons should not be treated as medical advice or as a complete basis for decisions about vaccination.

16. Why This Trial Matters Statistically

This trial illustrates why an outcome’s definition and denominator matter. The primary measure is the percentage of participants with any local reaction, not the total number of reactions, a severity score, or the percentage with a serious adverse event. The observation window is limited to Day 1 through Day 7. Those choices determine what the result describes and what remains outside its scope.

The registry reports several vaccine groups across three substudies, while the primary numerical results and comparisons concern SSA. This makes it important to distinguish an outcome-specific comparison from a study-wide conclusion. It also shows why the reference group must be identified: the listed pairwise estimates compare each specified group with vaccine 2A, rather than comparing every possible pair.

Precision and multiplicity are also central. The arm-level percentages have confidence intervals, and the pairwise results include unadjusted p-values. A reader can see which comparison intervals include zero, but cannot infer from the record whether the broader set of outcomes and comparisons was managed through a prespecified multiplicity strategy. This distinction is useful in clinical research, where a collection of outcomes may answer different questions and not all analyses carry the same evidentiary role.

Finally, the registry lists immunogenicity outcomes alongside safety outcomes, but does not report numerical results for those secondary measures. Keeping those aims separate prevents short-term reactogenicity findings from being mistaken for immune-response findings. The study is therefore a useful example of reading results at the level of the endpoint actually reported, while recognizing which design and analysis details are available and which are not reported in the registry record.

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

The primary numerical results posted by the registry record are limited to Substudy A. Although the study includes SSA, SSB, and SSC, the primary endpoint comparisons do not provide corresponding local-reaction percentages for all three substudies. Comparisons across different vaccine labels or substudies cannot be reconstructed from these primary results.

The outcome counts any local reaction of any grade during a 7-day period. It does not give separate results for pain, redness, swelling, individual severity grades, or reactions occurring outside that window. Results may also depend on diary completion and investigator recording. The registry defines the analyzed denominator as those with a yes-or-no response but does not report the number without a recorded response or the method used to handle missing data.

Numerical results for the eight listed HAI secondary outcomes are not reported in the registry record, so the immune-response part of the study’s stated purpose cannot be assessed from these results. The serious adverse event entries provide group counts, but the listed serious-event terms are not linked to particular groups in the available information. The record also does not report the masked parties, detailed allocation method, statistical analysis plan, original sample-size justification, or multiplicity procedure.

The unadjusted comparisons should be interpreted in light of those reporting gaps and the presence of several groups and outcomes. The record does not report a clinical importance threshold for local reactions. These limitations restrict the conclusions that can be drawn from the registry results; they do not establish that omitted procedures or analyses were not conducted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study About Modified RNA Vaccines Against Influenza in Healthy Adults — NCT06436703.
• Registry record last updated 2026-06-12; status last verified 2026-06.
• Results first posted 2026-06-12.
• 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 completed randomized, quadruple-masked, parallel-group Phase 1 and Phase 2 study, sponsored by Pfizer, evaluated modified RNA influenza vaccines in healthy adults. The study record lists enrollment of 1202 and describes three substudies, with a single injection on Day 1 in each group.

The primary posted outcome is the percentage of participants in SSA reporting any local reaction through Day 7. The reported percentages range across the listed arms from 42.6% in QIV 1 to 84.0% in vaccine 3A. Comparisons against vaccine 2A include unadjusted p-values and confidence intervals; the QIV 1 comparison interval excludes zero, while the three other comparison intervals include zero.

Serious adverse events and deaths are reported by group, and the registry lists immune-response outcomes. Numerical results for those secondary outcomes, the multiplicity strategy, missing-data handling, and the original sample-size rationale are not reported in the registry record.