A Study to Evaluate Different Dose Levels of Ad26.COV2.S in Healthy Adolescents From 12 to 17 Years Inclusive: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Different Dose Levels of Ad26.COV2.S in Healthy Adolescents From 12 to 17 Years Inclusive (NCT05007080), a randomized phase 2 study. The primary outcome is Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Solicited Local Adverse Events (AEs) at 7 Days Post-dose 1.

2. Clinical Question

The registry describes a randomized, observer-blind study intended to assess safety, reactogenicity, and humoral immune response. Its primary outcome is a count of participants reporting any of the specified local events in the 7 days after the first vaccination. It is not an assessment of the number, duration, or severity of individual events.

For the primary endpoint, the one-dose groups had 13.0, 16.0, and 17.0 participants with an event, while the two-dose groups had 11.0, 12.0, and 15.0. The corresponding analyzed group sizes ranged from 49.0 to 51.0. Those observed counts address the stated safety question; they do not establish whether one dose level or schedule is preferable. The registry record does not report a primary immunogenicity result in the information summarized for this outcome.

3. Trial Design

This was a randomized, observer-blind, phase 2, parallel-group study of Ad26.COV2.S in healthy adolescents aged 12 to 17 years inclusive. The registry lists double masking. Enrollment was 304, and the study status is completed. The study began on 2021-09-27, with primary completion on 2023-08-14.

Six groups covered three dose levels and two primary schedules. Groups 1, 2, and 3 received one dose on Day 1, followed by placebo on Day 57. Groups 4, 5, and 6 received two doses on Day 1 and Day 57. Participants in the one-dose groups were scheduled to receive a booster at dose level 1 on Day 184. The registry says participants in all groups were to be unblinded to the primary vaccination regimen 6 months after the first vaccination.

The registry’s primary outcome concerns solicited local adverse events in the 7 days after dose 1. Its safety analysis set included participants with at least one vaccine administration documented. The posted group counts for this outcome range from 49.0 to 51.0. The primary endpoint comparison figures use Group 1, the 2.5*10^10 vp one-dose group, as the reference.

The study’s stated purpose also included safety, reactogenicity, and humoral immune response. Secondary outcomes cover binding and neutralizing antibody titers, as well as adverse events after the scheduled booster in the one-dose groups. The registry record does not report the original design’s statistical assumptions, its sample-size justification, or a detailed statistical analysis plan. Those details cannot be inferred from the planning illustrations calculated from the posted results.

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: Of the 304 randomized participants, 3 participants were randomized to an arm that was closed prior to vaccination due to ethical reasons. One participant was excluded from the analysis due to lack of a valid informed consent form and is not presented in the below table.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analyses set included all participants with at least one vaccine administration documented.

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: Baseline analysis population included all participants with at least one vaccine administration documented.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Groups 1, 2, 3, 4, 5 and 6: Number of Participants With Solicited Local Adverse Events (AEs) at 7 Days Post-dose 1, measured over 7 days post-dose 1 on Day 1 (Day 8).

The primary endpoint is the number of participants with at least one solicited local adverse event during the 7 days after dose 1, given on Day 1. The registry defines these events as injection-site pain or tenderness, erythema, and swelling at the vaccination site. Participants were specifically asked about these pre-defined events and recorded them in a reactogenicity diary.

This endpoint is used to describe short-term local reactogenicity following vaccination. Counting participants with an event gives a straightforward summary of how many people reported at least one of the listed reactions in each group. It does not indicate how many separate events each participant experienced, how long an event lasted, or how severe it was. Those details are not reported for this primary outcome.

The outcome is based on the safety analysis set, which included participants with at least one documented vaccine administration. The registry reports 13.0 participants with an event in Group 1, 16.0 in Group 2, 17.0 in Group 3, 11.0 in Group 4, 12.0 in Group 5, and 15.0 in Group 6. The group denominators range from 49.0 to 51.0. These are observed counts over the specified period. They do not themselves show whether between-group differences are precise or compatible with no difference; that requires looking at the comparison estimates and their confidence intervals.

The outcome concerns events after the first dose only. It should not be read as a combined result for both primary doses or as a result after the later booster. The registry lists separate post-booster outcomes for the one-dose groups.

7. Results Posted in the Registry

• Group 2: Ad26.COV2.S 1.25*10^10 vp + Placebo: 32.0% (16/50) versus 25.5% (13/51) on control; risk difference 6.5 percentage points (95% CI -11.1 to 24.1), risk ratio 1.26 (0.68–2.33); unadjusted two-proportion z-test p = 0.470.
• Group 3: Ad26.COV2.S 0.625*10^10 vp + Placebo: 33.3% (17/51) versus 25.5% (13/51) on control; risk difference 7.8 percentage points (95% CI -9.8 to 25.5), risk ratio 1.31 (0.71–2.40); unadjusted two-proportion z-test p = 0.385.
• Group 4: Ad26.COV2.S 2.5*10^10 vp + Ad26.COV2.S 2.5*10^10 vp: 22.4% (11/49) versus 25.5% (13/51) on control; risk difference -3.0 percentage points (95% CI -19.8 to 13.7), risk ratio 0.88 (0.44–1.77); unadjusted two-proportion z-test p = 0.722.
• Group 5: Ad26.COV2.S 1.25*10^10 vp + Ad26.COV2.S 1.25*10^10 vp: 24.5% (12/49) versus 25.5% (13/51) on control; risk difference -1.0 percentage points (95% CI -18.0 to 16.0), risk ratio 0.96 (0.49–1.90); unadjusted two-proportion z-test p = 0.908.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Groups 1, 2 and 3: Number of Participants With Solicited Local AEs for 7 Days Post-booster Vaccination

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Group 2: Ad26.COV2.S 1.25*10^10 vp + Placebo: 33.3% (16/48) versus 37.3% (19/51) on control; risk difference -3.9 percentage points (95% CI -22.7 to 14.9), risk ratio 0.89 (0.52–1.53); unadjusted two-proportion z-test p = 0.683.
  • Group 3: Ad26.COV2.S 0.625*10^10 vp + Placebo: 34.7% (17/49) versus 37.3% (19/51) on control; risk difference -2.6 percentage points (95% CI -21.4 to 16.2), risk ratio 0.93 (0.55–1.57); unadjusted two-proportion z-test p = 0.790.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2: Ad26.COV2.S 1.25*10^10 vp + Placebo and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 3: Ad26.COV2.S 0.625*10^10 vp + Placebo and the control. The interval gives the range of effects that remain compatible with the data.

Groups 1, 2 and 3: Number of Participants With Solicited Systemic AEs for 7 Days Post-booster Vaccination

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Group 2: Ad26.COV2.S 1.25*10^10 vp + Placebo: 29.2% (14/48) versus 31.4% (16/51) on control; risk difference -2.2 percentage points (95% CI -20.3 to 15.9), risk ratio 0.93 (0.51–1.69); unadjusted two-proportion z-test p = 0.811.
  • Group 3: Ad26.COV2.S 0.625*10^10 vp + Placebo: 30.6% (15/49) versus 31.4% (16/51) on control; risk difference -0.8 percentage points (95% CI -18.9 to 17.4), risk ratio 0.98 (0.54–1.75); unadjusted two-proportion z-test p = 0.935.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2: Ad26.COV2.S 1.25*10^10 vp + Placebo and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 3: Ad26.COV2.S 0.625*10^10 vp + Placebo and the control. The interval gives the range of effects that remain compatible with the data.

Groups 1, 2 and 3: Number of Participants With Unsolicited AEs for 28 Days Post-booster Vaccination

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Group 2: Ad26.COV2.S 1.25*10^10 vp + Placebo: 16.7% (8/48) versus 11.8% (6/51) on control; risk difference 4.9 percentage points (95% CI -8.9 to 18.7), risk ratio 1.42 (0.53–3.78); unadjusted two-proportion z-test p = 0.484.
  • Group 3: Ad26.COV2.S 0.625*10^10 vp + Placebo: 20.4% (10/49) versus 11.8% (6/51) on control; risk difference 8.6 percentage points (95% CI -5.7 to 23.0), risk ratio 1.73 (0.68–4.41); unadjusted two-proportion z-test p = 0.239.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 2: Ad26.COV2.S 1.25*10^10 vp + Placebo and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Group 3: Ad26.COV2.S 0.625*10^10 vp + Placebo and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address several different questions. The registry lists binding antibody titers and neutralizing antibody titers across the six groups, and solicited and unsolicited adverse events after the booster in the one-dose groups. These outcomes complement the primary result because the primary endpoint concerns local reactions during the 7 days after dose 1, while the secondary outcomes cover immune response and later safety observations.

For post-booster solicited local events, the posted counts in the one-dose groups are 19.0, 16.0, and 17.0. For post-booster solicited systemic events, the counts are 16.0, 14.0, and 15.0. The counts for unsolicited adverse events in the 28 days after the booster are 6.0, 8.0, and 10.0. These are later observation periods and different event categories from the primary endpoint; they should not be treated as repetitions of the first-dose local-event result.

The registry record lists eight secondary outcome measures, but detailed numerical results for the antibody outcomes are not reported in the registry record. The available post-booster comparisons are unadjusted. They do not establish a consistent difference among the groups, and they are not substitutes for the primary endpoint or a prespecified analysis of the full outcome set.

Unadjusted secondary results carry less weight for confirmatory interpretation because multiple outcomes and group comparisons create more opportunities for chance findings. The registry record does not report a multiplicity adjustment, a hierarchy of secondary endpoints, or a complete analysis plan. In addition, different endpoints have different definitions and observation windows. Any overall interpretation must keep those distinctions in view rather than combining counts from unrelated outcome types.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Groups 1, 2, 3, 4, 5 and 6: Serological Response to Vaccination Measured by Binding Antibody Titers to Severe Acute Respiratory Syndrome Coronavirus(-2) (SARS-CoV-2) or Individual SARS-CoV-2 S Proteins as Assessed by ELISA
• Groups 1, 2, 3, 4, 5 and 6: Serological Response to Vaccination Measured by Neutralizing Antibody Titers to SARS-CoV-2
• Groups 1, 2 and 3: Number of Participants With Solicited Local AEs for 7 Days Post-booster Vaccination
• Groups 1, 2 and 3: Number of Participants With Solicited Systemic AEs for 7 Days Post-booster Vaccination
• Groups 1, 2 and 3: Number of Participants With Unsolicited AEs for 28 Days Post-booster Vaccination
• Groups 1, 2 and 3: Number of Participants With MAAEs Until 6 Months Post-booster Vaccination
• Groups 1, 2 and 3: Serological Response to Post-booster Vaccination Measured by Binding (S-ELISA) Antibody Titers
• Groups 1, 2 and 3: Serological Response to Post-booster Vaccination Measured by Neutralizing (VNA) Antibody Titers

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either had at least one of the specified solicited local events during the observation window or did not. The registry reports the number of participants with an event and the number in the safety analysis set for each group. This format is different from a continuous outcome, such as a laboratory measurement, and different from a time-to-event outcome, which records how long participants remain event-free.

For the group comparisons, a risk difference expresses the difference between the proportions with an event in two groups. A value above zero means the observed proportion was higher in the compared group than in the reference group; a value below zero means it was lower. The displayed estimates are unadjusted recalculations from the posted counts. The registry record does not list a reported primary-outcome analysis, so these should not be described as estimates from a reported adjusted model.

A confidence interval gives a range of values compatible with the data under the method used. In general, a wider interval indicates less precision. If an interval for a risk difference includes zero, the data are compatible with no difference, as well as with positive or negative differences within the interval. An interval is not a guarantee that the true value lies in that range, and its width does not address possible bias, differences in outcome recording, or missing data.

What does a p-value add?

A p-value summarizes how unusual data at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It does not give the probability that the null hypothesis is true, nor does it measure the size or importance of a difference. The primary comparison p-values are unadjusted. Because the registry record does not report an adjustment for multiple comparisons, they should be read as descriptive rather than as a set of confirmatory tests.

What does unadjusted mean?

An unadjusted comparison uses the posted group summaries without accounting for additional covariates or other model terms. That makes the calculation transparent, but it does not ensure that all features of a trial’s analysis plan have been represented. In this study, the posted comparison figures are simple summaries from event counts; a more detailed sponsor analysis is not reported in the registry record.

General statistical principle: the amount of information in a binary outcome comparison depends on the number of participants and the frequency of events. With group sizes around 49.0 to 51.0, a small change in the number of participants with an event can appreciably affect the estimated proportions. This helps explain why confidence intervals can remain broad even when the raw counts appear close.

How should six groups be considered?

The endpoint is posted for three one-dose and three two-dose groups. The comparison estimates use Group 1 as the reference and separately compare each of the other groups with it. Each estimate answers a pairwise question, not an overall test of whether all six groups differ. The registry record does not report an overall test, a dose-trend analysis, or a prespecified hierarchy among these comparisons. A pattern of point estimates alone is not a substitute for such an analysis.

General statistical principle: when many comparisons are examined, the chance of at least one apparently notable result can increase if each is judged independently. Multiplicity procedures can address this, but the appropriate approach depends on the study’s objectives and prespecified analysis plan. That plan is not reported in the registry record, so no adjustment should be assumed.

The endpoint definition and analysis population also matter. Solicited events were actively queried and diary-recorded, unlike unsolicited events, which are collected under a different process. The primary result refers specifically to local reactions in the 7 days after dose 1 among participants with a documented vaccine administration. It should not be pooled conceptually with later booster observations or with antibody outcomes, which measure different aspects of the study.

11. Confidence Intervals and Precision

The primary comparisons are imprecise. For Group 2 versus Group 1, the risk-difference estimate is 0.065 and its 95% confidence interval runs from -0.111 to 0.241. For Group 3 versus Group 1, the estimate is 0.078 and the interval runs from -0.098 to 0.255. For Group 4, the estimate is -0.030 with an interval from -0.198 to 0.137; for Group 5, -0.01 with an interval from -0.180 to 0.160; and for Group 6, 0.051 with an interval from -0.125 to 0.227.

Every interval includes zero. In general, zero represents no risk difference between the compared groups. Each interval also extends in both directions from its point estimate, indicating that the observed counts do not pin down the size or direction of a difference with precision. The interval endpoints should be read on the risk-difference scale; they are not event counts or percentages.

Small group sizes contribute to this uncertainty. The comparison groups contain 49.0 to 51.0 participants, and the number with an event ranges from 11.0 to 17.0. With relatively few observations, the estimates can shift with a small number of participants. The registry record does not report adjusted primary analyses or a different confidence-interval approach, so the displayed intervals should be understood as unadjusted summaries of the posted data.

Confidence intervals describe sampling uncertainty under the calculation’s assumptions. They do not account for every potential source of uncertainty, such as missing outcome records or changes to the analysis plan, and they do not establish equivalence. The registry record does not report an equivalence margin or a non-inferiority margin for this endpoint.

12. 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 for participants per arm, not total events. They use 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. These are planning assumptions for the illustrations; the trial’s original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the estimated number of participants per arm for a design with an 80% chance of detecting the specified effect under the listed assumptions, if that effect and the other assumptions hold. The 90% power column gives the corresponding number per arm for a design with a 90% chance. For example, the Group 2 comparison’s illustration for 100% of the observed effect gives 758 participants per arm for 80% power and 1,014 participants per arm for 90% power.

Rows planning for 75% or 50% of the observed effect assume a smaller difference to detect than the row planning for 100%. Smaller effects generally require more participants to distinguish from random variation under the same assumptions. The figures can therefore become very large when the observed effect is small. They are not proposed enrollment targets for this completed trial, and they do not indicate how likely this trial was to find a statistically significant result.

This is not observed power. It is a planning illustration based on the observed effect, not an estimate of the study’s original design or a measure of the probability that its conclusions are correct. The registry record does not report the original sample-size calculation or its assumptions.

13. 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 = 0.255; treatment proportion p₁ = 0.320; average p̄ = 0.287.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6400 = 1.2544.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6384 = 0.5373.
4. n = (1.2544 + 0.5373)² / (0.0651)² = 757.5, rounded up to 758 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 <- 0.254901960784314                          # control proportion
p1 <- 0.32                          # 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(5007080)
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 = 758 (80% power), 1,014 (90% power)
 75% of observed effect: n per arm = 1,325 (80% power), 1,773 (90% power)
 50% of observed effect: n per arm = 2,928 (80% power), 3,919 (90% power)
power.prop.test: 757.5 
Simulated power at n = 758 per arm: 0.794 (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.

14. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple primary comparisons against the Group 1 reference and multiple secondary outcomes. It does not report a multiplicity procedure, such as an adjustment or a testing hierarchy, for interpreting those comparisons. The posted p-values are unadjusted. They therefore should not be read as if the collection of tests had a controlled overall false-positive rate.

Missing-data handling is not reported in the registry record for the primary outcome. The stated safety analysis set includes participants with at least one documented vaccine administration, but the registry information summarized for this endpoint does not describe how participants with missing diary entries or incomplete follow-up were handled. It also does not report whether missing outcomes were imputed, excluded, or treated in another way.

The registry identifies an analysis set for safety, but a broader population definition for efficacy or immunogenicity analyses is not reported in the details available for these results. The primary outcome counts should consequently be interpreted in the context of the stated safety population rather than assumed to represent every enrolled participant.

The registry record does not report the sponsor’s detailed statistical analysis plan, any interim analyses, or a formal sample-size justification. These omissions limit assessment of which comparisons were intended to be confirmatory, how outcome multiplicity was managed, and whether analysis decisions were prespecified. The unadjusted calculations summarize the posted counts; they cannot resolve these design and reporting uncertainties.

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: vaginal cyst excision (2.0%), intentional overdose (2.0%), femur fracture (2.0%).

For serious adverse events, the registry reports one affected participant in Group 1, one in Group 2, none in Group 3, none in Group 4, one in Group 5, and none in Group 6. The corresponding numbers at risk are 51, 50, 51, 49, 49, and 49. The registry lists zero deaths in five groups and one death in Group 2. It does not report the cause of death in the information summarized for these results.

The registry also lists Vaginal Cyst Excision, Intentional Overdose, and Femur Fracture among the top serious-event terms, each at 2.0%. Those terms are not enough to determine whether an event was caused by vaccination. The registry record does not report attribution details in the information.

These counts are descriptive and come from small groups. They should not be treated as comparative evidence that one regimen causes more or fewer serious events than another. The number of participants with other recorded adverse events ranges from 26 to 35 across groups, but the posted detail does not define those events as serious or provide a causal assessment. Serious-event counts, other adverse-event counts, and solicited reactogenicity outcomes are distinct safety summaries.

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

The posted primary results show the observed number of participants reporting a solicited local event in the 7 days after dose 1 for each of six dose-and-schedule groups. The unadjusted risk-difference estimates compare each non-reference group with Group 1. Their confidence intervals are broad and include zero, so the comparisons do not precisely establish the direction or size of a difference.

These findings do not show that groups are equivalent. Demonstrating equivalence would require a defined margin and an analysis designed for that question; neither is reported in the registry record. Likewise, a lack of a statistically notable unadjusted comparison is not proof of no difference. The small group sizes and broad intervals leave uncertainty.

The primary outcome concerns short-term local reactogenicity, not prevention of COVID-19. Although prevention is listed as a study condition and the study’s stated purpose included humoral immune response, the primary endpoint is an adverse-event count. The registry record does not report efficacy results for preventing COVID-19 in the registry record for this endpoint. Antibody outcomes are listed as secondary measures, but detailed antibody results are not reported in the registry record in the information available for this account.

The comparison figures are unadjusted calculations from the posted summary counts. The registry record lists no reported primary analyses, and it does not provide the statistical plan, multiplicity approach, or missing-data methods needed for a fuller assessment. The most defensible interpretation is therefore descriptive: these are the observed counts and unadjusted comparisons, with uncertainty that remains substantial.

No conclusion about the overall benefit or risk of a regimen follows from this endpoint alone. Safety counts for a limited follow-up window and group sizes of this scale cannot, by themselves, settle uncommon-event risks or broader clinical questions. The record’s findings should be understood within the study population, the specified event definitions, and the time periods actually assessed.

17. Why This Trial Matters Statistically

This study illustrates why counts should be interpreted alongside effect estimates and confidence intervals. The raw numbers of participants with local events are easy to read, but they do not indicate how precisely the groups differ. The intervals show that the observed data are compatible with a range of risk differences, including no difference.

It also shows the distinction between a trial’s posted outcomes and a confirmatory statistical analysis. Several pairwise comparisons can be calculated from group summaries, but the registry record does not report a primary-outcome analysis or a multiplicity plan. Without that context, unadjusted comparisons are informative descriptions rather than a complete basis for confirmatory claims.

The six-group design includes different dose levels and schedules, while the primary outcome focuses narrowly on local events after dose 1. Keeping the outcome definition and timing explicit prevents confusion with later booster safety outcomes or antibody measurements. Those outcomes may speak to other study objectives but do not answer the same question.

Finally, the planning illustrations demonstrate how sample-size requirements depend on the effect selected for detection and the assumptions used. They are not the trial’s original design calculation and cannot be mistaken for evidence that the completed trial had adequate power for every comparison. This distinction is important whenever sample-size planning is reconstructed from an observed result.

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.

The primary endpoint group sizes are small, ranging from 49.0 to 51.0, and the comparison confidence intervals are wide. This limits precision, especially for conclusions about differences between dose levels or schedules. The registry record does not report a prespecified primary contrast among the six groups or a dose-trend analysis.

The comparison figures are unadjusted recalculations from summary counts. No reported primary analyses, detailed analysis plan, multiplicity method, interim-analysis information, or original sample-size justification is available in the registry record. Missing-data handling for diary-based outcomes is also not reported. These gaps constrain assessment of whether the posted comparisons match the intended analysis and how incomplete observations may have been handled.

The primary endpoint captures whether participants reported one or more specified local events within a defined period. It does not describe event severity, duration, or number of episodes. Its findings cannot be generalized automatically to systemic events, later booster reactions, immune response, or COVID-19 prevention. Detailed antibody results are not reported in the registry record in the information summarized for this analysis.

The study population is healthy adolescents from 12 to 17 years inclusive. The registry record’s stated population limits interpretation to that setting; results should not be assumed to apply to other populations. Group-level adverse-event counts are descriptive and do not establish causation, particularly for serious events. The registry record does not report event attribution details in the information summarized for these results.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Evaluate Different Dose Levels of Ad26.COV2.S in Healthy Adolescents From 12 to 17 Years Inclusive — NCT05007080.
• Registry record last updated 2025-02-04; status last verified 2025-01.
• Results first posted 2024-05-23.
• 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

NCT05007080 is a completed randomized, observer-blind, phase 2, parallel-group study of Ad26.COV2.S in healthy adolescents from 12 to 17 years inclusive. Enrollment was 304. Six groups studied three dose levels under one-dose or two-dose schedules, with booster vaccination planned for the one-dose groups.

The primary endpoint counted participants with solicited local adverse events during the 7 days after dose 1. Posted counts ranged from 11.0 to 17.0 across groups. Unadjusted comparisons against Group 1 had confidence intervals that included zero and were broad, reflecting limited precision. The registry record does not report a primary-outcome analysis, multiplicity procedure, missing-data method, or original sample-size justification.

Secondary outcomes include antibody measures and post-booster adverse events. Detailed antibody results are not reported in the registry record in the information. The posted findings are descriptive and do not establish efficacy against COVID-19 or equivalence among regimens.