A Study of Ad26.COV2.S in Healthy Pregnant Participants (COVID-19): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Ad26.COV2.S in Healthy Pregnant Participants (COVID-19) (NCT04765384), a na phase 2 study. The primary outcome is Number of Adult Participants With Solicited Local Adverse Events (AEs) for 7 Days Post First Vaccination.

2. Clinical Question

3. Trial Design

This was an open-label, Phase 2 study of Ad26.COV2.S in healthy pregnant participants. It is listed as completed, with a start date of 2021-08-27 and a primary completion date of 2023-11-24. The registry lists enrollment of 51. Allocation is recorded as not applicable, masking as none, and the model as single group. The study therefore does not provide a randomized, blinded comparison between the vaccine and a control intervention.

The intervention was a single intramuscular dose at the standard dose level. The study included previously vaccinated participants in Groups 1-3 and vaccine-naïve participants in Group 4. Group 4 participants who were no longer pregnant could potentially receive a booster; the registry description of that arm is incomplete, so further details are not reported in the registry record. The study purpose also included assessing the immune response in peripheral blood 28 days after vaccination.

The primary endpoint concerns solicited local adverse events from the first vaccination through 7 days post first vaccination, up to Day 8. Other listed outcomes include post-booster adverse events in Group 4 and pregnancy outcomes. The registry record lists 28 outcome measures but no analysis records. It does not report the study’s statistical analysis plan, sample-size justification, interim analyses, or a randomized comparison. The group-level safety summaries should therefore be read as descriptive results within the groups, not as estimates of comparative effects.

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: Per change in planned analyses, combined analysis was performed for Groups 2 and 3 in both adults and neonates in order to protect and maintain the privacy/confidentiality of the single participant enrolled in Group 2. Each adult participant in Group 4 received booster dose at a different timepoint, that is, any day from Day 84 up to Day 364.

Post-baseline: Adults

Reasons for not completing this period:

Post-natal: Neonates and Infants

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set - Adults (FAS-A) included all enrolled adult 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: Per planned analysis, data for baseline characteristics were collected and analyzed for the full analysis set - adults (FAS-A) which included all enrolled adult participants with at least one vaccine administration documented.

6. Primary Endpoint

The registry lists the primary outcome as Number of Adult Participants With Solicited Local Adverse Events (AEs) for 7 Days Post First Vaccination, measured over From first vaccination on Day 1 up to 7 days post first vaccination (up to Day 8).

The primary endpoint counts adult participants with solicited local adverse events during the 7 days after first vaccination, including the vaccination day and the following 7 days. The specified events are injection-site pain or tenderness, erythema, and swelling at the vaccination site. Participants were specifically asked about these pre-defined events, which were recorded in a reactogenicity diary.

This endpoint is used to describe short-term local reactogenicity: events occurring at or near the injection site after vaccination. A participant count is an accessible summary of how many people experienced at least one event in the defined category and timeframe. It does not, by itself, describe how many events each participant had, their severity, duration, or whether they were caused by the vaccine. The registry’s general definition of an adverse event also notes that an event need not have a causal relationship with the study agent.

The primary endpoint population is the Full Analysis Set - Adults, defined as enrolled adult participants with at least one vaccine administration documented. The result for this endpoint, including the count of participants with solicited local events, is not reported in the registry record. Consequently, the endpoint’s magnitude and precision cannot be assessed from that record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as open-label and single-group, with allocation not applicable and masking absent. These design features shape the statistical interpretation. Open-label means participants and study personnel were not masked to the intervention. A single-group structure means the listed groups are not equivalent to randomized treatment and control arms. General statistical principle: randomization helps balance measured and unmeasured factors on average; without it, group differences can reflect differences in participant characteristics, prior vaccination, follow-up, or other factors rather than an intervention effect.

What does a participant count represent?

The primary endpoint is a count of adults who experienced solicited local adverse events within a specified follow-up period. For a binary outcome, each participant is classified according to whether the event occurred or did not occur during that period. The count is useful as a direct description of the endpoint, but it does not describe the number of episodes or the duration or severity of events. The registry record does not report the primary count, so an event frequency for this endpoint cannot be evaluated.

The safety summaries report counts alongside the number at risk for each group. Those figures are descriptive. General statistical principle: when event counts are small, estimates based on them can be imprecise, and uncertainty is better understood with an interval estimate than from a count alone. The registry record does not report confidence intervals for the primary endpoint or the safety counts. It also does not provide a statistical analysis plan in the record, so the intended estimation procedures and inferential methods are not reported in the registry record.

How should the group summaries be compared?

The listed adult groups reflect prior vaccination status, and the study is not randomized. Any apparent difference in event counts between groups could arise from differences in who entered each group, follow-up, or other factors. General statistical principle: an unadjusted contrast between non-randomized groups does not isolate a causal treatment effect. No like-for-like control comparison is available in the registry record, and adjusted comparisons are not reported there. Thus, the reported numbers are most appropriately read as counts within groups, not as comparative estimates.

What does statistical precision mean?

General statistical principle: a confidence interval describes a range of values compatible with the data and the assumptions of the analysis. Its width reflects precision; narrower intervals indicate more precise estimates, while wider intervals indicate greater uncertainty. A confidence interval does not remove bias from a non-randomized design and does not establish causation. Since no interval for the primary endpoint is reported in the registry record, its precision cannot be judged. The record also does not report a primary endpoint hypothesis test or a p-value.

Planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe participants per arm for 80% or 90% power under specified fractions of an observed effect. These are planning illustrations, not the trial’s own design justification, and not observed power. The registry record does not report that the study was designed with those assumptions or that it conducted a randomized two-arm comparison. Any such illustration should not be read as evidence that the study had adequate power for its primary endpoint.

The sample-size assumptions refer to detecting stated fractions of an observed effect. General statistical principle: a planning calculation depends on its assumptions about the effect to detect, outcome variability, allocation, significance threshold, and analysis method. A calculation based on an observed effect is especially dependent on that effect estimate and does not retrospectively show that a study had a particular probability of finding a result. The registry record does not report a sample-size justification or an observed primary effect, so the planning illustrations cannot fill those gaps.

What is not available for independent checking?

The record lists 28 outcome measures but no analysis records. It does not provide the primary endpoint’s numerical result, a confidence interval, a p-value, details of a model, covariate adjustments, or an approach to missing outcome data. General statistical principle: an analysis is easier to assess when the planned endpoint definitions and analysis methods can be compared with the results reported. Those details are not reported in the registry record, so it is not possible to assess analysis choices against a prespecified plan from this record.

The safety counts should also be distinguished from formal statistical evidence. They describe events reported within named groups; they are not, on their own, tests of causal effects. The registry does not report whether event counts were compared statistically or whether multiplicity adjustments were applied. Since there are no listed analysis records, statistical significance or a confirmatory interpretation should not be inferred from the safety summaries.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group 1 (Adults): Ad26.COV2.S 5*10^10 vp", "Groups 2 and 3 (Adults): Ad26.COV2.S 5*10^10 vp", "Group 4 (Adults): Vaccine-naive: Ad26.COV2.S 5*10^")
n      <- c(12, 10, 29)
events <- c(10, 5, 20)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group 1 (Adults): Ad26.COV2.S 5*10^10 vp  12  10  83.3  51.6  97.9  55.2  95.3  54.6  95.0
ARM  Groups 2 and 3 (Adults): Ad26.COV2.S 5*10^10 vp  10  5  50.0  18.7  81.3  23.7  76.3  23.4  76.6
ARM  Group 4 (Adults): Vaccine-naive: Ad26.COV2.S 5*10^  29  20  69.0  49.2  84.7  50.8  82.7  50.6  82.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 28 outcome measures, including the primary solicited-local-event endpoint, other adverse-event outcomes, and pregnancy outcomes. It does not report an analysis plan specifying which outcomes were intended to support confirmatory conclusions, how multiple outcomes would be handled, or whether any multiplicity adjustment was used. These details are not reported in the registry record. Without them, the role of each secondary or exploratory outcome in formal inference is unclear.

The record lists no analysis records. It does not report statistical tests, confidence intervals, or p-values for the primary endpoint. Nor does it report whether interim analyses were planned or conducted. Such details are not reported in the registry record; none should be inferred from the study’s phase or its listed outcomes.

Missing-data methods and the extent of missing endpoint data are also not reported in the registry record. The primary endpoint population is defined as enrolled adults with at least one documented vaccine administration, but this definition alone does not describe how missing diary entries, incomplete follow-up, or participants without an endpoint assessment were handled. The record does not specify imputation, exclusion, or sensitivity analyses for missing data.

These omissions limit assessment of the robustness of the reported safety summaries and prevent evaluation of the primary endpoint’s precision. They do not demonstrate that a particular method was or was not used; they mean the method is not reported in the registry record.

12. 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: neonatal cholestasis (12.5%), bronchiolitis (12.5%), bronchitis viral (12.5%), covid-19 (12.5%), pneumonia bacterial (12.5%).

The serious adverse-event summaries give the number at risk and the number with a serious adverse event in each listed group. For adults, the counts are 4 of 12 in Group 1, 2 of 10 in Groups 2 and 3, and 3 of 29 in Group 4. For neonates and infants, they are 3 of 10 in Group 1, 4 of 8 in Groups 2 and 3, and 4 of 29 in Group 4. These are group-level descriptive counts, not randomized comparisons.

The record lists one death in the neonatal and infant Group 1 and zero deaths in the other groups. It does not report the cause or circumstances of the death in the information available in the registry record. Six serious adverse-event terms are listed at 12.5% each: Neonatal Cholestasis, Bronchiolitis, Bronchitis Viral, COVID-19, Pneumonia Bacterial, and Respiratory Distress. The term list should not be interpreted as evidence of causal association with vaccination.

General statistical principle: an adverse event occurring after an intervention is not necessarily caused by that intervention. Causal assessment requires context, including timing, clinical details, and an appropriate comparison. The registry record does not provide enough information to establish causality or compare risks fairly across these non-randomized groups.

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

The record describes a study designed to assess safety, reactogenicity, and immune response after Ad26.COV2.S in healthy pregnant participants. It identifies a primary short-term endpoint based on solicited local adverse events and gives selected serious-adverse-event summaries for adults and neonates and infants. Those descriptions help clarify what was monitored, but the primary endpoint result itself is not reported in the registry record.

The reported serious-event counts are observations within study groups. They do not show that the vaccine caused an event, and they do not establish whether the intervention increased or decreased risk relative to an untreated or alternative-treatment group. The study has no randomized comparator, and the groups are described by prior vaccination status. A direct causal comparison between those groups is therefore not supported by the design information in the registry record.

The immune-response aim is described as assessment of humoral response in peripheral blood 28 days after vaccination. Numerical immune-response results are not reported in the registry record. Likewise, the listed pregnancy outcome measure does not include a numerical result in the information available in the record. Conclusions about immune response or pregnancy outcomes cannot be drawn from those aims alone.

The study’s completion status and enrollment figure describe the conduct of the trial, not the size or certainty of an effect. The record does not provide the primary endpoint’s count, its confidence interval, or inferential analysis. It also does not report a sample-size justification, interim analysis approach, missing-data methods, or multiplicity plan. The absence of those details in the registry record limits statistical interpretation; it does not establish what methods were used outside the record.

Overall, the available evidence is descriptive and incomplete for judging the primary endpoint. It can be used to identify the questions the study set out to address and to read the safety counts as recorded. It cannot support a claim of efficacy, a causal safety comparison, or a precise estimate of the primary local-event outcome.

14. Why This Trial Matters Statistically

This trial is statistically notable because it studies a defined population—healthy participants during pregnancy—in an open-label, single-group design. That design can describe events observed after vaccination, but it cannot provide the same protection against confounding as a randomized comparison. The distinction matters when interpreting group summaries, especially when groups are defined by prior vaccination status.

The primary endpoint is a clearly time-bounded participant count for solicited local events. A defined event category and follow-up period can make a safety question more interpretable, but interpretation still depends on the actual result and its uncertainty. The registry record does not report that primary result, so the stated endpoint cannot be translated into an event frequency or precision estimate from the record.

The record also illustrates why safety counts need context. Counts for adults and neonates and infants are presented by group, and one neonatal/infant death is recorded. Such figures are important descriptive observations, but do not establish causality. The record’s lack of a randomized control comparison and the lack of event-level context limit what can be inferred from them.

Finally, the registry lists many outcome measures but no analysis records. Without reported methods for multiplicity, missing data, or statistical estimation, readers cannot assess how the outcomes were prioritized or how uncertainty was quantified. The study’s statistical importance is therefore partly in its population and endpoint definitions, and partly in the limits imposed by the reporting available in the registry record.

15. 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 most direct limitation for interpreting the primary question is that its result is not reported in the registry record. Although the endpoint definition specifies solicited local events in a defined follow-up period and population, the corresponding participant count and any measure of uncertainty are absent. No primary endpoint effect estimate or inferential result can therefore be assessed.

The study is open-label and single-group, with no randomized control comparison. The groups are characterized by prior vaccination status, so group differences may reflect differences in participant characteristics or other factors. The registry record does not report adjusted analyses that might address such differences. The adult and neonatal/infant safety counts should be treated as descriptive, not as causal comparisons.

Additional limitations are that the registry record does not report the sample-size justification, statistical analysis plan, missing-data approach, multiplicity strategy, or interim analysis procedures. It also does not report numerical immune-response results or pregnancy outcome results in the information available. Details of the circumstances and cause of the neonatal/infant death are not reported in the registry record.

The study’s completed status does not resolve these reporting gaps. The results available in the registry record allow readers to identify certain event counts and the intended endpoints, but not to evaluate the primary endpoint’s frequency, precision, or a causal effect of vaccination.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Ad26.COV2.S in Healthy Pregnant Participants (COVID-19) — NCT04765384.
• Registry record last updated 2025-05-25; status last verified 2025-05.
• Results first posted 2024-11-13.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed, open-label, Phase 2, single-group study of Ad26.COV2.S in healthy pregnant participants. Enrollment is listed as 51. The intervention was a one-dose intramuscular schedule at the standard dose level, with the study assessing safety, reactogenicity, and humoral immune response. The primary endpoint is the number of adults with solicited local adverse events during the 7 days after first vaccination.

The primary endpoint result is not reported in the registry record. The record does report serious adverse-event counts by adult and neonatal/infant groups, along with one death in neonatal/infant Group 1. These observations are descriptive; the design does not provide a randomized control comparison. Statistical analysis details, missing-data methods, multiplicity handling, and numerical immune-response and pregnancy outcome results are not reported in the registry record.