A Study to Evaluate the Safety and Immunogenicity of Oral Polio Vaccine Type 2 in Infants and Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Immunogenicity of Oral Polio Vaccine Type 2 in Infants and Children (NCT02521974), a na phase 4 study. The primary outcome is Number of Subjects Experiencing SAEs, Severe AEs (Grade 3), and/or IMEs.

2. Clinical Question

3. Trial Design

This was a phase 4 study of SABIN monovalent OPV2, recorded as completed, with Fidec Corporation listed as sponsor. The registry lists the study start as 2015-10 and primary completion as 2016-07. Enrollment was 164. It was a single-group study, with allocation recorded as not applicable and masking recorded as none. These design features matter when interpreting safety counts: the study was not structured as a randomized comparison between vaccine and control.

The study included healthy children aged 1 to 5 years and healthy infants previously vaccinated with bOPV/IPV. The registry’s primary-outcome description refers to children in Group 1 and infants in combined Groups 2+3. It reports that 50 children received the first dose and 47 received a second dose; it reports that all 110 infants in combined Groups 2+3 received a first dose and that 49 of 50 infants in Group 3 received two doses. The safety summary separately gives denominators of 50 for Group 1 and 114 for Group 2+3. The registry record does not explain the difference between the infant counts in these descriptions, so they should be read in the context of the specific reported outcome rather than treated as interchangeable.

The stated primary-outcome timeframe is six months. The registry identifies two outcome measures, but details for the other measure are not reported in the registry record. It lists no analysis records. The statistical analysis plan, prespecified analysis populations, sample-size justification and interim-analysis plans are not reported in the registry record. Consequently, the design can be described from its recorded structure and outcomes, but its unreported planning and analysis choices cannot be reconstructed.

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

Analysis population for the primary outcome, as defined in the registry: 50 (100%) children in Group 1 received the first dose of study vaccine and 47 (94%) children received the second dose. All 110 (100%) infants in combined Groups 2+3 received the first dose of study vaccine and 49 (98.0%) of the 50 infants in Group 3 received 2 doses of vaccine.

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: 4 early terminated subjects during the pre-vaccination phase, before receiving the investigational vaccine.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Experiencing SAEs, Severe AEs (Grade 3), and/or IMEs, measured over 6 months.

The primary endpoint is the number of participants experiencing serious adverse events, severe adverse events (grade 3), and/or important medical events considered consistent with a causal association to the study vaccine during the stated six-month timeframe. It is a participant-count endpoint: the focus is whether a participant experienced an event in the specified category, rather than the total number of event episodes. The registry describes the endpoint across all groups.

Safety endpoints of this kind are used to characterize events occurring after vaccination and to identify events meeting specified seriousness or severity criteria. They can describe what was observed in the study, but an event occurring after vaccination is not, by timing alone, proof that vaccination caused it. The endpoint’s description narrows the primary count to events considered consistent with a causal association, but the criteria and adjudication procedures used to make that assessment are not reported in the registry record.

The posted safety summary gives zero serious adverse events in each listed group. It also records one other adverse event in each group, but the posted endpoint description does not establish that these other events met the primary endpoint’s severe-event or important-medical-event criteria. Detailed primary-endpoint results beyond the safety counts are not reported in the registry record. The endpoint is therefore useful for describing the safety question the study set out to address, while the available counts do not provide a full account of every component of that endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant-count endpoint represent?

The primary endpoint is expressed as the number of participants experiencing one or more specified kinds of event. In general, participant counts differ from event counts: a participant with repeated episodes may still contribute only once to a count of participants with an event. The registry defines the endpoint as counting participants with serious adverse events, severe adverse events (grade 3), and/or important medical events considered consistent with a causal association to the vaccine. The precise rules for grouping overlapping events or deciding whether an event met those categories are not reported in the registry record.

The posted safety summary also distinguishes serious events from other adverse events and deaths. These categories should be kept separate. A zero in the serious-event column does not establish that no adverse events of any kind occurred; the summary records one other adverse event in each listed group. Conversely, the other-event count does not show that either event met the primary endpoint’s severity or medical-importance criteria.

Why is the design important for interpretation?

In general, random assignment can help make treatment groups comparable on average, supporting a causal comparison when outcomes are assessed appropriately. This study is recorded as single-group, with allocation not applicable and no masking. Its participant cohorts are not randomized vaccine and control arms. The group-specific counts therefore describe events in the cohorts, rather than a randomized estimate of what would have happened under a different intervention.

In general, masking can reduce some forms of measurement or reporting influence, depending on who is masked and how outcomes are assessed. Here masking is recorded as none. The registry does not describe outcome-adjudication procedures, so it is not possible to determine how event classification was protected from knowledge of vaccination or participant cohort. This limitation does not change the reported counts, but it is relevant context for interpreting subjective or clinically classified outcomes.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under a specified statistical model and procedure. It can show how imprecise an estimate may be; it does not by itself resolve bias, confounding or whether an event was caused by an intervention. The registry record does not report confidence intervals for the safety counts. Nor does it report a statistical test or an adjusted estimate for the primary endpoint. The counts can be stated as observed, but their sampling uncertainty cannot be quantified from the registry record as.

In general, sparse event counts require particular caution: a small observed count may still be compatible with a broad range of underlying event frequencies. A zero observed count is not proof that an event cannot occur. The interpretation of a zero also depends on the number of people observed, follow-up completeness, event definitions and ascertainment. The registry supplies group denominators for its safety summary, but does not report enough information about missing follow-up or ascertainment to resolve all of those considerations.

What do the planning illustrations mean?

The registry’s stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. It specifies participants per arm for outcomes other than time-to-event outcomes; time-to-event illustrations use total events. These are planning assumptions, not a record of the trial’s own design justification. The sample-size justification for this study is not reported in the registry record.

Because the study is single-group and does not have a randomized control comparison, the two-arm equal-allocation framework in those planning illustrations should not be mistaken for the structure of this trial. Such illustrations are hypothetical planning quantities, not observed power and not evidence that the study was designed to detect a particular effect. The registry does not report the statistical model, chosen effect fraction, or detailed planning values for the study itself.

What analysis information is absent?

The registry lists no analysis records. That means no analysis records are listed in the registry; it does not establish that investigators performed no analyses. The statistical analysis plan, inferential procedures, covariate adjustments, handling of repeated events, missing-data methods and prespecified analysis populations are not reported in the registry record. General statistical interpretation therefore needs to remain distinct from claims about methods actually used by investigators.

The registry lists two outcome measures, but only the primary safety outcome is described in the registry record for this analysis. The second outcome’s definition and results are not reported in the registry record. The study summary mentions immunogenicity and genetic stability as aims, but those aims alone do not specify how outcomes were measured or analyzed. No unreported methods or results can be inferred from the study’s aims.

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", "Group 2+3")
n      <- c(50, 110)
events <- c(0, 1)
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  50  0  0.0  0.0  7.1  0.0  7.1  0.0  7.0
ARM  Group 2+3  110  1  0.9  0.0  5.0  0.2  5.0  0.2  4.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, but the detailed information available for this analysis describes the primary safety endpoint only. The definition and results for the other outcome are not reported in the registry record. The study summary also names immunogenicity and genetic stability as aims; however, the registry entries do not identify the full set of planned comparisons or explain how those aims map onto the listed outcome measures.

Multiplicity arises in general when several outcomes, time points, subgroups or statistical tests are considered: interpreting many results can increase the chance that at least one appears noteworthy by chance. Statistical plans may address this through prespecified outcome hierarchies or adjustment procedures. Whether such steps were planned or used in this study is not reported in the registry record. No multiplicity-adjusted or unadjusted inferential results are listed, so there is no basis to describe a particular adjustment strategy.

The registry does not report missing-data methods, follow-up completeness for the safety outcomes, or the analysis populations used for the posted counts. It reports dose receipt for some cohorts and separate denominators in the safety summary, but does not explain the differences between all those figures. It is therefore not possible to establish from the registry record whether every enrolled participant was included in each outcome analysis, how participants with incomplete observation were handled, or whether the reported denominator reflects a prespecified safety population.

In general, missing outcome data can affect interpretation if participants with incomplete follow-up differ in their event experience from those observed. This is a methodological consideration, not evidence that missingness occurred in this study. The registry record does not provide enough detail to quantify or characterize any missingness. The reported counts should be read with their stated denominators and without assuming an unreported missing-data procedure.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry’s safety summary reports zero serious adverse events among 50 participants in Group 1 and zero among 114 participants in Group 2+3. It reports one other adverse event in each group and zero deaths in each group. These values are counts of participants with events in the categories represented by the safety summary, not estimates of comparative risk between randomized arms. The registry does not provide event descriptions for the other adverse events in the registry record for this analysis.

The primary endpoint also includes grade 3 severe adverse events and important medical events considered consistent with a causal association to the vaccine. The safety summary’s zero serious-event figures do not, by themselves, supply separate counts for those other endpoint components. Detailed component-level results and criteria for causal assessment are not reported in the registry record.

In general, zero observed events means that no events in the defined category were recorded in the reported observation, not that the underlying possibility is zero. Interpretation depends on the denominator, follow-up and event ascertainment. The registry gives a six-month primary-endpoint timeframe but does not report completeness of follow-up or detailed ascertainment procedures. These counts are descriptive safety observations, not proof that the vaccine caused or did not cause an event.

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

The posted data describe the safety observations recorded for two participant cohorts in a completed phase 4 study. The registry reports no serious adverse events and no deaths in either listed group, and one other adverse event in each group. These statements apply to the categories and denominators in the registry’s safety summary. They do not establish that every component of the primary endpoint had zero events, because separate counts for grade 3 severe events and important medical events are not reported in the registry record.

The findings also do not support a randomized comparison. The study is recorded as single-group, with no masking and allocation not applicable. Group 1 and combined Groups 2+3 are not described as randomized treatment and control arms. Any difference between cohorts would not isolate a vaccine effect, and the registry does not report a comparative causal analysis. The counts should therefore be interpreted as descriptive rather than as evidence of relative safety.

In general, an observed count summarizes events recorded during an observation period; it does not alone identify why an event occurred. The primary endpoint’s description refers to events considered consistent with a causal association, but the registry does not report the assessment process. Nor does the registry supply confidence intervals or another measure of statistical precision for the counts. A zero count should not be interpreted as demonstrating that an event is impossible, and a nonzero count does not by itself demonstrate causation.

The study summary explains that the investigation was intended to generate safety, immunogenicity and genetic-stability information for mOPV2 and to support future comparisons with potential new vaccines. That rationale is not itself a result. Immunogenicity and genetic-stability findings are not reported in the registry record available for this analysis. The reported safety counts alone therefore do not answer those other research questions or establish how the vaccine compares with another product.

14. Why This Trial Matters Statistically

This study illustrates why the design and denominator are part of a safety result, not background details. A participant count is meaningful only alongside its event definition, observation period and population. The registry identifies a six-month timeframe for the primary safety endpoint and gives separate denominators for Group 1 and combined Groups 2+3. It also reports dose-receipt figures in the endpoint description that do not exactly match the safety denominators for the infants. Since the registry does not explain the difference, readers should retain the denominator attached to each particular result rather than combine descriptions.

The study also illustrates the limits of descriptive safety evidence. A single-group study can document events observed after vaccination, but without randomized control allocation it cannot provide a like-for-like estimate of what would have occurred under a different intervention. This distinction remains important even when the reported serious-event count is zero. Counts describe recorded observations; they do not independently establish a causal relationship or exclude possible events outside the observed data.

Finally, the record separates a stated research rationale from posted outcome evidence. The summary explains an interest in safety, immunogenicity and genetic stability, but detailed results for all those aims are not reported in the registry record. It also lists no analysis records and does not report a statistical analysis plan or sample-size justification. For biostatisticians and clinical researchers, this makes transparent reporting of endpoint definitions, denominators, follow-up, missingness and analysis methods central to evaluating what a study can support. The sample-size assumptions listed for planning illustrations are hypothetical planning inputs, not observed power and not evidence of the study’s own design rationale.

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 main trial-specific limitation is the absence of a randomized comparator. The study is recorded as single-group, with allocation not applicable and masking none. The participant cohorts are not a like-for-like control comparison, so the safety counts cannot establish a causal difference between vaccination and an alternative. The registry does not report an adjusted comparative analysis.

The available safety summary does not provide separate results for every component of the primary endpoint. It reports serious-event counts, other adverse-event counts and deaths, while the primary endpoint also refers to grade 3 severe adverse events and important medical events considered consistent with a causal association. Their separate counts and event-assessment procedures are not reported in the registry record. Event descriptions for the other adverse events are also not reported in the registry record for this analysis.

The registry’s group and denominator descriptions are not fully aligned: the primary-outcome text reports 110 infants in combined Groups 2+3 receiving a first dose, while the safety summary lists 114 participants at risk in Group 2+3. The registry record does not explain this. It also does not report follow-up completeness, the analysis population, missing-data handling, confidence intervals, or the statistical analysis plan. These omissions limit assessment of precision and of how the posted counts were assembled.

The study was conducted in healthy children and infants as described in the registry, so its recorded observations pertain to those cohorts and this study context. The record does not report detailed immunogenicity or genetic-stability results, despite naming those aims. The statistical sample-size justification for the trial is not reported in the registry record; planning illustrations should not be read as its actual design basis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Immunogenicity of Oral Polio Vaccine Type 2 in Infants and Children — NCT02521974.
• Registry record last updated 2020-08-14; status last verified 2017-07.
• Results first posted 2020-08-14.
• 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

NCT02521974 is a completed phase 4, single-group study sponsored by Fidec Corporation. The registry lists enrollment of 164, a start date of 2015-10 and primary completion in 2016-07. The study evaluated SABIN monovalent OPV2 in healthy children aged 1 to 5 years and healthy infants previously vaccinated with bOPV/IPV.

The primary safety endpoint counted participants with serious adverse events, grade 3 severe adverse events and/or important medical events considered consistent with a causal association to vaccination over six months. The safety summary reports zero serious adverse events, one other adverse event and zero deaths in each listed group. The record does not provide separate counts for every primary-endpoint component or confidence intervals.

There was no randomized comparator, and masking was recorded as none. Analysis methods, missing-data handling, the trial’s sample-size justification and detailed results for the other listed outcome are not reported in the registry record.