Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine (NCT02434770), a randomized phase 3 study. The primary outcome is Number of Participants Experiencing Any Systemic Reactogenicity, by Maximum Severity.

2. Clinical Question

3. Trial Design

This was a Phase III randomized, controlled, single-blind, parallel-group study in healthy Kenyan infants. The registry lists PATH as the sponsor and records the study as completed. The start is recorded as 2015-08, and primary completion as 2016-06-17. The listed enrollment is 750.

Participants were assigned to BBIBP bOPV Lot 1, BBIBP bOPV Lot 2, or the BioFarma bOPV comparator. The recorded vaccination schedule for each group was administration in the first two weeks of life and again at 6, 10, and 14 weeks of age. The descriptions specify 2 drops delivered directly into the mouth at each scheduled vaccination. The two BBIBP lots are presented as separate study groups, while BioFarma is identified as the WHO-prequalified comparator.

Randomization can help balance measured and unmeasured participant characteristics across groups on average, although it does not guarantee identical groups. Single blinding means that some study procedures were masked, but the identity of the people who were blinded is not reported in the registry record. Allocation concealment, the randomization sequence method, and procedures for maintaining the blind are also not reported in the registry record.

The primary outcome was assessed during the 7 days after each vaccination, at Weeks 0, 6, 10, and 14. Parents recorded solicited reactions using a memory aid. The registry also lists secondary outcomes involving anti-hepatitis B surface antigen geometric mean titers, anti-hepatitis B surface antigen seroprotection, and anti-rotavirus immunoglobulin A geometric mean titers. Although the study objective refers to immunogenicity, numerical results for those secondary outcomes 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: Infants were enrolled prior to receipt of the birth dose of bivalent oral poliomyelitis vaccine (bOPV} and were were allocated to 1 of 3 arms: 1. Beijing Bio-Institute Biological Products Co., Ltd. (BBIBP) liquid bOPV Lot 1; 2. BBIBP liquid bOPV Lot 2; and 3. World Health Organization (WHO) prequalified comparator bOPV (BioFarma).

Week 1 to Week 18

Reasons for not completing this period:

Week 18 to Week

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety population included all enrolled participants who had safety data available, assigned according to the actual treatment received at Day 0.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing Any Systemic Reactogenicity, by Maximum Severity, measured over 7 days after each vaccination (Weeks 0, 6, 10, and 14).

The primary endpoint is the number of participants experiencing any solicited systemic reactogenicity event, with each participant classified by the maximum severity experienced. Events assessed during the week after vaccination included fever, vomiting, diarrhea, decreased appetite or poor feeding, irritability, and decreased activity. Parents recorded reactions using a memory aid.

The severity scale distinguishes mild reactions, which cause no or minimal interference with usual activities and require no medical intervention or therapy; moderate reactions, which cause greater than minimal interference and may require minimal intervention; severe reactions, which markedly limit usual activities or require medical intervention; and potentially life-threatening reactions, involving inability to perform basic functions or an indication for medical or operative intervention to prevent serious lasting harm or death. The registry's definition assigns the participant according to the maximum severity rather than counting each reaction as a separate participant.

As a safety measure, this endpoint captures whether participants experienced any of the solicited reactions and the highest severity recorded. It can describe the frequency and severity pattern of reported reactions during the specified follow-up windows. It is not itself a measure of antibody response, and it does not establish immunogenicity similarity. The registry record describes the endpoint but does not report its group-specific results, so the observed reactogenicity pattern cannot be assessed from the endpoint description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design and the outcome descriptions allow some statistical concepts to be explained, but the registry record does not provide the full analysis methods. It records random allocation, single masking, and a parallel-group design. These features describe how the comparison was organized; they do not by themselves specify the statistical model, the treatment of missing observations, or the decision rule for the study objective.

What does randomization contribute?

In general, randomization assigns participants by chance to study groups. It is intended to reduce systematic differences in baseline characteristics, so that an outcome contrast is less likely to reflect deliberate selection into a group. Chance imbalances can still occur. The registry does not report the sequence-generation method, allocation concealment procedures, or baseline characteristics needed to evaluate how the groups compared before vaccination.

How should the primary endpoint be understood?

The endpoint is a participant-level count: whether a participant experienced a solicited systemic reaction, with classification based on the maximum severity recorded. This is different from counting every reaction episode. A participant may have more than one type of reaction or may have reactions after more than one vaccination, but the registry description says the overall participant count is reported and grades are based on maximum severity per participant. It does not report the method used to combine observations across the scheduled follow-up windows or the resulting group counts.

For binary outcomes, a common general approach is to compare the proportion of participants with an event in each group. Such a comparison needs a clearly defined denominator, outcome window, and method for estimating uncertainty. The registry supplies the endpoint population definition but does not report the primary endpoint counts or a comparative estimate. No unadjusted re-calculation can therefore be made from the primary endpoint information in the registry record.

What do confidence intervals and tests contribute?

In general, a confidence interval expresses uncertainty around an estimated effect under specified statistical assumptions. A hypothesis test evaluates compatibility of the data with a stated null hypothesis. Neither a confidence interval nor a p-value alone establishes clinical importance, and an absence of a statistically significant result would not by itself prove equivalence or similarity. For a similarity or non-inferiority question, an acceptable margin or other decision criterion must be specified in advance and the estimate interpreted against that criterion. Such a margin and the primary endpoint inferential results are not reported in the registry record.

What can be said about planning calculations?

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are stated as assumptions for an illustration, not as the trial's own design justification. The record does not report a sample-size justification, the target effect used for the original design, or interim analyses. Planning calculations are not observed power and cannot establish the probability that this completed study detected an effect. The numerical planning outputs are not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation in count data exceeds what a chosen statistical model assumes. If a model understates that variation, its uncertainty estimates may be too small. This concept does not establish that over-dispersion occurred in this study. The primary outcome is presented as a count of participants with an event, and the registry record does not report a count model, a dispersion estimate, or an over-dispersion assessment.

The record lists 8 outcome measures and 11 analyses, but those totals do not reveal which statistical procedures were used or how analyses were prioritized. The analysis model, covariate adjustment, confidence interval method, missing-data approach, and multiplicity procedure are not reported in the registry record. Accordingly, the posted descriptive safety counts can be described as reported, but no unsupported inferential analysis should be attributed to the trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 11 analyses. The primary outcome concerns systemic reactogenicity, and the listed secondary outcomes include anti-hepatitis B surface antigen geometric mean titers, anti-hepatitis B surface antigen seroprotection, and anti-rotavirus immunoglobulin A geometric mean titers. With several outcomes or analyses, repeated testing can increase the chance of at least one apparently notable result arising by chance. In general, a prespecified multiplicity strategy can address this concern, but the registry record does not report whether any adjustment or hierarchical testing approach was planned or used.

The registry does not report which analyses were prespecified, whether any were exploratory, or how the primary objective was linked to the secondary outcomes. It also does not report a statistical analysis plan, an analysis hierarchy, or whether any interim analyses occurred. The counts of outcomes and analyses alone are not enough to reconstruct these decisions or infer the degree of multiplicity adjustment.

The primary safety population is described as enrolled participants with safety data available, assigned according to the treatment received at Day 0. The record does not state how participants with missing safety observations were handled, whether outcome data were imputed, or whether sensitivity analyses were conducted. The availability of safety data is therefore part of the population definition, but the extent and consequences of missing data cannot be evaluated from the registry record.

Other analysis populations, including any population used for immunogenicity outcomes, are not reported in the registry record. Nor are exclusions after randomization, protocol deviations, or reasons for missing measurements. These omissions limit assessment of whether results from different outcomes would be comparable and whether missingness could affect interpretation.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.8%), sepsis neonatal (2.0%), jaundice neonatal (1.2%), anemia (0.8%), gastroenteritis (0.8%).

The registry records serious adverse event counts by group, together with the number at risk: BBIBP bOPV Lot 1 had 13 participants affected among 249 at risk; BBIBP bOPV Lot 2 had 16 among 250 at risk; and BioFarma bOPV had 17 among 250 at risk. The record lists deaths as 1 for Lot 1, 0 for Lot 2, and 0 for BioFarma. These are descriptive counts as recorded, not evidence by themselves that vaccination caused an event or that group differences are statistically meaningful.

The counts for other adverse events are 143 among 249 at risk for Lot 1, 142 among 250 at risk for Lot 2, and 151 among 250 at risk for BioFarma. Serious and other adverse events should be kept distinct from the solicited systemic reactogenicity endpoint, which has its own event list and follow-up windows. The registry also lists serious-event terms including Pneumonia (2.8%), Sepsis neonatal (2.0%), Jaundice neonatal (1.2%), Anemia (0.8%), Gastroenteritis (0.8%), and Malaria (0.8%).

The record does not report event-level timing, relatedness assessments, recurrent-event counts, or comparative uncertainty for these safety figures. They should therefore be read as reported observations, not as adjusted comparisons or causal estimates.

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

The trial record describes a randomized comparison of BBIBP bOPV lots with a WHO-prequalified BioFarma comparator in healthy Kenyan infants. It establishes the study's stated objective, vaccination schedules, primary safety endpoint, and selected adverse-event counts. It does not report the primary endpoint's group results or the numerical immunogenicity results needed to assess the stated comparison objective.

Accordingly, the record does not show whether the BBIBP and BioFarma groups had similar immunogenicity, nor whether any observed difference met a predefined standard for similarity. The criterion for such a conclusion is not reported in the registry record. Similarly, the endpoint description alone cannot show how often solicited systemic reactions occurred or how their severity differed by group.

The recorded serious and other adverse event counts provide a descriptive account of events by group. They do not establish that an event was caused by a vaccine, and the registry information presented does not include comparative confidence intervals or a statistical test for those counts. The death counts are also descriptive and do not establish a causal relationship.

In general, a randomized design supports a fairer comparison by reducing systematic allocation differences, but interpretation still depends on complete outcome reporting, prespecified methods, adequate follow-up, and uncertainty estimates. Randomization cannot compensate for missing results in a registry record. It is also important to distinguish a lack of reported evidence from evidence of no effect: because the relevant primary and immunogenicity estimates are not reported, neither a positive nor a negative conclusion about those comparisons follows from this record.

The study is marked completed, but completion status does not itself indicate the direction or reliability of the results. The record supports a description of what was intended and how the study was organized; it does not support a definitive efficacy, immunogenicity, or comparative safety conclusion.

13. Why This Trial Matters Statistically

This trial raises several important statistical distinctions. Its stated objective is about immunogenicity similarity, whereas the designated primary outcome described in the registry is a safety measure based on solicited systemic reactions. Those are different scientific questions and require different outcome data. A study objective cannot be evaluated solely from the title or endpoint description; it needs reported measurements and a decision criterion matched to the objective.

The two BBIBP lots are identified separately, alongside the BioFarma comparator. That structure can be useful for examining consistency across lots, but the registry record does not report the inferential approach for any lot comparison or a rule for combining results. It would be inappropriate to infer a pooling strategy or to treat the lots as interchangeable without reported methods and results.

The endpoint also illustrates why outcome definitions matter. The primary measure concerns participants who experienced any specified reaction and uses each participant's maximum severity. This is not the same as a count of every episode or a measure of antibody response. Follow-up is defined in relation to the week after each vaccination, so interpretation should retain that timing and the distinction between solicited reactions and other adverse events.

Finally, the record shows why uncertainty and complete reporting are central to trial interpretation. Group counts for selected safety outcomes are informative descriptively, but the primary endpoint estimates, immunogenicity results, confidence intervals, and statistical analysis plan are not reported in the registry record. Without those elements, the stated comparison cannot be evaluated statistically. The appropriate conclusion is limited to what the record documents, rather than a claim that the study established similarity or difference.

14. 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.

A central limitation for interpreting this trial from its registry record is that the numerical primary endpoint results are not reported. The record describes systemic reactogenicity by maximum severity and specifies the follow-up windows, but it does not give the group-specific results. The immunogenicity outcomes listed as secondary measures also lack numerical results in the record. This prevents assessment of the study's stated immunogenicity objective and the primary safety comparison.

The registry does not report a similarity or non-inferiority margin, the original sample-size justification, or the statistical analysis plan. It is therefore not possible to determine from this record what degree of difference the study was designed to evaluate, which analyses were primary in the inferential sense, or how estimates and uncertainty were calculated. Details on missing observations, analysis populations for immunogenicity, and sensitivity analyses are also not reported.

Some procedural details are absent, including the randomization sequence method, allocation concealment, who was blinded, and how blinding was maintained. The event descriptions do not provide timing and relatedness for the listed serious adverse events. The registry record also does not explain the relationship among its stated study objective, the primary safety endpoint, and the multiple analyses.

These limitations concern the information available in the registry record; they do not establish that the study itself failed to collect or analyze these data. They do mean that the record alone cannot support a full assessment of comparative immunogenicity, the precision of safety differences, or the robustness of the conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine — NCT02434770.
• Registry record last updated 2020-03-10; status last verified 2020-02.
• Results first posted 2020-03-10.
• 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.

18. Record Summary

The registry identifies NCT02434770 as a completed Phase III randomized, single-blind, controlled, parallel-group study sponsored by PATH. It lists enrollment as 750 and describes healthy Kenyan infants receiving BBIBP bOPV Lot 1, BBIBP bOPV Lot 2, or WHO-prequalified BioFarma bOPV. Each regimen is recorded as 2 drops by mouth in the first two weeks of life and at 6, 10, and 14 weeks of age.

The primary outcome is the number of participants experiencing solicited systemic reactogenicity, classified by maximum severity during the 7 days after each vaccination. The registry also lists immunogenicity outcomes and reports selected adverse-event counts by group. Numerical results for the primary endpoint and the listed immunogenicity outcomes, as well as key statistical methods, are not reported in the registry record. The available information therefore supports a description of the study design and recorded safety counts, but not a conclusion about immunogenicity similarity or the primary endpoint comparison.