A Study to Evaluate Pharyngeal Immunity to Poliovirus Type-2: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Pharyngeal Immunity to Poliovirus Type-2 (NCT05677256), a randomized phase 4 study. The primary outcome is Number of Participants Shedding Detectable Levels of Poliovirus Type-2 by RT PCR..

2. Clinical Question

The study focuses on a laboratory measure of pharyngeal shedding following a challenge dose, not on a clinical diagnosis or a patient-important illness outcome. The registry’s primary outcome is titled as the number of participants shedding detectable levels of poliovirus type-2 by RT PCR. Its description specifies comparisons of presence in pharyngeal samples during the first week and at D14 and D28.

The key contrast is between the two priming schedules before the shared nOPV2 challenge. Thus, the reported difference concerns shedding in these study groups after challenge, within the stated analysis population. It is not a direct comparison of the challenge dose, which both groups received, and the listed primary endpoint does not describe a comparison of clinical disease.

3. Trial Design

This is a completed Phase IV, open-label, randomized, parallel-group study. The registry lists an enrollment of 501. It describes two groups of infants: one primed with IPV and one primed with bOPV. Both groups were scheduled to receive three priming doses at approximately 6, 10, and 14 weeks of age, then an nOPV2-002 challenge at approximately 18 weeks of age. The study intervention is listed as nOPV2.

The registry describes the main purpose as comparing poliovirus type-2 pharyngeal mucosal excretion in the first week and at 2 and 4 weeks following the challenge dose. The primary outcome description gives the corresponding assessment times as the first week, D14, and D28. It identifies RT PCR detection of poliovirus type-2 in pharyngeal samples as the measurement method.

The posted primary outcome counts are 4 participants in the IPV-primed Group, with 234 in the reported group denominator, and 6 participants in the bOPV-primed Group, with 229 in its denominator. These outcome denominators differ from the safety summaries, which list 250 participants at risk in each group. The registry identifies the VSP as the primary virological analysis population and defines it by prior type-2 sample status. It does not report why the primary outcome denominators differ from the safety population figures.

The study is listed as completed, with a start date of 2023-11-09 and primary completion date of 2024-02-20. Masking is listed as none. The registry record does not report the detailed randomization procedure, original sample-size justification, or a full statistical analysis plan.

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: 500 participants started the study, while 501 signed the informed consent. One of them resulted in Screening Failure.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The primary population for the virological analyses was the Viral Shedding Population (VSP) which consisted of all PP Population members who did not contribute a type-2 positive pharyngeal, nasal or stool sample prior to receipt of the nOPV2 challenge dose.

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 Shedding Detectable Levels of Poliovirus Type-2 by RT PCR., measured over 1 month.

The primary endpoint counts participants with detectable poliovirus type-2 in pharyngeal samples by RT PCR. The outcome description refers to the first week, D14, and D28 after the challenge dose, while the registry lists the timeframe as 1 month. The measure is binary at the participant level: a person either contributes to the count of participants with detectable virus or does not, according to the endpoint definition and assessment schedule.

RT PCR is used to detect viral material in a sample. A positive pharyngeal result is therefore a virological finding at the sampled site and time; it is not, by itself, a measure of illness or a complete account of infection at other sites. The study also lists secondary outcomes involving pharyngeal neutralizing antibodies, seroprotection, serious adverse events and important medical events, and poliovirus type-2-specific IgA concentrations. Those outcomes address different aspects of immune response and safety; they do not change what the primary shedding count measures.

General statistical context: a participant count makes the endpoint straightforward to describe, but a count alone is difficult to compare without its denominator. The posted results therefore need to be read alongside the group sizes and the comparison estimate. The table and plot present those summaries. They support interpretation of the observed difference in this study population, while the sampling uncertainty remains important because the number of participants with detectable shedding is small.

7. Results Posted in the Registry

• bOPV-primed Group: 2.6% (6/229) versus 1.7% (4/234) on control; risk difference 0.9 percentage points (95% CI -1.7 to 3.6), risk ratio 1.53 (0.44–5.36); unadjusted two-proportion z-test p = 0.500.

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: the primary endpoint is a binary participant-level outcome, summarized as the number with detectable shedding and the denominator assessed in each group. For this kind of outcome, the event count describes how many participants met the endpoint, while the denominator describes how many participants contributed to that group’s reported result. Both pieces are needed. A count without its denominator does not express how common the outcome was within a group.

What does the risk difference describe?

The risk difference compares the event risks in the two groups by subtracting one group’s risk from the other’s. It is an absolute-scale measure: it expresses the difference in outcome probability between groups rather than how many times larger one risk is than another. The posted estimate is 0.009, with the bOPV-primed Group as the comparison group against the IPV-primed Group. The associated confidence interval extends from -0.017 to 0.036. Because zero is included, the data are compatible with no difference as well as with values on either side of zero. The sign and size of an estimate should be read together with its uncertainty interval.

How do relative measures differ?

A risk ratio expresses one group’s risk relative to the other group’s risk; an odds ratio compares the odds of the event. These measures use a relative scale, unlike the risk difference. The registry comparison gives a risk ratio of 1.533 with a confidence interval from 0.438 to 5.36, and an odds ratio of 1.547 with a confidence interval from 0.431 to 5.556. The intervals are broad and include the no-association value for each relative measure. With few events, relative estimates may be especially unstable: a small change in the number of events can materially change the estimate. For that reason, the counts and absolute-risk comparison remain important companions to relative measures.

What does the p-value say?

The posted unadjusted p-value is 0.5. General statistical context: a p-value describes how unusual data at least as inconsistent with a specified null model would be if that model were true, under the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not quantify the probability that the result arose by chance in a simple everyday sense. The p-value does not measure the size or importance of a difference. Here, it should be considered alongside the point estimates and broad confidence intervals. The registry record does not report the exact test used or whether any adjustment beyond the unadjusted comparison was applied.

Why is a confidence interval useful?

General statistical context: a confidence interval gives a range of values reasonably compatible with the observed data and the method’s assumptions. Its width conveys precision: a narrow interval indicates greater precision than a wide interval. An interval that includes the no-difference value does not prove the groups are the same. It indicates that the data do not rule out that value at the confidence level used. The confidence level for this comparison is not stated in the registry record, so it should not be inferred.

What is the analysis population?

The registry identifies the VSP as the primary population for virological analyses. It consists of PP Population members who did not contribute a type-2 positive pharyngeal, nasal, or stool sample before the nOPV2 challenge dose. This definition matters because it sets which participants can contribute to the primary shedding analysis. The posted outcome denominators are 234 and 229, whereas the safety summaries show 250 at risk in each group. The registry record does not explain the difference between these populations or give a detailed account of exclusions and missing assessments.

What are the limits of the posted analysis details?

The registry lists the primary endpoint and the comparison summaries, but does not report a full statistical analysis plan, the detailed method used to calculate the intervals, or an adjustment strategy for multiple outcomes or time points. It also does not report how missing samples were handled. These details can affect how a result is interpreted, especially when an outcome is assessed at multiple times and several secondary outcomes are listed. The record lists four secondary outcomes and five outcome measures overall, but does not state how multiplicity was handled. General statistical context: when multiple hypotheses are examined, the chance of at least one apparently notable finding can increase unless the analysis plan accounts for the multiplicity. That is a general consideration, not a claim about an undocumented procedure in this trial.

Randomization can reduce systematic differences between groups on average, but the registry does not give the sequence-generation or allocation-concealment details. The study is open-label, with masking listed as none. The primary endpoint is based on laboratory testing, but the registry record does not describe laboratory masking or assay procedures in detail. These omissions limit what can be established about the conduct and analysis from the registry record alone.

10. Confidence Intervals and Precision

The most direct precision summary for the primary outcome is the confidence interval around the risk difference. The point estimate is 0.009, and the interval runs from -0.017 to 0.036. It crosses zero, so the range includes a small difference in one direction, no difference, and a difference in the other direction. The interval therefore does not isolate a single conclusion about the direction of the group contrast.

General statistical context: a confidence interval is a measure of uncertainty around an estimate, not a guarantee that the true value lies within that particular calculated interval. Under the method’s assumptions, the interval procedure is designed to cover the underlying parameter at its stated confidence level over repeated samples. The registry record does not state the confidence level or interval method. The interval should therefore be read as posted, without assuming an undocumented calculation procedure.

The relative estimates are also imprecise. The risk ratio interval runs from 0.438 to 5.36, and the odds ratio interval runs from 0.431 to 5.556. Both cover the no-association value and include a broad range of possible relative effects. The small event counts are important context for these wide intervals. A point estimate alone can make the comparison seem more definite than the data support.

The posted results do not support a claim of equivalence: that would require an appropriate equivalence framework and prespecified margins, which are not reported in the registry record. Nor do the intervals establish that a meaningful difference exists. They show uncertainty around the comparison. The calculated table and plot display the point estimate and uncertainty visually; the numerical interval remains the clearest way to see how little precision the comparison provides.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size table and curve are planning illustrations based on the observed effect, not the original trial design. For this binary outcome, the entries are participants per arm, not total event counts. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each row plans for a specified fraction of the observed effect: the full observed effect, 75% of the observed effect, or 50% of the observed effect. The registry record does not report the trial’s own original sample-size assumptions or justification.

The 80% power column gives the participants per arm in the planning illustration for a design with 80% probability of detecting the specified effect under the stated assumptions, if that effect is truly present. The 90% power column gives the corresponding per-arm number for a design with 90% probability under those same assumptions. These are design targets, not statements about the probability that the posted result is correct. This is not observed power.

The table and curve show that planning to detect smaller effects requires more participants. This follows because a smaller difference is harder to distinguish from sampling variation, all else being equal. The illustrations use fractions of the observed effect, so they inherit uncertainty from the observed estimate. In particular, the primary comparison is based on few shedding events and has a broad confidence interval. The planning figures should therefore be treated as conditional illustrations, not as a recommended enrollment target or as proof that a particular study size would settle the question.

These calculations do not reconstruct the completed trial’s design. The registry record does not report its original power target, anticipated effect, or sample-size rationale. The posted enrollment and the analysis denominators are descriptive details; they are distinct from the hypothetical per-arm planning values in the table.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.017; treatment proportion p₁ = 0.026; average p̄ = 0.022.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.2058 = 0.4034.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.2057 = 0.1731.
4. n = (0.4034 + 0.1731)² / (0.0091)² = 4,007.5, rounded up to 4,008 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 <- 0.0170940170940171                          # control proportion
p1 <- 0.0262008733624454                          # 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(5677256)
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 = 4,008 (80% power), 5,365 (90% power)
 75% of observed effect: n per arm = 6,759 (80% power), 9,048 (90% power)
 50% of observed effect: n per arm = 14,381 (80% power), 19,251 (90% power)
power.prop.test: 4007.5 
Simulated power at n = 4,008 per arm: 0.806 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary shedding outcome and four secondary outcomes: pharyngeal neutralizing antibodies to poliovirus type-2; seroprotection rate to poliovirus type-2 on D0, D28, and D56 in both groups; participants experiencing serious adverse events and important medical events; and pharyngeal poliovirus type-2-specific IgA concentrations. The record lists five outcome measures overall. Assessments at multiple time points and multiple outcomes create more than one opportunity to observe a result that appears noteworthy.

The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a strategy for deciding which comparisons are confirmatory. It is therefore not possible from this record to determine whether results across outcomes or time points were adjusted or how they were intended to be interpreted together. General statistical context: multiplicity procedures can control the overall chance of false-positive conclusions across a defined family of tests, while a prespecified hierarchy can distinguish primary from secondary questions. No such plan should be assumed.

The registry identifies the VSP as the primary population for virological analyses and describes who could enter that population. It does not report details about missing samples, participant flow into the VSP, or the analysis population used for each secondary outcome. The primary outcome denominators are 234 and 229; the safety summaries list 250 at risk in each group. The record does not explain these differences, and it does not state whether missing observations were excluded, imputed, or handled in another way.

The record also does not report the full statistical analysis plan, the exact test behind the posted unadjusted p-value, or the confidence interval method. The study is randomized and open-label, with no masking listed, but detailed sequence generation and concealment procedures are not reported in the registry record. These gaps limit a full assessment of analysis choices and potential sources of bias. They do not invalidate the posted summaries, but they mean that interpretation should remain tied to the outcome definitions and analysis details that are actually documented.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (1.2%), gastroenteritis (0.4%), pneumonia aspiration (0.4%), diarrhoea (0.4%), febrile convulsion (0.4%).

The safety summary lists 250 participants at risk in each group. It reports serious adverse events in 5 participants in the IPV-primed Group and 2 participants in the bOPV-primed Group. The summary records 0 in the other adverse-event category for each group and 0 deaths in each group. The serious-event counts are descriptive; the registry record does not provide a comparative safety analysis or a confidence interval for the difference.

The listed serious-event terms are Pneumonia at 1.2%, Gastroenteritis at 0.4%, Pneumonia aspiration at 0.4%, Diarrhoea at 0.4%, and Febrile convulsion at 0.4%. These are registry-listed terms and percentages; the record does not identify which group each term occurred in within the summary. The percentages should not be treated as group-specific rates unless the registry explicitly labels them that way.

General statistical context: event counts in a safety summary describe what was observed during the recorded period, but small counts provide limited precision for comparing groups or detecting uncommon events. The registry record does not provide detailed event timing, causality assessments, exposure-adjusted rates, or a fuller account of follow-up for these summaries. These figures should therefore be read as a concise description of reported events, not as a complete assessment of safety or evidence that an event was caused by a particular intervention.

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

The posted result answers a focused question: how many participants in each defined analysis group had detectable poliovirus type-2 in pharyngeal samples by RT PCR after an nOPV2 challenge. The counts are 4 in the IPV-primed Group and 6 in the bOPV-primed Group, with outcome denominators of 234 and 229. The reported risk difference is 0.009, with a confidence interval from -0.017 to 0.036, and the unadjusted p-value is 0.5. Together, these summaries show a small observed absolute difference with substantial uncertainty.

The result does not establish that the priming schedules are equivalent. The registry record does not report an equivalence margin or an equivalence analysis, and the confidence interval allows values on both sides of zero. It also does not establish a clear difference: the interval includes zero, and the unadjusted p-value does not provide strong evidence against the no-difference model. The data are therefore inconclusive about the direction and size of the underlying contrast.

The endpoint is a laboratory measure of pharyngeal shedding after a challenge dose. It is not a measure of clinical poliomyelitis, symptoms, or disease severity. The primary outcome does not describe shedding at every body site, and its interpretation is limited to the specified sampling schedule and the VSP definition. The secondary outcomes listed in the registry address other immunologic measures and safety events, but their results are not included in the registry record.

General statistical context: a lack of strong evidence in a study is not the same as evidence that no effect exists. Broad intervals can reflect limited information, particularly when few participants meet the endpoint. Conversely, an observed difference should not be treated as a stable estimate when uncertainty is substantial. The most defensible reading is descriptive: the posted counts are close, while the comparison remains imprecise.

These findings concern the trial’s groups, challenge conditions, endpoint definition, and analysis population. They should not be generalized beyond that setting without evidence from additional analyses or studies. The registry record does not provide the detail needed to assess all aspects of implementation, missing-data handling, or the statistical plan.

16. Why This Trial Matters Statistically

This trial illustrates why clinical researchers should read a binary outcome together with its denominator and uncertainty interval. The observed counts alone are 4 and 6, but the group denominators differ, and the comparison summary expresses the result on absolute and relative scales. The risk difference makes the absolute contrast visible, while the risk ratio and odds ratio express relative contrasts. Because the event counts are low, all of these estimates need to be considered with their uncertainty rather than interpreted as exact quantities.

The example also shows that a non-significant comparison is not the same as evidence of equivalence. The risk-difference interval includes zero and extends in both directions. The relative intervals are broad and include their respective no-association values. This combination makes precision central to interpretation: the point estimates are not enough to resolve whether there is a meaningful difference in the population.

From a design perspective, the sample-size illustrations demonstrate how planning depends on the effect a study aims to detect. The figures are conditional on the observed effect and stated planning assumptions; smaller effects require more participants in the illustration. They are not a record of the trial’s original design rationale, which is not reported in the registry record. This distinction matters when readers compare a completed study’s enrollment with a hypothetical future design.

The registry also illustrates how analysis populations can differ across outcomes. The primary virological population is defined by pre-challenge sample status, while the safety summaries list 250 participants at risk in each group. The record does not explain the denominator differences. Transparent reporting of population definitions, participant flow, and missing-data methods is important for understanding what each estimate represents.

Finally, open-label conduct, multiple listed outcomes, and limited analysis details are reasons to read registry findings within their documented scope. Statistical interpretation is strongest when effect estimates, uncertainty, endpoint definitions, and analysis choices are considered together.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary comparison has limited precision: the event counts are 4 and 6, and the risk-difference interval extends from -0.017 to 0.036. The registry does not report a confidence level or the method used to calculate this interval. The record also does not report the exact test behind the unadjusted p-value, so the comparison cannot be independently appraised from the registry description alone.

The primary analysis is restricted to the VSP, defined using membership in the PP Population and absence of a type-2 positive pharyngeal, nasal, or stool sample before challenge. The registry does not provide participant flow into this population, explain why the primary outcome denominators are 234 and 229 while 250 participants per group appear in the safety summary, or describe how missing samples and incomplete follow-up were handled.

The study is open-label, and the registry lists no masking. It does not describe whether laboratory personnel were masked to group assignment, the details of allocation concealment, or the laboratory assay procedures. Those matters cannot be inferred from the randomized designation or from the endpoint name.

Several secondary outcomes are listed alongside assessments at more than one time point. The registry record does not state a multiplicity strategy, how secondary outcomes were prioritized, or which analyses were prespecified. It also does not report the original sample-size justification, interim analyses, or a complete statistical analysis plan. The planning table is based on the observed effect and does not fill those gaps. These limitations constrain interpretation of the posted summary and do not establish that unreported procedures were or were not used.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study to Evaluate Pharyngeal Immunity to Poliovirus Type-2 — NCT05677256.
• Registry record last updated 2026-09-03; status last verified 2026-09.
• Results first posted 2026-09-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

NCT05677256 is a completed Phase IV, open-label, randomized, parallel-group study sponsored by Fidec Corporation. It enrolled 501 and compared infants primed with IPV or bOPV before both groups received an nOPV2-002 challenge dose. The posted primary outcome concerns pharyngeal poliovirus type-2 detection by RT PCR following challenge.

The primary outcome counts are 4 of 234 in the IPV-primed Group and 6 of 229 in the bOPV-primed Group. The comparison summary reports a risk difference of 0.009, with a confidence interval from -0.017 to 0.036, and an unadjusted p-value of 0.5. The interval is compatible with differences in either direction, and the estimate is imprecise.

The registry also lists secondary immunologic and safety outcomes. Safety summaries report serious adverse events in 5 participants in the IPV-primed Group and 2 in the bOPV-primed Group, with 0 deaths in either group. Detailed methods for missing data, multiplicity, and the original sample-size plan are not reported in the registry record.