Immunogenicity and Safety Study of Rotarix TM in Taiwanese Infants Who Received Hepatitis B Immunoglobulin After Birth.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety Study of Rotarix TM in Taiwanese Infants Who Received Hepatitis B Immunoglobulin After Birth. (NCT01198769), a na phase 4 study. The primary outcome is Number of Seroconverted Subjects for Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody..

2. Clinical Question

The question is about an antibody response after vaccination, not about prevention of rotavirus illness. The endpoint counts participants whose measured antibody concentration meets the registry definition. It does not, by itself, describe whether participants developed gastroenteritis, how severe any illness was, or how long an antibody response lasted beyond the stated assessment time.

The study record identifies 15 enrolled participants and one Rotarix Group. It lists safety and other immunogenicity outcomes, but the primary endpoint result is not reported in the registry record. The registry also reports no analyses. As a result, the central question can be described from the protocol-style endpoint definition, but the posted record does not show how many participants met that definition or how uncertain that result is.

3. Trial Design

This was a Phase 4, completed, single-group study sponsored by GlaxoSmithKline. The registry lists 15 participants as enrolled and one intervention, Rotarix TM. Its arm description states that participants received 2 oral doses at 2 and 4 months of age. The study was not masked, and allocation is recorded as NA. There was no concurrent control group, so the record does not support a direct treatment-versus-control comparison.

The study focused on healthy Taiwanese infants who received hepatitis B immunoglobulin after birth. The brief description specifies an age range of 6 to 12 weeks at the first vaccination. The planned primary immunogenicity assessment was 2 months after Dose 2, at study Month 4. The registry also lists serum anti-rotavirus IgA concentrations, solicited general symptoms, rotavirus in gastroenteritis stool samples, unsolicited adverse events, and serious adverse events among the secondary outcomes.

The registry records the study as completed. Its listed start date is 2010-11-11, and its primary completion date is 2011-04-18. These dates describe the record; they do not provide additional information about participant follow-up or the timing of every secondary assessment.

The record does not report a randomized allocation method, a masking procedure, or a comparator arm. The study's sample-size justification and detailed statistical plan are not reported in the registry record. The posted analysis count is 0, and the primary endpoint result is not reported in the registry record. These omissions matter: a completed status does not establish that every planned result is available in the registry, and enrollment alone does not show how many participants contributed data to a particular endpoint.

Because the design is single-group, any outcome describes the enrolled participants under the study conditions. Without a control group, changes in antibody measurements or observed events cannot be separated from other influences using a concurrent comparison. The study can still describe the recorded immune-response and safety outcomes in this population, but the registry results do not provide a comparative estimate.

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: The According-To-Protocol cohort for immunogenicity included subjects who received Hepatitis B immunoglobulin after birth, who were seronegative for serum anti-RV IgA antibody at Day 0, who complied with vaccination schedule for the Rotarix vaccine, who had no RV other than the vaccine strain in gastroenteritis stool sample up to Month 4.

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 Seroconverted Subjects for Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody., measured over 2 months post-Dose 2 (at study Month 4).

The primary endpoint is the number of subjects with seroconversion for serum anti-rotavirus immunoglobulin A, or IgA. The assessment is specified for 2 months post-Dose 2, at study Month 4. Seroconversion is defined as an IgA concentration of at least 20 U/mL in a participant whose concentration was below 20 U/mL before vaccination. Thus, the endpoint is a count of participants crossing a prespecified antibody threshold, rather than a comparison of average antibody concentrations.

This kind of threshold-based endpoint is used to summarize whether an immune marker reaches a defined level after vaccination. It makes the endpoint's classification rule explicit, but it does not describe the full distribution of antibody concentrations. Two participants with concentrations above the threshold may have different measurements and still both count as seroconverted. Conversely, a small change that remains below the threshold does not meet this endpoint definition.

The registry specifies the According-To-Protocol cohort for immunogenicity. It describes participants who received hepatitis B immunoglobulin after birth, were seronegative at Day 0, complied with the vaccination schedule, and met further criteria. The population text is cut off in the registry record, so its full eligibility description is not available.

The primary endpoint result is not reported in the registry record. Consequently, the posted information does not show the number who seroconverted, the number assessed, or an estimate of uncertainty around the count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is this?

The primary endpoint is binary at the participant level: each eligible participant either meets the seroconversion definition or does not. The reported quantity is the number of participants meeting that definition. This is different from an endpoint that reports the average antibody concentration, and it is different from a time-to-event outcome. A threshold turns a continuous laboratory measurement into a yes-or-no classification. The registry defines the threshold as at least 20 U/mL, with seronegativity before vaccination defined as below 20 U/mL.

In general, a threshold can make an outcome easier to interpret as a defined response category, but it also discards information about how far measurements lie above or below the cutoff. The record's secondary outcome of serum anti-rotavirus IgA antibody concentrations could describe measurements beyond the primary classification, but its results are not reported in the registry record.

What would a count need in order to be interpretable?

A participant count needs a clearly described analysis population and denominator. Here, the primary population is identified as the According-To-Protocol cohort for immunogenicity and is described as including participants who were seronegative at Day 0 and complied with the vaccination schedule. The description is truncated, so the full criteria are not reported in the registry record. The number enrolled is 15, but that is not necessarily the denominator for this cohort. The registry does not report how many participants were included in the primary endpoint analysis or how missing measurements were handled.

In general, a proportion is often easier to interpret than a count when the denominator is known, but no proportion should be reconstructed because the primary numerator and analysis denominator are absent. A count without its relevant denominator would not show the frequency of seroconversion in the analysis population.

Why does the single-group design matter?

The study has one group and no concurrent control. Its allocation field is NA and masking is none. A single-group result can describe outcomes among participants who received the study intervention, but it cannot directly estimate a difference from an untreated or alternative-treatment group. In general, a comparator helps distinguish an outcome observed after treatment from outcomes that might also occur for other reasons. Without one, the registry's posted information cannot make that distinction through a between-group analysis.

The open-label design also means that masking was not used. The registry does not describe procedures to reduce the influence of awareness of treatment assignment on assessments. This is more relevant to outcomes requiring judgment or reporting than to a laboratory measurement, although the record does not provide enough detail to evaluate assessment procedures. It would be inappropriate to infer additional design safeguards that are not described.

What statistical analysis is reported?

The registry reports 0 analyses. It does not report an analysis method for the primary endpoint, an inferential test, a confidence interval, or an adjusted estimate. The sample-size justification and full statistical plan are not reported in the registry record. In general, a confidence interval communicates statistical precision by showing a range of values compatible with a specified analysis; without a posted estimate and interval, the precision of the primary endpoint cannot be assessed from this record.

The outcome is a count, and the study includes only one group. In general, analyses of binary outcomes may summarize counts and proportions, while comparative analyses require suitable data from more than one group. Which method was planned or used is not reported in the registry record. It is therefore not possible to attribute a specific statistical procedure to the investigators.

How should the planning illustration be read?

The sample-size section is a planning illustration based on an observed effect, not the trial's own design calculation. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The registry's study itself had one group, so that hypothetical two-arm setup is not a description of the trial design.

In general, a sample-size calculation asks how much information a hypothetical design might need to detect a specified effect under stated assumptions. Such a calculation is not observed power and does not show the probability that the completed study detected an effect. Planning counts should not be read as participant counts actually enrolled, nor as evidence that the study was adequately powered. The trial's own sample-size justification is not reported in the registry record.

General statistical concepts such as over-dispersion apply when observed variability exceeds that expected under a chosen model. The registry record does not report a model or an over-dispersion assessment for this endpoint, and the primary result is absent. There is therefore no basis to describe over-dispersion as a feature of this study's analysis.

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("Rotarix Group")
n      <- c(15)
events <- c(15)
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  Rotarix Group  15  15  100.0  78.2  100.0  79.6  100.0  79.4  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary immunogenicity outcome and several secondary outcomes: serum anti-rotavirus IgA antibody concentrations, solicited general symptoms, rotavirus present in a gastroenteritis stool sample, unsolicited adverse events, and serious adverse events. It reports 6 outcome measures but 0 analyses. The registry does not describe whether or how the investigators planned to account for multiple outcomes, repeated assessments, or multiple statistical tests. Multiplicity handling is not reported in the registry record.

In general, when many outcomes or tests are examined, the chance of obtaining an apparently notable result by chance can increase. Statistical plans may address this in different ways, but the record does not state that any particular approach was used. The absence of an analysis description also means that no test hierarchy or distinction between confirmatory and exploratory analyses can be established from the registry information.

Missing-data handling for the primary endpoint is not reported in the registry record. The registry identifies an According-To-Protocol immunogenicity cohort, but does not report its final size or the number with a result at the specified assessment. It also does not describe exclusions, imputation, or sensitivity analyses. These details affect how a count should be interpreted because the enrolled population and the analyzed population can differ.

The record's population description ends mid-sentence, so the full primary analysis criteria are not available. It is also not clear from the posted results whether all listed secondary outcomes were assessed in every participant or at which exact timepoints. The endpoint-specific follow-up and missingness are not reported in the registry record.

In general, analysis-population definitions and missing-data methods help readers understand which participants contribute to each estimate and how incomplete observations are treated. Here, the record identifies the intended primary cohort in part but provides no endpoint analysis or supporting detail. These omissions limit assessment of both the analysis population and the robustness of any result.

12. Safety Results

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

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: bronchiolitis (6.7%).

The registry lists 15 participants at risk for serious adverse events in the Rotarix Group and 1 participant affected. It also identifies Bronchiolitis at 6.7% among the top serious terms. These figures describe the recorded safety information for the single study group. They are not a comparison with an untreated group or another vaccine group.

A serious adverse event is a safety category, but the registry entry alone does not establish that the event was caused by the intervention. The record does not provide a causal assessment in the information. The listed term should therefore be read as an event reported in the study, rather than as proof of a treatment-related effect.

The other adverse-event summary lists 15 at risk and 13 affected. Those figures concern a different safety grouping and should not be merged with the serious-event count. The registry also lists outcomes for solicited general symptoms and unsolicited adverse events, but the detailed results for these outcomes are not reported in the registry record.

In general, safety counts from a small, single-group study are descriptive. Without a concurrent comparator, they cannot show whether observed events occurred more or less often than they would under another condition. The posted data should be read as a record of observed events, not as a causal or comparative estimate.

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

This record establishes that a completed Phase 4 study examined immunogenicity and safety of Rotarix TM in healthy Taiwanese infants who received hepatitis B immunoglobulin after birth. It specifies a two-dose oral schedule and defines the primary endpoint as seroconversion for serum anti-rotavirus IgA at the stated post-vaccination assessment. It also gives descriptive safety counts for the study group.

What the record does not show is the primary endpoint result. The number of participants meeting the seroconversion definition is not reported in the registry record, and neither is the number included in the primary immunogenicity analysis. No confidence interval or inferential analysis is posted. The record therefore cannot establish the size or precision of the observed immune response.

The study also does not provide a concurrent control group. Its results, even if the primary endpoint count were available, would describe outcomes in the enrolled group rather than a direct contrast with another group. The registry information does not support a causal treatment comparison. The safety figures are likewise descriptive, and the listed serious adverse event does not by itself establish attribution to vaccination.

These limitations do not erase the value of a clearly defined population and endpoint. They do mean that interpretation must stay close to the information actually recorded. The completed status and the enrollment count are not substitutes for an outcome result. Nor do the planning illustrations on the page establish the study's original design justification or its observed power.

In short, this is a small, single-group record with a specified immunogenicity question, a defined antibody threshold, and some posted safety counts. The primary outcome result, analysis details, and full analysis population are not available in the registry record. The record can therefore inform readers about what was intended to be measured and which safety observations were listed, but not about the numerical primary response or a comparative effect.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a well-defined endpoint and a reported result. The registry gives a specific seroconversion rule: an initially seronegative participant must have serum anti-rotavirus IgA at or above the stated threshold at the specified follow-up. That definition clarifies what would count as an endpoint event. However, without the resulting count and analysis denominator, readers cannot evaluate the observed response.

The record also illustrates why design matters to interpretation. A single group can yield descriptive counts, but it does not offer a concurrent reference for separating outcomes associated with treatment from other influences. The absence of masking is another design feature to consider, particularly for outcomes based on symptoms or event reporting. The registry does not give enough detail to characterize any additional assessment safeguards.

Small enrollment makes transparent reporting of denominators and uncertainty especially useful. The record reports 15 enrolled, but does not state the number in the primary immunogenicity cohort or the number with an evaluable Month 4 result. In general, the denominator and a measure of precision help readers understand how stable a count might be. Neither is reported for the primary endpoint.

Finally, the sample-size illustrations serve a different purpose from an account of the study's actual design. They are hypothetical planning calculations, while the registry's trial is single-group and its design justification is not reported. Keeping those roles separate prevents a planning exercise from being mistaken for observed evidence. Together, these features make the record a useful case for careful reading of endpoint definitions, analysis populations, and the boundary between descriptive findings and comparative inference.

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 central limitation for interpreting this trial record is that the primary endpoint result is not reported in the registry record. The count of participants who seroconverted, the analysis denominator, and any measure of uncertainty are all absent. The record reports 15 enrolled, but does not establish that all enrolled participants contributed to the primary endpoint.

The primary analysis population description is incomplete. It identifies an According-To-Protocol immunogenicity cohort and lists some criteria, but the text ends mid-sentence. The complete set of eligibility and analysis rules is not reported in the registry record. The number excluded from that cohort and the reasons for any exclusions are also not reported.

The design is single-group, with no comparator and no masking. This limits comparative and causal interpretation of both immunogenicity and safety observations. The registry does not report the investigators' sample-size justification, detailed statistical plan, methods for handling missing measurements, or any multiplicity strategy. It lists 0 analyses, leaving no posted inferential results to assess.

Safety results are limited to descriptive counts in the registry information. The record lists 1 participant affected by a serious adverse event among 15 at risk and gives Bronchiolitis at 6.7% among the top serious terms. It does not provide a concurrent reference group, and the listed information does not establish causality. The detailed results for the listed symptom and adverse-event outcomes are not reported in the registry record.

The endpoint is a threshold classification at one stated timepoint. It does not summarize the complete distribution of antibody measurements or establish later persistence. The secondary antibody-concentration results and other outcome details are not reported in the registry record. These gaps restrict interpretation to the design, definitions, and descriptive safety entries that are posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Immunogenicity and Safety Study of Rotarix TM in Taiwanese Infants Who Received Hepatitis B Immunoglobulin After Birth. — NCT01198769.
• Registry record last updated 2018-08-20; status last verified 2016-09.
• Results first posted 2012-04-17.
• 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 Phase 4, single-group study of Rotarix TM in healthy Taiwanese infants who received hepatitis B immunoglobulin after birth. It lists 15 enrolled participants, no masking, and an oral two-dose schedule at 2 and 4 months of age.

The primary endpoint was the number of participants with serum anti-rotavirus IgA seroconversion 2 months after Dose 2, at study Month 4. The result and analysis denominator are not reported in the registry record. The record lists 0 analyses and does not provide the study's sample-size justification or detailed statistical plan.

For safety, the Rotarix Group lists 15 participants at risk for serious adverse events and 1 affected participant; Bronchiolitis is listed at 6.7% among the top serious terms. These are descriptive observations without a comparator. The record supports a description of the study design and endpoint definition, but not a numerical interpretation of the primary immunogenicity result.