Evaluation of Reactogenicity and Safety of GSK Biologicals' Rotarix™ (Human Rotavirus Vaccine) in Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Reactogenicity and Safety of GSK Biologicals' Rotarix™ (Human Rotavirus Vaccine) in Infants (NCT00779779), a registered phase not stated study. The primary outcome is Number of Subjects With at Least One >= Grade "2" Fever, Vomiting or Diarrhoea.

2. Clinical Question

3. Trial Design

This was a completed post-marketing surveillance study sponsored by GlaxoSmithKline. The registry lists the study start as 2008-11-22 and primary completion as 2009-05-25. Its stated focus was collecting reactogenicity and safety information in healthy infants receiving human rotavirus vaccine. Enrollment was 522.

The intervention was Rotarix, administered orally in two doses. The first dose was given from 6 weeks of age, with at least 4 weeks between doses; both doses were to be completed by 24 weeks of age. The registry describes one Rotarix group. It does not state an allocation method or identify a control arm. The registry record therefore does not support interpreting these data as a randomized, controlled treatment comparison.

The primary outcome counted subjects with at least one grade 2 or higher fever, vomiting, or diarrhoea during an 8-day solicited follow-up period. Secondary outcomes included the number of subjects reporting each type of solicited general symptom, unsolicited adverse events, and serious adverse events. The record lists four outcome measures overall, but does not report the primary outcome count or secondary outcome results beyond the adverse-event information described in the safety record.

Analysis was specified for the Total Vaccinated Cohort, defined as vaccinated subjects with at least one vaccine administration documented. That population definition does not establish how many subjects completed both doses or contributed information for each outcome. Dose completion and outcome-specific denominators are not reported in the registry record. The record also does not report a comparator, randomization, blinding, or a detailed 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the Total Vaccinated Cohort, which consisted of all vaccinated subjects with at least one vaccine administration documented.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With at Least One >= Grade "2" Fever, Vomiting or Diarrhoea, measured over During the 8-day solicited follow-up period.

The primary endpoint counts subjects who experienced at least one grade 2 or higher fever, vomiting, or diarrhoea during the 8-day solicited follow-up period. It is a participant count: a subject meeting more than one symptom criterion still contributes to the endpoint as a subject with at least one qualifying event. The registry does not report the observed count for this endpoint.

The grade definitions distinguish symptom intensity by observable criteria. Grade 2 fever was an axillary temperature above 38.0 to 39.0 degrees Celsius; grade 3 fever was above 39.0 degrees Celsius. Grade 2 vomiting meant 2 episodes per day, while grade 3 meant 3 or more episodes per day. Grade 2 diarrhoea meant 4-5 looser than normal stools per day, and grade 3 meant 6 or more looser than normal stools a day.

As a general statistical matter, combining several symptoms into one endpoint can describe whether a participant experienced any event meeting the stated criteria. The resulting count does not show which symptom occurred unless symptom-specific results are also reported. The endpoint is useful for summarizing solicited events within a defined follow-up period, but it is not a measure of every possible adverse event or of events outside that period. The registry record does not report the primary endpoint result, symptom-specific counts for this endpoint, or a confidence interval.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives outcome definitions and a population definition, but does not report a full statistical analysis plan. The interpretation below separates what the record states from general explanations of statistical ideas.

What does a participant count represent?

The primary endpoint is a count of subjects who experienced at least one qualifying symptom. This differs from a count of all episodes: a participant with repeated symptoms is still counted once for the combined endpoint. The measure is binary at the participant level—each subject either meets the endpoint definition or does not—and then summarized as a number of subjects. The registry record does not report the resulting primary count.

General statistical explanation: a binary outcome can be summarized as a count and, when the denominator is known, as a proportion. A proportion can describe how common an event was in a defined group and period. It does not by itself show whether the intervention caused the event, because a causal comparison requires a suitable counterfactual, usually represented by a comparison group or another valid design. This registry record describes one vaccine group and does not report a comparator.

Why does the follow-up window matter?

The primary endpoint applies to the 8-day solicited follow-up period. The definition is therefore time-bounded: it concerns the specified symptoms during that window, not all possible events over an unspecified period. The registry also lists other adverse-event outcomes, including unsolicited adverse events and serious adverse events, but the result descriptions do not establish a common follow-up period for those counts.

General statistical explanation: event counts can only be compared meaningfully when the observation windows and event definitions are aligned. A longer observation period creates more opportunity to record events. The record does not provide enough detail to assess the duration of observation for each safety measure.

How should a confidence interval be understood?

No confidence interval is reported for the primary endpoint or for the adverse-event counts. General statistical explanation: a confidence interval expresses the uncertainty around an estimate under a specified statistical model and sampling process. It is not a guarantee that the true value lies within the interval, and it does not remedy limitations such as lack of a comparison group or incomplete outcome reporting. Without a reported estimate and interval, the precision of the primary result cannot be assessed from this record.

For uncommon events, estimates can be imprecise even when a study includes many participants, because relatively few participants experience the event. General statistical explanation: the uncertainty around rare-event estimates depends strongly on the number of observed events and the analytic approach. The record reports one subject with a serious adverse event, but provides no interval estimate or inferential analysis for that count.

What can the analysis population tell us?

The primary analysis population was the Total Vaccinated Cohort, defined as all vaccinated subjects with at least one vaccine administration documented. This identifies who was eligible for the primary analysis in general terms. It does not say how many subjects had complete follow-up, received both doses, or had data available for each endpoint. Those outcome-specific counts are not reported in the registry record.

General statistical explanation: an analysis population affects the meaning of an estimate. A population that includes all participants who began an intervention answers a different question from one restricted to participants who completed the intended course. The record does not describe additional analysis populations or explain how missing outcomes were handled.

What do the planning illustrations mean?

Any sample-size planning illustrations are not observed results and are not evidence of observed power. The stated assumptions describe 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. For time-to-event outcomes, the stated convention is to give the total number of events; for other outcomes, it is participants per arm. Those assumptions are not a description of this study's design: the registry record describes one group, and its own sample-size justification is not reported.

General statistical explanation: a planning calculation asks what sample size would be needed under specified assumptions. It does not establish that a study had adequate power after completion, and it does not replace a reported effect estimate with uncertainty. A planning illustration based on an observed effect is especially dependent on that effect estimate and should not be confused with a prospective design rationale. The registry record does not report the study's sample-size justification or a formal power analysis.

The record lists zero analyses. That entry does not provide results for the listed outcomes, nor does it establish which statistical methods were used for the descriptive safety counts. No model, adjustment method, hypothesis-testing procedure, or confidence-interval method is reported in the registry record. In general, method details are needed to judge how estimates were produced and what assumptions support them.

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(522)
events <- c(78)
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  522  78  14.9  12.0  18.3  12.1  18.3  12.1  18.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary endpoint and secondary safety outcomes. It does not report a multiplicity strategy, such as a prespecified adjustment for testing several outcomes, or explain whether the outcomes were intended to support confirmatory claims. The record lists zero analyses. Consequently, there is no reported set of outcome-specific tests from which to assess how multiple testing was handled.

General statistical explanation: when several hypotheses are tested, the chance of obtaining at least one apparently notable result can increase if each test is interpreted independently. Adjustment methods can address that concern, but their relevance depends on the study questions and planned analysis. In the absence of a reported plan and test results, no conclusion about multiplicity control is possible.

The primary analysis population is the Total Vaccinated Cohort, meaning vaccinated subjects with at least one vaccine administration documented. The registry record does not describe missing-data handling, exclusions, endpoint-specific denominators, or whether follow-up was complete for all subjects. It also does not state how participants with incomplete symptom diaries or other missing observations, if any, were treated. Missingness and its handling are therefore not reported in the registry record.

General statistical explanation: missing outcomes can affect descriptive counts and comparisons, especially when the reason data are missing is related to participants' symptoms or follow-up. A clear report usually states how many outcomes were observed and how incomplete data were handled. Without those details, the effect of missingness on the reported safety counts cannot be assessed. The available population definition should not be taken as evidence that every participant contributed complete data to every endpoint.

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 4.6% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: crying (0.2%).

The adverse-event summary reports 522 subjects at risk in the Rotarix group. It reports 1 subject affected by a serious adverse event and 247 subjects affected by other adverse events. These are counts as recorded, not a comparison with another group. The registry lists Crying at 0.2% among the top serious terms; it does not provide further detail about that term in the information available.

The serious-event count is not the same as a count of all adverse events. A subject can contribute to more than one event category, and the record does not explain the overlap between serious and other adverse events. It also does not report the observation period for these safety counts, the event-specific denominators, or confidence intervals. Deaths are not reported in the registry record; that should not be interpreted as a reported count of zero.

General statistical explanation: safety counts describe events recorded under a study's definitions and observation procedures. They do not, by themselves, establish whether an event was caused by the intervention. The absence of a comparison group limits what can be inferred about the background frequency of events or the difference associated with vaccination. The counts should therefore be read as descriptive observations in the reported cohort.

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

The registry record establishes that a post-marketing surveillance study enrolled 522 infants and evaluated outcomes after Rotarix vaccination. It specifies a primary endpoint based on grade 2 or higher fever, vomiting, or diarrhoea during an 8-day solicited follow-up period. It also reports one subject with a serious adverse event and 247 subjects with other adverse events in the Rotarix group.

The primary endpoint's observed count is not reported in the registry record. There is no reported primary effect estimate, confidence interval, or hypothesis test. The safety figures are descriptive counts, and no control group is identified. The record therefore does not provide a randomized or otherwise stated like-for-like comparison for interpreting those counts.

General statistical explanation: a study can describe how many participants experienced recorded events without establishing whether the intervention caused those events. Causal interpretation depends on the design, comparison group, measurement, follow-up, and analysis. In a single-group record, background event occurrence cannot be separated from events associated with the intervention using the reported counts alone.

The results also do not establish the precision of the primary endpoint or the safety estimates. Confidence intervals are not reported, and the registry does not detail outcome-specific denominators or missing-data handling. An event count, without an interval or a comparator, cannot answer how much uncertainty surrounds an estimate or how it compares with an alternative.

Accordingly, the results support a limited description of reported safety observations in vaccinated infants, while leaving the primary outcome result and comparative interpretation unresolved. They do not establish that vaccination did or did not cause a particular event, and they should not be read as a general claim about efficacy or safety beyond the participants, definitions, and follow-up described in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative in part because it illustrates the distinction between defining an outcome and reporting its result. The registry gives a detailed definition for the primary endpoint: subjects with at least one grade 2 or higher fever, vomiting, or diarrhoea during an 8-day solicited follow-up period. But the observed endpoint count is not reported. Without that count, readers cannot assess the primary outcome's frequency or precision from the registry record.

The study also illustrates how design determines the claims that data can support. A single group can provide descriptive information about recorded events among vaccinated participants. It cannot, without a suitable comparator or another stated causal design, quantify how event occurrence differed from what would have happened under an alternative. Allocation is not stated, and no control arm is identified.

General statistical explanation: transparent outcome definitions, denominators, follow-up periods, missing-data methods, and uncertainty estimates are all important to interpreting clinical evidence. A count is more useful when its analysis population and observation window are explicit; a comparison is more informative when the groups are comparable and the analysis plan is clear. Here, the population definition and primary follow-up window are given, but several supporting details are not reported in the registry record.

The reported counts—1 subject with a serious adverse event and 247 with other adverse events—also show why safety reporting should distinguish seriousness, event type, and participant counts. These numbers are observations, not causal estimates. The registry record's limited analysis information makes clear that reporting the statistical context is as important as listing an endpoint or count.

15. Limitations

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

The most direct limitation is that the registry record does not report the result for the primary endpoint. Although the endpoint definition and follow-up period are stated, there is no observed count, effect estimate, confidence interval, or test result for it. The primary question therefore cannot be answered using the reported outcome result.

The record describes a Rotarix group but does not identify a comparator, and allocation is not stated. The safety counts cannot be interpreted as a between-group difference. The information also does not establish whether the 522 enrolled subjects all received both planned doses or completed the specified follow-up. Outcome-specific denominators are not reported.

Further details are absent for adverse-event observation periods, missing-data handling, and any statistical adjustment or hypothesis-testing plan. The record lists secondary outcomes for solicited general symptoms, unsolicited adverse events, and serious adverse events, but does not report their full results. Deaths are not reported in the registry record. The serious-event term listing includes Crying at 0.2%, without further context in the record.

These gaps limit assessment of precision, completeness, and potential bias. General statistical explanation: a descriptive event count may be affected by how long participants were observed, how events were solicited, and whether all participants contributed outcome data. Without those details, readers cannot determine how fully the reported counts represent the cohort's experience or how missing observations might affect interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Reactogenicity and Safety of GSK Biologicals' Rotarix™ (Human Rotavirus Vaccine) in Infants — NCT00779779.
• Registry record last updated 2018-08-28; status last verified 2011-02.
• Results first posted 2010-07-30.
• 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

NCT00779779 is a completed post-marketing surveillance study sponsored by GlaxoSmithKline. It enrolled 522 healthy infants in Sri Lanka and evaluated two oral doses of Rotarix, with at least 4 weeks between doses and both doses intended to be completed by 24 weeks of age. The primary analysis population was the Total Vaccinated Cohort.

The primary endpoint counted subjects with at least one grade 2 or higher fever, vomiting, or diarrhoea during the 8-day solicited follow-up period. Its observed result is not reported in the registry record. The safety summary reports 1 subject with a serious adverse event and 247 with other adverse events among 522 at risk. The registry does not identify a comparator or report a statistical analysis plan, primary effect estimate, or confidence interval.