This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Long-Term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Month Schedule (NCT00289718), a na phase 3 study. The primary outcome is Number of Subjects Reporting Serious Adverse Events (SAE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00289718 |
| Phase | Phase 3 |
| Condition | Hepatitis B, Hepatitis A |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 51 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adult volunteers in a long-term follow-up study after receiving combined hepatitis A and B vaccination. The registry record lists an enrollment of 51, but the primary endpoint’s analysis population was the Long Term Total cohort who received an additional vaccine dose; only 1 subject received such a dose.
Intervention
Twinrix adult, a combined hepatitis A and B vaccine. The study title refers to a 0,1,6 month schedule. The record describes the follow-up as assessing antibody persistence at Years 11, 12, 13, 14 and 15 after the first dose of a 3 dose vaccination schedule.
Comparator
There was no randomized comparator. The registry lists allocation as NA and the study model as single group. The Twinrix Group pooled participants from the primary study’s lot A, B and C groups for long-term follow-up analyses.
Primary question
The study’s stated long-term objective was to evaluate persistence of hepatitis A and B antibodies. The posted primary endpoint, however, is the number of subjects reporting serious adverse events during follow-up after additional vaccination, with a minimum 30-day period. Numerical antibody-persistence results are not reported in the registry record.
3. Trial Design
This is a Phase 3, single-group follow-up study of healthy adult volunteers. The registry record lists enrollment of 51 and status as completed. It names Twinrix adult as the biological intervention. The title identifies a 0,1,6 month vaccination schedule, while the follow-up description concerns antibody persistence at Years 11, 12, 13, 14 and 15 after the first dose of the 3 dose schedule.
The group description says participants received 2 doses of Twinrix in the primary study. Because lot-to-lot consistency was assessed during that primary study, participants from lot A, B or C were pooled into the Twinrix Group for long-term follow-up analyses. This is a pooled single group, not a randomized comparison between vaccine lots or between vaccinated and unvaccinated participants.
The registry lists allocation as NA and masking as none. It does not describe a concurrent control group. The reported primary endpoint is the number of subjects reporting serious adverse events after an additional vaccine dose, during a minimum 30-day follow-up period. Its analysis population was the Long Term Total cohort who received an additional dose; only 1 subject did so. That limited safety population is distinct from the overall enrollment listed for the study.
The registry record does not report a sample-size justification, further detail on the follow-up procedures, or numerical antibody-persistence findings. The title and stated objectives establish the long-term immune-persistence focus, but the posted primary endpoint is a safety count rather than an antibody measure.
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
| Stage | Twinrix Group |
|---|---|
| STARTED | 51 |
| COMPLETED | 51 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the Long Term According-to-Protocol (LT-ATP) cohort for immunogenicity, on subjects with available data for the defined timepoint
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.
| Characteristic | Unit | Twinrix Group |
|---|---|---|
| Participants analysed | 51 | |
| Age, Continuous | years | 36.4 (SD 5.65) |
| Sex: Female, Male: Female | Participants | 41 |
| Sex: Female, Male: Male | Participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Reporting Serious Adverse Events (SAE), measured over During the follow-up period after additional vaccination (minimum 30 days).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of subjects reporting serious adverse events during follow-up after additional vaccination, with a minimum 30-day period. A serious adverse event was defined as an untoward medical occurrence resulting in death, being life threatening, requiring or prolonging hospitalization, causing disability or incapacity, or constituting a congenital anomaly or birth defect in a study subject’s offspring.
The endpoint is a count of people with an event, not a measure of antibody concentration or persistence. Serious-event monitoring is used to describe important safety occurrences, including events with substantial consequences or requiring significant care. The registry definition also says that “any” event includes symptoms regardless of intensity grade or relationship to vaccination; a related event is one the investigator assessed as causally related to study vaccination.
The endpoint’s analysis population was restricted to subjects who received an additional vaccine dose. The record says only 1 subject received one. Numerical antibody-persistence results are not reported in the registry record, so this safety endpoint does not answer the stated immune-persistence objective by itself.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a long-term follow-up intended to assess hepatitis A and B antibody persistence at Years 11, 12, 13, 14 and 15. The numerical antibody results are not reported in the registry record. Consequently, the posted information does not establish the level or persistence of either antibody response at those time points, nor does it permit a statistical comparison of immune responses.
The primary endpoint instead concerns serious adverse events after an additional vaccine dose. The safety summary lists 1 subject at risk and 1 subject affected in the serious-event category. The listed top serious term is Hallux valgus, at 100.0%. These figures describe the small additional-dose safety group, not the full enrollment of 51. The record also lists 0 deaths.
With only 1 subject receiving an additional dose, the safety count is a description of that subject’s recorded experience, not a precise estimate of event frequency in a broader population. A confidence interval, if reported, would express the range of values reasonably compatible with the observed data under a statistical model; no confidence interval for this endpoint is reported in the registry record. The small analysis population means that these observations cannot characterize the range of possible uncommon or later events.
The endpoint definition distinguishes events that occurred from events judged by the investigator to be causally related to vaccination. The listed serious term does not, by itself, establish that the event was caused by the vaccine. The registry record does not state a causal assessment for Hallux valgus in the posted summary.
The study has no randomized comparator, and the registry identifies it as a single-group study. Therefore, the posted results cannot support a controlled estimate of a treatment difference. The pooled lot groups also do not constitute a comparison between lots. The record’s sample-size planning assumptions describe a hypothetical two-arm illustration, not the design or observed power of this single-group follow-up study.
9. Statistical Methods Explained
What kind of outcome is reported?
The primary endpoint is a binary event outcome summarized as a count of subjects with serious adverse events. For an individual participant, the outcome can be understood as whether at least one qualifying serious event was reported during the specified follow-up period. A count is useful for describing observed events, but without a sufficiently informative denominator and a suitable comparison it does not show whether a rate differs between groups.
The registry’s endpoint definition sets out what qualifies as serious, including death, life-threatening events, hospitalization or prolonged hospitalization, disability or incapacity, and congenital anomaly or birth defect in offspring. It also distinguishes the occurrence of an event from an investigator’s assessment that the event was causally related to vaccination. Those are different questions: an event may be recorded without being judged related.
Why does the analysis population matter?
The serious-event endpoint was assessed in the Long Term Total cohort among subjects who received an additional vaccine dose. The record says only 1 subject received an additional dose. The overall enrollment of 51 therefore should not be treated as the denominator for this endpoint. The relevant safety summary reports 1 subject at risk and 1 affected in the serious-event category. A small denominator makes a count highly sensitive to the experience of each participant and limits how precisely it can describe risk in a wider population.
How should uncertainty be considered?
In general, a confidence interval communicates the statistical uncertainty around an estimate: wider intervals indicate less precision, while narrower intervals indicate greater precision under the assumptions of the method. The registry record does not report a confidence interval for the primary endpoint. It also does not report an inferential analysis for the posted outcomes. The observed count should therefore be read descriptively, rather than as a precise estimate or a test of a treatment effect.
In general, over-dispersion means that observed variation is greater than a model expects. It can affect standard errors and confidence intervals when an analysis assumes less variability than the data contain. The registry record does not report a model for this endpoint, an over-dispersion assessment, or enough detail to determine whether such methods were considered. No model-based conclusion should be inferred from the count alone.
What do the planning assumptions describe?
The record includes a planning illustration based on a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes detecting a stated fraction of an observed effect. Those assumptions are not a description of the actual trial design: this follow-up is listed as single group, with allocation NA and no randomized comparator. The illustration is not observed power and should not be interpreted as evidence about the probability that the study detected an effect. No trial-specific sample-size justification is reported in the registry record.
The illustration’s equal-allocation, two-arm framework also does not match the reported safety analysis, which concerns the one subject who received an additional dose. Without a stated comparator and an analysis appropriate to the actual design, a two-arm planning calculation cannot supply a controlled estimate for this study. No new sample-size or power calculation can be derived from the posted summary alone.
What can be said about the immune-persistence objective?
The stated objective is to evaluate antibody persistence over Years 11 through 15, but numerical antibody outcomes and corresponding analyses are not reported in the registry record. The record lists 11 outcome measures and 0 analyses; those counts do not reveal the values of unreported antibody results. Without the numerical results, the methods used to summarize immune responses, the treatment of missing antibody measurements, and any uncertainty estimates for those outcomes are not reported in the registry record.
The lot groups were pooled for long-term follow-up because lot-to-lot consistency was assessed during the primary study. The registry record does not provide the results of that assessment or a comparative long-term analysis by lot. The pooled description should not be taken as evidence of equivalence between lots based on the follow-up summary alone.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Twinrix Group (Lot A) | 1 | 0 | 0.0% | 0.0% to 97.5% | 0.0% to 79.3% | 1.3% to 84.2% |
| Twinrix Group (Lot B) | 1 | 1 | 100.0% | 2.5% to 100.0% | 20.7% to 100.0% | 15.8% to 98.7% |
R code and output
arm <- c("Twinrix Group (Lot A)", "Twinrix Group (Lot B)")
n <- c(1, 1)
events <- c(0, 1)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Twinrix Group (Lot A) 1 0 0.0 0.0 97.5 0.0 79.3 1.3 84.2
ARM Twinrix Group (Lot B) 1 1 100.0 2.5 100.0 20.7 100.0 15.8 98.711. Multiplicity, Missing Data and Analysis Populations
The registry record lists 11 outcome measures and 0 analyses. It does not report how the outcome measures were prioritized beyond identifying the serious adverse event count as the primary endpoint. A multiplicity adjustment, hierarchy of tests, or other strategy for handling multiple outcomes is not reported in the registry record. Without the analysis results and plan, it is not possible to determine how multiple comparisons may have affected interpretation of the immune-persistence objectives.
Missing-data methods are also not reported in the registry record. The posted information does not describe how missing antibody measurements, missed visits, or incomplete follow-up were handled. It does not state whether every enrolled participant contributed measurements at each of Years 11, 12, 13, 14 and 15. The enrollment count alone does not establish the number with usable data at any particular time point.
The primary safety analysis population is described as the Long Term Total cohort who received an additional vaccine dose, and the record says only 1 subject received one. It does not provide further detail about the handling of incomplete serious-event follow-up for that subject. The results should therefore be read within the stated analysis population, without assuming that all enrolled participants were included in the primary safety count.
The registry record does not report an intention-to-treat analysis, a per-protocol analysis, or sensitivity analyses for missing data. It also does not provide enough detail to assess whether the reported population definitions were prespecified. These omissions limit evaluation of how selection into the additional-dose cohort and incomplete measurements may affect the findings.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Twinrix Group | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Twinrix Group | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Twinrix Group | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Twinrix Group |
|---|---|---|
| Hallux valgus | Musculoskeletal and connective tissue disorders | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Twinrix Group |
|---|---|---|
| Pain | General disorders | 1 of 1 |
| Nasopharyngitis | Infections and infestations | 1 of 1 |
Serious events with the highest arm-level rate: hallux valgus (100.0%).
The safety summary lists 1 subject at risk and 1 subject affected in the serious-event category. It identifies Hallux valgus as the top serious term, at 100.0%, and lists 0 deaths. The primary endpoint’s analysis population was the Long Term Total cohort who received an additional vaccine dose; the record says only 1 subject received one.
These figures are descriptive of this very small analysis population. They should not be interpreted as a stable estimate of how often serious events occur in a larger population. The “top serious term” percentage describes the listed term in the summary; it does not establish a causal relationship to vaccination. The registry definition says that an event is considered related when the investigator assesses it as causally related, but the posted summary does not report that assessment for Hallux valgus.
The record’s serious adverse event definition includes several types of consequential medical occurrence. A count of subjects reporting such events is distinct from a count of all symptoms, and the record’s definition of “any” event includes symptoms regardless of intensity or relationship. The reported safety figures should be understood within the stated follow-up after additional vaccination, not as a complete safety summary for all 51 enrolled participants.
13. What the Result Does, and Does Not, Mean
The record’s stated scientific objective is long-term persistence of hepatitis A and B antibodies following combined vaccination. It identifies Years 11, 12, 13, 14 and 15 as follow-up time points. However, numerical antibody-persistence results are not reported in the registry record. The posted information therefore does not show the antibody levels at those times or how they changed over follow-up.
The available primary endpoint is a count of subjects reporting serious adverse events after an additional vaccine dose. Its safety summary describes 1 affected subject among 1 at risk, lists Hallux valgus as the top serious term at 100.0%, and records 0 deaths. Because only 1 subject received an additional dose, these observations have limited ability to characterize safety beyond that subject’s reported experience.
The record does not establish that Hallux valgus was caused by vaccination. It also does not provide a randomized comparator, so the outcome cannot be contrasted with an untreated group or another intervention. The pooled lot groups are not a controlled comparison between vaccine lots.
These results do not provide a statistical estimate of an antibody response, a controlled treatment effect, or a precise estimate of serious-event frequency. They also do not establish that an event will or will not occur in other people. The record supports a narrow descriptive reading of the posted safety count and identifies an immune-persistence objective for which numerical results are not reported.
14. Why This Trial Matters Statistically
This study is statistically notable because its stated long-term objective and its posted primary endpoint address different kinds of outcomes. Antibody persistence is an immune-response question, while the primary endpoint is a serious adverse event count after an additional vaccine dose. Keeping those outcomes distinct is essential: a safety count cannot substitute for numerical antibody measurements, and an objective alone is not a result.
The difference between overall enrollment and the primary endpoint analysis population also matters. Although the registry lists enrollment of 51, only 1 subject received an additional dose and entered the stated population for that endpoint. The serious-event count therefore describes a very limited safety experience, rather than all enrolled participants. This illustrates why readers need to check the denominator attached to each outcome rather than assume that every result uses the full enrollment.
The study is listed as single group with allocation NA and no masking. The pooled lots do not create a randomized comparison. That design can support descriptive follow-up, but it does not provide a controlled estimate of differences between interventions or lots. The registry’s generic two-arm planning illustration should likewise be distinguished from the actual single-group design.
Finally, a completed study record does not necessarily contain every numerical result needed to assess its objectives. Here, the stated antibody-persistence outcomes are not reported numerically, and the record lists 0 analyses. That makes transparent reporting of outcome values, denominators, uncertainty, and missing-data handling particularly important for interpretation.
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 registry record does not report numerical antibody-persistence results for the stated follow-up at Years 11, 12, 13, 14 and 15. It therefore does not permit assessment of the size, precision, or pattern of the immune responses over time. The record lists 11 outcome measures and 0 analyses, but does not provide the numerical results or analysis details needed to interpret those measures.
The primary endpoint’s safety population is very small: only 1 subject received an additional vaccine dose. The posted serious-event summary is consequently a limited description and cannot characterize the range of safety experiences that might occur in a larger group. The full enrollment of 51 is not the denominator for this endpoint.
The study is single group, with allocation listed as NA and masking as none. No randomized control comparison is available in the registry record, and the pooled lot groups are not a comparative analysis. The record does not report a sample-size justification, a statistical analysis plan, missing-data methods, confidence intervals, or sensitivity analyses. It also does not report whether all participants were observed at every follow-up time point.
The registry’s primary endpoint is safety-focused, although the study title and objective emphasize immune persistence. The safety summary does not state whether the listed serious term was judged related to vaccination. The planning assumptions describe a hypothetical two-arm illustration and do not resolve these design or reporting limitations.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Long-Term Immune Persistence of GSK Biologicals' Combined Hepatitis A & B Vaccine Injected According to a 0,1,6 Month Schedule — NCT00289718.
- Registry record last updated 2018-02-15; status last verified 2016-11.
- Results first posted 2010-08-26.
- 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.
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19. Record Summary
This completed Phase 3 study followed healthy adult volunteers after combined hepatitis A and B vaccination, with the stated objective of evaluating antibody persistence at Years 11, 12, 13, 14 and 15. The registry lists enrollment of 51 and describes a pooled Twinrix Group. The design is single group, with allocation NA and masking none.
The posted primary endpoint is the number of subjects reporting serious adverse events during follow-up after additional vaccination, with a minimum 30-day period. Only 1 subject received an additional dose. The safety summary lists 1 subject affected among 1 at risk, Hallux valgus as the top serious term at 100.0%, and 0 deaths.
Numerical antibody-persistence findings, detailed analyses, missing-data methods, and a trial-specific sample-size justification are not reported in the registry record. The safety figures are descriptive and do not provide a controlled comparison or establish causality.