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 Follow-Up Study 16-20 Years After Hepatitis B Vaccination in Newborns of Mothers Who Were Seropositive for Hepatitis B Envelope Antigen (HBeAg) & Hepatitis B Surface Antigen (HBsAg) (NCT00240539), a non-randomized phase 4 study. The primary outcome is Number of Subjects Seropositive for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00240539 |
| Phase | Phase 4 |
| Condition | Hepatitis B |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 36 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Newborns enrolled in an earlier vaccination study, grouped according to their mothers’ HBsAg and HBeAg status and the number of vaccine doses received. The follow-up focused on participants remaining in the long-term immunogenicity cohort. The registry record notes that follow-up loss or removal from that cohort affected data availability, but the complete population description is not reported in the registry record.
Intervention
The study concerns Engerix-B™ vaccination in the earlier study. The long-term follow-up itself involved blood sampling, not a new vaccination intervention. No new subjects were recruited for this follow-up.
Comparator
The study groups distinguish maternal antigen status and whether participants received 4 or 5 doses in the primary study. The official title also describes comparison with a historical control group. The identity and details of that historical control are not reported in the registry record, and the study was non-randomized.
Primary question
At years 16, 17, 18, 19 and 20 after the first vaccine dose, how many participants were seropositive for anti-HBs antibodies, defined as an antibody concentration of at least 3.3 mIU/mL? The registry record does not report the observed counts or comparative estimates needed to answer that question numerically.
This is a question about persistence of an antibody response over long-term follow-up. It is not a randomized comparison of newly assigned treatments: participants had received their vaccination schedules in the primary study, and this follow-up observed them later. The endpoint is a laboratory-defined status at successive follow-up years. It does not, by itself, describe clinical illness or establish how well the groups compare on other outcomes.
3. Trial Design
The registry identifies this as a completed Phase 4, non-randomized, parallel-group study with no masking. Enrollment was 36. The study began in 2003-10 and had primary completion in 2008-07. These dates describe the registered study, while the endpoint timeframe is specified relative to each participant’s first vaccine dose.
The purpose was long-term follow-up of immune response after vaccination in an earlier study. No new subjects were to be recruited. The listed procedure for the follow-up was blood sampling. The study groups were based on maternal HBsAg and HBeAg status and on whether the newborn received 4 or 5 doses of Engerix™ in the primary study. The record names groups with HBsAg-positive, HBeAg-negative mothers; HBsAg-positive, HBeAg-positive mothers; and HBsAg-negative, HBeAg-negative mothers. The HBsAg-positive, HBeAg-positive category includes both a 4-dose and a 5-dose group.
The official title describes comparison with a historical control group, but the record does not fully explain how that control was selected or which group served that role. Because allocation was non-randomized, group membership should not be treated as an assigned intervention contrast. No randomization method, masking procedure, or allocation concealment method is reported in the registry record; masking is listed as none.
The record does not describe the protocol’s sample-size justification, the planned statistical analysis, or any interim analyses. Enrollment is the total registered enrollment and should not be read as the number contributing data to every endpoint or group. The primary endpoint population is the long-term according-to-protocol cohort for immunogenicity, and the record notes loss to follow-up or removal from that cohort. Group-specific numbers analyzed are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Participant Flow and Baseline measures are given for the year 20 time point in order to account for all subjects participating in this long-term follow-up study. Note that not all subjects returned and participated in each of the intermediate follow-up time points.
Overall Study
| Stage | HBsAg(+) & HBeAg(+) 5-dose Group | HBsAg(+) & HBeAg(-) 4-dose Group | HBsAg(+) & HBeAg(+) 4-dose Group | HBsAg(-) & HBeAg(-) 4-dose Group |
|---|---|---|---|---|
| STARTED | 2 | 2 | 31 | 1 |
| COMPLETED | 2 | 2 | 31 | 1 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The analyses were performed on the Long-Term According to protocol (ATP) cohort for immunogenicity. Due to subjects being lost to follow up or eliminated from the ATP cohort for immunogenicity, no data from subjects in HBsAg(+) \& HBeAg(-) 4-dose Group and HBsAg(-) \& HBeAg(-) 4-dose Group were analyzed.
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 | HBsAg(+) & HBeAg(+) 5-dose Group | HBsAg(+) & HBeAg(-) 4-dose Group | HBsAg(+) & HBeAg(+) 4-dose Group | HBsAg(-) & HBeAg(-) 4-dose Group | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 2 | 2 | 31 | 1 | 36 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 | 2 | 31 | 1 | 36 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Gender: Female | Participants | 2 | 2 | 18 | 1 | 23 |
| Gender: Male | Participants | 0 | 0 | 13 | 0 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Seropositive for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies, measured over At Years 16, 17, 18, 19 and 20 after primary vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who were seropositive for anti-hepatitis B surface antigen antibodies, also called anti-HBs antibodies. Seropositivity was defined as an anti-HBs concentration of at least 3.3 mIU/mL. The endpoint was assessed at years 16, 17, 18, 19 and 20 after primary vaccination.
This measure is used to describe persistence of a measurable antibody response over time. It converts a laboratory concentration into a binary outcome: a participant either meets the stated threshold or does not. A count of seropositive participants can therefore describe how many people in an analyzed group met that criterion at a specified follow-up time.
As a general statistical point, a threshold-based endpoint is straightforward to interpret, but it does not retain all the information in the underlying continuous antibody concentrations. Two participants with concentrations above the threshold are counted alike by this endpoint even if their concentrations differ. The registry record does not report the concentration distributions, group denominators, or numerical seropositive counts. It also does not report comparative estimates or uncertainty measures for this endpoint.
The measure is an immunogenicity outcome, not a direct count of hepatitis B infections or clinical disease. A seropositivity count alone cannot establish those other outcomes. The record’s stated endpoint supports a description of antibody status at the specified follow-up years; further conclusions would require results and analyses that are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registered question is whether anti-HBs seropositivity persisted at multiple long-term follow-up points among participants from the earlier vaccination study. The endpoint definition is explicit: seropositivity means an anti-HBs concentration of at least 3.3 mIU/mL, assessed at years 16 through 20 after the first dose. However, the registry record does not report the numerical counts of seropositive participants at any of those time points. It also does not report denominators, proportions, differences between groups, confidence intervals, or hypothesis-test results.
Accordingly, the record does not allow a reader to determine the observed level of seropositivity at a given year, how that level changed across follow-up, or how groups differed. The absence of numerical results is not evidence that no participants were seropositive, nor evidence that groups were alike or different. It means the posted record does not provide the outcome information required to judge those possibilities.
The total enrollment of 36 does not resolve the missing information. It is not a group-specific denominator and does not establish how many participants contributed data at each follow-up time. The primary population is described as the long-term according-to-protocol cohort for immunogenicity, and the registry notes that some participants were lost to follow-up or removed from that cohort. The complete description of the population text is not reported in the registry record, and analyzed counts by time and group are not reported in the registry record.
Any interpretation of between-group differences would also need to account for the non-randomized design. The groups reflect maternal antigen status and previous vaccine dose schedule, rather than assignment to comparable groups by randomization in this follow-up. The record’s reference to a historical control does not supply the information needed to assess its comparability with the followed participants. Associations between group and antibody status, if reported elsewhere, would not automatically establish that the group distinction caused the result.
In general, confidence intervals help show the precision of an estimated count, proportion, or contrast, while hypothesis tests address compatibility with a specified null model. Neither type of result is reported in the registry record. The registry also lists 0 analyses. Therefore, the available entry supports a description of the study’s objective, design and endpoint definition, but not a numerical conclusion about the observed antibody response or the precision of any comparison.
9. Statistical Methods Explained
The endpoint is binary at the participant level: anti-HBs concentration either meets the seropositivity threshold or does not. The primary measure is described as the number of participants meeting that threshold at each specified follow-up year. For a complete analysis, a reader would ordinarily need the number meeting the criterion and the number assessed in each group and at each time. Those results are not reported in the registry record.
What does a binary endpoint represent?
General explanation: a binary endpoint reduces an underlying measurement to two categories using a prespecified rule. This can make a result easy to communicate as a count or proportion. The trade-off is that measurements close to the threshold and measurements far above it are both classified as seropositive. The continuous antibody values can provide additional information about the distribution and magnitude of responses, but those values are not reported in the registry record.
The registry’s definition uses an anti-HBs concentration of at least 3.3 mIU/mL. The endpoint is intended to describe persistence of measurable antibody status after the earlier vaccination, not a clinical event count. No details about laboratory procedures, assay performance, or handling of values at the threshold are reported in the registry record.
How should repeated follow-up times be understood?
The endpoint timeframe lists years 16, 17, 18, 19 and 20 after primary vaccination. These are repeated long-term assessment points, not five independent treatment assignments. General explanation: when the same participants are assessed over time, their results may be related because observations from one person are not necessarily independent of that person’s other observations. An analysis of change over time can account for that within-person relationship, while separate descriptions at each time point can present each assessment individually. The registry record does not report which approach was used, and it does not provide the numerical time-specific results.
The record also does not explain whether every participant was assessed at every listed time, how missed visits were handled, or whether a participant could contribute to some time points but not others. Those details matter because the number observed can differ across follow-up assessments. They cannot be inferred from the total enrollment.
What can be concluded from group comparisons?
General explanation: a comparison of binary outcomes may describe differences in counts or proportions, and inferential analyses may quantify uncertainty around such contrasts. A confidence interval is a range of values compatible with the data and a specified statistical procedure; its width reflects precision as well as sample size and variability. A p-value, when used, describes how unusual the data would be under a specified null model. Neither measure replaces the observed group counts or establishes causation.
Here, no group-specific outcome counts, comparison estimates, confidence intervals, or p-values are reported in the registry record. The study is non-randomized, and the groups differ by maternal HBsAg and HBeAg status and prior vaccine dose schedule. These features can be associated with differences other than the group label. General explanation: random assignment can help balance measured and unmeasured characteristics on average, whereas non-randomized comparisons may require careful adjustment and still be vulnerable to confounding. The statistical adjustment plan is not reported in the registry record.
The official title refers to a historical control group. General explanation: historical comparisons can be affected by differences in participant selection, follow-up, measurement, and clinical or study procedures across cohorts. The record does not describe the source or eligibility criteria of that historical group, nor does it report an analysis that compares it with the follow-up groups.
What is known about the planned analysis?
The registry lists 0 analyses. It does not report a statistical analysis plan, a model for repeated observations, covariate adjustment, an approach to uncertainty, or handling of multiple time points. Those methods must not be assumed from the type of endpoint. In particular, the record does not state whether estimates were descriptive only or whether formal group comparisons were planned or conducted.
A separate planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of an observed effect. Those assumptions describe a planning illustration, not the study’s own design justification. They do not establish the actual allocation, the analysis method, or the number of participants analyzed. The record does not report the underlying observed effect or numerical planning outputs. Such illustrations are not observed power and should not be interpreted as evidence about the study’s results.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint is assessed at five stated follow-up years and across multiple study groups. The registry record does not report whether a multiplicity strategy was planned for the repeated time points or group comparisons. It also does not report which comparisons, if any, were designated as primary contrasts beyond the stated endpoint. No adjustment method or hierarchy of tests is reported in the registry record.
General explanation: when many outcomes or comparisons are examined, the chance of obtaining an apparently notable result by chance can increase. A prespecified analysis plan can distinguish confirmatory questions from exploratory ones and describe whether multiplicity is controlled. Without a reported plan and results, it is not possible to assess how any potential multiplicity was handled in this study.
The primary population is identified as the long-term according-to-protocol cohort for immunogenicity. The registry record says that participants were lost to follow-up or eliminated from that cohort and indicates that no data were available from the HBsAg-positive, HBeAg-negative 4-dose group and the HBsAg-negative, HBeAg-negative 4-dose group. The remainder of that population description is incomplete, so the exact reason those groups lacked data is not reported in the registry record. Group-specific numbers, reasons for missingness, and the number assessed at each time point are not reported in the registry record.
General explanation: missing follow-up can affect interpretation if the probability of having an observed result is related to antibody status or other participant characteristics. The record does not state whether missing results were imputed, whether analyses used only available measurements, or whether sensitivity analyses were performed. It also does not report how many participants were excluded from the according-to-protocol cohort or the criteria for exclusion. The extent and possible impact of missing data therefore cannot be evaluated from the registry entry.
11. What the Result Does, and Does Not, Mean
The study’s stated purpose is to evaluate persistence of anti-HBs antibodies years after vaccination in an earlier study. Its primary endpoint defines seropositivity using a laboratory threshold and names five long-term assessment years. These details clarify what the study intended to measure, but they do not supply the observed outcome.
The registry record does not report the number of participants who were seropositive, the number assessed, or the distribution of antibody concentrations. It also does not report estimates comparing groups or uncertainty around any estimate. Therefore, the record cannot establish from its posted results whether seropositivity was common or uncommon at any particular follow-up year, whether it changed over time, or whether the groups differed.
That limitation should not be mistaken for a negative finding. An unreported result is not the same as a result showing no seropositivity or no difference. Likewise, enrollment of 36 does not indicate how many contributed an outcome at each time point, and it should not be treated as a complete analyzed sample size.
The design also limits causal interpretation. This was a non-randomized follow-up of groups defined by maternal antigen status and the number of doses received in the earlier study. The registry record’s mention of a historical control does not describe the control group sufficiently to assess comparability. General explanation: an observed association in a non-randomized comparison can reflect differences between groups as well as the exposure or group distinction being studied.
The endpoint is an antibody-status measure. It is not itself a count of infection, illness, or other clinical outcomes. The record does not report those outcomes in the information available for this study summary. Thus, the appropriate reading is limited to the study’s long-term immunogenicity question and the fact that its numerical results are not reported in the registry record.
12. Why This Trial Matters Statistically
Long-term follow-up asks a different statistical question from an assessment made shortly after vaccination: whether a defined laboratory response is still present years later. The endpoint and follow-up schedule make that question explicit, while the registry’s study description also highlights a practical issue in long-term research: participants may be lost to follow-up or no longer meet an analysis population’s criteria.
The study is statistically informative as an example of why endpoint definitions, analysis populations, and time-specific denominators need to be read together. A binary threshold can produce an accessible count, but interpretation depends on knowing how many participants were assessed and how missing observations were handled. Here, the record identifies a threshold and the planned follow-up years, yet the numerical counts and analysis details are not reported in the registry record.
The non-randomized design is also important. Groups were formed according to maternal antigen status and prior dose schedule, and the title refers to a historical control. These features require caution when interpreting comparisons because group differences may reflect characteristics beyond the comparison of interest. The registry does not report the adjustment strategy or enough information about the historical group to evaluate those concerns.
Finally, this record illustrates the distinction between a registered study question and an evaluable result. The design and endpoint are described, but no numerical primary outcome results or analysis estimates are reported. Without those data, precision and between-group patterns cannot be assessed. The study’s stated objective remains clear, while its empirical answer is not available in the registry record.
13. 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 main limitation for interpreting the primary endpoint is that numerical results are not reported in the registry record. There are no seropositive counts, analyzed denominators, group contrasts, confidence intervals, or hypothesis-test results in the record summarized. The total enrollment of 36 does not show how many participants contributed outcome data at each time point.
The analysis population description is incomplete. It identifies a long-term according-to-protocol cohort for immunogenicity and notes loss to follow-up or removal from the cohort. It also indicates that data from two named 4-dose groups were unavailable, but the complete explanation is not reported in the registry record. Reasons for missing observations, exclusion criteria, and numbers excluded by group are not reported.
The study was non-randomized and unmasked. The group definitions reflect maternal antigen status and vaccination schedules from the primary study; the record does not report an adjustment plan to address differences among groups. Although the official title refers to a historical control group, the source and characteristics of that group are not reported in the registry record. This prevents assessment of its comparability.
The registry lists blood sampling as the follow-up procedure and defines a threshold-based antibody endpoint. It does not report assay details, the distribution of continuous antibody measurements, the handling of missed visits, or a statistical model for repeated follow-up. No multiplicity approach, interim analyses, or sample-size justification is reported in the registry record. These gaps limit assessment of the methods and the precision and robustness of any result.
14. Related Tutorials
15. Related Statistical Calculators
16. Sources
- ClinicalTrials.gov: Long Term Follow-Up Study 16-20 Years After Hepatitis B Vaccination in Newborns of Mothers Who Were Seropositive for Hepatitis B Envelope Antigen (HBeAg) & Hepatitis B Surface Antigen (HBsAg) — NCT00240539.
- Registry record last updated 2016-12-08; status last verified 2016-10.
- Results first posted 2009-11-17.
- 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.
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17. Record Summary
This completed Phase 4 study followed participants from an earlier hepatitis B vaccination study to assess anti-HBs antibody persistence at years 16 through 20 after the first dose. It was non-randomized, unmasked, and parallel-group, with enrollment of 36 and blood sampling listed as the follow-up procedure. No new subjects were to be recruited.
The primary endpoint was the number of participants with anti-HBs concentrations of at least 3.3 mIU/mL, analyzed in a long-term according-to-protocol immunogenicity cohort. The groups were defined by maternal HBsAg and HBeAg status and prior vaccine dose schedule. The registry record notes follow-up loss or removal from the cohort and indicates unavailable data for two groups.
Numerical endpoint results, group denominators, comparative estimates, and analysis methods are not reported in the registry record. The study description establishes the question and endpoint but does not permit a numerical assessment of long-term seropositivity or differences between groups.