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 Persistence of Immunity to Hepatitis B in Adults Vaccinated With GlaxoSmithKline (GSK) Biologicals' Hepatitis B Vaccine (HBV), Engerix-B (NCT02901951), a na phase 4 study. The primary outcome is Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02901951 |
| Phase | Phase 4 |
| Condition | Hepatitis B Vaccine |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 106 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Adults described as having received three or four doses of Engerix-B 20 to 30 years earlier. The arm description specifies ages 40 to 60 years; the brief summary instead describes subjects aged 18 to 40 years.
Intervention
A single challenge dose of hepatitis B vaccine, identified in the arm description as HBV vaccine and in the study record as Engerix-B.
Comparator
There is no separate comparator group. The study is described as single-group, and the participants’ antibody status before the challenge dose is used in defining the response.
Primary question
What percentage of participants met the registry’s definition of an anamnestic antibody response after the challenge dose, based on their pre-challenge antibody concentrations and the post-challenge measurement?
The registry record frames the study as an assessment of long-term protection against hepatitis B infection among adults vaccinated decades earlier. Its primary endpoint is an antibody-response measure after a challenge dose, rather than a comparison of infection outcomes between treatment groups. The endpoint definition distinguishes participants by whether their pre-challenge anti-HBs concentration was at least 6.2 mIU/mL or below 6.2 mIU/mL. It then applies a different post-challenge antibody criterion to each group.
The primary endpoint’s stated timeframe is 7 days after the challenge dose, while its definition refers to antibody concentrations one month after the challenge dose. That discrepancy makes the timing of the primary assessment unclear in the registry record. The record does not report the primary response percentage or its confidence interval, so the clinical question can be described but the observed answer cannot be read from the registry entry.
3. Trial Design
This is a completed Phase 4, single-group study sponsored by GlaxoSmithKline. The registry lists enrollment of 106 and one intervention, Engerix-B. Allocation is listed as not applicable, and masking is listed as none. There is no randomized control group or parallel comparator arm described in the record.
The study concerns adults previously vaccinated with three or four doses of Engerix-B 20 to 30 years earlier. The arm description says participants were aged 40 to 60 years and received a single challenge dose at Day 0 (Visit 1). The brief summary instead describes subjects aged 18 to 40 years. These age descriptions conflict, and the registry record does not resolve the discrepancy. The primary endpoint is based on the participants’ pre-challenge antibody status and their response after the challenge dose.
The listed start date is 2016-10-11, the primary completion date is 2017-05-01, and the study status is completed. The registry lists eight outcome measures, including antibody concentrations, antibody cut-off categories, and adverse-event outcomes. It does not list any analyses. A sample-size justification, protocol details, and an explanation for the chosen cohort size are not reported in the registry record.
Because all participants are described within one group, the design can characterize observations in that cohort but cannot, by itself, estimate a difference between a challenge-dose group and a concurrent untreated or alternative-treatment group. Comparisons based on pre-challenge antibody categories are not randomized comparisons: those categories describe participants’ baseline status. The study’s design and endpoint therefore address antibody response within the studied cohort, not a treatment contrast between independent groups.
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: 106 subjects were enrolled in the study but 3 subjects were withdrawn before vaccine administration. Therefore, the number of subjects started is 103.
Overall Study
| Stage | HBV Group |
|---|---|
| STARTED | 103 |
| COMPLETED | 103 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the According-to-protocol (ATP) cohort for analysis of immunogenicity which included all evaluable subjects who had received the challenge dose of HRV vaccine and for whom data concerning immunogenicity outcome measures at pre-challenge (Day 0) and one month post-challenge (Day 30) were available.
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 | HBV Group |
|---|---|---|
| Participants analysed | 103 | |
| Age, Continuous | Years | 48.6 (SD 5.9) |
| Sex: Female, Male: Female | Participants | 87 |
| Sex: Female, Male: Male | Participants | 16 |
| Race/Ethnicity, Customized: White - Caucasian / European Heritage | Participants | 103 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Subjects With an Anamnestic Response to the HBV Challenge Dose, Based on the Last Available Time Point Before the Challenge Dose, measured over 7 days after the challenge dose (Day 7).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of subjects with an anamnestic response to the hepatitis B challenge dose. The registry describes the outcome as based on the last available time point before challenge and gives a timeframe of 7 days after challenge. The response definition, however, refers to post-challenge antibody concentrations at one month, creating a timing inconsistency in the record.
The definition separates participants by pre-challenge anti-HBs concentration. For participants with a pre-challenge concentration at least 6.2 mIU/mL, a response is defined as a rise of at least 4-fold in the post-vaccination concentration. For those below 6.2 mIU/mL before challenge, the definition requires a post-challenge concentration at least 10 mIU/mL. Thus, the endpoint combines two criteria that depend on the participant’s pre-challenge antibody category.
In general, an antibody-response endpoint can describe whether a measured immune marker changes or reaches a specified threshold after exposure. It is not itself a direct count of infections or a direct estimate of clinical protection. The registry’s primary outcome is a percentage with a 95% confidence interval, but neither the percentage nor its interval is reported in the registry record. The record also does not clarify how the stated 7-day timeframe relates to the one-month measurement used in the definition.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies an antibody-response endpoint and its intended definition, but it does not report the observed primary outcome. No response percentage or 95% confidence interval is listed. Consequently, the magnitude of the observed response and its statistical precision cannot be assessed from this record. The study is marked completed, but completion status does not supply the missing outcome estimate.
The primary endpoint is a binary classification at the participant level: a person either meets the applicable response criterion or does not. The reported group result would ordinarily express the proportion meeting that definition, with a confidence interval describing uncertainty around the estimate. In general, a confidence interval represents a range of values compatible with the data under the method’s assumptions; it is not a guarantee that the true value lies in that range. Since the estimate and interval are absent, no conclusion about their width or the degree of precision is possible.
The design is single-group. It can describe response after a challenge dose among the enrolled participants, but it does not provide a concurrent control group for estimating what would have happened without that dose or under a different intervention. Any interpretation should therefore remain descriptive of the observed cohort and endpoint. The registry does not report an analysis comparing pre-challenge antibody categories, and it lists no analyses.
The endpoint also has a timing ambiguity. Its timeframe says 7 days after the challenge dose, while the response definition uses antibody concentrations one month after challenge. The record does not explain which timing governs the analysis. The age descriptions also differ: the brief summary gives ages 18 to 40 years, whereas the arm description gives ages 40 to 60 years. These inconsistencies limit clarity about the intended population and measurement schedule.
Safety information is recorded separately from the primary immunogenicity outcome. The HBV Group lists 103 participants at risk for serious adverse events and 0 with a serious adverse event. It also lists 103 at risk and 75 affected for other adverse events, and 0 deaths. These counts do not replace the missing primary endpoint result, and the registry does not provide further detail about the other-event categories in the information recorded.
The study’s stated aim concerns long-term protection, but the primary endpoint is an antibody response after a challenge dose. The registry record does not report infection outcomes. An antibody response result, even if available, would need to be interpreted as the specified immune-marker outcome rather than as direct evidence about infection incidence. No conclusion about treatment effectiveness is warranted from the information recorded.
9. Statistical Methods Explained
The main outcome is a percentage, because it counts the share of participants meeting a defined response criterion. For each participant, the criterion depends on the pre-challenge antibody category. The registry defines previously seropositive participants as those with anti-HBs at least 6.2 mIU/mL at the pre-challenge time point, and previously seronegative participants as those below 6.2 mIU/mL. The two categories have different criteria for a response after challenge.
What does the confidence interval describe?
The primary endpoint specifies a 95% confidence interval. In general, a confidence interval communicates sampling uncertainty around an estimated quantity. For a percentage, a narrower interval indicates greater precision under the method’s assumptions, while a wider interval indicates less precision. The interval does not show the range of individual participants’ antibody concentrations; it concerns uncertainty in the group-level percentage. Neither the primary percentage nor its interval is reported in the registry record, so precision cannot be evaluated from this entry.
Why does the endpoint definition matter?
The response classification combines a relative-change rule for participants who were already above the pre-challenge cut-off with an absolute post-challenge threshold for those below it. A fold-rise criterion asks whether a participant’s value increased sufficiently relative to the pre-challenge value. An absolute threshold asks whether the post-challenge value reached a specified concentration. These rules answer related but not identical questions. Their use means the overall percentage depends on the participants’ baseline categories as well as their post-challenge measurements.
The record says the primary endpoint is based on the last available time point before challenge. Its timeframe is stated as 7 days after challenge, but its definition refers to a one-month post-challenge antibody measurement. The entry does not reconcile those descriptions. In general, defining the assessment time consistently is important because a measured response can depend on when it is assessed. The record does not report enough detail to determine which timing was used for the primary analysis.
What can a single-group design estimate?
In general, a single-group study can estimate the frequency of an outcome in the observed cohort, subject to the quality and completeness of the measurements. It does not create a randomized comparison with an untreated group or an alternative intervention. Participants’ pre-challenge antibody categories are not treatment groups assigned by randomization. Any differences between those categories could reflect their different baseline antibody status or other participant characteristics, and the registry does not report adjusted comparisons.
The record lists allocation as not applicable and masking as none. It identifies the study model as single group. These details help distinguish the study from a blinded, randomized trial with a control arm. The registry record does not report a statistical analysis plan, a model for the primary endpoint, or details of any interim analysis. It lists no analyses. Those omissions prevent assessment of whether any additional adjustment, subgroup analysis, or prespecified decision rule was used.
How should the enrollment figure be read?
The registry lists enrollment of 106. This is the listed study enrollment, not necessarily the number included in every endpoint analysis. The primary outcome description refers to an according-to-protocol immunogenicity cohort consisting of evaluable subjects who received the challenge dose and had immunogenicity data at pre-challenge and one month post-challenge. The text of that cohort description is incomplete, and the number of participants in the cohort is not reported in the registry record. The endpoint’s analysis denominator therefore cannot be established from the entry.
In general, the analysis population matters because excluding participants without required measurements can change the population represented by the estimate. A confidence interval also depends on the number of participants contributing outcome data. Without the analysis denominator and outcome estimate, neither the extent of missing endpoint data nor its effect on precision can be assessed.
What do the safety counts show statistically?
The adverse-event information gives counts at risk and counts affected for the listed categories. For serious adverse events, the record lists 103 at risk and 0 affected. A zero count means no serious adverse event was recorded among those participants in that category; it does not establish that the underlying risk is zero. In general, rare outcomes can remain uncertain when no events are observed, especially without a comparison group and without further follow-up detail. No serious-event terms are listed.
The record lists 103 at risk and 75 affected for other adverse events, and 0 deaths. It does not identify the individual events in that count in the information recorded. These descriptive safety counts should not be treated as evidence of a comparative difference, because no separate control group is described. They also do not determine the primary antibody-response result.
Sample-size planning is distinct from observed statistical evidence. In general, planning calculations depend on assumptions about the effect to detect, significance level, allocation, and statistical method. The registry record does not report the trial’s sample-size justification. Any planning illustrations associated with a page should be understood as hypothetical design calculations rather than observed power or evidence about the study’s result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures, including antibody cut-off percentages, antibody concentrations, and adverse-event counts. It identifies one primary outcome, but does not report a multiplicity adjustment, a hierarchy for secondary outcomes, or a statistical plan for interpreting multiple endpoints. These details are not reported in the registry record. In general, examining multiple outcomes can increase the chance of finding an apparently notable result by chance, so a prespecified approach to multiplicity helps clarify how results should be interpreted. No correction or testing strategy can be inferred from the outcome list alone.
The record lists no analyses and does not provide the primary endpoint estimate or confidence interval. It also does not report the number included in the immunogenicity analysis cohort. The primary outcome description refers to evaluable participants with the challenge dose and relevant immunogenicity data, but the cohort description is incomplete. The amount and handling of missing outcome data are not reported in the registry record.
In general, missing measurements can affect both the analysis denominator and the estimate, particularly if participants without measurements differ systematically from those with them. The registry does not report imputation, sensitivity analyses, or reasons for missing data. It also does not explain how the conflicting endpoint timing descriptions were handled.
The record identifies an according-to-protocol immunogenicity cohort, but it does not provide a complete definition or cohort size. There is no reported comparison of that population with all enrolled participants. Thus, the available information does not establish how exclusions or missing measurements affected the primary analysis.
11. 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 |
|---|---|---|---|
| HBV Group | 0 | 103 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| HBV Group | 0 of 103 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| HBV Group | 75 of 103 |
Most frequent non-serious adverse event terms
| Event term | Organ system | HBV Group |
|---|---|---|
| Injection site pain | General disorders | 40 of 103 |
| Fatigue | General disorders | 29 of 103 |
| Headache | Nervous system disorders | 25 of 103 |
| Gastrointestinal disorder | Gastrointestinal disorders | 10 of 103 |
| Nasopharyngitis | Infections and infestations | 6 of 103 |
| Back pain | Musculoskeletal and connective tissue disorders | 4 of 103 |
| Injection site erythema | General disorders | 4 of 103 |
| Cough | Respiratory, thoracic and mediastinal disorders | 3 of 103 |
| Injection site swelling | General disorders | 3 of 103 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 3 of 103 |
For the HBV Group, the registry lists 103 participants at risk for serious adverse events and 0 participants with a serious adverse event. It lists 103 at risk and 75 affected for other adverse events, and 0 deaths. No serious adverse-event terms are listed.
These are descriptive counts in a single-group study. They do not estimate a difference from a control group, because the record describes no separate comparator. In general, observing no serious events in a study group does not prove that the risk is absent; it means that none was recorded among the participants counted in that category. The registry does not report further detail about event timing, duration, severity, or the individual events included among other adverse events.
The at-risk count for the safety outcomes is 103, while listed enrollment is 106. The registry does not explain that difference, so it should not be attributed to a specific reason. Safety counts should also be kept distinct from the primary immunogenicity endpoint: they describe adverse events, not antibody response or protection against infection.
12. What the Result Does, and Does Not, Mean
The study addresses antibody response after a challenge dose among adults described as vaccinated with Engerix-B 20 to 30 years earlier. Its primary outcome is the percentage meeting a specified anamnestic-response definition. The registry record does not report the observed percentage or its 95% confidence interval. As a result, the central numerical finding and its precision cannot be assessed from this record.
The design is single-group, so it describes outcomes in the study cohort rather than a randomized contrast with another group. The record does not report a comparison of challenge-dose recipients with unchallenged participants or recipients of another intervention. The pre-challenge antibody categories are components of the endpoint definition, not randomized treatment assignments.
The stated study aim refers to long-term protection against hepatitis B infection, but the primary endpoint is based on antibody response. The record does not report infection outcomes. In general, an antibody measure can be informative about an immune response, but it is not the same outcome as observed infection. The endpoint result, even if reported elsewhere, would need to be interpreted according to its actual definition and measurement time.
There are important reporting ambiguities. The endpoint timeframe is listed as 7 days after challenge, while its definition refers to a one-month post-challenge measurement. The brief summary describes ages 18 to 40 years, whereas the arm description states ages 40 to 60 years. The registry does not resolve either discrepancy. The primary analysis cohort description is also incomplete, and its size is not reported.
The safety record reports 0 serious adverse events among 103 at risk, 75 affected by other adverse events among 103 at risk, and 0 deaths. These figures are descriptive and do not establish comparative safety. Taken together, the entry documents the study’s design and planned outcome concepts, but it does not provide enough primary outcome information to quantify the observed antibody response or draw a comparative conclusion.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the distinction between a within-group response estimate and a treatment comparison. A single-group study can describe how often a defined response occurred in its cohort, but it cannot isolate the effect of a challenge dose by comparing participants with a concurrent randomized control group. That distinction is essential when interpreting an endpoint framed around response after an intervention.
It also highlights how endpoint definitions shape the quantity being estimated. The response rule uses a fold-rise criterion for participants above a pre-challenge antibody cut-off and an absolute threshold for those below it. The resulting percentage combines participants assessed under different criteria. Clear reporting of the analysis denominator, the timing of measurement, and the observed estimate is needed to understand what that percentage represents.
The registry entry is especially useful as an example of why outcome reporting and precision matter. It names a primary outcome and specifies a 95% confidence interval, yet does not report the estimate or interval. Without those figures, readers cannot judge the observed response magnitude or how precisely it was estimated. A completed status and an enrollment figure do not substitute for outcome results.
The record also contains inconsistencies in the stated age range and endpoint timing. Such discrepancies are statistically relevant because they affect the target population and the interpretation of when an outcome was measured. The entry does not explain how these issues were resolved. The listed safety counts, meanwhile, demonstrate the importance of distinguishing a zero observed count from proof of no risk and of avoiding unsupported comparisons when no control group is present.
14. 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 the primary endpoint percentage or its 95% confidence interval. It therefore does not permit evaluation of the response magnitude or precision. Although enrollment is listed as 106, the number included in the immunogenicity analysis is not reported. The according-to-protocol population description is incomplete, and the record does not explain missing measurements or exclusions.
The study has no separate comparator group. Its single-group design limits interpretation to outcomes observed in the cohort and does not support a randomized estimate of a difference between interventions. The record also does not report infection outcomes, despite the stated interest in long-term protection against hepatitis B infection.
Several descriptions are inconsistent or incomplete. The brief summary gives an age range of 18 to 40 years, while the arm description gives 40 to 60 years. The primary outcome timeframe says 7 days after challenge, but the endpoint definition uses a one-month post-challenge measurement. The record does not reconcile either discrepancy. The immunogenicity population wording also refers to an HRV vaccine even though the study concerns HBV vaccine; the record does not clarify this wording.
The registry lists eight outcome measures but no analyses. A statistical analysis plan, sample-size justification, handling of multiplicity, interim analyses, and missing-data methods are not reported in the registry record. Safety reporting gives aggregate counts without further detail about event types among the other adverse events. These limitations constrain both reproducibility and interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Long-term Persistence of Immunity to Hepatitis B in Adults Vaccinated With GlaxoSmithKline (GSK) Biologicals' Hepatitis B Vaccine (HBV), Engerix-B — NCT02901951.
- Registry record last updated 2020-01-02; status last verified 2019-12.
- Results first posted 2018-08-03.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02901951 is a completed Phase 4, single-group study sponsored by GlaxoSmithKline. It lists enrollment of 106 and examines adults described as having received three or four Engerix-B doses 20 to 30 years earlier, followed by a single challenge dose. The primary endpoint is the percentage meeting an anamnestic antibody-response definition, with a stated 95% confidence interval.
The registry record does not report the primary endpoint estimate or its interval and lists no analyses. It describes eight outcome measures and includes safety counts: 0 serious adverse events among 103 at risk, 75 with other adverse events among 103 at risk, and 0 deaths. The record contains unresolved differences in the stated age range and primary endpoint timing, and does not report the size of the immunogenicity analysis population.