Hepatitis B Booster Study in Adolescence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hepatitis B Booster Study in Adolescence (NCT02169674), a non-randomized phase 4 study. The primary outcome is Serum Anti-HBs Concentration 12 IU/L or Greater.

2. Clinical Question

The central question concerns persistence of an antibody measure years after infant immunization, rather than a randomized comparison of vaccine with no vaccine. The study focuses on two adolescent age groups and describes blood testing as the way to assess antibody levels. A subsequent vaccination and blood test were intended to assess recall response among participants below the stated threshold.

The registry record does not report how many participants met the primary endpoint in either group. It also does not report the number who had a booster response, the definition used for that response, or results from any second vaccination. Thus, the clinical question and planned sequence of assessments can be described, but the registry record does not establish what proportion retained the measured antibody level or responded after vaccination.

3. Trial Design

This is a completed phase 4 study sponsored by the University of British Columbia. The registry describes a parallel, non-randomized design with no masking. Enrollment was 359. The listed groups are 10–11 Year-olds and 15–16 Year-olds, and both group descriptions name recombinant hepatitis B virus vaccine, EngerixB, as the intervention.

The study began in 2014-09, had primary completion in 2015-08, and is marked completed. Those registry dates describe the study record; they do not, by themselves, tell a reader when every participant was assessed or how long individual follow-up lasted. The primary outcome timeframe is stated as 10 or more years after infant hepatitis B immunization.

The summary describes an initial blood test, an offer of a test vaccination for those without a minimal antibody level, and another blood test about one month later to assess whether a booster response occurred. It also describes offering a second hepatitis B vaccination to a few participants without a booster response. These details describe the study plan in the registry summary. The record does not report the number who received each step or whether all planned procedures were completed.

Because allocation was non-randomized, the age groups should not be interpreted as randomized treatment arms. The registry itself notes that they are not a like-for-like control comparison. Age group, time since infant immunization, and other group differences cannot be separated from one another through random allocation in this design. The registry record does not describe adjustment methods that might address such differences.

The record lists five outcome measures and no statistical analyses. It does not report a sample-size justification, a prespecified analysis plan, or any interim analyses. The sample-size assumptions described for planning illustrations are not the trial’s own design assumptions. Consequently, the design can be characterized from the registry description, but the reasoning behind the chosen enrollment and the details of the planned inferential analyses 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: Initially, 359 volunteers who met inclusion criteria where recruited, of whom 6 were deemed ineligible due to late disclosure of neonatal HBV vaccination (n=3), ineligible medical condition (n=2) or additional doses of HBV vaccine (n=1). Three early consent withdrawals resulted in 350 participants who underwent baseline testing.

Overall Study

Reasons for not completing this period:

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 Serum Anti-HBs Concentration 12 IU/L or Greater, measured over 10 or more years after infant HB immunization.

The primary endpoint is the number of participants with a serum anti-HBs concentration of at least 12 IU/L, described as persistent anti-HBs titer greater than 12 IU/L. It is assessed 10 or more years after infant hepatitis B immunization, with the primary outcome timeframe distinguishing the 10- or 15-year period after infant immunization. The endpoint is a participant count, not a continuous summary of antibody concentration.

Antibody concentration is used in this study as a marker of residual hepatitis B immunity. A threshold turns a laboratory measurement into a binary classification: a participant’s measured level is either at or above the stated threshold, or it is below that threshold. This makes it possible to report how many participants meet the registry’s definition of residual immunity. It does not make the antibody measure identical to a direct measure of hepatitis B disease or guarantee an individual’s future protection.

General: A threshold-based endpoint can be straightforward to interpret, but it discards information about how far a measurement lies from the cutoff. Two people on opposite sides of the threshold may have similar laboratory values, while people on the same side may have quite different values. The choice of threshold therefore matters to the endpoint’s meaning. The registry identifies the threshold but does not report a separate justification for its selection.

The record does not provide the number meeting the endpoint, the number tested, or a statistical estimate comparing the age groups. Without those results, the endpoint definition can be explained, but its observed frequency and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary outcome as a participant count. The endpoint classifies participants according to whether their anti-HBs concentration meets the stated threshold. No primary endpoint result is reported, so there is no observed count or estimate to interpret statistically.

What does a participant count tell the reader?

General: A count records how many observations fall into a defined category. For a binary outcome such as meeting or not meeting an antibody threshold, a count is most informative when paired with the number assessed. The count alone does not establish the frequency in the group, and a count from one group cannot be compared fairly with a count from another group when their denominators differ. The registry does not report the endpoint-specific denominators or counts needed to make that assessment.

The record lists 359 participants enrolled. Enrollment is not necessarily the number with a completed blood test or a non-missing primary endpoint. The number assessed, the number excluded from analysis, and the handling of participants with missing outcome data are not reported in the registry record. The separate adverse-event risk counts should not be substituted for missing endpoint denominators.

What does the non-randomized design imply?

General: Random allocation is one way to create groups expected to be comparable, on average, in characteristics that could affect outcomes. In a non-randomized study, differences between groups may be associated with factors other than the exposure or characteristic of interest. This study’s age groups are explicitly described as not being a like-for-like control comparison. The record does not report a method for adjusting for possible group differences, so a causal interpretation of an age-group contrast is not supported by the design information available.

The parallel structure means that the registry presents separate groups, rather than describing a crossover in which each participant receives multiple conditions in sequence. The record does not report individual-level data or analyses that would clarify how participants were assigned to the age groups. It also does not report a masking procedure; masking is listed as none. The consequences of measurement awareness depend on how outcomes are assessed, and details beyond the blood-test description are not reported.

How should a confidence interval be understood?

General: A confidence interval conveys uncertainty around an estimate under a specified statistical method. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the design, measurement, and assumptions used. An interval around a group-specific proportion or a contrast would help readers assess precision alongside the point estimate. The registry record reports no confidence intervals or other inferential estimates for the primary endpoint.

The record also reports zero statistical analyses. That does not mean the study had no statistical considerations; it means analyses are not listed in the registry information available for this description. The planned statistical model, estimation method, significance threshold for the primary analysis, and handling of potential confounding are not reported in the registry record.

What is the role of sample-size planning?

General: Sample-size planning illustrates how many observations might be needed to detect a specified effect under chosen assumptions. It is not an observed result and does not show that a study had a particular probability of finding a result after the data were collected. The planning illustration associated with this study is described as using 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 fraction of the observed effect. It is explicitly not the trial’s own design calculation. The actual illustration values and the observed effect are not reported in the registry record.

For binary outcomes, the event frequency and the number assessed affect the precision of estimates. The registry’s outcome is a count, but no primary result or endpoint denominator is reported, so no study-specific precision or detectable effect can be assessed. In general, planning assumptions and observed data answer different questions: planning concerns what a design may detect under assumptions, whereas an observed estimate describes the collected data. Neither should be substituted for the other.

Why can over-dispersion matter?

General: Over-dispersion occurs when observed variability exceeds what a statistical model assumes. It can make standard errors too small and confidence intervals too narrow if the model does not account for it. This general issue is relevant to some count-data analyses, but the registry record does not report an over-dispersion assessment or a count model for this trial. The primary endpoint is described as a participant count; no analysis details are available to determine what statistical model, if any, was used.

The study summary further describes a response assessment after vaccination, but the registry does not state how that response was defined statistically or how repeated blood-test measurements were analyzed. It does not report whether laboratory values were treated as continuous measurements in secondary analyses. These missing details prevent a more specific account of the statistical methods used.

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("10-11 Year-olds", "15-16 Year-olds")
n      <- c(137, 213)
events <- c(30, 76)
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  10-11 Year-olds  137  30  21.9  15.3  29.8  15.8  29.5  15.8  29.6
ARM  15-16 Year-olds  213  76  35.7  29.3  42.5  29.6  42.3  29.6  42.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, but it does not report the analysis results for them. It also lists no statistical analyses. The record does not identify which outcomes, if any, were designated secondary or exploratory for analysis, nor does it describe a hierarchy of hypotheses or a plan for controlling the chance of false-positive findings across multiple tests.

General: When several outcomes or comparisons are tested, the chance of obtaining at least one apparently notable result can increase if each test is interpreted without considering the others. Multiplicity procedures can address this issue, but they depend on the outcomes and comparisons planned. Since the registry record does not describe an analysis plan or test results, it is not possible to determine whether multiplicity was addressed.

Missing-data methods are also not reported. The record does not state how many participants had missing blood tests, incomplete follow-up, or unavailable endpoint measurements, or whether any imputation or other missing-data method was used. The enrollment figure does not establish the number included in an endpoint analysis. Without these details, the possibility that analyzed participants differed from those without outcome data cannot be assessed.

The analysis populations are not described. The registry record does not specify whether the primary analysis was intended to include all enrolled participants, only participants who completed the relevant blood tests, or another defined group. It also does not report exclusions, protocol deviations, or a participant flow account.

These omissions do not establish that multiplicity, missing data, or analysis populations were ignored in the study’s conduct. They mean the corresponding procedures and results are not reported in the registry record. As a result, readers cannot evaluate how those choices might affect estimates or their uncertainty.

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 0% reporting threshold.

The adverse-event information reports zero serious adverse events and zero other adverse events for each listed age group. The corresponding numbers at risk are 137 for the 10–11 Year-olds and 213 for the 15–16 Year-olds. These are reported event counts and denominators, not the primary endpoint results.

A reported count of zero means that no events of that category were recorded among the listed participants at risk in the registry’s adverse-event data. It does not establish that no event occurred outside the recorded collection period or that every possible event was captured. The registry record does not describe the safety monitoring period, event-collection procedures, severity definitions beyond the serious category, or how missing safety information was handled.

The record lists no top serious event terms. Death counts are not reported. The adverse-event figures should therefore be read narrowly as the counts posted for the groups, rather than as a complete assessment of safety or as evidence about the primary antibody outcome. The registry record does not provide additional detail that would support broader conclusions about the safety profile.

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

The study addresses persistence of an antibody marker after hepatitis B immunization in infancy. Its registry description identifies a threshold-based primary endpoint, two adolescent age groups, and a planned sequence of blood testing and vaccination for participants below the minimum antibody level. Those details clarify what the investigators intended to assess.

The record does not report the primary endpoint counts, endpoint-specific denominators, or statistical analyses. Therefore, it does not establish how many participants retained an antibody level at or above the stated threshold, whether the groups differed, or how precise any estimate would be. The absence of a posted result is not evidence that the outcome was absent, that the age groups were equivalent, or that the study found no difference.

The record’s description of a test vaccination and repeat blood test points to a separate question about antibody response among participants initially below the minimum. No response counts or analysis are reported. The record consequently cannot quantify how often a booster response occurred or describe the uncertainty around that response.

General: A laboratory marker and a clinical outcome are related but distinct kinds of evidence. Meeting an antibody threshold is the endpoint defined for this study; it is not itself a reported count of hepatitis B disease cases. The registry record does not report disease outcomes that would allow a direct assessment of disease incidence or clinical protection.

The non-randomized design also matters when interpreting any possible age-group contrast. The record cautions that the groups are not like-for-like controls, and no adjustment strategy is reported. Thus, even if a numerical difference were available, the design information alone would not identify its cause.

The posted safety counts are zero in the listed categories, with deaths not reported. These figures are limited to the adverse-event information recorded and do not supply missing primary efficacy results. Overall, the registry record describes the question and planned assessments but does not provide enough outcome or analysis information to draw a numerical conclusion about residual immunity or booster response.

14. Why This Trial Matters Statistically

This trial is statistically relevant because it asks a time-dependent question using a measurable antibody threshold. The endpoint links a laboratory result to a binary classification of residual immunity, while the study summary describes a later response assessment for participants below the stated minimum. These are related but distinct outcome questions and require their own denominators and results to interpret.

The age groups are non-randomized and are explicitly not described as like-for-like controls. This is an important reminder that a group contrast is not automatically a treatment effect. Differences between groups may reflect their composition or other factors, and the registry record does not report adjustment methods that would address those possibilities.

The record also illustrates why an endpoint definition is not the same as an endpoint result. A threshold and a timeframe specify what is to be measured, but interpretation requires the count meeting the definition, the number assessed, and an account of uncertainty. Those primary results and analyses are not reported in the registry record.

General: In studies of antibody persistence, readers should distinguish a marker-based endpoint from direct evidence about clinical disease. A threshold can support consistent classification, but it does not preserve all information in the underlying measurement, and its meaning depends on the stated definition. The record identifies the threshold but does not provide outcome results with which to assess its observed distribution.

Finally, the distinction between the trial’s design and planning illustrations matters. The described sample-size illustration uses stated assumptions and is not the trial’s own design calculation. It cannot be treated as an observed result or as evidence about the study’s ability to detect an effect. Taken together, the registry entries support a careful description of the research question and its statistical limitations, but not a numerical conclusion about the study outcome.

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 immediate limitation for interpreting results is that primary outcome counts and endpoint-specific denominators are not reported in the registry record. Without them, the frequency of participants meeting the antibody threshold cannot be described, and there is no basis for assessing the precision of that frequency.

The non-randomized age-group design limits causal comparisons. The registry cautions that the groups are not like-for-like controls, and the record does not report an adjustment strategy. Characteristics associated with age group or time since infant immunization could affect a comparison, but the record does not provide enough information to characterize or account for such factors.

The study summary describes several stages of assessment, including an initial blood test, an offered test vaccination for participants below the minimum level, a later blood test, and a possible second vaccination. The record does not report how many participants entered each stage, completed each procedure, or had usable measurements. It also does not report the definition or results of the booster response assessment.

The registry lists five outcome measures but no statistical analyses. The primary analysis method, handling of missing data, analysis populations, and any multiplicity approach are not reported. The record also does not provide a sample-size justification for the trial or interim-analysis details. These missing items limit assessment of the analytical plan, but do not show that such procedures were absent from the study’s conduct.

Safety information is limited to the posted adverse-event counts and numbers at risk. The period of safety follow-up, event ascertainment, and death counts are not reported. The registry record therefore supports a narrow reading of those counts, not a comprehensive safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hepatitis B Booster Study in Adolescence — NCT02169674.
• Registry record last updated 2019-03-21; status last verified 2018-12.
• Results first posted 2019-03-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed phase 4, parallel, non-randomized, unmasked study sponsored by the University of British Columbia. Enrollment was 359. The study began in 2014-09 and reached primary completion in 2015-08. Its two listed age groups are 10–11 Year-olds and 15–16 Year-olds, and the intervention is recombinant hepatitis B vaccine, EngerixB.

The primary endpoint is the participant count with an anti-HBs concentration meeting the stated threshold 10 or more years after infant immunization. The study summary describes blood testing and a vaccination-and-retesting sequence for participants below the minimum antibody level. The registry cautions that the age groups are not a like-for-like control comparison.

The registry record does not report primary endpoint results or statistical analyses. It lists zero serious and zero other adverse events in the two groups; deaths are not reported. Details about missing data, analysis populations, multiplicity, and the primary statistical method are not reported in the registry record.