Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths (NCT00107042), a randomized phase 2 study. The primary outcome is Qualitative Seroresponsiveness to Hepatitis B Surface Antigen.

2. Clinical Question

The study’s stated purpose was broader than this endpoint. It was designed to evaluate immunogenicity in youth, barriers to vaccine delivery, and factors associated with a diminished immune response. Because the participants were considered potential candidates for future HIV vaccine trials, the summary also describes preliminary assessments of understanding informed consent forms and willingness to participate in a vaccine trial and return for visits, including blood draws.

The registry identifies the primary endpoint as a qualitative response, classified according to an antibody threshold. That makes the central clinical question a comparison of the number classified as responders in the two vaccine groups, rather than a comparison of average antibody levels alone. The record does not report a numerical arm-to-arm result for this endpoint, so the comparative question cannot be answered from the outcome information recorded.

3. Trial Design

The registry describes a randomized, single-masked, parallel-group Phase 2 trial. The interventions were Recombivax and Twinrix, both licensed vaccine products according to the study summary. The record reports enrollment of 123 and identifies the sponsor as the University of North Carolina, Chapel Hill. The trial status is completed; the recorded start is 2004-02 and the primary completion is 2008-07.

Participants in the Recombivax arm were scheduled to receive doses at weeks 0 and 24. Participants in the Twinrix arm followed the same stated schedule. A risk-behavior assessment was administered at week 12 in both arms. Post-vaccination follow-up visits and bloodwork were scheduled at weeks 28 and 76. The primary outcome was assessed at week 28, described as one month after the second immunization.

Random allocation supports a comparison between assigned groups, while a parallel-group design means the groups received their respective interventions rather than crossing over between them. These are general features of the design; the registry does not report the method used to generate the allocation sequence or how allocation was concealed. The record labels masking as single but does not report who was masked.

The registry summary states that participants were included in the primary outcome population if vaccinated at least once and labels that population intent-to-treat. The record does not provide further detail about the handling of participants who did not receive a dose, missed a visit, or lacked a week 28 blood sample. It also does not report the age range, sites, or additional eligibility criteria. The trial included other areas of assessment, but the primary clinical comparison described in the registry is the qualitative antibody response at week 28.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants were included if they were vaccinated at least once (Intent-to-Treat)

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 Qualitative Seroresponsiveness to Hepatitis B Surface Antigen, measured over Week (Wk) 28 (One month after the second immunization).

The primary endpoint is qualitative seroresponsiveness to hepatitis B surface antigen at week 28. The registry defines a responder as a participant with a serum antibody level greater than or equal to 10 mIU/mL and a non-responder as a participant with a level less than 10 mIU/mL. Week 28 is described as one month after the second immunization. The outcome unit is participants, and the endpoint is recorded as a number rather than a continuous measurement.

This threshold converts a laboratory antibody measurement into a clinically interpretable classification: whether each participant crossed the specified response level. Such a binary endpoint can summarize the proportion of a group that reaches a prespecified antibody threshold. It does not preserve the full range of antibody values, so participants just above and far above the threshold are both classified as responders. Quantitative vaccine response is listed among the secondary outcomes, which addresses antibody levels in a different way.

The registry’s endpoint definition identifies what should be counted, but the primary outcome counts by arm are not reported in the registry record. The available description therefore supports explaining the endpoint, not estimating the response in either group or comparing the groups. The recorded primary outcome also refers to the week 28 assessment; the record does not provide a corresponding numerical result for the later follow-up visit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A useful statistical interpretation begins by separating the outcome definition from the outcome estimate. The registry defines the endpoint as the number of participants who met the response threshold, but the primary outcome values by arm are not reported in the registry record. Statistical methods can explain how such data would ordinarily be summarized; they cannot recover missing arm-specific results.

What does a binary endpoint represent?

The primary endpoint classifies each participant as a responder or non-responder using the antibody threshold of 10 mIU/mL. A binary outcome is useful when the scientific question concerns whether a defined criterion has been reached. In this trial, the classification can be expressed as a count or as a proportion within each arm, provided the relevant outcome denominator is known. The record describes the count-based endpoint, but it does not report the arm-specific counts or the number with an evaluable week 28 result.

Turning a continuous antibody value into a binary category simplifies interpretation, but discards information about how far an individual value is from the cutoff. A participant just below the threshold and one with a much lower value receive the same non-responder classification; the same loss of detail occurs among responders. This is a general property of threshold-based outcomes, not a claim about the distribution observed in this trial.

How would an arm comparison be interpreted?

In a randomized two-arm study, an unadjusted comparison of binary outcomes would ordinarily describe the response in each group and quantify the contrast between them. A confidence interval would describe the range of effect sizes compatible with the data under the method’s assumptions. Its width reflects precision: wider intervals indicate less precise estimation, while narrower intervals indicate greater precision. A confidence interval does not by itself establish that an effect is clinically important.

None of these comparative quantities can be stated for the primary endpoint from the registry record because the necessary outcome counts and denominators are not reported. No p-value or confidence interval for the primary comparison is reported in the record. It would be inappropriate to infer one from the enrollment figure or from the safety counts, since those describe different information.

What does randomization contribute?

Randomization is intended to make assigned groups comparable, on average, with respect to factors measured and unmeasured at baseline. It supports interpreting a between-group contrast as an effect of assignment when allocation and follow-up are implemented and analyzed appropriately. Randomization does not guarantee that every characteristic will be balanced in a particular trial. The registry identifies the allocation as randomized, but does not report the sequence-generation or concealment procedures, baseline characteristics, or a detailed analysis plan.

The trial is described as single-masked. Masking can reduce the influence of knowledge about treatment assignment on some aspects of care, reporting, or assessment, depending on who is masked and how outcomes are measured. The registry does not identify the masked party, so the exact protection against bias cannot be assessed from this description.

How should the secondary analyses be read?

The registry lists 29 outcome measures and 64 analyses. It names quantitative vaccine response and qualitative response analyses involving study arm and participant or site characteristics. These counts indicate a broad set of recorded outcomes and analyses, but do not tell which comparisons were prespecified as confirmatory, whether outcomes overlap, or which statistical methods were used. The record does not report a multiplicity adjustment or a hierarchy of hypotheses.

When many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed separately. This is a general statistical concern, not a statement that any particular result in this trial is spurious. Interpretation depends on the analysis plan, the purpose of each analysis, and the treatment of multiple comparisons; those details are not reported in the registry record.

What role do planning illustrations play?

The registry describes sample-size planning illustrations based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations are prospective planning calculations: they describe the number of participants per arm that a future study might require under stated assumptions. They are not observed power and do not establish the probability that this completed trial detected an effect. The registry’s assumption statement does not replace the absent primary outcome counts or provide a reported primary comparison.

Any planning calculation based on an observed effect is sensitive to the estimate used, and an observed effect may be imprecise. A planning illustration should therefore be understood as conditional on its assumptions rather than as a guarantee about a future study. The record does not report a sample-size justification or the trial’s original statistical plan, so the relationship between the planning assumptions and the original trial design is not reported in the registry record.

Why can missing outcome information matter?

Binary response analysis requires knowing both who met the threshold and who had an evaluable measurement. If some participants lack a week 28 result, the analysis depends on how their outcomes are treated and on whether missingness is related to response or group assignment. This is a general issue for outcome assessment. The registry record does not report missing-outcome counts, reasons for missingness, or an imputation or sensitivity-analysis method, so the impact of missing data cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry records 29 outcome measures and 64 analyses, including quantitative and qualitative vaccine response and analyses involving study arm, site effect, age, gender, Hispanic ethnicity, and race. A large analysis set can create multiplicity concerns because repeated statistical testing can produce apparently notable findings by chance. This is a general caution; it does not imply that any particular finding in this trial is false. The record does not report which analyses were designated primary beyond the named primary endpoint, how secondary analyses were prioritized, or whether any adjustment for multiple comparisons was used.

The primary outcome population is described as participants vaccinated at least once and is labeled intent-to-treat. That operational definition is narrower than simply assuming that every randomized participant contributed an outcome: the record does not state the number randomized to each arm or provide the number with a week 28 measurement. It also does not report how participants who did not receive a vaccine or who lacked an outcome measurement were handled. The specific analysis population and its relationship to all randomized participants therefore cannot be fully characterized.

Missing-data methods, reasons for missing week 28 measurements, and sensitivity analyses are not reported in the registry record. These omissions matter because a threshold-based response analysis requires an evaluable antibody result or an explicit rule for handling its absence. Without those details, the potential influence of missing outcomes on the comparison cannot be assessed.

The registry does not report the protocol’s sample-size justification, interim analyses, or a detailed statistical analysis plan. The planning assumptions recorded for sample-size illustrations do not establish what methods were used for the completed trial’s primary analysis.

11. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthenia (1.7%), forearm fracture (1.7%), road traffic accident (1.6%), anxiety (1.6%).

The registry lists serious adverse events for both vaccine groups. In the Recombivax group, 2 participants were affected among 60 at risk; in the Twinrix group, 2 participants were affected among 63 at risk. These are reported counts, not a comparison adjusted for follow-up or other factors. The record does not provide a statistical comparison of these figures, and the counts alone do not establish whether the groups differ.

For other adverse events, the registry reports 6 affected among 60 at risk in the Recombivax group and 4 among 63 at risk in the Twinrix group. These figures are listed separately from the serious adverse event counts. The registry also names Asthenia and Forearm Fracture at 1.7% each, and Road Traffic Accident and Anxiety at 1.6% each among its top serious terms. The record does not make clear in this listing whether these terms are arm-specific.

Deaths are not reported in the registry record. The event figures do not describe the timing, duration, severity distribution beyond the serious designation, or relationship to vaccination. They should be read as recorded safety counts, not as proof that an event was caused by a vaccine or that an unlisted event did not occur. These safety data address a different question from the week 28 antibody-response endpoint.

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

This trial is described as a randomized comparison of two hepatitis B vaccine products administered on the same two-dose schedule. The registry specifies a binary seroresponse endpoint at week 28 and gives a threshold for classifying participants as responders. These details define the intended comparison and make the endpoint understandable.

However, the primary outcome counts by arm are not reported in the registry record. The available record therefore does not establish the observed response in either group, the difference between groups, or the precision of that difference. It does not support a conclusion that one vaccine strategy produced a higher response, nor does it support a conclusion that the responses were equivalent. Absence of a reported comparison is not evidence of no difference.

The outcome is a threshold-based antibody measure, not a direct report of clinical hepatitis B events. A response classification can describe whether a laboratory level crossed the specified cutoff, but it does not by itself describe how long a response persisted or what clinical outcomes followed. Although bloodwork was scheduled at week 76, the registry information does not give a numerical week 76 result.

The trial summary also describes assessments of vaccine delivery barriers and participants’ understanding of informed consent and willingness to take part in future vaccine trials. These aims provide context for the study, but the registry record does not report results for those assessments in the registry entries. Nor does it report the estimated relationships between response and the listed participant or site factors.

The safety counts should be interpreted separately from the immunogenicity endpoint. They are descriptive registry entries, and the record does not provide an adjusted safety comparison or details sufficient to attribute events to vaccination. Overall, the record supports describing the design, schedule, endpoint definition, and recorded safety counts. It does not provide the primary efficacy-style outcome estimates needed to quantify comparative immunogenicity.

13. Why This Trial Matters Statistically

The trial is statistically informative as an example of the distinction between a clearly defined endpoint and a fully reported result. A threshold-based endpoint can be specified precisely: the registry states the antibody cutoff, the assessment time, and the intended analysis population. Yet without arm-specific counts and denominators, readers cannot estimate the response in either group or quantify the randomized comparison.

The design also illustrates how multiple research aims can coexist. The summary describes vaccine immunogenicity, barriers to delivery, factors that may predict diminished response, and preliminary questions relevant to future HIV vaccine trials. The registry lists 29 outcome measures and 64 analyses. That breadth makes it important to distinguish the primary question from secondary and exploratory analyses and to understand any multiplicity strategy. The record does not report that strategy.

Another statistical lesson concerns analysis populations. The registry labels the primary outcome population intent-to-treat while defining inclusion as vaccination at least once. A label alone is not enough to determine who contributed to an analysis. Clear participant flow, outcome availability, and handling of missing measurements are needed to assess how closely the analysis reflects randomized assignment; those details are not reported in the registry record.

Finally, a planning illustration is not a trial result. Sample-size calculations depend on assumptions and are intended to guide future research. They cannot replace observed outcome estimates, and they are not a measure of the completed trial’s observed power. For this trial, the reported endpoint definition is useful, but the absent primary comparison limits what can be concluded statistically from the registry record.

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 main limitation for interpreting the primary question is that arm-specific week 28 responder counts and denominators are not reported in the registry record. Without those values, the primary comparison cannot be quantified, and its precision cannot be assessed. The endpoint definition and the enrollment figure do not resolve this reporting gap.

The record identifies the primary outcome population as participants vaccinated at least once, but does not provide participant flow by arm or the number with an evaluable week 28 measurement. It does not report how missing measurements were handled, why they were missing, or whether sensitivity analyses assessed their possible influence. These details are needed to judge the robustness of a binary response comparison.

Several design and analysis details are also not reported in the registry record: the age range and additional eligibility criteria, the randomization and allocation-concealment procedures, the identity of the masked party, baseline characteristics, and the detailed statistical analysis plan. The record does not state whether interim analyses occurred, how multiplicity was handled, or the original sample-size justification. The listed secondary analyses do not include their estimates or uncertainty measures in the registry entries.

The safety entries lack detail on event timing, duration, attribution, and arm-specific distribution of the listed serious terms. Deaths are not reported in the registry record, which should not be interpreted as a confirmed absence of deaths. The later follow-up schedule is described, but numerical week 76 results are not reported in the registry entries. These limitations restrict interpretation to the registered design and outcome definitions, rather than a full assessment of comparative results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of Two Hepatitis B Vaccines in HIV-negative Youths — NCT00107042.
• Registry record last updated 2017-03-29; status last verified 2016-03.
• Results first posted 2012-12-04.
• 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.

18. Record Summary

The registry describes a completed, randomized, single-masked, parallel-group Phase 2 trial sponsored by the University of North Carolina, Chapel Hill. Enrollment is recorded as 123; the start is 2004-02 and primary completion is 2008-07. The study compared Recombivax and Twinrix, each scheduled at weeks 0 and 24, in youth described as HIV-negative in the title and at risk for hepatitis B and HIV infection in the summary.

The primary endpoint was qualitative seroresponsiveness to hepatitis B surface antigen at week 28, one month after the second immunization. A responder was defined by an antibody level of at least 10 mIU/mL. The record also describes a week 12 risk-behavior assessment and follow-up visits and bloodwork at weeks 28 and 76.

Arm-specific primary outcome results, missing-data methods, and detailed analysis procedures are not reported in the registry record. Safety entries include serious and other adverse event counts by group, while deaths are not reported in the registry record. The registered information defines the study question and endpoint, but does not quantify the primary comparison.