Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Engerix™-B in Adults With or Without Type 2 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Engerix™-B in Adults With or Without Type 2 Diabetes Mellitus (NCT01627340), a non-randomized phase 4 study. The primary outcome is Number of Subjects Seroprotected for Anti- Hepatitis B Surface Antigen (Anti-HBs) Antibodies.

2. Clinical Question

The study asked whether adults with type 2 diabetes and adults without a documented diagnosis or history of diabetes were seroprotected against hepatitis B after receiving Engerix™-B. Both groups received the same primary vaccination course: doses at 0, 1 and 6 months. The diabetes group included subjects diagnosed with type 2 diabetes within the five-year period before study start. The control group included subjects with no diagnosis or documented history of diabetes.

The primary endpoint was the number of participants classified as seroprotected for anti-hepatitis B surface antigen antibodies at one month after the third dose, identified as Month 7. Seroprotection was defined using an anti-HBs concentration threshold of at least 10 mIU/mL. This endpoint therefore concerns the proportion of evaluable participants meeting a specified antibody threshold, although the registry record identifies the primary measure as a count.

The comparison is between groups defined by diabetes status, not between a vaccine group and an untreated group: both groups received the vaccine. The study was non-randomized, so the groups were not assigned by chance. Differences in their outcomes could reflect diabetes status or other differences between the groups. The record itself cautions that the arms are not a like-for-like control comparison.

The registry record does not report the primary endpoint counts or the statistical comparison between groups. It therefore does not establish from the posted results how many participants in either group met the seroprotection threshold, how large any between-group difference was, or how precisely that difference was estimated.

3. Trial Design

This completed Phase 4 study evaluated the immunogenicity and safety of Engerix™-B in adults with or without type 2 diabetes mellitus. It was an open-label, parallel-group study with non-randomized allocation and no masking. The registry lists an enrollment of 667. The study began on 2012-07-24, and primary completion was recorded as 2013-12-18.

The two groups were defined by participants’ diabetes status. The diabetes group consisted of subjects diagnosed with type 2 diabetes within the five-year period before study start. The control group consisted of subjects with no diagnosis or documented history of diabetes. Both groups received three intramuscular doses of Engerix™-B at 0, 1 and 6 months, administered into the deltoid region of the non-dominant arm.

Because allocation was not randomized, diabetes status was not an assigned intervention. The groups could differ in characteristics other than diabetes status, including characteristics that might relate to immune response or safety. The registry specifically cautions that the arms are not a like-for-like control comparison. Results should consequently be read as a comparison between these enrolled groups, not as a randomized estimate of the effect of diabetes status.

The primary outcome was assessed one month after the third vaccine dose. The listed secondary outcomes include anti-HBs antibody concentration and counts of participants reporting solicited local symptoms, solicited general symptoms, unsolicited adverse events and serious adverse events. The registry record does not report the statistical analysis methods for these outcomes or results for the primary endpoint.

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: There was re-allocation of 7 subjects conducted due to certain discrepancies between subjects' attributes identified from two different sources and as a result of which, there was an increase in the number of subjects from the 667 subjects targeted initially.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects who received all 3 doses of the EngerixTM-B vaccine, for whom post-vaccination immunogenicity results were available and for those in the Control Group, a suitable match was available in the Diabetic Group.

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 Number of Subjects Seroprotected for Anti- Hepatitis B Surface Antigen (Anti-HBs) Antibodies, measured over At one month after the third dose of primary vaccination (Month 7).

The primary endpoint counts participants who met the study’s definition of seroprotection for anti-hepatitis B surface antigen antibodies. The record defines a seroprotected participant as a vaccinated subject whose anti-HBs antibody concentration was at least 10 mIU/mL. The endpoint was assessed one month after the third dose of the primary vaccination course, at Month 7.

This threshold-based outcome turns a laboratory measurement into a clinically interpretable classification: each evaluable participant either meets the stated threshold or does not. Comparing the number meeting the threshold between groups can describe how often seroprotection was observed in each group. The underlying antibody concentration is also listed as a secondary outcome, so the registry distinguishes the threshold-based primary measure from measurement of antibody concentration itself.

General statistical context: A threshold outcome is straightforward to describe, but it does not show how far above or below the threshold each person’s antibody concentration lies. Two groups could have similar counts meeting the threshold while differing in the distribution of antibody concentrations among participants. Conversely, a threshold-based group difference alone does not describe the full range of antibody responses.

The registry record gives the definition and assessment time but does not report the primary endpoint counts for either group. The size and precision of any observed group difference therefore cannot be assessed from the posted primary results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a parallel-group, open-label study with non-randomized allocation. It describes the outcome definitions and the intended analysis population, but does not report the statistical methods used for the primary or secondary analyses. The explanations below distinguish general statistical concepts from methods documented in the registry record.

What does non-randomized allocation mean for the comparison?

The groups were formed according to diabetes status rather than random assignment. That makes the comparison observational with respect to diabetes status: participants’ group membership was not allocated by the study. Randomization, as a general method, can help balance both measured and unmeasured characteristics across groups on average. With non-randomized groups, differences in other characteristics may remain and may influence outcomes. The registry record does not report an adjusted analysis that would address such differences, and it cautions that the arms are not a like-for-like control comparison.

Both groups received Engerix™-B, so the design does not compare vaccination with no vaccination. The central comparison is between the enrolled diabetes and control groups after the same vaccination course. Any group difference would be an association in this study population; the design alone would not show that diabetes status caused that difference.

What is measured by the primary endpoint?

The endpoint is a count of participants meeting a threshold for anti-HBs antibody concentration. The definition classifies a vaccinated participant as seroprotected when the concentration is at least 10 mIU/mL. The assessment is at Month 7, one month after the third dose. The record describes the primary analysis population as the According-to-Protocol cohort for immunogenicity: evaluable subjects who received all three doses and had post-vaccination immunogenicity results available. The description also refers to a suitable match for control-group participants, but the registry wording is incomplete and does not specify further details.

General statistical context: For a binary outcome such as meeting or not meeting a threshold, results may be summarized as counts and proportions. Comparisons may use differences or ratios of proportions, but the registry record does not report which effect measure, if any, was used. No effect estimate, confidence interval or primary endpoint test result is reported, so none can be interpreted.

What can the safety counts tell readers?

The registry lists participants with serious adverse events and the corresponding numbers at risk in each group. These counts describe reported events in the record. They do not, by themselves, show whether the groups differed beyond what might be expected from sampling variation, and the record does not give an inferential comparison for them. Because allocation was non-randomized, the counts also do not isolate an effect of diabetes status. The registry lists other outcome measures relating to symptoms and adverse events, but the corresponding results are not reported in the record.

How should uncertainty and over-dispersion be understood?

General statistical context: An estimate from a study is uncertain because the observed participants are only one sample from the population of interest. A confidence interval communicates this sampling uncertainty under the assumptions of the analysis. It does not account automatically for every potential source of bias, such as differences between non-randomized groups or missing outcome data.

Over-dispersion is a general concern when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and confidence intervals too narrow. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a model, a dispersion assessment or a correction for over-dispersion, so it is not possible to say whether any such method was used in this study.

What does the registry report about the statistical plan?

The record lists zero analyses and does not describe the inferential statistical plan, adjustment variables, handling of missing data, or multiplicity procedure. These details are not reported in the registry record. The record also does not provide a sample-size justification. Any sample-size planning illustration associated with the posted information should be understood as a planning exercise based on stated assumptions, not as an analysis of trial outcomes or observed power. No numerical planning estimates are reported in the record information available for interpretation.

In short, the design and endpoint definition are described, but key elements needed to reproduce or assess the statistical analysis are not reported. The absence of a documented analysis should not be filled in by assuming a particular test, model or adjustment strategy.

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("Diabetes Group", "Control Group")
n      <- c(378, 189)
events <- c(285, 155)
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  Diabetes Group  378  285  75.4  70.7  79.7  70.8  79.5  70.8  79.5
ARM  Control Group  189  155  82.0  75.8  87.2  75.9  86.8  75.9  86.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures: the primary seroprotection count, anti-HBs antibody concentration, and counts of participants reporting solicited local symptoms, solicited general symptoms, unsolicited adverse events and serious adverse events. It lists zero analyses. The record does not explain whether these outcomes were tested, how they were prioritized beyond identifying the primary endpoint, or whether any multiplicity procedure was planned or used.

General statistical context: When several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each is interpreted separately without accounting for the testing strategy. Procedures for controlling multiplicity can change how results are interpreted. Since the registry record does not report a multiplicity plan or analysis results, no conclusion about adjustment can be made.

The record describes the primary analysis population as the According-to-Protocol cohort for immunogenicity, including evaluable participants who received all three doses and had post-vaccination immunogenicity results available. That description indicates that the primary outcome was not simply defined over everyone enrolled. The record does not report the number included in this population, the number excluded, reasons for exclusion, or the amount and handling of missing outcome data. The reference to a suitable match for control-group participants is incomplete in the registry description, so further details should not be inferred.

General statistical context: Excluding participants without complete vaccination or outcome data can affect interpretation if inclusion is related to their likely outcome. Missingness can also reduce precision. Without participant flow, missing-data methods and analysis results, readers cannot assess these issues for this study. The registry record does not report an intention-to-treat analysis or a sensitivity analysis for missing data.

These omissions limit evaluation of how the analysis population was formed, how multiple outcomes were handled and whether missing results could influence the findings. They do not establish that the analysis was inappropriate; they mean the relevant details are not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (0.4%), gastroenteritis (0.4%), hypomagnesaemia (0.4%), hyponatraemia (0.4%), intestinal obstruction (0.4%).

The serious adverse event counts in the registry record are 16 participants with an event among 416 at risk in the diabetes group, and 4 participants with an event among 258 at risk in the control group. These are participant counts, not a reported statistical comparison. The record does not provide a confidence interval or p-value for the difference, and no adjusted comparison is reported.

The groups were non-randomized and differed by diabetes status. As the registry cautions, they are not a like-for-like control comparison. The counts therefore should not be interpreted as evidence that diabetes status caused a difference in serious adverse events. The record does not report details sufficient to assess possible differences in follow-up, participant characteristics or other influences on these counts.

The registry also lists serious-event terms, including Dehydration, Gastroenteritis, Hypomagnesaemia, Hyponatraemia, Intestinal obstruction and Leukocytosis, each at 0.4%. These entries do not replace the group-level counts or establish a comparison between groups. The record lists additional safety outcomes for solicited symptoms and unsolicited adverse events, but their results are not reported in the registry record.

These figures describe what the registry reports for serious adverse events. They do not, on their own, establish a causal safety effect or a difference between the groups.

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

The registry record establishes that Engerix™-B was given to adults with and without type 2 diabetes in a three-dose course at 0, 1 and 6 months, and that seroprotection was defined using an anti-HBs threshold of at least 10 mIU/mL one month after the third dose. It also provides selected serious adverse event counts. These details clarify what the study set out to measure and which groups were observed.

The record does not report the primary seroprotection counts, antibody concentration results, or statistical comparisons. It therefore does not show the observed immunogenicity result for either group or quantify how the groups compared. It also does not provide a confidence interval or other measure of precision for the primary outcome. The absence of these results means the registry record cannot support a conclusion about the direction or size of a group difference.

The serious adverse event counts describe reported events among participants at risk, but they do not demonstrate a causal relationship or a statistically reliable difference. The non-randomized design is important: participants were grouped according to diabetes status, and the record cautions that the arms are not a like-for-like control comparison. Any comparison could reflect differences beyond diabetes status.

General statistical context: A study result can be estimated imprecisely even when the direction of the estimate is known, and a result that is statistically compatible with no difference is not proof that groups are identical. Conversely, a numerical difference does not by itself establish clinical importance or causation. Those judgments require outcome estimates, uncertainty information, study-design context and relevant clinical interpretation.

Enrollment and the described analysis population should not be confused. Enrollment is reported as 667, while the primary analysis is described for an evaluable According-to-Protocol cohort; the number analyzed is not reported in the registry record. As a result, the reader cannot determine from the record how many participants contributed to the primary endpoint analysis.

In practical terms, this record documents a study question and design, but the posted results do not include the primary outcome information needed to answer that question quantitatively. It should not be read as evidence of either equivalence or a meaningful difference between groups.

14. Why This Trial Matters Statistically

This study illustrates why a clear endpoint definition and a complete results record are both necessary for statistical interpretation. The registry defines seroprotection using a specified anti-HBs threshold and an assessment time after the vaccination course. That makes the intended primary outcome understandable. But without the group counts or a reported comparison, the endpoint definition alone cannot indicate what the study observed.

The non-randomized design also matters. The groups were defined by diabetes status rather than randomized assignment, and the registry warns that they are not a like-for-like control comparison. This is a useful reminder that a parallel-group layout does not itself ensure comparability. Statistical adjustment can sometimes address measured differences, but the registry record does not report an adjustment strategy or analysis results, and adjustment cannot automatically remove all sources of bias.

The distinction between an enrolled population and an analysis population is another important statistical issue. The record reports enrollment and describes an According-to-Protocol immunogenicity cohort, but does not report how many participants were analyzed or how missing outcomes were handled. Readers need that information to understand the basis of the endpoint estimates and their precision.

Finally, safety counts and immunogenicity outcomes answer different questions. The serious adverse event counts provide descriptive safety information, while the primary endpoint concerns antibody-based seroprotection. Neither type of information can stand in for the other. The registry record’s missing primary results and analysis details limit what can be concluded, even though the study’s main measurement and general design are identifiable.

The statistical lesson is not that the study found no effect, but that design information and outcome definitions cannot substitute for reported estimates, uncertainty and analysis methods. Transparent reporting of those elements is needed for readers to assess both the observed data and the strength of any comparison.

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 important limitation for interpreting this trial record is that the primary endpoint results are not reported. The registry describes the definition of seroprotection and its assessment time, but gives no group counts, effect estimate, confidence interval or statistical test for that outcome. The listed secondary outcomes likewise do not have reported results in the record information.

The non-randomized allocation limits causal interpretation. Participants entered groups according to diabetes status, and the registry explicitly cautions that the arms are not a like-for-like control comparison. The record does not report group characteristics or an adjusted statistical analysis that could help assess differences beyond diabetes status.

The record does not report the number of participants in the primary analysis population, participant flow, reasons for exclusions, or the handling of missing outcomes. The description of the According-to-Protocol population is incomplete where it refers to a suitable match for control-group participants. The enrollment figure should not be treated as the number analyzed for the primary endpoint.

Details of the statistical plan are also absent: the registry lists zero analyses and does not report a model, comparison method, multiplicity procedure, or sample-size justification. These details are not reported in the registry record, so a specific statistical method or rationale should not be assumed.

The safety information is limited for comparative interpretation. Serious adverse event counts are listed, but no uncertainty estimates or statistical comparison are reported. The record’s listed serious-event terms do not resolve those limitations, and the reported counts should be treated descriptively.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Engerix™-B in Adults With or Without Type 2 Diabetes Mellitus — NCT01627340.
• Registry record last updated 2018-07-31; status last verified 2017-01.
• Results first posted 2015-01-09.
• 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

This completed Phase 4 study evaluated Engerix™-B in adults with or without type 2 diabetes. It used an open-label, parallel-group, non-randomized design. Both groups received three doses at 0, 1 and 6 months. The primary endpoint was the number of participants meeting the anti-HBs seroprotection threshold of at least 10 mIU/mL at Month 7.

The registry record reports enrollment of 667 and describes the primary analysis population as an According-to-Protocol immunogenicity cohort. It lists serious adverse events for both groups, but does not report the primary endpoint results, statistical comparisons, analysis population size, or detailed statistical plan. Because group allocation was non-randomized, the registry cautions that the groups are not a like-for-like control comparison.