Study to Assess the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) When Co-administered With GSK Biologicals' Diphtheria, Tetanus and Pertussis Vaccine (Boostrix®) in Adults Aged 50 Years and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) When Co-administered With GSK Biologicals' Diphtheria, Tetanus and Pertussis Vaccine (Boostrix®) in Adults Aged 50 Years and Older (NCT02052596), a randomized phase 3 study. The primary outcome is Antibody Concentrations Against Glycoprotein E (Anti-gE).

2. Clinical Question

The clinical question is about the immune response and safety of two vaccine schedules, not about preventing herpes zoster as a clinical outcome. The primary endpoint is an antibody concentration measured by enzyme-linked immunosorbent assay. The registry also describes reactogenicity and safety outcomes, including solicited symptoms, unsolicited adverse events, serious adverse events, and potential immune-mediated diseases.

The timing differs by group because the second GSK1437173A dose occurred at different visits: the primary measurement was at Month 3 for the GSK1437173A Group and Month 5 for the Control Group. Both measurements are described as one month after Dose 2. The study therefore compares responses at a common interval after that dose, despite the different calendar points in each schedule.

3. Trial Design

This was a randomized, phase 3, parallel-group study with no masking. Its stated purpose was to assess immunogenicity, reactogenicity, and safety when the first dose of the GSK herpes zoster subunit vaccine was co-administered with Boostrix, compared with separate administration. The condition listed in the registry is herpes zoster, and enrollment was 935.

The two groups differed in the timing of the first GSK1437173A dose relative to Boostrix. In the GSK1437173A Group, participants received both vaccines at the first visit and a second GSK1437173A injection at the third visit, two months later. In the Control Group, Boostrix was given at the first visit; the two GSK1437173A injections followed at the third and fourth visits, with two months between visits. Thus, the comparison concerns co-administration of Boostrix with the first herpes zoster vaccine dose versus giving those vaccines separately.

The registry records the study start as 2014-02-07, primary completion as 2015-06-16, and status as completed. It lists GlaxoSmithKline as sponsor. The primary immunogenicity outcome was assessed one month after Dose 2: at Month 3 for the GSK1437173A Group and Month 5 for the Control Group.

The primary immunogenicity analysis population was the According-to-Protocol cohort. The registry describes this as subjects meeting all eligibility criteria with available data for the immunogenicity endpoint. This is not necessarily the same population used for safety summaries: the posted safety figures have different at-risk denominators. The registry does not report the reasons for differences between analysis populations or denominators, so they should not be treated as interchangeable.

The trial is described as randomized and parallel, but the registry record does not report the randomization procedure, allocation ratio, or details of any stratification. Masking is listed as none. Further operational details, including the exact visit dates for individual participants, 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: For one subject, the reason for withdrawal was incorrectly entered into the eCRF as "lost due to Crohn's disease." The subject withdrew from the study due to a combination of irritable bowel syndrome and time constraints associated with employment. This information was clarified after database freeze.

Active Phase

Reasons for not completing this period:

Safety Phase

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 subjects meeting all eligibility criteria for whom data concerning immunogenicity endpoint measures were available, only for subjects in the GSK1437173A 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 Antibody Concentrations Against Glycoprotein E (Anti-gE), measured over At 1 month post-Dose 2 (Month 3 for GSK1437173A Group adn Month 5 for Control Group).

The primary endpoint is the concentration of antibodies against glycoprotein E, or anti-gE, measured one month after the second GSK1437173A dose. Concentrations were assessed by enzyme-linked immunosorbent assay and expressed in mIU/mL. The registry reports the endpoint as a geometric mean concentration (GMC) with a 95% confidence interval. The reference seropositivity cutoff was an anti-gE concentration of at least 97 mIU/mL.

In general, a GMC is used for measurements that are positive and often have a skewed distribution. It summarizes concentrations on a logarithmic scale and then expresses the summary on the original measurement scale. It is not the arithmetic average. This can make group summaries more suitable for antibody data, where a small number of high values can otherwise have a strong influence on an arithmetic mean.

The concentration endpoint describes the measured immune response; it is not itself a count of infections or a direct measure of clinical protection. The seropositivity cutoff provides a reference for classifying concentrations, but the posted primary results are group GMCs and their confidence intervals. The registry does not report an individual-level seropositivity proportion as the primary endpoint.

Assessing the response at the same interval after Dose 2 makes the post-dose timing comparable across schedules, even though the visits are at Month 3 in the GSK1437173A Group and Month 5 in the Control Group. The GMC comparison addresses whether antibody concentrations differ between the co-administration schedule and separate administration. It does not, by itself, establish the duration of the response or its relationship to clinical outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean concentration describe?

In general, antibody measurements can be unevenly distributed, with some values much higher than others. A geometric mean summarizes such measurements after applying a logarithmic transformation, averaging on that transformed scale, and converting back to the original scale. It describes a typical multiplicative level rather than the arithmetic average. For this trial, the primary outcome was anti-gE antibody concentration in mIU/mL, summarized as a GMC for each group.

The posted GMCs were 51690 for the GSK1437173A Group and 58000 for the Control Group. Each has a 95% confidence interval. The interval reflects uncertainty in estimating the group GMC under the analysis assumptions; it does not represent the spread of individual participant measurements. The registry does not report a separate standard deviation or other measure of individual-level dispersion for these results.

How should the confidence intervals be read?

In general, a confidence interval is a range of estimates compatible with the observed data and the statistical model at the stated confidence level. Its width reflects the precision of the estimate under that model. A confidence interval is not a guarantee that the true value lies within the observed endpoints, and it is not a prediction interval for future participants. The 95% intervals reported for the group GMCs and the adjusted ratio are therefore uncertainty summaries, not ranges of individual antibody responses.

The adjusted GMC ratio is reported as 1.11 with a 95% confidence interval from 1.02 to 1.21. A ratio expresses one group summary relative to another on a multiplicative scale. The registry labels this as a non-inferiority analysis, but does not report its margin, adjustment covariates, or decision rule. Those details are important because non-inferiority is judged against a prespecified margin, not by interpreting the ratio in isolation.

What does randomization contribute?

In general, random allocation is intended to make comparison groups similar, on average, in factors measured and unmeasured at the time of assignment. It can reduce confounding in a treatment comparison, provided the trial conduct and analysis preserve the benefits of allocation. This study is recorded as randomized, parallel, and unmasked. The registry does not report the sequence-generation or allocation-concealment methods, and it does not give additional details about the allocation process.

Parallel-group design means participants were assigned to one of the vaccine schedules rather than crossing between schedules. The schedules were different in the timing of the first GSK1437173A dose relative to Boostrix. The primary measurement was made one month after Dose 2 in each group, although this fell at Month 3 for the GSK1437173A Group and Month 5 for the Control Group.

Why does the analysis population matter?

The primary endpoint analysis used the According-to-Protocol cohort for immunogenicity. The registry describes inclusion as meeting all eligibility criteria and having available immunogenicity endpoint data. In general, an according-to-protocol analysis focuses on participants who met specified protocol requirements and had usable endpoint information. The criteria can affect who contributes to the estimate and should be considered when interpreting a randomized comparison.

The registry does not report the detailed exclusions, the number excluded for each reason, or a complete account of missing endpoint data. Nor does it describe a missing-data imputation method for the primary endpoint. The reported immunogenicity group sizes are 369 and 380, while the safety at-risk denominators are 412 and 418. These figures refer to different posted analyses and should not be assumed to describe the same analytic population.

What does over-dispersion mean in general?

In general, over-dispersion occurs when the observed variability in data exceeds what a statistical model assumes. It can make standard errors too small if not handled appropriately, leading to confidence intervals that are too narrow and tests that are too optimistic. It is a concern for some count outcomes, especially when events are more variable than a simple count model allows. The registry does not report whether over-dispersion was assessed or whether a particular model for symptom or adverse-event counts was used.

How should multiple outcomes be considered?

The registry lists 11 outcome measures, seven secondary outcomes, and six analyses. In general, examining multiple outcomes or comparisons increases the chance of finding an apparently notable result by chance if each is interpreted without regard to the others. Statistical approaches can adjust for multiplicity or define a hierarchy of outcomes, but the registry record does not report whether a multiplicity adjustment or hierarchy was used. The presence of several outcome measures does not itself indicate that a particular adjustment was applied.

Planning calculations, when presented, are illustrations based on the observed effect, not evidence of the trial's design justification or observed power. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The registry does not report that these assumptions were used to plan the trial. No sample-size justification or interim analysis plan is reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the sponsor's adjusted GMC ratio as 1.11, with a 95% confidence interval from 1.02 to 1.21, and labels the analysis as non-inferiority. The posted arm-level GMCs and their confidence intervals are descriptive summaries; they are not the same statistic as the adjusted ratio. An adjusted comparison can account for features of the analysis that are not reflected in a simple comparison of the two posted GMC summaries.

The registry does not report the adjustment method, the covariates used, or the non-inferiority margin. Those omissions limit independent interpretation of the sponsor's non-inferiority conclusion. A non-inferiority result depends on comparing the confidence interval with a prespecified margin under the trial's analysis plan. The ratio and interval alone cannot supply that missing criterion.

The registry record does not flag a discrepancy between the posted values and the sponsor analysis. The sponsor's reported adjusted analysis should therefore be read as the trial's stated analysis, while recognizing that it cannot be fully evaluated without the margin and method details. No separately calculated adjusted estimate is reported in the registry record.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and seven secondary outcomes, including solicited local symptoms, solicited general symptoms, symptom duration, potential immune-mediated diseases, unsolicited adverse events, and serious adverse events. It also records six analyses. These outcomes cover distinct questions, but the record does not describe how they were prioritized or whether any were considered confirmatory beyond the primary anti-gE endpoint.

In general, when many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if no adjustment or prespecified hierarchy is used. This does not mean that a finding is invalid; it means that readers need to know the analysis plan to judge the evidential strength of multiple results. A multiplicity adjustment, a gatekeeping approach, or clearly defined exploratory analyses can address this issue. Whether any such approach was used is not reported in the registry record.

The registry defines the primary immunogenicity population as the According-to-Protocol cohort, including subjects meeting all eligibility criteria with available immunogenicity endpoint data. It does not report a detailed participant flow, the reasons for exclusions, or the handling of missing antibody measurements. The missing-data assumptions and any imputation method are not reported in the registry record.

Safety results have at-risk denominators of 412 for the GSK1437173A Group and 418 for the Control Group. The immunogenicity summaries have group sizes of 369 and 380. These denominators are tied to different analyses; the registry does not explain the difference. They should not be combined or treated as substitutes for each other.

The registry also does not report the full statistical analysis plan, interim analyses, or sample-size justification. Without these details, readers cannot determine whether every planned endpoint and analysis is represented in the posted results, or how missing data and multiple comparisons were handled. The absence of a reported detail should not be taken as evidence that a particular method was or was not used.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: cardiac failure congestive (1.0%), chronic obstructive pulmonary disease (0.7%), osteoarthritis (0.5%), pneumonia (0.5%), anaemia (0.2%).

The posted serious adverse event figures are 21 affected participants among 412 at risk in the GSK1437173A Group and 31 among 418 at risk in the Control Group. The registry also records 4 deaths in the GSK1437173A Group and 5 in the Control Group. These are observed counts, not proof that a vaccine or schedule caused an event. The record does not provide a causal attribution for these counts.

The registry lists serious adverse event terms with percentages: cardiac failure congestive, 1.0%; chronic obstructive pulmonary disease, 0.7%; osteoarthritis, 0.5%; pneumonia, 0.5%; anaemia, 0.2%; and acute myocardial infarction, 0.2%. These are listed terms and percentages; the record does not specify in this listing how they are distributed by treatment group. They should not be assigned to a particular group based on the overall event counts.

In general, safety counts depend on the event definitions, the time period of observation, and which participants were considered at risk. The registry lists other adverse-event counts of 368 among 412 at risk in the GSK1437173A Group and 380 among 418 at risk in the Control Group, but the category and reporting rules should be considered when interpreting these figures. The registry record does not provide enough detail in the posted figures to establish a causal difference between schedules.

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

The primary result describes anti-gE antibody concentrations one month after Dose 2 for two schedules of GSK1437173A and Boostrix. The GSK1437173A Group GMC was 51690 mIU/mL, and the Control Group GMC was 58000 mIU/mL. The sponsor-reported adjusted GMC ratio was 1.11, with a 95% confidence interval from 1.02 to 1.21. These results address an immunogenicity comparison at a defined post-dose time.

They do not directly show whether either schedule prevents herpes zoster, how long an antibody response persists, or what an individual participant's response will be. The registry lists a seropositivity reference cutoff of at least 97 mIU/mL, but that cutoff is not presented as an individual guarantee of clinical protection. Antibody concentration and clinical outcomes are related kinds of evidence, but they are not interchangeable measures.

The registry labels the adjusted analysis as non-inferiority. Interpreting that label requires the non-inferiority margin and the prespecified statistical decision rule, neither of which is reported in the registry record. The ratio and confidence interval should not be used alone to make a definitive claim about whether a non-inferiority criterion was satisfied.

The safety results describe observed events in the study groups. They do not establish that a reported event was caused by vaccination, and the available serious-event counts do not support a complete causal comparison. The event denominators differ from the primary immunogenicity group sizes, and the record does not report the reasons for that difference in these figures.

Overall, the posted information can be used to understand the measured antibody summaries, the reported adjusted comparison, and the recorded safety counts. It cannot replace details absent from the registry, including the adjustment method, non-inferiority margin, complete missing-data approach, and multiplicity plan. No medical recommendation follows from these statistical results alone.

14. Why This Trial Matters Statistically

This trial raises a practical statistical question about co-administration: whether the measured antibody response after the second herpes zoster vaccine dose differs when Boostrix is given with the first dose rather than separately. The randomized parallel design provides a structured comparison of those schedules. Measuring the primary endpoint one month after Dose 2 aligns the assessment to the dose while allowing the visit month to differ between groups.

The endpoint is a GMC rather than a simple event count. That choice reflects the nature of antibody concentration data and makes the result interpretable as a group-level immune response. Reporting confidence intervals alongside the GMCs communicates estimation uncertainty, while the adjusted ratio offers a relative comparison. Each summary answers a different statistical question; the ratio is not interchangeable with either group GMC.

The non-inferiority label also illustrates why an estimate is not enough to interpret a trial conclusion. A margin and a decision rule are central to a non-inferiority analysis, but they are not reported in the registry record. Without them, a reader can describe the adjusted estimate and its uncertainty but cannot independently assess the criterion behind the conclusion.

The study also illustrates why analysis populations and denominators need context. The primary immunogenicity summaries and safety figures use different group sizes. Those figures cannot simply be compared as if they came from the same set of participants, and the registry does not explain the denominator differences. Separate outcome definitions, missing-data handling, and multiplicity procedures also affect interpretation.

These statistical features matter because a clear account of the estimate, population, uncertainty, and decision rule is necessary for readers to judge what a trial result supports. The registry provides useful core information about the endpoint, schedules, and posted results, while leaving several analysis details not reported.

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 registry describes the primary endpoint and the According-to-Protocol immunogenicity cohort, but it does not provide the adjustment method for the reported GMC ratio. It also does not report the non-inferiority margin or the full decision rule. These omissions prevent independent evaluation of the sponsor's non-inferiority analysis from the posted result alone.

The primary endpoint summaries are based on group sizes of 369 and 380, whereas the safety denominators are 412 and 418. The registry does not explain why these analysis populations differ. It does not give a detailed participant flow, exclusions by reason, or a complete account of missing endpoint data. These limits make it difficult to assess how selection into each analysis may affect interpretation.

The registry lists a range of secondary outcomes, but does not report whether multiplicity was addressed or how outcomes were prioritized. It does not provide the full statistical analysis plan, sample-size justification, or interim analysis details. Consequently, the record does not establish whether the posted analyses represent all planned analyses or how the study was designed to control statistical error across endpoints.

The primary outcome is an antibody concentration at one defined time after Dose 2. The registry record does not report later antibody measurements in the primary comparison or a clinical herpes zoster outcome. The result therefore cannot answer questions about persistence or clinical effectiveness. It also does not describe all assay-performance details beyond the ELISA method and reference seropositivity cutoff.

Finally, the safety figures are counts and listed event terms, with limited information on attribution and the time period represented. The registry does not specify how the listed serious-event percentages relate to individual groups. These data should be read as descriptive safety reporting rather than as proof of a causal difference between schedules.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) When Co-administered With GSK Biologicals' Diphtheria, Tetanus and Pertussis Vaccine (Boostrix®) in Adults Aged 50 Years and Older — NCT02052596.
• Registry record last updated 2018-04-24; status last verified 2017-09.
• Results first posted 2018-04-24.
• 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

NCT02052596 is a completed randomized phase 3, parallel-group, unmasked study sponsored by GlaxoSmithKline. It enrolled 935 adults aged 50 years and older and compared co-administration of the first GSK1437173A herpes zoster vaccine dose with Boostrix against separate administration. The primary endpoint was anti-gE antibody GMC, measured by ELISA one month after Dose 2.

The posted GMCs were 51690 mIU/mL for the GSK1437173A Group and 58000 mIU/mL for the Control Group. The sponsor-reported adjusted GMC ratio was 1.11, with a 95% confidence interval from 1.02 to 1.21, and was labeled as a non-inferiority analysis. The registry does not report the non-inferiority margin or adjustment details.

Safety outcomes included solicited symptoms, adverse events, serious adverse events, and potential immune-mediated diseases. Serious adverse event counts were 21 among 412 at risk in the GSK1437173A Group and 31 among 418 at risk in the Control Group. The registry does not report several details needed for full evaluation of the statistical plan, missing data, multiplicity, and safety attribution.