Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine GSK1437173A When Administered Subcutaneously Intramuscularly in Adults Aged ≥50 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine GSK1437173A When Administered Subcutaneously Intramuscularly in Adults Aged ≥50 Years (NCT01777321), a randomized phase 3 study. The primary outcome is Number of Subjects With Anti-Glycoprotein E (Anti-gE) Antibody Concentrations Higher Than or Equal to (≥)18 Milli-international Units Per Milliliter (mIU/mL).

2. Clinical Question

The study’s stated purpose was to assess immunogenicity, safety and reactogenicity when the vaccine was administered subcutaneously compared with intramuscularly. The central statistical contrast is therefore between two routes of administering the same vaccine, not between vaccination and no vaccination. The outcome definition focuses on the presence of an antibody concentration meeting a specified assay cut-off, rather than on a clinical herpes zoster outcome.

The registry lists 60 participants enrolled, with 30 assigned to each route in the adverse-event information. It identifies the study as Phase 3 and as completed. These details describe the planned comparison and the recorded enrollment; they do not establish that every enrolled participant contributed data at every assessment. The primary results, including the numbers meeting the seropositivity threshold at the listed time points, are not reported in the registry record.

3. Trial Design

The registry identifies NCT01777321 as a randomized, parallel-group, open-label Phase 3 study sponsored by GlaxoSmithKline. It enrolled 60 participants and is marked completed. The study began on 2013-06-17, and the recorded primary completion date is 2013-10-10. These registry dates describe the recorded study timeline; they do not, by themselves, indicate how long any individual participant was followed.

Participants were assigned to receive the herpes zoster subunit vaccine by one of two routes: subcutaneous administration or intramuscular administration. Both arm descriptions specify a 0 and 2-month schedule. The intervention is identified as the biological product GSK1437173A. Because the study was open-label, masking is recorded as none. The registry does not report whether outcome assessors or laboratory personnel were masked separately from participants and study staff.

The randomized parallel-group structure is intended to compare outcomes across participants assigned to different routes, rather than to compare each participant with themselves. Random allocation can support a balanced comparison in expectation, but it does not guarantee that the groups will be similar in every characteristic, particularly in a study of this size. The registry information does not provide baseline characteristics or enough detail to assess the achieved balance between groups.

The stated study purpose covers immunogenicity, safety and reactogenicity. The primary outcome is a count of participants whose anti-glycoprotein E antibody concentration meets the defined seropositivity cut-off. Secondary outcomes include anti-gE concentrations, participants meeting a separate antibody threshold, vaccine response, potential immune-mediated diseases and serious adverse events. The registry lists 16 outcome measures, but does not provide outcome analyses in the information recorded for this study. Specific details of allocation concealment, the randomization sequence, protocol deviations, and the planned statistical methods 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: During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

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 had met all eligibility criteria and for whom data concerning immunogenicity outcome measures were available.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Anti-Glycoprotein E (Anti-gE) Antibody Concentrations Higher Than or Equal to (≥)18 Milli-international Units Per Milliliter (mIU/mL), measured over Before vaccination (PRE), two months after Dose 1 (M2) and one month after Dose 2 (M3).

The primary endpoint counts participants whose anti-glycoprotein E antibody concentration is at least 18 mIU/mL. The registry calls a participant seropositive when the measured concentration is at least the assay cut-off of 18 mIU/mL. Assessments are specified before vaccination, two months after Dose 1 (M2), and one month after Dose 2 (M3).

This is a binary classification based on a continuous laboratory measurement: each participant either meets the cut-off or does not at a given assessment. Counting participants above a prespecified threshold can make the result straightforward to interpret as the proportion of an analysis population meeting the assay-defined criterion. However, the thresholded count does not show the full distribution of antibody concentrations. Participants with measurements just below and well below the cut-off are both outside the seropositive count, while participants with different concentrations above the cut-off are both counted as meeting it.

The registry also lists anti-gE antibody concentrations and other antibody-related secondary outcomes, including a count meeting a threshold of 97 mIU/mL and a count with vaccine response. Those measures address related but distinct aspects of the immune response; they should not be substituted for the primary definition. The primary endpoint is measured at multiple time points, so interpretation requires attention to when the measurement was made and to the corresponding analysis population. The registry record does not report the primary endpoint counts or the associated statistical comparisons.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is recorded as randomized, parallel-group and open-label. In a randomized design, participants are allocated to groups according to a chance-based process, which aims to reduce systematic differences in prognostic characteristics between groups. Randomization does not ensure that the groups are identical, and it is especially important to inspect group characteristics and participant flow in a small study. Those details, as well as the method used to generate and conceal the allocation sequence, are not reported in the registry record.

What does the primary outcome count?

The primary measure is a binary outcome at each assessment: whether a participant’s anti-gE antibody concentration is at least 18 mIU/mL. A binary endpoint reduces a laboratory value to a yes-or-no classification using the stated assay cut-off. This can simplify reporting, but discards information about how far a measurement lies above or below the threshold. The registry also lists antibody concentration as a secondary outcome, which is conceptually different because it retains the measured concentration rather than only the threshold classification.

The stated assessments are before vaccination, two months after Dose 1 (M2), and one month after Dose 2 (M3). Repeated assessments allow the response to be described at different stages of the dosing schedule. They also raise analysis questions: whether each time point is a separate endpoint, whether change over time is evaluated, and how correlations among measurements from the same participant are handled. The statistical plan for these choices is not reported in the registry record.

Why does the analysis population matter?

The primary analysis is described as using the According-to-Protocol cohort for immunogenicity. The registry defines this cohort as evaluable participants who met all eligibility criteria and had data available for immunogenicity outcomes. This definition means the analysis is not necessarily a count of every participant randomized. Excluding participants after randomization can affect comparability if the reasons for exclusion or missing measurements differ by group. The number included at each assessment and the reasons for any exclusions are not reported in the registry record.

An analysis based on participants with available, evaluable measurements can be useful for describing the immune response among those assessed under the specified protocol conditions. It does not automatically answer the same question as an analysis retaining all randomized participants. The record does not report whether an intention-to-treat analysis was performed, whether missing measurements were imputed, or what assumptions were made about missing data.

How should statistical uncertainty be understood?

A confidence interval is a statistical range that conveys the precision of an estimated effect under the assumptions of the analysis. A wider interval generally indicates less precision, while a narrower interval indicates greater precision. For a binary endpoint, uncertainty depends in part on the number of participants and the distribution of outcomes between groups. A p-value, when reported, addresses compatibility between the data and a specified null hypothesis under the test’s assumptions; it does not measure the size or importance of an effect.

No primary endpoint confidence intervals, p-values, or effect estimates are reported in the registry record. Consequently, the statistical precision of the route comparison cannot be evaluated. The total enrollment alone cannot establish whether an estimate would be precise enough for any particular purpose, and no conclusion about statistical significance can be drawn without the results and analysis details.

What can the safety counts tell readers?

The safety information includes counts of participants with serious adverse events, other adverse events, and deaths. Counts are useful for describing what was recorded, but they are not a full analysis of event rates or comparative risk. Interpretation depends on the definitions, observation periods, participant time at risk, how recurrent events were handled, and whether events were judged related to vaccination. Those details are not reported in the registry record. With relatively small groups, uncommon events may also be difficult to characterize precisely; this is a general limitation of interpreting sparse event counts, not an additional finding about this study.

The record identifies a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation and a normal approximation. The illustration is not the trial’s own design justification. No numerical sample-size illustration is included in the study information, and the record does not report the trial’s original sample-size rationale or planned power. A planning calculation based on an observed effect is not observed power and should not be interpreted as evidence that the study had a particular probability of detecting an effect after the fact.

What methods remain unclear?

The registry does not report the specific statistical test or model used for the primary outcome, how multiplicity across assessments and secondary outcomes was handled, whether interim analyses were planned, or how protocol deviations and missing data were addressed. It also does not report adjusted analyses or prespecified subgroup analyses. These details matter because different analysis choices can yield different estimates and uncertainty statements, even when they use the same underlying observations. Without the posted endpoint results and method details, the defensible interpretation is limited to the study design, endpoint definition and descriptive safety counts recorded.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is evaluated at three specified times: before vaccination, two months after Dose 1 (M2), and one month after Dose 2 (M3). The registry also lists several secondary outcomes, including antibody concentrations, counts meeting another antibody threshold, vaccine response, potential immune-mediated diseases and serious adverse events. Testing multiple outcomes or time points can increase the chance of obtaining at least one apparently notable result by chance. Statistical approaches to multiplicity can include prespecifying a primary comparison, adjusting significance thresholds, or treating secondary analyses as exploratory. Which approach, if any, was planned or used is not reported in the registry record.

The primary immunogenicity population is the According-to-Protocol cohort. It includes evaluable participants who met eligibility criteria and had outcome data available. The record does not report the number analyzed at each time point, the number with missing measurements, reasons for missingness, or how missing observations were handled. It also does not report whether all randomized participants were analyzed in a separate population or whether protocol deviations led to exclusions.

Missingness matters because a complete-case or evaluable-participant analysis can be biased if the chance of having an observed measurement is related to the participant’s outcome or differs between groups. This is a general statistical concern; it does not establish that missingness occurred or caused bias in this study. The registry information is not sufficient to assess that possibility. Details on prespecified analysis populations, multiplicity control, interim analyses and missing-data methods are not reported in the registry record.

11. 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: spinal compression fracture (3.3%), chronic obstructive pulmonary disease (3.3%), mallet finger (3.3%).

The registry lists serious adverse events in 2 participants in the subcutaneous group and 1 participant in the intramuscular group. It records 30 participants at risk in each group and no deaths in either group. The listing also records other adverse events in 30 participants in the subcutaneous group and 28 in the intramuscular group. These are participant counts, not a complete account of the number, duration or severity of all events.

The serious-event terms listed are spinal compression fracture, chronic obstructive pulmonary disease and mallet finger, each with a recorded percentage of 3.3%. The record information does not specify the group for each term or clarify the denominator used for those percentages. It also does not state whether the events were considered related to vaccination. Those entries should not be assigned to either route or interpreted as causal evidence.

Serious adverse-event counts are descriptive. Comparing small counts without event timing, exposure time, definitions and uncertainty estimates cannot establish a meaningful difference between routes. The record does not report statistical comparisons for safety. Zero recorded deaths means none were recorded in the listed groups; it does not establish the absence of every possible safety risk.

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

The registry record establishes the question the trial was designed to address: whether antibody responses and safety outcomes differed when the same herpes zoster subunit vaccine was administered subcutaneously rather than intramuscularly. It specifies a randomized, open-label, parallel-group design, a total enrollment of 60, and a primary seropositivity definition based on anti-gE antibody concentrations of at least 18 mIU/mL. It also records assessments before vaccination and after each dose at the stated times.

Those design features do not, on their own, answer the comparative question. The primary outcome results are not reported in the registry record, so the number of participants meeting the antibody threshold in either group is unknown from the recorded information. There are no reported primary effect estimates or measures of statistical precision. It is therefore not possible to say whether the groups had similar or different measured antibody responses, how large any difference may have been, or how uncertain an estimate would be.

The safety counts provide a limited descriptive account: serious adverse events were recorded for 2 participants in the subcutaneous group and 1 in the intramuscular group, while no deaths were recorded. Other adverse events were recorded for 30 and 28 participants, respectively. Without further details and uncertainty estimates, these counts do not demonstrate that one route is safer, or that an event was caused by vaccination. Nor does the absence of a reported primary result imply that no result was observed; it means that the outcome values are not included in the registry information available for this analysis.

The study also does not establish a clinical effect on herpes zoster itself through the primary endpoint described. That endpoint is an antibody measure, not a count of herpes zoster cases. Antibody measurements can characterize an immune response, but the registry record alone does not show how the route comparison relates to clinical outcomes. Any broader interpretation would require results and supporting evidence beyond the endpoint definition and descriptive counts recorded.

13. Why This Trial Matters Statistically

This study poses a focused statistical comparison: two administration routes for the same vaccine, delivered on the same stated schedule, with an antibody-based primary endpoint. That structure is useful for thinking about how a randomized comparison can isolate a delivery-route question from differences in the vaccine itself. The open-label design and the small recorded enrollment also illustrate why readers need to consider how study procedures, analysis populations and outcome measurement affect interpretation.

The primary endpoint uses a threshold applied to antibody concentration. This makes the outcome easy to describe as a count meeting an assay-defined criterion, while highlighting a general trade-off in statistical analysis: a binary classification can be interpretable but loses information contained in the underlying continuous measurement. The registry’s additional antibody outcomes reflect related ways of characterizing immunogenicity, but each has its own definition and should be interpreted separately.

The study is also a reminder that an endpoint definition is not the same as a result. The registry record describes the primary measure and its time points, but does not report the corresponding outcome counts or comparative estimates. Statistical interpretation depends on both the design and the observed data, together with uncertainty and analysis details. Without those results, the study’s comparative immunogenicity question remains unanswered by the record.

Finally, the safety information shows why counts require context. Serious-event and other-event counts can describe what was recorded, but details about event definitions, timing, attribution and analysis are needed for a careful comparison. Reporting those limitations is part of distinguishing descriptive evidence from a claim of difference or causation.

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 the primary endpoint results are not reported in the registry record. The record defines the seropositivity threshold and assessment times but includes no group-specific counts, antibody estimates, effect estimates, confidence intervals or p-values. The comparative immunogenicity finding therefore cannot be evaluated from these registry entries.

The enrollment was 60, but the number included in the According-to-Protocol immunogenicity cohort is not reported. Nor are participant flow, exclusions, missing measurements, reasons for missingness or the number analyzed at each time point. This leaves uncertainty about how closely the analyzed participants represent everyone randomized and whether availability of outcome data differed between groups.

The registry identifies the trial as open-label and does not report masking of laboratory personnel or assessors. It also does not give baseline characteristics, allocation concealment details, the randomization procedure, or the statistical methods used for the primary and secondary outcomes. Without these details, readers cannot assess group comparability, potential measurement influences, or the suitability of the analysis for repeated assessments and multiple outcomes.

Safety reporting is limited to participant counts, deaths and a short list of serious-event terms with percentages. Event timing, definitions, exposure time, repeated events, severity beyond seriousness, attribution, and statistical comparisons are not reported in the registry record. The serious-event terms are not linked to a group in the recorded details. As a result, the safety information is descriptive and does not support a precise route comparison.

The registry does not report a sample-size justification, planned power, interim analyses, multiplicity strategy, missing-data method, or the full statistical analysis plan. The planning illustration described in the record is based on an observed effect and is not the trial’s original design rationale. These omissions constrain assessment of whether the study was planned and analyzed to answer its stated questions with a prespecified level of precision.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine GSK1437173A When Administered Subcutaneously Intramuscularly in Adults Aged ≥50 Years — NCT01777321.
• Registry record last updated 2018-10-25; status last verified 2018-08.
• Results first posted 2017-01-06.
• 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

NCT01777321 is a completed, randomized, open-label, parallel-group Phase 3 study sponsored by GlaxoSmithKline. It enrolled 60 adults aged 50 years or older to compare subcutaneous with intramuscular administration of herpes zoster subunit vaccine GSK1437173A. Both groups had a stated schedule at 0 and 2 months. The recorded study start date is 2013-06-17, and the primary completion date is 2013-10-10.

The primary endpoint counts participants with anti-gE antibody concentrations of at least 18 mIU/mL before vaccination, two months after Dose 1 and one month after Dose 2. The immunogenicity analysis population is described as the According-to-Protocol cohort. Primary endpoint results and statistical comparisons are not reported in the registry record.

The safety information records serious adverse events in 2 participants in the subcutaneous group and 1 in the intramuscular group, other adverse events in 30 and 28 participants, respectively, and no deaths in either group. Further details needed for a comparative safety interpretation are not reported.