This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) in Adults ≥ 65 Years of Age With and Without Zostavax® Vaccination at Least 5 Years Earlier (NCT02581410), a non-randomized phase 3 study. The primary outcome is Anti-glycoprotein E (Anti-gE) Antibody (Ab) Concentrations.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02581410 |
| Phase | Phase 3 |
| Condition | Herpes Zoster |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 430 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Adults ≥ 65 years of age with a history of Zostavax® vaccination at least 5 years earlier, or adults ≥ 65 years of age who had never received Zostavax®. The primary immunogenicity analysis used the According-To-Protocol cohort: evaluable participants who met eligibility criteria, complied with protocol requirements, and had Month 3 immunogenicity measurements.
Intervention
Two doses of the GSK Biologicals HZ/su vaccine, with the first dose at Month 0 and the second dose 2 months later.
Comparator
The comparison was between participants who had received Zostavax® at least 5 years earlier and participants who had never received it. Both groups received HZ/su vaccine in this study. The registry identifies the allocation as non-randomized, so this is not a randomized comparison or a like-for-like control comparison.
Primary question
One month after dose 2, at Month 3, what were the adjusted geometric mean concentrations of antibodies to varicella zoster virus glycoprotein E in the two groups? The registry also describes safety and secondary immunogenicity outcomes, including gE-specific CD4+ T-cells and adverse events. The primary antibody concentrations and a comparison estimate are not reported in the registry record, so the magnitude and precision of any group difference cannot be described from this record.
3. Trial Design
This completed Phase 3 study evaluated the immunogenicity and safety of the GSK Biologicals HZ/su vaccine in adults ≥ 65 years of age. The registry lists enrollment as 430. It describes a parallel-group design with non-randomized allocation and no masking. The groups were defined by prior Zostavax® vaccination: one included participants who had received it at least 5 years earlier, and the other included participants who had never received it.
Participants in both groups received two doses of HZ/su vaccine. The first dose was given at Month 0 and the second dose 2 months later. Thus, the comparison concerns antibody responses and safety among two prior-vaccination groups who both received HZ/su, rather than a comparison of HZ/su against no vaccine or another treatment. Because allocation was non-randomized, differences between groups may reflect characteristics associated with prior Zostavax® vaccination as well as any difference in response. The registry explicitly cautions that the arms are not a like-for-like control comparison.
The study began on 2015-12-15, had primary completion on 2016-08-30, and is listed as completed. The registry describes the primary immunogenicity assessment at Month 3, one month after dose 2. That analysis used the According-To-Protocol cohort for immunogenicity, which included evaluable participants meeting eligibility and protocol requirements with Month 3 immunogenicity measurements available. The registry record does not report further details about allocation procedures, the rationale for the enrollment target, or the statistical plan.
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.
Vaccination Phase
| Stage | GSK1437173A Group | Control Group |
|---|---|---|
| STARTED | 215 | 215 |
| COMPLETED | 213 | 212 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | GSK1437173A Group | Control Group |
|---|---|---|
| Adverse Event | 2 | 1 |
| Withdrawal by Subject | 0 | 1 |
| Migrated/moved from study area | 0 | 1 |
End of Study Phase
| Stage | GSK1437173A Group | Control Group |
|---|---|---|
| STARTED | 215 | 215 |
| COMPLETED | 210 | 204 |
| NOT COMPLETED | 5 | 11 |
Reasons for not completing this period:
| Reason | GSK1437173A Group | Control Group |
|---|---|---|
| Adverse Event | 4 | 3 |
| Withdrawal by Subject | 1 | 2 |
| Migrated/moved from study area | 0 | 3 |
| Lost to Follow-up | 0 | 2 |
| Other-transfer of subject not completed | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects who met all eligibility criteria, who complied with the protocol requirements and for whom immunogenicity measures were available at Month 3.
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.
| Characteristic | Unit | GSK1437173A Group | Control Group | Total |
|---|---|---|---|---|
| Participants analysed | 215 | 215 | 430 | |
| Age, Continuous | Years | 71.1 (SD 4.5) | 70.8 (SD 4.6) | 70.9 (SD 4.6) |
| Sex: Female, Male: Female | Participants | 109 | 111 | 220 |
| Sex: Female, Male: Male | Participants | 106 | 104 | 210 |
| Race/Ethnicity, Customized: White - Caucasian / European Heritage – White - Caucasian / European Heritage | Participants | 215 | 215 | 430 |
6. Primary Endpoint
The registry lists the primary outcome as Anti-glycoprotein E (Anti-gE) Antibody (Ab) Concentrations, measured over One month after dose 2, at Month 3.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | mIU/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was anti-glycoprotein E antibody concentration, measured one month after dose 2, at Month 3. The assay measured varicella zoster virus gE immunoglobulin G using an enzyme-linked immunosorbent assay. Concentrations were expressed in mIU/mL and summarized as geometric mean concentrations, adjusted for a group-matching variable.
A geometric mean is a way to summarize positive measurements that can vary over a wide range. In general, it is calculated on a logarithmic scale and then expressed back on the original scale. This can make the summary more appropriate than an arithmetic mean when measurements are multiplicative or strongly right-skewed. The registry also gives a 95% confidence interval as the measure of dispersion. In general, a confidence interval describes the uncertainty around an estimated quantity under the analysis assumptions; it is not a range containing every participant’s measurement.
Antibody concentration is an immunogenicity measure: it describes the measured antibody response to gE. It is not, by itself, a clinical outcome such as the occurrence of herpes zoster. The registry record does not report the geometric mean concentrations, confidence intervals, or a group-comparison estimate. Therefore, the endpoint’s reported numerical results and the precision of the comparison are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive issue is that the registry describes the primary endpoint but does not report its numerical result. It specifies adjusted geometric mean antibody concentrations at Month 3 and a 95% confidence interval, but neither the estimates nor a contrast between groups is reported in the registry record. Consequently, the antibody response in either group, the size of any difference, and the uncertainty around that difference cannot be characterized from the available record. The absence of these values is not evidence that the groups had the same response.
The comparison also needs to be read in light of the study design. Allocation was non-randomized, and the arms were defined by prior Zostavax® vaccination. Participants in both groups received two doses of HZ/su. The comparison therefore describes outcomes in groups with different vaccination histories; it does not isolate the effect of assigning prior Zostavax® vaccination, nor does it compare HZ/su with an untreated control. The registry cautions that the arms are not a like-for-like control comparison. Statistical adjustment for a group-matching variable is stated for the primary endpoint, but the variable and the details of adjustment are not reported in the registry record.
The safety information gives counts of participants affected by serious adverse events and other adverse events, along with deaths, for each group. These are descriptive counts. The registry record does not report a randomized safety comparison, adjusted risk estimates, confidence intervals, or a formal test of between-group differences. The counts therefore should not be interpreted as establishing that one group had more or fewer events because of treatment or prior vaccination. The serious-event terms and listed percentages provide additional descriptive information, but the record does not establish a causal explanation for those events.
Several kinds of uncertainty remain distinct. The confidence interval for the primary endpoint would describe statistical uncertainty in the estimated antibody concentration, but those intervals are not reported. Non-randomized allocation creates a separate concern: groups may differ in relevant characteristics, whether or not a model adjusts for a matching variable. The registry record does not describe enough detail to assess the extent of such differences or the adequacy of adjustment.
Accordingly, the record supports describing the study question, its non-randomized structure, the antibody endpoint, and the reported safety counts. It does not support a numerical conclusion about the primary immunogenicity comparison, a claim that the groups were equivalent, or a causal interpretation of group differences. The study’s secondary outcomes are named, but their numerical results are not reported in the registry record.
9. Statistical Methods Explained
The registry identifies a geometric mean concentration (GMC) as the primary summary for anti-gE antibody measurements. It also states that the GMC was adjusted for a group-matching variable and that uncertainty was expressed with a 95% confidence interval. The actual adjusted GMCs and intervals are not reported in the registry record.
Why use a geometric mean?
General explanation: Biological measurements can be positive and spread over a wide range, with some values much larger than others. An arithmetic mean can be pulled upward by unusually large measurements. A geometric mean summarizes the central level using multiplicative rather than additive changes. It is commonly obtained by taking logarithms of the measurements, calculating a mean on that scale, and transforming the result back. This description explains the general statistical idea; the registry record does not report every computational detail used for this analysis.
The measure is stated in mIU/mL, so the GMC remains interpretable on the original measurement scale. However, a group-level GMC does not describe the full distribution of individual antibody values. It also does not indicate how many participants had a particular value or how much individual responses varied. The confidence interval addresses uncertainty in the estimated GMC, not the range of individual observations.
What does the confidence interval convey?
General explanation: A confidence interval is an interval estimate constructed using a statistical procedure. Under the assumptions of that procedure, it conveys how precisely a quantity is estimated. A narrower interval generally indicates greater precision than a wider interval. It does not mean that a fixed proportion of individual participants’ measurements lie inside the interval. Nor does an interval alone establish whether a difference between groups is important; interpretation depends on the endpoint, the comparison, and the question being asked.
Here, the registry says the endpoint has a 95% confidence interval, but does not report its limits. There is also no reported contrast with its own interval. The precision of the primary group comparison therefore cannot be assessed from the registry record. No p-value for this endpoint is reported in the registry record.
What does adjustment mean in this record?
The registry says that the geometric mean antibody concentrations were adjusted for a group-matching variable. In general, adjustment accounts statistically for a measured characteristic included in an analysis. It can make a comparison conditional on that characteristic, but it cannot automatically remove differences in characteristics that were not measured or not included. The identity of the matching variable, the model specification, and the exact adjustment procedure are not reported in the registry record. The stated adjustment should therefore not be treated as proof that the non-randomized groups were otherwise comparable.
The primary analysis population was the According-To-Protocol cohort for immunogenicity. It included evaluable participants who met all eligibility criteria, complied with protocol requirements, and had immunogenicity measures available at Month 3. This defines who contributed to the primary analysis as described in the registry. It is not necessarily the same as everyone enrolled, and the record does not report the number included in that analysis or reasons participants may have been excluded.
How should planning illustrations be read?
The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. They are based on fractions of the observed effect. These are planning illustrations, not observed power and not a report of the trial’s original design justification. They do not show that the study had a particular probability of detecting an effect after the fact. The registry record does not report the protocol’s sample-size justification or explain whether these illustration assumptions match the original design.
General explanation: A planning calculation asks how much information a future study might need under chosen assumptions about the effect and statistical procedure. Results depend on those assumptions. If the assumed effect is smaller, more information is generally needed to distinguish it from random variation; if it is larger, less may be needed. This is a general principle, not a numerical result for this study. The registry’s illustrations should be understood as hypothetical planning aids rather than evidence about the strength of the completed study.
The registry record does not report enough detail to reconstruct the endpoint analysis. In particular, the model form, handling of missing measurements, diagnostic checks, and any analysis-specific sensitivity procedures are not reported in the registry record. General statistical concepts can clarify the stated summaries, but they do not fill in those missing methods or results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary outcomes that include anti-gE antibody concentrations, frequencies of gE-specific CD4+ T-cells, and counts of participants with any and related serious adverse events or any pIMDs. It reports 12 outcome measures. Considering multiple outcomes or multiple comparisons can increase the chance of at least one apparently unusual result when each is assessed separately. In general, statistical plans may address this through prespecified outcome hierarchies or multiplicity adjustments. Whether such methods were planned or used is not reported in the registry record.
The record also does not report a complete statistical analysis plan, the number of hypothesis tests, or whether any analyses were exploratory. The registry lists one analysis, but that listing does not establish how every outcome was analyzed or whether multiplicity was addressed. No multiplicity procedure should be inferred from the outcome list alone.
For the primary immunogenicity analysis, the registry defines an According-To-Protocol cohort that required an available Month 3 measure, along with eligibility and protocol compliance. This describes the stated analysis population, but the number analyzed and the handling of participants without measurements are not reported in the registry record. Reasons for missing measurements, any imputation procedure, and sensitivity analyses for missing data are also not reported in the registry record.
These omissions matter because an analysis restricted to participants with available measurements can be affected if availability is related to antibody response or other participant characteristics. That is a general concern, not evidence that missingness biased this study. The registry record does not provide the information needed to assess whether missing data affected the findings.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| GSK1437173A Group | 18 | 215 | 8.4% |
| Control Group | 22 | 215 | 10.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| GSK1437173A Group | 2 of 215 |
| Control Group | 3 of 215 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| GSK1437173A Group | 199 of 215 |
| Control Group | 197 of 215 |
Most frequent serious adverse event terms
| Event term | Organ system | GSK1437173A Group | Control Group |
|---|---|---|---|
| Cellulitis | Infections and infestations | 2 of 215 | 1 of 215 |
| Dehydration | Metabolism and nutrition disorders | 1 of 215 | 2 of 215 |
| Atrial fibrillation | Cardiac disorders | 2 of 215 | 0 of 215 |
| Coronary artery disease | Cardiac disorders | 0 of 215 | 2 of 215 |
| Diverticulitis | Infections and infestations | 1 of 215 | 1 of 215 |
| Leukocytosis | Blood and lymphatic system disorders | 0 of 215 | 1 of 215 |
| Arrhythmia | Cardiac disorders | 0 of 215 | 1 of 215 |
| Atrioventricular block | Cardiac disorders | 0 of 215 | 1 of 215 |
| Cardiac arrest | Cardiac disorders | 0 of 215 | 1 of 215 |
| Myocardial infarction | Cardiac disorders | 0 of 215 | 1 of 215 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GSK1437173A Group | Control Group |
|---|---|---|---|
| Pain | General disorders | 189 of 215 | 181 of 215 |
| Fatigue | General disorders | 114 of 215 | 111 of 215 |
| Erythema | Skin and subcutaneous tissue disorders | 96 of 215 | 73 of 215 |
| Headache | Nervous system disorders | 80 of 215 | 89 of 215 |
| Myalgia | Musculoskeletal and connective tissue disorders | 82 of 215 | 78 of 215 |
| Chills | General disorders | 51 of 215 | 37 of 215 |
| Gastrointestinal disorder | Gastrointestinal disorders | 49 of 215 | 38 of 215 |
| Swelling | General disorders | 50 of 215 | 37 of 215 |
| Pyrexia | General disorders | 36 of 215 | 32 of 215 |
Serious events with the highest arm-level rate: atrial fibrillation (0.9%), coronary artery disease (0.9%), cellulitis (0.9%), dehydration (0.9%), leukocytosis (0.5%).
The registry reports serious adverse events for both study groups. In the GSK1437173A Group, 18 participants were affected among 215 at risk; in the Control Group, 22 were affected among 215 at risk. The record also lists other adverse events affecting 199 among 215 at risk in the GSK1437173A Group and 197 among 215 at risk in the Control Group. Deaths are listed as 2 and 3, respectively. These are descriptive counts, not adjusted comparisons.
The registry lists serious-event terms with frequencies: atrial fibrillation, coronary artery disease, cellulitis, and dehydration at 0.9% each; leukocytosis and arrhythmia at 0.5% each. The record does not specify in this listing which group each percentage refers to, so these values should not be assigned to a group based on the information reported.
Counts alone do not establish whether events were caused by vaccination or whether group differences reflect a treatment effect. The study was non-randomized, and the registry does not report uncertainty estimates or formal comparative safety analyses. These figures describe the reported safety experience in the registry record; they do not establish that the groups had equivalent safety profiles.
12. What the Result Does, and Does Not, Mean
This study addresses an immunogenicity question in adults ≥ 65 years of age who received two doses of HZ/su and differed in their history of Zostavax® vaccination. Its primary endpoint was the adjusted geometric mean concentration of anti-gE antibody measured at Month 3. The registry record provides the endpoint definition and analysis population, but not the numerical antibody results. Without the estimates and confidence intervals, the magnitude and precision of the primary comparison cannot be assessed.
The study also reports descriptive safety counts. These convey how many participants were recorded as affected by serious and other adverse events, and the number of deaths in each group. They do not by themselves show why an event occurred or whether any apparent difference between groups is attributable to vaccination. The registry record does not report formal comparative estimates or uncertainty intervals for these safety counts.
The design sets an important boundary on interpretation. Participants were not randomly allocated, and both groups received HZ/su. Their distinction was prior Zostavax® vaccination at least 5 years earlier versus no prior Zostavax® vaccination. The comparison can describe the groups as studied, but cannot be treated as a randomized estimate of the effect of prior vaccination. The registry specifically warns that the arms are not a like-for-like control comparison.
These limitations do not make the study question uninformative. They clarify what the record can support: a description of the study population, vaccine schedule, primary antibody measure, analysis cohort, and reported safety counts. They also clarify what it cannot support: a numerical claim about the primary antibody response, equivalence between groups, or a causal explanation for group differences. Secondary outcomes are named, but their results are not reported in the registry record.
In general, immunogenicity measures and clinical outcomes answer different questions. An antibody concentration describes a laboratory-measured response; it is not itself a count of disease cases or a direct estimate of clinical protection. The registry record does not report a clinical effectiveness endpoint or a relationship between antibody measurements and clinical outcomes. Interpretation should remain within the outcomes and results actually reported.
13. Why This Trial Matters Statistically
The statistical value of this study lies partly in the population contrast it describes: older adults with different histories of Zostavax® vaccination received the same two-dose HZ/su schedule. That makes the registry’s question relevant to understanding antibody responses and safety across these histories. The primary endpoint is clearly identified as an adjusted GMC of anti-gE antibody at Month 3, with a confidence interval intended to convey precision.
At the same time, the non-randomized design illustrates why a comparison is not automatically causal simply because two groups are reported. Prior vaccination history defines the groups and may be associated with other characteristics. Adjustment is stated for a group-matching variable, but the registry record does not identify that variable or provide enough methodological detail to judge its role. The record itself cautions that the arms are not a like-for-like control comparison.
The study is also a useful example of separating the endpoint specification from the availability of results. A carefully described measure does not allow readers to infer the estimate when its values and confidence intervals are absent. Statistical interpretation depends on both the analysis method and the reported results. Here, the primary numerical results are not reported in the registry record, so the central comparison cannot be quantified.
Finally, the safety counts demonstrate the difference between descriptive reporting and comparative inference. Event counts provide a record of what was observed, while causal and comparative conclusions require an appropriate design and statistical estimates with their uncertainty. The registry record offers descriptive safety information but not those comparative estimates. Reading these elements together helps distinguish what this completed study set out to measure from what can be concluded from its reported 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 principal limitation for interpreting the primary question is that the registry record does not report the adjusted anti-gE GMCs, their confidence intervals, or a between-group estimate. The magnitude and precision of the primary comparison therefore cannot be evaluated from the record. Numerical results for the listed secondary outcomes are also not reported in the registry record.
The non-randomized allocation is a further limitation. The groups differed by prior Zostavax® vaccination history, and both received HZ/su. The registry cautions that the groups are not a like-for-like control comparison. Although the primary GMCs were adjusted for a group-matching variable, the variable and adjustment details are not reported in the registry record. The extent of any remaining group differences cannot be assessed from the reported information.
The primary analysis used an According-To-Protocol immunogenicity cohort that required evaluability, protocol compliance, eligibility, and an available Month 3 measurement. The number included in that analysis, exclusions, and reasons for unavailable measurements are not reported in the registry record. Nor does the record describe missing-data methods or sensitivity analyses.
Further limitations include the absence of reported details about the statistical analysis plan, multiplicity procedures, and sample-size justification. The sample-size material is described as a planning illustration based on the observed effect, with stated assumptions; it is not observed power or evidence of the original design rationale. Safety information is descriptive, without reported comparative uncertainty estimates. These limitations constrain causal and quantitative interpretation without changing the study design and outcomes that the registry does describe.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) in Adults ≥ 65 Years of Age With and Without Zostavax® Vaccination at Least 5 Years Earlier — NCT02581410.
- Registry record last updated 2018-08-28; status last verified 2018-07.
- Results first posted 2017-09-26.
- 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.
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18. Record Summary
This completed Phase 3 study enrolled 430 adults ≥ 65 years of age and used a parallel, non-randomized design with no masking. Participants in both groups received two doses of HZ/su, with the second dose 2 months after the first. The groups differed in prior Zostavax® vaccination history.
The primary endpoint was adjusted anti-gE antibody GMC at Month 3, measured by ELISA and reported in mIU/mL with a 95% confidence interval. The primary analysis population was the According-To-Protocol cohort for immunogenicity. The antibody estimates and confidence intervals are not reported in the registry record. Descriptive serious and other adverse-event counts and deaths are reported, but the record does not provide comparative safety estimates. Non-randomized allocation limits causal interpretation of differences between groups.