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 Cross-vaccination Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK 1437173A) in Subjects Who Previously Received Placebo in ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) Studies. (NCT02690207), a na phase 3 study. The primary outcome is Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02690207 |
| Phase | Phase 3 |
| Condition | Herpes Zoster |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8687 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Participants were at least 50 years of age and had previously received placebo in ZOSTER-006 or ZOSTER-022. The study enrolled 8687 participants. The primary analysis population was the total vaccinated cohort: participants with at least one documented HZ/su vaccine administration and available data.
Intervention
Participants received the herpes zoster subunit vaccine, HZ/su (GSK 1437173A), by intramuscular injection in the deltoid of the non-dominant arm. The study’s stated purpose was to cross-vaccinate these former placebo recipients and collect safety data.
Comparator
There was no concurrent comparison group. The registry lists allocation as not applicable, masking as none, and the study model as single group. The earlier placebo assignment identifies participants’ history; it does not make the current study a randomized comparison of vaccine with placebo.
Primary question
The primary question concerned how many vaccinated participants had any, grade 3, or vaccination-related unsolicited adverse events during the 30 days after any vaccination, across doses. The registry record defines this outcome but does not report its participant counts or statistical analyses. The study also collected serious adverse-event and potential immune-mediated disease safety information.
Statistically, this is a descriptive safety question in a vaccinated group, not an estimate of the difference between vaccine and control. Counts can describe the observed experience among participants included in the relevant analysis, but without a concurrent control they cannot by themselves isolate the contribution of vaccination from other causes or background events. The registry record does not report a control-group outcome for this study.
3. Trial Design
This phase 3 study was designed to vaccinate people who had previously received placebo in ZOSTER-006 or ZOSTER-022 and to collect safety information. Its title describes the work as a cross-vaccination study. The registry lists a single-group model, no masking, and allocation as not applicable. Enrollment was 8687, and the study status is completed.
The intervention was the HZ/su vaccine. Participants received it intramuscularly in the deltoid of the non-dominant arm. The primary outcome concerned unsolicited adverse events during 30 days after any vaccination, across doses. The registry also identifies serious adverse events and potential immune-mediated diseases as safety topics in the study’s purpose. A secondary outcome is the number of participants with at least one suspected herpes zoster case.
The registry lists a start date of 2016-03-16 and a primary completion date of 2019-03-15. Those dates describe the study record; they do not, by themselves, specify each participant’s follow-up duration or when every safety assessment occurred. Apart from the stated 30-day period for the primary unsolicited adverse-event outcome, additional outcome timeframes are not reported in the registry record.
Because this is a single-group study, it provides no randomized, concurrent estimate of what would have happened to comparable participants without vaccination. The design is therefore suited to describing reported events among vaccinated participants, but it cannot support a direct treatment-versus-control comparison. Details of recruitment, allocation procedures beyond the registry’s not-applicable designation, and any protocol-based sample-size justification 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: 8687 subjects were enrolled in this study and received Herpes Zoster sub-unit vaccine. Of these, 8434 subjects completed the trial and 253 subjects withdrew.
Overall Study
| Stage | HZ/su Group |
|---|---|
| STARTED | 8687 |
| COMPLETED | 8434 |
| NOT COMPLETED | 253 |
Reasons for not completing this period:
| Reason | HZ/su Group |
|---|---|
| Lost to Follow-up | 48 |
| Withdrawal by Subject | 46 |
| Protocol Violation | 2 |
| Serious adverse event | 110 |
| Non-serious Adverse Event | 18 |
| Migrated/moved from study area | 5 |
| Suspected HZ Episode | 1 |
| Other reasons for withdrawal | 23 |
Analysis population for the primary outcome, as defined in the registry: This analysis was performed on Total vaccinated cohort, which included all subjects with at least one HZ/su vaccine administration documented for whom data 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.
| Characteristic | Unit | HZ/su Group |
|---|---|---|
| Participants analysed | 8687 | |
| Age, Continuous | Years | 72.6 (SD 9.4) |
| Age, Customized: Age 18-64 years | Participants | 2326 |
| Age, Customized: Age 65-84 years | Participants | 5574 |
| Age, Customized: Age 85 years and over | Participants | 787 |
| Sex/Gender, Customized: Female | Participants | 5254 |
| Sex/Gender, Customized: Male | Participants | 3433 |
| Race/Ethnicity, Customized: African Heritage/ African American | Participants | 72 |
| Race/Ethnicity, Customized: American Indian or Alaskan Native | Participants | 7 |
| Race/Ethnicity, Customized: Asian-Central/South Asian Heritage | Participants | 5 |
| Race/Ethnicity, Customized: Asian-East Asian Heritage | Participants | 1202 |
| Race/Ethnicity, Customized: Asian-Japanese Heritage | Participants | 254 |
| Race/Ethnicity, Customized: Asian-South East Asian Heritage | Participants | 12 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 3 |
| Race/Ethnicity, Customized: White-Arabic/North African Heritage | Participants | 47 |
| Race/Ethnicity, Customized: White-Caucasian / European Heritage | Participants | 6361 |
| Race/Ethnicity, Customized: Other | Participants | 724 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs), measured over During 30 days (Days 0-29) after any vaccination (across doses).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with any, grade 3, or vaccination-related unsolicited adverse events. The registry defines an unsolicited adverse event as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. “Any” includes unsolicited events regardless of intensity or relationship to vaccination. A grade 3 event is defined as one that prevented normal, everyday activities. Relatedness is the investigator’s assessment that the event was related to vaccination.
The outcome covers the 30 days after any vaccination, across doses. It is intended to describe events reported during that specified period, using participants as the unit of counting. Such safety endpoints are useful for organizing event frequency and severity in a defined vaccinated population. They do not, without a comparison group, establish how many events would have occurred in the absence of vaccination.
The registry record does not report the primary endpoint’s participant counts, including counts for any, grade 3, or related unsolicited events. It also does not report statistical analyses for this endpoint. The endpoint definition and timeframe are therefore available, but the registry record does not provide the primary outcome results needed to quantify the observed frequency.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed, phase 3, single-group vaccination study with 8687 participants. Its primary safety outcome is defined as the number of participants with any, grade 3, or related unsolicited adverse events during 30 days after any vaccination, across doses. However, no participant counts for those primary categories are reported in the registry record, and the record lists no statistical analyses. As a result, the primary outcome’s observed frequency and statistical precision cannot be assessed from the registry information.
The safety listing records 734 participants with serious adverse events among 8687 at risk. It also lists 5101 participants in a separate other adverse-event category, among 8687 at risk, and records 107 deaths. These are descriptive counts in the registry record. No comparisons, adjusted estimates, or uncertainty intervals are reported for them. The serious-event terms listed most frequently include pneumonia (0.6%), cardiac failure (0.3%), atrial fibrillation (0.3%), acute myocardial infarction (0.2%), myocardial infarction (0.2%), and urinary tract infection (0.2%). The registry presents these as percentages; it does not provide event-specific counts in the information available for this analysis.
These figures should not be read as evidence that vaccination caused the listed events. Serious adverse events can occur during a study for many reasons, and temporal occurrence after vaccination is not itself proof of causation. The registry’s listing does not provide a control group or an analysis that estimates the excess event frequency attributable to vaccination. The number of deaths is likewise a count, not an attribution of cause.
The record defines the primary analysis population as the total vaccinated cohort: participants with at least one documented vaccine administration and available data. A population definition helps clarify whose outcomes are intended to be counted, but it does not explain how missing outcome information was handled. That handling is not reported in the registry record.
Overall, the available information describes study structure, outcome definitions, and some safety counts. It does not report primary endpoint results or inferential comparisons. The evidence is therefore descriptive as presented, and its precision and causal interpretation are limited by the absence of reported analyses and a concurrent comparator.
9. Statistical Methods Explained
The registry describes a single-group study and lists no statistical analyses. That distinction matters: an outcome definition tells readers what investigators intended to count, while an analysis plan explains how those counts would be summarized, compared, or adjusted. The registry record provides the former for the primary endpoint but does not report the latter. No p-values, confidence intervals, or adjusted effect estimates for the primary outcome are reported in the registry record.
What does a participant count represent?
The primary outcome is expressed as a count of participants with events, rather than as a continuous measurement. The registry defines the total vaccinated cohort as participants with at least one documented HZ/su vaccination and available data. For this type of outcome, a count describes how many members of the analysis population met the event definition. A count alone is not a complete measure of frequency unless the relevant denominator and outcome definition are also clear. Here, the primary outcome definition and population are described, but the primary outcome counts are not reported.
The primary endpoint combines categories that capture different aspects of unsolicited events: any event, an event meeting the grade 3 definition, and an event judged related to vaccination. These labels should not be treated as interchangeable. “Any” is defined regardless of intensity or relation. Grade 3 refers to an event that prevented normal, everyday activities. Relatedness is an investigator assessment. The record does not report the results for these categories separately.
What can a confidence interval tell readers?
In general, a confidence interval describes the uncertainty around an estimate under the assumptions of the statistical method used. A narrow interval indicates greater precision than a wide interval, but neither width nor location alone resolves possible bias or limitations in study design. No confidence interval for the primary outcome is reported in the registry record, so its statistical precision cannot be characterized from the posted results.
In general, a p-value evaluates how compatible data are with a specified statistical model or null hypothesis. It is not a measure of the size or clinical importance of an effect, and it does not establish causation. Since the registry reports no analyses, there is no reported p-value for the primary endpoint to interpret. No hypothesis or testing procedure for that endpoint is reported in the registry record.
Why does the absence of a comparator matter?
The study has a single vaccinated group and no concurrent control. A single-group count can describe what occurred among participants observed in the study, but it cannot directly estimate a contrast between vaccinated and unvaccinated participants under comparable conditions. A comparison with earlier placebo experience would require specified data, compatible follow-up and outcome definitions, and an appropriate analysis; such a comparison is not reported in the registry record. The earlier placebo history does not itself supply a concurrent control for this study.
General statistical methods for comparing groups can account for sampling uncertainty, and some methods can adjust for measured differences between groups. Adjustment cannot guarantee that groups are comparable on unmeasured factors. More fundamentally, the registry record does not describe a comparison analysis for this single-group study. No causal effect estimate should be inferred from the event counts alone.
How should the planning illustration be understood?
The stated assumptions for a planning illustration are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is defined in relation to a stated fraction of an observed effect. Such calculations are planning scenarios: they show how a hypothetical future comparison might be sized under specified assumptions. They are not observed power, do not add participants to this completed single-group study, and do not establish that the study detected an effect.
For an illustration based on an observed effect, the meaning depends on the effect estimate and its definition. The registry record does not report the primary endpoint result or an observed effect for it. Accordingly, the planning assumptions cannot fill in the missing primary outcome result or establish the precision of an effect estimate from this study.
Over-dispersion is a general concern when observed variability exceeds what a simple statistical model assumes; ignoring it can make uncertainty estimates too small. The registry record does not report a model for the primary outcome or indicate whether over-dispersion was assessed. It would therefore be inappropriate to claim that any particular model or correction was used.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists four outcome measures, including the primary unsolicited adverse-event outcome and a secondary outcome counting participants with at least one suspected herpes zoster case. It does not report a multiplicity procedure or explain whether analyses of multiple outcomes were adjusted. In general, when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that issue. No specific testing strategy can be inferred for this study.
The registry lists zero analyses. This means the record does not provide inferential results to interpret, such as p-values or confidence intervals. The registry record does not report a statistical analysis plan, a hierarchy for outcome testing, or interim analyses. Their presence or absence outside the registry record cannot be established from the information reported.
The primary population is defined as the total vaccinated cohort, including participants with at least one documented vaccine administration and available data. The meaning of “available data” is not further detailed. The registry record does not report the amount or pattern of missing outcome information, how missing data were handled, or whether any sensitivity analysis was conducted. It also does not describe exclusions from the analysis population beyond the stated definition.
In general, missing data can affect descriptive counts and comparisons, especially if the likelihood of missingness is related to participants’ outcomes. Without details on the extent and handling of missingness, readers cannot evaluate that possibility for the primary endpoint. These reporting gaps also limit assessment of whether the analysis population and outcome data fully represent the enrolled participants.
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 |
|---|---|---|---|
| HZ/su Group | 734 | 8687 | 8.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| HZ/su Group | 107 of 8687 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| HZ/su Group | 5101 of 8687 |
Most frequent serious adverse event terms
| Event term | Organ system | HZ/su Group |
|---|---|---|
| Pneumonia | Infections and infestations | 54 of 8687 |
| Cardiac failure | Cardiac disorders | 28 of 8687 |
| Atrial fibrillation | Cardiac disorders | 25 of 8687 |
| Acute myocardial infarction | Cardiac disorders | 18 of 8687 |
| Myocardial infarction | Cardiac disorders | 18 of 8687 |
| Urinary tract infection | Infections and infestations | 17 of 8687 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 15 of 8687 |
| Cardiac failure congestive | Cardiac disorders | 14 of 8687 |
| Cerebrovascular accident | Nervous system disorders | 14 of 8687 |
| Angina pectoris | Cardiac disorders | 12 of 8687 |
Most frequent non-serious adverse event terms
| Event term | Organ system | HZ/su Group |
|---|---|---|
| Injection site pain | General disorders | 3173 of 8687 |
| Injection site erythema | General disorders | 1311 of 8687 |
| Pyrexia | General disorders | 1038 of 8687 |
| Injection site swelling | General disorders | 928 of 8687 |
| Headache | Nervous system disorders | 678 of 8687 |
| Myalgia | Musculoskeletal and connective tissue disorders | 386 of 8687 |
| Fatigue | General disorders | 384 of 8687 |
| Chills | General disorders | 319 of 8687 |
| Injection site pruritus | General disorders | 248 of 8687 |
| Nasopharyngitis | Infections and infestations | 228 of 8687 |
Serious events with the highest arm-level rate: pneumonia (0.6%), cardiac failure (0.3%), atrial fibrillation (0.3%), acute myocardial infarction (0.2%), myocardial infarction (0.2%).
The registry’s serious adverse-event listing reports 734 participants with a serious adverse event among 8687 at risk. It lists pneumonia at 0.6%, cardiac failure and atrial fibrillation at 0.3% each, and acute myocardial infarction, myocardial infarction, and urinary tract infection at 0.2% each. These term-specific percentages are descriptive entries in the registry. Event-specific counts and the method used to calculate the percentages are not reported in the registry record.
The listing also records 5101 participants in a separate other adverse-event category among 8687 at risk, and 107 deaths. These counts should be kept distinct: the record does not state that the other adverse-event category is a subset of serious events, nor does it provide a causal assessment for the deaths. A death count does not establish that deaths were related to vaccination.
In general, a serious adverse event is a safety classification and does not, by itself, mean that an event was caused by the study intervention. Attribution requires an assessment beyond noting that an event occurred during a study. Here, the available information does not provide a concurrent control or an analysis estimating the contribution of vaccination. The figures describe events recorded in the study population; they do not establish comparative risk or causation.
12. What the Result Does, and Does Not, Mean
The record establishes that the study enrolled 8687 people and evaluated safety after HZ/su vaccination in a single group of participants who had previously received placebo in two earlier studies. It defines the primary unsolicited adverse-event outcome and its 30-day observation period. It also gives descriptive serious adverse-event counts, selected serious-event terms and percentages, a count for another adverse-event category, and a death count.
Those details do not provide the primary endpoint results. The registry record does not report how many participants had any, grade 3, or related unsolicited adverse events, and it lists no statistical analyses. Therefore, readers cannot use the registry record to quantify the primary endpoint’s frequency, its precision, or the statistical strength of an association. This is a limitation of the information reported, not evidence that no events occurred.
The study’s design also constrains interpretation. It has no concurrent comparison group, so the observed safety counts cannot determine how event frequency differs from what would have occurred without vaccination. The figures do not establish that vaccination caused any particular serious event or death. Nor do the counts alone show whether event frequency was higher or lower than in another population.
In general, a descriptive safety study can help characterize events recorded among participants exposed to an intervention. Interpretation depends on the definitions, follow-up, completeness of outcome data, and available comparison. The registry specifies the primary endpoint’s definition and timeframe, but additional follow-up details, missing-data handling, and analysis methods are not reported in the registry record.
The defensible reading is limited but useful: the registry documents a substantial vaccinated cohort and some safety counts, while leaving the primary unsolicited-event results and inferential analyses unavailable. Any stronger conclusion about comparative safety, causal attribution, or statistical precision would go beyond what the registry record reports.
13. Why This Trial Matters Statistically
This study is statistically important as an example of a safety question that is not a randomized comparison. Participants had previously received placebo in ZOSTER-006 or ZOSTER-022, but the study vaccinated them in a single group. That history does not create a contemporaneous placebo arm. Recognizing this distinction helps readers avoid treating an observed event count as a vaccine-versus-control effect.
The endpoint also illustrates why outcome definitions matter. “Any” unsolicited adverse event, grade 3 events, and events judged related to vaccination capture different classifications. The registry defines each, including a functional definition for grade 3 and investigator-assessed relatedness. Without reported counts for these primary categories, however, the endpoint cannot be quantified from the registry record.
The safety listing provides descriptive counts and selected term-specific percentages, but those summaries answer a different question from a comparative analysis. They record events among participants at risk; they do not show what would have happened in a control group. Statistical interpretation requires attention to both the data summarized and the design that generated them.
Finally, the record demonstrates that registration information can be incomplete for evaluating statistical evidence even when it contains a study description and safety listings. No analyses are reported, and details about multiplicity, missing-data handling, and the statistical plan are not reported in the registry record. These are not grounds to infer an unreported result. They identify which questions remain unresolved when interpreting the posted information.
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 is that the registry record does not report the primary endpoint counts or statistical analyses. Although it defines any, grade 3, and related unsolicited adverse events and gives a 30-day timeframe, the corresponding results are unavailable in the record. The stated secondary outcome of suspected herpes zoster cases also has no result reported in the information available for this analysis.
The single-group design provides no concurrent control for comparison. The prior placebo history of participants in earlier studies does not, on its own, establish a like-for-like comparator in this study. The registry record does not report a comparative analysis, adjustment strategy, or causal estimate.
Further details needed to assess outcome completeness and precision are not reported in the registry record. These include the amount and pattern of missing outcome data, the handling of missingness, and methods for estimating uncertainty. The record also does not report a statistical analysis plan, multiplicity procedures, interim analyses, or a protocol-based sample-size justification. The assumptions stated for a planning illustration do not substitute for those study-specific details.
The serious-event listing gives counts and selected percentages, but the information available does not include event-specific participant counts for the listed terms or explain their calculation. The count of deaths has no reported causal attribution in this record. These gaps limit detailed interpretation of the safety summaries and do not allow comparison with an unvaccinated group.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Cross-vaccination Study of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK 1437173A) in Subjects Who Previously Received Placebo in ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) Studies. — NCT02690207.
- Registry record last updated 2021-03-04; status last verified 2021-02.
- Results first posted 2020-03-12.
- 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
NCT02690207 is a completed phase 3, single-group study of HZ/su vaccination in people who had previously received placebo in ZOSTER-006 or ZOSTER-022. The registry lists enrollment of 8687, no masking, and allocation as not applicable. The vaccine was administered intramuscularly in the deltoid of the non-dominant arm.
The primary outcome was the number of participants with any, grade 3, or related unsolicited adverse events during 30 days after any vaccination, across doses. The total vaccinated cohort included participants with at least one documented vaccine administration and available data. The registry record does not report primary outcome counts or statistical analyses.
Safety listings report 734 participants with serious adverse events among 8687 at risk, 5101 participants in another adverse-event category among 8687 at risk, and 107 deaths. These are descriptive figures without a concurrent control or reported causal analysis. The registry record does not report missing-data methods, multiplicity procedures, or a statistical analysis plan.