Safety & Immunogenicity of GlaxoSmithKline Biologicals' Herpes Zoster Vaccine 1437173A: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety & Immunogenicity of GlaxoSmithKline Biologicals' Herpes Zoster Vaccine 1437173A (NCT00920218), a randomized phase 2 study. The primary outcome is Number of Subjects With Any and Grade 3 Solicited Local Symptoms.

2. Clinical Question

3. Trial Design

NCT00920218 is a completed, randomized Phase 2 trial sponsored by GlaxoSmithKline. The registry record lists an enrollment of 121 and identifies herpes zoster as the condition. The trial began on 2009-07-14, and primary completion was recorded as 2011-04-26. These dates describe the trial record and do not, by themselves, establish the observation period for each endpoint.

The stated purpose was to evaluate safety and immunogenicity of the investigational vaccine when administered as two doses or three doses to hematopoietic stem cell transplant recipients. The intervention list names vaccine 1437173A and saline placebo. Arm descriptions distinguish formulation 1 and formulation 2 groups receiving three vaccine doses, a group receiving placebo followed by two doses of formulation 1, and a group receiving three placebo doses. The schedules are described as 0,1,3-months.

The record labels the design parallel, randomized and triple-masked. Its brief summary describes the study as observer-blind. The identities of the people masked, the randomization procedure, and the allocation ratio are not reported in the registry record. Although total enrollment is listed, the enrolled totals assigned to each randomized arm are not reported in the registry record.

The primary outcome concerns solicited local symptoms, while the secondary outcomes cover cellular and antibody immune measures and confirmed herpes zoster cases. The record lists 22 outcome measures and 4 analyses. The primary endpoint analysis population is the Total Vaccinated cohort, defined as vaccinated participants with at least one documented vaccine administration and completed symptom sheets. Details of analysis populations for every secondary endpoint 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: Out of the 121 subjects enrolled into this study, 1 subject was eliminated due to not receiving study vaccination and hence only 120 subjects started.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one vaccine administration documented, who had their symptom sheets filled in.

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 Any and Grade 3 Solicited Local Symptoms, measured over During the 7-days (Days 0-6) post-vaccination period following each dose and across doses.

The primary endpoint is the number of participants with any solicited local symptom and the number with Grade 3 solicited local symptoms. Symptoms were pain, redness and swelling. “Any” means a symptom occurred regardless of intensity. Grade 3 pain meant pain that prevented normal activity; Grade 3 redness or swelling meant spread beyond 100 millimeters of the injection site.

Assessments covered the 7-days (Days 0-6) post-vaccination period following each dose and across doses. Capturing both any symptom and Grade 3 symptoms distinguishes the occurrence of local reactions from reactions meeting the registry’s more restrictive severity descriptions. Counting participants is a binary-outcome approach: each participant is classified according to whether the specified event occurred, rather than measuring a continuous quantity such as symptom intensity on a scale.

Solicited symptoms are specified in advance for collection, which can make symptom reporting more systematic than relying only on spontaneous reports. The endpoint is relevant to safety and tolerability assessment, but it does not, by itself, describe immune response or protection from herpes zoster. The registry record defines the endpoint and its analysis cohort but does not report the participant counts, arm-specific estimates, or statistical comparisons for this primary outcome. Therefore the size and precision of any between-group differences cannot be assessed from the reported primary endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the outcome definition, the population analyzed, the comparison being made and the way uncertainty is reported. The registry record identifies the primary outcome as participant counts for solicited local symptoms, but does not report the primary results or a statistical analysis for that endpoint. The explanations below describe general statistical concepts; they do not imply that a particular method was used in this trial unless the registry record says so.

What does a participant count represent?

The primary outcome is binary at the participant level: a participant either met the definition for the event or did not. The registry separately defines “any” symptom and Grade 3 symptoms, and identifies pain, redness and swelling as solicited local symptoms. Counts can describe how many participants experienced an event, but a count alone does not make a fair comparison when the number assessed differs between groups. Interpretation usually also needs the relevant group denominators and a clearly specified analysis population. The record defines the Total Vaccinated cohort for the primary analysis but does not report primary outcome counts or group-level estimates.

For a treatment comparison, an effect estimate describes the contrast between groups, while a confidence interval describes the range of values compatible with the data under the statistical method used. A narrower interval indicates greater precision; a wider interval indicates more uncertainty. A point estimate without an interval can obscure that uncertainty. Neither an estimate nor a confidence interval for the primary endpoint is reported in the registry record, so the size and precision of the contrast cannot be evaluated.

Why distinguish any symptoms from Grade 3 symptoms?

“Any” includes an occurrence regardless of intensity. The Grade 3 definitions identify more restrictive events: pain preventing normal activity or redness or swelling spreading beyond 100 millimeters of the injection site. These categories answer different descriptive questions. Reporting both can help distinguish symptom occurrence from symptoms meeting the specified severity criteria. The definitions do not establish the causes of symptoms, and they do not substitute for the missing participant counts and comparative estimates.

What do repeated assessments mean?

The primary endpoint timeframe covers the 7-days (Days 0-6) after each vaccination and across doses. Repeated measurement can yield results organized by dose, by post-vaccination period, or across the vaccination course. Those approaches do not necessarily answer the same question. Analyses across multiple doses may also need to account for repeated observations from the same participants, depending on the endpoint and chosen method. The registry record does not report the statistical method used to handle repeated observations, nor does it provide a single primary comparison that resolves the multiple categories and time points.

The record explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Consequently, it would be inappropriate to infer a single primary effect from the endpoint description alone. The exact set of contrasts, any prioritization among them, and the approach to multiplicity are not reported in the registry record.

What does over-dispersion mean in general?

Over-dispersion is a general concern for count data when the observed variability is greater than a statistical model assumes. If ignored, uncertainty estimates can be too small and inferential conclusions too confident. The primary endpoint is described as counts of participants with binary events, not as a model for event rates or recurrent event counts. The registry record gives no evidence that an over-dispersion model was used or needed for this endpoint. This concept should therefore not be taken as a description of the trial’s analysis.

How should planning calculations be read?

Sample-size illustrations based on an observed effect are planning exercises, not measures of the trial’s achieved power. The stated assumptions for such illustrations are a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation, with the effect set as a fraction of the observed effect. For time-to-event outcomes, the stated quantity is total events; other outcomes use participants per arm. These assumptions describe an illustration and not necessarily the trial’s original design. The registry record does not report the trial’s own sample-size justification, target effect, or design assumptions. Any planning illustration must not be interpreted as observed power or as evidence that the trial was adequately powered.

What statistical plan is documented?

The record lists 22 outcome measures and 4 analyses, but the registry entries do not give a complete statistical analysis plan. The specific tests, models, adjustment variables, estimands, confidence-interval methods, missing-data procedures and multiplicity strategy are not reported in the registry record. No recalculated result is described for the primary endpoint. In the absence of these details and the outcome estimates, statistical significance, clinical relevance and precision cannot be judged from the endpoint definitions alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is described across several symptom categories and time points: any symptom, Grade 3 symptoms, individual local symptoms, the period after each dose and the period across doses. The registry record indicates that the outcome was not reduced to one comparison because it has several categories or time points. It does not report which comparisons were designated as primary within that set, whether any contrasts were prioritized, or whether a multiplicity adjustment was used.

Multiplicity matters when many outcomes or comparisons are examined. In general, the more statistical tests considered, the greater the chance that at least one result may appear notable by chance if the analysis does not account for the testing strategy. This general concern applies to interpretation of multiple endpoints and comparisons; it does not establish that any particular adjustment was required or used in this trial. The record lists 22 outcome measures and 4 analyses, but the specific analysis plan is not reported in the registry record.

The primary analysis population is identified as the Total Vaccinated cohort: participants with at least one documented vaccine administration and completed symptom sheets. This definition excludes vaccinated participants without completed symptom sheets from that endpoint analysis, but the number excluded and the handling of incomplete symptom data are not reported in the registry record. The record also does not report missing-data assumptions, imputation methods, sensitivity analyses, or endpoint-specific analysis populations for the secondary outcomes.

Because the primary outcome results and the handling of missing observations are not reported, it is not possible to assess whether missingness differed across groups or how that might affect the estimates. The number of participants enrolled does not establish how many contributed to each endpoint analysis. The registry record also does not report an interim-analysis plan, so no such plan should be inferred.

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: pneumonia (6.7%), pyrexia (6.5%), cellulitis (6.5%), multiple myeloma (6.5%), cough (6.5%).

The registry lists serious adverse event counts as participants at risk and participants affected in each group: GSK 1437173A F1 Group, 6 of 30; GSK 1437173A F2 Group, 9 of 29; Placebo-GSK 1437173A F1 Group, 10 of 31; and Placebo Group, 8 of 30. It lists other adverse event counts as 29 of 30, 27 of 29, 29 of 31 and 21 of 30, respectively. These are descriptive group counts; the registry record does not report a statistical comparison or establish whether events were considered related to the intervention.

The listed deaths are 3 in the GSK 1437173A F1 Group, 1 in the GSK 1437173A F2 Group, 2 in the Placebo-GSK 1437173A F1 Group and 3 in the Placebo Group. A death count alone does not establish cause or treatment attribution. The registry record does not provide those details in the registry entries.

Serious adverse event terms listed include pneumonia (6.7%), pyrexia (6.5%), cellulitis (6.5%), multiple myeloma (6.5%), cough (6.5%) and febrile neutropenia (3.4%). The listed percentages are not identified by group in the available record details. The event observation period, definitions beyond the serious-event label, and the clinical relationship of these events to vaccination are not reported in the registry record. These data should be read as reported counts and terms, not as evidence of causation or a comparative safety conclusion.

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

The trial record describes a randomized study of an investigational herpes zoster vaccine in hematopoietic stem cell transplant recipients, including vaccine formulation groups and placebo groups. It identifies solicited local symptoms as the primary endpoint and lists immune-response and confirmed herpes zoster outcomes as secondary measures. This information clarifies what the trial was designed to assess, but endpoint definitions are not outcome results.

The primary endpoint counts and comparative estimates are not reported in the registry record. Therefore, the registry entries do not show how often participants experienced any solicited symptom or a Grade 3 symptom, nor how those outcomes compared across groups. They also do not show the precision of any comparison. A conclusion about the primary endpoint would require the outcome data and the relevant statistical analysis, neither of which is reported in the registry record.

The record does include descriptive adverse event and death counts. These numbers provide limited safety context, but they do not establish whether an event was caused by vaccination, whether groups differed statistically, or whether the groups were equivalent. The event observation period and additional details needed to interpret the listed serious adverse event terms are not reported in the registry record.

The secondary outcome names indicate that immune responses and confirmed herpes zoster cases were of interest. Their numerical results are not reported in the registry record, so the outcome names cannot support conclusions about the magnitude or direction of immune responses or the occurrence of herpes zoster. Nor can the title or study purpose substitute for trial findings.

Overall, the available record supports a description of the design, endpoints and selected safety counts, but not an efficacy conclusion or a definitive comparative safety conclusion. The absence of reported endpoint results is an information limitation; it is not evidence that an outcome was absent, equal across groups or statistically inconclusive.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly defined endpoint and a reported result. The registry specifies what counted as any local symptom and what qualified as Grade 3 pain, redness or swelling. It also names the assessment period and defines the primary analysis cohort. Those details matter because results are interpretable only when the event, timeframe and population are clear.

The design includes formulation groups, a placebo group and a group receiving placebo before vaccine. This makes it important to know which group contrasts address the intended question and how outcomes across doses are summarized. The registry describes assessments after each dose and across doses, while also noting that the primary outcome has several categories or time points. Without a reported analysis strategy and corresponding results, the intended inferential comparison remains unclear.

The contrast between the trial’s stated focus on safety and immunogenicity and the limited numerical outcome reporting illustrates why registry descriptions and outcome results serve different purposes. Endpoint labels show what was assessed; they do not reveal the size, direction or precision of findings. The listed serious adverse event counts are useful descriptive information, but they cannot independently establish comparative risks or causation.

The record also illustrates why analysis populations and missing-data handling matter. The primary analysis cohort required completed symptom sheets, but the number of participants with missing sheets and the handling of incomplete observations are not reported in the registry record. Without those details, readers cannot assess the completeness of the primary endpoint data.

For biostatistical interpretation, the central lesson is to separate design, outcome definitions, descriptive counts and inferential results. The first three are partly described in the record; primary outcome estimates, uncertainty, multiplicity handling and key analysis details are not reported. Recognizing that boundary avoids turning an incomplete report into a treatment conclusion.

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 most direct limitation is that the registry record does not report the primary endpoint counts or comparisons, despite defining the endpoint and its analysis population. It also does not report numerical results for the listed cellular immune, antibody concentration or confirmed herpes zoster outcomes. The central safety and immunogenicity questions therefore cannot be evaluated from the available result information.

Important design and analysis details are not reported in the registry record. These include the allocation procedure and ratio, the identities of those masked, group enrollment totals, the statistical tests or models, confidence intervals, adjustment variables, and the multiplicity strategy. The record’s description as triple-masked and the brief summary’s description as observer-blind are both noted, but the masking roles are not specified.

The primary endpoint spans symptom categories and post-dose periods, but the record does not describe how repeated observations were analyzed or how comparisons were selected. It defines the Total Vaccinated cohort but does not report the number of participants with completed symptom sheets by group, the extent of missing data, or the method used to handle missing observations. Endpoint-specific analysis populations for secondary outcomes are also not reported.

The safety data are limited to selected counts and terms. The observation period, event attribution, and group assignment of the listed serious adverse event percentages are not reported in the registry entries. The counts should therefore not be interpreted as causal or adjusted comparisons. The registry record also does not report the trial’s sample-size justification or interim-analysis details. These limitations concern what can be interpreted from the record; they do not establish that the unreported analyses or information were absent from other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety & Immunogenicity of GlaxoSmithKline Biologicals' Herpes Zoster Vaccine 1437173A — NCT00920218.
• Registry record last updated 2017-12-12; status last verified 2017-08.
• Results first posted 2017-12-12.
• 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.

18. Record Summary

NCT00920218 is a completed, randomized Phase 2 trial sponsored by GlaxoSmithKline, with an enrollment of 121 and herpes zoster listed as the condition. It assessed safety and immunogenicity of vaccine 1437173A in hematopoietic stem cell transplant recipients. The record lists formulation 1 and formulation 2 vaccine groups, a placebo group, and a group receiving placebo followed by vaccine.

The primary endpoint counted participants with any and Grade 3 solicited local symptoms during the 7-days (Days 0-6) after vaccination and across doses. The primary analysis population was the Total Vaccinated cohort with documented vaccination and completed symptom sheets. Secondary outcomes included cellular immune measures, antibody concentrations and confirmed herpes zoster cases.

Selected adverse event and death counts are reported, but primary endpoint results, numerical secondary outcome results and comparative estimates are not reported in the registry record. Statistical methods for multiplicity and missing data are also not reported.