Study to Evaluate Efficacy, Safety and Immunogenicity of GSK Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults Aged 50 Years and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Efficacy, Safety and Immunogenicity of GSK Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults Aged 50 Years and Older (NCT01165177), a randomized phase 3 study. The primary outcome is Number of Subjects With Confirmed Herpes Zoster (HZ) Cases.

2. Clinical Question

The registry describes a randomized, triple-masked, parallel-group Phase 3 study. Its primary outcome is a count of participants with confirmed herpes zoster, rather than a measure of symptom severity or duration. The posted analysis separates participants into age bands as well as reporting an overall-ages comparison. Those age-specific results are best read as subgroup findings alongside the overall comparison, not as independent replacements for the main study question.

The registry also lists outcomes concerning post-herpetic neuralgia, pain, complications, hospitalization, mortality, and use of pain medication. These capture consequences or features of confirmed herpes zoster rather than the primary occurrence endpoint itself. A separate concurrently conducted study, ZOSTER-022, was intended to contribute to a pooled analysis contingent on each study achieving its objectives; the results are the reported results for NCT01165177, not a pooled estimate.

3. Trial Design

This completed Phase 3 trial randomized participants to GSK1437173A or placebo in a parallel-group design. The registry identifies the masking as triple and describes the study in its summary as observer-blind. Enrollment was 16165. The study began on 2010-08-02, and primary completion was recorded on 2014-05-09. The registry lists the study status as completed.

Participants assigned to the vaccine group were scheduled to receive GSK1437173A at 0 and 2 months. The placebo group was scheduled to receive NaCl solution on the same schedule. The primary endpoint covered the entire study period, described as a 3 to 5 year period following Day 0. The registry does not report a single identical follow-up duration for every participant in the primary outcome description.

The main endpoint analysis used the modified total vaccinated cohort. This population was drawn from the total vaccinated cohort but excluded people who did not receive the second vaccination and people who developed confirmed herpes zoster before one month after the second vaccination. The registry does not report additional detail about how participants were selected for each age subgroup beyond the age-group labels used in the results.

The study was conducted concurrently with ZOSTER-022. The registry summary says that a pooled analysis of both studies would be conducted contingent on each study achieving its objectives, and that the ZOSTER-022 protocol also addresses pooled-analysis outcomes. The registry record does not report the original sample-size justification, the trial’s detailed statistical plan, or whether interim analyses were planned or performed. Those design details should not be inferred from the posted enrollment or from calculations based on the outcome results.

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 all the subjects enrolled into this study, only 15405 received vaccination and were hence considered to start the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was based on the modified total vaccinated cohort, which included subjects from the total vaccinated cohort, except those who were not administered with the second vaccination or who developed a confirmed case of Herpes Zoster prior to 1 month after the second vaccination.

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 Confirmed Herpes Zoster (HZ) Cases, measured over During the entire study period (3 to 5 year period following Day 0).

The primary endpoint counts participants with confirmed herpes zoster during the study. It is a binary participant-level outcome: each participant either had a confirmed case during the specified period or did not. The registry identifies the unit as participants and states that cases were assessed in the modified total vaccinated cohort. The assessment period is described as the entire study period, a 3 to 5 year period following Day 0.

Counting participants with a confirmed case addresses the occurrence of the disease outcome, which is directly relevant to the trial’s stated aim of evaluating vaccine efficacy. It differs from counting episodes, days of pain, medication use, complications, or hospitalizations. Those other outcomes concern aspects of disease burden or consequences and are listed among secondary outcomes.

The endpoint definition and analysis population matter when interpreting the reported counts. The mTVc excludes participants who were not administered the second vaccination and those who developed a confirmed case before one month after the second vaccination. Thus, the primary results do not represent every person enrolled without qualification. The registry does not report further details about case adjudication procedures, the operational definition of a confirmed case, or missing-outcome handling. Those elements are not reported in the registry record, so the count should be interpreted according to the posted endpoint description rather than an assumed case definition or follow-up rule.

7. Results Posted in the Registry

• GSK1437173A 50-59 YOA Group: 0.1% (3/3492) versus 2.5% (87/3525) on control; risk difference -2.4 percentage points (95% CI -2.9 to -1.9), risk ratio 0.03 (0.01–0.11); unadjusted two-proportion z-test p = <0.001.
• GSK1437173A 60-69 YOA Group: 0.1% (2/2141) versus 2.5% (87/3525) on control; risk difference -2.4 percentage points (95% CI -2.9 to -1.8), risk ratio 0.04 (0.01–0.15); unadjusted two-proportion z-test p = <0.001.
• GSK1437173A Over 70 YOA Group: 0.1% (1/1711) versus 2.5% (87/3525) on control; risk difference -2.4 percentage points (95% CI -2.9 to -1.9), risk ratio 0.02 (0.00–0.17); unadjusted two-proportion z-test p = <0.001.
• GSK1437173A Overall Ages Group: 0.1% (6/7344) versus 2.5% (87/3525) on control; risk difference -2.4 percentage points (95% CI -2.9 to -1.9), risk ratio 0.03 (0.01–0.08); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Subjects With Any Episodes of Post-Herpetic Neuralgia (PHN)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • GSK1437173A 50-59 YOA Group: 0.0% (0/3491) versus 0.2% (8/3523) on control; risk difference -0.2 percentage points (95% CI -0.4 to -0.1); unadjusted two-proportion z-test p = 0.005.
  • GSK1437173A 60-69 YOA Group: 0.0% (0/2140) versus 0.2% (8/3523) on control; risk difference -0.2 percentage points (95% CI -0.4 to -0.1); unadjusted two-proportion z-test p = 0.027.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for GSK1437173A 50-59 YOA Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for GSK1437173A 60-69 YOA Group than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Subjects With a Reduction of Duration of Severe 'Worst' HZ-associated Pain

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Placebo 60-69 YOA Group: 82.2% (74/90) versus 88.3% (91/103) on control; risk difference -6.1 percentage points (95% CI -16.2 to 3.9), risk ratio 0.93 (0.83–1.05); unadjusted two-proportion z-test p = 0.228.
  • Placebo Over 70 YOA Group: 91.8% (56/61) versus 88.3% (91/103) on control; risk difference 3.5 percentage points (95% CI -5.8 to 12.7), risk ratio 1.04 (0.94–1.15); unadjusted two-proportion z-test p = 0.483.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo 60-69 YOA Group and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo Over 70 YOA Group and the control. The interval gives the range of effects that remain compatible with the data.

Number of Subjects With HZ Related Complications

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Placebo 60-69 YOA Group: 3.3% (3/90) versus 1.0% (1/103) on control; risk difference 2.4 percentage points (95% CI -1.8 to 6.5), risk ratio 3.43 (0.36–32.43); unadjusted two-proportion z-test p = 0.250.
  • Placebo Over 70 YOA Group: 3.3% (2/61) versus 1.0% (1/103) on control; risk difference 2.3 percentage points (95% CI -2.5 to 7.2), risk ratio 3.38 (0.31–36.47); unadjusted two-proportion z-test p = 0.286.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo 60-69 YOA Group and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo Over 70 YOA Group and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes concerning post-herpetic neuralgia, severe herpes-zoster-associated pain, complications, hospitalization, mortality, and use or duration of pain medication. Across these outcomes, the broad pattern is that many concern events occurring after confirmed herpes zoster and therefore involve fewer participants or events than the primary endpoint. The secondary outcomes address additional dimensions of disease burden; they are not interchangeable with the primary count of confirmed cases.

The primary result concerns the occurrence of confirmed herpes zoster over the study period. Secondary outcomes can add context about consequences among affected participants, but they do not independently establish or negate the primary efficacy finding. Their interpretation depends on their own definitions, analysis populations, and event counts. In some secondary outcomes, the registry posts counts but does not report a sponsor analysis. Results from a limited number of participants can be particularly uncertain.

Secondary findings also require caution because many outcomes and comparisons are considered. General explanation: when multiple statistical tests are conducted, the chance of obtaining at least one apparently unusual result can increase, even if no corresponding effect exists. A multiplicity adjustment is one approach to address that issue, but the registry record does not report whether secondary analyses were adjusted or how they were prioritized. Accordingly, unadjusted secondary p values, where present, carry less weight than a prespecified primary analysis and should be treated as exploratory rather than as a set of definitive independent conclusions.

The registry lists 22 outcome measures and reports 8 analyses for the primary outcome record; 21 secondary outcomes are posted. Those counts indicate a broad outcome set, but do not by themselves establish which analyses were planned as confirmatory. The registry does not report a hierarchy or a complete plan for interpreting the secondary outcomes. The overall secondary pattern is therefore best viewed as supplementary context, not as a substitute for the primary endpoint.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Subjects With Any Episodes of Post-Herpetic Neuralgia (PHN)
• Number of Subjects With a Reduction of Duration of Severe 'Worst' HZ-associated Pain
• Number of Subjects With Confirmed HZ Episode Related Mortality
• Number of Subjects With HZ Related Complications
• Number of Subjects With Confirmed HZ Episode Related Hospitalizations
• Number of Subjects With a Confirmed HZ Episode Having a Reduction of Duration of Pain Medication Associated With HZ
• Number of Subjects With a Confirmed HZ Episode Taking Pain Medication Associated With HZ
• Number of Days With Severe 'Worst' HZ-associated Pain.

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports the sponsor’s primary efficacy analyses using a Poisson exact test. Separate analyses compare the vaccine and placebo groups in each age band and in the overall-ages group. The reported parameter is vaccine efficacy, with a 95% confidence interval and a p value for each comparison. A Poisson exact method is a way to evaluate event-count data under a specified statistical model. General explanation: exact procedures can be useful when event counts are small, because they do not rely on some large-sample approximations in the same way as simpler methods. The registry record does not report the detailed model assumptions or implementation choices beyond naming the test.

What does a confidence interval communicate?

In general, a confidence interval describes the range of values reasonably compatible with the data and the method used, while reflecting sampling uncertainty. A narrower interval indicates greater precision under that method; a wider interval indicates more uncertainty about the estimate. The confidence intervals in the sponsor’s reported analyses are on the vaccine-efficacy scale. They should be read together with the corresponding point estimates, rather than as a guarantee that the true effect lies within a particular range.

How should the p values be read?

In general, a p value measures how incompatible the observed data, or more extreme data, would be with a specified null hypothesis under the statistical model. It is not the probability that the null hypothesis is true, and it does not measure the chance that the result occurred “by chance.” The sponsor’s primary p values are reported for the Poisson exact comparisons. They should not be interpreted as a measure of clinical importance or as proof that the result will be the same in another population.

What do the unadjusted re-calculations represent?

The additional risk-difference calculations are simple, unadjusted re-calculations from posted summary statistics. A risk difference expresses the contrast between the observed proportions in the compared groups. General explanation: such a calculation can provide a direct absolute-scale description, but it does not automatically reproduce a sponsor’s model-based analysis. Here the registry identifies a discrepancy between those calculations and the sponsor’s reported results. The sponsor’s own analysis takes precedence, and the re-calculations should be read as limited checks rather than as the trial’s official inferential analysis.

The re-calculation uses the counts and denominators listed in the posted results. A comparison built from summary counts may not capture modeling choices, population definitions, or other features of the sponsor’s analysis. The registry record does not report enough detail to reconcile the discrepancy. No explanation for it should be guessed.

Why do small event counts matter?

General explanation: when outcomes are uncommon, a small change in the number of observed events can have a noticeable effect on estimated rates and on the width of intervals. Sparse events also make subgroup estimates less stable. Exact methods address some aspects of inference with sparse counts, but they cannot create information that is absent from the observed data. The small case counts in the vaccine groups and the wider interval for the over-70 comparison should therefore inform how finely the results are interpreted.

The primary analysis population is explicitly defined as the modified total vaccinated cohort. The registry does not report the detailed handling of missing outcome data, the full statistical analysis plan, a multiplicity adjustment, or interim-analysis procedures. Those unreported details cannot be reconstructed from the endpoint counts or p values. The registry also describes a planned pooled analysis with ZOSTER-022, but the primary results discussed in this analysis are for NCT01165177 alone.

11. Confidence Intervals and Precision

The sponsor’s overall-ages efficacy estimate is 97.2, with a 95% confidence interval from 93.7 to 99. This interval indicates that the reported estimate is not infinitely precise: values across that range remain compatible with the data and the specified Poisson exact method. The interval is comparatively more informative than the p value alone because it communicates both the direction and the range of uncertainty in the estimate.

The age-specific intervals are 89.6 to 99.3 for ages 50-59 YOA, 90.1 to 99.7 for ages 60-69 YOA, and 87.9 to 100 for participants over 70 YOA. They are less precise than the overall-ages estimate, with especially broad uncertainty in the over-70 comparison. The registry reports only 1 confirmed case in the vaccine group over 70 YOA, compared with 48 in the corresponding placebo age group. Sparse outcomes limit the amount of information available to estimate an age-specific effect.

In general, confidence intervals reflect sampling variation under the chosen method and assumptions; they do not account automatically for every possible source of bias, missing data, endpoint misclassification, or analysis choice. The registry does not report enough detail to assess all such possibilities. The interval reaching 100 in the over-70 analysis also does not mean that efficacy is known to be exactly 100; it marks the reported upper limit for that interval.

The recalculated risk-difference intervals are a separate, unadjusted analysis and differ from the sponsor’s reported efficacy intervals. Given the identified discrepancy, they should not replace the sponsor’s intervals when describing the sponsor’s primary result. Precision should be judged from the sponsor-reported confidence intervals for its analyses, with particular caution when interpreting age-specific estimates based on few cases.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations translate selected effect sizes into the approximate number of participants per arm needed under the stated planning assumptions. They are based on the observed effect and show scenarios for planning for 100%, 75%, and 50% of that observed effect. The figures are participants per arm, not total participants or total events.

The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record, so these illustrations should not be read as a description of how the trial was originally designed.

The 80% power column describes the planned number of participants per arm for a design intended to have an 80% chance of detecting the specified effect under the assumptions, if that effect is present. The 90% power column gives the corresponding planning target for a design intended to have a 90% chance. These are design calculations, not guarantees about results in a particular study. Smaller effects require more participants to detect under otherwise identical assumptions. This is not observed power.

Because the observed estimates can be unstable, especially when event counts are small, planning around a fraction of the observed effect is a sensitivity exercise rather than a prediction that a future study will reproduce that effect. The illustrations do not account for additional design features or adjustments unless they are among the stated assumptions. For outcomes where the registry’s calculation describes total events rather than participants per arm, that distinction should be read from the stated outcome-specific convention; the primary endpoint illustrations discussed for this binary participant outcome are expressed as participants per arm.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.025; treatment proportion p₁ = 0.001; average p̄ = 0.013.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.1588 = 0.3112.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.1579 = 0.1329.
4. n = (0.3112 + 0.1329)² / (-0.0238)² = 347.6, rounded up to 348 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0246808510638298                          # control proportion
p1 <- 0.000859106529209622                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1165177)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 348 (80% power), 465 (90% power)
 75% of observed effect: n per arm = 762 (80% power), 1,019 (90% power)
 50% of observed effect: n per arm = 2,032 (80% power), 2,720 (90% power)
power.prop.test: 347.6 
Simulated power at n = 348 per arm: 0.911 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor reports vaccine efficacy from Poisson exact tests for the three age bands and the overall-ages group. The overall-ages estimate is 97.2, with a 95% confidence interval from 93.7 to 99 and p < 0.001. The age-specific estimates and intervals are also sponsor-reported results. These are the analyses to use when describing the registry’s formal primary efficacy findings.

Separate calculations based directly on the posted group counts produce unadjusted risk differences. The registry identifies a discrepancy between those re-calculations and the sponsor’s analysis. Since the re-calculations do not reproduce the reported result, they should not be used to overrule or substitute for the sponsor’s efficacy analysis. They offer a simpler summary-statistic comparison, but they are not the reported Poisson exact analyses.

The registry does not report sufficient detail to explain why the results differ, and no explanation should be inferred. The sponsor’s own analysis takes precedence, while the discrepancy remains a limitation on independently reconstructing the primary result from the posted counts. In particular, the re-calculations should not be presented as a correction to the sponsor’s result.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, subgroups, or comparisons. In general, conducting many tests can make at least one small p value more likely, even if the null hypothesis is true for all comparisons. Statistical plans may address this through outcome hierarchies, adjustment procedures, or by treating some analyses as exploratory. The registry lists numerous outcome measures and analyses, but a multiplicity strategy is not reported in the registry record.

The reported primary efficacy analyses include overall ages and age-specific comparisons. The registry does not report whether the age-specific comparisons were prespecified as confirmatory, whether a formal comparison of effects across age groups was conducted, or whether any adjustment was applied across these tests. Therefore, the separate p values should not be treated as if they establish differences among age groups. A small p value within one age stratum and a different p value in another do not, by themselves, test whether the treatment effect differs by age.

The record defines the primary analysis population as the modified total vaccinated cohort, including specified exclusions related to second vaccination and early confirmed cases. Further details of missing-data handling are not reported in the registry record. It is not reported how participants with incomplete follow-up or missing outcome status were treated, or whether any sensitivity analyses assessed the impact of missingness.

The registry record also does not report the full statistical analysis plan, the trial’s original sample-size justification, or interim-analysis procedures. These omissions limit assessment of whether all reported analyses follow a prespecified plan. The mention of a planned pooled analysis with ZOSTER-022 does not supply those missing details for this trial. Conclusions about multiplicity control, missing-data assumptions, or interim monitoring should not be inferred from the reported estimates alone.

16. 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 (0.5%), myocardial infarction (0.4%), cardiac failure (0.3%), atrial fibrillation (0.2%), cerebrovascular accident (0.2%).

The safety results list 7695 participants at risk in the GSK1437173A group and 7710 in the placebo group for serious adverse events. Serious adverse events affected 727 participants in the vaccine group and 731 in the placebo group. The registry also lists 5586 participants with other adverse events in the vaccine group and 1893 in the placebo group, and reports 11 deaths and 15 deaths, respectively.

These figures are descriptive counts in the registry record. They do not, by themselves, establish that an event was caused by the assigned intervention. The registry does not report the detailed definitions, timing, severity breakdown, or attribution procedures for these safety summaries in the registry record analyzed. The listed serious-event terms include pneumonia at 0.5%, myocardial infarction at 0.4%, cardiac failure at 0.3%, atrial fibrillation at 0.2%, cerebrovascular accident at 0.2%, and acute myocardial infarction at 0.2%. They are presented as leading serious-event terms, not as evidence of a causal relationship.

Safety comparisons should be read in the context of the at-risk group sizes and the registry’s reporting definitions. These aggregate counts do not describe individual risk or determine what a person should do medically.

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

The registry results show that the sponsor’s primary analysis reported high vaccine-efficacy estimates in each age band and in the overall-ages group. The overall-ages estimate was 97.2, with a 95% confidence interval from 93.7 to 99. The reported overall comparison had p < 0.001. The estimates describe the trial’s comparison in its modified total vaccinated cohort over the stated follow-up period.

These results do not mean that every participant in the vaccine group avoided herpes zoster, nor do they mean that the outcome is impossible. The registry reports 6 confirmed cases in the vaccine overall-ages group and 210 in the placebo overall-ages group. The results are group-level estimates, not predictions for a particular participant. They also do not establish the effect beyond the population, endpoint definition, follow-up period, and analysis used in this trial.

The primary endpoint concerns confirmed disease occurrence. It does not directly quantify pain severity, duration, complications, or other individual experiences. Those topics appear among the secondary outcomes, whose interpretation is more limited by event counts, multiple comparisons, and the absence of a reported multiplicity plan. The trial’s findings should therefore be described as results for the specified primary endpoint, rather than as proof about every possible outcome related to herpes zoster.

The sponsor’s reported analysis and the simple unadjusted re-calculations do not agree. The sponsor’s own analysis takes precedence, but the discrepancy limits independent reconstruction from the posted counts. Confidence intervals communicate statistical uncertainty under the analysis method; they do not cover every source of uncertainty, such as unreported missing-data handling or other design details.

These statistical results are not medical advice. They do not determine an individual’s treatment choice, and they do not establish that a treatment will work for every person or in every setting. They describe the evidence recorded for this particular randomized comparison.

18. Why This Trial Matters Statistically

This trial illustrates why the analysis population and outcome definition matter. The headline endpoint is a count of participants with confirmed herpes zoster, but the primary analysis is not simply all enrolled participants: it uses a modified total vaccinated cohort with stated exclusions. Understanding that definition is necessary before interpreting the group counts or the efficacy estimate.

It also shows how sparse outcomes shape inference. The vaccine groups had few confirmed cases, particularly in age-specific comparisons. The sponsor used a Poisson exact test, and the reported confidence intervals vary in width across the age groups. This is a useful reminder that a striking point estimate can coexist with uncertainty, and that subgroup estimates may be less precise than an overall estimate.

A second statistical lesson is the distinction between a sponsor-reported analysis and a simple recalculation from summary counts. Risk differences can be useful absolute-scale descriptions, but they need not reproduce a model-based efficacy analysis. When the registry identifies a discrepancy, the two results should not be blended or treated as interchangeable; the sponsor’s analysis takes precedence for the reported efficacy finding.

Finally, a broad outcome set makes multiplicity and selective emphasis important considerations. Secondary outcomes may provide valuable context, but without a reported testing hierarchy or adjustment strategy, their p values require more restraint. The missing detail about the original sample-size justification, missing outcomes, and interim procedures also illustrates why a registry result is informative but not a complete statistical report.

19. 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.

Several trial-specific limitations constrain interpretation of the posted results. The primary analysis uses the modified total vaccinated cohort, excluding people who did not receive the second vaccination and people with a confirmed case before one month after that vaccination. This population definition is explicit, but results should not be generalized automatically to every enrolled participant or to populations with different eligibility or follow-up characteristics.

The study period is described as 3 to 5 years after Day 0, rather than as one uniform duration for all participants. The registry does not report the detailed follow-up distribution, case-adjudication procedures, or operational confirmation criteria. These details would help assess outcome measurement and differences in exposure time, but they are not reported in the registry record.

Event counts are sparse in the vaccine groups, limiting precision for age-specific analyses and secondary outcomes. The sponsor’s reported efficacy estimates differ from simple unadjusted re-calculations based on posted summary counts, and the registry does not explain the discrepancy. The sponsor’s analysis takes precedence, but the difference prevents a straightforward reconstruction from the summary data alone.

The registry does not report the original sample-size justification, full analysis plan, multiplicity handling, missing-data methods, or interim-analysis procedures. It also does not report a formal test for variation in effect across age groups. These gaps restrict assessment of prespecification, robustness, and subgroup interpretation. Finally, the concurrently conducted ZOSTER-022 study was intended to contribute to a pooled analysis under stated conditions, but its results are not part of the individual-trial estimates.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study to Evaluate Efficacy, Safety and Immunogenicity of GSK Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults Aged 50 Years and Older — NCT01165177.
• Registry record last updated 2021-02-10; status last verified 2021-01.
• Results first posted 2017-05-01.
• 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.

23. Record Summary

NCT01165177 is a completed randomized, triple-masked, parallel-group Phase 3 study of GSK1437173A versus NaCl solution placebo in adults aged 50 years and older. Enrollment was 16165. The primary outcome was confirmed herpes zoster during a 3 to 5 year period following Day 0, assessed in the modified total vaccinated cohort.

The sponsor reported overall-ages vaccine efficacy of 97.2, with a 95% confidence interval from 93.7 to 99 and p < 0.001. Age-specific efficacy estimates were also reported. Simple unadjusted re-calculations differ from the sponsor’s analyses, so the sponsor’s results take precedence. The registry record does not report several details needed for a full assessment, including the original sample-size justification, missing-data methods, and multiplicity plan.