A Study on the Immune Response and Safety of a Vaccine Against Herpes Zoster in Adults Aged 50 Years and Older in India: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on the Immune Response and Safety of a Vaccine Against Herpes Zoster in Adults Aged 50 Years and Older in India (NCT05219253), a randomized phase 3 study. The primary outcome is Percentage of Participants Showing a Vaccine Response for Anti-glycoprotein E (gE).

2. Clinical Question

3. Trial Design

The registry identifies NCT05219253 as a Phase 3, randomized, observer-blind, placebo-controlled, multicentre study in adults aged 50 years and older in India. The registered allocation was randomized, the masking designation was quadruple, and the model was parallel. The study is marked completed. Enrollment was 288. The sponsor was GlaxoSmithKline.

The intervention was the herpes zoster subunit vaccine, called HZ/su in the record, and the comparator was placebo. The HZ/su group received two doses at Day 1 and Month 2; the placebo group followed the same stated schedule. The main purpose recorded for the study was to evaluate humoral immunogenicity and safety in this population. The registry lists herpes zoster as the condition.

The registry gives a start date of 2022-02-02 and a primary completion date of 2022-10-11. These are record dates, not a description of the duration of follow-up for every participant. The primary endpoint was assessed at 1 month post-Dose 2, corresponding to Month 3. The secondary serious-adverse-event endpoint covers the period from Dose 1 at Day 1 up to study end at Month 8.

The primary analysis was conducted in the Per Protocol Set. The available population description says that it included eligible participants who received all doses as per protocol and complied with allowed dosing and blood-draw intervals, without intercurrent conditions that may have interfered with immunogenicity and without prohibited concomitant medication. The wording ends before the full definition is complete; any additional criteria are not reported in the registry record. The registry's account of how participants were assigned, how masking was implemented, and how missing observations were handled is not reported in the registry record beyond the design labels.

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: All 288 participants enrolled in this study received 2 doses of the study interventions and were included in the Exposed Set. A total of 285 participants completed the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis was performed on the Per Protocol Set, which included all eligible participants who received all doses as per protocol, complied with allowed dosing/blood draw intervals, without intercurrent conditions that may have interfered with immunogenicity, without prohibited concomitant medication/vaccination and with immunogenicity results available at the specified time point post-Dose 2.

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 Percentage of Participants Showing a Vaccine Response for Anti-glycoprotein E (gE), measured over At 1 month post-Dose 2 of study intervention administration (Month 3).

The primary endpoint is the percentage of participants showing a vaccine response for anti-glycoprotein E, or anti-gE, at 1 month post-Dose 2 of study intervention administration, identified as Month 3. It summarizes whether a participant's antibody concentration met a prespecified fold-rise definition, rather than reporting an average antibody concentration or a clinical herpes zoster outcome.

For participants who were seropositive at baseline, the registry defines response as a post-last-vaccination anti-gE antibody concentration at least 4-fold greater than the pre-vaccination concentration. For participants who were seronegative at baseline, the post-last-vaccination concentration must be at least 4-fold greater than the antibody cut-off value for seropositivity. Thus, the response criterion depends on baseline serostatus.

A percentage-based response endpoint gives a direct count-based summary of how many participants met this antibody criterion in each group. The registry also reports 95% confidence intervals for the percentages, which convey uncertainty around those estimates. The endpoint is used to assess humoral immunogenicity. By itself, an antibody response does not establish the size of any effect on herpes zoster incidence, because disease occurrence is not the primary outcome.

The primary analysis population was the Per Protocol Set, not everyone enrolled. The registry describes this set in terms of eligibility, protocol-compliant dosing and blood-draw intervals, and absence of specified conditions that might interfere with immunogenicity. The complete operational definition is not reported in the registry record.

7. Results Posted in the Registry

• HZ/suSeq Group: 85.7% (108/126) versus 7.8% (10/129) on control; risk difference 78.0 percentage points (95% CI 70.3 to 85.6), risk ratio 11.06 (6.07–20.14); 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.

Percentage of Participants Reporting SAEs

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • HZ/suSeq Group: 0.7% (1/143) versus 1.4% (2/145) on control; risk difference -0.7 percentage points (95% CI -3.0 to 1.7), risk ratio 0.51 (0.05–5.53); unadjusted two-proportion z-test p = 0.570.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between HZ/suSeq Group and the control. The interval gives the range of effects that remain compatible with the data.

The registry's secondary outcome list spans several different questions: antibody concentration and between-group geometric mean concentration ratios, solicited administration-site and systemic events, unsolicited adverse events, serious adverse events, and potential immune-mediated diseases. These outcomes complement the primary anti-gE response endpoint by addressing antibody levels and safety experience, rather than repeating the primary threshold-based response question.

The available secondary numerical comparison described for this analysis concerns serious adverse events from Dose 1 at Day 1 up to study end at Month 8. Numeric results for the other listed secondary outcomes are not reported in the registry record. As a result, the broader pattern across antibody concentrations, solicited events, unsolicited events, and potential immune-mediated diseases cannot be characterized from the posted results addressed. Their inclusion in the outcome list does not itself establish what the findings were.

The primary endpoint and secondary endpoints should be interpreted as related but distinct evidence. The primary endpoint assesses whether participants met a defined anti-gE fold-rise criterion at Month 3. Safety outcomes count reported events over stated observation periods. A strong difference in the antibody-response percentages does not determine the direction or size of differences in safety outcomes, and the safety outcomes do not directly measure the primary immunogenicity response.

Secondary results generally carry less inferential weight when many outcomes are examined and no multiplicity strategy is reported. General statistical explanation: testing multiple outcomes creates more opportunities for an apparently unusual result to arise by chance. A prespecified hierarchy or adjustment can help address that issue, but the registry's multiplicity plan is not reported in the registry record. The unadjusted comparison for a secondary outcome should therefore be read as a descriptive or exploratory result unless the analysis plan establishes otherwise. The registry record does not provide enough detail to determine whether any secondary endpoint was designated for confirmatory inference.

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

• Anti-gE Antibody Concentrations Expressed as Geometric Mean Concentrations (GMCs) and Between-group GMC Ratios
• Percentage of Participants Reporting Solicited Administration Site Events
• Percentage of Participants Reporting Solicited Systemic Events
• Percentage of Participants Reporting Unsolicited Adverse Events (AEs)
• Percentage of Participants Reporting Serious Adverse Events (SAEs)
• Percentage of Participants Reporting Potential Immune-mediated Diseases (pIMDs)
• Percentage of Participants Reporting SAEs
• Percentage of Participants Reporting pIMDs

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: each analyzed participant either met the registry's vaccine-response definition or did not. A group percentage summarizes the frequency of responses. This kind of endpoint is often useful when the scientific question is framed around how many participants achieve a defined threshold, rather than the average magnitude of a continuous measurement. Here the threshold is based on anti-gE antibody concentrations and differs according to baseline serostatus.

What does the confidence interval describe?

A confidence interval expresses the uncertainty associated with an estimate under the statistical procedure used to construct it. The primary group percentages are accompanied by 95% confidence intervals: 85.7% with an interval from 78.4% to 91.3% for HZ/su, and 7.8% with an interval from 3.8% to 13.8% for placebo. The risk-difference estimate is 0.780, with an interval from 0.703 to 0.856. These intervals help show the range of values reasonably compatible with the observed data and the analysis assumptions. They are not guarantees that the true value lies within a particular interval, and they do not account for unreported sources of uncertainty such as missing-data assumptions or the choice of analysis population.

How should the group comparison be read?

The risk difference compares the response proportions on the proportion scale. Its interval is entirely above zero, while the posted unadjusted p-value is <0.001. In general, a p-value evaluates how compatible the observed data are with a specified null hypothesis, under the model and assumptions used. It does not measure the probability that the null hypothesis is true, and it does not quantify the importance of an effect. The confidence interval supplies additional information about the estimated contrast and its precision.

The comparison also lists a risk ratio of 11.06, with a 95% confidence interval from 6.071 to 20.14, and an odds ratio of 71.4, with a 95% confidence interval from 31.58 to 161.4. These are alternative relative summaries of the same binary response data. Relative measures can appear large when the comparison-group response is low, so interpretation should remain anchored to the group percentages and the endpoint definition. The registry comparison is unadjusted; any adjusted analysis is not reported in the registry record.

Why does the analysis population matter?

The primary analysis used the Per Protocol Set. Such a population is defined by protocol eligibility and adherence requirements, and the registry's partial description indicates that dosing, blood-draw timing, intercurrent conditions and prohibited concomitant medication were relevant. Because the complete definition and details of exclusions are not reported in the registry record, readers cannot fully assess how the analyzed set was formed or how it compares with all enrolled participants. A per-protocol estimate describes the participants included in that set; it is not automatically interchangeable with an estimate based on all randomized participants.

The number analyzed was 126 in the HZ/su group and 129 in the placebo group for the primary endpoint. The registry separately records enrollment of 288. Reasons why the primary analysis denominators differ from the enrollment total, including the roles of eligibility, missing measurements or protocol deviations, are not reported in the registry record. This prevents a detailed assessment of the flow from enrollment to the primary analysis.

What does over-dispersion mean in general?

General statistical explanation: over-dispersion occurs when variability in observed data is greater than a model assumes. It can make standard errors too small and confidence intervals too narrow if ignored. For a binary percentage endpoint, the model and variance procedure used to produce an interval matter, particularly when event counts are small. The registry identifies the dispersion as a 95% confidence interval but does not report the precise interval-construction method or whether any alternative variance method was used.

What analysis details remain unclear?

The registry reports one primary comparison and an unadjusted p-value. The analysis plan, covariate adjustment, interim analyses, missing-data method, and multiplicity procedure are not reported in the registry record. General statistical practice distinguishes a prespecified primary hypothesis from a family of secondary hypotheses; when many outcomes are tested, the chance of at least one apparently unusual result can increase unless multiplicity is addressed. Without a reported plan, it is not possible to determine whether or how the secondary tests were controlled.

The registry reports the primary endpoint in the Per Protocol Set and supplies the response definition, but the complete population definition is truncated. It is also not reported in the registry record whether any sensitivity analyses were conducted to assess robustness to alternative analysis populations or missing-data assumptions. The primary percentages and comparison can therefore be interpreted as posted, while recognizing that some analytic choices needed for independent reproduction are unavailable.

11. Confidence Intervals and Precision

The primary percentages have 95% confidence intervals of 78.4% to 91.3% for HZ/su and 3.8% to 13.8% for placebo. These intervals describe uncertainty around each group estimate. The interval for the risk difference, 0.703 to 0.856, is also entirely above zero. Together with the posted estimate of 0.780, it indicates a clearly separated contrast for the measured antibody-response endpoint in the Per Protocol Set.

Precision is not the same as clinical importance. A narrow interval can indicate that an estimate is relatively well determined under the model, but it cannot establish that the endpoint is a clinical outcome or that the result applies to people outside the analyzed population. The primary endpoint records whether participants crossed a specified antibody threshold at a specified time. It does not directly measure herpes zoster incidence.

The interval estimates also depend on the analysis population and statistical method. The primary denominators were 126 for HZ/su and 129 for placebo. The registry does not report the full Per Protocol Set definition, the interval-construction method, or how missing endpoint measurements were handled. These omissions limit independent evaluation of whether other reasonable analytic choices would yield similar precision.

For the secondary serious adverse event endpoint, the confidence intervals are much broader relative to the reported percentages: 0.0% to 3.8% for HZ/su and 0.2% to 4.9% for placebo. The risk-difference interval ranges from -0.030 to 0.017. Such an interval includes values on either side of zero, so the posted data do not estimate the between-group difference precisely. This is distinct from the primary immunogenicity result and should not be conflated with it.

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 planning figures are participants per arm, not total participants, for the binary percentage comparisons. The planning assumptions listed in the registry are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to a stated fraction of the observed effect. The original trial's own sample-size justification and design assumptions are not reported in the registry record.

For the primary response comparison, the planning illustration lists 6 participants per arm for 80% power and 7 participants per arm for 90% power when planning for 100% of the observed effect. For 75% of the observed effect, the corresponding figures are 10 and 13 participants per arm. For 50% of the observed effect, they are 20 and 26 participants per arm. The pattern illustrates a general planning principle: smaller effects are harder to distinguish from chance variation and therefore require more participants to reach the same target power.

The serious adverse event comparison has a much smaller observed contrast, and its planning figures are correspondingly much larger. For 100% of the observed effect, the illustration gives 3,491 participants per arm for 80% power and 4,673 for 90% power. For 75% of the observed effect, it gives 6,708 and 8,980 participants per arm. For 50% of the observed effect, it gives 16,222 and 21,716 participants per arm.

In plain language, the 80% power column gives the modeled number of participants per arm for an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true effect. The 90% column applies the same idea to a 90% chance. These are planning illustrations based on observed effects, not observed power. They are sensitive to the effect size used and should not be read as the trial's original design target.

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 = 0.078; treatment proportion p₁ = 0.857; average p̄ = 0.467.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7056 = 1.3829.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4404 = 0.3707.
4. n = (1.3829 + 0.3707)² / (0.7796)² = 5.1, rounded up to 6 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 <- 0.0775193798449612                          # control proportion
p1 <- 0.857142857142857                          # 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(5219253)
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 = 6 (80% power), 7 (90% power)
 75% of observed effect: n per arm = 10 (80% power), 13 (90% power)
 50% of observed effect: n per arm = 20 (80% power), 26 (90% power)
power.prop.test: 5.1 
Simulated power at n = 6 per arm: 0.887 (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. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary analysis and lists 11 posted secondary outcomes. The primary endpoint is the percentage of participants showing an anti-gE vaccine response at Month 3. The secondary outcomes cover antibody concentrations, solicited and unsolicited events, serious adverse events, and potential immune-mediated diseases. Testing several outcomes raises a multiplicity question: if each is evaluated separately, the overall chance of at least one chance finding can exceed the chance associated with any single test.

The registry record does not report a multiplicity adjustment, a testing hierarchy, or which secondary outcomes, if any, were intended as confirmatory. It also does not report the statistical analysis plan. The primary unadjusted p-value can be interpreted as the posted result for the primary comparison, but the status of secondary p-values cannot be placed within a broader error-control strategy from the information recorded. Secondary comparisons should consequently be interpreted cautiously.

Missing-data handling is not reported in the registry record. The primary endpoint analysis used the Per Protocol Set, and the available description gives some eligibility and protocol-compliance criteria, but it does not provide a complete population definition or explain how participants with missing antibody measurements were treated. Reasons for exclusion from the analysis and any sensitivity analyses are also not reported. Without these details, it is not possible to assess the effect of missing observations or compare the per-protocol result with an analysis of all randomized participants.

The registry identifies randomization and quadruple masking, but the precise randomization procedure, masking implementation, and analysis adjustments are not reported in the registry record. Interim analyses are not reported in the registry record. The original sample-size justification is also not reported; the planning illustrations based on observed effects do not establish what assumptions were used to design the trial. These reporting gaps limit a full audit of prespecification and robustness, even though the posted primary estimate and interval can still be described on their own terms.

15. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (0.7%), accidental poisoning (0.7%), head injury (0.7%).

For serious adverse events from Dose 1 at Day 1 up to study end at Month 8, the HZ/su group had a reported percentage of 0.7% among 143 participants, with a 95% confidence interval from 0.0% to 3.8%. The placebo group had a reported percentage of 1.4% among 145 participants, with a 95% confidence interval from 0.2% to 4.9%. The posted event counts were 1 and 2, respectively.

The unadjusted risk-difference estimate is -0.007, with a 95% confidence interval from -0.030 to 0.017, and an unadjusted p-value of 0.57. The interval includes zero and extends in both directions, so these data do not estimate the group difference precisely. Few events were observed, and the confidence intervals allow a range of possible differences.

The registry reports zero deaths in each group. Pneumonia, accidental poisoning and head injury are each listed at 0.7% among the top serious terms. These figures describe the posted safety observations over the stated period; they do not establish that all possible harms were captured or that the groups are equivalent in safety. Other safety endpoint results are not reported in the registry record.

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

The primary result shows a marked difference in the percentage meeting the registry's anti-gE vaccine-response definition at Month 3: 85.7% in the HZ/su group and 7.8% in the placebo group. The confidence intervals and posted unadjusted comparison indicate that this separation is unlikely to be explained by random variation alone under the analysis used. The result is evidence about humoral immunogenicity in the Per Protocol Set.

That conclusion has a specific scope. The endpoint is an antibody response based on a fold-rise threshold, with the reference determined by baseline serostatus. It is not a clinical herpes zoster endpoint. The record does not report a comparison of disease incidence, and the antibody-response percentage should not be translated into vaccine efficacy or a claim about the number of illnesses prevented.

The analysis applies to the participants included in the Per Protocol Set. Its full definition is not available in the registry record, and the reasons for participants not appearing in the primary analysis denominators are not reported. The result therefore cannot automatically be generalized to every enrolled participant or to populations beyond the registered study population of adults aged 50 years and older in India.

The safety evidence is separate from the immunogenicity evidence. The serious adverse event percentages were 0.7% and 1.4%, with broad confidence intervals and an unadjusted p-value of 0.57. That comparison is imprecise and does not establish either a meaningful difference or equivalence. The registry's numerical results for most other listed safety outcomes are not reported in the registry record, so the overall safety profile cannot be reconstructed from these figures alone.

In general, interpretation of any trial result depends on its endpoint, analysis population, follow-up, and statistical plan. The registry does not report the full analysis plan, missing-data approach, multiplicity procedure, or original sample-size justification. The posted result supports a conclusion about the measured antibody-response endpoint at the stated time, while broader clinical and statistical conclusions remain outside what these registry results establish.

17. Why This Trial Matters Statistically

This study provides a useful example of the distinction between an immunogenicity endpoint and a clinical outcome. The primary endpoint counts participants who meet a prespecified antibody fold-rise criterion. It is not a herpes zoster case endpoint. Reading the estimate alongside its definition prevents an antibody-response percentage from being mistaken for a direct measure of disease prevention.

The result also illustrates why absolute group percentages, relative summaries and confidence intervals should be read together. The primary group estimates are 85.7% and 7.8%, while the posted risk difference is 0.780 and the risk ratio is 11.06. Relative measures describe contrast on a different scale and can be especially large when the comparator response is low. The interval around each estimate helps show how much uncertainty remains.

The safety comparison provides a contrasting statistical situation. Serious adverse events were uncommon in both groups, and the estimate has a broad interval that includes zero. A non-significant comparison with sparse events is not evidence that the groups are equivalent. It indicates that the observed safety data do not precisely distinguish the groups for this endpoint.

Finally, the record highlights the value of reporting analysis populations, missing-data methods, multiplicity plans and sample-size assumptions. The registry includes a Per Protocol Set description and planning illustrations based on observed effects, but the complete analysis definition and the original design justification are not reported. Those omissions matter because they affect how readers assess the scope, reproducibility and confirmatory status of the findings.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint is an antibody-response measure rather than a clinical herpes zoster outcome. The registry record does not report a disease-incidence comparison, so the posted immunogenicity result cannot by itself quantify clinical protection. The endpoint also uses different response references for baseline-seropositive and baseline-seronegative participants, making the precise definition central to interpretation.

The primary analysis was conducted in the Per Protocol Set, whose available description is incomplete. The registry reports primary analysis denominators of 126 and 129, while enrollment was 288, but reasons for the difference are not reported in the registry record. Missing-data handling, exclusions, and sensitivity analyses are not reported. This limits assessment of selection effects and the robustness of the analysis population.

The trial record identifies randomization, quadruple masking and a parallel design, but further operational details are not reported in the registry record. The statistical analysis plan, original sample-size assumptions, interim analyses and multiplicity approach are also not reported. Consequently, it is not possible to establish from the record whether all analysis choices were prespecified or how secondary findings were intended to be interpreted.

For safety, the serious-adverse-event comparison is based on few posted events and has broad confidence intervals. Numeric findings for most other listed safety outcomes are not reported in the registry record. The reported observation period for serious adverse events ends at study end, identified as Month 8; longer-term outcomes are not described in the registry record for this analysis. The record also does not provide enough detail to evaluate the completeness of event ascertainment or the consequences of any missing safety observations.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study on the Immune Response and Safety of a Vaccine Against Herpes Zoster in Adults Aged 50 Years and Older in India — NCT05219253.
• Registry record last updated 2025-05-15; status last verified 2025-05.
• Results first posted 2024-04-08.
• 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.

22. Record Summary

NCT05219253 is a completed Phase 3 randomized, observer-blind, placebo-controlled, multicentre study of HZ/su in adults aged 50 years and older in India. Enrollment was 288, and the registered schedule was two doses at Day 1 and Month 2.

The primary endpoint was the percentage showing an anti-gE vaccine response at Month 3 in the Per Protocol Set. The posted percentages were 85.7% for HZ/su and 7.8% for placebo, with an unadjusted p-value of <0.001. The endpoint measures antibody response, not herpes zoster incidence.

The serious adverse event percentages were 0.7% and 1.4%, respectively, with an unadjusted p-value of 0.57. The registry does not report complete analysis-plan, missing-data, multiplicity or original sample-size details, and numeric results for most listed secondary outcomes are not reported in the registry record.