Persistence of Protection by Shingrix: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Persistence of Protection by Shingrix (NCT04169009), a non-randomized phase 4 study. The primary outcome is Magnitude of Varicella-Zoster Virus (VZV) DNAemia.

2. Clinical Question

3. Trial Design

This is a Phase 4, parallel, non-randomized study sponsored by University of Colorado, Denver. The registry record gives the study title as Persistence of Protection by Shingrix and the official title as Persistence of Protection Conferred by Shingrix Against Herpes Zoster. Its status is completed. The recorded start date is 2020-07-28, the primary completion date is 2023-03-31, and enrollment is 105.

The four cohorts are distinguished by prior vaccine history. Participants in the ZVL >5 years previously cohort and the SRX >5 years previously cohort received the intradermal challenge in the non-dominant deltoid; a skin biopsy at the injection site was planned for 20 subjects in each of those cohorts. Participants who received ZVL 6-12 months previously also received the intradermal challenge. Participants with no previous ZVL were to receive the 2 standard doses of RZV, followed six months later by the challenge.

Allocation is recorded as non-randomized, masking as none, and the model as parallel. Thus, the cohort differences are part of the study structure rather than groups assigned by random allocation. Comparisons can describe how measured DNAemia differs across the recorded histories, but differences cannot be separated from other possible differences between cohorts using randomization. The registry record does not report further details of recruitment, eligibility, protocol adherence, or the rationale for the cohort sizes.

The registry record lists one primary outcome measure and zero analyses. It does not report observed primary-endpoint values or statistical comparisons. Consequently, the design and measurement question can be described, but no estimate of persistence or contrast between the vaccine-history cohorts can be interpreted from the posted outcome information.

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.

Overall Study

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 Magnitude of Varicella-Zoster Virus (VZV) DNAemia, measured over Until VZV DNA is undetectable in the blood, measured up to Day 7.

The primary endpoint is the magnitude of VZV DNAemia. The registry record describes measurement by polymerase chain reaction (PCR) as a surrogate for viremia over the first 7 days after an intradermal vOka challenge. The endpoint is the area under the concentration-time curve of VZV DNAemia, expressed in DNA copies/ml of blood. Measurement is described as continuing until VZV DNA is undetectable, up to Day 7.

General: An area under a concentration-time curve combines measurements across the stated observation period into a summary of the measured signal over time. It is therefore not the same as a single PCR result at one moment. A higher or lower curve summary would describe the measured DNAemia signal, but the registry record does not give observed values or establish how such values relate to clinical herpes zoster outcomes.

The registry record labels the endpoint as a geometric mean with standard deviation as its dispersion measure. General: A geometric mean summarizes measurements on a multiplicative scale, while a standard deviation describes spread around a measure of central tendency. The registry record does not provide the actual estimate, its standard deviation, or further calculation details. It therefore supports a description of the planned measurement, not a conclusion about the amount or duration of DNAemia in any cohort.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record states the outcome definition but does not report a statistical analysis plan. It identifies the primary parameter as a geometric mean and the dispersion as standard deviation, and says the measurement is the area under the concentration-time curve of PCR-measured VZV DNAemia. It lists zero analyses. The statistical methods used to produce a result, if any, are not reported in the registry record.

What does the endpoint summarize?

General: A concentration-time curve represents a measured quantity across time. Its area under the curve compresses information across the observation period into a summary of the accumulated measured signal. Here, the registry describes VZV DNAemia measured by PCR after an intradermal challenge, with observation until VZV DNA is undetectable and measurement up to Day 7. The endpoint description does not provide individual measurements, the timing of each planned measurement, or rules for handling values that are undetectable.

The unit is DNA copies per/mL in the registry’s endpoint metadata, while the description expresses the curve as DNA copies/ml of blood. The record does not give a numerical endpoint value. It also does not explain whether the stated geometric mean applies to participant-level area-under-the-curve values, or give the precise calculation procedure. Those details should not be inferred from the endpoint label alone.

What do the geometric mean and standard deviation indicate?

General: The arithmetic mean describes a center using addition and division. A geometric mean instead summarizes values on a multiplicative scale, often useful when measurements vary by multiplicative rather than additive amounts. A standard deviation describes variability around a central estimate in the units or scale used by the analysis. These are general definitions; the registry record does not explain its transformation or calculation conventions for this endpoint.

The choice of summary can affect interpretation. If values are strongly skewed or vary multiplicatively, a geometric mean may communicate central tendency differently from an arithmetic mean. General: Over-dispersion means that observed variability is greater than a model assumes; ignoring it can make standard errors too small and uncertainty appear narrower than warranted. The record does not report a distributional assessment, a model, or whether over-dispersion was evaluated. It is therefore not possible to say whether those considerations affected an analysis.

How should cohort comparisons be understood?

The design is parallel and non-randomized, with no masking. General: In a parallel design, participants belong to separate groups rather than crossing through each group’s intervention. Random allocation can support causal comparisons by reducing systematic baseline differences, whereas non-randomized group membership can be related to participant characteristics. This study’s groups are explicitly defined by prior vaccine history and timing. Without a reported analysis plan, it is unknown whether any adjustment, matching, or other method was intended to address differences among cohorts.

The record labels the overall study kind as other and says it is not reduced to one comparison. That is consistent with several distinct cohort histories rather than a single randomized contrast. No specific pairwise comparison, reference cohort, or adjusted effect estimate is reported. A descriptive presentation of each cohort, if available, would not by itself establish that vaccine history caused a difference in DNAemia.

What can the planning illustration tell readers?

The registry record describes sample-size assumptions for a planning illustration computed from the observed effect, not from the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is stated as a fraction of the observed effect. Such a calculation is a planning illustration, not observed power and not a substitute for the actual outcome analysis. The record does not report a sample-size justification for the study’s design, and the posted information does not supply an observed effect to interpret alongside the planning assumptions.

General: Power is a design-stage probability tied to an assumed effect, variability, sample size, and statistical procedure. It does not measure whether a completed study has found a true effect, and retrospective calculations based on an observed effect do not establish that the design was adequate. Since the registry record lists no primary-outcome analyses, the planning assumptions cannot be used to infer the result or its precision.

What information is missing for statistical appraisal?

The registry record does not report the statistical model, treatment of repeated measurements, handling of undetectable PCR results, analysis population, missing-data method, covariate adjustment, confidence intervals, or hypothesis tests. It also does not report whether interim analyses were planned or conducted. These details affect how an endpoint estimate and its uncertainty should be interpreted. Without them, a methodological account can describe the intended endpoint and the non-randomized cohort structure, but cannot reconstruct the analysis or evaluate its execution.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, magnitude of VZV DNAemia, and zero analyses. It does not report hypothesis tests, confidence intervals, or a multiplicity strategy. It is therefore not possible to determine whether the study planned multiple statistical comparisons, how any family of tests would have been defined, or whether adjustment for multiple testing was intended.

General: When multiple outcomes, time points, or pairwise comparisons are tested, the chance of obtaining at least one apparently notable result can increase. A prespecified testing hierarchy or multiplicity adjustment can help control that concern. These methods cannot be evaluated in the absence of a reported statistical plan and analyses. The cohort structure includes multiple vaccine histories, but the record does not state which cohort contrasts, if any, were intended as formal tests.

The registry record does not report missing-data methods or an analysis population for the primary endpoint. In particular, it does not say how participants without a complete PCR series, with undetectable readings, or without an endpoint calculation would be handled. The endpoint timeframe refers to measurement until VZV DNA is undetectable, up to Day 7, but this does not by itself define a missing-data rule.

General: Missingness can affect estimates when the availability of measurements is related to participant characteristics or outcomes. A complete-case analysis, an imputation method, or another approach makes assumptions that should be described before results can be judged. The registry record does not identify which, if any, approach was used. Interim analyses and stopping rules are also not reported in the registry record. Accordingly, multiplicity, missingness, analysis-population choices, and interim monitoring cannot be assessed from the posted information.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists serious adverse events in four cohorts. The numbers at risk are 18 in ZVL >5 Years Previously (Cohort 1), 32 in ZVL 6-12 Months Previously (Cohort 3), 35 in No Previous ZVL (Cohort 4), and 20 in SRX >5 Years Previously (Cohort 2). The number with a serious adverse event is 0 in each cohort, and deaths are 0 in each cohort.

For other adverse events, the numbers at risk are the same cohort counts. The record lists 0 affected in each ZVL cohort and 16 affected in No Previous ZVL (Cohort 4); it lists 1 affected in SRX >5 Years Previously (Cohort 2). These are recorded counts, not estimates of relative risk or evidence that an event was caused by the challenge or vaccine history. No serious adverse event terms are listed.

The counts are specific to the categories and cohorts reported. The registry record does not provide event descriptions, severity details for other adverse events, exposure-adjusted rates, or an analysis comparing safety across cohorts. Zero recorded serious adverse events does not establish that no serious events could occur in other circumstances; it describes the entries in this record. Safety counts do not provide the missing primary endpoint results.

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

The registry record supports a limited but clear account of what the study set out to measure: PCR-based VZV DNAemia after an intradermal vOka challenge, summarized as an area under the concentration-time curve. It also documents four cohorts defined by prior shingles-vaccine history, non-randomized allocation, no masking, recorded enrollment of 105, and completed status. The posted record lists one primary outcome measure and zero analyses.

It does not report the primary outcome values, cohort estimates, uncertainty intervals, or statistical tests. Therefore, it cannot show from the posted results whether DNAemia differed among the cohorts, how large any difference was, or how precisely it was estimated. The absence of posted analyses should not be interpreted as evidence of no difference or as evidence of a particular direction of effect.

The endpoint is a surrogate measurement described as a measure of VZV DNAemia over the first 7 days after challenge. It is not a reported count of clinical herpes zoster cases. The registry record does not report an analysis linking DNAemia values to clinical disease or establish that the measured surrogate predicts clinical protection. The study objective in the brief summary concerns learning about protection and immune response, but the available primary-outcome information is confined to the DNAemia measure.

Because participants were not randomly allocated and cohorts differ by prior vaccine and timing, any cohort contrast would also need cautious interpretation. The record does not report covariate adjustment or other methods intended to address baseline differences. The safety entries provide counts within reported categories, but they do not resolve the missing efficacy or surrogate-endpoint analysis. In short, the record documents a biological measurement design and selected safety counts, not an interpretable estimate of persistence of protection or a causal effect of one vaccine history compared with another.

13. Why This Trial Matters Statistically

This study is statistically notable because its central question concerns persistence, while its primary endpoint is a post-challenge biological measurement rather than a reported clinical herpes zoster outcome. The registry describes PCR measurement of VZV DNAemia after an intradermal challenge and summarizes it as an area under the concentration-time curve. That distinction matters: the endpoint quantifies a surrogate signal over time, and the registry record does not report a clinical outcome analysis connecting that signal to protection.

The cohort structure also shapes what comparisons can mean. Participants are grouped by prior ZVL or SRX history and by the time since ZVL for two cohorts. One cohort had no previous ZVL and was to receive the 2 standard doses of RZV before challenge. Since allocation was non-randomized, cohort contrasts are descriptive unless a reported analysis supports stronger interpretation. The record does not report such an analysis.

General: Statistical interpretation depends not only on the question and measurement, but also on the design, analysis population, model, missing-data handling, and uncertainty estimates. A clear endpoint definition is useful, but it does not replace results or methods needed to evaluate precision and bias. Here, the record identifies the measurement and design while listing zero analyses. That makes the boundary between documented study structure and unreported statistical evidence especially important.

The sample-size assumptions are described as a planning illustration based on an observed effect, not as the study’s own design justification. This distinction prevents planning calculations from being mistaken for evidence about whether an effect was observed or whether the completed study could detect it. With no primary analysis reported, neither a planning illustration nor the enrollment figure provides an estimate of the cohort differences.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting the statistical question is that the registry record lists no primary-outcome analyses. It provides no observed VZV DNAemia estimates, uncertainty intervals, or formal comparisons. Consequently, magnitude, direction, and precision of any cohort differences cannot be assessed.

The non-randomized design limits causal interpretation of comparisons across vaccine-history cohorts. The cohorts differ by prior vaccine and, for the ZVL groups, timing of vaccination. The record does not report baseline characteristics or adjusted analyses that would help assess whether other cohort differences could influence DNAemia. Masking is recorded as none, and the record does not describe safeguards against measurement or assessment bias.

The endpoint is a PCR-based surrogate measured after challenge, not a reported clinical herpes zoster endpoint. The registry record does not provide evidence about how the DNAemia measure relates to clinical protection. It also does not give the actual timing and number of PCR measurements, handling of undetectable results, or the precise procedure for calculating the area under the concentration-time curve.

Further limitations are that the analysis population, missing-data approach, statistical model, multiplicity plan, and interim-analysis plans are not reported in the registry record. The sample-size assumptions are described as a planning illustration, not as the trial’s design justification. The adverse-event entries give cohort counts but not event descriptions or comparative analyses. These gaps restrict evaluation of both the endpoint analysis and safety patterns; they do not establish that unreported procedures or results were absent outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Persistence of Protection by Shingrix — NCT04169009.
• Registry record last updated 2024-10-15; status last verified 2024-07.
• Results first posted 2024-10-15.
• 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

NCT04169009 is a completed Phase 4, parallel, non-randomized study sponsored by University of Colorado, Denver. Its recorded enrollment is 105. The study began on 2020-07-28, with primary completion on 2023-03-31. It examines VZV DNAemia after an intradermal vOka challenge among cohorts defined by prior ZVL or SRX history.

The primary outcome is the magnitude of VZV DNAemia, measured by PCR and expressed as an area under the concentration-time curve in DNA copies/ml of blood, until VZV DNA is undetectable, measured up to Day 7. The record lists one outcome measure and zero analyses. It reports no primary-endpoint results or statistical comparisons. Serious adverse events and deaths are recorded as 0 in each cohort; other adverse-event counts vary by cohort as described in the safety information.