ZOSTAVAX in Persons Imminently Receiving Chemotherapy for Solid Organ Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ZOSTAVAX in Persons Imminently Receiving Chemotherapy for Solid Organ Tumors (NCT02444936), a randomized phase 4 study. The primary outcome is Measuring the Efficacy of ZOSTAVAX in Chemotherapy Patients (Changes in ZOSTAVAX-specific IFN-gamma Spot Forming Units Will be Measured by ELISPOT).

2. Clinical Question

This is a question about an immune assay outcome, rather than a direct comparison of shingles cases. The registry description does not report a clinical shingles endpoint or results for one. Although the study was randomized, the posted primary outcome cannot establish whether the groups differed in the planned immune measure because that measure was not obtained.

3. Trial Design

The registry describes a randomized, single-masked, parallel-group Phase 4 pilot study. Participants were assigned to ZOSTAVAX or a control arm, with no drug given to the control group. The enrollment recorded was 22. Randomization is intended to allocate participants to groups by chance; masking is intended to limit the influence of knowledge of assignment. The registry record does not report who was masked or how allocation was generated or concealed.

The primary outcome was a count of participants, with a planned timeframe of 3 years. Its description specifies an assay of changes in ZOSTAVAX-specific IFN-gamma spot forming units measured by ELISPOT. The study was intended to evaluate vaccination before chemotherapy or surgery followed by chemotherapy among people with solid organ tumors. The registry does not report further details about the timing or number of assay measurements.

The status is terminated. The registry states that recruitment was too low and that no samples underwent the ELISPOT analysis. The posted primary outcome has no analyzable participants in either arm, and no two-arm binary comparison is estimable from those outcome data. Thus, the randomized design describes the intended comparison, but the planned primary assessment did not produce an observed outcome comparison.

The registry record does not report the planned sample-size justification, a detailed statistical analysis plan, the randomization procedure, or the masking procedure. It also does not report interim analyses. The information available therefore supports describing the assigned groups and intended endpoint, but not reconstructing unreported design or analysis decisions.

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

Analysis population for the primary outcome, as defined in the registry: The recruitment was too low and we terminated the study. No samples underwent the ELISPOT analysis.

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 Measuring the Efficacy of ZOSTAVAX in Chemotherapy Patients (Changes in ZOSTAVAX-specific IFN-gamma Spot Forming Units Will be Measured by ELISPOT), measured over 3 years.

The primary endpoint was intended to assess cellular immunologic response to ZOSTAVAX. It focused on changes in vaccine-specific IFN-gamma spot forming units, measured by ELISPOT, and was recorded as a count of participants. The registry gives a timeframe of 3 years. It does not specify the exact definition of a response, the threshold for classifying a participant, or how changes in assay values would be summarized for a comparison.

In general, an immune assay can provide a measurable laboratory indicator of cellular immune activity. ELISPOT counts spots associated with cells producing a specified signal; a change in the vaccine-specific signal can therefore be used as an immunologic outcome. Such an endpoint is not itself a measure of whether participants developed shingles. The registry record does not report a primary clinical shingles outcome.

For this trial, the planned assay result is unavailable: the registry says no samples underwent ELISPOT analysis because recruitment was too low. The posted arm results therefore cannot be interpreted as observed immune responses. The zeros recorded for the primary outcome do not show that participants had no immune response; they reflect the lack of analyzed participants for that outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to groups by chance. When implemented as intended, it can reduce systematic differences between groups at baseline and support a causal interpretation of a comparison. It does not guarantee that groups will be identical, especially in a small study. Nor can randomization compensate for an outcome that was never measured. Here, the registry describes randomized allocation to ZOSTAVAX or control, but no primary ELISPOT comparison is available.

What would an endpoint comparison estimate?

In general, a treatment-effect estimate describes the contrast between outcomes in the assigned groups. For a binary endpoint, an analysis might compare the probability or count of participants meeting a defined outcome. Such an estimate depends on a clear outcome definition and observed data in each group. The record identifies the primary outcome as a count of participants, but no participants underwent the ELISPOT analysis. As a result, an effect estimate for this endpoint cannot be obtained from the posted data.

Why are uncertainty intervals important?

In general, a confidence interval gives a range of values compatible with the observed data under the method's assumptions. It conveys precision as well as the direction and size of an estimate. A narrow interval indicates greater precision than a wide interval, while an interval spanning values on both sides of a null contrast can reflect substantial uncertainty. No confidence interval for the primary outcome is reported because no assay outcome was available for analysis. This is different from an interval that is wide but still based on observed data.

Why does the binary comparison matter?

The posted analysis identifies the two-arm binary comparison as not estimable because values are missing or not estimable. In general, estimation of a binary contrast requires outcome information from the groups and a defined event. Without those data, the comparison cannot yield a meaningful effect estimate or its uncertainty. Substituting zeros for unavailable observations would incorrectly treat missing measurement as a measured absence of response. The registry's note that no ELISPOT samples were analyzed is the key context for interpreting the primary outcome values.

How should the planning assumptions be read?

In general, a sample-size calculation depends on a target effect, a significance level, allocation, and assumptions about the statistical distribution. The planning illustration described for these results uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not a report of the study's original sample-size justification. The registry record does not report that original justification.

A planning calculation based on an observed effect is only informative when the observed effect can be estimated. Here, the primary assay was not performed, and the two-arm comparison is not estimable. Thus, no planning count based on an observed primary effect can be interpreted as a target derived from this trial's outcome data. Any sample-size illustration is a planning exercise, not observed power, and it cannot supply evidence missing from the trial.

What does a zero count mean in this setting?

In general, an observed zero event count can be a valid result if participants were assessed and no events occurred. A zero attached to an outcome that was never measured has a different meaning: it cannot be treated as evidence that the underlying event or response was absent. The registry's primary outcome values are accompanied by the explicit statement that no samples underwent ELISPOT analysis. The absence of assay data, rather than a measured lack of immune response, determines the interpretation.

More generally, sparse data can make estimates unstable and uncertainty wide. Over-dispersion is a situation in which observed variability exceeds what a statistical model assumes; accounting for it can matter when analyzing variable count outcomes. These are general considerations, not methods reported for this trial. The registry record does not report an analysis model for ELISPOT results, a dispersion estimate, an interim analysis, or a detailed statistical plan. Given the lack of analyzed samples, there is no basis to infer which model would have been used or what its result would have been.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 2 outcome measures, but no secondary outcome is posted. It reports 0 analyses and 0 secondary outcomes posted. These details limit the available results, but they do not establish how many endpoints were originally planned or whether any multiplicity procedure was specified. A multiplicity adjustment or strategy is not reported in the registry record.

In general, multiplicity arises when several outcomes or comparisons are tested: repeated testing can increase the chance of at least one apparently significant result. A prespecified hierarchy or adjustment can address this issue, but neither should be assumed without documentation. The registry record does not report such a plan, so it is not possible to assess whether multiplicity was addressed.

Missing outcome data are central to interpretation. The registry states that recruitment was too low, the study was terminated, and no samples underwent ELISPOT analysis. It does not report an analysis population, an intention-to-treat analysis, imputation, or other missing-data method. Those details are not reported in the registry record. Because there are no analyzed primary assay results, the posted data cannot support an analysis of how missingness might have affected an estimated immunologic effect.

In general, missingness can limit both validity and precision, particularly if the probability of having an observed outcome is related to participant characteristics or outcomes. The registry record does not provide enough information to characterize such relationships. It also does not give a complete participant disposition account. No assumptions about the reasons for missing assay results or the likely direction of any resulting bias can therefore be justified.

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 registry records serious adverse events for 0 of 10 participants at risk in the ZOSTAVAX group and 0 of 12 participants at risk in the control group. It reports other adverse events for 2 of 10 at risk in the ZOSTAVAX group and 0 of 12 at risk in the control group. Deaths are recorded for 2 participants in the ZOSTAVAX group and 4 in the control group.

These are counts as posted, not estimates of comparative risk. In general, adverse-event counts describe reported events within the registry's reporting framework; interpretation depends on definitions, observation periods, completeness, and attribution. The record does not provide the timing or causes of the deaths, or whether any event was considered related to the intervention. The serious adverse event terms are not listed.

The counts should not be used to infer that treatment caused or prevented an event. In particular, the absence of recorded serious adverse events does not establish absence of risk. The registry does not report enough information about follow-up or event ascertainment to make broader safety conclusions. These data are separate from the unmeasured primary ELISPOT endpoint.

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

The trial record documents an attempt to compare ZOSTAVAX with a no-drug control among people imminently receiving chemotherapy for solid organ tumors. Its primary question concerned changes in vaccine-specific IFN-gamma spot forming units measured by ELISPOT. The study ended after recruitment was too low, and no samples underwent the planned assay.

What the result means is limited: the posted record does not contain an observed primary immunologic comparison. It cannot show the size or direction of a difference between the assigned groups, and it cannot provide precision for such a difference. The zeros in the primary outcome entries are not evidence of zero immune response, because the registry explicitly reports that no samples were analyzed.

What the result does not mean is that the groups had the same response, that ZOSTAVAX had no immunologic effect, or that an effect was established. All of those interpretations would require observed endpoint data and a valid analysis. A nonsignificant result is also not the right description: no test result for the primary endpoint is reported. The comparison is unavailable, rather than an observed comparison that failed to meet a statistical threshold.

The safety counts are descriptive registry entries and do not answer the primary immunologic question. The record lists serious adverse events, other adverse events, and deaths by group, but lacks timing and cause information for deaths and does not state event relationships to treatment. They cannot support a treatment-effect conclusion on their own.

More broadly, a randomized design can support a comparative estimate only when outcomes are observed and analyzed. This record documents the intended design and the reason the primary assessment was not completed; it does not provide evidence sufficient to settle the immunologic question. Further conclusions about efficacy, safety, or applicability are not supported by the posted results.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a planned randomized comparison and an estimable result. Random assignment can be valuable for balancing groups, but it cannot create endpoint measurements. Because no samples underwent ELISPOT analysis, the central immunologic comparison is unavailable even though the study had randomized arms.

The distinction between zero observations and a measured zero is especially important. In a complete assessment, an observed zero could describe a group in which no participants met a defined outcome. Here, the registry says the assay was not performed. Treating the reported zeros as measured outcomes would change the meaning of the record and could lead to an invalid comparison.

The study also shows why sample-size planning and observed evidence must be kept separate. Planning illustrations rely on assumptions and a target effect; they do not show what a trial found. A planning calculation based on an observed effect is not informative when the primary effect itself is unavailable. It is not a substitute for an outcome analysis, and it is not observed power.

Finally, the termination reason matters to interpretation. The registry attributes termination to low recruitment, which prevented the planned assay assessment. The record provides no original sample-size justification or detailed analysis plan, so the statistical consequences of the intended design cannot be reconstructed in full. Transparent reporting of non-completion helps readers distinguish an inconclusive study from a completed comparison that found little or no difference.

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 trial-specific limitation is that recruitment was too low and the study was terminated before any samples underwent the planned ELISPOT analysis. As a result, the primary immunologic endpoint has no observed participant-level results or comparative estimate. The enrollment recorded in the registry does not change this: the record reports no participants analyzed for the primary assay.

The registry does not explain the disposition of participants after enrollment, so it is not possible to determine from this record why each participant did or did not contribute an outcome. The exact response definition, assay schedule, and handling of assay results are not reported. The masking details, allocation procedure, and analysis population are also not reported in the registry record.

The record does not provide the original sample-size justification, a detailed statistical plan, or interim-analysis information. It lists 2 outcome measures but no secondary outcome is posted, and no analyses are reported. These omissions prevent a fuller evaluation of the intended multiplicity strategy and analysis decisions. No assumptions about unreported design choices can fill those gaps.

Safety information is also limited: the registry gives event and death counts but does not report death causes, timing, or relationships to treatment. The adverse-event counts therefore have limited interpretability beyond the entries recorded by arm. Overall, the registry documents the intended design and the failure to obtain the primary assay, but not enough detail to assess all aspects of trial conduct or participant follow-up.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ZOSTAVAX in Persons Imminently Receiving Chemotherapy for Solid Organ Tumors — NCT02444936.
• Registry record last updated 2026-09-23; status last verified 2026-09.
• Results first posted 2018-04-06.
• 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

NCT02444936 is a Phase 4 randomized, single-masked, parallel pilot study of ZOSTAVAX versus a no-drug control in people with solid organ tumors imminently receiving chemotherapy. The registry records enrollment of 22 and a terminated status. The primary outcome was a count of participants assessed for changes in ZOSTAVAX-specific IFN-gamma spot forming units by ELISPOT, with a 3-year timeframe.

The registry states that recruitment was too low and no samples underwent ELISPOT analysis. Thus, no primary immunologic comparison is available. Safety entries include serious adverse events, other adverse events, and deaths by arm, but the registry does not report causes or timing of deaths. It lists 0 analyses and no secondary outcomes posted. The original sample-size justification, detailed statistical plan, and analysis population are not reported in the registry record.