Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors (NCT03771157), a na early/phase 1 study. The primary outcome is Number of Participants With Humoral Response to Vaccination 4 Weeks After the Second Vaccine Administration.

2. Clinical Question

The study asks whether patients with Chronic Lymphocytic Leukemia (CLL) or Waldenström Macroglobulinemia (WM) receiving first-line BTK inhibitors can generate a measurable humoral immune response after vaccination with Shingrix. Its primary question concerns antibody response to the varicella virus glycoprotein E subunit, assessed 4 weeks following the second vaccination, at approximately 3 months.

The question is about an immune-response measure in a defined treatment context. It is not a randomized comparison of vaccination strategies, nor does the registry describe a comparison with patients who did not receive the vaccine. The secondary outcome listed concerns cellular response 4 weeks after the second vaccine administration. The registry record does not report the primary response count or the cellular-response result, so the degree of response cannot be assessed from the outcome information listed.

3. Trial Design

The registry describes a completed pilot study, classified as Early Phase 1. It uses a single-group design and has no randomized allocation or masking. The intervention is Shingrix, described as a two-dose vaccination course: the first injection is given on day one, and the second is administered approximately 2 months later. The registry lists 33 participants as enrolled.

The stated objective is to assess the ability of patients with CLL or WM treated with first-line BTK inhibitors to generate an immune response to Shingrix. The primary outcome is a count of participants with a humoral response, assessed 4 weeks after the second administration. A secondary outcome concerns cellular response at the same stated follow-up. The registry also lists four outcome measures, but the detailed outcome results needed to interpret the primary response count are not reported in the registry record.

Without a separate control group, the design can describe responses observed in the enrolled group but cannot establish a randomized contrast against another treatment or against no vaccination. The absence of masking is also part of the registered design. The record lists the study as completed, with a start date of 2019-02-01 and a primary completion date of 2020-09-01. It does not report a protocol rationale for the design, a sample-size justification, or details about how participants were selected beyond the disease and treatment context.

The registry lists University of Rochester as sponsor. It does not report a formal statistical analysis in the analysis entries. Consequently, interpretation should distinguish the study's stated objective and outcome definitions from results or inferential claims that are not reported.

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 Number of Participants With Humoral Response to Vaccination 4 Weeks After the Second Vaccine Administration, measured over 4 weeks following the second vaccination, at approximately 3 months.

The primary endpoint is the number of participants with a humoral response to vaccination, assessed 4 weeks following the second vaccine administration, at approximately 3 months. It uses blood antibody levels to the varicella virus glycoprotein E subunit, referred to in the registry description as anti-gE. The registry defines baseline as the pre-vaccination anti-gE titer in participants who were seropositive and as the lower limit of detection in participants who were seronegative.

This endpoint is used to describe an antibody-based immune response after vaccination in the study population. A participant count is a binary-outcome summary: each participant is classified according to whether the response criterion is met, and the endpoint counts those classified as responders. The registry does not report the response threshold or a rule for classifying a participant as having a response. It also does not report the observed responder count. These omissions prevent readers from determining the response frequency or evaluating how the baseline definition was applied in practice.

The endpoint is a laboratory-based immune measure, not a clinical disease outcome. The registry's primary outcome description does not state that it measures prevention of shingles or another clinical event. Therefore, the endpoint can address the stated immunologic question only to the extent that its response definition and observed result are available. The response result and its uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a participant count, so it is a binary endpoint summarized by the number classified as having a humoral response. A count is not itself a response probability. To interpret a proportion, readers need both the responder count and the relevant denominator, and to evaluate precision they need an uncertainty estimate or data from which one can be calculated. The registry record does not report the primary responder count, its denominator, or a confidence interval.

What does a confidence interval add?

General: A confidence interval expresses uncertainty around an estimate. For a binary response, an interval around the response proportion would show the range of values reasonably compatible with the observed data under the method's assumptions. An interval is especially useful when a study is small, because a point estimate alone can make an uncertain result appear more definite than it is. No such interval for the primary endpoint is reported in the registry record, so its precision cannot be judged.

Why does the outcome definition matter?

The registry identifies anti-gE blood antibody levels as the basis of the humoral-response measure. It defines the baseline differently for people who were seropositive and seronegative before vaccination. That distinction describes how baseline is represented, but it does not give the response threshold or classification rule. A clear threshold is needed to know which measurements count as a response and to reproduce the endpoint classification. That rule is not reported in the registry record. The timing is stated as 4 weeks after the second vaccination, at approximately 3 months, but the record does not describe how results outside that timing window would be handled.

What can the design estimate?

The study is registered as a single-group study, with allocation listed as not applicable and masking listed as none. In general, a single-group study can describe outcomes among participants who received the intervention. It does not create a randomized estimate of the difference between vaccination and a comparator condition. Since there is no separate control group, a response observed after vaccination cannot be interpreted as a controlled treatment effect. The registry does not report an analysis that adjusts for other factors or compares the group with an external reference.

For a binary endpoint, a statistical analysis might report the response count, the denominator, and an interval for the proportion. The registry record does not state that this approach was used and does not provide those primary outcome results. No p-value or formal primary-endpoint analysis is listed. It is therefore not appropriate to infer a test, model, or degree of statistical evidence from the endpoint description alone.

How should planning calculations be read?

General: Sample-size calculations are design tools: they describe how much information a future study might need under specified assumptions. They are not evidence that a study had a particular probability of detecting an effect after it was completed. The registry's planning assumptions describe an illustration using a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation, with the effect to detect expressed as a stated fraction of an observed effect. Those are assumptions for the planning illustration, not a description of the actual single-group allocation. The record does not report the study's own sample-size justification. Any planning figures should therefore be read as illustrations, not as observed power or as proof that the actual study was sized to answer its primary question.

General: A significance level is a threshold used in a specified hypothesis-testing procedure; it does not measure the probability that a result is true. A normal approximation is a computational approach whose suitability depends on the data and analysis. The registry does not report a primary endpoint test or the details needed to judge whether any particular test's assumptions were checked. No inferential conclusion should be attributed to the stated planning assumptions.

There are no analysis entries listed. The registry record does not report the statistical analysis population, treatment of missing antibody measurements, a method for calculating uncertainty, or adjustments for other variables. These missing details leave the planned and performed statistical procedures unclear. They also mean that the posted record cannot be used to reconstruct the primary response analysis from the outcome description alone.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Shingrix Vaccine")
n      <- c(32)
events <- c(24)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Shingrix Vaccine  32  24  75.0  56.6  88.5  57.9  86.7  57.7  86.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary humoral-response outcome and a secondary cellular-response outcome, and it reports four outcome measures overall. It does not report a multiplicity strategy for interpreting more than one outcome. In general, when several outcomes or tests are considered, a multiplicity plan explains how the analysis will address the possibility of chance findings from repeated testing. Without such a plan or the related analysis details, the relationship between the primary and secondary outcomes in any inferential interpretation is unclear. No analyses are listed in the registry record.

The record does not report how missing antibody measurements, missing cellular-response measurements, withdrawals, or unavailable follow-up data were handled. It does not specify whether analyses used all enrolled participants, only participants with available measurements, or another analysis population. The enrollment figure alone does not identify the denominator for the primary endpoint. The safety entries list 32 participants at risk, but the record does not state that this was the primary endpoint population or explain its relation to the enrollment figure.

These omissions affect both the estimated response and how representative it may be of the enrolled group. If endpoint measurements are unavailable, the observed-case count and the full enrolled group may lead to different interpretations; the registry does not say which approach applies. No imputation approach or sensitivity analysis is reported. The absence of these details does not establish that data were missing or that a particular handling method was used. It means only that missing-data procedures and analysis populations are not reported in the registry record.

Accordingly, the endpoint definition and planned follow-up can be described, but the analytic denominator, missing-data handling, and multiplicity implications cannot be evaluated from the record.

12. 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

Serious events with the highest arm-level rate: atrial fibrillation (3.1%).

The registry lists 32 participants at risk for the serious-event summary, with 1 serious adverse event, 0 other adverse events in the listed category, and 0 deaths. Atrial fibrillation appears among the top serious terms at 3.1%. These figures are descriptive entries in the registry record; they do not establish that vaccination caused an event.

The safety denominator is not the same as the listed enrollment figure, and the record does not explain the difference. The denominator for the primary humoral-response endpoint is not reported, so the safety figures should not be used to infer the primary outcome population. The record also does not provide event-level timing, exposure duration, a comparator group, or a causal assessment. Without those details, readers cannot determine the context of the serious event or compare event rates with another group.

General: adverse-event counts describe events recorded under a particular study's monitoring and reporting procedures. A count of zero in a category does not prove that an event is impossible, while a reported event does not by itself establish causation. The safety figures support only a descriptive reading of the registry entries, not a comparative safety conclusion.

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

The study addresses an immunologic question in patients with CLL or WM receiving first-line BTK inhibitors: whether a humoral response to Shingrix can be measured after the two-dose course. The registry gives the outcome's antibody basis and follow-up timing, and it also identifies a cellular-response outcome. However, the primary humoral-response count and the cellular-response result are not reported in the registry record. Without the primary result and its denominator, the posted record cannot establish the observed response level or its precision.

The single-group design is important to what the study can mean. A response measure within the vaccinated group would describe participants in that group, but it would not supply a randomized comparison with a group receiving a different strategy or no vaccine. The design therefore does not estimate a comparative effect. The registry also does not report a formal analysis, an uncertainty interval, or details of missing-data handling that might clarify the strength and robustness of a response estimate.

The safety entries report 1 serious adverse event among 32 at risk, 0 other adverse events in the listed category, 0 deaths, and atrial fibrillation at 3.1% among the top serious terms. These entries should be read as descriptive observations rather than evidence that the vaccine caused or prevented an event. The registry does not present a controlled safety comparison.

The result does not establish a clinical benefit, a clinical risk, or a comparative treatment effect. The primary endpoint is an antibody-response measure, not a clinical disease outcome. The available record supports describing what the investigators set out to assess and the limited safety counts entered; it does not support a conclusion about the magnitude or reliability of the primary immune response. A fuller interpretation would require the response result, its denominator, uncertainty, and analysis details, none of which are reported in the registry record.

14. Why This Trial Matters Statistically

This pilot study is statistically notable for the narrow question it asks and the limits of the design used to answer it. The population is defined by CLL or WM and treatment with first-line BTK inhibitors, while the primary endpoint focuses on an antibody response to a vaccine. Such a question requires a clear laboratory response rule, an outcome denominator, and a description of uncertainty. The registry supplies the antibody target and timing, but the response threshold and observed response count are not reported.

The single-group design is useful for describing outcomes within the enrolled group, but it does not provide a randomized comparator. This distinction helps prevent a descriptive response result, if reported, from being mistaken for a controlled treatment effect. Likewise, safety counts without a control group cannot establish comparative risk or causation. These are design-based limits, not conclusions about whether a response or event occurred.

Statistically, the record also illustrates why an endpoint definition is not equivalent to an endpoint result. A count of participants is interpretable only alongside the number evaluated and the classification rule. Precision requires an uncertainty estimate or enough reported information to derive one. The record lists no analysis entries and gives no primary endpoint estimate, so neither statistical significance nor precision can be evaluated.

The study's pilot and Early Phase 1 classification signal that the record is an early investigation, but no sample-size rationale is reported. Planning assumptions described in the registry are illustrations rather than evidence of observed power or a justification for this study's enrollment. Keeping these distinctions explicit helps readers separate a study's scientific question, its design, its planning assumptions, and its reported evidence.

15. 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 limitations specific to this record constrain interpretation. The primary outcome result is not reported: there is no humoral-response count, denominator, or uncertainty interval. The registry describes anti-gE antibody levels and a baseline convention for seropositive and seronegative participants, but it does not state the criterion used to classify a participant as having a response. As a result, readers cannot reproduce the outcome classification or assess the primary result.

The single-group design has no randomized comparator, and masking is listed as none. It can describe outcomes in the study group but cannot establish a comparative effect. The registry record does not report participant-selection details beyond the disease and treatment context, or explain how the enrollment figure relates to the safety population at risk. It lists 33 enrolled and 32 at risk for the safety summaries, without explaining that difference.

The record does not report how missing outcome measurements were handled, which participants were included in the primary analysis, or whether sensitivity analyses were conducted. It also does not report a statistical analysis plan, formal primary outcome analysis, or multiplicity procedure. These are reporting gaps; they do not show that a particular procedure was or was not used in practice.

The safety results are limited to registry counts and a listed serious-event term. No event-level details, comparator, or causal assessment are reported. Finally, although the registry describes planning assumptions, it does not report a study-specific sample-size justification. These limitations mean that neither the primary response's magnitude and precision nor a comparative interpretation can be established from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Serologic Response to SHINGRIX Vaccine in Patients With CLL and WM Treated With BTK Inhibitors — NCT03771157.
• Registry record last updated 2024-03-15; status last verified 2024-02.
• Results first posted 2024-01-22.
• 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.

19. Record Summary

NCT03771157 is a completed Early Phase 1, single-group pilot study sponsored by University of Rochester. The registry lists 33 enrolled participants with CLL or WM treated with first-line BTK inhibitors. Participants were to receive two Shingrix injections, with the second administered approximately 2 months after the first.

The primary outcome is the number of participants with a humoral response based on anti-gE antibody levels, assessed 4 weeks following the second vaccination, at approximately 3 months. A cellular-response outcome is also listed. The primary response count, its denominator, and statistical analyses are not reported in the registry record.

The safety entries list 32 at risk, 1 serious adverse event, 0 other adverse events in the listed category, and 0 deaths. Atrial fibrillation is listed among the top serious terms at 3.1%. The registry does not report a randomized comparison or a formal analysis.