Gardasil Vaccination in Post Stem Cell Transplant Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gardasil Vaccination in Post Stem Cell Transplant Patients (NCT01092195), a non-randomized phase 1 study. The primary outcome is Percentage of Subjects Who Developed Antibody Response to the Vaccine..

2. Clinical Question

The study asks whether an antibody response is observed after vaccination across these different clinical groups. It also assesses safety, but the registry record does not report a numerical primary antibody-response result. The endpoint description identifies the response being assessed; it does not establish the magnitude of the response in any cohort.

3. Trial Design

This is a Phase I, parallel, non-randomized, unmasked study of Gardasil vaccination after stem cell transplantation. The registry lists an enrollment of 64 and describes three cohorts: female transplant recipients with chronic GVHD requiring systemic immunosuppression, female transplant recipients on no systemic immunosuppression, and healthy female volunteers. Each cohort is described as receiving the vaccine regimen.

Vaccination was described as three separate 0.5ml intramuscular injections at 0, 2, and 6 months. The primary antibody-response assessment has a 12-month timeframe. The registry describes the study's objective as assessing safety and immune response among female transplant recipients who are either off or on stable doses of immunosuppression, with healthy volunteers also eligible.

Because allocation was non-randomized, the cohort membership was not assigned by random allocation. The groups also differ in clinical status: one consists of transplant recipients requiring systemic immunosuppression for chronic GVHD, another of transplant recipients on no systemic immunosuppression, and the third of healthy volunteers. Their outcome patterns therefore cannot be read as a like-for-like comparison of randomized groups. Differences, if reported, could reflect group characteristics as well as any differences associated with the clinical setting.

The study is marked completed. Its listed start date is 2010-06-02, and its primary completion date is 2016-07-19. The sponsor is the National Heart, Lung, and Blood Institute (NHLBI). The registry record does not report a sample-size justification or further details of how recruitment or cohort assignment was conducted.

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 Percentage of Subjects Who Developed Antibody Response to the Vaccine., measured over 12 months.

The primary endpoint is the percentage of subjects who developed an antibody response to the quadrivalent HPV vaccine by 12 months. The registry describes the targeted responses as anti-HPV-6/11/16/18-specific antibodies, measured in serum using L1 Virus Like Particle ELISA. The outcome is listed as a count of participants, even though its title refers to a percentage; a percentage requires both the number meeting the response definition and the relevant denominator.

Antibody response is an immunogenicity measure: it records whether a measurable immune response was observed after vaccination. It is used to characterize the immune response rather than to directly measure prevention of infection, genital warts, precancer, or cancer. The registry record does not give the response threshold or other details defining when an individual participant counted as having developed an antibody response.

The primary endpoint description identifies the measurement and timeframe, but the numerical outcome itself is not reported in the registry record. No cohort-specific response counts, percentages, or uncertainty estimates are listed. Consequently, the endpoint can be explained, but the observed antibody-response frequency and the precision of any estimate cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies one primary outcome measure and lists no analyses. It describes a binary participant outcome: whether a subject developed an antibody response to the quadrivalent HPV vaccine by 12 months. A binary outcome has two states for each participant under the specified response definition: response or no response. The registry describes the outcome as a count of participants, while the endpoint title frames it as a percentage. To interpret a percentage, readers need both the count of participants meeting the response definition and the denominator included in that analysis.

What does a response proportion represent?

General statistical context: a response proportion describes the share of an analyzed group classified as having the outcome. It is a descriptive summary of the observed participants, not automatically an estimate that applies to every person in a broader population. Its meaning depends on the response definition, the participants included in the denominator, and how missing or unevaluable measurements are handled. The registry record does not report the response threshold, cohort-specific response counts, analysis denominators, or the handling of missing antibody measurements.

Why do uncertainty intervals matter?

General statistical context: an uncertainty interval conveys how much imprecision remains around an estimate. A wider interval signals that the data are compatible with a broader range of underlying response frequencies; a narrower interval signals greater precision under the chosen method and assumptions. An interval does not remove design limitations, such as non-randomized group membership, and it is not a statement that a particular value is guaranteed. The registry record does not report an interval or another uncertainty measure for the primary endpoint.

How should the cohorts be compared?

The study uses non-randomized, parallel cohorts, with no masking. The cohorts are transplant recipients on systemic immunosuppression, transplant recipients on no systemic immunosuppression, and healthy volunteers. These groups differ by clinical status and are not randomized comparison arms. General statistical context: random allocation can help balance known and unknown participant characteristics across groups, on average. Without random allocation, group differences can arise from characteristics associated with cohort membership, as well as from any differences in the outcome. A crude comparison would therefore be descriptive and would not, by itself, establish a causal effect of immunosuppression status or vaccination.

The registry record does not report a statistical model, covariate adjustment, confidence intervals, hypothesis tests, or a prespecified comparative analysis. It also does not report an analysis population, such as whether the primary endpoint was assessed among all enrolled participants or only those with a measured antibody result. Without such details, the analysis approach and the treatment of participants without an evaluable measurement are not reported in the registry record.

What does the planning description mean?

The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. This is a planning framework, not an observed trial outcome. The description further distinguishes participant counts per arm for non-time-to-event outcomes from total event counts for time-to-event outcomes. No numerical sample-size illustration is reported in the registry record details, and the record does not state that this planning approach was the trial's own design justification. It should not be treated as observed power or as evidence about the primary endpoint.

General statistical context: a planning calculation describes the sample size associated with chosen assumptions about the effect and statistical procedure. It does not demonstrate that a study had a particular probability of finding a result after the data have been observed. Sample-size illustrations are conditional on their assumptions, and they cannot replace a report of the observed outcome and its uncertainty. The registry record does not report the protocol's sample-size justification, so the rationale for the enrollment target is not reported in the registry record.

What can be learned from the posted analysis information?

The registry lists no analyses. This does not supply a test statistic, an adjusted result, a subgroup analysis, or an inferential comparison. Nor does it clarify whether analyses were conducted but not entered into the registry record. The primary endpoint description and safety counts remain useful for identifying what was intended to be measured and what adverse-event counts were posted, but they do not provide a complete statistical results report.

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("Transplant With Immunosuppression", "Transplant With no Immunosuppression", "Healthy Volunteer")
n      <- c(23, 21, 20)
events <- c(18, 20, 20)
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  Transplant With Immunosuppression  23  18  78.3  56.3  92.5  58.1  90.3  57.8  90.2
ARM  Transplant With no Immunosuppression  21  20  95.2  76.2  99.9  77.3  99.2  77.2  98.9
ARM  Healthy Volunteer  20  20  100.0  83.2  100.0  83.9  100.0  83.9  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, but it does not report a multiplicity strategy. It does not describe a hierarchy among outcomes, adjustment for multiple comparisons, or whether multiple antibody types or cohort comparisons were tested separately. The endpoint names responses to HPV types 6, 11, 16, and 18, but the record does not say whether the primary outcome required response to each type, how a combined response was defined, or how any separate tests were handled.

Missing-data methods are not reported in the registry record. The record does not state how participants without a serum measurement at 12 months were handled, whether a measurement could be classified as unevaluable, or how missing outcome information affected denominators. It also does not identify an imputation method or a sensitivity analysis for missing measurements.

The analysis populations are not reported in the registry record. There is no description of whether the primary analysis included all enrolled participants, only vaccinated participants, or only participants with evaluable antibody measurements. Although the registry lists enrollment of 64 and provides cohort-specific safety counts, those details do not define the primary endpoint analysis population.

The registry lists no analyses and does not report interim analyses, a prespecified statistical analysis plan, or a rationale for the planned sample size. These omissions limit assessment of how outcomes were selected and analyzed, but they do not establish that a particular method was or was not used outside the registry 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 non-serious adverse event terms

The registry reports serious adverse-event figures separately for three groups. For transplant recipients with immunosuppression, 0 serious adverse events are listed among 23 at risk. For transplant recipients with no immunosuppression, 0 are listed among 21 at risk. For healthy volunteers, 0 are listed among 20 at risk. Deaths are listed as 0 in each group. The registry also lists other adverse events affecting 23 of 23 participants with immunosuppression, 18 of 21 without immunosuppression, and 20 of 20 healthy volunteers.

These counts should be read as descriptive registry entries, not as a randomized safety comparison. The cohorts differ clinically and were not randomly allocated. The record does not report the event definitions, severity breakdown for other adverse events, observation periods, or whether adverse events were judged related to vaccination. It lists no serious adverse-event terms.

Zero recorded serious events does not demonstrate that serious events cannot occur or establish the absence of risk. It means that none are listed for the stated at-risk groups in this record. The registry does not provide additional detail on ascertainment or follow-up that would support a broader safety conclusion.

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

The record establishes that a Phase I study was conducted to assess safety and antibody response after Gardasil vaccination in female transplant recipients and healthy female volunteers. It specifies a 12-month antibody-response endpoint and the serum assay used. It also records cohort-specific adverse-event counts and deaths. These details describe the study question, measurement, and some posted safety results.

The record does not report the primary antibody-response count, percentage, or uncertainty estimate. It therefore cannot answer from the posted results how many participants developed the specified response or how the response frequency differed among cohorts. The result also cannot establish the precision of any cohort estimate. Enrollment alone cannot fill this gap, because the number enrolled is not necessarily the number with an evaluable endpoint measurement.

The non-randomized design also limits what any between-cohort difference could mean. The groups have different clinical characteristics, including immunosuppression status and whether participants are transplant recipients or healthy volunteers. Such comparisons would not isolate the effect of immunosuppression, and they would not establish a causal effect of vaccination. The registry record does not report an adjusted analysis that would clarify whether differences in participant characteristics were considered.

The serious adverse-event entries show zero events listed in the three cohorts, and the registry lists zero deaths in each. These counts are reassuring as descriptions of the posted record, but they do not prove that serious adverse events are impossible or that the vaccine is risk-free. The broader safety interpretation is limited by the absence of further event definitions and follow-up information.

In short, the registry record describes a completed study and its intended immunogenicity outcome, but the central antibody-response result is not reported in the registry record. Conclusions about the observed immune response, its precision, and comparative effects cannot be drawn from the endpoint description alone.

14. Why This Trial Matters Statistically

This trial raises a statistical question that is especially relevant to studies involving clinically distinct groups: how to interpret outcomes when participants are not randomly allocated. Here, the cohorts include transplant recipients on systemic immunosuppression, transplant recipients on no systemic immunosuppression, and healthy volunteers. Those groups provide different clinical contexts, but they are not exchangeable by design. Statistical comparisons must therefore distinguish description from causal inference.

The endpoint also illustrates why an outcome definition and an outcome result are not the same thing. The registry names a 12-month antibody-response measure and identifies the serum assay, but it does not report participant response counts or percentages. Without the result and its denominator, the intended measurement cannot be translated into an estimate of response frequency or its precision.

For immunogenicity studies, a binary response summary can be easy to communicate, but its interpretation depends on the criteria used to classify a response, the analyzed population, and the handling of missing measurements. Those details are not reported in the registry record. Their absence makes it difficult to judge how directly a reported result, if available elsewhere, would represent all enrolled participants.

The study also demonstrates the importance of separating safety counts from conclusions about safety. Zero serious adverse events are recorded in each cohort, but descriptive counts do not show that risk is absent. Context about definitions, follow-up, and ascertainment is needed to assess what a zero count can support.

Finally, the posted record distinguishes a planning illustration from the trial's own design justification. Planning calculations depend on assumptions, while observed evidence requires reported outcome estimates and uncertainty. Keeping those concepts separate prevents a planned sample-size scenario from being mistaken for evidence about the study's actual antibody response.

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.

The most direct limitation for interpretation is that the primary antibody-response result is not reported in the registry record. Although the endpoint and its 12-month timeframe are described, there are no cohort-specific response counts, percentages, denominators, or uncertainty estimates. The study's central immunogenicity question therefore cannot be answered from the posted results.

The response definition is also incomplete in the registry description. It identifies anti-HPV-6/11/16/18-specific antibodies and an L1 Virus Like Particle ELISA assay, but does not report the threshold for classifying a participant as having developed an antibody response. It is not reported whether the endpoint required responses to all listed types or used another combined definition.

Interpretation of cohort comparisons is limited by the non-randomized design and the clinical differences among groups. The transplant cohorts differ by immunosuppression status, and the healthy volunteers are a separate population. The registry record does not report adjustment for participant characteristics or a comparative statistical analysis.

Further limitations include the absence of reported missing-data methods, analysis populations, and details of endpoint denominators. The registry does not report a sample-size justification, interim analyses, or a statistical analysis plan. Safety entries lack further information about event definitions, relatedness, and observation periods. These details are not reported in the registry record, so their handling cannot be evaluated from the posted information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gardasil Vaccination in Post Stem Cell Transplant Patients — NCT01092195.
• Registry record last updated 2019-08-06; status last verified 2018-07.
• Results first posted 2019-07-01.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01092195 is a completed Phase I, parallel, non-randomized, unmasked study of Gardasil vaccination after stem cell transplantation. The registry lists enrollment of 64 and three cohorts: transplant recipients with systemic immunosuppression, transplant recipients without systemic immunosuppression, and healthy female volunteers. The described regimen consists of three 0.5ml intramuscular injections at 0, 2, and 6 months.

The primary outcome is antibody response to HPV types 6, 11, 16, and 18 at 12 months, measured in serum by L1 Virus Like Particle ELISA. The numerical primary outcome is not reported in the registry record. Serious adverse events and deaths are listed as 0 in each cohort; other adverse-event counts are also recorded. The registry lists no analyses, and does not report the statistical analysis plan, missing-data methods, or analysis populations.