Study of Safety, Tolerability and Immunogenicity of Gardasil®9 in Immunocompromised Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Safety, Tolerability and Immunogenicity of Gardasil®9 in Immunocompromised Patients (NCT03525210), a non-randomized phase 3 study. The primary outcome is Seroconversion Following 3 Doses of 9-valent HPV Vaccines.

2. Clinical Question

The clinical context stated in the registry is that patients with immunodeficiencies are at increased risk of persistent HPV infection and HPV-related disease. The study was designed to assess antibody responses and safety in two patient groups, not to compare vaccination with no vaccination or another vaccine. The registry record does not report the observed seroconversion percentages, their confidence intervals, or the analysis results for the primary endpoint. It therefore does not establish the size or precision of the antibody response in either group.

3. Trial Design

This was a Phase III, open-label study with non-randomized allocation and a parallel-group model. The registry lists HIV patients and SOT patients as the two groups; all participants in both groups received the study vaccine. With no randomized control group, the study is not a controlled comparison of vaccine versus no vaccine, or of the vaccine versus another intervention.

The registry reports enrollment of 271 participants and a completed status. The study began on 2018-04-04, and primary completion was listed as 2019-09-01. These are registry-level design and status details; they do not show how many participants contributed data to each endpoint or analysis population. Group-specific enrollment and endpoint denominators are not reported in the registry record.

The intervention was a nine-valent HPV vaccine, with three doses scheduled at 0, 2 and 6 months. The primary endpoint concerned neutralizing antibodies against HPV genotypes 6/11/16/18/31/33/45/52/58, assessed one month after the final dose. Its timeframe is listed as 7 months for each subject. A secondary outcome concerned adverse reactions following vaccination.

The registry describes the study as open-label, so masking was absent. The method used to form or recruit the two patient groups, details of any protocol amendments, and a fuller account of the study procedures are not reported in the registry record. Nor is a statistical analysis plan described. The design supports descriptive reporting of antibody responses and safety outcomes in the enrolled groups; it does not support treating differences between the groups as randomized treatment effects.

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: were seronegative to the appropriate HPV type at Day 1, had serology results based on acceptable day ranges and had no protocol deviations that could interfere with the subject's vaccine as judged by the principal investigator.

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 Seroconversion Following 3 Doses of 9-valent HPV Vaccines, measured over 7 months (for each subject).

The primary endpoint is the percentage of participants who seroconverted to neutralizing antibodies against each of the nine HPV vaccine genotypes after receiving three doses. Seroconversion was assessed one month after the last dose. The endpoint’s stated population is restricted to participants seronegative at baseline for the HPV type being assessed, with serology collected within acceptable day ranges and no protocol deviation judged to interfere with vaccination.

Seroconversion is an immunogenicity measure: it records whether an antibody response meeting the study’s seroconversion definition was observed. It is not itself a measure of HPV infection, HPV-related disease, or protection from a clinical outcome. The registry record does not define the threshold used to classify seroconversion, so that operational detail is not reported in the registry record.

Reporting the percentage gives a direct description of the proportion meeting the endpoint in the assessed population. The 95% confidence interval is intended to convey uncertainty around that estimate. In general, confidence intervals help readers judge how precisely an effect or proportion has been estimated; they do not remove limitations arising from who was included or how the study was designed.

The endpoint description names the genotypes separately, but the registry record does not report the observed seroconversion percentages or confidence intervals. It also does not give genotype-specific denominators. The endpoint’s measure and timing are therefore clear, while its numerical results and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either meets the seroconversion definition for the HPV type being assessed or does not. A percentage summarizes the number meeting that definition relative to the eligible participants assessed. General statistical interpretation: the estimate is most informative when its denominator and the rules for inclusion are clear, because both affect what population the percentage describes.

The registry specifies a 95% confidence interval for the primary endpoint. General statistical interpretation: a confidence interval expresses the uncertainty associated with an estimated proportion under the statistical method used. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The interval does not show the range of individual participants’ antibody responses, and it does not address systematic biases from selection, missing measurements, or study design. The registry record does not name the interval method or provide the endpoint estimates and intervals.

The endpoint is assessed separately for nine HPV genotypes. A participant may be eligible for one genotype-specific assessment but not another, because the primary population requires seronegativity at baseline for the relevant type. General statistical interpretation: separate outcomes can have distinct denominators and estimates. Readers need genotype-specific results and analysis populations to understand how much information supports each estimate. Those details are not reported in the registry record.

There are two patient groups, but the study is non-randomized and both groups receive the same intervention. General statistical interpretation: randomization helps balance measured and unmeasured baseline characteristics, on average, between assigned groups. Without randomization and without a control group, contrasts between the HIV and SOT groups are descriptive rather than a clean estimate of a treatment effect. Differences in outcome may reflect group composition or other factors in addition to any response associated with vaccination. The registry record does not describe an adjusted comparison or a model for between-group differences.

The posted sample-size illustrations are based on the observed effect and assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider an effect defined as a stated fraction of the observed effect. General statistical interpretation: changing the target effect changes the planning question; planning for a smaller effect generally requires more information than planning for a larger one. These calculations are illustrations, not the trial’s own sample-size justification, and they should not be called observed power. The registry record does not report the protocol’s sample-size rationale. Because the primary result is not reported in the registry record, the illustrations cannot be used to recover it.

The registry lists adverse outcomes as counts of affected participants among those at risk in each group. General statistical interpretation: a count gives the number of participants with at least one event as defined for that outcome, while a participant-level count does not convey the number, duration, severity, or timing of all events unless those details are separately reported. The registry record does not explain the event-counting rules or provide a full account of event-level data.

General statistical interpretation: over-dispersion matters when observed variability exceeds what a statistical model assumes. It can make standard errors too small if a model fails to allow for extra variability, leading to confidence intervals that are too narrow. The registry record does not report a model for the binary endpoint or a concern about over-dispersion, so no claim can be made about whether this issue arose in the trial’s analysis.

More broadly, an analysis plan would ordinarily specify outcome definitions, analysis populations, handling of missing observations, and any adjustment for multiple outcomes. These details are not reported in the registry record. The results fields therefore do not allow verification of the statistical methods used for the primary endpoint or whether reported analyses followed a prespecified plan.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint concerns seroconversion against nine HPV genotypes, and the registry also lists an adverse-reaction outcome. Multiple endpoints create a multiplicity question: when several statistical tests or estimates are considered together, the chance of at least one apparently notable result can increase. General statistical interpretation: a prespecified strategy may address this issue, for example by defining a hierarchy or adjustment. The registry record does not report a multiplicity strategy or state whether formal testing across genotypes was planned.

The record identifies the primary endpoint and its 95% confidence interval, but does not provide the numerical results, genotype-specific denominators, or a statistical analysis plan. It lists two outcome measures overall, including the adverse-reaction outcome. Whether additional outcomes or analyses were conducted is not reported in the registry record; no analyses are listed there.

The primary endpoint population requires baseline seronegativity for the relevant HPV type, acceptable serology timing, and no protocol deviation judged to interfere with vaccination. The number excluded or included under each criterion, and the reasons for missing endpoint data, are not reported in the registry record. The record also does not explain how missing serology or participants who did not complete the vaccine schedule were handled.

These omissions limit assessment of how representative the analyzed participants were of everyone enrolled and whether missing observations could have influenced the estimates. They also prevent checking whether the analysis population matched the endpoint definition for each genotype. The registry record does not report an intention-to-treat analysis population, a per-protocol analysis population, or sensitivity analyses for missing data.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory infections (5.9%), gastro-intestinal infections (4.1%), respiratory pathology (2.9%), urogenital infection (1.8%), dysregulation glycemia (1.8%).

The registry reports serious adverse events separately for HIV patients and SOT patients. In the HIV group, 3 of 99 participants at risk were affected; in the SOT group, 28 of 170 were affected. It reports other adverse events for 80 of 99 participants at risk in the HIV group and 127 of 170 in the SOT group. No deaths are reported in either group.

These are counts of participants, not a complete description of every event or its timing, duration, or outcome. The registry also lists serious-event terms with percentages: respiratory infections, 5.9%; gastro-intestinal infections, 4.1%; respiratory pathology, 2.9%; urogenital infection, 1.8%; dysregulation glycemia, 1.8%; and Abbdominal pain, 1.2%. The record does not report the denominators or other detail needed to interpret these term-specific percentages fully.

Both groups received the vaccine and there was no randomized control group. These safety figures are descriptive and do not establish that the vaccine caused an event or that an event was unrelated to vaccination. The registry record does not provide a comparative safety analysis or further detail about event definitions, seriousness criteria, or attribution.

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

The study addresses antibody responses and safety after three doses of a nine-valent HPV vaccine in HIV patients and SOT patients. Its primary endpoint is defined as seroconversion to neutralizing antibodies against the vaccine genotypes among participants who were seronegative for the relevant type at baseline and met the stated assessment criteria. That definition identifies an immunogenicity outcome, not a clinical disease outcome.

The registry record does not report the primary seroconversion percentages or their confidence intervals. It therefore does not establish the observed antibody response, the precision of that response, or whether estimates differed across genotypes or patient groups. The study’s completed status and enrollment of 271 do not substitute for those results.

The safety record includes serious and other adverse-event counts, along with selected serious-event terms and no reported deaths. These data describe events in the two vaccinated groups, but without a control group they cannot determine how many events were caused by vaccination. The record also does not provide the detail needed to interpret every listed event or its course.

The design does not establish a causal comparison between HIV patients and SOT patients, because group assignment was non-randomized and the groups may differ in ways not described in the registry. It also does not compare vaccination with no vaccination or another intervention. General statistical interpretation: an antibody response is a biological measure, and by itself it does not establish the effect of an intervention on infection or disease outcomes.

Accordingly, the registry entry describes the study question and some safety counts, but does not provide enough primary outcome results to quantify the antibody response. It should not be read as evidence of a clinical benefit or as a definitive comparative safety assessment.

13. Why This Trial Matters Statistically

This trial is statistically notable for asking a genotype-specific immunogenicity question in two clinically distinct patient groups. The primary endpoint is not simply an overall antibody percentage: it is defined among participants seronegative at baseline for each relevant HPV type, with additional timing and protocol-deviation criteria. Those criteria make the analysis population central to interpreting each estimate.

The non-randomized, open-label, parallel-group design also matters. Both groups received the vaccine, so the study can describe responses and adverse outcomes in the enrolled patients but does not include a randomized untreated comparison. Any group contrast would need to be interpreted cautiously, and the registry record does not report a comparative analysis.

The absence of posted primary outcome estimates is consequential for statistical interpretation. Although the endpoint and confidence-interval type are named, the registry record does not provide the seroconversion percentages, confidence intervals, or genotype-specific denominators. Readers therefore cannot assess either the magnitude or precision of the primary response from this record.

The record’s safety counts illustrate why denominators and outcome definitions matter: counts are reported separately for HIV and SOT patients, while the study lacks a control group for estimating comparative risk. In general, descriptive safety counts and comparative causal evidence answer different questions.

Finally, the registry does not report the analysis plan, missing-data methods, multiplicity strategy, or the trial’s own sample-size justification. These gaps limit reproducibility and make it difficult to assess how the intended analyses relate to the reported record. The design and endpoint definitions remain useful context, but they do not fill in unreported results or methods.

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 efficacy-related statistics is that the registry record does not report the primary seroconversion results. It gives no percentages, confidence intervals, or genotype-specific denominators. As a result, neither the response magnitude nor its precision can be assessed from the registry entry.

The groups were non-randomized, both received the vaccine, and masking was absent. There was no like-for-like control comparison. Differences between the HIV and SOT groups cannot be attributed to group status or vaccination from this design alone, particularly because baseline characteristics and adjusted analyses are not reported in the registry record.

Enrollment was 271, but group-specific enrollment and primary endpoint analysis denominators are not reported in the registry record. The primary population’s requirements may exclude participants from particular genotype assessments, and the record does not give the number meeting those requirements. Missing-data reasons, completion of the three-dose schedule, and sensitivity analyses are also not reported.

The registry does not define the seroconversion threshold, identify the confidence-interval method, describe a statistical analysis plan, or state how multiplicity was handled across genotypes. Its serious-event terms are accompanied by percentages, but relevant denominators and fuller event details are not reported in the registry record. The trial’s sample-size rationale is also not reported in the registry record. These limitations constrain interpretation without establishing that any particular analysis was inappropriate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Safety, Tolerability and Immunogenicity of Gardasil®9 in Immunocompromised Patients — NCT03525210.
• Registry record last updated 2020-12-11; status last verified 2020-11.
• Results first posted 2020-12-11.
• 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

NCT03525210 is a completed Phase III, open-label, non-randomized parallel study of Gardasil®9 in HIV patients and solid organ transplant recipients. The registry reports enrollment of 271 and a three-dose schedule at 0, 2 and 6 months. Primary completion was listed as 2019-09-01.

The primary endpoint is seroconversion to neutralizing antibodies for nine HPV genotypes, assessed one month after the final dose among participants meeting the stated baseline seronegativity and assessment criteria. The endpoint specifies a 95% confidence interval, but observed seroconversion results and confidence intervals are not reported in the registry record.

The record reports serious adverse events in 3 of 99 HIV patients and 28 of 170 SOT patients, other adverse events in 80 of 99 and 127 of 170, respectively, and no deaths in either group. Because there was no randomized control group, these safety counts are descriptive rather than comparative evidence of causation.