Recombinant Human Papillomavirus Nonavalent Vaccine in Preventing Human Papilloma Virus in Younger Healthy Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Recombinant Human Papillomavirus Nonavalent Vaccine in Preventing Human Papilloma Virus in Younger Healthy Participants (NCT02568566), a na phase 2 study. The primary outcome is Change in Human Papilloma Virus (HPV)16/18 Antibody Titer.

2. Clinical Question

The trial asks how HPV 16/18 antibody titers change after a nonavalent HPV vaccine is given on a prime and deferred-booster schedule. Its official title describes a prospective, single-arm, open-label, non-randomized phase IIA study among 9-11 year-old girls and boys. The primary endpoint concerns changes in antibody titer during the period after the prime dose and before the second dose.

The registry also lists changes in antibody titers for other HPV types, adverse-event incidence and vaccine reactogenicity as secondary outcomes. Those outcomes broaden the planned description of immune response and safety, but they do not create a control group or establish comparative effects.

3. Trial Design

This is a prospective, single-arm, open-label, non-randomized phase IIA trial sponsored by the National Cancer Institute. The registry records enrollment of 201 and lists the study status as active, not recruiting. The recorded start date is 2016-05-19, and the primary completion date is 2020-02-06.

All participants are assigned to the prevention arm described as Gardasil 9. The intervention description specifies recombinant human papillomavirus nonavalent vaccine administered intramuscularly at baseline, with booster injections at 24 and 30 months. Laboratory biomarker analysis is also listed as an intervention. The study is not masked, and allocation is recorded as not applicable because it is a single-group design.

The primary outcome is a continuous antibody measure: mean change in HPV 16/18 antibody titer, expressed in Log10 IU/ml, with standard deviation as the stated dispersion measure. The specified assessment concerns differences in log-transformed antibody levels between 6 and 12 months, between 12 and 18 months, and between 18 and 24 months after the prime dose. The primary-outcome timeframe is described as between 6 and 24 months after the prime dose and before administration of the second dose.

The primary analysis population is described as participants who provided blood samples at all study visits. The registry lists secondary outcomes covering antibody titers for additional HPV types, adverse-event incidence graded under National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, and vaccine reactogenicity. The record reports no analyses. Numerical estimates for the primary endpoint and detailed methods for handling missing measurements are not reported in the registry record.

Because there is no randomized comparator, changes over time can be described within the enrolled group, but the design does not isolate the vaccine schedule’s effect from other explanations for change. The record does not report a control group or a prespecified comparative estimand.

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: Analysis on participants who provided blood samples in all study visits

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 Change in Human Papilloma Virus (HPV)16/18 Antibody Titer, measured over Between 6 and 24 months after prime dose and prior to the administration of the second dose.

The primary endpoint is change in HPV 16/18 antibody titer, reported as a mean on the log-transformed scale in Log10 IU/ml. It is intended to describe how antibody levels vary over time following the prime dose, with observations taken before the second dose. The registry specifies intervals between 6 and 12 months, 12 and 18 months, and 18 and 24 months after the prime dose.

Antibody titers are laboratory measures of immune response. A log transformation expresses values on a scale where differences in the transformed values correspond to multiplicative changes on the original scale; that is a general statistical property, not a reported trial result. Reporting a mean change can summarize the average pattern across participants, while the standard deviation describes how dispersed individual measurements are around that mean.

The endpoint is used to characterize immunogenicity over the stated follow-up period. It does not directly measure clinical HPV infection or cancer incidence. The registry record does not report the observed mean changes, standard deviations, confidence intervals or p-values for these comparisons, so the size and precision of the antibody changes cannot be assessed from the record.

The primary analysis population is restricted in the description to participants with blood samples at all study visits. That definition makes completeness of repeated measurements relevant to interpretation: the participants contributing to the endpoint may not represent everyone enrolled if some lack a visit sample. The number with complete samples and the approach to incomplete measurements are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial uses a single-group longitudinal design. Participants receive the same vaccine schedule, and antibody measurements are specified at multiple follow-up intervals. In general, repeated measurements allow investigators to describe change within participants over time. A comparison of measurements from the same participant can account for stable characteristics of that participant, but it does not provide the protection against time-related confounding that random allocation to a concurrent control group can offer.

What does the mean represent?

The primary endpoint is a mean change in log-transformed antibody titer. A mean is an average that summarizes the center of a set of measurements. It can be informative when the distribution is reasonably represented by an average, but it may not describe every participant’s trajectory. The registry specifies standard deviation as the measure of dispersion. In general, standard deviation describes how spread out the measurements are around their mean; it is not a measure of uncertainty in the estimated mean. The registry record does not provide the endpoint’s numerical mean or standard deviation.

Why use a log scale?

Log-transformed values are often used when measurements span a wide range or when changes are more naturally understood in relative rather than additive terms. In general, a difference on a log scale corresponds to a ratio on the original scale. The stated unit is Log10 IU/ml, and the endpoint description refers to log-transformed HPV 16/18 antibody levels. No back-transformed estimates or explanation of how readers should interpret the scale are reported in the registry record. The scale description alone is not a result.

What does a confidence interval show?

In general, a confidence interval gives a range of values compatible with the data and the model used to calculate it, reflecting statistical uncertainty in an estimate. A narrow interval indicates greater precision than a wide interval, all else equal. A confidence interval is not a guarantee that the true value lies within that particular interval. The registry record does not report confidence intervals for the primary endpoint, so precision cannot be assessed from the posted results.

What would a p-value address?

In general, a p-value measures how incompatible observed data are with a specified null model, under the assumptions of the analysis. It does not measure the size or importance of an effect, and it does not establish causation. The record reports no analyses and gives no primary-outcome p-value. Therefore, there is no reported hypothesis-test result to interpret. A p-value, even if available, would need to be considered alongside the estimated change, its uncertainty, the design and the endpoint’s relevance.

Why does the design affect inference?

Randomization helps create groups that are comparable on average at the start of a study. Here, there is a single group and no random allocation. The repeated endpoint can describe within-group changes, but no randomized between-group contrast is available. General changes over time, participant characteristics, measurement conditions and other influences cannot be ruled out as explanations for a pattern solely by observing change in one group. Open-label status also means the study is not masked, although the primary outcome is a laboratory biomarker. The record does not describe additional safeguards or analytic adjustments.

How should missing measurements be considered?

The primary analysis population is described as participants who provided blood samples in all study visits. In general, restricting analysis to complete cases can reduce the amount of data used and may introduce selection bias if having complete measurements is related to the outcome or participant characteristics. Other methods can use incomplete repeated measurements under explicit assumptions, but the registry record does not report such a method or any assumptions. It also does not report the number of participants with complete samples, the extent of missingness, or reasons for missing visits.

What does over-dispersion mean in general?

Over-dispersion is a general concern for count outcomes when their variability is greater than a statistical model expects. Models that fail to account for excess variability may understate uncertainty. It is not directly a feature of this primary continuous antibody endpoint, which is summarized by a mean and standard deviation. It could be relevant to some adverse-event analyses depending on how event counts were modeled, but no such modeling method is reported in the registry record. No count-model results should be inferred from the posted safety counts.

What do the planning illustrations mean?

Sample-size illustrations are planning calculations, not observed evidence and not observed power. The registry’s stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The record also states that time-to-event illustrations use total events, while other illustrations use participants per arm. Those assumptions describe planning examples rather than the design of this single-group trial. There is no randomized two-arm comparison in the trial design, and the record does not report the numerical values of those illustrations in the information available for interpretation. Such calculations cannot substitute for the missing primary outcome estimates or be read as proof that the study did or did not have adequate power.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary antibody endpoint and secondary outcomes covering antibody titers for additional HPV types, adverse-event incidence and vaccine reactogenicity. The primary endpoint description includes multiple time intervals. When multiple outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. In general, a prespecified multiplicity strategy can address that issue by defining which comparisons are primary and whether adjustment or a hierarchical testing approach is used.

The registry record does not report a multiplicity adjustment, testing hierarchy, or detailed statistical analysis plan. It reports no analyses. It is therefore not possible to determine whether the listed outcomes or intervals were treated as confirmatory, exploratory, or subject to an adjustment. The record does not provide p-values that could be evaluated in light of multiple comparisons.

The primary analysis population is described as participants who provided blood samples in all study visits. The record does not report the number with complete samples, the number with missing samples, reasons for missingness, or a method for handling incomplete measurements. It also does not report whether participants were analyzed according to any other population definition. In general, complete-case analysis can be affected if the availability of all measurements is related to antibody response or other participant characteristics. Without missing-data details, the extent and direction of any such effect cannot be assessed.

Although the registry lists an enrollment of 201, that figure does not establish how many participants contributed to each outcome analysis. The participant count for the primary analysis population and outcome-specific denominators are not reported in the registry record. The absence of an analysis description also leaves the handling of protocol deviations and measurement-level exclusions unclear.

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: appendicitis (0.5%), wheezing (0.5%).

The registry safety summary for the Prevention (Gardasil 9) group records 201 at risk for serious adverse events, 2 affected by serious adverse events, 201 at risk for other adverse events, and 151 affected by other adverse events. It records 0 deaths. The listed top serious-event terms are appendicitis and wheezing, each shown at 0.5%.

These are descriptive safety figures. The at-risk counts identify the group denominator recorded for each category; they should not be mistaken for evidence that every event was caused by the vaccine. The registry record does not provide a concurrent control group, so these counts cannot establish whether the frequency differs from what would occur without this schedule. The term listings also do not include event-level detail, timing, severity, outcome or an attribution assessment in the information recorded.

The record identifies adverse-event grading according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 as a secondary outcome. The posted summary does not give further detail on how the listed events were collected or adjudicated. Serious and other adverse events are distinct categories in the registry summary and should not be added together, because the record does not explain overlap between those categories. These figures describe what the registry reports; they do not establish causality or comparative safety.

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

The study is structured to describe antibody response after a nonavalent HPV vaccine schedule that includes a prime dose and deferred boosters. Its primary endpoint focuses on HPV 16/18 antibody-titer changes during the period after the prime dose and before the second dose. The registry also identifies secondary immunogenicity and safety outcomes. This makes the record useful for understanding what the investigators set out to measure and how the intervention was scheduled.

The registry record does not include numerical results for the primary endpoint. It therefore does not show the observed direction, magnitude or precision of antibody changes. There are no reported primary-outcome confidence intervals or p-values to interpret. The record’s silence on those results should not be read as evidence of no change, nor as evidence of a particular response.

The single-group, non-randomized design means the study does not directly compare this schedule with another schedule or a control condition. Within-group change, if reported, would describe participants’ measurements over time, but would not by itself establish that the schedule caused the change. The registry’s enrollment figure also does not establish the number of participants included in every endpoint analysis, especially because the primary analysis population requires blood samples at all study visits.

The antibody endpoint is a biomarker measure. It is not itself a count of HPV infections or cancers. The record does not report clinical disease outcomes as the primary endpoint, nor does it report a direct relationship between antibody changes and clinical outcomes in this trial. Therefore, the primary endpoint as registered cannot be used alone to make claims about disease prevention.

The safety summary offers descriptive counts and selected event terms, but lacks a concurrent comparator and further detail needed for causal attribution. Overall, the record supports a description of the study question, design, schedule and selected safety figures. It does not support a conclusion about the size or clinical meaning of the antibody response, comparative effectiveness, or comparative safety.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining repeated biomarker measurements with a single-group design. The repeated measurements are intended to characterize changes in antibody titer over time after a prime dose. Such longitudinal data can describe trajectories and within-participant variation, but the absence of a randomized comparator limits causal interpretation. The design determines which questions can be answered, irrespective of how the measurements are summarized.

The timing of the endpoint is also important. The primary outcome concerns specified intervals after the prime dose and before the second dose, while the intervention schedule includes later booster injections at 24 and 30 months. Clearly identifying which measurements precede a subsequent dose helps distinguish the question about post-prime antibody change from questions about response after later doses. The registry record defines that timing, although it does not report numerical results for the endpoint.

The primary analysis population requires blood samples at all study visits. This highlights a common issue in longitudinal research: the people with complete follow-up may differ from those without it. Without the number of complete cases, missingness details and analysis method, readers cannot determine how representative the endpoint analysis is of the enrolled group. Transparent reporting of those details is important when a result depends on repeated observations.

The record also illustrates the distinction between an immune biomarker and a clinical outcome. An antibody-titer endpoint can answer a question about laboratory-measured immune response, while clinical outcomes require their own measurement and analysis. Keeping these endpoints distinct avoids overstating what a biomarker result can establish. Here, numerical antibody findings are not reported in the registry record, so even the magnitude of the biomarker pattern cannot be evaluated.

Finally, the posted safety counts are descriptive in a single group. Their interpretation depends on denominators, event definitions, follow-up and the absence or presence of comparison data. The record provides some basic counts and selected terms but not a comparative analysis. These design and reporting features are integral to statistical interpretation, not merely technical details.

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.

Several limitations specific to this trial shape what can be concluded from the registry record. First, it is a single-arm, open-label, non-randomized study. With no concurrent comparator group, the design cannot provide a randomized contrast for antibody response or adverse events. Observed changes over time, if numerical results were available, would not alone isolate the effect of the vaccine schedule from other influences.

Second, the registry record does not report numerical primary-outcome results. The planned mean change, standard deviation, confidence intervals and p-values are not included. Although the endpoint is defined in terms of HPV 16/18 antibody titers and repeated intervals, the size, direction and precision of any changes cannot be evaluated. The record also reports no analyses.

Third, the stated primary analysis population includes participants with blood samples at all study visits. The number meeting this criterion, the extent and reasons for missingness, and the method for incomplete data are not reported in the registry record. This prevents assessment of potential selection effects from requiring complete follow-up.

Fourth, the registry lists multiple outcomes and time intervals but does not report how multiplicity was handled or which analyses were prespecified as confirmatory. Without the analysis details, the status and interpretation of any comparisons are unclear. The record also does not report a detailed statistical plan or sample-size justification.

Finally, the primary endpoint is a laboratory biomarker, not a clinical disease outcome. The safety summary includes counts and selected serious-event terms, but it does not provide a control group or sufficient detail for causal attribution. These limitations concern both the design and the information reported in the registry; they should not be mistaken for evidence that a particular result was favorable or unfavorable.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Recombinant Human Papillomavirus Nonavalent Vaccine in Preventing Human Papilloma Virus in Younger Healthy Participants — NCT02568566.
• Registry record last updated 2026-07-10; status last verified 2026-07.
• Results first posted 2022-04-05.
• 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

NCT02568566 is a prospective, single-arm, open-label, non-randomized phase IIA trial of a nonavalent prophylactic HPV vaccine among healthy girls and boys aged 9-11 years. The registry records enrollment of 201, lists the National Cancer Institute as sponsor, and identifies the study status as active, not recruiting. Recorded dates are a start date of 2016-05-19 and a primary completion date of 2020-02-06.

The intervention schedule is an intramuscular vaccine dose at baseline, followed by booster injections at 24 and 30 months. The primary endpoint is mean change in HPV 16/18 antibody titer, measured in Log10 IU/ml, with standard deviation specified as the dispersion measure. The primary analysis population is described as participants who provided blood samples in all study visits.

The registry lists secondary outcomes for antibody titers to other HPV types, adverse-event incidence and reactogenicity. Its safety summary records 2 serious adverse-event-affected participants, 151 participants with other adverse events and 0 deaths. Numerical primary-outcome results and detailed analysis methods are not reported in the registry record.