Randomized Trial of Alternative HPV Vaccination Schedules in Males in a University Setting: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Trial of Alternative HPV Vaccination Schedules in Males in a University Setting (NCT01184079), a randomized na study. The primary outcome is Immunogenicity After Dose 3.

2. Clinical Question

In practical statistical terms, the trial was designed to compare antibody response after the third dose under two schedules. The registry describes measurement one month after dose three: the example time points are month 7 for the six-month schedule and month 13 for the twelve-month schedule. Thus, the comparison is aligned to time since the third dose, rather than to one shared calendar month after the first dose.

The non-inferiority question is not simply whether the groups have identical titers. It asks whether the response in the delayed-dose group is not unacceptably lower than the response in the usual-timing group, using a margin set in advance. Because the margin and numerical outcome estimates are not reported in the registry record, the stated question can be described, but the non-inferiority conclusion cannot be assessed from the posted results described there.

3. Trial Design

The registry record describes a randomized, open-label, parallel-group trial at a university setting. It lists an enrollment of 220 and a completed status. The recorded start is 2010-10, and primary completion is 2012-05. No masking was used. These design features mean participants were assigned to one of the dose-timing groups, and the trial description does not indicate that participants or study personnel were blinded to assignment.

Both groups were to receive the first and second vaccine doses according to schedule. The randomized difference was the timing of dose three: one group received it at six months and the other at twelve months. The vaccine was quadrivalent human papillomavirus vaccine in both groups. The comparison therefore isolates the planned timing contrast within the described regimen, though the registry record does not supply further details about allocation procedures, adherence to earlier doses, or other protocol procedures.

The primary outcome is titled “Immunogenicity After Dose 3.” It is described as the geometric mean titer, with a 95% confidence interval, measured one month after dose three. The description says the comparison is in the per-protocol population, while the population field says intention-to-treat. Since those labels describe different analysis populations, the registry record leaves uncertainty about which population was intended for the posted primary analysis.

Compliance with dose three and safety profile are listed as secondary outcomes. The registry record names two biological interventions, each described as quadrivalent human papillomavirus vaccine, corresponding to the two timing arms. It does not report a detailed statistical analysis plan, the randomization method, how protocol deviations were handled, or how the secondary outcomes were analyzed. Those details are not reported in the registry record and should not be inferred from the broad design description.

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.

Before assignment: Exclusion criteria were: \>4 lifetime sexual partners, health problems that would interfere with the immune response or ability to complete the study, a hospitalization during the past year, hypersensitivity to yeast or HPV vaccine components, inability to complete appointments, received HPV vaccine or immunosuppressive medications.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat

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 Immunogenicity After Dose 3, measured over 1 month after dose 3 (e.g., month 7 if third dose at 6months or month 13 if third dose at 12 months).

The primary endpoint measures antibody response after the third vaccine dose using a geometric mean titer, or GMT. Titers are a measure of the amount of antibody detected in a sample. The listed unit is mM units/ml, and the registry specifies measurement one month after dose three. Because the third dose occurs at different planned times in the two arms, the corresponding example assessment times are month 7 after a six-month dose and month 13 after a twelve-month dose.

A geometric mean is used when measurements are positive and may be distributed asymmetrically: it averages on a logarithmic scale and then returns the result to the original scale. In general, this can make a central summary less dominated by unusually large measurements than an arithmetic mean. The registry’s hypothesis is also defined using logarithms of the group GMTs, consistent with comparing the groups on a log scale.

The endpoint is relevant to the stated question because the trial focuses on immunogenicity under alternative dose schedules. The registry describes a 95% confidence interval around each titer estimate and a comparison between groups. In general, a confidence interval communicates the precision of an estimate by indicating a range of values compatible with the data and method used. The numerical GMTs and confidence intervals are not reported in the registry record as a single reduced comparison, so their magnitude and precision cannot be interpreted from the record’s outcome summary.

The outcome description names a per-protocol population, but the population field names intention-to-treat. That difference matters because the endpoint’s estimate can depend on who is included. The registry record does not resolve the discrepancy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial’s methods are best understood through the distinction between its design, its outcome definition, and the statistical decision it intended to make. The registry describes random assignment to two parallel groups, with dose three at six or twelve months. It calls the study open label and reports no masking. These details identify the planned comparison, but do not provide a complete statistical analysis plan.

What does the non-inferiority hypothesis mean?

In general, a non-inferiority study asks whether a new or alternative approach is not worse than a reference approach by more than an agreed margin. The margin defines the largest difference that would still be considered compatible with non-inferiority for the statistical question. The trial description states that the twelve-month group is the test group and the six-month group is the usual-timing control. It expresses the contrast as the logarithm of the test-group GMT minus the logarithm of the control-group GMT, and states a null and alternative hypothesis using a pre-specified margin. The numerical margin is not reported in the registry record. It is therefore possible to explain the form of the question, but not to apply its decision threshold.

The scale is important. A contrast between logarithms of GMTs is a comparison on a log scale. In general, analysis on a log scale is often used for measurements that are positive and whose variation is more naturally interpreted proportionally than as an additive difference. Returning from a log-scale estimate to the original scale can yield a ratio-type interpretation. No such transformed estimate is reported in the registry record, so no ratio or other derived quantity should be inferred.

Why are confidence intervals important?

The primary outcome description specifies GMTs with 95% confidence intervals. In general, a confidence interval shows the uncertainty associated with an estimated quantity under the assumptions of the statistical method. It is not a guarantee that a particular range contains the true value, and its width depends on the data and method. For a non-inferiority assessment, the interval around the treatment contrast is especially important because the question concerns whether plausible values cross the non-inferiority boundary. Here, the registry record does not give the numerical interval for a single comparison, nor the margin needed to interpret such an interval.

The endpoint is measured one month after dose three. This timing means that the two groups are assessed at different points on the calendar schedule, with the registry giving month 7 and month 13 as examples. The endpoint description thus aligns assessment to the interval after the third dose. The record does not describe additional endpoint time points or how any multiple measurements were combined or selected for the primary analysis.

Which analysis population is intended?

The record contains two descriptions: the endpoint text refers to the per-protocol population, while the population field says intention-to-treat. In general, intention-to-treat analysis retains randomized participants in their assigned groups, regardless of adherence, whereas per-protocol analysis focuses on participants meeting protocol requirements defined by the study. Neither label alone gives the inclusion rules, treatment of missing measurements, or handling of participants who received dose three outside the planned timing. Those rules are not reported in the registry record. The discrepancy should therefore remain explicit rather than being resolved by assumption.

The distinction can be important in non-inferiority settings. As general context, exclusions or non-adherence can affect estimates, and analyses of different populations may provide complementary perspectives. The registry record does not state whether both analyses were performed, which one was primary in the final analysis, or how results compared. It also does not report an analysis plan that would clarify the population discrepancy.

What can be said about planning illustrations?

Planning illustrations associated with the posted material are based on the observed effect, not on the trial’s original design. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. These are illustrations, not observed power and not evidence about the design justification used by the investigators. For non-time-to-event outcomes, the convention is participants per arm; time-to-event calculations, when applicable, use total events. The registry record does not report the trial’s own sample-size justification, its assumed effect, or a protocol calculation. No planning count should be interpreted as the number actually enrolled or as a measure of achieved power.

More broadly, the registry reports an enrollment of 220, but does not provide a detailed account of the number randomized to each group for the primary outcome analysis, the number with evaluable titers, or the number included after protocol adherence criteria. The adverse-event risk counts are reported separately and should not be substituted for analysis denominators. A clear interpretation of an outcome estimate would require knowing its analysis population and denominator as well as its estimate and uncertainty.

The posted record does not report adjustment methods, model specifications, handling of assay values outside measurement limits, or sensitivity analyses. Those features can matter for laboratory outcomes, but their use in this trial cannot be inferred. The defensible methods description is therefore limited to the randomized parallel design, dose-timing contrast, GMT endpoint, confidence-interval description, and stated non-inferiority hypothesis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description refers to titers and confidence intervals, while the registry indicates that the primary outcome has several categories or time points and is not reduced to one comparison. This leaves no single numerical result to interpret. The record does not say how multiple categories or time points were prioritized, whether one time point was designated as the principal test, or whether any multiplicity adjustment was planned. Those details are not reported in the registry record.

In general, testing several outcomes or time points can increase the chance that at least one result appears unusual by chance. Statistical plans may address this through a prespecified hierarchy, an adjustment, or a clearly defined primary comparison. None of those approaches should be attributed to this trial without a reported plan. The record also lists compliance with dose three and safety profile as secondary outcomes but does not describe their analysis or any adjustment across outcomes.

Missing-data handling is not reported in the registry record. The primary outcome’s analysis population is described inconsistently: the outcome text names per-protocol, and the population field names intention-to-treat. The registry does not state how participants without a titer measurement were handled, whether incomplete vaccination schedules affected inclusion, or whether any imputation or sensitivity analysis was used.

These omissions limit interpretation independently of the missing numerical comparison. Even if group estimates were available, conclusions would depend on which participants contributed data, how missing measurements were treated, and how multiple measurements were handled. The record does not provide enough detail to reconstruct those choices. No particular missing-data or multiplicity procedure should be assumed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The adverse-event entries list the twelve-month administration group with 111 participants at risk and 0 affected in the serious-event field; its other-event field also lists 111 at risk and 0 affected. For the six-month administration group, the corresponding entries are 109 at risk and 0 affected for serious events, and 109 at risk and 0 affected for other events. These are the registry’s recorded counts, not estimates of comparative risk.

The record lists no top serious-event terms. The deaths fields are null, which means deaths are not reported in the registry record; a null field should not be restated as a count of zero. The record does not explain the precise event collection procedures, observation period, severity definitions, or completeness of reporting. Nor does it provide event-level descriptions for the other-event category.

In general, a count of zero recorded events does not establish that the true event frequency is zero. It describes what was entered in the registry for the specified fields and recorded participants at risk. Because the entries do not include additional detail about ascertainment or follow-up, they support only a narrow descriptive reading: the registry reports zero affected participants in these event fields for both groups. They do not establish equivalence between schedules or rule out events not represented by these entries.

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

The registry record establishes that this was a completed randomized, open-label comparison of two schedules for the third dose of quadrivalent HPV vaccine in males aged 18–24 years. It describes an immunogenicity endpoint based on geometric mean titers measured one month after dose three, with 95% confidence intervals, and frames the principal question as non-inferiority of the twelve-month schedule relative to the six-month schedule.

That description identifies what the investigators sought to compare, but it is not enough to determine what the trial found. The primary outcome is not reduced to one comparison in the registry record, and numerical group GMTs, confidence intervals, and a non-inferiority estimate are not reported there. The pre-specified margin is also not reported in the registry record. Therefore, the stated non-inferiority hypothesis cannot be evaluated from these outcome details.

In general, a completed trial can have an inconclusive or otherwise hard-to-interpret registry record if numerical estimates, uncertainty, and analysis details are not presented in a usable form. Completion status does not supply those missing elements. Nor does the number enrolled by itself establish precision or show whether the study met its objective.

The safety fields report zero affected participants in the listed serious and other adverse-event categories in both arms, with the recorded at-risk counts. These data are descriptive and limited to those fields. They do not establish that the groups have identical safety profiles, and the null death entries are not reported counts of zero.

The meaning of the record is therefore primarily methodological: it documents a randomized dose-timing question and a planned non-inferiority framework, while leaving the numerical efficacy comparison and key interpretive details unavailable. Conclusions about the actual size, precision, or direction of the immunogenicity difference should not be made from the record’s summary alone.

13. Why This Trial Matters Statistically

This trial is statistically notable because it illustrates how a non-inferiority question differs from a conventional search for any difference between groups. The objective was not simply to test whether titers differed. It was to assess whether titers after the twelve-month schedule were no worse than those after the six-month schedule by more than a pre-specified margin. That makes the margin central to the interpretation, not a peripheral detail.

The record also highlights the need to report both an estimate and its uncertainty. A GMT and its confidence interval describe the response and its precision, while a direct contrast and an appropriate interval are needed to evaluate the stated non-inferiority question. The registry record does not provide one reduced comparison with numerical values, and the margin is not reported. The statistical framework can therefore be understood, but its decision cannot be checked.

The mismatch between the endpoint’s per-protocol description and the intention-to-treat population field is another important reporting issue. In general, an analysis population defines who contributes to an estimate and the question that estimate answers. In a randomized schedule comparison, adherence and missing measurements can affect that population. The record does not specify the operational rules or reconcile the labels.

Finally, the trial demonstrates the difference between a registered design and an interpretable results record. Randomization, an enrollment of 220, and completed status describe important features, but they do not replace outcome estimates, analysis denominators, or details on missing data and multiplicity. The record’s limits are a reminder that statistical conclusions require transparent reporting of the planned threshold, analysis population, and uncertainty around the comparison.

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 most direct limitation for interpretation is the absence of a single numerical primary comparison. The registry identifies the GMT endpoint and 95% confidence intervals, but does not report the primary outcome as one reduced comparison. The actual group estimates, uncertainty intervals, and direct contrast are therefore not available in the registry record in a form that allows assessment of the stated objective.

The non-inferiority margin is mentioned but its value is not reported in the registry record. Since that margin defines the boundary for the statistical question, its absence prevents readers from determining what difference the investigators considered acceptable. The record also does not report a p-value or a clear statement that the non-inferiority criterion was met.

Analysis-population reporting is internally inconsistent: the endpoint description names per-protocol, while the population field identifies intention-to-treat. The record does not define either population’s inclusion rules or explain which was used for the result. It also does not report numbers with evaluable titers, handling of missing measurements, or sensitivity analyses.

Other relevant details are not reported in the registry record, including the randomization procedure, the statistical model, the trial’s own sample-size justification, and any multiplicity strategy for several outcome categories or time points. The registry lists secondary compliance and safety outcomes but does not provide their detailed analysis methods. These limitations concern reporting and interpretability; they should not be taken as evidence that a particular method was or was not used outside the registry description.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Randomized Trial of Alternative HPV Vaccination Schedules in Males in a University Setting — NCT01184079.
• Registry record last updated 2014-03-27; status last verified 2014-02.
• Results first posted 2014-02-26.
• 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

NCT01184079 is a completed randomized, open-label, parallel-group trial sponsored by the University of Pittsburgh. It lists an enrollment of 220, a start in 2010-10, and primary completion in 2012-05. The study compared quadrivalent HPV vaccine schedules in males aged 18–24 years, with dose three planned at six months or twelve months after the first doses given according to schedule.

The primary outcome was immunogenicity after dose three, described as geometric mean titer with 95% confidence intervals one month after that dose. The stated objective was non-inferiority of the twelve-month group relative to the six-month control group. The numerical margin and a single reduced outcome comparison are not reported in the registry record. The endpoint text refers to a per-protocol population, while the population field says intention-to-treat.

Compliance with dose three and safety profile are listed as secondary outcomes. Adverse-event fields record zero affected participants in the serious and other categories for both groups; the deaths fields are null. The posted record does not provide enough numerical or methodological detail to determine whether the primary non-inferiority criterion was met.