This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Randomized Trial of Alternative Quadrivalent Human Papilloma Virus (HPV) Vaccination Schedules in a University Setting (NCT00572832), a randomized na study. The primary outcome is Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00572832 |
| Phase | NA |
| Condition | Human Papillomavirus Infection |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 200 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pittsburgh |
| Results posted | Yes |
2. Clinical Question
Population
Participants in a university-setting trial of quadrivalent human papillomavirus vaccine. The registry lists Human Papillomavirus Infection as the condition and an enrollment of 200. For the primary analysis, participants with positive baseline antibody titers were excluded only for the virus type or types for which they were seropositive, so the analyzed population could differ by type.
Intervention
The delayed schedule: three vaccine doses at 0, 2, and 12 months. The registry describes this as the alternative schedule, with the third dose administered at 12 months.
Comparator
The standard schedule: three vaccine doses at 0, 2, and 6 months. All participants were to receive the first and second doses according to schedule before assignment to one of the third-dose timings.
Primary question
One month after the third dose, were geometric mean antibody titers by virus type in the delayed-schedule group non-inferior to those in the standard-schedule group? The registry states a non-inferiority hypothesis based on the difference between log geometric mean titers and a prespecified margin. The margin value and the observed titers and confidence intervals are not reported in the registry record.
3. Trial Design
The registry describes a randomized, open-label, parallel-group trial comparing two timings for the third dose of quadrivalent human papillomavirus vaccine. The trial was conducted in a university setting and lists an enrollment of 200. The listed phase is NA. The sponsor is the University of Pittsburgh. The record lists the study as completed, with a start in 2007-09 and primary completion in 2009-04.
Both groups followed the same timing for the first two doses. The standard-schedule group received doses at 0, 2, and 6 months; the alternative-schedule group received doses at 0, 2, and 12 months. The registry calls the standard timing the control and the delayed timing the test group in its hypothesis description. Because masking is listed as none, the trial was open label.
Blood was to be drawn before the first dose and one month after the third dose. The primary endpoint timeframe is one month after dose three, corresponding to 7 months for the standard schedule and 13 months for the alternative schedule. The primary outcome compares antibody titers after dose three by virus type. The registry says the analysis was by intention to treat, with baseline-positive participants excluded only from the analysis for the relevant type.
Random allocation is recorded, but the method used to generate or conceal the allocation sequence is not reported in the registry record. Details about recruitment, eligibility criteria beyond the described population, adherence, deviations from assigned timing, and participant flow are also not reported in the registry record. The record therefore establishes the basic schedule comparison but does not provide enough detail to assess all operational features of trial conduct.
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
| Stage | 6 Month Standard Schedule | 12 Month Alternative Group |
|---|---|---|
| STARTED | 100 | 100 |
| COMPLETED | 100 | 88 |
| NOT COMPLETED | 0 | 12 |
Reasons for not completing this period:
| Reason | 6 Month Standard Schedule | 12 Month Alternative Group |
|---|---|---|
| Lost to Follow-up | 0 | 11 |
| Pregnancy | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was by intention to treat. Participants who had positive baseline antibody titers were excluded from further analyses only for the type(s) for which they were seropositive.
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.
| Characteristic | Unit | 6 Month Standard Schedule | 12 Month Alternative Group | Total |
|---|---|---|---|---|
| Participants analysed | 100 | 100 | 200 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 100 | 100 | 200 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 20.3 (SD 1.3) | 20.1 (SD 1.4) | 20.2 (SD 1.3) |
| Sex: Female, Male: Female | Participants | 100 | 100 | 200 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 5 | 2 | 7 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 8 | 8 | 16 |
| Race (NIH/OMB): White | Participants | 83 | 89 | 172 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 4 | 1 | 5 |
| Region of Enrollment: United States | participants | 100 | 100 | 200 |
| Body Mass Index | kg/m^2 | 24.2 (SD 4.7) | 24.5 (SD 5.1) | 24.3 (SD 4.9) |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Mean Antibody Titers Following the Third Dose of Human Papilloma Virus (HPV) Vaccine by Virus Type and by Administration Schedule, measured over 1 month post-dose 3 (i.e., 7 months for standard schedule and 13 months for alternative schedule).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | milliMerck units per mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the geometric mean antibody titer measured one month after the third dose, reported in milliMerck units per mL. It is assessed by virus type and compared between the standard and delayed administration schedules. The relevant assessment occurs at 7 months for the standard schedule and 13 months for the alternative schedule.
A geometric mean summarizes measurements on a multiplicative scale. In general, this can be useful for antibody measurements because values may be right-skewed and comparisons are often naturally expressed as ratios. Taking logarithms converts multiplicative comparisons into differences, which is the scale described in the registry hypothesis. The registry’s stated contrast is the log geometric mean titer in the test group minus the log geometric mean titer in the control group.
Antibody titers describe an immune response measured in blood; they are not, by themselves, a count of infections or a direct measure of clinical disease. The registry record does not report the observed titers, group contrasts, confidence intervals, or conclusions about non-inferiority. It also does not state the virus-type-specific values or the prespecified margin in numeric form.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a clear timing comparison: a third vaccine dose at 6 months versus a third dose at 12 months, with the first two doses scheduled at 0 and 2 months in both groups. The primary question concerns post-dose antibody titers by virus type, assessed one month after the third dose. These design details describe what was intended to be compared; they do not establish the size or direction of any observed difference.
The primary outcome results are not reported in the registry record. No group-specific geometric mean titers, between-group estimates, confidence intervals, or test results are included. Consequently, the degree of similarity or difference between schedules cannot be judged from the registry information. A non-inferiority claim also cannot be assessed: the record gives the form of the hypothesis but not the numeric non-inferiority margin or the outcome estimates needed to compare with it.
In general, a confidence interval expresses uncertainty around an estimated effect. Its width indicates how precisely the effect has been estimated, while its position relative to a prespecified non-inferiority margin informs whether the data are compatible with the non-inferiority criterion. The registry lists 95% confidence intervals as the endpoint’s dispersion measure, but does not report the intervals themselves. Therefore, neither precision nor whether an interval met the stated criterion can be determined.
The primary analysis excludes people with positive baseline antibody titers from the analysis for the corresponding virus type. The registry says the analysis was by intention to treat, with this type-specific exclusion. This means the population contributing to an estimate may vary across types; the number analyzed for each type is not reported in the registry record. The record does not provide outcome values to indicate how these exclusions affected the estimates.
Safety information is limited to aggregate adverse-event counts. The registry records zero serious adverse events among 100 at risk in each group, and 57 other adverse events in the standard-schedule group and 55 in the alternative group, each with 100 at risk. These entries do not provide event descriptions or establish whether counts represent people with at least one event or total events. Death counts are not reported in the registry record. These safety entries should be read separately from the antibody-titer endpoint; they do not answer the non-inferiority question.
The record therefore supports a description of the trial’s design, endpoint, and selected safety counts, but not a conclusion about the comparative antibody response. No treatment effect should be inferred from the absence of posted primary outcome values.
9. Statistical Methods Explained
The registry describes a non-inferiority objective using geometric mean antibody titers. Its hypothesis is expressed on the logarithmic scale: the contrast is the log geometric mean titer in the test group minus the log geometric mean titer in the control group. The null hypothesis is that this contrast is less than or equal to the negative of the non-inferiority margin; the alternative is that it is greater than that boundary. The numeric margin is not reported in the registry record.
What does non-inferiority test?
In general, a non-inferiority design asks whether an intervention’s outcome is not worse than a comparator by more than a prespecified acceptable amount. It is not the same as testing whether two groups are exactly equal. The margin sets the boundary for what difference is considered acceptable for the study question. A result must be interpreted in relation to that boundary, rather than from a nonsignificant difference test alone. For this trial, the registry provides the hypothesis structure but not the margin value or the estimate and confidence interval required to evaluate it.
Why use a logarithmic scale?
In general, a geometric mean is formed by working with logarithms of measurements, averaging on that scale, and transforming back. This is suited to data where relative changes are meaningful or where values vary multiplicatively. On the log scale, a difference in group means corresponds to a ratio on the original scale. The trial record defines its group contrast using log geometric mean titers, but does not report the calculated group values or the contrast.
How should confidence intervals be read?
In general, a confidence interval gives a range of effect estimates compatible with the data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, though precision alone does not establish clinical or scientific importance. For a non-inferiority analysis, the interval must be assessed relative to the prespecified margin and the direction of the contrast. The endpoint description names 95% confidence intervals, but actual intervals are not reported in the registry record.
Why can analyzed sample sizes vary by virus type?
The registry specifies that participants with positive baseline titers were excluded for the particular type for which they were seropositive. This type-specific rule means that the number contributing to an analysis may differ across virus types. The record does not give the counts analyzed for each type. As a result, the precision of a type-specific estimate may also vary, but the extent cannot be assessed without the analysis counts and results.
What can planning calculations tell readers?
In general, sample-size calculations describe how many participants might be needed under chosen assumptions; they are not a measure of the observed study’s power after results are known. The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. It distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes. The registry record does not report the resulting planning values or a trial-specific sample-size justification. The described illustration should therefore not be treated as evidence of the trial’s design rationale or as observed power.
The record does not report additional details of the statistical model, handling of values below or above assay limits, transformations beyond the stated log-scale contrast, covariate adjustment, or rules for missing measurements. These details matter because they can affect how estimates and uncertainty are calculated. Their absence limits independent assessment of the analysis, rather than establishing that any particular method was or was not used.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is assessed by virus type, so the trial involves several type-specific comparisons. The registry does not report a multiplicity adjustment, a hierarchy among virus types, or a rule identifying one type as the sole confirmatory comparison. Whether the analyses were intended as separate confirmatory tests or as a set of descriptive estimates is not reported in the registry record.
In general, when several hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis accounts for the number and structure of comparisons. Adjustments can control that risk, while a prespecified hierarchy can define which tests carry confirmatory weight. The registry provides no information to determine whether such procedures were planned. No type-specific results or p-values are reported, so multiplicity cannot be evaluated from the results either.
Baseline-positive participants were excluded only for the corresponding virus type, and the registry identifies the analysis as intention to treat subject to this exclusion. This explains why type-specific analysis populations may differ. The actual numbers included for each type are not reported in the registry record. The record also does not describe how missing post-dose blood samples, incomplete measurements, protocol deviations, or participants who did not receive the assigned third-dose timing were handled.
In general, missing-data methods rely on assumptions about why measurements are missing and how missing values relate to observed outcomes. Without counts and handling rules, readers cannot judge the potential influence of missing measurements. The registry record does not report sensitivity analyses or alternative analysis populations. It also does not report interim analyses or stopping rules.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 6 Month Standard Schedule | 0 | 100 | 0.0% |
| 12 Month Alternative Group | 0 | 100 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 6 Month Standard Schedule | 57 of 100 |
| 12 Month Alternative Group | 55 of 100 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 6 Month Standard Schedule | 12 Month Alternative Group |
|---|---|---|---|
| Soreness at the injection site | Skin and subcutaneous tissue disorders | 57 of 100 | 55 of 100 |
| syncope | General disorders | 1 of 100 | 0 of 100 |
The registry lists 100 participants at risk for serious adverse events in each group, with zero serious adverse events recorded in the 6 Month Standard Schedule group and zero in the 12 Month Alternative Group. It also lists 57 other adverse events in the standard-schedule group and 55 in the alternative group, with 100 at risk in each group.
The record does not define the category of other adverse events or say whether those counts refer to participants with at least one event or to event occurrences. It does not list serious adverse-event terms; the serious-event term list is empty. Death counts are not reported in the registry record. The displayed counts therefore offer only a limited summary and do not describe event types, timing, severity beyond the serious-event classification, or attribution.
These figures should not be interpreted as a complete safety comparison. The registry record does not provide further detail needed to assess the nature or distribution of events. The counts also do not supply evidence about the primary antibody-titer question, which is a separate outcome.
12. What the Result Does, and Does Not, Mean
The registry establishes that a randomized, open-label, parallel-group trial compared two schedules for the third dose of quadrivalent human papillomavirus vaccine. It specifies the intended timing of doses, the antibody-titer endpoint, the assessment timing, and a non-inferiority hypothesis. It also reports limited aggregate adverse-event counts.
The primary outcome results are not reported in the registry record. Without group-specific titers, an estimated contrast, confidence intervals, and the numeric non-inferiority margin, readers cannot determine whether the observed antibody response met the stated non-inferiority criterion, how large any difference was, or how precisely it was estimated. The design and stated hypothesis alone do not establish the outcome.
In general, antibody titers are laboratory measures of immune response. They are not equivalent to observed infection rates or a direct demonstration of protection against disease. The record does not report infection outcomes, and its stated primary endpoint is antibody titer rather than a clinical disease outcome. Conclusions about clinical outcomes therefore cannot be drawn from the described endpoint.
The safety entries show zero recorded serious adverse events in each group in the listed at-risk populations and different counts for the category of other adverse events. The record does not provide event-level detail or definitions sufficient to interpret those counts fully. They should not be treated as a complete account of safety or as proof of equivalence between schedules.
The registry also leaves important aspects of analysis and conduct unspecified, including the numeric margin, type-specific analysis counts, missing-data handling, and multiplicity procedures. These omissions do not show that a particular procedure was absent from the trial; they mean it cannot be assessed from the registry record.
13. Why This Trial Matters Statistically
This trial poses a statistical question that is distinct from asking whether two schedules produce exactly the same antibody response. Its stated aim is non-inferiority: whether the response under delayed third-dose timing is not below the standard-schedule response by more than a prespecified margin. That distinction matters because interpreting a non-inferiority comparison requires a margin chosen in advance and an estimate precise enough to evaluate against it.
The endpoint also illustrates why scale matters. Geometric mean titers are analyzed through logarithms in the registry’s stated contrast. In general, this makes relative differences natural to express and can be useful when measurements vary multiplicatively. Clear reporting should connect the log-scale estimate, its uncertainty, and the margin to the interpretation on the original measurement scale. The registry record does not include the values needed to make that assessment.
Another statistical feature is the type-specific exclusion of participants with positive baseline titers. This makes the analysis population potentially different for each virus type, rather than a single fixed population across all comparisons. Reporting the counts and estimates by type would be important for understanding precision and the scope of each result. Those details are not reported in the registry record.
Finally, the registry shows how a trial’s design can be documented without its primary outcome results. Randomization, open-label status, schedules, endpoint timing, and the form of the hypothesis are informative, but they cannot substitute for estimates and uncertainty. The limited safety counts likewise require careful interpretation because their categories and event-level details are not specified. Keeping these distinctions clear prevents design descriptions from being mistaken for evidence of an outcome.
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 important limitation of the registry information is that primary outcome estimates are not reported. There are no geometric mean titers by group and virus type, no between-group contrasts, and no 95% confidence intervals. The numeric non-inferiority margin is also not reported in the registry record, so the primary statistical criterion cannot be independently evaluated.
The record says baseline-positive participants were excluded by virus type, but does not report how many participants remained in each type-specific analysis. It does not provide a participant-flow account or explain how missing post-dose measurements were handled. Thus, the analysis populations and the possible effect of missing outcome data cannot be assessed from the registry information.
Although the registry specifies multiple virus-type comparisons, it does not report how multiplicity was addressed or whether one type was designated as primary for confirmatory inference. It also does not report full details of the statistical model, the handling of assay limits, or any sensitivity analyses. The particular analysis methods used beyond the stated outcome and hypothesis are not reported in the registry record.
The safety information is limited to aggregate counts. Definitions for other adverse events, event descriptions, and death counts are not reported in the registry record. The record lists zero serious adverse events in each group, but does not provide further detail with which to assess event ascertainment or follow-up.
Finally, the registry lists enrollment and trial dates but does not provide information about recruitment, adherence, deviations from assigned schedules, or the method for sequence generation and allocation concealment. These are limits of what can be assessed from the registry record, rather than evidence that the relevant procedures or data were absent from the trial itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized Trial of Alternative Quadrivalent Human Papilloma Virus (HPV) Vaccination Schedules in a University Setting — NCT00572832.
- Registry record last updated 2010-08-17; status last verified 2010-08.
- Results first posted 2010-02-25.
- 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.
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18. Record Summary
The registry describes a completed randomized, open-label, parallel-group trial sponsored by the University of Pittsburgh, with an enrollment of 200. It compared quadrivalent HPV vaccine schedules in which the third dose was given at 6 months or 12 months, after shared first and second doses at 0 and 2 months.
The primary endpoint was geometric mean antibody titer by virus type, measured one month after dose three. The stated objective was non-inferiority, using a log-scale contrast and a prespecified margin. Participants positive at baseline were excluded for the relevant type.
Primary outcome estimates and the numeric margin are not reported in the registry record. Safety entries list zero serious adverse events among 100 at risk in each group, along with 57 and 55 other adverse events, respectively. Further definitions and event details are not reported in the registry record.