Study of an Investigational Vaccine in Pre-Adolescents and Adolescents (Gardasil)(V501-016): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of an Investigational Vaccine in Pre-Adolescents and Adolescents (Gardasil)(V501-016) (NCT00092495), a randomized phase 3 study. The primary outcome is Number of Subjects Who Seroconverted for HPV 6 by Week 4 Postdose 3.

2. Clinical Question

The study’s stated purpose was to assess immune response and tolerability in pre-adolescents and adolescents. Its primary measure concerns an antibody response to HPV 6, not a count of cervical cancer or genital warts. The registry lists those conditions, but the primary endpoint described in the record is immunogenicity. It does not report a primary-outcome estimate, a comparison of formulations on this endpoint, or a confidence interval. Consequently, the clinical question can be described from the endpoint definition, but the registry record does not establish the magnitude or precision of the observed response.

3. Trial Design

This was a phase 3 randomized, double-masked, parallel-group study of Gardasil formulations. The registry records enrollment of 3055 and describes the study as completed. The listed study start is 2002-12 and the primary completion is 2004-09. The sponsor was Merck Sharp & Dohme LLC.

The intervention was a quadrivalent HPV vaccine directed at types 6, 11, 16, and 18. The registry identifies four formulation arms: 100%, 60%, 40%, and 20%. These are formulation labels in the record; no further details about their composition or administration are reported. The registry does not report the allocation ratio, the randomization procedure, or which people involved in the trial were masked. The parallel-group label indicates the study’s design classification, but the record does not provide additional operational details.

The primary endpoint is the number of participants who seroconverted for HPV 6 by Week 4 Postdose 3, identified in the record as Month 7. Its analysis population is restricted to the 100% dosage and to participants meeting the stated per-protocol conditions. The registry also lists 16 outcome measures and 40 analyses, indicating that the study record covers outcomes and analyses beyond the primary endpoint. It does not provide enough detail to describe the full analysis plan or to identify the methods used for every outcome.

The study’s stated aims were to assess immune response and tolerability and to determine end-expiry specifications for the vaccine. The primary endpoint definition addresses immune response. The registry entries do not describe how the end-expiry aim was assessed, nor do they give a separate result for it. Although the record is marked completed, completion status alone does not provide the outcome estimates or the degree of uncertainty around them.

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.

Base Study Vaccination Period

Reasons for not completing this period:

Base Study Follow-up Period

Reasons for not completing this period:

Extension Study

Analysis population for the primary outcome, as defined in the registry: Per-protocol population: subjects must have no major protocol violations, must be seronegative at baseline to the relevant HPV type, and must have post-vaccination data. Restricted to subjects receiving 100% dosage.

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 Number of Subjects Who Seroconverted for HPV 6 by Week 4 Postdose 3, measured over Week 4 Postdose 3 (Month 7).

The primary endpoint is a count: the number of participants who seroconverted for HPV 6 by Week 4 Postdose 3, described as Month 7. Seroconversion is defined as a change from seronegative at baseline to seropositive after vaccination. The record defines seropositivity as an anti-HPV 6 titer of at least 20 mMU/mL. The endpoint therefore combines a laboratory threshold with a change in status over time.

This measure is used to assess immunogenicity: whether participants developed the specified antibody response. It is not a direct measure of cervical cancer, genital warts, or another clinical disease outcome. A count describes how many participants met the stated criterion in the analysis population; by itself, it does not describe the size of an effect relative to another formulation or the precision of that estimate.

The endpoint applies to the per-protocol population receiving the 100% dosage. The record says participants had to have no major protocol violations, be seronegative at baseline for the relevant HPV type, and have post-vaccination data. These restrictions define who contributes to the primary analysis and distinguish that group from the overall enrollment. The registry record gives the endpoint definition and timeframe but does not report the observed count or a corresponding estimate of uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a number of participants meeting a binary response definition: seroconversion for HPV 6 by Week 4 Postdose 3. Each eligible participant either meets the stated definition or does not, and the primary measure is the resulting count in the specified analysis population. The registry record does not report the observed count, an estimate of uncertainty, or a statistical test for this endpoint.

What does the endpoint definition do?

It sets a laboratory threshold and a baseline-to-follow-up condition. A participant must be seronegative at baseline and reach the stated seropositivity threshold after vaccination to meet the definition. This turns antibody measurements into a categorical outcome. Such a definition can make the response criterion explicit, but it does not show how far above or below the threshold an individual’s antibody level lies. The registry does not report individual titer distributions or a continuous-titer primary analysis.

What does the per-protocol restriction mean?

The primary population excludes participants who do not meet the stated conditions: no major protocol violations, baseline seronegativity for the relevant HPV type, and available post-vaccination data. In general, a per-protocol analysis focuses on participants meeting specified study requirements. It can differ from an analysis based on everyone randomized, particularly when eligibility for analysis depends on events after randomization. The registry record does not report the number excluded from the primary population, the reasons for exclusion, or an analysis of all randomized participants for this endpoint.

How should counts and uncertainty be understood?

General statistical explanation: an event count gives the number meeting a definition, while a confidence interval describes the range of values reasonably compatible with the data under the interval’s assumptions. A count without an interval gives no direct measure of precision. For a comparison, the interpretation also depends on the contrast being estimated, the analysis population, and the statistical method. The registry record does not report a confidence interval or comparison for the primary endpoint, so neither can be reconstructed from the endpoint definition alone.

What can be inferred from the design labels?

Randomization is intended, in general, to support comparisons by allocating participants to study groups through a chance-based process. Double masking is a design feature intended to limit the influence of knowledge of assignment. The registry identifies the trial as randomized and double-masked, but does not report the randomization procedure, allocation ratio, masking details, or methods for preserving masking. These labels do not substitute for outcome estimates or establish that all possible sources of bias were prevented.

What does the planning approach describe?

The registry’s planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. This is a planning framework, not a report of the trial’s original design justification. The record does not report the trial’s own sample-size justification or the planning results in the registry record for this account. A planning sample size is not observed power; it describes a hypothetical design under stated assumptions and does not measure how much power the completed study actually had.

General statistical explanation: power calculations depend on the effect assumed for planning, variability or event frequency, the significance criterion, allocation, and the analysis method. If the assumed effect is based on an observed estimate, that estimate may itself be uncertain. Over-dispersion matters when count variability is greater than a model assumes: ignoring it can make standard errors too small and intervals too narrow. The registry identifies the primary measure as a count but does not report a model or dispersion estimate for that endpoint. No claim about over-dispersion or a specific count model can therefore be made.

What analysis details remain unclear?

The registry lists 40 analyses across 16 outcome measures, but it does not report a complete statistical analysis plan in the record. The test used for the primary endpoint, any adjustment for covariates, the handling of multiplicity, and the treatment of missing data are not reported in the registry record. These details matter because they determine how estimates and uncertainty are calculated and how several analyses are interpreted. The available design and endpoint descriptions are not enough to infer those choices.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures and 40 analyses. Multiple outcomes and analyses raise a general multiplicity issue: when many statistical questions are examined, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of the tests. The registry record does not report whether any multiplicity adjustment was planned or used, which outcomes were treated as confirmatory, or how the analyses were prioritized. No conclusion about the control of false-positive findings can be drawn from the count of listed outcomes and analyses alone.

The primary endpoint is defined for a per-protocol population receiving the 100% dosage. Participants must have no major protocol violations, be seronegative at baseline for the relevant HPV type, and have post-vaccination data. The record does not report the numbers meeting or failing these criteria, the reasons for missing post-vaccination data, or whether any sensitivity analyses addressed missingness. A missing-data strategy for the primary endpoint is not reported in the registry record.

The record also does not report whether an intention-to-treat analysis was performed for this endpoint or how participants were handled across analyses. The sample-size planning assumptions do not establish how the completed trial’s primary endpoint was analyzed. Without the full analysis plan and outcome results, the primary analysis population can be described, but its relationship to other populations and the handling of missing outcomes cannot be assessed.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: adverse drug reaction (0.2%), convulsion (0.2%), failed trial of labour (0.2%), hyperemesis gravidarum (0.2%), anorexia nervosa (0.2%).

The registry reports serious adverse-event and other adverse-event counts by formulation group. For serious adverse events, the recorded affected counts and at-risk counts are 5 of 496 for the 20% formulation, 2 of 509 for the 40% formulation, 1 of 500 for the 60% formulation, and 4 of 1498 for the 100% formulation. For other adverse events, the corresponding figures are 434 of 496, 426 of 509, 431 of 500, and 1276 of 1498.

These figures are descriptive. They should be read within each group and not as a direct comparison of risk: group sizes differ, and the record does not provide comparative estimates, confidence intervals, or a statistical test for these counts. The adverse-event observation period and the detailed event-collection procedures are not reported in the registry record. The categories should not be treated as interchangeable; serious adverse events and other adverse events are separately recorded.

The record lists Adverse drug reaction, Convulsion, Failed trial of labour, Hyperemesis gravidarum, Anorexia nervosa, and Tachycardia foetal among the serious-event terms, with 0.2% shown for each. The record does not make clear how those term percentages relate to the formulation groups or provide term-specific denominators. Death counts are not reported in the registry record. These descriptive figures alone do not establish a causal relationship between vaccination and an event.

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

The central result available from this record is a definition of the primary outcome, not its observed value. The study planned to count HPV 6 seroconversions by Week 4 Postdose 3, or Month 7, among per-protocol participants receiving the 100% dosage. The record explains the baseline and antibody-threshold criteria but does not report the resulting count, a proportion, a comparison, or an interval describing precision.

That distinction matters because an endpoint definition tells readers what would count as a response, whereas an outcome estimate tells readers how often that response was observed. A comparator estimate and a statistical contrast would be needed to describe differences between formulation groups. The primary endpoint’s stated population is restricted to the 100% dosage, and the registry does not report a primary-outcome contrast with the other formulations.

The endpoint measures immunogenicity, not a clinical disease outcome. The study title and condition list refer to cervical cancer and genital warts, but the primary measure described in the record is antibody seroconversion for HPV 6. The endpoint definition alone cannot establish the effect of vaccination on those conditions. The study purpose also includes tolerability, and the record gives adverse-event counts, but those counts are not accompanied by comparative uncertainty estimates or a reported observation period.

The record identifies the study as randomized, double-masked, parallel-group, and phase 3, and it marks the study completed. Those design features describe how the trial was classified; they do not supply the missing outcome estimates. The posted information supports understanding which response was assessed, in whom, and at what stated time. It does not establish the magnitude or precision of that response, whether formulation groups differed, or how the results relate to clinical disease outcomes.

13. Why This Trial Matters Statistically

This study is statistically notable for the way its primary outcome is defined and restricted. It uses a binary immunogenicity criterion based on both baseline status and a follow-up antibody threshold, then reports the intended measure as a count of participants meeting that criterion. This makes the endpoint’s interpretation dependent on the specified threshold, timing, and analysis population. Readers can identify those elements in the registry record even though the observed primary result is not reported there.

The four listed formulation groups also make the choice of comparison important. The primary endpoint is restricted to the 100% dosage, and the registry does not identify a primary-outcome contrast with another formulation. A count within a group and a comparison between groups answer different questions. The distinction is especially important when the study record includes numerous outcome measures and analyses: the registry lists 16 outcomes and 40 analyses, but does not report the multiplicity strategy or complete analysis plan.

The safety record provides affected counts alongside at-risk counts for serious and other adverse events in each formulation group. These are useful descriptive information, but they do not by themselves quantify comparative uncertainty. The absence of reported comparative estimates, confidence intervals, and an adverse-event observation period limits interpretation of between-group differences.

More broadly, the record illustrates why trial design labels and endpoint definitions are not substitutes for results. Randomization and masking are important design features, while the estimate, its precision, the analysis population, and the planned comparisons determine what can be concluded statistically. Here, the design and endpoint are described, but the primary outcome estimate and several analysis details are not reported in the registry record.

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 registry record does not report the observed primary endpoint count, an uncertainty interval, or a statistical comparison. This prevents assessment of the magnitude and precision of the HPV 6 seroconversion result from the record. The primary analysis is also restricted to participants receiving the 100% dosage, so the endpoint definition does not itself provide a comparison across the 100%, 60%, 40%, and 20% formulations.

The per-protocol criteria are stated, but the record does not report how many participants met those criteria or how many were excluded and why. It does not describe missing-data handling or provide an intention-to-treat result for the primary endpoint. The randomization and double-masking labels are recorded, but procedural details, allocation ratio, and masking arrangements are not reported.

The record lists 16 outcome measures and 40 analyses, while the multiplicity approach and complete statistical analysis plan are not reported. That makes it difficult to determine which analyses were prespecified as primary or how multiple analyses were handled. The registry’s description of planning assumptions does not establish the trial’s own sample-size justification, and the planning assumptions are not a substitute for outcome estimates.

For safety, the record gives affected and at-risk counts, but does not report the adverse-event observation period, comparative uncertainty estimates, or the method used to assess differences between groups. The serious-event terms are listed with percentages without enough detail to assign them to particular formulation groups. Death counts are not reported in the registry record. Finally, the primary endpoint is an antibody-response measure, not a direct clinical outcome for cervical cancer or genital warts; no clinical disease outcome result is reported in the registry record for this account.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of an Investigational Vaccine in Pre-Adolescents and Adolescents (Gardasil)(V501-016) — NCT00092495.
• Registry record last updated 2015-01-13; status last verified 2014-12.
• Results first posted 2010-03-08.
• 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

NCT00092495 is a completed phase 3 randomized, double-masked, parallel-group study sponsored by Merck Sharp & Dohme LLC. The registry lists enrollment of 3055, a study start of 2002-12, and primary completion in 2004-09. Its stated purpose was to assess immune response and tolerability for Gardasil in pre-adolescents and adolescents and to determine end-expiry specifications.

The vaccine targeted HPV types 6, 11, 16, and 18, with 100%, 60%, 40%, and 20% formulation groups listed. The primary endpoint was the number of participants seroconverting for HPV 6 by Week 4 Postdose 3, identified as Month 7, in a restricted per-protocol population receiving the 100% dosage. The registry defines seropositivity using an anti-HPV 6 titer threshold of at least 20 mMU/mL. It does not report the primary endpoint result or a comparative estimate. Adverse-event counts are recorded by formulation group, while the adverse-event observation period and the full analysis plan are not reported in the registry record.