Safety, Tolerability and Immunogenicity of HPV (Human Papilloma Virus) Vaccine in Healthy Females 9 to 15 Years of Age in India (V501-029): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability and Immunogenicity of HPV (Human Papilloma Virus) Vaccine in Healthy Females 9 to 15 Years of Age in India (V501-029) (NCT00380367), a na phase 3 study. The primary outcome is Percentage of Participants Who Seroconvert to Each HPV Serotype (Types 6, 11, 16, 18) at Month 7.

2. Clinical Question

3. Trial Design

This was a Phase 3, completed, single-group study identified as NCT00380367. The registry lists enrollment of 110 participants and describes the population as healthy females aged 9 to 15 years in India. The study began on 2007-05-03, and primary completion was recorded as 2008-02-04. The intervention was the quadrivalent HPV vaccine containing VLPs for HPV types 6, 11, 16, and 18.

Each participant was scheduled to receive 3 intramuscular injections: on Day 1, Month 2, and Month 6. The principal immunogenicity assessment was at Month 7, one month after dose 3. The primary endpoint concerns seroconversion separately for each of the four types. The registry also lists safety and tolerability as study aims. It reports 2 outcome measures, but the endpoint estimates and related analyses are not reported in the registry record.

The design has no concurrent control group: allocation is listed as not applicable, masking as none, and the model as single group. The study can therefore describe outcomes among participants who received the vaccine, but it cannot by itself establish how those outcomes compare with another intervention or with no vaccination. There is no randomized, like-for-like contrast in the record.

The immunogenicity endpoint uses a per-protocol population with eligibility conditions tied to protocol adherence, baseline serostatus, vaccination timing, and availability of a Month 7 sample. This makes the stated endpoint population narrower than all enrolled participants. The registry record does not report a statistical analysis plan, a sample-size justification, or details of interim analyses. Those design features should not be inferred from the Phase 3 label or from the enrollment count.

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: Open-label, single-arm, nonrandomized study. Females \>9 to 15 years of age, who have not had coitarche and did not plan on becoming sexually active through the course of the study, who did not have a feverish feeling within 24 hours prior to the first injection, were included in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-Protocol (P-P) immunogenicity population: All participants who were not general protocol violators, received all 3 vaccinations within acceptable day ranges, were sero-negative at Day 1 for the relevant HPV type(s), and had a Month 7 serum sample collected within an acceptable day range.

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 Percentage of Participants Who Seroconvert to Each HPV Serotype (Types 6, 11, 16, 18) at Month 7, measured over One month post-dose 3 (Month 7).

The primary endpoint is the percentage of participants who seroconverted to each of HPV types 6, 11, 16, and 18 at Month 7, one month after dose 3. It uses the quadrivalent HPV competitive Luminex Immunoassay, version 2.0, to detect antibodies to the corresponding VLPs. The registry describes type-specific seropositivity cutoffs: 20 mMU/mL for HPV 6, 16 mMU/mL for HPV 11, 20 mMU/mL for HPV 16, and 24 mMU/mL for HPV 18. Samples below the relevant cutoff were classified as serostatus negative; samples equal to or above it were classified as serostatus positive.

In general, an antibody-response endpoint can provide evidence that the immune system produced a measurable response to an antigen. A percentage expresses how common the defined response was among the participants included in the analysis. Here, the endpoint is assessed separately by HPV type, so a result for one type would not automatically describe the response to the others. The endpoint is not a direct measure of clinical disease prevention.

The stated analysis population includes participants who were seronegative at Day 1 for the relevant type or types and who had an eligible Month 7 sample, in addition to meeting protocol and vaccination-timing requirements. The registry record does not report the observed percentages or confidence intervals. Therefore, the endpoint definition is available, but the magnitude and precision of the Month 7 responses cannot be evaluated from the figures reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level for each HPV type: a participant is classified according to whether the relevant seroconversion criterion is met. In general, binary outcomes are often summarized as counts and percentages. The percentage gives the share of the analysis population with the specified response, while the count indicates how many participants contributed a response. The registry record states that the outcome is expressed as a percentage of participants, but it does not report the type-specific estimates or their underlying response counts.

What does the assay classification mean?

The registry describes use of a competitive Luminex Immunoassay, version 2.0, to detect antibodies to VLPs for HPV types 6, 11, 16, and 18. The assay uses a separate cutoff for each type. A measured value below the applicable cutoff is classified as serostatus negative; a value equal to or above the cutoff is classified as serostatus positive. The stated cutoffs are 20 mMU/mL for HPV 6, 16 mMU/mL for HPV 11, 20 mMU/mL for HPV 16, and 24 mMU/mL for HPV 18. These are assay classification thresholds, not estimates of the percentage of participants who responded.

The Month 7 endpoint is framed as seroconversion among participants who were seronegative at Day 1 for the relevant type or types. The registry description also specifies the per-protocol requirements, including all 3 vaccinations within acceptable day ranges and a Month 7 sample within an acceptable day range. The exact size of that analysis population is not reported in the registry record. The existence of an endpoint definition does not reveal the observed response rate.

How should a confidence interval be read?

In general, a confidence interval gives a range of values compatible with an estimate under the method’s assumptions and sampling variability. It communicates precision, not a guarantee that the true value lies within the interval. For a percentage, its width depends in part on the number of participants contributing data and the distribution of responses. A comparatively small analysis population may yield less precise estimates than a larger one, especially when responses are uncommon or common near the boundaries of the percentage scale. These are general statistical principles; the registry record does not report interval values or the analysis population size needed to assess the precision of this endpoint.

The record identifies 95% confidence intervals as the dispersion measure for the primary outcome. It does not report the exact interval construction method. Different interval procedures can behave differently, particularly when sample sizes are limited or percentages are near zero or one hundred. Without the reported estimates, counts, and method details, no further assessment of the interval calculation is possible.

Why does the analysis population matter?

The per-protocol immunogenicity population excludes participants who do not meet the stated conditions: no general protocol violations, all 3 vaccinations within acceptable day ranges, seronegativity at Day 1 for the relevant type or types, and a Month 7 sample collected within an acceptable day range. In general, this kind of population focuses the analysis on participants with the scheduled vaccine exposure and the required measurements. However, because it is defined by post-enrollment adherence and sample availability, its results may not describe every enrolled participant. The registry record does not report how many participants met each condition or why any participant might have been excluded.

Missing endpoint data can affect an estimate if participants without measurements differ from those with measurements. In general, the extent and direction of such effects depend on the amount and pattern of missingness and on the assumptions used to handle it. No missing-data method, imputation procedure, or sensitivity analysis is reported in the registry record. It is therefore not possible to determine how missing Month 7 measurements were treated.

What does the single-group design allow?

In general, a single-group study estimates outcomes within the participants studied rather than a contrast between randomized groups. It can describe the frequency of an endpoint or adverse events in that group, but without a concurrent comparator it cannot directly estimate a relative effect. The registry lists allocation as not applicable, masking as none, and a single-group model. This makes descriptive interpretation more appropriate than a comparative treatment-effect interpretation.

The registry record reports 2 outcome measures and 0 analyses. It does not state the statistical analysis plan, any adjustment for multiple endpoint tests, or interim-analysis procedures. The primary endpoint covers four HPV types, which creates multiple type-specific results to interpret. In general, multiplicity refers to the increased chance of at least one misleading finding when multiple hypotheses are tested; procedures for controlling it depend on the planned inferential goal. No such procedure is reported, so no adjustment or testing framework should be assumed.

The registry record also does not report a sample-size justification. General planning calculations can illustrate how sample size relates to a chosen effect, significance level, power, and allocation, but they are not observed power and do not establish the rationale used to design a completed study. No design rationale can be inferred from the enrollment figure alone.

10. Multiplicity, Missing Data and Analysis Populations

The primary immunogenicity outcome is assessed separately for HPV types 6, 11, 16, and 18. In general, making several statistical assessments raises a multiplicity question: the chance of at least one apparently notable result can increase as the number of tests grows. Whether and how to adjust depends on the study’s objectives and prespecified analysis plan. The registry record does not report a multiplicity strategy, a hierarchy among the type-specific outcomes, or whether confidence intervals or tests were adjusted. No particular procedure should be presumed.

The immunogenicity population is defined per protocol and requires baseline seronegativity for the relevant type or types, receipt of all 3 vaccinations within acceptable day ranges, no general protocol violations, and a Month 7 sample within an acceptable day range. The record does not report the number meeting those requirements. It also does not describe missing-data handling, reasons for missing samples, imputation, or sensitivity analyses. In general, excluding participants without endpoint measurements can affect interpretation if missingness is related to response or other participant characteristics; whether that occurred in this study is not reported in the registry record.

The registry lists 2 outcome measures and 0 analyses. It does not report a statistical analysis plan, interim analyses, or a sample-size justification. These omissions limit the ability to assess whether the reported endpoint definitions, analysis population, and any unreported tests followed prespecified methods. They do not establish that a particular method was or was not used; those details are simply not reported in the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety summary reports 108 participants at risk for serious adverse events, with 0 affected. For other adverse events, it reports 108 participants at risk and 63 affected. These are counts for the recorded categories; the registry record does not provide a time window, event-level descriptions for the other adverse events, or a definition of the categories in this entry. The list of top serious-event terms is empty. The death count is not reported in the registry record.

In general, a count of participants affected is not necessarily the same as a count of individual events: one participant could experience more than one event, depending on how the outcome is defined. The registry summary does not give enough detail to establish the event-counting rules or timing. It also does not report confidence intervals for these safety counts, so their statistical precision cannot be assessed from this record.

The 0 count describes the recorded number of participants affected by a serious adverse event in the safety summary; it should not be expanded into claims about risks outside the observed study group or observation period. Likewise, the count for other adverse events does not, by itself, indicate severity, causality, or comparison with another intervention. No concurrent control group is reported.

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

The registry record documents a study of quadrivalent HPV vaccine in healthy females aged 9 to 15 years in India, using 3 intramuscular injections on Day 1, Month 2, and Month 6. Its primary immunogenicity endpoint is the percentage who seroconverted to each of HPV types 6, 11, 16, and 18 at Month 7. The endpoint definition, assay approach, and per-protocol population are described. However, the seroconversion percentages and 95% confidence intervals are not reported in the registry record. The magnitude and precision of the antibody responses therefore cannot be stated from the recorded results.

The safety summary reports 0 participants affected by serious adverse events among 108 at risk and 63 participants affected by other adverse events among 108 at risk. The registry record does not give the safety observation period or details sufficient to interpret the other-adverse-event count by event type or timing. The death count is not reported in the registry record. These limitations mean the counts are descriptive, not a complete account of all safety questions.

The single-group design means there is no randomized comparison with another treatment or with no intervention. Results from such a design do not quantify a comparative effect. They also do not establish the extent to which an outcome would differ under another care condition. The study record should not be read as a direct estimate of clinical disease prevention: the primary endpoint is an antibody response, not a clinical disease endpoint.

In general, a trial result is most informative when the outcome estimate, uncertainty, population, and analysis methods can all be evaluated. Here, the registry record gives the endpoint and analysis-population definition but not the primary numerical results, the analysis-population size, or key analysis details such as missing-data handling and multiplicity procedures. The available information therefore supports a description of the design and the recorded safety counts, but not a complete quantitative judgment about the primary immunogenicity outcome.

13. Why This Trial Matters Statistically

This study illustrates the distinction between an endpoint definition and an endpoint result. The registry record gives a clear description of the Month 7 seroconversion question, the four HPV types assessed, the assay cutoffs, and the per-protocol conditions. Yet the observed percentages and confidence intervals are not reported in the registry record. Without those estimates, readers cannot assess the response magnitude or precision, even though the outcome itself is specified.

It also highlights why analysis populations matter. The per-protocol group is defined by vaccination timing, baseline serostatus, protocol adherence, and availability of a Month 7 sample. In general, those conditions determine whose data contribute to the endpoint and can make the analysis group different from the full enrolled cohort. The group size and participant flow are not reported, limiting assessment of how much the endpoint represents the enrolled population.

The single-group design is another important statistical feature. It supports description of outcomes within the vaccine group, but it does not create a randomized contrast. This distinction prevents a within-group percentage from being interpreted as a comparative treatment effect. The registry record also provides safety counts, which are useful descriptive information, while leaving the observation window and detailed event information unreported.

Finally, examining seroconversion across four types raises general questions about multiplicity and precision. The record does not state whether the type-specific assessments were adjusted or how the sample size was justified. These omissions do not imply a particular analytical choice, but they restrict independent evaluation of the inferential framework. The case demonstrates why design, endpoint definition, analysis population, numerical estimates, and uncertainty all need to be considered together.

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 available registry entries leave important questions unanswered for this specific study. Although the primary endpoint is described for each of HPV types 6, 11, 16, and 18, the observed seroconversion percentages and 95% confidence intervals are not reported in the registry record. The number of participants in the per-protocol immunogenicity population is also not reported. As a result, neither the size nor the precision of the primary endpoint estimates can be evaluated.

The trial is single group, with no randomized comparator. That prevents a direct estimate of differences between the vaccine regimen and another intervention or control condition. The record does not report masking, which is listed as none, and does not provide further operational details that would clarify how outcome assessment was conducted. It does not report a statistical analysis plan, multiplicity procedure, missing-data method, or interim-analysis details.

The per-protocol population depends on adherence, baseline serostatus, and availability of a Month 7 sample. The registry record does not report how many participants were excluded at each step, the reasons for missing samples, or whether any sensitivity analyses addressed these issues. Those omissions limit assessment of possible selection or missing-data effects; they do not establish that such effects occurred.

For safety, the record provides counts of participants affected but does not report the observation period, detailed event terms for other adverse events, or the death count. The reported safety counts therefore cannot be placed in a fuller time-based or event-specific context from the registry entry alone. A sample-size justification is also not reported, so enrollment cannot be interpreted as evidence that the study was sized for a particular precision or statistical objective.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability and Immunogenicity of HPV (Human Papilloma Virus) Vaccine in Healthy Females 9 to 15 Years of Age in India (V501-029) — NCT00380367.
• Registry record last updated 2023-05-31; status last verified 2023-05.
• Results first posted 2009-04-14.
• 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

NCT00380367 is a completed Phase 3, single-group study of quadrivalent HPV vaccine in healthy females aged 9 to 15 years in India. The registry lists enrollment of 110 participants, a start date of 2007-05-03, and primary completion on 2008-02-04. Participants received 3 intramuscular injections on Day 1, Month 2, and Month 6.

The primary outcome concerns seroconversion to HPV types 6, 11, 16, and 18 at Month 7. The record describes assay cutoffs and a per-protocol immunogenicity population, but the observed percentages, confidence intervals, and analysis-population size are not reported in the registry record. Safety counts include 0 participants with serious adverse events and 63 with other adverse events among 108 at risk in each category. The death count is not reported in the registry record. No comparator group is listed.