A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501, qHPV) in Mid-Adult Women (V501-019): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501, qHPV) in Mid-Adult Women (V501-019) (NCT00090220), a randomized phase 3 study. The primary outcome is Incidence Rate of HPV 6/11/16/18 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer.

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, double-masked, parallel-group study of quadrivalent HPV vaccine versus placebo. The registry lists enrollment as 3819 and the status as completed. The study start date was 2004-06-16, and primary completion was 2009-05-21. Merck Sharp & Dohme LLC is listed as the sponsor.

The base-study vaccine schedule was Day 1, Month 2, and Month 6. Participants assigned to placebo received blinded placebo on the same schedule and were eligible for open-label qHPV vaccination in Extension 1. The registry’s brief description says the study assessed safety, immunogenicity, efficacy, and long-term effectiveness. The primary outcome reported for this analysis is an incidence rate, not an immune-response measure.

The primary analysis was not described as covering every enrolled participant. Its stated population was restricted to participants with no major protocol violations who received all three vaccinations, met the specified serology and PCR criteria for the relevant HPV type, and provided follow-up data after Month 7. The registry reports 1601 in the qHPV arm and 1599 in the placebo arm for the posted primary outcome. The difference between these analysis counts and the overall enrollment is not explained in the registry record, so it should not be interpreted as a measure of withdrawal or missingness without further information.

The placebo group’s eligibility for open-label vaccination in Extension 1 is relevant when reading longer-term outcomes. The primary endpoint covers follow-up up to 48 months after the first base-study vaccine dose; the listed extension outcomes include later follow-up periods and are separate from this primary comparison. Details of the original design assumptions, including the planned sample-size justification and any planned interim analyses, are not reported in the registry record.

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 1 (EXT1)

Reasons for not completing this period:

Long-term Follow-up (EXT2)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants who had no major protocol violations, received all 3 vaccinations, were seronegative to the relevant HPV type at Day 1 and PCR negative to the relevant HPV type Day 1 through Month 7, and provided follow-up data after Month 7

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.

Population: All randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Incidence Rate of HPV 6/11/16/18 Related Persistent Infection, Genital Warts, VIN, VaIN, Vulvar Cancer, Vaginal Cancer, Cervical Dysplasia, Cervical AIS, and Cervical Cancer, measured over Up to 48 months (4 years) after the first dose of qHPV vaccine in the Base Study.

The primary endpoint is the incidence rate of persistent infection or specified HPV-related disease associated with HPV types 6, 11, 16, and 18. The listed events include genital warts; VIN and VaIN; vulvar, vaginal, and cervical cancer; cervical dysplasia; and cervical AIS. The registry states that the four HPV types were determined by PCR testing. VIN means vulvar intraepithelial neoplasia, VaIN means vaginal intraepithelial neoplasia, and AIS means adenocarcinoma in situ.

The endpoint is expressed as incidence per 100 person-years. In general, an incidence rate relates the number of events to the amount of time participants contribute under observation. That makes it useful when follow-up time may vary between participants, rather than treating every participant as if they contributed the same observation time. It is an event-rate measure, not a direct statement about the proportion of participants who experienced an event.

The analysis timeframe was up to 48 months (4 years) after the first qHPV dose in the base study. The analysis population was restricted by vaccination, protocol adherence, serology, PCR results, and availability of follow-up data after Month 7. Consequently, the endpoint describes the comparison in that defined population and timeframe; it does not, on its own, describe every participant enrolled or every HPV type.

7. Results Posted in the Registry

• qHPV in Base Study: 0.20 versus 1.70 (Incidence per 100 person-years) on control; rate ratio 0.12 (95% CI 0.07–0.21, approximate, Poisson model); p ≈ <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is an event rate, with units of incidence per 100 person-years. The posted comparison is between qHPV in the base study and placebo in the base study. The trial’s randomization and double masking are features of its design; they do not, by themselves, specify the statistical model or every analysis decision. The registry record does not report the method used for the sponsor’s primary analysis.

What does an incidence rate represent?

In general, an incidence rate expresses the number of events relative to accumulated time at risk. Participants may contribute different amounts of observation time, so a rate uses exposure time rather than relying only on the number of people assigned to a group. An incidence rate is not the same quantity as the fraction of participants who ever experienced an event. It can also count events rather than only classifying each participant as having or not having an event, depending on the endpoint and analysis definition; the registry record does not give additional detail about event counting for this endpoint.

The registry gives the two arm rates as 0.2 and 1.7 per 100 person-years and reports exposure-related event inputs of 12.81 and 108.7. These are the summaries used for the unadjusted re-calculation. They should not be converted into participant percentages or treated as raw participant counts. The primary endpoint combines persistent infection and multiple disease outcomes associated with the specified HPV types, so its overall rate does not identify the contribution of each component.

What does the rate-ratio re-calculation add?

In general, a rate ratio compares the event rate in one group with the rate in another. A value below the no-effect reference corresponds to a lower rate in the numerator group; a value above it corresponds to a higher rate. The posted re-calculation is a simple, unadjusted comparison based on the summarized rates and exposure information. It uses a Poisson approach, as identified in the registry results. The registry also gives an unadjusted p-value of p < 0.001. This calculation does not account for covariates unless such adjustment is specified; no adjustment is reported for this re-calculation.

For count outcomes, a Poisson model is often used to relate event counts to exposure time. In general, the model’s uncertainty depends on assumptions about the event process and dispersion. Over-dispersion means that the event counts vary more than the model assumes; if it is present and not accommodated, standard errors and confidence intervals may not reflect the actual variability. The registry does not report a dispersion estimate or describe an adjustment for over-dispersion. The re-calculation therefore should be understood as a simple statistical check based on the posted summaries, not as a full reconstruction of the sponsor’s analysis.

How does the sponsor’s reported measure differ?

The sponsor’s posted result is a percent relative risk reduction of 88.7, with a 95% confidence interval from 78.1 to 94.8. The re-calculation is expressed as a rate ratio. Although these measures are related in their direction of comparison, they are not identical in form or necessarily identical in analysis population, assumptions, or method. The registry record does not report the sponsor’s method, so it is not possible to determine from this record alone how the sponsor’s estimate was produced or exactly how its analysis relates to the unadjusted re-calculation.

When the registry flags a discrepancy between a sponsor analysis and a re-calculation, the sponsor’s own analysis takes precedence. The discrepancy flag for this result is false. That does not make the re-calculation the sponsor’s analysis: the sponsor’s separately posted estimate remains the reported sponsor result, while the re-calculation is an additional, unadjusted summary-based analysis. The lack of a discrepancy flag means that the record does not identify a discrepancy; it does not supply missing details about the sponsor’s statistical method.

Why do the analysis criteria matter?

The endpoint analysis population was restricted to participants with no major protocol violations, all three vaccinations, type-specific seronegativity at Day 1, type-specific PCR negativity from Day 1 through Month 7, and follow-up data after Month 7. In general, such eligibility rules define which participants contribute to a particular analysis and can affect how broadly its estimate applies. Here, the rules are part of the registry’s stated endpoint definition. They should be considered when interpreting the arm counts and effect estimates.

The record does not report how missing observations were handled, whether any imputation was used, or whether alternative analysis populations were assessed. Nor does it describe the sponsor’s model, covariate adjustments, or model diagnostics. Those items are not recoverable from the posted endpoint summary and should not be assumed from the trial’s randomized, double-masked design alone.

What is not established by the posted analysis?

The outcome is a combined incidence endpoint over up to 48 months after the first dose. It is not a separate analysis of each listed disease, a direct measure of immune response, or a result for the later extension periods. The registry lists additional secondary outcomes, including outcomes for other HPV types and later follow-up windows, but their detailed estimates are not included in the primary comparison. The record reports 41 outcome measures and 3 analyses, but does not describe a multiplicity strategy for interpreting the collection of results. General statistical practice recognizes that examining multiple endpoints can increase the chance of at least one apparently notable finding; how that issue was handled in this study is not reported in the registry record.

10. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimated effect. The sponsor-reported percent relative risk reduction is 88.7, with a 95% confidence interval from 78.1 to 94.8. The interval communicates a range of values compatible with the sponsor’s analysis under its statistical assumptions. It is an interval for the relative-reduction measure, not for either arm’s incidence rate, and it should not be read as a range containing a specified proportion of individual participant outcomes.

The registry also includes a confidence interval for the unadjusted rate-ratio re-calculation. The interval lies below the no-effect reference for a ratio, consistent with the direction of the posted arm rates. The re-calculation uses a Poisson approach and is not reported as confidence-interval-based for the sponsor analysis. Since the two results use different effect scales and the sponsor’s method is not reported in the registry record, their intervals should not be treated as if they were generated by the same analysis.

The primary endpoint is a combined event-rate outcome, and the analysis population is restricted by protocol, vaccination, serology, PCR, and follow-up criteria. The confidence intervals quantify statistical uncertainty under the relevant analysis; they do not capture every source of uncertainty, such as differences in how an analysis population was defined or limitations in reporting. The registry record does not provide confidence intervals for the individual arm rates or separate intervals for each component of the combined endpoint.

The sponsor’s interval is bounded away from no relative reduction, while the re-calculated ratio interval is reported as below its null reference. This supports a clear direction in the posted comparisons, but interval width still matters: the range represents uncertainty about the effect’s magnitude. Statistical precision should be considered alongside the endpoint definition, the selected analysis population, and the absence of reported details about the sponsor’s method and missing-data handling.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effect, not the trial’s original design calculation. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the listed fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

For this rate outcome, the displayed planning figures are participants per arm. The rows represent planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. At 100% of the observed effect, the illustration gives 240 participants per arm for 80% power and 321 participants per arm for 90% power. At 75% of the observed effect, it gives 268 participants per arm for 80% power and 359 participants per arm for 90% power. At 50% of the observed effect, it gives 395 participants per arm for 80% power and 529 participants per arm for 90% power.

In plain terms, the 80% power column gives the estimated number of participants per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one. The 90% power column applies the same interpretation at a higher target probability. Smaller effects require more participants in these illustrations, because distinguishing a less pronounced effect from random variation generally requires more information. These planning values are not observed power and do not describe the power achieved by the completed trial.

The figures are hypothetical planning scenarios, not observed group sizes or a restatement of the trial enrollment. They depend on the assumptions and on using the observed effect, or a specified fraction of it, as the effect to detect. They should not be interpreted as a recommendation for a future study without a separate design assessment.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, λ₀ and λ₁ are event rates per patient-year, and T is follow-up per participant in years. This assumes Poisson counts and equal follow-up.

Worked calculation for this trial

1. Control rate λ₀ = 0.0170; treatment rate λ₁ = 0.0020 events per patient-year; follow-up T = 4.00 years.
2. n = (1.96 + 0.842)² × (1/0.0170 + 1/0.0020) / (4.00 × [ln(0.118)]²) = 239.4, rounded up to 240 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
lambda0 <- 0.017                      # control rate, events per patient-year
lambda1 <- 0.002                      # treatment rate
tt      <- 4                       # follow-up per participant, years
n_per_arm <- function(power, frac = 1) {
  l1 <- lambda0 * (lambda1 / lambda0)^frac   # smaller effect = fraction of the observed log rate ratio
  ceiling(round((z_a + qnorm(power))^2 * (1 / lambda0 + 1 / l1) / (tt * log(l1 / lambda0)^2), 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Simulation 1: Poisson counts. Simulation 2: over-dispersed counts (variance = 1.5 x mean), analysed with the matching variance.
set.seed(90220)
n    <- n_per_arm(0.80)
reps <- 20000
m0 <- lambda0 * n * tt; m1 <- lambda1 * n * tt
x0 <- rpois(reps, m0); x1 <- rpois(reps, m1)
z  <- log(x1 / x0) / sqrt(1 / x0 + 1 / x1)
cat(sprintf("Simulated power, Poisson counts, n = %s per arm: %.3f\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE)))
phi <- 1.5
y0 <- rnbinom(reps, mu = m0, size = m0 / (phi - 1)); y1 <- rnbinom(reps, mu = m1, size = m1 / (phi - 1))
z2 <- log(y1 / y0) / sqrt(phi * (1 / y0 + 1 / y1))
cat(sprintf("Simulated power, over-dispersed counts (phi = 1.5), same n: %.3f\n", mean(abs(z2) > z_a, na.rm = TRUE)))

Output from running the code

100% of observed effect: n per arm = 240 (80% power), 321 (90% power)
 75% of observed effect: n per arm = 268 (80% power), 359 (90% power)
 50% of observed effect: n per arm = 395 (80% power), 529 (90% power)
Simulated power, Poisson counts, n = 240 per arm: 0.938
Simulated power, over-dispersed counts (phi = 1.5), same n: 0.691

The first simulation draws Poisson counts and should land close to the target power. The second allows extra variability (variance 1.5 times the mean, a purely illustrative value), which lowers the power at the same sample size, so rate trials usually need more participants than the Poisson formula suggests.

13. Analyses Reported by the Sponsor

The registry reports the sponsor’s own analysis as a percent relative risk reduction of 88.7, with a 95% confidence interval from 78.1 to 94.8. The statistical method for that analysis is not reported in the registry record. Separately, the posted re-calculation uses the arm event-rate summaries and exposure information to produce an unadjusted rate-ratio comparison with a Poisson approach and p < 0.001.

These are related but distinct summaries: one is the sponsor-reported relative risk reduction, and the other is a re-calculation on the rate-ratio scale. The record does not give enough methodological detail to establish whether they use precisely the same estimand or analysis choices. The discrepancy flag is false, so the record does not identify a discrepancy between them. The re-calculation should still not be presented as if it were the sponsor’s method or result. The sponsor’s posted analysis remains the sponsor result, and the re-calculation is best read as a simple check based on posted summary statistics.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists 41 outcome measures and 3 analyses, including the primary endpoint and secondary outcomes. The listed secondary outcomes span HPV-related persistent infection and disease, cumulative incidence and incidence-rate assessments of HPV 6/11-related condyloma over different follow-up windows, and outcomes related to HPV types 31/33/35/52/58. The primary comparison described in this analysis is one component of a broader outcome record.

When several outcomes or analyses are considered, multiplicity is a statistical issue: repeated testing can raise the chance of finding at least one apparently unusual result even if there is no underlying effect. A prespecified approach might control or otherwise address this issue, but the multiplicity strategy is not reported in the registry record. The unadjusted p-value should therefore be understood as belonging to the posted comparison, not as evidence that any broader family of tests was adjusted.

The primary endpoint analysis population is clearly restricted in the record: participants had to have no major protocol violations, receive all three vaccinations, meet the relevant serology and PCR criteria, and provide follow-up data after Month 7. The record does not state how missing observations were treated, whether data were imputed, or whether sensitivity analyses addressed missingness. It also does not report an intention-to-treat analysis for this endpoint or explain how the endpoint population relates to other analysis populations.

The posted arm sizes for the primary outcome are 1601 in the qHPV group and 1599 in the placebo group, while overall enrollment is listed as 3819. These figures refer to different descriptions in the record; the record does not explain the flow from enrollment to the endpoint population. No inference about reasons for exclusion, withdrawal, or missing follow-up should be drawn from those values alone.

The registry record does not report the sponsor’s statistical method, covariate adjustments, interim-analysis plan, or a detailed statistical analysis plan for this endpoint. Their absence limits assessment of whether the posted result followed a prespecified strategy and how the primary finding fits into the full set of outcomes. It does not establish that such plans or analyses were absent; it means they are not reported in the registry record.

15. 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: cardio-respiratory arrest (0.2%), overdose (0.2%), neonatal aspiration (0.1%), pelvic inflammatory disease (0.1%), vomiting (0.1%).

The registry’s base-study safety groups list serious adverse events for 15 participants among 1890 at risk in the qHPV vaccine group, and 17 among 1888 at risk in the placebo group. These are counts within the recorded safety groups, not rates adjusted for follow-up time. The record also lists other adverse events for 1565 among 1890 at risk in the qHPV group and 1390 among 1888 at risk in the placebo group. Those other adverse-event counts should not be conflated with serious adverse events.

The record lists separate safety groups for qHPV vaccine in EXT1 and long-term follow-up in EXT2. EXT1 lists 6 serious adverse events among 1327 at risk and 2 other adverse events among 1327 at risk. EXT2 lists 6 serious adverse events among 1336 at risk and 0 other adverse events among 1336 at risk. These extension groups represent different periods and group descriptions from the base-study comparison, so their counts should not be combined with the base-study groups or treated as a direct randomized comparison.

The most frequent serious-event terms listed include cardio-respiratory arrest and overdose at 0.2% each, and neonatal aspiration, pelvic inflammatory disease, vomiting, and coronary artery insufficiency at 0.1% each. Death counts are not reported in the registry record. These summaries describe recorded events and do not by themselves establish causation or provide a complete account of safety.

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

The posted results show a lower primary-outcome incidence rate in the qHPV group than in the placebo group: 0.2 versus 1.7 per 100 person-years in the specified analysis population. The sponsor reports a relative risk reduction of 88.7, with a 95% confidence interval from 78.1 to 94.8. The unadjusted re-calculation reports p < 0.001. Together, these describe the direction and statistical uncertainty of the reported comparison for the combined primary endpoint.

The endpoint combines persistent infection and several HPV-related diseases associated with types 6, 11, 16, and 18. It does not show how each component contributed to the combined result. Nor does it give a separate primary comparison for each HPV type. The registry lists additional secondary outcomes, but their names alone do not supply their results. The primary timeframe is up to 48 months after the first qHPV dose in the base study; the result should not be extended to the later follow-up periods without examining their separate analyses.

The analysis is restricted to participants meeting the stated vaccination, protocol, serology, PCR, and follow-up criteria. It is not automatically a result for every enrolled participant or a direct estimate for people outside the study population. The registry record does not report how missing follow-up data were handled or provide the sponsor’s statistical method, limiting assessment of those aspects.

Statistical significance does not by itself establish the importance of an effect, the balance of benefits and harms, or an outcome for an individual. These results describe a trial comparison under its recorded conditions; they are not medical advice. They do not establish an effect on outcomes beyond those measured, and they should not be interpreted as a guarantee about any individual participant’s experience.

17. Why This Trial Matters Statistically

This trial illustrates why the scale of an outcome matters. The primary result is an incidence rate per 100 person-years, rather than a simple percentage of participants with an event. Reading the rate as a participant percentage would change its meaning. The distinction is important whenever follow-up time contributes to the analysis and the outcome is reported relative to exposure time.

The trial also shows how a registry can contain more than one statistical representation of a result. The sponsor reports a percent relative risk reduction with a confidence interval, while the posted summary-based re-calculation is a rate-ratio analysis. These measures offer related views of the comparison but should not be silently substituted for one another. Keeping the reported sponsor estimate distinct from a re-calculation helps readers understand both the primary report and the assumptions behind a secondary check.

Eligibility criteria are another essential part of statistical interpretation. The primary endpoint population is defined by protocol adherence, vaccination completion, type-specific serology and PCR results, and follow-up availability. Those rules tell readers whom the result describes. Without reported missing-data methods or a clear account of how this endpoint population relates to enrollment, the result should not be generalized beyond its stated analysis population without qualification.

Finally, the record lists many outcomes and analyses, while the approach to multiplicity is not reported. A p-value for one comparison must be read in that context. This is a useful example of why effect estimates, confidence intervals, analysis populations, endpoint definitions, and reporting gaps all matter alongside a test result.

18. 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.
• Rate comparisons use a Poisson approximation unless the sponsor posted confidence limits; real event counts are often over-dispersed.

The primary endpoint is a composite of persistent infection and several disease outcomes associated with HPV types 6, 11, 16, and 18. A single combined rate does not reveal the pattern for each component, and the registry record does not give separate primary-outcome estimates for those components. It also does not report the frequency or severity distribution for each component within this endpoint.

The endpoint analysis applies to a selected population: participants had to receive all three vaccinations, have no major protocol violations, meet type-specific serology and PCR criteria, and provide follow-up data after Month 7. The record does not explain why the analysis counts differ from overall enrollment, how missing follow-up was handled, or whether sensitivity analyses were performed. This makes it difficult to assess the influence of exclusions and incomplete observation from the registry summary alone.

The sponsor’s analysis method is not reported, and details such as model specification, covariate adjustment, and diagnostics are not available in the registry record. The re-calculation is explicitly an unadjusted Poisson-based summary comparison; it should not be treated as a reconstruction of the sponsor’s full analysis. The record does not report a multiplicity strategy despite listing 41 outcome measures and 3 analyses.

The primary outcome timeframe is up to 48 months after the first dose. The record lists extension outcomes and later follow-up periods, but those are distinct from this primary comparison. The primary result should not be taken as a result for those later periods or for outcomes not included in the primary endpoint. Finally, death counts are not reported in the registry record, and the adverse-event summaries do not by themselves establish whether an event was caused by vaccination.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety, Immune Response, and Efficacy of Gardasil (V501, qHPV) in Mid-Adult Women (V501-019) — NCT00090220.
• Registry record last updated 2017-04-21; status last verified 2017-03.
• Results first posted 2010-02-01.
• 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.

22. Record Summary

The registry describes a completed, randomized, double-masked, parallel phase 3 study of quadrivalent HPV vaccine versus placebo in mid-adult women. Enrollment is listed as 3819. The primary outcome is an incidence rate for a combined set of persistent infections and HPV-related diseases associated with types 6, 11, 16, and 18, assessed up to 48 months after the first qHPV dose.

The primary analysis population had defined vaccination, protocol, serology, PCR, and follow-up requirements. The posted rates were 0.2 and 1.7 per 100 person-years for qHPV and placebo, respectively. The sponsor reported a percent relative risk reduction of 88.7, with a 95% confidence interval from 78.1 to 94.8. An unadjusted re-calculation reports p < 0.001. The sponsor’s method, missing-data handling, and multiplicity strategy are not reported in the registry record.