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 A Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine/Cervarix TM Vaccine in Healthy Females Aged 15-25 Years (NCT00485732), a randomized phase 3 study. The primary outcome is Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00485732 |
| Phase | Phase 3 |
| Condition | Infections, Papillomavirus |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 225 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Healthy female subjects aged 15–25 years. The primary immunogenicity analysis was performed among initially seronegative subjects in the According-to-Protocol cohort for immunogenicity.
Intervention
HPV-16/18 L1 VLP AS04 vaccine, identified as Cervarix, administered intramuscularly.
Comparator
Placebo. The registry record describes the study as randomized, controlled, double-blind, and parallel-group.
Primary question
Among initially seronegative participants in the specified immunogenicity cohort, how many had seroconverted for anti-HPV-16 and/or anti-HPV-18 antibodies one month after Dose 3, at Month 7?
The primary outcome is a count of participants meeting an antibody-based definition, not a direct count of HPV infections or cervical disease. Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies at or above the stated assay cut-off in participants who were seronegative before vaccination. The anti-HPV-16 cut-off was 8 EL.U/mL, and the anti-HPV-18 cut-off was 7 EL.U/mL.
The clinical question therefore concerns whether antibody responses were recorded after vaccination in the defined analysis population, with placebo as the comparison group. The listed outcome title refers to seroconversion for both antibody types, but the registry record does not reduce the primary outcome to a single comparison. It does not report a numerical primary-endpoint result or an effect estimate in the record. This limits what can be concluded about the size or precision of any difference between groups from the registry information alone.
3. Trial Design
The registry identifies this as a Phase III study, while the official title describes it as Phase IIIb. It was randomized, double-blind, controlled, and used a parallel-group model. The intervention was the HPV-16/18 L1 VLP AS04 vaccine, Cervarix, and the comparator was placebo. Enrollment was 225. The registry record identifies GlaxoSmithKline as the sponsor and records the study status as completed.
The study population was healthy female subjects aged 15–25 years. The primary immunogenicity population was narrower: initially seronegative subjects in the According-to-Protocol cohort for immunogenicity. This distinction matters because the endpoint definition depends on the participant being seronegative before vaccination. The record does not provide further eligibility criteria or explain how many enrolled participants entered each analysis population.
The primary outcome concerned participants who seroconverted for anti-HPV-16 and/or anti-HPV-18 antibodies, assessed one month post Dose 3, at Month 7. Secondary outcomes listed antibody titres, solicited local and general symptoms, unsolicited adverse events, new onset chronic diseases and medically significant conditions, serious adverse events, and pregnancies and their outcomes. The registry lists 8 outcome measures, but records 0 analyses.
Although the registry provides some safety counts, it does not provide a single numerical comparison for the primary immunogenicity outcome. It also does not report the randomization ratio, allocation-concealment procedure, vaccine schedule details beyond the endpoint’s reference to Dose 3, or the statistical plan used by the investigators. Those details should not be inferred from the design labels.
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 | Cervarix Group | Placebo Group |
|---|---|---|
| STARTED | 149 | 76 |
| COMPLETED | 141 | 67 |
| NOT COMPLETED | 8 | 9 |
Reasons for not completing this period:
| Reason | Cervarix Group | Placebo Group |
|---|---|---|
| Protocol Violation | 1 | 3 |
| Withdrawal by Subject | 5 | 4 |
| Lost to Follow-up | 2 | 2 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on initially seronegative subjects from the According-to-Protocol (ATP) cohort for immunogenicity.
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 | Cervarix Group | Placebo Group | Total |
|---|---|---|---|---|
| Participants analysed | 149 | 76 | 225 | |
| Age, Continuous | years | 22.0 (SD 2.24) | 21.9 (SD 2.63) | 22.0 (SD 2.37) |
| Sex: Female, Male: Female | Participants | 149 | 76 | 225 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies, measured over One month post Dose 3 (Month 7).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who seroconverted for anti-HPV-16 and/or anti-HPV-18 antibodies. Seroconversion means that antibodies appeared at or above the specified assay cut-off in sera from subjects who were seronegative before vaccination. The stated thresholds were 8 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Assessment was scheduled one month after Dose 3, at Month 7.
This endpoint is used to describe an immune response in the defined population. Restricting the primary immunogenicity analysis to initially seronegative participants aligns the outcome with the stated definition: a new detectable antibody response after vaccination. The threshold turns an assay measurement into a categorical outcome, so each participant is classified according to whether the antibody criterion was met. This makes the endpoint interpretable as a count of participants who met the seroconversion definition, rather than as a change in antibody concentration.
That classification also means the endpoint does not, by itself, show the magnitude or durability of antibody responses, clinical protection, or changes in HPV infection or disease. Antibody titres are listed separately as a secondary outcome. The registry record does not report the primary endpoint’s numerical results or a treatment-effect estimate, so the relative frequency of seroconversion cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the design and endpoint definition, but it does not provide the primary immunogenicity result in a form that permits a direct treatment comparison. The primary outcome is a participant count for seroconversion against HPV-16 and/or HPV-18 antibodies, measured at Month 7 in initially seronegative participants in the According-to-Protocol cohort for immunogenicity. The registry notes that the primary outcome has several categories or time points and is not reduced to one comparison. No primary numerical estimate or uncertainty measure is reported in the registry record.
Consequently, the record does not support a quantitative statement about how the vaccine and placebo groups differed on the primary endpoint. It is not possible to describe the size, direction, or precision of a primary immunogenicity effect from the information recorded. The absence of a single comparison should not be mistaken for evidence that the groups were identical; it means the registry information does not provide the result needed to assess that question.
The safety information is more directly numerical. The serious-adverse-event fields list 2 participants among 149 at risk in the Cervarix Group and 1 participant among 76 at risk in the Placebo Group. The registry also lists serious-event terms with recorded percentages: viral gastroenteritis at 1.3%, ruptured ovarian cyst at 0.7%, and pelvic inflammatory disease at 0.7%. These entries are descriptive. Without further detail about event-level coding, timing, severity, attribution, and the analysis method, they do not establish that an event was caused by a study intervention. Death counts are not reported in the registry record.
The posted information also lists other safety outcomes, including solicited symptoms, unsolicited adverse events, chronic diseases, medically significant conditions, and pregnancy outcomes. Their presence in the outcome list does not substitute for numerical results for each endpoint. The registry records 0 analyses, and the statistical analysis procedures, adjustment strategy, and handling of incomplete observations are not reported in the registry record.
Overall, the record supports a description of what was intended to be measured and provides selected safety counts, but it does not support a complete inferential assessment of the primary endpoint. Any conclusion about comparative immunogenicity would require the corresponding group results and an analysis that accounts for the defined population and endpoint structure.
9. Statistical Methods Explained
Randomization assigns participants to study groups using a chance-based process. In general, this helps limit systematic differences between groups at the start of a trial, although it does not guarantee that every characteristic will be balanced. The record identifies this study as randomized but does not report the sequence-generation method, allocation concealment, or randomization ratio. The parallel-group label means participants were assigned to a study group rather than being described as crossing between interventions; details beyond that design label are not reported in the registry record.
What does double-blind mean?
In general, blinding means that specified people involved in a trial do not know which intervention a participant has received. Blinding can reduce the influence of expectations on participant reporting, clinical assessment, or study conduct. The record labels the study double-blind, but it does not identify which roles were blinded or describe how blinding was maintained. Those particulars should not be assumed from the label alone.
What kind of outcome is seroconversion?
Seroconversion is a binary outcome at the participant level: a participant either meets the stated antibody criterion or does not. Here, the criterion is the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies at or above the corresponding assay cut-off among participants who were seronegative before vaccination. A count of participants meeting the criterion can be used to describe how many experienced the defined response. For a comparative analysis, the group counts would generally need to be accompanied by denominators and an effect estimate with an uncertainty interval. Those primary results are not reported in a single comparison in the registry record.
Binary endpoints simplify interpretation, but they discard information about how far an antibody measurement lies above or below a threshold. Antibody titres, listed as a secondary outcome, can describe the measured level more directly. The registry record does not provide numerical titre results in the information, so it is not possible to assess the distribution or magnitude of antibody measurements.
How should uncertainty be understood?
In general, a confidence interval describes a range of values compatible with the data under a specified statistical procedure. It reflects the precision of an estimate, not the probability that a particular treatment effect is true. An interval around a group contrast would help readers distinguish a relatively precise estimate from one with substantial uncertainty. No primary effect estimate or confidence interval is reported in the registry record, so this kind of precision assessment cannot be made for the primary endpoint.
A p-value, when reported, measures how surprising data at least as inconsistent with a specified null hypothesis would be under the assumptions of the statistical model. It does not measure the size or clinical importance of an effect. The registry records no analyses, and no p-value for the primary comparison is reported. A statistical test or its result should therefore not be inferred.
What do the planning assumptions mean?
The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. Such an illustration concerns planning for a hypothetical future study; it is not observed power for this completed trial. The record does not report numerical planning estimates or the numerical observed effect needed to interpret them.
In general, a sample-size calculation estimates how much information a planned study would need under stated assumptions. Its result depends on the target effect, variability or event frequency, significance level, power target, allocation, and model assumptions. If the target effect is smaller, more information is generally needed to distinguish it from random variation. These are general statistical principles, not claims about the investigators’ design rationale. The registry record does not report a sample-size justification or the trial’s own planning procedure.
How do the safety counts differ from comparative analysis?
Counts of participants with serious adverse events are descriptive unless linked to a defined comparative analysis. In general, comparing event counts requires attention to the number of participants at risk, observation time, event definitions, and whether multiple events can occur in the same participant. A difference in raw counts alone does not quantify a causal effect. The registry’s serious-adverse-event figures can be described as recorded, but the statistical method and any adjusted comparison are not reported in the registry record.
Over-dispersion is a general issue for count outcomes when observed variation exceeds what a chosen model expects. It can make standard errors too small if ignored. The primary endpoint is specified as a participant count meeting a binary criterion, not as a repeated-event count, and the record does not state that an over-dispersion model was used. No particular model should be attributed to the investigators.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 8 outcome measures, including the primary seroconversion outcome and secondary antibody, symptom, adverse-event, chronic-condition, and pregnancy outcomes. Multiple outcomes create a multiplicity issue: in general, testing many hypotheses can increase the chance of at least one apparently notable result arising by chance. Statistical plans may address this by designating a primary outcome, controlling error across selected comparisons, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, a hierarchy of tests, or adjusted analyses.
The primary outcome itself is described as having several categories or time points and is not reduced to one comparison. The registry records 0 analyses. It therefore does not provide a single primary comparison or the analysis details needed to interpret multiple endpoint results together. The absence of a reported adjustment does not show that none was performed; the procedure is not reported in the registry record.
The primary analysis population is described as initially seronegative subjects in the According-to-Protocol cohort for immunogenicity. That is a defined analysis population, but the record does not report the counts eligible for or included in this analysis, how exclusions were handled, or whether other analysis populations were used. The number of enrolled participants does not by itself establish the size of the primary endpoint analysis set.
Missing-data handling is also not reported in the registry record. In general, missing outcome measurements can affect a result if the chance of missingness is related to participant characteristics or outcome status. Different assumptions and methods can yield different estimates. The record does not explain how unavailable antibody measurements, withdrawals, or deviations from protocol were treated, so no missing-data assumptions can be attributed to the analysis.
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 |
|---|---|---|---|
| Cervarix Group | 2 | 149 | 1.3% |
| Placebo Group | 1 | 76 | 1.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cervarix Group | 144 of 149 |
| Placebo Group | 70 of 76 |
Most frequent serious adverse event terms
| Event term | Organ system | Cervarix Group | Placebo Group |
|---|---|---|---|
| Gastroenteritis viral | Infections and infestations | 0 of 149 | 1 of 76 |
| Ovarian cyst ruptured | Reproductive system and breast disorders | 1 of 149 | 0 of 76 |
| Pelvic inflammatory disease | Infections and infestations | 1 of 149 | 0 of 76 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cervarix Group | Placebo Group |
|---|---|---|---|
| Pain | General disorders | 140 of 149 | 64 of 76 |
| Redness | General disorders | 109 of 149 | 35 of 76 |
| Fatigue | General disorders | 103 of 149 | 39 of 76 |
| Myalgia | General disorders | 97 of 149 | 33 of 76 |
| Swelling | General disorders | 89 of 149 | 19 of 76 |
| Headache | General disorders | 73 of 149 | 30 of 76 |
| Gastrointestinal symptoms | General disorders | 52 of 149 | 16 of 76 |
| Arthralgia | General disorders | 35 of 149 | 8 of 76 |
| Rash | General disorders | 29 of 149 | 8 of 76 |
| Upper respiratoy tract infection | Infections and infestations | 20 of 149 | 3 of 76 |
Serious events with the highest arm-level rate: gastroenteritis viral (1.3%), ovarian cyst ruptured (0.7%), pelvic inflammatory disease (0.7%).
The registry’s serious-adverse-event fields list 2 participants among 149 at risk in the Cervarix Group and 1 participant among 76 at risk in the Placebo Group. These are the recorded participant counts and corresponding at-risk counts; they should not be converted into a causal comparison without the analysis details. The registry also lists viral gastroenteritis at 1.3%, ruptured ovarian cyst at 0.7%, and pelvic inflammatory disease at 0.7% among the top serious-event terms.
Serious adverse events are distinct from solicited symptoms and other adverse events. The registry lists those outcomes separately, but their presence does not establish whether any individual event was related to an intervention. The record does not report the adjudication process, event timing, exposure duration, or a statistical comparison for serious events. A participant count also does not show the number of separate events if an individual could have experienced more than one event.
Death counts are not reported in the registry record. The available serious-event entries are descriptive and should be interpreted within the limitations of the reporting detail; they do not establish causation or provide a complete safety assessment.
12. What the Result Does, and Does Not, Mean
The record describes a randomized, double-blind, placebo-controlled study of Cervarix in healthy females aged 15–25 years, with an antibody-based primary outcome assessed one month after Dose 3. It defines seroconversion using antibody cut-offs among participants who were seronegative before vaccination, and it identifies the immunogenicity analysis population as initially seronegative subjects in the According-to-Protocol cohort.
However, the registry record does not give a single numerical result for the primary endpoint or a comparative effect estimate. It is therefore not possible to determine from this information how many participants in each group met the seroconversion definition, how the groups differed, or how precisely any difference was estimated. The absence of a reported primary comparison is not evidence of no effect; it is a limit on what the record permits readers to assess.
The serious-adverse-event counts and listed event terms provide selected descriptive safety information. They do not, without further context and analysis, establish whether events were caused by vaccination or whether the groups differed in safety. Other outcomes are listed, but their numerical findings and analysis details are not reported in the registry record.
More broadly, an antibody response is an immunogenicity measure, not a direct measurement of infection, cervical disease, or long-term clinical outcomes. The registry record does not establish the duration of antibody responses or connect the primary endpoint to a clinical outcome. These distinctions keep interpretation aligned with what was measured and what was actually reported.
13. Why This Trial Matters Statistically
This study illustrates a common distinction in clinical research: a biologically relevant measurement is not necessarily a clinical outcome. The primary endpoint counts participants meeting a seroconversion definition based on anti-HPV-16 and/or anti-HPV-18 antibody thresholds. That endpoint can describe a measured immune response in the specified population, while leaving separate questions about antibody magnitude, persistence, infection, and disease unanswered.
It also shows why the analysis population matters. The endpoint applies to subjects who were initially seronegative and were included in the According-to-Protocol cohort for immunogenicity. Results from that group would not automatically describe every enrolled participant. Clear reporting of eligibility for analysis, exclusions, and missing measurements is important for understanding which participants the estimate represents; those details are not reported in the registry record.
The record further highlights the difference between an outcome being named and a result being interpretable. It identifies a primary endpoint and numerous secondary outcomes, but records 0 analyses and does not reduce the primary outcome to a single comparison. Without a group-level result and an uncertainty measure, readers cannot judge the size or precision of a comparative immunogenicity finding.
Finally, the serious-adverse-event entries demonstrate the limits of descriptive counts. Counts and event labels can inform readers about what the registry recorded, but they are not a substitute for a defined comparative safety analysis or an assessment of causality. Statistical interpretation depends not only on the study design and endpoint, but also on complete reporting of the analysis and its uncertainty.
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 main limitation for interpretation is that the registry record does not present a single numerical comparison for the primary seroconversion endpoint. The endpoint is described as having several categories or time points, and the record lists 0 analyses. There is no primary effect estimate or uncertainty interval in the registry record. This prevents assessment of the direction, magnitude, and precision of the primary result.
The immunogenicity population is described as initially seronegative participants in the According-to-Protocol cohort, but the record does not report the number included in that analysis or how participants were selected into it. It also does not report missing-data handling, protocol deviations, or the effect of exclusions. These details matter because an analysis restricted to a protocol-defined population may not represent all enrolled participants.
The record does not state the statistical model, hypothesis-testing procedure, adjustment for multiple outcomes, or any interim-analysis approach. It also does not describe the sample-size justification. The planning assumptions refer to an illustration based on the observed effect, but numerical planning estimates and the effect value are not reported in the registry record. Such planning illustrations should not be interpreted as observed power.
For safety, the serious-adverse-event fields provide selected counts and event terms, but the registry does not report a comparative statistical analysis, event timing, attribution procedures, or death counts. The listed entries therefore support description, not causal conclusions. The record also does not provide enough detail to judge the completeness of safety follow-up or the interpretation of the other listed safety outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine/Cervarix TM Vaccine in Healthy Females Aged 15-25 Years — NCT00485732.
- Registry record last updated 2018-07-20; status last verified 2016-11.
- Results first posted 2009-12-17.
- 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
NCT00485732 is a completed Phase III study, described in its official title as Phase IIIb, of Cervarix versus placebo in healthy female subjects aged 15–25 years. The design is recorded as randomized, double-blind, controlled, and parallel-group, with enrollment of 225.
The primary endpoint counts participants who seroconverted for anti-HPV-16 and/or anti-HPV-18 antibodies one month after Dose 3, at Month 7. Its analysis population is initially seronegative subjects in the According-to-Protocol cohort for immunogenicity. The registry record does not provide a single numerical primary comparison or a reported analysis.
Selected serious-adverse-event counts are recorded for both groups, along with several event terms and percentages. The analysis methods, missing-data procedures, multiplicity approach, and death counts are not reported in the registry record.