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 Evaluation of the Immune and Safety Response of GlaxoSmithKline (GSK) Biologicals' HPV Vaccine in Healthy Indian Women (NCT00344032), a randomized phase 3 study. The primary outcome is Number of Subjects Who 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 | NCT00344032 |
| Phase | Phase 3 |
| Condition | Infections, Papillomavirus |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 354 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy Indian female subjects aged 18-35, as stated in its official title. The primary immunogenicity analysis was restricted to subjects who were initially seronegative and belonged to the According-to-Protocol cohort for analysis of immunogenicity. These details define the group relevant to the primary question; they do not establish how many subjects in that cohort contributed to the endpoint.
Intervention
The intervention was the HPV-16/18 VLP/AS04 vaccine, identified in the registry as Cervarix. Subjects assigned to this group received three doses at months 0, 1, and 6. The registry describes the study as evaluating the vaccine’s immunogenicity and safety.
Comparator
The comparator was placebo, also given as three doses at months 0, 1, and 6. The study used randomized allocation, double masking, and a parallel-group design. The registry record does not report details of the randomization procedure or how masking was maintained.
Primary question
At month 7, how many initially seronegative subjects in the immunogenicity analysis cohort had seroconverted for anti-HPV-16 and anti-HPV-18 antibodies? Seroconversion was defined using antibody thresholds of 8 EL.U/mL for anti-HPV-16 and 7 EL.U/mL for anti-HPV-18. The registry record identifies this endpoint but does not report its arm-specific results, so the posted information does not show how many participants met either threshold or permit a comparison between groups.
3. Trial Design
The registry describes a randomized, double-blind, controlled, parallel-group Phase 3 study. Its official title characterizes it as Phase IIIb. The study enrolled 354 participants and is marked completed in the registry record. The title specifies healthy Indian female subjects aged 18-35. GlaxoSmithKline is listed as the sponsor.
Participants were assigned to the HPV-16/18 VLP/AS04 vaccine, named Cervarix in the record, or placebo. Both groups were scheduled to receive three doses at months 0, 1, and 6. The primary immunogenicity endpoint was assessed at month 7, after the described dosing schedule. The record does not report the number randomized to each group for the primary analysis or the number who completed each dose.
The registry lists a study start date of 2006-07-28 and a primary completion date of 2007-12-01. The dates provide the recorded study timeline; they do not describe the timing of individual participant follow-up beyond the endpoint timeframe. The record identifies HPV infection as the condition and lists antibody titers and several safety outcomes among the secondary outcomes.
Randomization and masking are design features intended to limit systematic differences in treatment assignment and assessment. In general, randomization can support a fair comparison by balancing participant characteristics on average, while masking can reduce the influence of expectations on care or outcome assessment. The registry record does not describe the allocation sequence, masking procedures, or any deviations from the planned design. It also does not report a statistical analysis plan or the rationale used to choose the enrollment target.
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 | Placebo |
|---|---|---|
| STARTED | 176 | 178 |
| COMPLETED | 162 | 168 |
| NOT COMPLETED | 14 | 10 |
Reasons for not completing this period:
| Reason | Cervarix | Placebo |
|---|---|---|
| Adverse Event | 0 | 1 |
| Withdrawal by Subject | 6 | 2 |
| Lost to Follow-up | 4 | 6 |
| Physician Decision | 4 | 1 |
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 analysis of 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 | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 176 | 178 | 354 | |
| Age, Continuous | Years | 28.5 (SD 4.70) | 28.5 (SD 4.97) | 28.5 (SD 4.83) |
| Sex: Female, Male: Female | Participants | 176 | 178 | 354 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects Who Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies, measured over At 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 subjects who seroconverted for anti-HPV-16 and anti-HPV-18 antibodies at month 7. The registry defines seroconversion as the appearance of antibodies above the predefined cutoff in a subject who was seronegative before vaccination. The listed cutoffs are 8 EL.U/mL for anti-HPV-16 and 7 EL.U/mL for anti-HPV-18. The analysis population is described as initially seronegative subjects in the According-to-Protocol cohort for analysis of immunogenicity.
This is an immunogenicity endpoint: it records whether an antibody response crossed a specified laboratory threshold. Such a threshold makes the outcome interpretable as a count of participants meeting a defined response criterion, rather than as a continuous antibody concentration. In general, a binary endpoint can be useful when the scientific question concerns the proportion of participants meeting a prespecified definition. It also discards information about how far an antibody level lies above or below the threshold.
Seroconversion is not itself a clinical disease endpoint. The registry record does not report an endpoint measuring cervical cancer or HPV infection prevention. It also does not report the month 7 seroconversion counts or a comparison between treatment groups. Therefore, the endpoint’s definition and timing can be described, but the posted record does not establish the observed immunogenicity results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a clear primary outcome definition: seroconversion for anti-HPV-16 and anti-HPV-18 antibodies at month 7 among initially seronegative subjects in the immunogenicity According-to-Protocol cohort. It also gives the cutoffs used to classify a response. However, it does not report the numbers of participants who seroconverted in either group, the corresponding analysis denominators, or an estimated difference between groups. The primary results are therefore not reported in the registry record.
This omission limits what can be concluded statistically. Without arm-specific event counts and denominators, it is not possible to describe the observed response frequency, quantify a between-group contrast, or assess the precision of such a contrast. No confidence interval or primary-outcome significance test is reported in the registry record. The registry lists zero analyses, which means the record does not include a reported analysis result for this endpoint. It does not mean that no analysis was conducted outside the posted record.
The registry identifies 354 enrolled participants overall, but that total is not the same as the endpoint analysis population. The primary population was limited to initially seronegative participants in the specified immunogenicity cohort. The number meeting those eligibility conditions and the number included in the endpoint analysis are not reported in the registry record. Consequently, the overall enrollment cannot be used as the denominator for interpreting the primary endpoint.
The listed secondary outcomes cover antibody titers and several safety categories, including solicited symptoms, unsolicited adverse events, new onset chronic diseases, other medically significant events, and serious adverse events. Their presence identifies outcomes of interest, but their presence in the registry does not supply their results. In particular, the record does not include secondary antibody-titer findings or counts for the listed symptom and adverse-event categories, apart from the safety figures described separately.
For the serious adverse event counts, the record gives 2 events among 176 participants at risk in the Cervarix group and 4 among 178 at risk in the placebo group. These are descriptive counts. The record does not provide a comparative estimate, confidence interval, or inferential test for these figures. The listed serious-event terms are each reported at 0.6%; the record does not establish from this information whether the terms were considered related to vaccination.
In general, a confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A wider interval indicates less precision, while a narrower interval indicates greater precision. Because no primary-outcome estimate or interval is reported, the precision of the month 7 antibody comparison cannot be evaluated from the registry record. The posted information supports description of the design, endpoint definition, and some safety counts, but not a conclusion about the primary between-group result.
9. Statistical Methods Explained
What kind of endpoint is this?
The primary endpoint is a binary participant outcome: a subject either met the seroconversion definition or did not. The registry defines that status separately for anti-HPV-16 and anti-HPV-18 antibodies. A binary outcome is often summarized by the number of participants with the event and the number assessed. A comparison may then describe how event occurrence differs between randomized groups. These are general statistical descriptions, not reported analyses for this trial.
Binary summaries depend on both the numerator and the denominator. A count without its denominator does not show how common an outcome was in the analyzed group, and a denominator without a count does not show how many participants met the criterion. Here the registry record states the endpoint definition and analysis population but does not report the primary arm-specific counts or denominators. It therefore does not support a numerical estimate of the group contrast.
How does seroconversion classification work?
Seroconversion is defined in the record as the appearance of antibodies above the applicable cutoff in someone who was seronegative before vaccination. The specified cutoff is 8 EL.U/mL for anti-HPV-16 and 7 EL.U/mL for anti-HPV-18. This approach converts a laboratory measurement into a category based on a threshold. In general, threshold-based classification can make an outcome easier to communicate, but participants with measurements close to opposite sides of a cutoff may be assigned to different categories despite having similar measured values. A binary endpoint also does not convey the full distribution of antibody titers.
The primary outcome title refers to seroconversion for both antibody types. The registry does not report whether a combined rule was used to define a single joint success, how results for the two types were presented separately, or how multiple endpoint tests were handled. Those details are not reported in the registry record, so an interpretation should not assume a particular combined endpoint or testing procedure.
What does the analysis population imply?
The primary analysis is described as involving initially seronegative subjects from the According-to-Protocol cohort for analysis of immunogenicity. This is a defined subset rather than the full enrollment. In general, an according-to-protocol population may exclude participants who do not meet specified study requirements, while an initially seronegative restriction selects participants who could meet the stated seroconversion definition. The registry record does not provide the cohort’s detailed membership rules, the number of participants included, or the reasons any participants may have been excluded.
Analysis population choices affect the question answered. An analysis of participants who meet protocol criteria describes outcomes in that selected group; it is not automatically equivalent to an analysis of every randomized participant. The registry record does not report an intention-to-treat analysis or other alternative primary-population analysis, so the effect of population choice cannot be assessed from the posted information.
How should uncertainty and tests be understood?
In general, an estimate compares groups using a defined measure, such as a difference in event proportions. A confidence interval conveys the range of values compatible with the observed data and the statistical method, subject to its assumptions. A significance test addresses compatibility with a specified null hypothesis; a p-value alone does not measure the size or practical importance of an effect. None of these primary-outcome estimates or inferential results is reported in the registry record.
For event counts, precision depends in part on how many participants contribute information and how often the event occurs. Small counts commonly yield less precise estimates than larger counts. This general principle is relevant when reading sparse safety events, but the record does not report a comparative uncertainty estimate for the serious adverse event counts.
What do the planning illustrations represent?
The sample-size assumptions describe planning illustrations based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. For non-time-to-event outcomes, those illustrations are expressed as participants per arm; time-to-event illustrations use total events. These are planning calculations, not observed trial results or observed power. The primary endpoint has several categories or time points and was not reduced to one comparison, so a single primary-outcome comparison is not available from the record for interpreting such an illustration.
In general, a planning calculation asks how much information might be needed for a future comparison under assumed conditions. It does not establish that a completed study had a particular probability of detecting an effect, and it does not replace the observed estimate and its uncertainty. The registry record does not report the trial’s own sample-size justification, the assumed target effect, or the design calculations used by the investigators. The posted planning assumptions should therefore be read only as illustrations, not as the study’s documented design rationale.
Why can over-dispersion matter?
For count outcomes, a simple model may assume variability follows a specified relationship to the average count. Over-dispersion means the observed variation is greater than that model assumes. In general, ignoring it can make uncertainty estimates too small and tests too optimistic. The primary outcome is a participant-level binary count, and the registry does not report an over-dispersion assessment or a model-based primary analysis. This general concept should not be mistaken for a method documented for this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure describing the number of subjects who seroconverted for anti-HPV-16 and anti-HPV-18 antibodies at month 7, as well as secondary outcomes covering antibody titers and safety. The record does not explain whether the two antibody types were treated as separate tests, whether a joint criterion was used, or whether any adjustment was made for multiple comparisons. A multiplicity strategy is not reported in the registry record.
In general, testing several outcomes can increase the chance of at least one apparently unusual result under a collection of null hypotheses. Statistical plans may address this by defining a hierarchy, adjusting test thresholds, or interpreting secondary outcomes as exploratory. The registry does not report which, if any, approach was used. The number of outcome measures listed does not by itself establish how many tests were performed.
The primary population is described as initially seronegative participants in the According-to-Protocol immunogenicity cohort. The record does not report how many participants were eligible for that analysis, how many had missing month 7 antibody measurements, or how missing observations were handled. It also does not state whether participants with incomplete vaccination or protocol deviations were included in any analysis.
These omissions matter because missing-data handling and analysis-population definitions can affect the estimate and its interpretation. In general, excluding participants with unavailable outcomes can produce a selected analysis group, while different assumptions about missing outcomes can lead to different estimates. The registry record does not report sensitivity analyses or a missing-data strategy, so the potential impact cannot be assessed. The record also does not report an interim-analysis plan or whether interim testing occurred.
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 | 2 | 176 | 1.1% |
| Placebo | 4 | 178 | 2.2% |
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 | 153 of 176 |
| Placebo | 132 of 178 |
Most frequent serious adverse event terms
| Event term | Organ system | Cervarix | Placebo |
|---|---|---|---|
| Aborption spontaneous | Pregnancy, puerperium and perinatal conditions | 0 of 176 | 1 of 178 |
| Appendicitis | Infections and infestations | 1 of 176 | 0 of 178 |
| Bronchogenic cyst | Congenital, familial and genetic disorders | 0 of 176 | 1 of 178 |
| Cataract | Eye disorders | 0 of 176 | 1 of 178 |
| Lymph node tuberculosis | Infections and infestations | 1 of 176 | 0 of 178 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 0 of 176 | 1 of 178 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cervarix | Placebo |
|---|---|---|---|
| Pain | General disorders | 137 of 176 | 105 of 178 |
| Fatigue | General disorders | 84 of 176 | 83 of 178 |
| Headache | General disorders | 72 of 176 | 71 of 178 |
| Swelling | General disorders | 69 of 176 | 35 of 178 |
| Fever (above 37.5 degree Celsius) | General disorders | 51 of 176 | 48 of 178 |
| Redness | General disorders | 56 of 176 | 24 of 178 |
| Gastro-intestinal symptoms | General disorders | 25 of 176 | 28 of 178 |
| Arthralgia | General disorders | 19 of 176 | 16 of 178 |
| Myalgia | General disorders | 10 of 176 | 11 of 178 |
Serious events with the highest arm-level rate: appendicitis (0.6%), lymph node tuberculosis (0.6%), aborption spontaneous (0.6%), bronchogenic cyst (0.6%), cataract (0.6%).
The registry reports serious adverse events for 176 participants at risk in the Cervarix group, with 2 serious adverse events, and for 178 participants at risk in the placebo group, with 4 serious adverse events. These are the posted counts and denominators; they should be read as descriptive safety information rather than as evidence of a treatment-related effect. The record does not provide a comparative estimate, confidence interval, or statistical test for these figures.
The listed serious adverse event terms are Appendicitis, Lymph node tuberculosis, Aborption spontaneous, Bronchogenic cyst, Cataract, and Pneumothorax. Each is reported at 0.6%. The registry record does not assign those terms to a particular study group in the listed information, nor does it state whether they were judged related to study treatment. The term Aborption spontaneous is retained as recorded.
The record does not report deaths. It lists other adverse-event counts of 153 among 176 participants at risk in the Cervarix group and 132 among 178 at risk in the placebo group, but the figures do not by themselves describe severity or causality. Adverse-event counts are not proof that an event was caused by an intervention. Interpretation also depends on definitions, observation time, event ascertainment, and participant context; details beyond the listed figures are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this randomized, double-blind, parallel-group study was designed to assess antibody response and safety after three doses of HPV-16/18 VLP/AS04 vaccine or placebo. It defines month 7 seroconversion thresholds for anti-HPV-16 and anti-HPV-18 and specifies that the primary analysis concerned initially seronegative subjects in an immunogenicity According-to-Protocol cohort. These details identify the intended immunogenicity question.
The posted record does not report the primary seroconversion counts, denominators, group comparison, or uncertainty. It therefore does not show the observed primary outcome result. No claim about the magnitude or precision of an antibody-response difference can be made from the registry information. The overall enrollment of 354 does not substitute for the unreported endpoint-specific analysis population.
The endpoint concerns antibody thresholds, not a reported clinical disease outcome. In general, an antibody response can describe an immune measure, but the meaning of that measure depends on evidence connecting it to outcomes of interest. The registry record does not provide such an analysis, nor does it report results for prevention of HPV infection or cervical cancer. The study’s stated purpose and biological rationale should not be treated as a finding of clinical benefit.
The serious adverse event counts are available as descriptive figures: 2 among 176 at risk in the vaccine group and 4 among 178 at risk in the placebo group. The record does not report an inferential comparison or establish causality for these events. The counts alone do not determine whether groups differ beyond what could be expected from chance or other sources of uncertainty.
Accordingly, the posted information supports a description of the study design, endpoint definition, and selected safety counts. It does not support a conclusion about the primary immunogenicity effect, its precision, or a causal safety difference. Those conclusions would require results and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why a registry’s endpoint definition and its outcome results must be distinguished. The record describes a specific antibody-based primary endpoint, the month of assessment, the threshold values, and the immunogenicity population. Those details make the intended question identifiable. But without the arm-specific counts and denominators, the endpoint cannot be translated into an observed comparison.
It also illustrates the importance of matching the denominator to the analysis population. The study enrolled 354 participants overall, while the primary analysis was limited to initially seronegative subjects in an According-to-Protocol cohort. Those populations are not interchangeable. In general, reporting the analyzed population and the number with observed outcomes is essential for interpreting any event count or estimated group contrast.
The endpoint is binary even though it is based on antibody measurements. Thresholding makes a result easy to classify, but it does not show the distribution of titers or the distance of measurements from the cutoff. The record lists antibody titers as a secondary outcome, but does not report those results. This distinction matters statistically because a count meeting a threshold and a continuous antibody measure answer related but different questions.
The safety figures offer another useful reading lesson. Counts and at-risk denominators provide descriptive information, while uncertainty estimates and a clear assessment of causality are needed for stronger comparisons. Neither a difference in raw counts nor a listed adverse-event term alone identifies a treatment effect. Here, the registry does not report a statistical comparison of serious adverse events.
Finally, the planning assumptions are not observed trial findings. General sample-size illustrations can help explain how assumptions relate to a future study’s information needs, but they do not recover missing outcome results or establish observed power. The record’s lack of a reported analysis plan, sample-size justification, and primary results limits the statistical conclusions available from this study entry.
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 principal limitation of the posted record for interpreting the primary question is that it does not report the month 7 seroconversion results. Arm-specific counts, analysis denominators, an effect estimate, and an uncertainty interval are not reported in the registry record. Without them, the primary comparison cannot be quantified or assessed for precision.
The primary analysis population is described, but its size and detailed membership are not reported. The overall enrollment of 354 does not reveal how many participants were initially seronegative, met the According-to-Protocol criteria, or had evaluable month 7 measurements. Missing-data rules, exclusions, and sensitivity analyses are also not reported in the registry record.
The endpoint description covers seroconversion for two antibody types, but the record does not explain whether they were analyzed separately or combined, nor does it describe multiplicity control. The statistical analysis methods, model choices, confidence-interval methods, and inferential tests are not reported. The study’s sample-size justification and target effect are also not reported in the registry record.
For safety, the record supplies selected serious adverse event counts and terms but does not report a comparative analysis, event attribution, or deaths. Details of event collection and follow-up are not reported. The presence of these limitations does not show that relevant procedures or analyses were absent; it means they are not documented in the registry information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of the Immune and Safety Response of GlaxoSmithKline (GSK) Biologicals' HPV Vaccine in Healthy Indian Women — NCT00344032.
- Registry record last updated 2018-07-20; status last verified 2016-11.
- Results first posted 2009-12-15.
- 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
NCT00344032 is a completed randomized, double-blind, parallel-group Phase 3 study sponsored by GlaxoSmithKline. Its official title describes a Phase IIIb study in healthy Indian female subjects aged 18-35. The registry lists 354 participants and study dates from 2006-07-28 to primary completion on 2007-12-01.
Participants received three doses of HPV-16/18 VLP/AS04 vaccine, identified as Cervarix, or placebo at months 0, 1, and 6. The primary endpoint was month 7 seroconversion for anti-HPV-16 and anti-HPV-18 antibodies among initially seronegative subjects in the immunogenicity According-to-Protocol cohort. The registry defines cutoffs of 8 EL.U/mL and 7 EL.U/mL, respectively.
Primary outcome results and analysis details are not reported in the registry record. Serious adverse events are reported as 2 among 176 at risk with Cervarix and 4 among 178 at risk with placebo. The record also lists serious-event terms, each at 0.6%, without a reported causal assessment.