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 Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older (NCT00294047), a randomized phase 3 study. The primary outcome is Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00294047 |
| Phase | Phase 3 |
| Condition | Infections, Papillomavirus, Papillomavirus Vaccines |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 5752 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
The study asked whether Cervarix, given as a three-dose course, was associated with fewer cases of persistent HPV-16 or HPV-18 infection and related cervical lesions than an aluminium hydroxide control among healthy adult women. The primary outcome combined persistent infection, defined over an approximately six-month interval, with histopathologically confirmed CIN1+ associated with HPV-16 and/or HPV-18 cervical infection. The registry lists the primary outcome timeframe as up to Month 48.
Population
Healthy women aged 26 years and older were eligible for the study. The primary-outcome description specifies an according-to-protocol efficacy cohort that included participants with normal or low-grade cytology at Month 0 who received three doses. The complete population description and the full criteria for inclusion in this cohort are not reported in the registry record.
Intervention
Participants in the Cervarix Group received three intramuscular doses in the deltoid region of the non-dominant arm, on a 0, 1, 6 months schedule.
Comparator
The control arm is described as the Aluminium Hydroxide Group. Participants received three intramuscular doses of aluminium hydroxide in the deltoid region of the non-dominant arm, on the same 0, 1, 6 months schedule. The brief study summary also calls the comparator a control.
Primary question
How did the number of participants meeting the combined persistent-infection or CIN1+ endpoint compare between the randomized groups? The comparative primary-outcome results are not reported in the registry record, so the direction and precision of any group difference cannot be assessed from this record.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group Phase 3 study sponsored by GlaxoSmithKline. The registry reports enrollment of 5752 and a completed status. The study start is listed as 2006-02-16, and primary completion as 2014-01-29. These registry dates describe the study record; they do not establish how long any individual participant was followed.
The planned comparison was between Cervarix and a control. The intervention descriptions clarify that the control arm received aluminium hydroxide, rather than no injection, and that both groups followed the same three-dose schedule: 0, 1, 6 months. The arm descriptions specify intramuscular administration into the deltoid region of the non-dominant arm. Randomization supports a comparison between assigned groups, while masking is intended generally to reduce the influence of knowledge of assignment on participant or study-team behavior and assessments. The registry does not specify which four roles were masked.
The brief summary describes a multicentre study. Under Protocol Amendment 3, planned participation was approximately 48 months with eleven scheduled visits; under Protocol Amendment 4, participation was to last up to 84 months with a maximum of seventeen scheduled visits. These are descriptions of planned follow-up and visits, not evidence that every participant completed the same duration or all visits. The primary endpoint timeframe is separately listed as up to Month 48.
The registry lists 49 outcome measures and 0 analyses. It does not report comparative primary-outcome results, a primary effect estimate, or a confidence interval. The detailed statistical analysis plan, allocation procedures, and the reasons for any protocol amendments 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.
Before assignment: Enrolment was stratified by (1) age, with the majority of subjects in age strata 26 - 35 years and 36 - 45 years (about 45% each) and about 10% in the age stratum 46+ years, and (2) previous HPV history (in each age stratum, the number of women with a history of HPV infection/treatment was limited to approximately 15%).
Month 48
| Stage | Cervarix Group | Aluminium Hydroxide Group |
|---|---|---|
| STARTED | 2881 | 2871 |
| Participated up to Month 48 | 2305 | 2281 |
| COMPLETED | 2456 | 2438 |
| NOT COMPLETED | 425 | 433 |
Reasons for not completing this period:
| Reason | Cervarix Group | Aluminium Hydroxide Group |
|---|---|---|
| Adverse Event | 28 | 13 |
| Protocol Violation | 4 | 4 |
| Withdrawal by Subject | 111 | 115 |
| Lost to Follow-up | 272 | 287 |
| Other | 10 | 14 |
Month 84
| Stage | Cervarix Group | Aluminium Hydroxide Group |
|---|---|---|
| STARTED | 2877 | 2870 |
| COMPLETED | 1904 | 1881 |
| NOT COMPLETED | 973 | 989 |
Reasons for not completing this period:
| Reason | Cervarix Group | Aluminium Hydroxide Group |
|---|---|---|
| Adverse Event | 4 | 2 |
| Protocol Violation | 1 | 1 |
| Withdrawal by Subject | 33 | 31 |
| Lost to Follow-up | 187 | 190 |
| Absent Cervix | 2 | 0 |
| Work related reasons | 4 | 2 |
| Center closed, subject did not transfer | 1 | 0 |
| Family problems | 2 | 2 |
| Lack of time | 3 | 1 |
| Personal reason | 2 | 4 |
| Subject does not want male physician | 1 | 0 |
| Transport reimbursement delayed | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The According-To-Protocol cohort for efficacy included subjects who had a normal or low-grade cytology (negative or atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL)) at Month 0, who received 3 doses. A 15% subset of women enrolled with prior history of HPV infection was excluded.
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 | Aluminium Hydroxide Group | Total |
|---|---|---|---|---|
| Participants analysed | 2881 | 2871 | 5752 | |
| Age, Continuous | Years | 37.0 (SD 7.24) | 37.0 (SD 7.32) | 37.0 (SD 7.28) |
| Sex: Female, Male: Female | Participants | 2881 | 2871 | 5752 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection., measured over Up to Month 48.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is a participant count for a combined endpoint: persistent HPV-16 or HPV-18 infection and/or histopathologically confirmed CIN1+ associated with HPV-16 and/or HPV-18 cervical infection. CIN1+ is defined in the registry as CIN grades 1, 2 and 3, adenocarcinoma in situ, and invasive cervical cancer. Persistent infection means the same HPV type or types were detected by PCR in cervical samples at two consecutive evaluations over approximately a six-month interval.
A combined endpoint can capture more than one clinically relevant event type in a single outcome measure. Here, it brings together a virologic measure of persistent infection and a tissue-based measure of cervical abnormality with the specified HPV association. A participant meeting either part of the combined definition may contribute to the endpoint, but the registry record does not report the component-specific primary results. That omission prevents assessment of how much each component contributed to any overall comparison.
The listed timeframe is up to Month 48. The primary-outcome population is described as an according-to-protocol efficacy cohort that included participants with normal or low-grade cytology at Month 0 who received three doses. The rest of that population description is incomplete in the registry record. The primary endpoint is a count of participants, not a reported rate or time-to-event measure. Comparative event counts, denominators for the primary analysis, and an effect estimate are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes the design and definitions of the primary comparison, but it does not provide the primary-outcome results. Consequently, there is no reported count for either randomized group on the combined endpoint, no comparative estimate, and no uncertainty interval to interpret. The record alone cannot establish whether the groups differed, the direction of a difference, or how precisely any difference was estimated.
The primary measure is a count of participants meeting the endpoint, with a defined eligible efficacy cohort and a timeframe up to Month 48. Counts are most informative for a group comparison when read alongside the relevant analysis denominators and a measure of uncertainty. Those primary-outcome counts and denominators are not reported in the registry record. The enrollment figure is not a substitute for the number analyzed on this endpoint: the outcome population is specified as according-to-protocol, and the full analysis population details are not available.
The endpoint also combines persistent infection with CIN1+ associated with specified HPV types. An overall combined result, if reported, would describe the combined definition; it would not by itself show the separate results for persistent infection and cervical lesions. The registry lists several related secondary outcomes, including persistent infection under six-month and twelve-month definitions and lesion outcomes. Their presence indicates that related measures were considered, but their comparative estimates are not reported in the registry record.
General statistical interpretation: an effect estimate describes the magnitude and direction of a group contrast, while a confidence interval describes the range of values compatible with the estimate under the method used. A narrow interval generally indicates more precision than a wide one, but neither can be interpreted without the outcome definition and analysis population. No primary effect estimate or interval is available in the record, so no claim about magnitude or precision is possible.
The registry lists 0 analyses despite listing 49 outcome measures. This distinction matters: outcome definitions do not constitute analyzed results. The endpoint description and trial design can be examined, but the comparative efficacy conclusion cannot be reconstructed from the information reported. A reader should distinguish the study’s planned question from an answer supported by posted outcome data.
9. Statistical Methods Explained
The statistical details below distinguish what the registry reports from general principles for interpreting a randomized trial. The registry provides an outcome definition and trial-design details, but does not report the primary comparative analysis or its statistical plan.
What does a participant count represent?
The primary outcome is expressed as the number of participants meeting a binary event definition. For each participant, the endpoint definition determines whether the event is counted as present or absent. A group count is not, on its own, a group risk or a comparison. To interpret a count, the relevant analysis denominator is needed, along with a clearly specified analysis population and follow-up context. The registry does not report the primary outcome counts or their analysis denominators.
General statistical explanation: a risk is a count of participants with an event relative to the number of participants under consideration. A risk difference compares two such risks by subtraction, while a risk ratio compares them by division. These are different ways of expressing a group contrast and answer different questions about scale. No primary risks or contrasts are reported for this study in the registry record, and no new contrast can be calculated from the information available.
Why does the endpoint definition matter?
The endpoint combines two forms of evidence: persistent detection of HPV-16 or HPV-18 and histopathologically confirmed CIN1+ associated with HPV-16 and/or HPV-18 infection. The registry defines persistence through detection of the same type or types by PCR in samples at two consecutive evaluations over approximately a six-month interval. CIN1+ includes CIN grades 1, 2 and 3, adenocarcinoma in situ, and invasive cervical cancer. The outcome therefore depends on the specified test, timing, pathology definition, and HPV association. A change to any of these rules could change who qualifies as an endpoint event.
General statistical explanation: composite outcomes can increase the number of events available for analysis, but an overall composite can conceal differences among its components. Interpretation is strongest when component results and the composite definition are both clear. The registry lists secondary measures for persistent infection and cervical lesions, but does not report their comparative results.
How should uncertainty be assessed?
General statistical explanation: an estimate is a summary of the observed contrast in a sample, and a confidence interval conveys its statistical precision under a stated method and assumptions. A confidence interval is not a guarantee that the true value lies within its limits. Its width depends in part on the amount of information in the analysis, including the number of events and the analysis population. A p-value, when reported, addresses compatibility with a specified null model; it does not measure the size or clinical importance of an effect.
No primary effect estimate, confidence interval, or p-value is reported in the registry record. Therefore, statistical significance, compatibility with no difference, and precision cannot be assessed for the primary outcome. A count or a description of the design cannot fill that gap.
What does the record say about planning calculations?
The planning assumptions describe illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The intended effect to detect is stated as a fraction of the observed effect. These are planning illustrations, not observed power. They should not be read as the trial's own sample-size justification or as evidence that the study was adequately powered. The trial's own sample-size justification and a statistical plan are not reported in the registry record. No numerical planning estimates are stated in the registry information addressed.
General statistical explanation: a planning calculation depends on assumptions about the target effect, event frequency, allocation, significance level, and analysis method. Altering an assumed target effect changes the planning requirement. A fraction of an observed effect is a hypothetical planning target, not a separately observed trial result. A normal approximation is a method choice, not evidence that its assumptions were checked or met. No additional assumptions should be inferred beyond those explicitly described.
What can randomized assignment support?
General statistical explanation: random assignment is designed to make groups comparable on average at allocation, including with respect to factors that may not have been measured. It does not guarantee identical groups, eliminate loss to follow-up, or determine how participants with missing outcomes should be handled. Masking may reduce certain sources of measurement or behavioral bias, but the registry does not identify the masked roles or report how masking was maintained. These design features inform how a comparison could be interpreted; they do not replace the missing outcome analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 49 outcome measures and 0 analyses. Multiple outcomes can raise multiplicity concerns because examining many outcomes may increase the chance of at least one apparently notable result by chance. General statistical practice may address this through a prespecified hierarchy, adjustment, or cautious interpretation, but the registry record does not report a multiplicity strategy, testing hierarchy, or statistical analysis plan. It is therefore not possible to determine which outcomes were intended to be confirmatory or whether any adjustment was applied.
The primary population is described as an according-to-protocol efficacy cohort, including participants with normal or low-grade cytology at Month 0 who received three doses. The description also refers to DNA- and serostatus-defined groups and an overall HPV-type group: the former are defined using Month 0 and Month 6 DNA status and Month 0 serostatus, while the overall group is defined by DNA status regardless of initial serostatus. The full primary population description is incomplete in the registry record. The record does not provide the primary analysis denominators or comparative results for these groups.
Missing-data handling is not reported in the registry record. The record also does not explain how incomplete follow-up, missed evaluations, or unavailable specimen results were handled for the primary endpoint. These details matter because the outcome depends on repeated evaluations and laboratory and histopathological assessments. No interim-analysis plan, imputation method, or sensitivity analysis is reported in the registry record. Their absence from the record should not be taken as proof that none existed outside it; it means the reported information does not permit evaluation of these procedures.
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 | 291 | 2881 | 10.1% |
| Aluminium Hydroxide Group | 269 | 2871 | 9.4% |
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 | 2543 of 2881 |
| Aluminium Hydroxide Group | 2236 of 2871 |
Most frequent serious adverse event terms
| Event term | Organ system | Cervarix Group | Aluminium Hydroxide Group |
|---|---|---|---|
| Abortion spontaneous complete | Pregnancy, puerperium and perinatal conditions | 19 of 2881 | 16 of 2871 |
| Abortion spontaneous incomplete | Pregnancy, puerperium and perinatal conditions | 19 of 2881 | 13 of 2871 |
| Appendicitis | Infections and infestations | 13 of 2881 | 12 of 2871 |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | 13 of 2881 | 12 of 2871 |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 13 of 2881 | 9 of 2871 |
| Abortion missed | Pregnancy, puerperium and perinatal conditions | 10 of 2881 | 11 of 2871 |
| Cholelithiasis | Hepatobiliary disorders | 5 of 2881 | 9 of 2871 |
| Blighted ovum | Pregnancy, puerperium and perinatal conditions | 6 of 2881 | 7 of 2871 |
| Abortion threatened | Pregnancy, puerperium and perinatal conditions | 4 of 2881 | 7 of 2871 |
| Ovarian cyst | Reproductive system and breast disorders | 5 of 2881 | 6 of 2871 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cervarix Group | Aluminium Hydroxide Group |
|---|---|---|---|
| Pain | General disorders | 2411 of 2881 | 1862 of 2871 |
| Headache | General disorders | 1165 of 2881 | 1074 of 2871 |
| Fatigue | General disorders | 1116 of 2881 | 916 of 2871 |
| Redness | General disorders | 1058 of 2881 | 530 of 2871 |
| Swelling | General disorders | 1080 of 2881 | 428 of 2871 |
| Myalgia | General disorders | 878 of 2881 | 622 of 2871 |
| Gastrointestinal | General disorders | 664 of 2881 | 592 of 2871 |
| Arthralgia | General disorders | 580 of 2881 | 439 of 2871 |
| Fever | General disorders | 308 of 2881 | 248 of 2871 |
| Urticaria | General disorders | 258 of 2881 | 201 of 2871 |
Serious events with the highest arm-level rate: abortion spontaneous complete (0.7%), abortion spontaneous incomplete (0.7%), appendicitis (0.5%), abortion spontaneous (0.5%), uterine leiomyoma (0.5%).
The registry lists 291 participants with serious adverse events among 2881 at risk in the Cervarix Group, and 269 among 2871 at risk in the Aluminium Hydroxide Group. For other adverse events, it lists 2543 participants among 2881 at risk in the Cervarix Group and 2236 among 2871 at risk in the Aluminium Hydroxide Group. These are group-specific counts and at-risk figures, not comparative estimates adjusted for follow-up or other factors. Death counts are not reported in the registry record.
The registry also lists serious adverse-event terms with percentages: abortion spontaneous complete, 0.7%; abortion spontaneous incomplete, 0.7%; appendicitis, 0.5%; abortion spontaneous, 0.5%; uterine leiomyoma, 0.5%; and abortion missed, 0.4%. The record does not specify the denominator or further context for these listed percentages in the information available, so they should not be interpreted as group-specific rates or used to compare groups.
General statistical explanation: adverse-event counts describe what was recorded, while a causal safety interpretation requires careful consideration of definitions, timing, exposure, follow-up, and comparative analysis. The figures alone do not establish that an event was caused by an assigned intervention. The registry record does not report a comparative safety analysis or uncertainty estimates for these counts.
12. What the Result Does, and Does Not, Mean
The record supports a description of a randomized, quadruple-masked, parallel-group Phase 3 study of Cervarix compared with an aluminium hydroxide control. It specifies the dosing schedule, a combined primary endpoint, and the intended primary timeframe. It also reports group-level adverse-event counts. These registry entries help readers understand what the trial was designed to study and what safety counts the registry records.
The record does not report the primary endpoint results or comparative estimates. It therefore does not show whether the groups differed on persistent HPV-16 or HPV-18 infection and/or associated CIN1+, how large a difference might have been, or how precise an estimate would be. No conclusion about the primary question can be drawn from the design description alone. Likewise, the recorded adverse-event counts and listed terms are descriptive information, not proof of a causal effect or a complete comparative safety assessment.
The endpoint's combined definition is important to the meaning of any future comparison. It includes persistent infection over an approximately six-month interval and histopathologically confirmed CIN1+ associated with HPV-16 and/or HPV-18. A combined result would not necessarily reveal the separate pattern for infection and lesion outcomes. The registry lists relevant secondary outcomes, but their results are not reported in the registry record.
General statistical explanation: a trial design describes how evidence was intended to be collected; an outcome analysis describes what was observed under a specified definition and population. Neither enrollment nor a planned follow-up schedule is an outcome result. The registry's completed status does not supply missing comparative estimates. The information supports careful description of the study, but not a claim that the intervention did or did not change the primary outcome.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way its primary outcome combines persistent infection with a pathology-confirmed cervical endpoint. That makes endpoint interpretation dependent on both laboratory detection across consecutive evaluations and histopathological classification. The definitions and timing are therefore central to understanding what an event means, rather than treating the outcome as a generic count.
The according-to-protocol population also matters. The registry describes eligibility for the primary efficacy cohort in terms of baseline cytology and receipt of three doses, and additionally describes DNA- and serostatus-defined groups. These choices define which participants contribute to the intended analysis. Since the full population description and primary denominators are not reported in the registry record, the reader cannot evaluate how the analyzed population relates to all randomized participants.
The record illustrates an important distinction between a registered outcome and an analyzed result: it lists 49 outcome measures but 0 analyses. A detailed outcome definition can make the research question clear without providing evidence about the observed group comparison. Likewise, randomized allocation and masking are design features, not substitutes for estimates and measures of uncertainty.
Finally, the record includes group counts for serious and other adverse events, but does not report a comparative safety analysis. Statistical reading requires separating descriptive counts from estimates of between-group differences and from causal interpretation. The missing primary results and analysis details limit conclusions, even though the study design and endpoint definitions are described.
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 for interpreting efficacy is that the registry record does not report primary-outcome counts, denominators, comparative estimates, or uncertainty intervals. The primary endpoint is combined, and component-specific comparative results are also not reported. Although secondary outcomes are listed, their results are not reported in the registry record.
The primary efficacy population description is incomplete. It identifies an according-to-protocol cohort with normal or low-grade cytology at Month 0 who received three doses, then ends before all eligibility details are given. The record also describes DNA- and serostatus-defined groups, but does not provide their primary outcome results or denominators. This prevents a clear assessment of the full analysis population and how it was constructed.
Methods needed to assess the reliability of an outcome comparison are not reported in the registry record, including missing-data handling, a detailed statistical analysis plan, multiplicity procedures, and any interim-analysis approach. The registry does not report the sample-size justification. The planning assumptions describe illustrations, but these are not a replacement for the trial's documented design rationale or a reported primary analysis.
For safety, counts are listed, but a comparative analysis and uncertainty estimates are not reported. Death counts are not reported. The context and denominator for the listed serious adverse-event percentages are not specified in the registry information addressed. The study's completed status and planned follow-up descriptions do not resolve these omissions or establish that all participants had the same follow-up.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older — NCT00294047.
- Registry record last updated 2020-01-02; status last verified 2019-12.
- Results first posted 2012-03-27.
- 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
NCT00294047 is a completed randomized, quadruple-masked, parallel-group Phase 3 study sponsored by GlaxoSmithKline. It enrolled 5752 and compared three intramuscular doses of Cervarix with three doses of an aluminium hydroxide control, on a 0, 1, 6 months schedule, in healthy women aged 26 years and older.
The primary outcome was a participant count for persistent HPV-16 or HPV-18 infection and/or associated histopathologically confirmed CIN1+, with a timeframe up to Month 48. The registry lists 49 outcome measures and 0 analyses. Comparative primary-outcome results, effect estimates, and uncertainty intervals are not reported in the registry record. Safety information includes group counts for serious and other adverse events; death counts are not reported.