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 Cobas® 4800 HPV Test for the Detection of High-grade Cervical Disease (NCT00709891), a na na study. The primary outcome is Percentage of Participants With a Diagnosis of ≥ CIN2.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00709891 |
| Phase | NA |
| Condition | Human Papilloma Virus (HPV) |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | Triple |
| Enrollment | 47208 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned women undergoing routine cervical cancer screening. The primary outcome population was narrower: evaluable participants with atypical squamous cells of undetermined significance (ASC-US). The registry defines this population as all enrolled participants with an ASC-US diagnosis, but does not report its size or describe how many participants contributed endpoint data.
Intervention
The test under evaluation was the cobas® 4800 HPV Test. It identifies pooled high-risk oncogenic HPV types and reports genotypes 16 and 18 individually. This was an evaluation of a diagnostic device, not a comparison of assigned clinical treatments.
Comparator
The study is listed as a single-group study, and allocation is recorded as NA. No like-for-like control group is described. The record therefore does not establish a randomized comparison between the test and another screening strategy.
Primary question
The primary question was what percentage of participants in the evaluable ASC-US population received a diagnosis of at least CIN2 during the baseline period, up to 12 weeks. Diagnosis was based on central pathology review of histology. The percentage, numerator, denominator, and comparative accuracy estimates are not reported in the registry record.
The broader study description says the baseline, cross-sectional phase involved approximately 45,000 women undergoing routine screening. Approximately 7,400 were selected for colposcopy and biopsy or endocervical curettage at baseline. Some participants with normal cytology entered a follow-up phase with annual cytological evaluation for 3 years; colposcopy and tissue assessment during follow-up were performed only when cytology was considered not normal. Those design details describe how evaluation was organized, but they do not supply the primary outcome result or a comparison of screening strategies.
3. Trial Design
The registry classifies the study as a single-group evaluation of the cobas® 4800 HPV Test. Allocation is recorded as NA, so the record does not describe random assignment or a randomized control group. The masking entry is TRIPLE, but which people or roles were masked, and what information was concealed from them, are not reported in the registry record. The phase is listed as NA.
The study enrolled 47208 participants. Its recorded start is 2008-05, and its primary completion is 2013-06; the status is completed. These registry dates do not, on their own, describe the timing of each participant’s assessments or establish when every analysis was finalized.
The brief study description distinguishes a baseline, cross-sectional phase from a follow-up phase. At baseline, approximately 45,000 women undergoing routine screening were included, and approximately 7,400 were selected for colposcopy and biopsy or endocervical curettage. A selected group of women with normal cytology also entered follow-up, with annual cytological evaluation for 3 years. During follow-up, colposcopy and tissue assessment were performed only for women whose cytology was considered not normal at an annual visit.
The device combines pooled detection of high-risk oncogenic HPV types with individual identification of genotypes 16 and 18. The record describes performance assessment for identifying histologically confirmed high-grade cervical disease. It does not describe a treatment allocation or a clinical strategy comparison. Details such as the planned recruitment targets, eligibility criteria beyond the primary population definition, test procedures, assessor roles, and protocol deviations are not reported in the registry record. A sample-size justification and a more detailed statistical plan are also not reported.
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: Participants who had not met the study primary clinical endpoint of ≥ CIN2 were invited to participate in the longitudinal follow-up phase.
Baseline, Cross-sectional Phase
| Stage | Cobas® 4800 HPV Test |
|---|---|
| STARTED | 47208 |
| COMPLETED | 45758 |
| NOT COMPLETED | 1450 |
Longitudinal Follow-up Phase
| Stage | Cobas® 4800 HPV Test |
|---|---|
| STARTED | 10002 |
| COMPLETED | 5020 |
| NOT COMPLETED | 4982 |
Analysis population for the primary outcome, as defined in the registry: Evaluable ASC-US participant population: All enrolled participants with a diagnosis of atypical squamous cells of undetermined significance (ASC-US).
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: Eligible population: All participants who met the study inclusion/exclusion criteria, had not been enrolled in the study previously, and had not withdrawn consent before undergoing any study procedures. Of the enrolled population, 321 participants did not meet these criteria.
| Characteristic | Unit | Cobas® 4800 HPV Test |
|---|---|---|
| Participants analysed | 46887 | |
| Age, Continuous | years | 39.8 (SD 12.3) |
| Sex: Female, Male: Female | Participants | 46887 |
| Sex: Female, Male: Male | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With a Diagnosis of ≥ CIN2, measured over Baseline to the end of the Baseline period (up to 12 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants diagnosed with at least CIN2. CIN2 is cervical intraepithelial neoplasia grade 2. The registry’s definition also includes CIN3, adenocarcinoma in situ, squamous cell carcinoma, and adenocarcinoma. The diagnosis was based on central pathology review, which specifies the review basis for classifying histology but does not provide information about agreement between reviewers or other quality-control procedures.
The timeframe is baseline to the end of the baseline period, up to 12 weeks. The stated analysis population is the evaluable ASC-US participant population: all enrolled participants with an ASC-US diagnosis. The endpoint is a percentage rather than a time-to-event measure. It is intended to describe how often a histologically defined diagnosis occurred in that specified population during the stated period.
Such an endpoint can be useful in a diagnostic evaluation because it connects test assessment to a clinically defined disease finding. However, a percentage of participants diagnosed with disease is not, by itself, a complete measure of diagnostic accuracy. Sensitivity, specificity, predictive values, and comparisons with another test would require additional reported data and analysis definitions. Those results are not reported in the registry record. The primary endpoint’s numerator, denominator, percentage, and uncertainty interval are also not reported, so the magnitude and precision of the endpoint cannot be described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a primary endpoint and its population, but does not report the primary endpoint result. In particular, it gives no number of ASC-US participants diagnosed with at least CIN2, no denominator for the evaluable population, and no endpoint percentage. It also reports no confidence interval, hypothesis test, or analysis estimate for this outcome. Consequently, the registered information does not show the observed frequency of the primary outcome or how precisely that frequency was estimated.
The record lists 2 outcome measures: the primary measure is the percentage with a diagnosis of at least CIN2, and the secondary measure is the percentage with a diagnosis of at least CIN3. It does not give the result for either measure. It also records 0 analyses. This means there is no posted statistical analysis result to interpret alongside the outcome definitions. It does not establish what analyses may have been conducted outside the registry record.
The study’s single-group classification matters when interpreting the stated objective. The record describes an evaluation of a diagnostic test, not a randomized comparison of two groups. A single-group outcome percentage, even if reported, would not by itself show that one screening approach outperformed another. In this record, even that percentage is unavailable. The test description and study population identify what was evaluated, but they do not establish diagnostic accuracy or comparative performance.
The broader study description includes baseline tissue assessment for a selected group and follow-up cytology for a selected group with normal cytology. During follow-up, tissue assessment was undertaken only after cytology was considered not normal. This means that the described assessment pathway differed according to cytology status. The registry does not provide enough analysis detail to determine how that pathway affected endpoint ascertainment or how results from baseline and follow-up were combined. Those details are not reported in the registry record.
Some registered information can still be read descriptively. The record reports enrollment of 47208 and describes approximate baseline and colposcopy populations. It names histologically confirmed disease as the evaluation target and specifies central pathology review for the primary diagnosis. These are design and definition details, not evidence of a particular diagnostic result. The study’s completed status does not fill the gap: status alone does not communicate endpoint estimates, uncertainty, or whether an analysis supports a specific conclusion.
For this reason, any interpretation of performance should be limited to the fact that the study was designed to evaluate the test in the described screening setting and that the registry defines the primary outcome. The result, its precision, and the analytic basis for claims about test performance are not reported in the registry record. No conclusion about whether the test identifies disease accurately or comparatively can be drawn from the posted outcome information.
9. Statistical Methods Explained
What does a percentage endpoint describe?
General statistical explanation: a percentage endpoint describes the share of a defined analysis population meeting a specified outcome definition during a defined period. Its interpretation depends on both parts of the calculation: the number of participants who meet the outcome definition and the number of participants included in the denominator. A clearly defined population and observation window help readers understand what the percentage represents, but the estimate itself is needed to describe the observed frequency.
For this study, the stated primary measure is the percentage of evaluable ASC-US participants diagnosed with at least CIN2 at baseline, through the end of the baseline period, up to 12 weeks. The record supplies the outcome definition and population description but not the numerator, denominator, or percentage. It is therefore not possible to assess the observed frequency, or whether the endpoint was available for all participants in the defined population.
What does an uncertainty interval add?
General statistical explanation: a confidence interval expresses the uncertainty associated with an estimate under a specified statistical method. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. An interval does not remove uncertainty or establish that an estimate applies beyond the population and conditions studied. Its interpretation also depends on the analysis population, outcome definition, and handling of incomplete observations.
No confidence interval for the primary or secondary endpoint is reported in the registry record. Without an estimate and interval, readers cannot assess either the outcome frequency or the precision of an estimate. The record also does not provide a test statistic or p-value for these outcomes. The absence of those results should not be mistaken for evidence of no effect or no association; it means the registry record does not report an analysis result from which such an interpretation could be made.
Why does the study structure matter?
General statistical explanation: a single-group evaluation can describe results in the group studied, but it does not create the same direct comparison as a design with separate groups assigned to different strategies. A comparison requires clear group definitions and results for each group, along with an analysis that accounts for the design. The registry lists a single-group study and allocation as NA. It does not describe a like-for-like control group, so comparative treatment or screening claims are not supported by the design information recorded.
The study description includes both baseline assessment and a follow-up pathway. A selected group underwent colposcopy and biopsy or endocervical curettage at baseline. A selected group with normal cytology entered annual cytological follow-up for 3 years, and tissue assessment during follow-up was limited to participants with cytology considered not normal. General statistical explanation: when verification of disease depends on an earlier test result, the set of participants with a definitive disease assessment may differ from the full screened population. Appropriate interpretation then depends on the analysis plan and on how unverified participants are handled. The registry does not report enough detail to establish how these issues were addressed in endpoint analyses.
How should a planning illustration be understood?
General statistical explanation: a sample-size planning illustration describes the sample size associated with stated assumptions; it is not a measure of the observed study’s power after results are known. The registry describes an illustration using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. It specifies that non-time-to-event illustrations are expressed as participants per arm. The registry classifies this study as single-group, so assumptions involving two equally allocated arms should not be read as a description of the study’s actual design.
The numerical sample-size illustration values and the effect fractions are not reported in the registry record. The study’s own sample-size justification is not reported either. Any planning illustration should be distinguished from observed enrollment, observed endpoint findings, and an analysis of achieved precision. It does not supply missing outcome estimates or establish that the study had a particular level of observed power.
What is not available about the analysis?
General statistical explanation: an analysis plan explains how the endpoint is estimated, which participants are included, how missing observations are handled, and whether adjustments are made for multiple outcomes or comparisons. These details help distinguish a prespecified analysis from an exploratory one and clarify what the reported uncertainty represents. For diagnostic evaluations, the definitions of positive and negative test results, the reference assessment, and the handling of participants without reference results can be especially important.
The registry record does not report a detailed statistical analysis plan, diagnostic accuracy estimates, missing-data procedures, interim analyses, or a multiplicity strategy. It does not identify statistical models or describe whether estimates were adjusted for participant characteristics. None of these methods can be inferred from the endpoint label, the masking entry, or the completed status. The registry reports 0 analyses, so the posted record contains no analysis output on which to evaluate these methodological choices.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures: a primary percentage with a diagnosis of at least CIN2 and a secondary percentage with a diagnosis of at least CIN3. It does not report a multiplicity strategy, such as whether one endpoint was designated for formal inference, whether any adjustment was planned, or how results across outcomes were to be interpreted together. Such details are not reported in the registry record. The number of listed outcomes alone does not establish that formal statistical tests were performed or that any particular adjustment was needed.
The record identifies the primary analysis population as evaluable ASC-US participants and defines it as all enrolled participants with an ASC-US diagnosis. It does not report the size of that population, how many had a histological assessment, or how many contributed data to the primary endpoint. Missing-data rules, reasons for missing assessments, and sensitivity analyses are not reported in the registry record. It is therefore not possible to determine whether the posted endpoint population would include every participant meeting the definition or how incomplete verification was addressed.
The follow-up description states that annual cytology was conducted for 3 years in a selected group with normal cytology, with colposcopy and tissue assessment only when follow-up cytology was considered not normal. The registry does not report how participants who did not complete follow-up were handled, nor whether outcomes from follow-up were included in either endpoint analysis. Details about analysis populations beyond the stated evaluable ASC-US population are not reported.
The record lists 0 analyses. This does not establish that no analysis took place outside the registry; it means no analysis result is posted in the registry record. Without analysis results and methods, readers cannot evaluate the influence of multiplicity, missing observations, or population selection on the estimated outcomes.
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 |
|---|---|---|---|
| Cobas® 4800 HPV Test | 1 | 47208 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cobas® 4800 HPV Test | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Cobas® 4800 HPV Test |
|---|---|---|
| Urogenital haemorrhage | Vascular disorders | 1 of 47208 |
Serious events with the highest arm-level rate: urogenital haemorrhage (0.0%).
The serious adverse event summary lists the Cobas® 4800 HPV Test group with 47208 participants at risk and 1 participant affected by a serious adverse event. The category for other adverse events lists 0 at risk and 0 affected. These figures describe the registry’s adverse-event summary; they do not provide a complete account of all events, their timing, or their clinical circumstances.
The listed top serious adverse event term is Urogenital haemorrhage, reported as 0.0%. This is a rounded percentage in the registry record. A displayed 0.0% should not be interpreted as proof that no event was recorded, particularly because the same summary reports 1 participant affected by a serious adverse event. The record does not explain the relationship between the term listing and the affected-participant count, or provide event-level details.
The deaths value is not reported in the registry record. The listed figures do not establish that the test caused an adverse event, nor do they establish that no other adverse events occurred. Attribution, severity details beyond the serious-event classification, follow-up duration for safety, and a fuller safety analysis are not reported in the registry record. These counts should be read as a limited registry summary rather than as a complete assessment of safety.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study evaluated the cobas® 4800 HPV Test in women undergoing routine cervical cancer screening and defined a primary histology-based outcome in an evaluable ASC-US population. It also describes baseline tissue assessment for selected participants and annual cytological follow-up for a selected group with normal cytology. These details identify the intended setting and outcome framework.
They do not establish the test’s observed performance. The primary and secondary outcome results are not reported in the registry record, and no diagnostic accuracy estimates or confidence intervals are given. The registry’s completed status and its enrollment of 47208 do not substitute for those missing results. Without the endpoint findings, readers cannot determine the observed proportion diagnosed with high-grade disease in the primary population or the precision of such an estimate.
The record also does not describe a randomized or like-for-like comparator. The study is listed as single-group, and allocation is NA. Accordingly, the posted information does not support a comparative claim about alternative tests, screening strategies, or clinical management. Even a reported percentage from this single group would need to be interpreted in light of the population assessed, the reference assessment, and the way participants with incomplete verification were handled.
General statistical explanation: diagnostic performance is usually assessed by relating test classifications to a defined reference assessment and reporting suitable estimates with uncertainty. A disease percentage alone is not sufficient to establish sensitivity or specificity, and those measures cannot be reconstructed without the underlying classifications and analysis definitions. The registry does not report those classifications or analyses.
The most defensible interpretation is therefore limited: the registry documents an evaluation design and endpoint definitions, but not the findings needed to characterize diagnostic performance. Missing results should not be interpreted as a positive result, a negative result, or evidence that the test does or does not identify disease. Conclusions about clinical usefulness or comparative performance are not reported in the registry record.
13. Why This Trial Matters Statistically
This study is statistically relevant because it illustrates the distinction between a diagnostic device evaluation and a randomized comparison. The registry identifies a single-group evaluation, while the target is histologically confirmed high-grade cervical disease. That combination makes the definitions of the tested population, reference assessment, and verification pathway central to interpretation. The record provides some of those design definitions, including the primary ASC-US population and central pathology review, but does not provide the endpoint results needed to quantify performance.
The study description also highlights that disease verification was not described as uniform across all participants at every stage. Approximately 7,400 participants were selected for colposcopy and tissue assessment at baseline from approximately 45,000 women in the baseline phase. In follow-up, women with normal cytology received annual cytological evaluation for 3 years, with colposcopy and tissue assessment only after cytology was considered not normal. General statistical explanation: when reference assessment is conditional on earlier findings, the method used to analyze participants without that assessment can affect estimates. The registry does not report how that issue was handled.
The record’s limitations are themselves informative for statistical reading. It defines a primary outcome and a secondary outcome, but gives no analysis results, uncertainty intervals, or statistical plan. As a result, the design can be discussed, but the results cannot be independently assessed from the registry record. This distinction helps prevent enrollment size, completed status, or endpoint labels from being mistaken for evidence about diagnostic accuracy.
The record also lists a planning illustration based on assumptions involving equal allocation between two arms, while classifying the evaluation as single-group. This is a reminder that planning assumptions must be separated from the actual design and from observed results. The study’s own sample-size justification is not reported. Overall, the statistical importance lies in recognizing what information a diagnostic evaluation needs for interpretation and what remains unavailable in this registry 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 primary limitation for statistical interpretation is that the registry does not report the primary or secondary outcome results. It provides neither the number of participants meeting either disease definition nor the corresponding analysis denominators. No confidence intervals, p-values, or diagnostic accuracy estimates are reported. Thus, the central performance question cannot be answered from the posted results.
The stated primary population is evaluable participants with ASC-US, but its size and the meaning of evaluable are not further detailed. The record does not report missing-data procedures, the extent of incomplete assessment, or sensitivity analyses. It also does not explain how the selective use of colposcopy and tissue assessment was handled in analyses. These omissions prevent assessment of the potential effects of population selection and incomplete reference verification.
The single-group classification and NA allocation mean that the record does not describe a direct control comparison. The masking entry is TRIPLE, but the masked parties and masking procedures are not reported. The detailed statistical plan, including multiplicity handling and interim analyses, is not reported in the registry record. Neither the registry’s completed status nor the total enrollment resolves these uncertainties.
The safety summary is limited as well: it gives a serious adverse event count and a rounded term percentage but not event-level context, attribution, or a complete safety analysis. The deaths value is not reported in the registry record. Finally, the study’s own sample-size justification is not reported. Together, these limitations mean that the available record describes important aspects of the study’s design and outcome definitions, but does not permit a quantitative or comparative assessment of test performance.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of the Cobas® 4800 HPV Test for the Detection of High-grade Cervical Disease — NCT00709891.
- Registry record last updated 2015-02-09; status last verified 2015-02.
- Results first posted 2015-02-09.
- 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
NCT00709891 is a completed, single-group evaluation of the cobas® 4800 HPV Test for detecting high-grade cervical disease in women undergoing routine screening. Enrollment was 47208. The registry records a start of 2008-05 and primary completion of 2013-06, lists masking as TRIPLE, and gives allocation and phase as NA.
The primary outcome is the percentage of evaluable ASC-US participants diagnosed with at least CIN2 during baseline, up to 12 weeks, based on central pathology review. The secondary outcome concerns diagnosis of at least CIN3. The record describes baseline assessment and selected follow-up, but reports 0 analyses and no endpoint results. The sample-size justification, detailed analysis methods, and missing-data procedures are not reported in the registry record. The posted information therefore defines the evaluation but does not quantify its diagnostic findings.