Clinical Evaluation of the APTIMA® HPV Assay Using the TIGRIS® System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Evaluation of the APTIMA® HPV Assay Using the TIGRIS® System (NCT00973362), a non-randomized phase 3 study. The primary outcome is Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+.

2. Clinical Question

The two study populations address different clinical settings: a group with negative cytology results and a group with ASC-US results. The record lists separate outcome measures for assay performance in the ASC-US study arm, including CIN2+ detection by each assay. Those secondary outcomes do not change the stated primary question, which is focused on the Adjunct study arm. The record gives the trial's overall enrollment as 12896, but does not report the primary outcome's result, an effect estimate, or its precision. It therefore establishes what comparison was planned for reporting, but does not establish how the assays performed relative to one another.

3. Trial Design

The registry classifies this as a phase 3, non-randomized, unmasked, single-group study. Its stated purpose is to evaluate the performance of the APTIMA HPV Assay using the TIGRIS System. The study includes an Adjunct cohort described as women 30 years of age or older with negative cytology results, and an ASC-US cohort described as participants with ASC-US Pap test results. The registry lists enrollment of 12896 and a completed status.

The primary outcome concerns the comparison of APTIMA HPV Assay performance with an FDA-approved HPV assay for detecting CIN2+ in the Adjunct study arm. The timeframe is baseline evaluation. The registry also lists secondary outcomes for CIN2+ detection in the ASC-US study arm, separately describing performance for the APTIMA HPV Assay and the FDA-approved HPV DNA assay. These descriptions identify the clinical comparison and populations, but do not give the underlying assay results or the statistical measures used to express performance.

Because allocation is recorded as non-randomized and the model as single group, this should not be read as a randomized treatment-versus-control trial. The assay comparison is not a like-for-like control comparison based on randomized allocation. The registry does not report whether readings were paired within participants, how specimens were allocated or processed, or whether assay order was controlled. Masking is recorded as none. Further operational details, including the exact participant flow and the numbers included in each outcome analysis, are not reported in the registry record.

The record gives the study start as 2008-03 and primary completion as 2013-06. Those dates describe the registry timeline; they do not provide the timing or conduct of individual analyses. A protocol-level statistical plan, including any sample-size justification or interim analysis plan, is 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.

Baseline Evaluation

Reasons for not completing this period:

3-Year Follow-up

Reasons for not completing this period:

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: Baseline Evaluable Analysis Population

6. Primary Endpoint

The registry lists the primary outcome as Adjunct Study Arm: Compare Assay Performance for Aptima HPV Assay to a FDA-Approved HPV Assay for Detecting CIN2+, measured over Baseline Evaluation.

The primary outcome is described as a comparison of APTIMA HPV Assay performance with an FDA-approved HPV assay for detecting CIN2+ in the Adjunct study arm. CIN2+ refers in the registry wording to the disease threshold being detected. The endpoint's timeframe is baseline evaluation, and its unit is participants. The listed parameter is a number, but the registry description does not specify whether the primary comparison is based on sensitivity, specificity, predictive values, agreement, or another performance measure. Nor does it report the actual counts or estimates.

In general, diagnostic performance outcomes are used to describe how well a test classifies participants relative to a disease status reference. A disease threshold such as CIN2+ makes the target condition explicit, while a defined clinical population clarifies the setting to which performance estimates apply. Different performance measures answer different questions: for example, sensitivity concerns detection among people with the condition, while specificity concerns classification among those without it. These measures are not interchangeable, and interpretation depends on which was prespecified and reported.

The registry's outcome description signals the target condition and the comparison, but does not supply enough detail to identify the precise statistic or interpret its size. The result and its uncertainty are not reported in the registry record. Accordingly, the endpoint description establishes the intended subject of evaluation, not evidence of the assays' relative performance.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a diagnostic performance comparison estimate?

In general, diagnostic studies compare a test's classifications with a method used to establish whether the target condition is present. A performance estimate summarizes a particular aspect of that classification. Sensitivity and specificity describe different parts of the classification process; predictive values answer different questions and can depend on how common the condition is in the tested population. Agreement statistics address whether tests produce matching classifications, which is not identical to whether either test correctly identifies disease.

The registry's primary outcome names CIN2+ as the target and describes a comparison between the APTIMA HPV Assay and an FDA-approved HPV assay. It does not name the specific diagnostic statistic, give the underlying classifications, or provide a numerical estimate. Therefore, no one performance measure can be attributed to the primary outcome from the registry description alone.

Why does the population matter?

In general, diagnostic performance can vary with the population being evaluated, including differences in clinical presentation and disease prevalence. Estimates from people with negative cytology results need not describe performance in people with ASC-US results. This record identifies those as separate study settings and lists separate outcome measures for the ASC-US cohort. Results for one cohort should not be assumed to represent the other.

The Adjunct group is described as women 30 years of age or older with negative Pap test results, and the ASC-US group as participants with ASC-US Pap test results. The record's primary question pertains to the Adjunct group. It does not report the primary analysis population or establish whether every enrolled participant contributed usable results to that analysis.

What is the role of a reference assessment?

In general, estimates of diagnostic accuracy rely on a reference assessment that classifies disease status. The ASC-US description says disease status is based on colposcopic biopsy results. For the Adjunct study, the description refers to known cervical disease but does not provide the specific ascertainment process. The registry also does not report whether all participants received the same reference assessment, how indeterminate results were handled, or the timing between assay testing and disease assessment. These details matter because different procedures can affect the classification counts used in diagnostic estimates.

How should uncertainty be read?

In general, a confidence interval describes a range of values compatible with the observed data under the statistical model and confidence procedure used. A narrow interval indicates greater precision than a wide interval, but does not by itself show that a result is clinically important. A point estimate without an interval gives limited information about precision. The registry record does not report confidence intervals or any other uncertainty interval for the primary outcome.

In general, a p-value evaluates how compatible data are with a specified null model, subject to the analysis assumptions. It is not a measure of the probability that a hypothesis is true, nor does it express the size or clinical relevance of a difference. No primary p-value or testing procedure is reported in the registry record.

What do the planning illustrations mean?

The planning assumptions describe illustrations based on an observed effect, not the trial's own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The illustrations are planning quantities, not observed power and not evidence that the study had a particular probability of detecting an effect. The effect estimate on which such planning illustrations depend is not reported in the registry record, and the record does not report the trial's sample-size justification.

In general, over-dispersion means that variability is greater than expected under a model that assumes a particular mean-variance relationship. When present, it can make standard errors and confidence intervals based on that simpler model too small. The primary outcome is described as a number of participants, and the registry does not report a model for the outcome or a dispersion parameter. Over-dispersion therefore cannot be assessed for this outcome from the registry record.

Overall, the available methods description identifies the study type, population settings, comparator, and target condition. It does not provide sufficient detail to reproduce or evaluate the primary statistical analysis. The analysis model, estimand, handling of missing or indeterminate measurements, and method for estimating uncertainty are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and 22 analyses. It does not report how the analyses correspond to the outcome measures, which analyses were designated primary or secondary beyond the outcome labels, or whether any multiplicity adjustment was planned or applied. When multiple outcomes or analyses are considered, the chance of obtaining an apparently notable result can increase if each is tested without an appropriate strategy. In general, adjustment methods or a prespecified hierarchy can address that issue, but the record does not identify such a method.

Missing-data procedures and analysis populations are not reported in the registry record. The record does not say how missing assay results, missing biopsy assessments, indeterminate classifications, or incomplete follow-up were handled. It also does not give the numbers of participants included in each primary or secondary analysis. The enrollment figure alone does not establish the denominator for any specific diagnostic outcome.

These omissions limit interpretation of both the size and reliability of any estimate. In general, excluding participants with incomplete results can affect a diagnostic comparison if the likelihood of missingness is related to test results or disease status. Whether that issue arose in this study cannot be determined from the registry record. No imputation method, sensitivity analysis, or analysis-population definition is reported.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The adverse-event record lists the Adjunct group with 11644 at risk and zero serious adverse events and zero other adverse events. The ASC-US group is listed with 1252 at risk and zero serious adverse events and zero other adverse events. These are the recorded event counts for the listed groups; they do not describe diagnostic performance or the primary CIN2+ outcome.

The deaths field is not reported in the registry record. The record also does not provide additional detail about how adverse events were defined, collected, assessed for relatedness, or monitored over time. The absence of recorded events in these entries should therefore be read as a description of the registry counts, not as proof that no events occurred outside the recorded reporting process. The record does not explain whether the listed at-risk counts are the same populations used in any outcome analysis.

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

The registry record establishes that a phase 3 study evaluated the APTIMA HPV Assay using the TIGRIS System in two cytology-defined settings. Its primary question was whether assay performance for detecting CIN2+ in the Adjunct study arm compared with an FDA-approved HPV assay. It also lists ASC-US outcome measures for both assays. These details describe the study's purpose and scope, but they do not provide a numerical answer to the primary question.

The record does not report assay-specific counts, diagnostic estimates, confidence intervals, p-values, or the primary analysis denominator. It therefore does not show the direction or size of any performance difference, or how precisely that difference was estimated. No conclusion that one assay performed better, worse, or equivalently is supported by the registry entry alone.

In general, a diagnostic comparison is specific to its population, disease definition, reference assessment, and analysis methods. Findings in women 30 years of age or older with negative Pap test results would not automatically describe the ASC-US cohort or other populations. The record's non-randomized allocation and single-group classification also mean the comparison is not a randomized treatment effect.

The planning illustrations, if consulted alongside the record, should be understood as sample-size planning quantities based on an observed effect and stated assumptions, not as observed power or as trial results. The registry does not report the trial's own sample-size justification. Taken together, the entry indicates what was evaluated and how the study was broadly classified, while leaving the clinical performance results and their uncertainty unreported.

13. Why This Trial Matters Statistically

This study is statistically notable for asking a diagnostic-performance question across two cytology-defined settings rather than comparing randomized treatment assignments. The distinction matters: a diagnostic comparison concerns how assay classifications relate to a disease threshold, whereas a randomized treatment comparison concerns outcomes under assigned interventions. The registry classifies this study as non-randomized, unmasked, and single group, so its design should be interpreted accordingly.

The primary question focuses on the Adjunct study arm and detection of CIN2+. The ASC-US cohort has its own listed outcomes, including performance measures for each assay. Keeping the populations separate is important because diagnostic estimates apply to the population in which they were obtained and may not transfer directly to another setting.

The record also illustrates why a clearly named endpoint and its analysis details are important. It identifies the target disease threshold and comparator, but does not state the precise performance statistic, provide counts, or report uncertainty. Without those elements, readers cannot evaluate the magnitude or precision of the comparison. A registry description can identify a clinically relevant question, but a complete statistical interpretation requires results and enough methods detail to understand how they were estimated.

Finally, the listed planning assumptions should not be confused with evidence about the observed study result. Planning calculations and outcome analyses answer different questions. The registry does not report a protocol-level sample-size justification, and the planning illustrations are not observed power. This distinction helps prevent design-oriented quantities from being mistaken for evidence of assay performance.

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 most direct limitation for interpretation is that numerical results for the primary outcome are not reported in the registry record. No assay-specific counts, effect estimate, confidence interval, or p-value is available for the stated comparison. The precise diagnostic performance measure is also not identified in the outcome description, so the intended statistical estimand cannot be established from the record.

The design is recorded as non-randomized, unmasked, and single group. Accordingly, it is not a randomized control comparison, and the record does not establish that assay comparisons were protected from possible differences in assessment or interpretation. The registry does not report who read the assays, how disease status was determined in the Adjunct cohort, or whether testing was paired within participants.

Further limitations arise from missing analysis details. The primary analysis denominator, analysis populations, handling of missing and indeterminate results, statistical model, and uncertainty procedure are not reported in the registry record. Multiplicity handling for the listed four outcome measures and 22 analyses is also not reported. These gaps prevent independent assessment of analysis choices and precision.

The record's enrollment figure and adverse-event group counts do not fill those gaps: neither establishes the number included in the primary diagnostic analysis. The deaths field is not reported in the registry record, and adverse-event collection details are absent. These limitations concern what can be concluded from the registry entry; they do not establish that the underlying study lacked additional methods or results outside the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Clinical Evaluation of the APTIMA® HPV Assay Using the TIGRIS® System — NCT00973362.
• Registry record last updated 2017-01-06; status last verified 2016-11.
• Results first posted 2017-01-06.
• 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.

18. Record Summary

The registry describes a completed phase 3, non-randomized, unmasked, single-group evaluation of the APTIMA HPV Assay using the TIGRIS System. Enrollment is listed as 12896. The study includes an Adjunct cohort of women 30 years of age or older with negative Pap test results and an ASC-US cohort. The primary outcome compares assay performance for detecting CIN2+ in the Adjunct study arm at baseline evaluation, with an FDA-approved HPV assay as comparator.

The record lists four outcome measures and 22 analyses. It does not report numerical primary results, the specific diagnostic performance statistic, analysis denominators, or uncertainty estimates. It also does not report the statistical plan, multiplicity strategy, missing-data methods, or analysis populations. The adverse-event entries list zero serious and zero other adverse events in the two groups; deaths are not reported in the registry record. The entry therefore describes the study question and broad design, but does not provide enough results to assess the relative diagnostic performance of the assays.