Use of High-Resolution Microendoscopy (HRME) in Patients With Adenocarcinoma In-Situ (AIS) of the Cervix: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of High-Resolution Microendoscopy (HRME) in Patients With Adenocarcinoma In-Situ (AIS) of the Cervix (NCT02206048), a na na study. The primary outcome is Feasibility of Acquiring In-vivo High-Resolution Microendoscopy (HRME) Images of Cervix Prior to Conization.

2. Clinical Question

3. Trial Design

The registry describes a completed, single-group study of HRME imaging in participants with AIS of the cervix. Its allocation is listed as not applicable, and masking is listed as none. The study is not a randomized trial and does not include a like-for-like control group. The registry lists the phase as not applicable and reports enrollment of 9.

The procedure description places imaging before cold knife cone biopsy. Before imaging, 0.01% proflavine solution was applied topically to the cervix. The HRME probe was then applied and high-resolution images were obtained. The description says cervical biopsies were taken from abnormal areas noted with colposcopy and/or HRME. Further procedural detail is not reported in the registry record.

The listed primary outcome concerned feasibility of acquiring in-vivo HRME images before conization, with a timeframe of 1 day. A secondary outcome concerned distinguishing AIS from normal cervical tissue using HRME imaging. The registry lists 2 outcome measures and 0 analyses. It states that data were not collected because enrollment requirements were not met; consequently, the record does not provide outcome estimates for image acquisition or tissue discrimination.

The study began on 2015-10-02, reached primary completion on 2021-04-21, and has a completed status. These administrative milestones do not establish that outcome data were collected or that the study’s clinical questions were resolved. A more detailed statistical 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Due to not meeting enrollment requirements, data was not collected

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.

6. Primary Endpoint

The registry lists the primary outcome as Feasibility of Acquiring In-vivo High-Resolution Microendoscopy (HRME) Images of Cervix Prior to Conization, measured over 1 day.

The primary endpoint was feasibility of acquiring in-vivo HRME images of the cervix before conization. The registry specifies an image-acquisition criterion of 18 of 20 participants. This endpoint addresses whether the imaging procedure can produce images in the intended setting, rather than whether the images accurately identify a tissue diagnosis or improve a clinical outcome. A feasibility measure can help determine whether a procedure is workable enough to study further, but it does not by itself establish diagnostic performance.

The outcome timeframe was 1 day. However, the registry states that data were not collected because enrollment requirements were not met. It therefore reports no observed image-acquisition result and no estimate of uncertainty around the feasibility criterion. The endpoint’s definition is present, but its measured outcome is not.

The registry also lists distinguishing AIS from normal cervical tissue as a secondary outcome. No corresponding results or analysis are reported. Although the procedure description mentions cervical biopsies of abnormal areas, the registry record does not report how tissue findings were paired with HRME images or used in an analysis. Those details would be important for interpreting a diagnostic endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

There is no outcome analysis reported for this study. The registry lists 0 analyses and states that data were not collected because enrollment requirements were not met. This means that statistical methods can be discussed only as general concepts relevant to the stated questions; they should not be mistaken for methods used to produce study results.

What does a feasibility endpoint measure?

In general, a feasibility endpoint asks whether a procedure can be carried out and produce the intended data in the setting being studied. Here, the specified task was acquiring in-vivo HRME images before conization. The registry defined a target of 18 of 20 participants. That target is a decision rule written into the outcome description; it is not an observed success rate. Because the record reports no collected outcome data, it gives no numerator for successful image acquisition and no estimate of the proportion meeting the imaging objective.

For a binary feasibility outcome, an analysis might ordinarily report the number meeting the criterion and the number assessed, along with an interval expressing uncertainty. The exact analysis plan for this study is not reported in the registry record. General statistical interpretation would consider both the estimated proportion and its precision: a result from a limited number of observations would ordinarily leave more uncertainty than a result based on a broader set of observations. In this record, no such estimate or interval is available.

How would diagnostic discrimination be assessed?

In general, assessing whether an imaging method distinguishes diseased from normal tissue requires a defined unit of analysis, an image interpretation rule, and a way to classify tissue status. Investigators may compare image classifications with an independent tissue assessment and summarize agreement or diagnostic accuracy. Such analyses need clarity about how ambiguous images are handled, whether readers know tissue findings, and whether multiple images or tissue sites from one participant are treated as related observations.

The registry lists a secondary outcome about distinguishing AIS from normal cervical tissue, and it describes biopsies of abnormal areas noted with colposcopy and/or HRME. It does not report an analysis, classification threshold, reference-standard procedure, reader blinding, or results for that secondary outcome. These elements must not be assumed. In particular, the procedural mention of biopsy does not specify how biopsy results were linked to individual images or used in an accuracy calculation.

What is the role of a confidence interval?

In general, a confidence interval describes the uncertainty associated with an estimate under a statistical model. It is not a guarantee that the true value lies within the interval, and its width depends on factors including the amount and variability of data. An interval could have helped convey the precision of a feasibility proportion or a diagnostic measure if such outcomes had been collected and analyzed. No confidence interval is reported for this study, and there is no estimate to which one could be attached.

Likewise, a p-value would address compatibility between data and a specified statistical hypothesis under assumptions. It would not establish that an imaging method is useful, accurate, or clinically beneficial. The registry does not report a p-value or a hypothesis test for either listed outcome. No significance result should be inferred from the completed status or from the presence of outcome definitions.

What do the planning assumptions mean?

The statistical material associated with the record describes sample-size planning illustrations based on an observed effect, rather than the study’s own design. The stated assumptions include 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. For time-to-event illustrations, the stated quantity is a total number of events using the Schoenfeld method; other illustrations are expressed as participants per arm.

These are general planning assumptions, not observed results, and the planning illustrations are not the trial’s own design. The registered study is single-group, so an equal-allocation two-arm planning scenario is not a description of its enrollment structure. The registry does not report an effect estimate from collected outcome data, and the record does not describe a trial-specific sample-size justification. Planning illustrations cannot supply missing outcome observations or be interpreted as observed power.

Over-dispersion is a general issue for count outcomes: it occurs when observed variation exceeds what a simple model assumes, potentially making standard errors too small if the model does not account for it. The listed primary endpoint is feasibility of image acquisition, not a count outcome, and the registry does not report an over-dispersion analysis. More broadly, because no outcome analysis is reported, no model assumptions or diagnostic checks can be evaluated for the study’s primary or secondary question.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary feasibility outcome and a secondary outcome about distinguishing AIS from normal cervical tissue. It also lists 2 outcome measures and 0 analyses. The statistical plan for handling more than one outcome, including any adjustment for multiple testing or prioritization among secondary measures, is not reported in the registry record. In general, when several outcomes or tests are examined, the chance of finding an apparently notable result by chance can increase; methods for managing that issue depend on the study’s analysis plan. No such plan or results are available to assess.

Missing outcome data are central to interpretation. The registry explicitly states that data were not collected because enrollment requirements were not met. It does not report individual-level outcome availability, reasons for noncollection beyond that statement, or any method for handling missing values. Since the primary feasibility outcome was not collected, there is no observed estimate to analyze. No imputation, sensitivity analysis, or other missing-data procedure is reported in the registry record.

The record does not describe an analysis population, such as which participants would have been included in the primary endpoint analysis or how exclusions would be handled. It is therefore not possible to determine whether an intention-to-treat, per-protocol, or other population was specified. The registry’s enrollment figure and its statement that data were not collected do not establish the makeup of any analysis set. In general, transparent reporting of analysis populations and missingness helps readers understand which observations support an estimate; those details are not reported for this study.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

The registry’s HRME group safety entry reports 8 participants at risk for serious adverse events, with 0 serious adverse events affecting participants. It also reports 8 at risk for other adverse events, with 0 other adverse events affecting participants, and 0 deaths. These are the posted counts for the listed safety categories.

These counts should not be read as proof that the procedure has no risks. They describe what the registry reports for the listed group and categories; the record does not provide event definitions, collection methods, or detailed follow-up information. It also does not explain why the safety denominator is 8 while enrollment is reported as 9. The two figures should not be combined or reconciled by assumption.

The registry lists no serious adverse-event terms. Zero reported events means no events are recorded in these fields; it does not establish that every possible adverse event was actively assessed or that no unlisted event occurred. The safety figures do not answer the separate question of whether images could be acquired or distinguish AIS from normal tissue.

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

The registry establishes that the study aimed to assess whether HRME images could be acquired from the cervix before conization and whether those images could distinguish AIS from normal cervical tissue. It describes topical application of 0.01% proflavine and use of an HRME probe before CKC. It also defines the primary feasibility criterion as image acquisition in 18 of 20 participants.

The record does not establish whether the feasibility target was met. It reports enrollment of 9 and states that data were not collected because enrollment requirements were not met. There is no reported image-acquisition count or estimate of feasibility. The completed study status is an administrative status, not evidence that outcome data were analyzed.

The record also does not establish whether HRME images distinguished AIS from normal cervical tissue. No diagnostic results, accuracy estimates, or analysis methods are reported. The existence of a secondary outcome definition and a description of cervical biopsies does not show that image classifications were compared with tissue findings or that diagnostic performance was quantified.

More generally, a feasibility study and a diagnostic-accuracy study answer different questions. Evidence that images can be obtained would not by itself show that they classify tissue correctly. Diagnostic discrimination would require reported comparisons and suitable analyses. Neither question can be resolved from the outcome information in this registry record.

The safety fields report zero serious events, zero other events, and zero deaths among the listed participants at risk, but the record does not provide enough detail to interpret these counts as a comprehensive safety assessment. Overall, the record describes the intended procedure, endpoints, and design, but it does not provide outcome evidence for the primary or secondary clinical question.

13. Why This Trial Matters Statistically

This study is statistically informative because it distinguishes a clearly stated endpoint from an observed result. The primary outcome description gives a specific feasibility criterion: image acquisition in 18 of 20 participants. But the registry also states that data were not collected because enrollment requirements were not met. A prespecified threshold is not a result, and a completed status does not replace outcome data. Keeping those concepts separate prevents an objective from being mistaken for evidence that the objective was achieved.

The record also illustrates why feasibility and diagnostic performance should not be conflated. Acquiring an image is a procedural outcome. Determining whether an image separates AIS from normal tissue requires additional information about tissue classification, image interpretation, and analysis. The registry lists both questions, but reports no analyses for either. This makes the limits of inference explicit: the planned diagnostic purpose does not establish accuracy.

Another statistical lesson is the importance of denominators and analysis populations. Enrollment is reported as 9, while the safety fields list 8 participants at risk for each adverse-event category. The record does not explain the difference. A careful reading preserves each figure in its stated context rather than assuming they refer to identical populations or correcting one using the other.

Finally, planning illustrations and trial results serve different purposes. Sample-size assumptions can describe how a future study might be planned under particular conditions, but they cannot replace observations that were not collected. The registry’s single-group design also differs from the equal-allocation two-arm assumptions described for planning illustrations. This distinction helps readers avoid interpreting a planning scenario as the design or result of the registered study.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting this study is that the registry reports no collected outcome data. It therefore provides no observed primary feasibility result and no result for the secondary tissue-discrimination outcome. Without outcome observations, effect estimates, uncertainty intervals, or statistical comparisons cannot be assessed.

The registry reports enrollment of 9 and says data were not collected because enrollment requirements were not met, while the primary outcome description defines a criterion using 18 of 20 participants. The record does not further explain the enrollment requirements or how the criterion was intended to be applied in the circumstances. No explanation should be inferred beyond the registry’s statement.

The registered design is single-group, with allocation listed as not applicable and masking listed as none. The record does not report how HRME images were interpreted, whether readers had access to clinical or tissue findings, how biopsies related to the imaging outcomes, or what analysis would have been used to compare imaging with tissue status. These omissions prevent assessment of potential measurement and interpretation biases.

The safety information is also limited: the registry gives zero counts for the listed event categories, but does not describe event definitions or collection procedures. It lists 8 participants at risk for safety outcomes, without explaining how that group relates to the enrollment figure. Finally, a detailed statistical analysis plan, analysis populations, missing-data methods, and trial-specific sample-size justification are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Use of High-Resolution Microendoscopy (HRME) in Patients With Adenocarcinoma In-Situ (AIS) of the Cervix — NCT02206048.
• Registry record last updated 2022-07-25; status last verified 2022-07.
• Results first posted 2022-07-25.
• 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

This completed single-group study evaluated HRME imaging before cervical conization in the setting of AIS. The procedure description includes topical 0.01% proflavine, HRME probe application, image acquisition, and biopsies of abnormal areas noted with colposcopy and/or HRME. The primary outcome was feasibility of acquiring in-vivo images before conization, with an image-acquisition criterion of 18 of 20 participants. A secondary outcome concerned distinguishing AIS from normal cervical tissue.

The registry reports enrollment of 9 and states that data were not collected because enrollment requirements were not met. It lists 0 analyses, so no primary or secondary outcome result is available. Safety fields report zero serious adverse events, zero other adverse events, and zero deaths among 8 participants at risk for each listed category. The record does not explain the safety denominator or provide detailed statistical methods or analysis populations.