Confocal Endoscopic Microscopy for Detection of Early Stage Gastric Cancer in Subjects With Hereditary Diffuse Gastric Cancer Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Confocal Endoscopic Microscopy for Detection of Early Stage Gastric Cancer in Subjects With Hereditary Diffuse Gastric Cancer Syndrome (NCT03648879), a na phase 2 study. The primary outcome is Percentage of Participants With Detectable Confocal Endoscopic Microscopy (CEM) w/Greater Sensitivity for Detection of Signet Ring Cells (SRC)Foci in Cadherin-1 (CDH1) Germline Mutation Carriers Compared to Current Method of Standard White Light Endoscopy.

2. Clinical Question

The study addressed whether adding microscopic inspection could help identify early gastric cancer findings in people at inherited risk. Its design permits a within-procedure comparison of two inspection methods, but the registry record does not report the primary outcome values needed to determine how their detection results compared. No conclusion about relative performance can be drawn from the posted results described in the registry record.

3. Trial Design

This was a Phase II, completed, single-group study sponsored by the National Cancer Institute (NCI). The registry lists enrollment of 37 participants, no allocation to separate treatment groups, and no masking. The study began on 2019-02-11 and had a primary completion date of 2020-04-20.

Participants underwent upper white-light endoscopy first. After fluorescein was administered, the endoscopic evaluation was repeated using confocal endoscopic microscopy. Biopsies were taken from different stomach areas during the procedure. The listed intervention was an endoscope with a Cellvizio(R) 100 microscope. The registry describes the arm as upper white-light endoscopy and confocal endoscopic microscopy, consistent with use of both techniques in the same group rather than assignment to parallel groups.

This arrangement is important when interpreting the comparison. It does not provide a separate group examined only with WLE as a randomized control. Instead, both methods were applied within the endoscopic procedure. The registry record does not report whether the order of examination was varied, whether readers were blinded to findings from the other method, or whether any other safeguards against assessment bias were used. Masking is listed as none.

Eligibility included adults with a personal or family history of hereditary gastric cancer syndrome or a mutation known to lead to gastric cancer. The primary outcome specifically concerned CDH1 germline mutation carriers. The record states that 36/37 participants were evaluable for this outcome and that one participant was classified as having a CDH1 variant of uncertain significance. Further details about recruitment, the number screened, or the characteristics of enrolled participants 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 36/37 were evaluable for this outcome measure. One participant was determined to have Cadherin-1 (CDH1) variant of uncertain significance.

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 Percentage of Participants With Detectable Confocal Endoscopic Microscopy (CEM) w/Greater Sensitivity for Detection of Signet Ring Cells (SRC)Foci in Cadherin-1 (CDH1) Germline Mutation Carriers Compared to Current Method of Standard White Light Endoscopy, measured over 14 days.

The primary endpoint was the percentage of participants with detectable CEM and greater sensitivity for detecting signet ring cell (SRC) foci in CDH1 germline mutation carriers compared with standard white-light endoscopy. The registry defines sensitivity for CEM and WLE as the percentage of participants with detectable cancer on endoscopic biopsy. It sets the assessment timeframe at 14 days.

Sensitivity is used to describe detection among cases with the target finding. In general, a more sensitive examination identifies a greater share of cases that are present, although estimates depend on how the target condition and reference assessment are defined. Here, the registry’s operational definition refers to participants with detectable cancer on biopsy. Biopsy findings therefore provide the stated basis for determining whether cancer was detectable.

The endpoint is relevant to a study asking whether microscopic inspection can identify SRC foci that may be missed by standard endoscopy. However, the registry record does not report the endpoint percentages for either method, the number of biopsy-positive participants, or a between-method estimate. It also does not report a confidence interval or a statistical test for the primary comparison. The endpoint’s stated purpose can be described, but its observed magnitude and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help frame the study, while the specific analysis methods used for the primary endpoint are not reported in the registry record. The definitions below are general explanations, not descriptions of an unreported analysis plan.

What does sensitivity describe?

In general, sensitivity describes how often a method identifies a target finding when that finding is present. The registry gives its own operational definition for this study: the percentage of participants with detectable cancer on endoscopic biopsy, assessed for CEM and WLE. The comparison is intended to address detection of SRC foci in CDH1 germline mutation carriers. The record does not report the observed sensitivity values, so neither the absolute detection level nor the comparative result can be stated.

Endpoint definitions matter because the meaning of an estimate depends on the population, the target finding, and the method used to establish whether that finding is present. Here, the stated biopsy-based definition anchors the outcome to endoscopic biopsy. Details such as how biopsy findings were classified, how multiple biopsy locations were combined into a participant-level result, and how disagreement between assessments was handled are not reported in the registry record.

Why does the single-group design matter?

Both WLE and CEM were used in the same procedure, with WLE first and CEM after fluorescein administration. In general, measurements from two methods applied to the same participant are paired: the comparison depends on how often the methods agree and where they differ within individuals. A paired analysis can account for this dependence. Treating the two sets of observations as if they came from unrelated groups can misrepresent uncertainty because each participant contributes information to both assessments.

The registry record does not identify the statistical test or model used for the primary comparison, so it cannot be stated whether a paired method was used. The sequence also means the examinations were not described as interchangeable or randomized in order. Possible effects of sequence, prior inspection, or knowledge of earlier findings are considerations for interpretation; the registry does not report how these were addressed. Allocation is listed as not applicable, and masking as none.

What would an uncertainty interval add?

In general, a confidence interval describes a range of values compatible with the data under a specified statistical procedure. It communicates precision as well as the direction and size of an estimate. A narrow interval indicates more precise estimation than a wide interval, while an interval spanning values on both sides of no difference may leave the comparative result uncertain. The registry record does not report a confidence interval for either method or for their comparison. It also does not report a primary p-value.

A p-value, in general, measures how compatible the observed data are with a specified null hypothesis under the assumptions of a statistical test. It does not describe the size or clinical importance of an effect, and it is not a substitute for an interval estimate. Since the registry record does not report the test or its result, no significance conclusion can be drawn from it.

How should planning illustrations be read?

Sample-size illustrations, when based on an observed effect, are planning exercises rather than observed trial results. The assumptions listed for the illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Those assumptions describe a hypothetical planning framework and do not change the actual single-group design. Any calculated sample sizes in such an exercise would not be observed power. Observed power is not a substitute for reporting the estimated effect and its uncertainty.

The registry record does not report the trial’s own sample-size justification or design assumptions. It also does not report how the sample size was selected, what effect was anticipated for the original design, or whether the trial was intended to support a particular precision. Therefore, the planning assumptions should not be attributed to the investigators as the protocol’s rationale.

What can the enrollment count establish?

Enrollment of 37 describes the number entered in the registry record; it does not by itself establish the effective sample size for the primary endpoint. The stated evaluable count is 36/37, with one participant classified as having a CDH1 variant of uncertain significance. The record does not report the number of biopsy-positive participants, the distribution of findings across the two methods, or how many observations contributed to any analysis. Those details are necessary to evaluate the information available for sensitivity estimates.

Over-dispersion is a general concern when binary outcomes vary more than an assumed model expects, for example because observations cluster by participant or by biopsy site. In this study, repeated assessment and biopsies from different stomach areas make the unit of analysis and handling of within-participant observations important. The registry record does not report a model for clustering or over-dispersion, nor does it give enough outcome data to assess whether either issue affected precision. These are methodological considerations, not evidence that the analysis had a particular problem.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and describes a primary endpoint as well as a secondary outcome concerning the percentage of participants with SRC foci not identified by CEM. Details for the other outcome measures are not reported in the registry record. The record does not describe a multiplicity adjustment, a hierarchy of hypothesis tests, or which outcomes were intended to support confirmatory conclusions. Without that information, the implications of examining multiple outcomes cannot be determined.

The primary endpoint population is described as 36/37 evaluable participants. One participant had a CDH1 variant of uncertain significance. The registry record does not report an intention-to-treat analysis, a per-protocol analysis, or additional analysis populations. It does not explain whether the participant with the variant of uncertain significance was excluded under a prespecified rule or how that decision was made.

Being unevaluable because of a variant classification is not necessarily the same as having a missing outcome measurement. The registry record does not report whether any other participants lacked outcome data, why any data might be unavailable, or whether missing-data methods were used. The amount and pattern of missing outcome information therefore cannot be assessed.

Interim analyses, stopping rules, and a statistical analysis plan are not reported in the registry record. No claim about their presence or absence in the underlying study protocol can be made from this registry information. These gaps limit assessment of how outcome multiplicity, exclusions, and incomplete observations were handled.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event figures list 36 participants at risk for serious adverse events and 0 affected, with 0 deaths. The registry also lists 36 participants at risk for other adverse events and 1 affected. These counts describe the events recorded in the registry; they do not by themselves explain the event’s nature, timing, severity, or relationship to the procedure.

No serious adverse event terms are listed. The record does not report whether the one other adverse event was considered related to endoscopy, fluorescein, or CEM. It also does not provide a description of the event or a broader account of how adverse events were collected and classified. Those details are not reported in the registry record.

Zero recorded serious adverse events should be read as a count in this study record, not as proof that serious events are impossible or that risk is absent. Similarly, the single other adverse event cannot be characterized further from the available description. These safety counts are descriptive and do not establish comparative safety because the trial did not include a separate randomized control group.

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

The registry record describes a Phase II evaluation of CEM alongside standard WLE for detecting early gastric cancer findings in people with hereditary gastric cancer risk. It identifies the primary question, the examination sequence, the biopsy-based outcome definition, and the number evaluable for that outcome. These details make clear what the study intended to assess.

What the record does not provide is the primary outcome result. It gives no sensitivity estimate for CEM or WLE, no direct comparison, and no confidence interval or p-value. Consequently, it is not possible to quantify the detection performance of either method or judge the precision of a comparative estimate from the registry record. The stated objective that CEM might offer greater sensitivity remains a question, not a documented finding.

The single-group design also limits what a comparison can establish. Both techniques were used during the same procedure, rather than in separately randomized groups. If comparative estimates were reported, their interpretation would depend on the paired observations, the biopsy reference assessment, the examination sequence, and any potential assessment bias. The registry record does not report enough analysis detail to assess these features.

The enrollment count and completed status do not fill the gap in outcome reporting. Nor do the safety counts answer the primary detection question. The record supports a description of the study’s aim and conduct, but it does not support a conclusion that CEM improves detection, performs equivalently, or performs less well than WLE. Any stronger interpretation would require outcome estimates and methodological details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises a statistical question about comparing two diagnostic examination methods in the same participants. Such comparisons are not equivalent to comparing independent treatment groups. The within-participant structure can be informative because each participant receives both examinations, but valid uncertainty estimates depend on preserving that pairing in the analysis. The registry record does not identify the statistical method used.

The endpoint also illustrates why a clearly stated outcome definition is essential. The registry defines sensitivity using detectable cancer on endoscopic biopsy, while the study objective concerns SRC foci. Interpretation depends on how the biopsy findings were used to determine participant-level detection and how observations from different stomach areas were combined. Those operational details are not reported in the registry record.

Another important issue is the distinction between an intended comparison and a reported result. A study may be designed to ask whether one method has greater sensitivity, but an objective alone does not show that the anticipated difference was observed. Without estimates and measures of uncertainty, readers cannot judge the size, direction, or precision of the comparison.

Finally, the study record shows why enrollment totals and evaluability should be interpreted separately. Although enrollment was 37, the primary endpoint population was 36/37, with one participant classified as having a CDH1 variant of uncertain significance. Understanding that distinction, and how it was handled in analysis, is important for assessing what population an estimate would describe. The registry record identifies the evaluable count but does not report the primary estimate or full analysis details.

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 registry record does not report primary outcome values, so the central comparison cannot be quantified. Sensitivity estimates for CEM and WLE, a direct comparative estimate, and measures of uncertainty are not reported. This prevents assessment of effect size, precision, and statistical evidence for a difference.

The trial used a single group, with WLE followed by CEM in the same procedure. The record lists no masking and does not describe a separate control group. It does not report whether readers were blinded to other findings, whether examination order was varied, or how potential assessment effects were addressed. These design features matter when interpreting a diagnostic comparison.

The primary outcome was evaluable for 36/37 participants; one participant was determined to have a CDH1 variant of uncertain significance. The record does not give further details about this classification decision, the analysis populations, other missing outcome data, or methods for handling missingness. The number of participants with biopsy-detectable cancer is also not reported.

Details about biopsy interpretation, the reference assessment, participant-level aggregation across stomach sites, the statistical test or model, and multiplicity handling are not reported in the registry record. The record also does not report a sample-size justification or statistical analysis plan. These limitations are specific to what the registry record documents and do not establish what information may be available in other study materials.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Confocal Endoscopic Microscopy for Detection of Early Stage Gastric Cancer in Subjects With Hereditary Diffuse Gastric Cancer Syndrome — NCT03648879.
• Registry record last updated 2021-07-12; status last verified 2021-06.
• Results first posted 2021-03-25.
• 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

The record describes NCT03648879, a Phase II, completed, single-group study sponsored by the National Cancer Institute (NCI). It enrolled 37 participants and evaluated upper white-light endoscopy followed by confocal endoscopic microscopy, with fluorescein administered before the CEM examination. The primary outcome concerned detection of SRC foci in CDH1 germline mutation carriers.

The primary outcome timeframe was 14 days. The registry states that 36/37 participants were evaluable and that one participant had a CDH1 variant of uncertain significance. It lists 3 outcome measures, including a secondary measure concerning SRC foci not identified by CEM. The primary outcome result and comparative estimates are not reported in the registry record.

The record lists 0 serious adverse events, 1 other adverse event, and 0 deaths among the stated risk counts. Further details about the other event are not reported.