Cytosponge Protocol IRB 11-006429: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cytosponge Protocol IRB 11-006429 (NCT01585103), a na na study. The primary outcome is Percent Specificity of the Cytosponge.

2. Clinical Question

The study’s stated purpose was to collect data on the potential use of the Cytosponge as a non-invasive tool for evaluating patients with eosinophilic esophagitis. The primary endpoint focuses on specificity: among samples classified as negative by the reference assessment, how often does the Cytosponge also give a negative classification? The endpoint description says cytology specimens would be read by one pathologist, without knowledge of the biopsy results.

This question concerns agreement with a reference assessment, not whether the device changes disease activity or improves patient outcomes. A single-group diagnostic study can describe how test classifications compare within the enrolled group, but it does not create a randomized control group. The registry record does not report the numerical endpoint result, the underlying classification counts, or an analysis. Therefore, the stated question can be described, but its answer cannot be determined from the registry record.

3. Trial Design

The registry identifies this as a single-group device study of the Cytosponge in eosinophilic esophagitis. The sponsor is Mayo Clinic. The listed enrollment is 86, and the status is terminated. The recorded start is 2012-12, and primary completion is listed as 2016-06-07. Phase and allocation are recorded as NA; masking is recorded as none.

Participants with eosinophilic esophagitis who were undergoing endoscopy and biopsy for clinical reasons were to be asked to swallow the Cytosponge two hours before endoscopy. The clinical reasons described were initial diagnosis or monitoring disease activity. The primary endpoint compares Cytosponge specificity with upper endoscopy and biopsy or swab testing. The endpoint description further says a pathologist would read cytology specimens without knowing biopsy results. That reader-level blinding detail is distinct from the registry’s overall masking designation of none.

Because the design is single group, it does not compare outcomes between randomized intervention and control groups. The reference assessments serve as the basis for evaluating diagnostic classifications, rather than as a separate study arm. This structure can address whether the device’s classifications correspond to the named reference assessments in the observed study group, subject to how participants and samples were selected and assessed.

The registry record does not report the reason for termination, recruitment progress, eligibility criteria beyond the description of the study group, or the number of participants who completed each assessment. It also does not report protocol details such as a sample-size justification, a prespecified interim-analysis plan, or a full statistical analysis plan. The listed enrollment should not be treated as evidence that every participant contributed to the primary endpoint, because endpoint-specific analysis counts are 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.

Overall Study

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.

6. Primary Endpoint

The registry lists the primary outcome as Percent Specificity of the Cytosponge, measured over Baseline.

The primary endpoint is titled “Percent Specificity of the Cytosponge.” It is described as the percentage of samples for which the Cytosponge correctly identifies the absence of eosinophilic esophagitis, relative to upper endoscopy and biopsy or swab testing. The registry’s stated calculation uses true negatives divided by the sum of true negatives and false positives, expressed as a percentage.

Specificity is useful when a test is intended to classify people or samples who do not have the condition as negative. In general, a false positive is a test-positive classification in a case that the reference assessment classifies as negative. A true negative is a negative classification under both the test and the reference assessment. Specificity therefore describes performance within the reference-negative group; it does not by itself describe performance among reference-positive cases.

The endpoint description says one pathologist would review the cytology specimens without knowledge of biopsy results. This is intended to keep the cytology interpretation from being influenced by the reference result. The registry record does not report the observed percentage, the numbers of true negatives or false positives, or the number of samples included in the endpoint calculation. The endpoint’s definition is available, but its numerical result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Diagnostic accuracy endpoints compare a test’s classifications with those from a reference assessment. In this study, the named test is the Cytosponge, and the named reference assessments are upper endoscopy and biopsy or swab testing. General statistical explanation: each usable paired assessment can be classified according to whether the Cytosponge and reference assessment are positive or negative. Specificity is calculated among reference-negative assessments, as the proportion that the test also classifies as negative.

What does specificity describe?

Specificity addresses false-positive classifications among cases that the reference assessment classifies as negative. It is different from sensitivity, which addresses positive classifications among reference-positive cases. Neither measure alone describes all aspects of diagnostic performance. A complete account may also need information about the study population, the reference assessment, the handling of indeterminate results, and the number of evaluable paired assessments. The registry record gives a definition for specificity but does not report the classification counts or the resulting estimate.

Why does the reference assessment matter?

A diagnostic accuracy estimate depends on how the reference status is established. If the reference assessment is imperfect or varies across participants, the test-versus-reference comparison may not represent comparison with an error-free truth. This is a general consideration, not a finding about this study. The registry names endoscopy and biopsy or swab testing, but does not report enough detail to establish how reference results were combined, whether the same procedures were used for every participant, or how discordant results were handled.

What does blinded reading contribute?

The endpoint description says one pathologist would read the cytology specimens without knowledge of biopsy results. In general, blinding an assessment reader to a comparator result can reduce the chance that knowledge of that result influences interpretation. The registry’s overall masking field is none, so the reader-level statement should not be expanded into a claim that participants, clinicians, or all study personnel were blinded. Other safeguards for independent interpretation are not reported in the registry record.

How should precision be judged?

An estimate is more informative when its uncertainty is also reported. In general, a confidence interval gives a range of values that are reasonably compatible with the data under the analysis method. Its width reflects precision: a wider interval indicates greater uncertainty than a narrower one. No confidence interval or numerical specificity estimate is reported in the registry record, so precision cannot be assessed. The listed enrollment does not replace an endpoint-specific denominator; the number of participants or samples contributing to the calculation is not reported.

What can a single-group design establish?

A single-group diagnostic study can describe classifications in the assessed group and compare the device result with a reference assessment. It does not, by itself, provide a randomized comparison of alternative interventions. General explanation: estimates from a diagnostic study can also depend on who was enrolled and why testing was performed. The registry describes people undergoing clinically indicated endoscopy and biopsy for diagnosis or disease monitoring. It does not report the distribution of those reasons or enough detail to assess how closely the enrolled group represents other settings.

The record lists sample-size assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. It also specifies that these are planning illustrations, not the trial’s own design. Since the registered study is single group and no primary analysis result is reported, these assumptions should not be read as evidence of a completed comparison or observed power. The numerical planning outputs are not described in the registry record.

The registry record does not report the statistical method used for the primary endpoint, any adjustment for clustering or repeated samples, or any approach to uncertainty estimation. General explanation: if multiple samples from one participant are analyzed, their results may be correlated rather than independent; treating correlated observations as independent can make uncertainty appear smaller than it is. The record does not state whether there were repeated samples or how such data, if any, were handled. No additional method should be inferred from the endpoint formula alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures, but only the primary measure, specificity of the Cytosponge, is described in the available record. The other outcome measure is not reported in the registry record. The record lists zero analyses, so no analysis results or detailed analysis populations are presented.

When a study evaluates multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable finding can increase. General methods for addressing this include prespecifying a primary outcome, controlling error rates across tests, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, a hierarchy of tests beyond identifying the primary endpoint, or whether any adjustment was planned. It is not possible to determine how multiplicity was handled.

The record does not report a missing-data plan, the number of missing or unusable Cytosponge assessments, the number of missing reference assessments, or how indeterminate classifications were treated. It also does not report an analysis population definition, such as whether all enrolled participants or only those with paired interpretable results would be included. Enrollment is listed as 86, but the endpoint-specific analysis denominator is not reported in the registry record.

These omissions limit interpretation because diagnostic estimates require both a test result and a reference classification for the observations included in the calculation. General explanation: exclusions or missing paired assessments can affect which observations contribute to an estimate, particularly if missingness is related to test performance or participant characteristics. The registry record does not provide information to assess whether that concern arose in this study or how it was addressed.

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 registry’s adverse-event figures list the Cytosponge/Brushing group with 86 at risk for serious adverse events and 0 affected; deaths are listed as 0. The record also lists 86 at risk for other adverse events and 2 affected. These are counts as recorded; no percentage is calculated.

Serious adverse events and other adverse events are separate categories in the registry record. A count of zero affected for the serious category does not mean that no adverse events of any kind occurred, because the record separately lists other adverse events. The registry does not report the terms for those other events, their severity, timing, relationship to the device, or whether any event led to discontinuation. The list of top serious-event terms is empty.

These figures are descriptive and do not establish a comparative safety effect. The study has a single group and no randomized control arm, so the counts cannot be interpreted as a between-group contrast. The record does not report the duration or completeness of safety follow-up, and the figures should not be extended beyond the recorded group and event categories.

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

The registry record documents a study intended to collect information about the potential use of the Cytosponge as a non-invasive evaluation tool for eosinophilic esophagitis. It describes a primary diagnostic endpoint: specificity relative to endoscopy and biopsy or swab testing. It also describes a reader who would assess cytology specimens without knowing biopsy results. These details define the intended question and one feature of its assessment process.

The record does not report a numerical specificity result, its uncertainty, or the counts used to calculate it. It therefore does not show how the Cytosponge performed on this endpoint in the study. The study’s termination status also does not supply an answer about diagnostic performance; the reason for termination is not reported in the registry record.

Even when an accuracy estimate is available, specificity is only one component of diagnostic performance. In general, it describes results among cases classified as negative by the reference assessment. It does not reveal sensitivity, the performance among reference-positive cases, or the balance of positive and negative classifications in a different population. Those outcomes and contextual details are not reported in the registry record.

The design is single group rather than a randomized comparison between interventions. Accordingly, this record should not be used to claim a comparative advantage over another diagnostic approach. The described reference assessments are used to evaluate test classifications; they are not a separate randomized treatment group. Further, the listed enrollment does not establish the endpoint analysis denominator or show that every enrolled participant had complete, interpretable paired assessments.

The result that can be stated is limited: a specificity endpoint was defined, but its numerical result is not reported in the registry record. The safety entries record zero serious adverse events affected and two people affected by other adverse events in the listed group, with the event details and follow-up context not reported. These descriptive entries do not establish broader safety or effectiveness conclusions.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it illustrates the difference between a diagnostic question and a treatment comparison. The intended primary question concerns whether a device’s classifications agree with reference assessments among reference-negative samples. That calls for a diagnostic accuracy measure, not a comparison of outcomes across randomized treatment groups. The registry identifies a single-group design and names specificity as the primary endpoint.

It also shows why an endpoint definition is not enough to interpret a study. The registry explains the formula for specificity and describes a blinded cytology review, but does not report the resulting estimate, its uncertainty, or the classification counts. Without these elements, readers cannot judge the magnitude or precision of the observed performance from the record.

The study description highlights several design features that matter to interpretation: assessments were tied to clinically indicated endoscopy and biopsy, participants could be undergoing initial diagnosis or monitoring, and the cytology reader was to be unaware of biopsy results. Such features define the intended context, but the record does not report enough detail to evaluate selection, completeness of paired assessments, or other sources of uncertainty.

Finally, the planning assumptions should be separated from the registered design and from observed results. The record describes hypothetical two-arm, equal-allocation planning calculations, while listing this study as single group. Such illustrations do not provide evidence of an observed effect or a completed statistical analysis. Keeping design, planned methods, and reported findings distinct is essential when interpreting an incomplete registry record.

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 central limitation is that the primary endpoint result is not reported in the registry record. The record provides neither the specificity estimate nor the underlying classification counts, endpoint denominator, or confidence interval. The number of participants with complete paired Cytosponge and reference-assessment results is also not reported.

The registry describes the reference assessments as upper endoscopy and biopsy or swab testing, but does not report how these assessments were standardized or combined, how disagreements were resolved, or whether indeterminate findings could occur. The endpoint description says one pathologist would read cytology specimens without knowledge of biopsy results; further information about independent assessment procedures is not reported in the registry record.

Participants were described as undergoing clinically indicated endoscopy and biopsy for initial diagnosis or monitoring. The record does not provide the distribution across those circumstances or enough detail to assess the selection of participants and samples. It also does not report eligibility criteria in full, participant flow, missingness, exclusions, or the analysis population.

The study is listed as single group, with no allocation and no masking overall. It cannot provide a randomized intervention comparison. The reason the study was terminated, the status of individual outcomes, and the missing outcome measure are not reported in the registry record. Although enrollment is listed as 86, that figure alone cannot resolve these limitations or establish the number included in the primary analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cytosponge Protocol IRB 11-006429 — NCT01585103.
• Registry record last updated 2022-06-13; status last verified 2022-06.
• Results first posted 2022-05-18.
• 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 record describes a Mayo Clinic single-group device study of the Cytosponge in eosinophilic esophagitis. Enrollment is listed as 86; status is terminated. The recorded start is 2012-12, and primary completion is listed as 2016-06-07. Allocation and phase are recorded as NA, and masking is recorded as none.

Participants undergoing clinically indicated endoscopy and biopsy were to swallow the Cytosponge two hours before endoscopy. The primary endpoint is percent specificity relative to endoscopy and biopsy or swab testing. The endpoint description says one pathologist would read cytology specimens without knowledge of biopsy results. The numerical endpoint result and its analysis are not reported in the registry record.

The safety entries list 0 affected by serious adverse events and 2 affected by other adverse events in the group. The registry lists two outcome measures and zero analyses; the other outcome measure, analysis details, reason for termination, and missing-data procedures are not reported in the registry record.