Evaluation of Effect of CryoBalloon Focal Ablation System on Human Esophageal Epithelium: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Effect of CryoBalloon Focal Ablation System on Human Esophageal Epithelium (NCT02534233), a na na study. The primary outcome is Number of Participants With Complete Eradication of Esophageal Dysplasia.

2. Clinical Question

3. Trial Design

This is a completed, single-group device study of CryoBalloon ablation. The registry lists the intervention as a device and describes patients having ablation of dysplastic tissue in the esophagus. Enrollment is 58. The study start is recorded as 2015-04 and primary completion as 2024-08. The listed phase is NA, allocation is NA, and masking is NONE. The sponsor is Johns Hopkins University.

Because the design has a single group, the registered structure does not compare CryoBalloon with another treatment or with a control group. Radiofrequency Ablation, Argon Plasma Coagulation, and carbon dioxide Cryotherapy appear in the brief summary as examples of standard ablation therapies, not as trial arms. The registry record does not describe random assignment or a blinded assessment process. It also does not report the protocol details for treatment delivery, the number or timing of treatment sessions, or the criteria used to determine which patients received the intervention.

The primary endpoint population is described as 51 assessable adult patients with data collected at 12 months. That population description differs from the enrollment count of 58, but the reasons for the distinction and the status of the other enrolled participants are not reported in the registry record. The primary endpoint is a participant count for complete eradication of esophageal dysplasia. A secondary outcome concerns participants with complete eradication of intestinal metaplasia. The record lists four outcome measures, but it does not report outcome results or analyses for them.

The completed status indicates that the study is recorded as completed; it does not supply the missing endpoint result. Details needed to assess the planned statistical approach, including a statistical analysis plan and a sample-size justification for the trial itself, are not reported in the registry record. Accordingly, interpretation is limited to the registered design, endpoint definitions, participant counts, and adverse-event summaries that are present.

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: 5 subjects were determined ineligible with index endoscopy finding exclusions, strictures restricting therapeutic scope or invasive disease.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 51 assessable adult patients with data collected at 12 months

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 Number of Participants With Complete Eradication of Esophageal Dysplasia, measured over 12 months.

The primary endpoint is the number of participants with complete eradication of esophageal dysplasia at 12 months. The registry description defines the assessment through histopathology of esophageal tissue and specifies absence of Barrett's esophagus or squamous dysplasia after cryoablation treatments. The endpoint is therefore a binary status for each assessed participant: the specified finding is either present or absent at the assessment. The registered outcome is expressed as a participant count.

Histopathology is the specified basis for determining whether dysplasia remains. In general, a tissue-based endpoint can represent a direct assessment of the condition being targeted, rather than relying only on symptoms or a participant's impression. Its interpretation depends on how tissue is sampled, how specimens are evaluated, and how the outcome definition is applied. Those procedural details are not reported in the registry record, so they cannot be evaluated from the posted information.

The endpoint is assessed at 12 months, giving a stated time point for the outcome. The record identifies 51 assessable adult patients with data collected at that time. It does not report how many participants met the endpoint, how many did not, or an estimate of uncertainty around the result. The outcome result is therefore not reported in the registry record. The presence of an endpoint definition alone does not establish how often eradication occurred.

A secondary outcome is the number of participants with complete eradication of intestinal metaplasia. The registry lists four outcome measures overall, but the other measure definitions and their results are not included in the registry record recorded. The endpoint definitions indicate what the study intended to assess; they do not by themselves establish the magnitude, precision, or comparative effect of CryoBalloon treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary outcome is a count of participants who meet a binary endpoint: complete eradication of esophageal dysplasia at 12 months. In general, a binary outcome records whether each participant meets a defined condition or does not. A count of participants is one way to present such an outcome. A proportion could also describe the share of assessed participants meeting the condition, but the registry record does not report the primary endpoint count or a proportion. No value should be inferred from the endpoint definition or the number of assessable patients.

The stated assessment uses histopathology of esophageal tissue and specifies absence of Barrett's esophagus or squamous dysplasia. In general, endpoint definitions should be sufficiently explicit for consistent classification. Interpretation may also depend on how tissue is obtained, which locations are sampled, how specimens are read, and whether readers know the treatment history. Those details are not reported in the registry record. Masking is listed as NONE, but the record does not explain whether outcome assessors were masked independently of the study's masking designation.

The endpoint has a 12-month timeframe. A fixed assessment time can make the target observation point clear, but a result at that time does not necessarily describe what happened earlier or what persists later. The registry does not report other assessment schedules, follow-up after 12 months, or how the primary assessment was selected if multiple assessments were available. The primary population is described as 51 assessable adults with data collected at 12 months, while enrollment is 58. The reasons for this difference and the handling of participants without assessable 12-month data are not reported.

In general, a confidence interval communicates the uncertainty around an estimated outcome. Its width depends on factors such as the amount of information and the variability in the outcome. No confidence interval for the primary endpoint is reported in the registry record. No hypothesis test, p-value, or other primary analysis result is reported either. The registry lists zero analyses, so there is no posted statistical analysis to interpret. The statistical method planned for the primary endpoint, including any adjustment or model, is not reported in the registry record.

The study is single-group, with allocation listed as NA and masking listed as NONE. In general, an outcome observed in one treated group can describe what occurred among participants, but it cannot establish how those same participants would have fared under a different treatment. A concurrent comparison group can help distinguish treatment-related differences from other influences, while a single-group design cannot make that direct contrast. The registry names other ablation therapies as context, but does not list them as study arms.

The record lists four outcome measures, including the primary dysplasia-eradication measure and a secondary measure of complete eradication of intestinal metaplasia. In general, assessing multiple outcomes raises the question of multiplicity: the chance of at least one apparently notable result can increase when many outcomes or tests are considered. A prespecified approach may address that issue, but a multiplicity strategy and statistical analysis plan are not reported in the registry record. Since outcome analyses and results are absent, no adjustment can be assessed.

General considerations for binary outcomes include the distinction between the number of participants with an event and the number of event episodes. A participant count does not necessarily describe how many times an event occurred. The primary endpoint is explicitly a participant count. The safety summary likewise gives participants affected and lists serious adverse-event terms; the record does not provide enough detail to infer the number of distinct episodes or whether a participant could contribute to more than one term.

The registry's sample-size assumptions describe planning illustrations, not the trial's own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. Time-to-event illustrations use the total number of events under the Schoenfeld method; other illustrations are stated as participants per arm. In general, such calculations ask how much information might be needed under specified assumptions. They are not observed power, do not replace the trial's sample-size justification, and do not create a valid randomized comparison for this single-group study. The trial's own sample-size justification is not reported in the registry record.

Over-dispersion is a general concern for count outcomes when variation exceeds what a simple count model assumes. It can make uncertainty estimates too small if not handled appropriately. The primary endpoint is a count of participants meeting a binary condition, but the registry does not report a count model or any model-based analysis. Over-dispersion therefore cannot be evaluated as a feature of a posted primary analysis. This general concept should not be read as evidence that a particular model was used or that a model assumption was violated in this study.

In general, prespecification helps readers distinguish planned analyses from choices made after results are known. The registry does not report the trial's statistical analysis plan, interim analyses, or the basis for selecting the primary endpoint population. No assumptions about those elements can be made from the completion status or endpoint description. Interpretation should remain limited to the stated design, recorded population, listed outcome definitions, and available safety figures.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("CryoBalloon Ablation")
n      <- c(51)
events <- c(51)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  CryoBalloon Ablation  51  51  100.0  93.0  100.0  93.0  100.0  93.2  100.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, with complete eradication of esophageal dysplasia as the primary outcome and complete eradication of intestinal metaplasia as a secondary outcome. It does not report the results for these outcomes or any analyses. A multiplicity strategy, such as a prespecified hierarchy or adjustment for testing more than one outcome, is not reported in the registry record. Without the analysis plan and results, it is not possible to assess how multiple outcomes were handled or whether any findings were designated as confirmatory.

The endpoint population is described as 51 assessable adult patients with data collected at 12 months, while total enrollment is 58. The record does not explain why the population used for the endpoint is smaller than enrollment, identify the status of the other participants, or state whether missing outcome data were excluded, imputed, or handled in another way. The definition of assessable is not reported in the registry record. These details matter because different approaches to incomplete follow-up can lead to different interpretations.

The analysis population is not fully specified beyond the endpoint population description. The registry does not report whether all enrolled participants were included in an intention-to-treat analysis, whether a per-protocol population was defined, or how deviations from treatment or follow-up requirements were handled. The statistical analysis plan, any interim analyses, and a sample-size justification for the trial itself are also not reported. The registry lists zero analyses, so there is no posted analysis from which to evaluate these choices.

These omissions do not establish that missing-data or multiplicity procedures were absent from the study's conduct. They mean that the procedures are not reported in the registry record and cannot be assessed from the posted information.

12. 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.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: esophageal stricture requiring dilation (11.3%), post cryoablation treatment pain requiring narcotics (3.8%), gi bleeding (1.9%).

For the CryoBalloon Ablation group, the registry records 53 participants at risk and 9 participants affected by serious adverse events. It records 0 participants affected by other adverse events and 0 deaths. These are participant counts in the posted safety summary; they do not provide a comparison with an untreated group or another treatment group.

The listed serious adverse-event terms are esophageal stricture requiring dilation at 11.3%, post cryoablation treatment pain requiring narcotics at 3.8%, and GI Bleeding at 1.9%. The record does not explain whether these terms overlap within participants, how the percentages were calculated, or whether the list includes every reported serious event. The listed percentages should be read as registry summaries rather than as a complete description of each participant's course.

In general, safety counts describe events recorded under the study's definitions and observation period. Their interpretation depends on event definitions, follow-up duration, and the completeness of reporting. The registry record does not provide detailed timing, duration, recurrence, or participant-level event histories. The figures describe the posted safety information, but cannot establish comparative safety or explain the cause of an event.

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

The registry record gives a clear outline of a study asking whether esophageal dysplasia was completely eradicated at 12 months after CryoBalloon ablation. It identifies a single-group device study, enrollment of 58, an endpoint population of 51 assessable adult patients, and safety figures for 53 participants at risk. It also names a secondary outcome concerning complete eradication of intestinal metaplasia.

What the record does not give is the actual number of participants who met the primary endpoint. It does not report an effect estimate, confidence interval, p-value, or analysis of the endpoint. The secondary outcome result is also not reported. Consequently, readers cannot quantify the observed rate of complete eradication from this record or judge the precision of such a result. Completed status is not a substitute for a posted outcome result.

The single-group design also limits what an observed outcome could mean. In general, outcomes in a treated group can be described, but without a concurrent comparator they do not directly show how outcomes would differ under another treatment or no treatment. The therapies named in the brief summary are contextual alternatives, not trial comparison arms. The study therefore does not provide a registered head-to-head comparison with them.

The safety counts and listed serious-event terms provide a summary of events reported for the treated group. They do not offer a comparative safety estimate, and the record lacks participant-level detail needed to assess overlap among event terms, timing, or duration. The safety information should be interpreted within those reporting limits.

The endpoint definition, timeframe, and recorded population are useful for understanding what was intended to be assessed. However, the absent outcome analysis, unexplained difference between enrollment and the assessable endpoint population, and lack of a reported statistical plan restrict interpretation. The record neither establishes an efficacy result nor supports a conclusion about comparative treatment effects. It documents the study structure and selected safety information, while leaving the central efficacy result unreported.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a defined endpoint and the absence of a posted endpoint result. The primary question is specific: the number of participants with complete eradication of esophageal dysplasia at 12 months, assessed through histopathology. Yet the registry record does not report how many participants met that definition or provide an uncertainty estimate. A well-described outcome is not the same as a reported outcome analysis.

The single-group structure is important when interpreting any eventual outcome count. In general, a treated-group count can describe what occurred among assessed participants, but it cannot directly separate treatment effects from the influence of participant characteristics, changes over time, or other factors. A comparator is necessary for a direct treatment contrast. The listed standard therapies do not form study arms in this record.

The difference between enrollment of 58 and the description of 51 assessable adults at 12 months also highlights the importance of reporting analysis populations and missing data. The record does not explain the difference or state how incomplete follow-up was handled. Statistical interpretation depends not only on the endpoint definition but also on which participants contribute information and how unavailable outcomes are treated.

The registry lists four outcome measures and no analyses. This makes the planned handling of multiple outcomes particularly difficult to assess: the statistical analysis plan and any multiplicity approach are not reported. The sample-size assumptions describe planning illustrations under two-arm assumptions, while the actual study is single-group. Those illustrations are not the trial's own design justification and are not evidence of observed power.

Together, these details show why transparency about outcome results, analysis populations, uncertainty, and prespecified methods matters. The posted information supports a description of the design and selected safety figures, but leaves the principal statistical result and its precision unreported.

15. 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 interpreting efficacy is that the registry record does not report the primary endpoint result. It specifies complete eradication of esophageal dysplasia at 12 months, but gives no count of participants meeting the endpoint, no estimate of uncertainty, and no analysis. The secondary outcome of complete eradication of intestinal metaplasia is listed without a result. Although four outcome measures are recorded, their complete definitions and results are not reported.

The study has a single-group design and no concurrent comparison arm. This means the record does not support direct comparison with the other ablation approaches mentioned in the brief summary. It also cannot determine from the registered structure alone how outcomes would compare with another treatment. Allocation is listed as NA and masking as NONE, but further details about assessment procedures are not reported.

Enrollment is 58, while the primary endpoint population is described as 51 assessable adult patients with data collected at 12 months. The reasons for this difference, the definition of assessability, and the disposition of participants without endpoint data are not reported in the registry record. The approach to missing data and the analysis populations are also not reported. These gaps limit assessment of selection and follow-up effects.

The record does not report the trial's statistical analysis plan, sample-size justification, interim analyses, multiplicity procedures, or methods used to estimate uncertainty. It lists zero analyses. The sample-size assumptions are planning illustrations based on two-arm assumptions and do not describe the single-group trial's own design rationale.

Safety information is limited to participant counts, deaths, and selected serious adverse-event terms with percentages. Timing, duration, recurrence, overlap among terms, and detailed event histories are not reported. The posted safety summary therefore cannot support a comparative safety assessment or a detailed account of event patterns.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Effect of CryoBalloon Focal Ablation System on Human Esophageal Epithelium — NCT02534233.
• Registry record last updated 2025-08-01; status last verified 2025-07.
• Results first posted 2025-08-01.
• 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.

19. Record Summary

NCT02534233 is a completed, single-group device study sponsored by Johns Hopkins University, evaluating CryoBalloon ablation for dysplastic esophageal tissue and early esophageal cancer. Enrollment is 58; the primary endpoint population is described as 51 assessable adult patients with data collected at 12 months. The primary outcome is the number of participants with complete eradication of esophageal dysplasia.

The registry lists four outcome measures and no analyses. It does not report the primary or secondary outcome results, an effect estimate, or an uncertainty interval. The safety summary records 9 participants affected by serious adverse events among 53 at risk, 0 affected by other adverse events, and 0 deaths, with three serious-event terms and associated percentages listed. Because the study has no concurrent comparison group, it does not provide a direct comparison with the alternative therapies named in its summary.