CryoBalloon Ablation for Treatment of Duodenal Adenomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CryoBalloon Ablation for Treatment of Duodenal Adenomas (NCT03847636), a non-randomized na study. The primary outcome is Safety of CryoBalloon Ablation in Treating Non-ampullary Non-polypoid Duodenal Adenomas (DAs) as Assessed by Participants With Adverse Events.

2. Clinical Question

The C2D2 trial asks whether cryoballoon ablation can be used to treat nonampullary, nonpolypoid duodenal adenomas, and what safety events are observed following treatment. The registry record describes a prospective, multicenter interventional study of cryoballoon ablation using the C2 Cryoballoon device. Its primary endpoint is the number of participants with any adverse event following cryoablation, assessed per patient over 1 year.

The population includes individuals with duodenal adenomas. The treatment description includes individuals with familial adenomatous polyposis (FAP) and Spigelman class 2, 3 or 4 disease, as well as individuals with at least 1 sporadic duodenal adenoma measuring 1-5 cm in maximum diameter. All participants in the described group received cryoballoon ablation. There is no separate control group in the registry record, so the central question is about outcomes observed after treatment, not a randomized comparison against another treatment or no treatment.

The registry also lists secondary outcomes concerning technical failure, progression to high-grade dysplasia or duodenal cancer, eradication of eligible adenomas at 1 year, number of treatments to eradication and eligible adenomas treated. Observed results for those outcomes are not reported in the registry record. The stated question therefore has a safety focus in the posted outcome data, while the broader efficacy questions cannot be answered from the results.

3. Trial Design

The registry record describes a prospective, multicenter interventional study of cryoballoon ablation. Its allocation is non-randomized, its model is single-group, and masking is listed as none. These features mean the participants received the intervention without assignment by randomization and without a separate comparator group described in the record. The study enrolled 33 participants and is listed as completed.

The intervention is cryoballoon ablation, identified as a device intervention. The group description includes people with duodenal adenomas and FAP with Spigelman class 2, 3 or 4, as well as people with at least 1 sporadic adenoma between 1-5 cm in maximum diameter. The record describes cryoballoon ablation for both groups. It does not report a treatment allocation procedure, a control arm, or a masked outcome assessment.

The primary outcome concerns participants with any adverse event following cryoablation, measured per patient over 1 year. The outcome description includes serious adverse events—hospitalization, emergency room visit or bleeding requiring intervention—and post-procedure upper abdominal pain, nausea and gas-bloat. The registry also names secondary outcomes covering technical failure, disease progression, complete eradication at 1 year, treatments to eradication and eligible adenomas treated. Although these outcomes are listed, their results are not reported in the registry record.

The registry lists a start date of 2019-05-13 and a primary completion date of 2025-06-01. Completion status does not, by itself, establish that every participant completed the stated follow-up or that every outcome was reported. The registry record does not report follow-up completeness, the number of participants with evaluable data for each outcome, or a detailed analysis population. It also does not report a randomized comparison or a statistical plan for comparing groups. The design supports describing the observed experience in the treated group, but it does not create a like-for-like treatment comparison.

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: All participating individuals with duodenal adenomas treated in the trial.

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 Safety of CryoBalloon Ablation in Treating Non-ampullary Non-polypoid Duodenal Adenomas (DAs) as Assessed by Participants With Adverse Events, measured over 1 year.

The primary endpoint counts participants with any adverse event following cryoablation, using a per-patient analysis and a stated timeframe of 1 year. It is a count endpoint: the quantity of interest is the number of participants who experienced an event, rather than a measurement of event severity or a rate per unit of follow-up time. The endpoint description includes serious events such as hospitalization, an emergency room visit or bleeding requiring intervention, together with post-procedure upper abdominal pain, nausea and gas-bloat.

A participant-level endpoint can provide a broad account of how many people experienced at least one event. It is useful for describing safety because it avoids treating multiple events in one person as if they were events in different people. It does not, on its own, describe the total number of events, how long events lasted, their severity beyond the stated categories, or whether they were caused by the intervention. Those details are not reported in the registry record.

The posted adverse-event figures include participants with serious and other adverse events, but the registry record does not establish whether these categories overlap. They should not be added together to obtain a unique participant count. The record also does not report a separate result value for the named primary endpoint beyond the adverse-event counts. Consequently, the counts can be described as posted safety information, but the extent to which they fully represent every component of the primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, non-randomized trial and provides a primary safety endpoint expressed as a count of participants with an event. Understanding those design and outcome features helps distinguish a descriptive safety summary from a comparative treatment-effect estimate. The points below explain the statistical concepts generally and identify what is, and is not, reported for this trial.

What does a participant count represent?

For a participant-level binary outcome, each person is classified according to whether the specified event occurred during the relevant observation period. The resulting count describes participants who met the definition. It is distinct from an event count: one participant may experience more than one event, but a per-patient summary counts that participant once for the endpoint. The primary outcome is described as a count of participants with any adverse event over 1 year. The registry does not provide a separate event-by-event account sufficient to reconstruct that endpoint.

It is also important to distinguish participants with serious events from participants with other events. Unless the record states that categories are mutually exclusive, one participant could potentially appear in more than one category. Here, whether the serious and other adverse-event groups overlap is not reported in the registry record. Adding the counts would therefore risk double-counting, and no combined count is stated.

What does a single-group design allow?

In a randomized comparison, random assignment is used to make treatment groups comparable in expectation, helping support an estimate of the contrast between assigned treatments. This trial is non-randomized and single-group, with no separate comparator described. Its posted data can describe outcomes among participants who received cryoballoon ablation, but cannot estimate a randomized between-group difference. The data cannot show what would have happened to the same participants under a different treatment.

General statistical interpretation also depends on who enters the study and who contributes outcome data. Differences in participant characteristics, follow-up and treatment selection can influence outcomes in non-randomized studies. The registry record does not report adjustment methods or enough analysis detail to assess whether such factors were addressed. No causal interpretation should be inferred from the treatment-group counts alone.

How should uncertainty be understood?

A confidence interval is a general statistical tool for expressing the precision of an estimate. For a participant count or an event proportion, an interval can show a range of values compatible with the observed data under the method’s assumptions. A narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. An interval is not a guarantee that the true value lies within its bounds, and its interpretation depends on the statistical procedure used.

The registry record does not report a confidence interval or other uncertainty estimate for the primary safety endpoint. It also reports no analysis entries. Therefore, the counts should not be mistaken for precise estimates of the frequency of events in a wider population. The record does not provide the information needed to assess the uncertainty of the result with an interval or a formal hypothesis test.

What do the planning assumptions mean?

The registry information describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two hypothetical arms and a normal approximation. Such assumptions belong to a sample-size planning exercise, not to the observed single-group trial design. They do not establish that the trial itself randomized participants equally between arms. The registry specifically characterizes the illustration as separate from the trial’s own design.

In general, a sample-size calculation asks how many participants would be needed under specified assumptions to detect a chosen effect with a stated probability of rejecting a null hypothesis when that effect is present. The effect used for planning matters: planning for a smaller effect generally requires more information than planning for a larger effect, all else being equal. These are general statistical relationships, not trial-specific results. The registry record does not report the protocol’s sample-size justification or the planning effect used as the trial’s design target.

Any sample-size values derived from the described illustration are planning quantities, not observed power. Observed power is not a substitute for examining the estimate and its uncertainty after a study. Moreover, because this trial has no control group, a two-arm planning illustration does not turn the observed data into a two-arm comparison. Its assumptions should be read as hypothetical planning conditions rather than as features of the enrolled study.

Why can over-dispersion matter?

General statistical models sometimes assume that variation in the data follows a particular distribution. Over-dispersion occurs when the observed variation is greater than that assumed by a model. If ignored, it can make standard errors too small and confidence intervals too narrow, overstating precision. This is especially relevant when outcomes are counts of events that may cluster within participants, or when observations are more heterogeneous than the model allows. The registry record does not report an over-dispersion assessment or a model for count outcomes. This general issue should not be taken to mean that over-dispersion was present in this trial.

Overall, the statistical methods that can be confirmed from the registry are limited: a single-group, non-randomized design; a participant-level primary safety count; and a stated 1-year timeframe. The registry does not report an inferential analysis, an interval estimate, adjustment methods, or a protocol-level statistical plan. Interpretation should therefore remain descriptive and be limited to the recorded counts and outcome definitions.

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("Individuals With Duodenal Adenomas")
n      <- c(29)
events <- c(12)
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  Individuals With Duodenal Adenomas  29  12  41.4  23.5  61.1  25.5  59.3  25.5  59.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes in addition to the primary safety outcome. They address technical failure, progression to high-grade dysplasia or duodenal cancer, eradication of eligible treated adenomas at 1 year, the mean number of cryoballoon treatments per patient to achieve eradication, and eligible adenomas treated. The record does not report observed results for these outcomes.

When a study evaluates multiple outcomes, the chance of at least one apparently unusual result can rise if each is tested separately without accounting for the number of tests. This is the general issue of multiplicity. A prespecified hierarchy, an adjustment procedure or a clear distinction between confirmatory and exploratory outcomes can help readers interpret multiple statistical tests. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or a statistical analysis plan. No claim about adjustment or confirmatory status can therefore be made.

Missing-data handling is also not reported in the registry record. The record does not state how participants without a recorded outcome, incomplete follow-up or unavailable measurements were handled. It does not report the number with evaluable data for each endpoint or whether any imputation was used. A completed status and a stated 1-year timeframe do not establish complete follow-up for every participant.

The analysis population is not described in detail. The primary endpoint is identified as a per-patient analysis, but the record does not specify an intention-to-treat, per-protocol or other named analysis population. It also does not list analysis entries. These omissions limit assessment of whether participants were included consistently across outcomes and how missing observations may have affected the posted results.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory failure (3.0%), motor vehicle accident (3.0%).

The registry lists 2 participants with serious adverse events and 17 with other adverse events among 33 at risk in the duodenal adenoma group. It separately lists 2 deaths. These figures are counts, not a causal assessment. The record does not report whether the serious-event and other-event counts overlap, or whether the deaths occurred among participants counted in either adverse-event category. The categories should not be added together to create a unique participant total.

Respiratory failure and motor vehicle accident are the top serious-event terms listed, each at 3.0%. The registry record does not clarify whether those percentages refer to participants or event reports, and it does not state whether the events were judged related to treatment. The event labels should therefore be read as reported safety terms, not as evidence that cryoballoon ablation caused them.

The primary endpoint includes any adverse event and is described over 1 year, but the registry does not provide detail on event timing, duration, severity beyond the listed categories, or follow-up completeness. It also does not give an attribution assessment for the deaths. The posted figures describe the safety entries in the record; they do not establish an underlying risk for other populations or a comparison with another treatment.

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

The result information available in the registry is a set of descriptive safety counts from a group treated with cryoballoon ablation. It records 2 participants with serious adverse events, 17 with other adverse events and 2 deaths, with 33 listed at risk in the group. The record also identifies respiratory failure and motor vehicle accident as top serious-event terms, each at 3.0%. These details indicate what is recorded, but the registry does not provide enough information to determine attribution, overlap between categories, or the completeness of follow-up.

The trial’s stated primary outcome concerns participants with any adverse event, rather than a comparative measure of benefit. The record lists secondary outcomes addressing technical performance and adenoma outcomes, but their observed results are not reported in the registry record. As a result, the posted information does not establish how often complete eradication occurred, whether progression was observed, or how many treatments were needed to achieve eradication.

The single-group, non-randomized design also limits what can be concluded. Without a comparator, outcomes after ablation cannot be contrasted with outcomes under another treatment or without treatment. The record does not report a causal analysis or an adjusted comparison. Observed adverse events and deaths should not be attributed to the device on the basis of these counts alone, and the counts cannot establish that treatment prevented or caused any outcome.

Statistical precision is not fully characterized. No confidence interval, p-value or analysis entry is reported. The observed counts are therefore not accompanied by a formal estimate of uncertainty, and the record does not establish how representative the group is of other people with duodenal adenomas. The sample-size planning illustration is hypothetical and is not evidence of observed power or of a randomized comparison in this trial.

In short, the registry record permits a cautious description of the posted safety information and study design. It does not support a comparative efficacy conclusion, a causal safety conclusion, or a complete assessment of long-term outcomes. Those questions would require outcome and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial matters statistically because its treatment question and its design answer different kinds of questions. The registry describes cryoballoon ablation as an intervention for sporadic and familial nonampullary nonpolypoid duodenal adenomas. Its single-group, non-randomized design can document outcomes among treated participants, while lacking the randomized comparator needed to estimate a treatment contrast under the trial design itself.

The primary endpoint is framed at the participant level, which helps readers distinguish how many people experienced at least one adverse event from how many events occurred. That distinction is important in safety reporting: multiple events in one person and one event in each of several people are not equivalent patterns, even if a total event count were the same. The record’s serious and other adverse-event categories do not state whether they overlap, making it especially important not to combine the posted counts as though each person could appear in only one category.

The listed secondary outcomes also show why a clear reporting plan matters. Technical failure, progression, eradication and treatment burden represent different clinical and statistical questions. The registry record lists these outcomes but does not report their results or a multiplicity strategy. Without those details, the safety counts cannot stand in for evidence about the other questions.

Finally, the record illustrates the difference between a planning calculation and an observed analysis. Its sample-size illustration uses hypothetical two-arm assumptions, whereas the described trial is single-group. Planning values do not create an actual comparison and do not demonstrate observed power. Clear separation of design, endpoints, uncertainty and analysis is essential when interpreting clinical trial results, especially when the posted data are descriptive.

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.

Several limitations specific to this trial constrain interpretation of the registry record. First, the study is non-randomized and single-group, with no comparator described. Differences from other treatments or from the expected course of disease cannot be estimated from the posted group counts. The registry record also does not report any adjustment method that might account for differences among participants.

Second, the participant population includes distinct eligibility descriptions for FAP-associated disease and sporadic adenomas, including specified Spigelman classes and a stated adenoma size range. The record does not provide outcome results separately for these groups. It is therefore not possible to assess whether safety or other outcomes differed across the described populations.

Third, the primary safety endpoint combines a broad set of events, including serious events and post-procedure symptoms. The registry does not report detailed event timing, duration, severity beyond the categories described, attribution to treatment, or whether the adverse-event categories overlap. The two deaths are listed without a reported relationship to treatment. Follow-up completeness for the stated 1-year timeframe is not reported.

Fourth, results for the listed secondary outcomes are not reported in the registry record. No confidence intervals, p-values or analysis entries are listed, and missing-data procedures and analysis populations are not described. This limits evaluation of precision, outcome completeness and robustness. The record’s planning illustration is not the trial’s own design justification and does not resolve these gaps.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CryoBalloon Ablation for Treatment of Duodenal Adenomas — NCT03847636.
• Registry record last updated 2026-08-05; status last verified 2026-08.
• Results first posted 2026-08-04.
• 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

The registry record describes the C2D2 trial, a prospective, multicenter, non-randomized, single-group study of cryoballoon ablation for duodenal adenomas. Masking is listed as none. The record lists 33 enrolled participants, a start date of 2019-05-13, a primary completion date of 2025-06-01 and completed status.

The primary outcome is a participant count for any adverse event following cryoablation over 1 year. The posted safety information lists 2 participants with serious adverse events, 17 with other adverse events and 2 deaths among 33 at risk. The record does not report attribution, category overlap or follow-up completeness. Results for the listed secondary outcomes, inferential analyses, confidence intervals, missing-data methods and a detailed analysis population are not reported in the registry record.