Cryoablation System FIM/CE Mark Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cryoablation System FIM/CE Mark Study (NCT03723070), a na na study. The primary outcome is Primary Safety Outcome: Percentage of Participants With Procedure Related Adverse Events OR Device Related Adverse Events OR Serious Adverse Device Effects.

2. Clinical Question

3. Trial Design

The Cryterion Cardiac Cryoablation System CE Mark Study is registered as NCT03723070 and is marked completed. It is described as a multicenter, open-label, prospective clinical study intended to establish acute safety and performance. Enrollment was 88. The study dates in the registry record are 2018-05-15 for start and 2020-12-22 for primary completion.

The design is single-group, with no masking and allocation recorded as NA. The intervention is the Cryterion Cardiac Cryoablation System, used for pulmonary vein cryoablation in participants with atrial fibrillation. No parallel control arm is described. The record labels the study as phase NA.

These design details define the scope of interpretation. Adverse-event counts can describe what was recorded among participants treated in the study, but a single-group study cannot estimate a treatment contrast against a concurrent control group. The open-label design also means that participants and study personnel were not masked, although the record does not describe how outcome assessment was conducted.

The registry lists five outcome measures, including the primary safety outcome and secondary outcomes concerning procedure-related or device-related adverse events and pulmonary vein isolation findings. The planned sample-size justification, eligibility criteria, enrollment flow, and analysis populations are not reported in the registry record. The record also does not report a detailed statistical analysis plan.

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 Primary Safety Outcome: Percentage of Participants With Procedure Related Adverse Events OR Device Related Adverse Events OR Serious Adverse Device Effects, measured over 12 months.

The primary endpoint is a safety composite: the percentage of participants with a procedure-related adverse event, a device-related adverse event, or a serious adverse device effect during the 12 months timeframe. The composite description includes serious events such as death, myocardial infarction, cardiac perforation or pericardial tamponade, cerebral infarct or systemic embolism, major bleeding requiring transfusion, valvular damage, persistent diaphragmatic paralysis from phrenic nerve damage, symptomatic pulmonary vein stenosis, atrio-esophageal fistula, and life-threatening air embolism, as well as other serious adverse device effects.

A composite endpoint can capture several clinically important types of harm in one outcome. The OR rule means that a participant meeting any listed component can count toward the composite. This is useful for safety monitoring when relevant events may differ in their specific presentation. It also means that interpretation depends on clear definitions, attribution, and consistent ascertainment of each component.

The primary outcome is expressed as a percentage of participants, but the registry record does not report a primary composite estimate or its uncertainty. The posted adverse-event summary gives serious and other event counts, but does not establish which events were procedure-related, device-related, or included as serious adverse device effects for the primary composite. Those counts alone therefore do not reconstruct the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted study design is single-group and open-label. This matters because the principal statistical information available is descriptive: counts of participants with adverse events in the intervention group. There is no randomized comparison and no separate control arm. The record reports no analyses, so there is no sponsor-reported statistical estimate or test to interpret for the primary outcome.

What does a participant count represent?

For a binary outcome, each participant is classified according to whether the event definition is met. A count reports how many participants had an event; the corresponding percentage uses the number assessed as its denominator. Here, the adverse-event summary reports 88 at risk for both the serious and other event categories, with 6 and 56 affected, respectively. These are descriptive summaries. The registry does not report a calculated primary-composite percentage.

General statistical explanation: a count is easiest to interpret when the outcome definition, follow-up period, and denominator are clear. If people have different follow-up or if some outcome data are missing, the observed count may not represent the same opportunity for event detection for everyone. The registry gives a 12 months timeframe for the primary safety endpoint, but details of follow-up completeness and missing outcome data are not reported in the registry record.

Why does the composite definition matter?

The primary safety endpoint uses an OR rule across procedure-related adverse events, device-related adverse events, and serious adverse device effects. Under such a rule, a participant qualifies if at least one of the specified conditions is met. Composite endpoints can combine several safety concerns, but a single summary can obscure which components account for the outcome. Component counts and clear rules for attribution are therefore important to interpretation. The registry lists examples of serious events in the endpoint definition, but does not report a component-level primary-outcome analysis or a composite estimate.

The adverse-event summary distinguishes serious from other adverse events. It does not, in the available record, establish that all serious events meet the primary composite's relatedness criteria, or that all other events are excluded from it. Seriousness and relatedness are different classifications: an event may be serious without being attributed to the procedure or device. The primary outcome's exact numerator therefore cannot be inferred from the serious-event count alone.

What can a single-group design estimate?

General statistical explanation: a single-group event proportion can describe the frequency of an outcome in the observed study group, subject to how outcomes are ascertained and how complete follow-up is. A treatment comparison requires a contrast with another group or a prespecified external benchmark, together with assumptions that justify the comparison. The record does not describe such a comparator or benchmark. The posted counts consequently do not establish a difference attributable to the system.

Open-label conduct means masking was recorded as none. General statistical explanation: awareness of treatment can influence behavior, reporting, and outcome assessment, depending on the outcome and procedures used. The registry record does not describe blinded adjudication or other methods that might reduce such influence. It would be inappropriate to assume either that bias occurred or that it was prevented.

How should uncertainty be considered?

General statistical explanation: a confidence interval expresses uncertainty around an estimate under the chosen statistical model. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the study design and analysis assumptions. No confidence interval or other uncertainty measure for the primary outcome is reported in the registry record. The adverse-event counts alone do not show the precision of an estimate.

The record includes sample-size planning assumptions for hypothetical two-arm illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. The record's actual design is single-group. The planning illustrations should therefore not be read as a description of the study's own design or as observed power. The trial's sample-size justification and any target power are not reported in the registry record.

What can be concluded from the analysis record?

The registry lists five outcome measures, but reports no analyses. It therefore does not provide a model, adjustment strategy, test result, confidence interval, or analysis population for the primary endpoint. The record's adverse-event counts remain useful as descriptive safety information, but they do not substitute for the prespecified composite analysis. Any more detailed statistical conclusion would require information not reported in the registry record.

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("PV Cryoablation")
n      <- c(88)
events <- c(50)
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  PV Cryoablation  88  50  56.8  45.8  67.3  46.4  66.7  46.4  66.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including a primary safety outcome and secondary outcomes. It does not report any analyses. A statistical multiplicity strategy—such as an ordering of hypotheses, an adjustment method, or a statement that the outcomes are descriptive—is not reported in the registry record.

General statistical explanation: when several outcomes or hypotheses are tested, the chance of at least one apparently unusual result can increase if each is judged separately without accounting for the set of tests. Methods for addressing this depend on the study's aims and analysis plan. Since no analysis results or multiplicity approach are reported, no multiplicity-adjusted interpretation can be made.

The registry record does not report how missing data were handled, whether all enrolled participants completed the 12 months timeframe, or which analysis population was used for any endpoint. It also does not describe exclusions from the adverse-event denominators. The adverse-event summary lists 88 at risk for each reported category, but that does not establish the completeness of follow-up for every outcome or the handling of missing observations.

These omissions limit assessment of the primary endpoint. A complete account would ordinarily clarify the denominator, follow-up status, event classification, and analysis population, especially for a composite that depends on procedure and device relatedness. No details on these points should be inferred from the counts alone.

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: episodic aphasia (1.1%), hematochezia (1.1%), cholecystitis (1.1%), cholelithiasis (1.1%), embolism in right femoral artery (1.1%).

The adverse-event summary reports 6 participants with serious adverse events among 88 at risk, and 56 with other adverse events among 88 at risk. It reports 0 deaths. These are counts within the single PV Cryoablation group, not comparative estimates. The serious-event terms listed include episodic aphasia, hematochezia, cholecystitis, cholelithiasis, embolism in the right femoral artery, and atrial arrhythmia; each is reported at 1.1%.

The counts do not establish that serious events were caused by the device or procedure. Nor does the record show that the serious-event count is identical to the number meeting the primary composite definition. Do not add the serious and other counts: the record does not say whether the categories overlap. Likewise, the listed terms may not represent distinct participants. The registry does not report a comparative safety analysis or uncertainty estimates for these counts.

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

The posted information supports a descriptive account of adverse events recorded in the single-group study: 6 participants had serious adverse events, 56 had other adverse events, and 0 deaths were reported. The registry also lists several serious-event terms, each at 1.1%. These observations describe the study group and the registry's event reporting.

They do not establish a comparative safety effect. There is no separate control group, and the record reports no inferential analyses. The data therefore do not show how the event experience compares with another treatment or with an untreated group. They also do not establish that an event was caused by the device or procedure.

The primary endpoint is a composite of procedure-related events, device-related events, or serious adverse device effects during 12 months. The registry record does not report an analyzed estimate of this composite. The broader adverse-event counts cannot be substituted for that result without knowing the required event attribution and composite classification.

General statistical explanation: a descriptive count is informative about what was observed, while an estimate with an uncertainty measure helps indicate how precisely an underlying event frequency is characterized. Neither alone establishes causation in a single-group design. Here, no primary-outcome estimate or uncertainty measure is reported, so the level of precision for that endpoint cannot be evaluated.

The study's prospective, multicenter design and defined safety outcome provide a framework for recording safety and performance information. However, the registry does not report enough analysis detail to support a formal conclusion about the primary outcome. The counts should be read as registry-reported observations, with their limitations in denominator, attribution, and comparison kept in view.

14. Why This Trial Matters Statistically

This trial is statistically notable because its central safety question is framed as a composite outcome, while the registry's posted results are adverse-event counts rather than an analyzed composite estimate. That distinction illustrates why the endpoint definition and the result format must align before a count can be interpreted as the primary outcome.

The single-group design also clarifies the role of descriptive statistics. Counts can document events among the participants treated with the Cryterion Cardiac Cryoablation System, but without a comparator they cannot estimate a between-group difference. This is not a flaw in the arithmetic; it is a limit on the questions the design can answer.

The registry lists multiple outcomes but reports no analyses. For statistical readers, this makes it important to distinguish an outcome's presence in a registration record from a completed analysis of that outcome. The record gives a 12 months timeframe for the primary safety endpoint, yet does not report a primary composite estimate, an uncertainty measure, or analysis details.

The sample-size assumptions also warrant careful reading. They describe hypothetical two-arm planning illustrations, whereas the registered trial is single-group. Such planning information cannot be interpreted as observed power or as evidence that the actual study was sized to detect a particular effect. The study-specific sample-size justification is not reported in the registry record.

Together, these features make the trial useful for teaching the separation between design, outcome definition, descriptive event reporting, and inferential conclusions. They also show why missing analysis details should remain explicit rather than being filled in by assumptions.

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 registry record does not report a control group, so the adverse-event counts cannot be used to estimate a comparative effect. The study is single-group, with allocation recorded as NA. It is also open-label, and the record does not describe blinded outcome assessment or adjudication.

The record reports no analyses. It therefore does not provide a primary composite estimate, confidence interval, hypothesis test, model, or adjustment strategy. Although the primary endpoint has a 12 months timeframe, follow-up completeness and missing-data handling are not reported in the registry record.

The adverse-event summary gives serious and other event counts, but does not clarify whether those categories overlap, how multiple events per participant are handled, or how events were attributed to the procedure or device. It does not show how individual events map onto the primary composite definition. The serious-event terms are listed with percentages, but the record does not establish whether the terms correspond to distinct participants.

The registry lists five outcome measures and no analyses. Multiplicity handling and analysis populations are not reported in the registry record. Eligibility criteria and further population characteristics are also not reported, limiting assessment of how broadly the observed event counts apply.

Finally, the registry's planning assumptions refer to hypothetical two-arm illustrations, while the study itself is single-group. A trial-specific sample-size justification is not reported in the registry record. These limitations constrain interpretation of precision, attribution, and comparative safety, without changing the descriptive counts reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cryoablation System FIM/CE Mark Study — NCT03723070.
• Registry record last updated 2025-04-04; status last verified 2021-06.
• Results first posted 2021-07-19.
• 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

NCT03723070 is the completed Cryterion Cardiac Cryoablation System CE Mark Study, sponsored by Boston Scientific Corporation. It is described as a prospective, multicenter, open-label, single-group study of cryoablation for atrial fibrillation. Enrollment was 88, and the primary safety outcome timeframe was 12 months.

The registry reports 6 participants with serious adverse events and 56 with other adverse events among 88 at risk; deaths were 0. Six serious-event terms are listed, each at 1.1%. The record does not report an analyzed estimate of the primary composite endpoint or any inferential analyses. Consequently, the posted counts are descriptive and do not provide a comparison with another group.