Hysteroscopic Cryomyolysis for the Treatment of Submucosal Leiomyomata: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Hysteroscopic Cryomyolysis for the Treatment of Submucosal Leiomyomata (NCT00731341), a na na study. The primary outcome is Number of Adverse Events.

2. Clinical Question

The clinical question concerns whether hysteroscopic, ultrasound-guided cryoablation could be performed as a feasible procedure for symptomatic uterine fibroids in women who did not desire further pregnancies, and what procedure-related safety events were observed. The registered study purpose also refers to technical success and safety. The primary outcome focuses on adverse events through up to 4 weeks post procedure.

This is a feasibility and safety question, not a comparative efficacy question. The registry also lists secondary outcomes concerning patient-reported pain, return to normal activity, discharge on the procedure day, procedure length and physician satisfaction. Those outcomes may describe different aspects of the experience, but their numerical results are not reported in the registry record.

3. Trial Design

The record describes a completed feasibility study of hysteroscopic cryoablation treatment of symptomatic uterine fibroids. It identifies Boston Scientific Corporation as the sponsor. The study started in 2008-07, and primary completion was recorded in 2009-02. Enrollment was 3. The phase is listed as NA, allocation as NA, masking as NONE and model as SINGLE GROUP.

One group underwent hysteroscopic ultrasound-guided cryoablation for uterine fibroids. No control arm is listed. This matters for interpretation: observations after treatment can be described, but the design does not directly estimate how outcomes would have differed under another treatment or without the procedure. In particular, a before-and-after description, if available, would not by itself separate changes associated with treatment from changes over time or other influences.

The stated purpose was to evaluate technical success, safety and procedure feasibility among women who did not desire further pregnancies. The primary outcome recorded for the study is adverse events, assessed by incidence and severity of intra-procedure and post-procedure events. Its timeframe is up to 4 weeks post procedure. The registry lists five secondary outcome descriptions: self-reported pain on a visual analogue scale, time to return to normal activity, discharge on the day of cryoablation, average procedure length and physician satisfaction with ease and convenience. The record reports six outcome measures and 0 analyses.

The registry does not report a detailed protocol, a sample-size justification, a comparator rationale or a statistical analysis plan. It also does not report further detail about recruitment, eligibility criteria, treatment delivery or follow-up completeness. Those omissions limit how fully the design and conduct can be reconstructed from the 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

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 Adverse Events, measured over up to 4 weeks post procedure..

The primary endpoint is titled Number of Adverse Events, with participants as the unit. Its description says that procedure safety will be assessed through the incidence and severity of intra-procedure and post-procedure related adverse events. The stated timeframe is up to 4 weeks post procedure. This endpoint is intended to capture safety observations around the procedure, rather than a measure of symptom improvement or comparative treatment effect.

Counting participants affected is different from counting every event. A participant may, in principle, experience more than one event; a participant count indicates how many had an event, not the total number of events. The registry's adverse-event summary separately reports participants at risk and participants affected for serious and other adverse events. The serious-event summary reports 3 at risk and 0 affected; the other-event summary reports 3 at risk and 1 affected. The record does not identify the non-serious event term or provide its severity, timing or relationship details.

Safety endpoints are useful in a feasibility study because procedural problems can affect whether a technique is practical to study further. However, the endpoint definition does not alone establish that all events were captured or that the observed counts precisely characterize risk beyond the participants enrolled and the recorded follow-up period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on what was measured, who was counted and whether the design supports a comparison. For this study, the endpoint is a participant count for adverse events, and the design is single group. The methods concepts below are general explanations; they do not imply that an unreported analysis was performed.

What does a participant count tell the reader?

A participant count records whether participants experienced an event under the registry's definition. It is not necessarily the same as a count of event episodes. If one participant experiences multiple events, participant-level and event-level summaries can differ. The registry uses participants as the primary outcome unit and separately lists participants at risk and affected in the safety summary. It does not give event-level descriptions sufficient to reconstruct how many episodes occurred.

Denominators matter because a count alone does not show how many people were observed. Here the serious and other adverse-event summaries each list 3 participants at risk. The listed affected counts are 0 for serious events and 1 for other events. These counts should be interpreted within the recorded study group and follow-up, rather than as estimates that automatically apply to other populations or settings.

Why does the single-group design matter?

In a single-group study, there is no listed control group against which to compare the observed outcomes. Descriptive summaries can report what was recorded among participants who underwent the procedure. They cannot, on their own, estimate a difference between treatment strategies. A causal comparison requires an appropriate comparator and a design and analysis that address differences between groups; those elements are not listed for this study.

General statistical interpretation also distinguishes an observed outcome from an underlying probability. The count is fixed for the enrolled participants, while the probability of an event in a wider target population is uncertain. A confidence interval, when reported, expresses uncertainty around an estimate under specified assumptions. No confidence interval for the primary outcome is reported in the registry record. Its absence means the precision of an underlying event-rate estimate cannot be assessed from a reported interval.

What can a zero count establish?

A zero observed count means that no affected participants were recorded for that outcome in the available summary. It does not mean the underlying risk is exactly zero. With sparse observations, plausible values for the underlying risk can remain uncertain. This is a general property of inference from limited event data, not a claim that any particular unreported interval applies to this study. The registry does not report an interval or a model for the serious adverse-event count.

Similarly, the other adverse-event count identifies a participant-level observation but not its clinical character. Interpretation of safety commonly depends on event type, severity, timing, duration, seriousness criteria and relatedness assessment. The primary outcome description mentions incidence and severity, but the posted summary does not report those details for the event affecting a participant. They are not reported in the registry record.

What does a statistical test add?

A hypothesis test evaluates data against a specified statistical model and question, such as whether an observed difference is inconsistent with a null hypothesis. It does not by itself measure clinical importance, establish causation or correct limitations in study design. This study has no listed comparison group, and the registry reports 0 analyses. No primary-outcome p-value or test result is reported. A test of comparative effect would not be supported by the listed single-group design without an appropriate comparison.

Statistical methods can also adjust for factors that affect outcomes, but adjustment requires measured variables, a prespecified model and adequate information. The registry does not report an adjusted analysis, covariates or a statistical model for this endpoint. It would therefore be inappropriate to infer that adjustment was performed or to supply an adjusted result.

How should planning illustrations be read?

Planning illustrations are different from analyses of observed study outcomes. The record describes illustrations based on an observed effect and assumptions of a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. Such scenarios are planning calculations, not observed power. They do not show that the completed study had a particular probability of finding an effect, and they do not convert this single-group study into a two-arm comparison.

In general, planning calculations depend on assumptions about the effect, variability, allocation, test and target power. Changing assumptions changes the resulting planning requirement. A scenario based on a fraction of an observed effect is an illustration conditional on that effect and those assumptions; it is not independent confirmation that the effect is real. No planning output should be interpreted as an observed result. The registry does not report its own sample-size justification, so the stated illustration assumptions should not be treated as the rationale used to design this feasibility study.

Over-dispersion is a general concern when event counts vary more than a chosen statistical model expects. A model that assumes less variability than the data-generating process can make uncertainty appear too small. The record does not report a count model, a dispersion estimate or enough event-level data to assess over-dispersion. This concept therefore explains a possible modeling consideration, not a feature demonstrated in this trial.

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("Cryoablation for the Treatment of Uterine Fibroids")
n      <- c(3)
events <- c(1)
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  Cryoablation for the Treatment of Uterine Fibroids  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary adverse-event outcome and secondary outcomes concerning pain, return to normal activity, discharge on the procedure day, procedure length and physician satisfaction. Considering multiple outcomes can raise a multiplicity issue when formal hypothesis tests are conducted: the more questions tested, the greater the opportunity for an apparently notable result to arise by chance under a set of null hypotheses. Methods such as prespecifying a primary endpoint or adjusting testing can address particular multiplicity concerns, but the appropriate approach depends on the aims and analysis plan.

The registry reports 0 analyses. It does not report a multiplicity strategy, a hierarchy among secondary outcomes, or a statistical analysis plan. Accordingly, no adjustment or testing procedure should be inferred. The primary endpoint's designation does not establish that a formal test was performed.

The registry does not report missing-data counts, reasons for missingness, imputation methods or analysis-population definitions. The safety summary lists 3 participants at risk for serious events and 3 at risk for other events, but these summaries alone do not document completeness of follow-up or whether all recorded outcome information was available for every participant. The primary timeframe is up to 4 weeks post procedure; the record does not describe visit schedules or the handling of observations outside that window.

In general, missingness can matter if the probability of an outcome being observed is related to the outcome itself or to participant characteristics. Analyses may use different assumptions about such missing information, and those assumptions can affect estimates. No such assumptions or sensitivity analyses are reported. Therefore, the posted counts are best read as the registry's recorded summaries, without assuming a particular missing-data method or a defined analysis population beyond the participants at risk listed in the safety summary.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The safety summary lists 3 participants at risk for serious adverse events and 0 participants affected. For other adverse events, it lists 3 participants at risk and 1 participant affected. The unit is participants, so these figures describe people recorded as affected, not necessarily the total number of event episodes.

The serious-event count of 0 is limited to this study's recorded observations and should not be interpreted as evidence that the risk is absent. The other-event count does not identify the event, its severity or its timing. Although the primary outcome description says incidence and severity of intra-procedure and post-procedure related events will be assessed, those event details are not reported in the registry record. The record also does not report deaths; the death value is not specified in the available safety summary.

These are descriptive safety counts from a single-group study, with no listed comparator. They cannot establish whether the procedure caused an event or how its safety compares with another approach. The stated primary-outcome timeframe is up to 4 weeks post procedure, and the record does not provide further detail about completeness of ascertainment within that period.

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

The result supports a limited descriptive statement about the recorded safety observations: the registry lists 0 participants affected by serious adverse events and 1 participant affected by other adverse events, with 3 at risk in each category. It does not support a precise estimate of the frequency of events in a wider population. The small enrollment and lack of a reported confidence interval leave uncertainty about how well these observations represent outcomes beyond the enrolled group.

The study's purpose also included technical success and feasibility. Numerical results for those aims are not reported in the registry record, so the safety counts cannot establish whether the procedure was technically successful or feasible according to any specific criterion. The record does not state a quantitative success threshold. Results for the listed secondary outcomes are also not reported, so no conclusions can be drawn from this record about pain, recovery of normal activity, discharge on the procedure day, procedure duration or physician satisfaction.

The study does not establish comparative benefit or harm. No comparator group is listed, and no randomized comparison is described. Even if an outcome was observed after the procedure, a single-group result does not show what would have happened to the same population under another treatment or without the procedure. Nor does the adverse-event summary by itself establish causation or exclude events that were not captured.

These limitations do not make the observations meaningless. Descriptive feasibility data can document what was recorded in an early investigation and identify questions for further study. Their role is narrower than that of a controlled comparison: they characterize observations in this enrolled group, without demonstrating a treatment effect, comparative safety, or a definitive risk profile.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between documenting outcomes and estimating a comparative treatment effect. The registry describes a completed feasibility study with a single group and enrollment of 3. Its adverse-event summary is useful as a record of observed counts, but the design does not provide a control group for estimating a difference between approaches.

Sparse safety observations also make precision central to interpretation. A count of 0 serious adverse-event-affected participants is not equivalent to certainty that serious events cannot occur. An interval or other uncertainty analysis could help express the range of underlying values compatible with observations, but no such analysis is reported in the registry record. The same caution applies to the other adverse-event count: the participant count is known, while the event description and uncertainty are not.

The study's stated aims include technical success, safety and procedure feasibility, but only the safety counts described in the record can be discussed quantitatively. The distinction between registered aims and reported results is important: listing an outcome does not establish what the outcome showed. The secondary measures may be relevant to a feasibility assessment, yet their numerical results are not reported in the registry record.

Finally, planning calculations and observed analyses answer different questions. The record describes assumptions for planning illustrations, but those do not constitute observed power or an analysis of this single-group study. Keeping design, planning and outcome summaries separate prevents a small feasibility dataset from being interpreted as a comparative trial or as a conclusive estimate of safety.

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 are specific to the information recorded for this study. Enrollment was 3, and the design is single group. With no listed comparator, the study cannot directly estimate how outcomes differ from an alternative treatment or from no procedure. The record does not report a sample-size justification, so the basis for the enrollment target is not reported in the registry record.

The primary outcome is described as assessing incidence and severity of related intra-procedure and post-procedure adverse events through up to 4 weeks post procedure. However, the safety summary does not identify the event affecting a participant, its severity, timing, duration or assessed relationship to the procedure. It does not report whether all events were collected using a specified assessment process. Deaths are not specified in the available summary.

The registry lists technical success and feasibility among the study purpose, but it does not provide numerical results or definitions for those outcomes. Numerical results for the listed secondary outcomes are also not reported. The record reports 0 analyses, with no reported confidence intervals, hypothesis tests, adjusted estimates, analysis populations, missing-data methods or multiplicity plan.

Further information about eligibility, participant characteristics, procedure details, follow-up completeness and protocol deviations is not reported in the registry record. These omissions constrain assessment of generalizability and outcome ascertainment. The posted adverse-event counts should consequently be understood as limited descriptive observations, not a complete account of every aspect of study conduct or of the procedure's risk in other settings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Hysteroscopic Cryomyolysis for the Treatment of Submucosal Leiomyomata — NCT00731341.
• Registry record last updated 2021-07-19; status last verified 2021-07.
• Results first posted 2011-07-01.
• 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

NCT00731341 is a completed, single-group feasibility study of hysteroscopic cryoablation for symptomatic uterine fibroids in women who did not desire further pregnancies. Boston Scientific Corporation is listed as sponsor. Enrollment was 3; the study began in 2008-07 and primary completion was recorded in 2009-02.

The primary outcome was Number of Adverse Events, measured in participants through up to 4 weeks post procedure. The safety summary lists 0 participants affected by serious adverse events among 3 at risk, and 1 participant affected by other adverse events among 3 at risk. The registry reports 0 analyses. Results for technical success, feasibility and the listed secondary outcomes are not reported in the registry record.