Cryoanalgesia vs. Epidural in the Nuss Procedure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cryoanalgesia vs. Epidural in the Nuss Procedure (NCT02721017), a randomized phase 4 study. The primary outcome is Length of Hospitalization.

2. Clinical Question

The clinical question links pain control to a practical recovery outcome: the duration of the in-hospital stay after admission for the Nuss procedure. Length of stay is not itself a direct pain score, so it can reflect more than pain control. In general, discharge timing may also depend on recovery, care practices, and other clinical or logistical considerations; details about those factors are not reported in the registry record.

The comparison was randomized and parallel-group, with 10 participants in each arm. The registry record identifies the study as unmasked. It does not report how the random sequence was generated, whether allocation was concealed, or whether outcome assessment was masked. Those omissions limit assessment of how the assignment process and knowledge of treatment might have influenced the results.

The stated purpose was to determine whether cryoanalgesia provides better pain control. The primary endpoint and the listed secondary outcomes address different aspects of that question: hospital stay, narcotic usage during the postoperative hospital stay, and neuropathic pain score at one year. Cost analysis is also listed as a secondary outcome, but its results are not reported in the registry record.

3. Trial Design

The registry record describes a prospective, randomized, phase 4 trial with a parallel-group design. The study is marked completed, with enrollment of 20 participants. The recorded start was 2016-05, and primary completion was 2018-08-28. The study was sponsored by the University of California, San Francisco.

Participants were allocated to cryoanalgesia or thoracic epidural. The cryoanalgesia arm had 10 participants, and the thoracic epidural arm had 10 participants. Cryoanalgesia was performed thoracoscopically under general anesthesia by the patient’s surgeon at the time of the Nuss procedure. The epidural intervention is described as ropivicaine and fentanyl. The registry record classifies masking as none; it does not report whether any outcome assessor or other study personnel were separately masked.

The primary outcome was length of hospitalization, defined as the length of the patient’s in-hospital stay following admission for the Nuss procedure. It was recorded in postoperative days and summarized using the median and full range. Its timeframe is described as “estimated one week or less.” The record also lists narcotic usage, mean neuropathic pain score at one year, and cost analysis as secondary outcomes. Results are posted for narcotic usage and one-year neuropathic pain score; cost analysis results are not reported in the registry record.

These design details identify the broad comparison but do not fully describe trial conduct. The registry record does not report eligibility criteria beyond the condition and procedure context available in the record, participant characteristics, allocation concealment, adherence, protocol deviations, or analysis populations. It also does not report a trial-specific sample-size justification or a detailed statistical analysis plan. Those omissions should be kept distinct from the reported group summaries: a completed randomized design does not by itself establish how every planned analysis was performed.

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: Exclusion criteria were age \<13 years, chest wall anomaly other than pectus excavatum, previous repair or other thoracic surgery, and chronic use of pain medications.

Hospital Stay

Participant Follow Up

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 Length of Hospitalization, measured over estimated one week or less.

The primary endpoint is length of hospitalization after admission for the Nuss procedure, expressed in postoperative days. The registry record specifies a median and full range, with a timeframe described as “estimated one week or less.” In the posted results, the cryoanalgesia group has a median stay of 3 days, with a full range of 2 to 4 days. The thoracic epidural group has a median stay of 5 days, with a full range of 4 to 6 days.

A median describes the middle of the ordered observations. It can be useful when a distribution is skewed or when a few unusually long stays could pull an arithmetic mean away from what is typical. The full range gives the smallest and largest reported values, but it does not show how observations are distributed between those endpoints. In general, neither a median nor a range alone quantifies uncertainty in a between-group contrast.

Length of stay is a practical endpoint because it records the duration of hospitalization after surgery. It is not a direct measure of pain intensity. General clinical and organizational factors can also shape discharge timing, and the registry record does not describe how discharge decisions were standardized or whether other influences were measured. The record does not report an inferential comparison for the median endpoint; values for a two-arm comparison are not available or estimable in the posted results. The group summaries therefore describe the observed stays but do not establish the precision or statistical significance of a difference between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registered primary endpoint is a median, so its analysis differs from the mean-based calculations posted for the secondary outcomes. The primary results give a median and full range for each group. A median is the central observation after values are ordered; it is less affected than a mean by extreme observations. A range reports the minimum and maximum, but it gives no information about how many participants had values near either end or how concentrated the rest of the observations were.

What can the primary summaries establish?

The medians and ranges describe the recorded stays in the two groups. They do not, by themselves, provide a confidence interval for the difference between medians or a test of that difference. A method for comparing medians would need to account for the data structure and its assumptions. The registry record does not report such a method or a primary comparison estimate. It specifically lacks values that can be used for a two-arm comparison of this median-time endpoint. No primary p-value or confidence interval is reported in the registry results.

It is also important not to confuse the ranges with uncertainty intervals. The full range is a description of the observed data. A confidence interval instead describes uncertainty about an estimated quantity, such as a group contrast, under a statistical procedure. A range can overlap between groups even when a formal comparison suggests a difference, or fail to overlap without itself serving as a formal test. The range alone cannot resolve the inferential question.

How are the secondary comparisons formed?

The narcotic-usage and one-year neuropathic-pain outcomes are summarized with group means and standard deviations. The posted mean differences and confidence intervals are unadjusted recalculations from those summary statistics. A mean difference expresses the contrast between the two group averages; the sign depends on the order used for the comparison. The narcotic comparison is oriented as thoracic epidural relative to cryoanalgesia, and the neuropathic-pain comparison uses the same arm ordering.

A standard deviation describes the spread of individual observations around a group mean. It is not the same as a standard error, which describes the estimated sampling variability of a statistic. In general, the standard error of a mean depends on both the spread of observations and the sample size. In a two-group comparison, uncertainty in the mean difference reflects uncertainty from both groups. The posted calculations use the group sizes and standard deviations recorded for each outcome.

A confidence interval for a mean difference gives a range of values compatible with the estimate under the calculation’s assumptions. If the interval is wide, the estimate is less precise. Whether an interval includes zero can help describe statistical evidence for a nonzero difference under the model, but does not identify whether a difference is important in practice. Statistical significance and clinical importance are separate questions. The registry record does not specify a clinically important threshold for either secondary outcome.

What do the p-values mean?

A p-value is calculated under a null hypothesis and a statistical model. It describes how unusual the observed data, or data more extreme, would be if the null hypothesis and model were correct. It is not the probability that the null hypothesis is true, nor does it measure the probability that the result will replicate. The posted secondary p-values are unadjusted. They do not account for testing multiple outcomes or other analyses.

The registry record lists no sponsor-reported analyses for these secondary outcomes. The posted comparisons are therefore best treated as unadjusted recalculations from summary data, rather than as a full account of the trial’s prespecified analysis. The record does not report whether transformations, covariate adjustment, or other methods were planned or used. It also does not report whether any observed values were excluded from those calculations.

What do the planning illustrations represent?

The sample-size illustrations use the observed effect and consider planning for 100%, 75%, and 50% of that observed effect. Their stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. The listed quantities are participants per arm for 80% or 90% power for these mean-based comparisons. They are planning illustrations, not the trial’s original design justification and not a retrospective measure of power. The registry record does not report the trial’s own sample-size justification or show that these assumptions were used when the study was designed.

In general, a planning calculation estimates the sample size needed to detect a chosen effect under specified assumptions. Smaller target effects generally require more information to distinguish them from random variation. Such calculations depend on assumptions about variability, allocation, significance level, and the analysis method. A planning result derived from an effect observed in a small trial may be unstable, so it should not be interpreted as a guarantee that a future study will achieve a particular result.

The record does not report a detailed analysis plan, interim analyses, missing-data methods, or analysis populations. Those elements matter because they define which observations enter a calculation and how uncertainty is handled. Without them, the calculations can be interpreted only as the posted unadjusted summary-statistic comparisons, with the assumptions explicitly attached to the planning illustrations.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when more than one outcome or statistical comparison is assessed. In general, repeated testing can increase the chance of obtaining at least one nominally significant result even when no underlying effect is present. A trial may address this through a prespecified outcome hierarchy, adjustment of significance levels, or another stated strategy. The registry record does not report a multiplicity plan, a hierarchy among secondary outcomes, or how any such plan was applied.

The record lists narcotic usage, mean neuropathic pain score at one year, and cost analysis as secondary outcomes. Numerical results and unadjusted recalculations are posted for the first two, while cost analysis results are not reported in the registry record. The registry record lists no reported analyses for the secondary outcomes. The unadjusted calculations therefore should not be read as if they incorporate correction for examining multiple outcomes.

Missing-data handling is also not reported in the registry record. It does not state how many participants contributed observations to each outcome, whether any outcomes were missing, why data might have been missing, or whether imputation or other methods were used. The posted group summaries list 10 participants per arm, but that does not establish that all 10 contributed data to every endpoint. The available record does not permit assessment of whether missingness could have influenced the estimates.

Analysis populations are not described in the registry record. It does not state whether results followed an intention-to-treat approach, included only participants who received the assigned intervention, or used another population definition. The record also does not report exclusions, protocol deviations, or adherence. These details matter because analyses based on different participant sets can answer different questions and can produce different estimates.

Interim analyses, stopping rules, and a detailed statistical analysis plan are not reported in the registry record. Their absence from the available information should not be taken as evidence that a particular procedure was or was not used. Rather, these features cannot be assessed from the record. Together, the unreported multiplicity, missing-data, and analysis-population details limit the scope of the inferential conclusions that can be drawn from the secondary results.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: symptomatic pneumothorax (10.0%), urinary retention (10.0%), paraplegia (0.0%), wound infection (0.0%), infection from indwelling thoracic epidural catheter (0.0%).

The registry record reports serious adverse events for 0 of 10 participants in the cryoanalgesia group and 2 of 10 participants in the thoracic epidural group. It reports no other adverse events in either group and no deaths in either group. These counts describe what was recorded in this small trial; they do not by themselves establish a comparative safety difference.

The listed serious-event terms and percentages are Symptomatic Pneumothorax, 10.0%; Urinary Retention, 10.0%; Paraplegia, 0.0%; Wound Infection, 0.0%; and Infection from indwelling thoracic epidural catheter, 0.0%. The registry record’s listing does not provide enough detail to assign each listed term to a particular treatment arm or to determine whether terms refer to unique participants or event counts. The percentages should therefore be read as posted, without inferring more detail than the record states.

In general, safety counts in a small trial are imprecise: an event may be uncommon and still not appear in a limited sample. The registry record does not report detailed event timing, severity beyond the serious-event classification, relatedness assessments, or follow-up completeness. These figures are descriptive and do not establish that either intervention is safer or less safe.

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

The registry results describe a randomized comparison of cryoanalgesia and thoracic epidural in 20 participants undergoing the Nuss procedure. The primary outcome summaries show different observed medians for postoperative hospital stay, with full ranges reported for each arm. Those summaries are useful descriptions of the enrolled participants, but the registry record does not report a primary inferential comparison, confidence interval, or p-value. The primary results therefore do not quantify the uncertainty around a between-group difference.

The secondary outcomes add information about narcotic usage during the postoperative hospital stay and neuropathic pain score at one year. Their posted mean differences, confidence intervals, and p-values are unadjusted recalculations from the group summaries. They do not replace the missing inferential analysis of the primary endpoint, and the registry record does not state how multiplicity was handled. The cost analysis is listed but its results are not reported in the registry record.

These findings do not show that an observed group pattern will recur in another study. With 10 participants in each arm, estimates may be sensitive to individual observations, and the record does not report enough information to assess missingness, analysis populations, allocation concealment, or adherence. The absence of a reported primary comparison also means that the primary summaries alone cannot support a conclusion about the precision of the contrast.

In general, statistical evidence and clinical importance are distinct. A difference can be estimated precisely yet be small in practical terms, or appear large while remaining uncertain. The registry record does not report thresholds for a clinically important change in length of stay, narcotic usage, or pain score. It also does not provide detailed information about other factors that may influence hospital discharge or the measured outcomes.

The results should therefore be understood as the posted descriptions and unadjusted secondary calculations for this completed trial, not as definitive evidence of a treatment effect. They do not establish a benefit or lack of benefit, and they do not justify a treatment choice. The limits of the registry record and the small group sizes should remain part of any statistical reading.

13. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a clinically motivated question and the endpoint used to represent it. The stated aim concerns pain control, while the primary endpoint is length of hospitalization. Length of stay is readily expressed in postoperative days, but it is not a direct pain measure and may reflect factors beyond pain. Interpreting that endpoint requires attention to what was actually measured, not only to the study’s stated purpose.

The choice to summarize the primary endpoint with medians and ranges is also consequential. Those summaries can describe a small sample without assuming that its distribution is symmetric, but they do not automatically provide a formal estimate of the group contrast or its uncertainty. In the registry record, the median summaries are posted without an inferential comparison. This makes clear why descriptive presentation and statistical inference should not be conflated.

The secondary results illustrate another important issue: a small randomized trial can produce numerical contrasts that look different in size and direction across outcomes. Their meaning depends on measurement scale, timing, uncertainty, and the multiplicity context. The posted unadjusted calculations are not equivalent to a prespecified, comprehensive analysis, and the registry record does not explain how the secondary outcomes were prioritized or whether adjustment was planned.

The trial also underscores why registry reporting details matter. Information on missing data, analysis populations, allocation procedures, and sample-size justification helps readers judge how much confidence to place in an estimate. When those details are not reported in the registry record, the appropriate response is to limit the claims to the available results rather than fill gaps with assumptions. That discipline is especially important when group sizes are small and the primary endpoint lacks an inferential comparison.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation for statistical interpretation is that the registry record reports primary group medians and ranges but no inferential comparison for the primary endpoint. No confidence interval or p-value for a between-group contrast is reported. The summaries therefore describe the observed stays without establishing the precision of a group difference.

Each arm includes 10 participants. With small groups, estimates can be sensitive to individual values, and the information available may be insufficient to characterize variability reliably. Participant-level data are not reported, so the distribution of hospital stays and secondary outcomes cannot be examined beyond the posted summaries. The registry record also does not report baseline characteristics, making it difficult to assess the groups’ comparability beyond random assignment.

The record identifies the trial as randomized and unmasked, but does not report sequence generation or allocation concealment. It does not describe analysis populations, adherence, protocol deviations, or missing-data methods. It is therefore not possible to determine from the registry record whether all randomized participants contributed to every outcome or how incomplete observations were handled.

For the secondary outcomes, the posted comparisons are unadjusted recalculations, and no sponsor-reported analyses are listed. A multiplicity strategy is not reported. The record also does not provide a detailed analysis plan, trial-specific sample-size justification, or information about interim analyses. These omissions limit assessment of whether the posted analyses correspond to prespecified methods.

The primary endpoint, length of stay, is an indirect measure of pain control. The record does not describe discharge criteria or other factors that could affect hospitalization. The listed cost analysis has no results reported in the registry record. The available adverse-event counts are also limited in scope and do not include details about timing, relatedness, or follow-up completeness. Together, these features call for a cautious, descriptive reading rather than broad conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cryoanalgesia vs. Epidural in the Nuss Procedure — NCT02721017.
• Registry record last updated 2021-05-05; status last verified 2021-05.
• Results first posted 2021-05-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02721017 is a completed, phase 4, prospective randomized parallel-group trial sponsored by the University of California, San Francisco. The registry record lists enrollment of 20 and no masking. The recorded study start was 2016-05, and primary completion was 2018-08-28.

The trial compared thoracoscopic cryoanalgesia performed during the Nuss procedure with thoracic epidural using ropivicaine and fentanyl. The primary outcome was postoperative length of hospitalization, summarized by median and full range. Posted secondary results cover narcotic usage during the postoperative hospital stay and mean neuropathic pain score at one year. Cost analysis is listed as a secondary outcome, but its results are not reported in the registry record.

The primary results are descriptive; an inferential comparison is not reported. The secondary mean comparisons are unadjusted recalculations from summary statistics, and the registry record lists no reported analyses for those outcomes. Sample-size justification, multiplicity handling, missing-data methods, and analysis populations are not reported in the registry record.