This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Efficacy, and Side Effects Study of Interventional Cryotherapy in the Pleural Space("ICE PLS") (NCT00747916), a na phase 4 study. The primary outcome is To Reduce Tumor Burden in the Pleural Space, as Determined by Visual Inspection and Biopsy of the Treatment Sites 2-5 Days Post Treatment. Safety Endpoint Clinical and Radiographic Status at 30 Days Post CryoSpray Treatment and Adverse Events..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00747916 |
| Phase | Phase 4 |
| Condition | Cancer, Pleural Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | CSA Medical, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
People with cancer or pleural neoplasms were the population of interest. The study enrolled 3 participants, but the registry record says zero participants were analyzed because the study ended early. It does not report further eligibility details or characteristics of the enrolled participants.
Intervention
The intervention was the CryoSpray Ablation System, a device used to deliver cryotherapy to neoplastic lesions on the parietal pleural surface. The arm description specifies up to 3 cycles of 10-40 second sprays. The record does not report how many participants received treatment or what treatment exposure they received.
Comparator
There was no comparator group. The study is listed as a single-group design, with allocation recorded as NA and masking as none. Its outcomes therefore cannot be interpreted as a randomized or controlled comparison with another treatment or with no treatment.
Primary question
The primary question combined whether treatment reduced tumor burden, assessed by visual inspection and biopsy of treatment sites 2-5 days after treatment, with safety assessed through clinical and radiographic status at 30 days and adverse events. The record reports no analyzed participants for this outcome, so it supplies no estimate of tumor response or an interpretable primary-outcome result.
3. Trial Design
ICE PLS was a pilot study of the safety, efficacy, and side effects of interventional cryotherapy for disease in the pleural space. The registry lists the study as Phase 4 and as a single-group, non-randomized study. Allocation is recorded as NA, and masking as none. The sponsor was CSA Medical, Inc. The study status is terminated.
The registry lists enrollment of 3 participants. The study start is recorded as 2008-08 and primary completion as 2009-08. These dates describe the registry record; they do not establish how long each participant was followed or when each participant received treatment. The listed primary-outcome timeframe is 1 year, while the outcome description also specifies assessment of treatment sites 2-5 days after treatment and clinical and radiographic status at 30 days. The record does not explain how these time references relate to one another.
The intervention was the CryoSpray Ablation System. The arm description says participants would receive cryotherapy using up to 3 cycles of 10-40 second sprays. It does not report treatment delivery for individual participants, dose actually received, or deviations from the intended regimen.
Because this was a single-group study, its design does not provide a concurrent control for separating treatment effects from other explanations for observed changes. More importantly, the registry states that zero participants were analyzed for the primary outcome due to early termination. No primary analyses are listed. The registry record does not report a protocol rationale for the planned enrollment, details of early termination, or the statistical 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
| Stage | All Participants ICE PLS |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: zero participants analyzed due to early termination of 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.
| Characteristic | Unit | All Participants ICE PLS |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 1 |
| Age, Continuous | years | 59 (49 to 67) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as To Reduce Tumor Burden in the Pleural Space, as Determined by Visual Inspection and Biopsy of the Treatment Sites 2-5 Days Post Treatment. Safety Endpoint Clinical and Radiographic Status at 30 Days Post CryoSpray Treatment and Adverse Events., measured over 1 year.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint combines a tumor-burden assessment with safety follow-up. Tumor burden was to be assessed through visual inspection and biopsy of treatment sites 2-5 days after treatment. Visual inspection can document visible changes at the treated site, while biopsy can provide tissue-level evidence about disease at the sampled location. These measures address local findings, but the registry record does not specify scoring criteria, biopsy procedures, how findings would be combined, or what change would count as a response.
The endpoint description also includes clinical and radiographic status at 30 days and adverse events as safety measures. Clinical and radiographic assessments can capture aspects of status beyond a biopsy site, while adverse-event monitoring records harms observed during follow-up. The record does not define the safety measures in more detail or state how they were to be summarized.
The timeframe field lists 1 year, which is not aligned explicitly with the shorter assessment times named in the endpoint description. The registry record does not clarify whether the listed timeframe applies to all components or how outcomes were to be assessed across follow-up. It reports zero participants analyzed for the primary outcome, so no tumor-burden or safety endpoint estimate is available from that outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registry record reports zero participants analyzed for the primary outcome because of early termination. It therefore provides no analyzed estimate of tumor-burden change, no estimate of the primary safety endpoint, and no precision measure such as a confidence interval for either. The absence of an analyzed primary result is not evidence that treatment had no effect; it means the primary question is unanswered by the results recorded for this outcome.
The enrollment field lists 3 participants, but enrollment is not the same as analysis. The record does not state how many participants received the device, had post-treatment assessments, or contributed to any particular outcome. It also does not provide individual results or explain why the study ended early. Those gaps prevent reconstruction of treatment exposure, outcome completeness, or the reasons for non-analysis.
The study has no comparator arm. Even if change in tumor burden had been reported, an uncontrolled before-and-after observation would not by itself distinguish an intervention-associated change from other causes. In this record, the absence of a primary analysis means even that descriptive within-group comparison is unavailable.
The adverse-event record lists 3 participants at risk for serious adverse events and 0 affected; it also lists 3 at risk for other adverse events and 0 affected. These are the posted counts, not a complete safety estimate. The record does not provide event-term listings, follow-up completeness, or an explanation of how adverse events were collected and coded. The death field is not reported in the registry record. In particular, zero events recorded cannot be taken as evidence that an intervention is free of risk, especially when the study was small and terminated early.
The registry lists two outcome measures and no analyses. It provides no numerical treatment-effect estimate, statistical test, confidence interval, or account of model-based adjustment. The statistical plan is not reported in the registry record. Consequently, there is no basis for judging statistical significance, the magnitude of any treatment-associated effect, or how precisely such an effect was estimated.
Planning illustrations, if consulted alongside the registry information, must be kept separate from trial findings. The stated planning assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, although the actual study is a single-group design. Such illustrations are not the trial's observed power and do not replace an analysis of observed outcomes. The registry record does not report an analyzed effect estimate to serve as a clinical result.
9. Statistical Methods Explained
Statistical interpretation depends on the distinction between a study's design, the outcomes it planned to measure, and the data actually analyzed. ICE PLS is listed as a single-group study, with allocation recorded as NA and masking as none. Its primary outcome description identifies intended assessments, but the registry record says zero participants were analyzed for that outcome. An endpoint can be specified without an analyzable result being available. In that situation, there is no treatment-effect estimate to interpret and no sampling uncertainty around an estimate to quantify.
What does an estimate tell the reader?
An estimate is a numerical summary of the observed outcome, such as a mean change, a proportion meeting a response definition, or a difference between groups. The registry record does not report a primary-outcome estimate of any of these kinds. It also does not define a response threshold or provide the participant-level measurements needed to construct an unadjusted estimate. It would therefore be inappropriate to infer an effect from the study title, its objectives, or the planned endpoint descriptions.
What would a confidence interval add?
In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values compatible with different conclusions can leave substantial uncertainty. An interval does not correct design limitations, missing observations, measurement problems, or bias. No confidence interval for the primary outcome is reported in the registry record, because no participants were analyzed for that outcome.
Why does the absence of a comparator matter?
In general, a concurrent control group helps distinguish changes associated with an intervention from changes that might have occurred for other reasons. A single-group study can describe outcomes among participants who receive an intervention, but it cannot make a like-for-like randomized comparison against a control group. Here, the absence of a comparator is part of the registered design, not a statistical adjustment that can be repaired after the fact. Since the primary outcome also has no analyzed participants, the record does not offer even a descriptive primary result for the treated group.
What does the planning language mean?
The stated sample-size assumptions describe a planning illustration, not the actual design of ICE PLS. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, and describes the target effect as a stated fraction of an observed effect. The actual study is listed as single-group, so the equal-allocation assumption is not a description of its enrolled arms. The registry record does not report a primary-outcome effect estimate from analyzed participants. For that reason, planning values should not be interpreted as evidence about an effect observed in this trial or as observed power.
In general, power is a design-stage probability calculated under assumptions about an effect, variability, analysis, and sample size. It is not a measure of whether a completed study found a real effect. A planning calculation can illustrate what a hypothetical design might detect if its assumptions hold, but it cannot substitute for outcome data. The statistical plan and sample-size justification for the trial itself are not reported in the registry record.
How should event counts be read?
Adverse-event counts are descriptive counts of participants recorded as affected within the reported risk group. They do not, by themselves, describe severity beyond the categories recorded, timing, duration, relationship to treatment, or completeness of surveillance. General safety interpretation also depends on the number with adequate follow-up and on the rules for collecting and coding events. Those details are not reported in the registry record. A recorded count of zero is therefore a report about the entries in the registry, not proof that no unrecorded event occurred or that the intervention has no risk.
Why can over-dispersion matter?
In general, a count outcome can vary more than a model assumes, a property called over-dispersion. If that extra variability is ignored, a model may understate uncertainty and make estimates appear more precise than they are. Methods that account for over-dispersion can be appropriate for some count outcomes, depending on the study design and data. The registry record does not identify a count model, provide analyzed count outcomes, or report an analysis that could be evaluated for over-dispersion. This general point does not imply that such a model was used or was needed for ICE PLS.
More broadly, statistical methods must match the outcome, design, and data available. The registry record identifies visual inspection, biopsy, clinical and radiographic status, and adverse events, but does not give enough detail to identify the planned statistical summaries or models. It lists no analyses. Therefore, model assumptions, adjustment choices, handling of repeated measurements, and uncertainty calculations cannot be assessed from the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures, but it does not describe how many hypotheses were planned, which outcomes were intended to be confirmatory, or whether any adjustment for multiple testing was planned. When several outcomes or tests are assessed, multiplicity can increase the chance of at least one apparently positive result by chance. In general, prespecifying a primary outcome and a testing strategy helps readers interpret results across multiple analyses. The registry names a primary outcome, but the statistical plan and any multiplicity procedure are not reported in the registry record. No analyses are listed, so there are no reported tests to evaluate for multiplicity.
The primary outcome description contains multiple components: tumor burden assessed by visual inspection and biopsy, clinical and radiographic status, and adverse events. The record does not explain whether these were intended to be separate outcomes, combined into a single endpoint, or interpreted independently. It also does not state how discordant findings would be handled. The timeframe field lists 1 year, while the description specifies assessments at 2-5 days and 30 days; the registry record does not clarify the relationship between these time points.
For missing data, the record states that zero participants were analyzed for the primary outcome due to early termination. It does not report how many participants had each assessment, why data were unavailable, or whether any observations were excluded from other outcomes. It does not describe a missing-data method or assumptions about why values might be missing. No analysis population, such as an intention-to-treat or treated population, is defined in the registry record. Enrollment alone does not establish who received the intervention or was included in an outcome analysis.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| All Participants ICE PLS | 0 | 3 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| All Participants ICE PLS | 0 of 3 |
The adverse-event record lists 3 participants at risk for serious adverse events, with 0 affected. It also lists 3 participants at risk for other adverse events, with 0 affected. These are counts in the registry record; they should be read as such rather than as evidence that serious or other adverse events are impossible or absent in all participants who might receive this intervention.
The registry does not list serious adverse-event terms. The death field is not reported in the registry record, which is different from a reported count of zero deaths. The record also does not provide event-level descriptions, timing, duration, severity beyond the serious-versus-other grouping, attribution to treatment, or details of follow-up and ascertainment. These omissions limit what can be concluded about safety.
In general, a zero recorded count is most informative when event collection is complete and the number and duration of observation are adequate for the question. Early termination and the statement that zero participants were analyzed for the primary outcome make it especially important not to treat the posted adverse-event counts as a comprehensive safety assessment. They describe the reported registry entries, not a definitive safety profile.
12. What the Result Does, and Does Not, Mean
The registry record establishes that ICE PLS was registered as a pilot study of the CryoSpray Ablation System for neoplastic lesions on the parietal pleural surface. It records a single-group design, enrollment of 3 participants, and a status of terminated. It identifies intended assessments of tumor burden, clinical and radiographic status, and adverse events. These details describe the study's question and design, not the findings of an efficacy analysis.
The primary-outcome entry says zero participants were analyzed because of early termination. As a result, the registry record does not establish whether tumor burden changed after treatment, how findings from inspection and biopsy compared, or what clinical and radiographic status was observed. There is no reported primary effect estimate or precision interval. The result therefore cannot be characterized as demonstrating benefit, demonstrating no benefit, or ruling out an effect.
The safety counts are limited descriptive information: the record lists 0 serious adverse events and 0 other adverse events among 3 participants at risk in each category. The registry does not supply event terms or details that would support a fuller safety analysis, and the death field is not reported. These entries do not establish that the treatment is safe or that adverse events did not occur outside the reported record.
More generally, an uncontrolled pilot study is not designed to provide the same comparative evidence as a randomized trial with a control group. Even with complete observations, a single-group study has limited ability to separate treatment-associated changes from other explanations. In this case, early termination and the lack of primary-outcome analyses further restrict interpretation. The registry record is informative about the planned question and the incompleteness of its reported results, but not about the treatment's efficacy.
13. Why This Trial Matters Statistically
ICE PLS illustrates why a registered objective and a measurable endpoint should not be mistaken for a completed statistical result. The record describes a clinically focused question and identifies assessments that were intended to address tumor burden and safety. Yet it also reports zero participants analyzed for the primary outcome because the study ended early. That distinction is fundamental: a well-defined question does not itself yield an estimate, and an estimate is needed before its magnitude or precision can be judged.
The record also highlights the interpretive limits of a single-group design. Without a comparator, observed changes would be difficult to distinguish from other causes, even if results were available. In ICE PLS, there are no primary analyses to describe such changes. This makes clear that statistical interpretation depends on both design and data, not only on the intervention or endpoint named in the registry.
The safety entries offer another useful lesson. Zero recorded events are counts, not proof of zero risk. Their meaning depends on ascertainment, follow-up, and completeness, details the registry record does not provide. The small enrollment and early termination reinforce the need to avoid turning a sparse registry entry into a broad safety claim.
Finally, planning calculations and observed results serve different purposes. A planning illustration can show how assumptions about an effect, allocation, and analysis relate to a hypothetical design. It cannot fill in the missing outcome data or create evidence from an analysis that was not reported. The registry record therefore matters statistically as an example of the limits imposed by incomplete outcome reporting and a design without a control group.
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 study's early termination and the report of zero participants analyzed for the primary outcome are the most direct limitations for interpreting its efficacy question. The registry record does not explain why the study was terminated or whether any assessments were collected before termination. It also does not state how many participants received the CryoSpray device, so enrollment cannot be treated as treatment exposure.
The single-group design has no like-for-like control comparison. The record lists allocation as NA and masking as none, and it does not describe any method to reduce assessment bias. It does not report eligibility criteria in detail, baseline characteristics, treatment adherence, or participant-level outcome data. These omissions make it impossible to assess comparability, changes from baseline, or the influence of missing observations.
The endpoint description combines several types of assessment and gives different time references: a timeframe of 1 year and specified assessments at 2-5 days and 30 days. The registry record does not clarify how these fit together. It also does not provide operational definitions, assessment rules, or a statistical plan. The record lists two outcome measures but no analyses and does not describe multiplicity handling or a missing-data strategy.
Safety interpretation is limited by the absence of event terms and details about ascertainment, follow-up, attribution, and severity. The death field is not reported in the registry record. Taken together, these limitations mean that the posted information supports description of the registered design and reported counts, but not a reliable estimate of efficacy or a comprehensive safety conclusion.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Efficacy, and Side Effects Study of Interventional Cryotherapy in the Pleural Space("ICE PLS") — NCT00747916.
- Registry record last updated 2015-07-16; status last verified 2015-06.
- Results first posted 2015-06-08.
- 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.
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18. Record Summary
ICE PLS was a Phase 4, single-group pilot study of the CryoSpray Ablation System for neoplastic lesions on the parietal pleural surface. The registry lists enrollment of 3 participants, no masking, allocation as NA, and terminated status. It records a study start of 2008-08 and primary completion of 2009-08.
The primary outcome combined tumor-burden assessment by visual inspection and biopsy at 2-5 days with clinical and radiographic status at 30 days and adverse events; its listed timeframe is 1 year. The registry states that zero participants were analyzed for the primary outcome due to early termination and lists no analyses. For safety, it records 0 serious and 0 other adverse events among 3 participants at risk in each category. Serious-event terms are not listed, and the death field is not reported. The record does not provide an analyzed efficacy estimate or a comparator-based result.