Fetal Tracheal Balloon Study in Diaphragmatic Hernia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fetal Tracheal Balloon Study in Diaphragmatic Hernia (NCT00966823), a na phase 2 study. The primary outcome is Newborn Survival at Birth.

2. Clinical Question

Statistically, this is a descriptive question about outcomes among participants receiving the intervention, rather than a randomized comparative question. With enrollment of 3 and no reported primary result, the record does not establish the frequency of survival in the study group. Nor does it provide a basis for estimating how that outcome would differ under another approach. The secondary outcomes listed include newborn survival at 30 days, maternal complications, fetal morbidity, and in utero lung growth measured using LHR. Results for these outcomes are not reported in the registry record. The study's intended clinical question and its posted statistical evidence are therefore distinct: the record states what the intervention was intended to examine, but it does not report outcome data that answer that question.

3. Trial Design

This was a phase 2 study of fetal tracheal balloon intervention for diaphragmatic hernia. The registry identifies Rhode Island Hospital as the sponsor, records enrollment of 3, and lists the study status as terminated. The recorded start was 2008-09 and primary completion was 2015-01. A reason for termination is not reported in the registry record.

The design is classified as single-group. Allocation is listed as NA, and masking is listed as none. The intervention is described as fetal tracheal obstruction with a detachable balloon; the arm description says fetuses were treated with endoscopic tracheal occlusion. No separate control arm is reported. Because there is no like-for-like control comparison, any outcome description would concern the treated group alone and could not isolate the intervention's effect from other influences using a randomized contrast.

The registry lists newborn survival at birth as the primary outcome, measured as participants during the newborn period (1 day). Secondary outcomes are newborn survival at 30 days, maternal complications, fetal morbidity, and the number of participants with in utero lung growth (LHR) >1.4. These outcome labels identify what was intended to be assessed; they do not supply outcome results.

The record does not report eligibility criteria, participant baseline characteristics, the number who received the procedure, or whether all enrolled participants completed follow-up. The distinction matters because enrollment is not necessarily the same as the number included in an endpoint analysis. An analysis population, protocol details, and the reason the study ended are not reported in the registry record. The record also lists no analyses. Consequently, the design can be described from its high-level registry classification, but details needed to reconstruct how participants entered the study or how outcomes were analyzed are unavailable.

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: 1 participant met inclusion criteria and was enrolled, but was excluded immediately before intervention (active labor), and was therefore excluded from the trial.

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 Newborn Survival at Birth, measured over Newborn period (1 day).

The primary endpoint is titled Newborn Survival at Birth. It is recorded as a number of participants, with the timeframe specified as the newborn period (1 day). The registry record does not give a definition of survival beyond this label, explain how the endpoint was ascertained, or report the observed number of participants meeting it.

General: Survival is a clinically meaningful outcome because it describes whether the event of interest occurred for participants within a stated period. A clearly specified observation window is important: outcomes measured at different times answer different questions. Survival at birth and survival at 30 days are distinct endpoints, even when they concern the same participants. A count can describe how many participants experienced the outcome, while a proportion or rate would also require a clearly defined denominator and analysis population.

The registry names newborn survival at birth as the primary outcome, so it is the central outcome intended to address the study's stated purpose. However, a primary label alone is not evidence of an observed outcome or of a treatment effect. With no result or analysis reported, the record does not show the survival count, its uncertainty, or how the endpoint relates to the intervention. The listed endpoint is therefore useful for understanding the intended question, but it cannot support a numerical conclusion about survival in this study.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the study as single-group, with no masking and allocation listed as NA. It records no analyses. The posted information therefore supports a description of the design and endpoint labels, but not a reconstruction of an inferential analysis. A statistical method should not be attributed to the study unless the registry record reports it.

What does a single-group design estimate?

General: A single-group study can describe outcomes among participants who receive an intervention. If the outcome and analysis population are clearly defined, a count or proportion can summarize what happened in that group. Such a description does not, by itself, estimate the difference between intervention and control. Without a concurrent comparison group, the study cannot directly separate the intervention's contribution from the natural course of illness, participant selection, or other care.

For this study, the primary outcome is stated as a number of participants with newborn survival at birth. The result is not reported in the registry record. The number enrolled is 3, but enrollment alone is not the endpoint numerator or proof that all enrolled participants were analyzed. The record does not state the analyzed population, the number followed for the primary endpoint, or how missing endpoint information was handled.

What does the outcome format tell the reader?

The primary endpoint is binary in meaning: a participant either meets the stated survival outcome within its timeframe or does not. The registry describes the measure as a participant count. General: Binary outcome data can be presented as counts and, when the denominator is specified, as proportions. A count without a clearly connected denominator does not convey a rate, and a proportion without uncertainty can be difficult to interpret when the group is small. No primary count, proportion, or uncertainty estimate is reported.

The listed secondary outcomes are not all the same kind of measure. Survival, complications, and morbidity concern events, while the LHR outcome is described as the number of participants exceeding a stated threshold. The registry record does not provide operational definitions, assessment procedures, or analyses for these measures. The stated threshold is LHR >1.4; no result for the number meeting it is reported.

What is a confidence interval?

General: A confidence interval expresses the precision of an estimate by giving a range of values compatible with the data under the assumptions of the analysis. It is not a guarantee that the true value lies within a particular interval, and its interpretation depends on the method and study design. For a very small group, limited information generally means less precision. No confidence interval for the primary outcome is reported in the registry record, so the precision of any primary estimate cannot be assessed.

How should significance testing be understood?

General: A significance test evaluates how compatible the observed data are with a specified null hypothesis under a statistical model. A p-value is not the probability that the null hypothesis is true, and it does not measure clinical importance. In a single-group study, an inferential test would need a meaningful reference value or hypothesis to test. The registry record reports no primary analysis or p-value, and it does not report a statistical analysis plan or a prespecified reference for testing the endpoint.

What do the sample-size assumptions represent?

The registry's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is not a description of this trial's single-group design. No sample-size illustration values or observed effect are reported in the registry record. General: A planning illustration estimates the number of participants that might be needed under stated assumptions; it is not observed evidence and is not observed power. The result depends on the effect size assumed, the statistical model, and the chosen error and power criteria. A planning calculation cannot substitute for a trial's reported outcome data, and it cannot resolve the absence of a comparator.

The record does not report the protocol's sample-size justification, analysis plan, interim analyses, or analysis populations. Those omissions prevent readers from checking whether the reported design followed prespecified statistical decisions or whether outcome analyses were selected after data collection. They also limit assessment of how uncertainty, multiplicity, and incomplete follow-up were addressed. The available registry information is sufficient to identify the study as a small, single-group phase 2 study, but not to reproduce or evaluate an outcome analysis.

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("Detachable Balloon")
n      <- c(2)
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  Detachable Balloon  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including newborn survival at birth and secondary outcomes for newborn survival at 30 days, maternal complications, fetal morbidity, and in utero lung growth (LHR) >1.4. It reports no analyses. Results for these outcomes and any plan for prioritizing or interpreting multiple outcomes are not reported in the registry record.

General: When a study assesses multiple outcomes, the chance of obtaining at least one apparently notable result can increase if each is tested separately without adjustment or a prespecified hierarchy. Methods for addressing this can include designating a primary outcome, specifying a testing order, or adjusting inference. The registry identifies a primary outcome, but it does not report a multiplicity strategy or explain how secondary outcomes were intended to inform conclusions. With no outcome analyses posted, it is not possible to assess how multiplicity was handled in practice.

Missing-data procedures and analysis populations are also not reported in the registry record. The enrollment is 3, while the adverse event record identifies 2 participants at risk; the registry does not explain the participant accounting. It does not state whether anyone was lost to follow-up, whether endpoint information was incomplete, or how any such information would have been treated. This absence should not be interpreted as proof that data were missing, nor as proof that all data were complete.

General: Missing outcomes can affect both the denominator and the interpretation of a result. A complete-case analysis, an imputation method, and other approaches rely on different assumptions; without a stated method and information about missingness, readers cannot determine whether a reported estimate would be robust. Here, no primary outcome estimate is reported, so there is no analysis to evaluate for missing-data bias. The registry record also does not report interim analyses, a statistical analysis plan, or a protocol-based description of the analysis set.

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 0% reporting threshold.

The serious adverse event record lists the detachable balloon group with 2 participants at risk and 0 affected. The other adverse event count lists 2 participants at risk and 0 affected. No serious adverse event terms are listed. The deaths field is not reported in the registry record.

These figures describe the counts entered in the registry; they do not establish that no adverse events occurred outside the categories or reporting scope represented by these fields. The record does not explain the definitions used, the duration of safety follow-up, or whether the counts include every enrolled participant. Enrollment was 3, but the adverse event group lists 2 at risk. The reason for that difference and the safety analysis population are not reported in the registry record.

General: A zero count is an observed count, not proof that the underlying risk is zero. Precision depends on the number of participants observed, the follow-up period, and the event definition. A safety count also does not show whether a reported event was caused by the intervention. No comparator is described, so these counts do not provide a relative safety estimate. They should be read as limited registry entries for the stated group, not as a complete safety assessment.

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

The record establishes that a phase 2, single-group study of fetal tracheal balloon intervention was registered for diaphragmatic hernia, with enrollment of 3 and a primary endpoint of newborn survival at birth. It also identifies secondary outcomes and records the study as terminated. These details clarify the study's intended scope and its broad design.

The posted results do not report the primary outcome count, an effect estimate, a confidence interval, or a statistical analysis. They also do not report results for the listed secondary outcomes. As a result, the record does not establish how many participants survived at birth, how precisely survival was estimated, or whether outcomes differed from what might have occurred without the intervention.

The adverse event counts show 0 affected among 2 participants at risk for both the serious and other adverse event fields. Those figures do not establish the absence of all harms, explain the relation between the safety group and total enrollment, or indicate causation. The deaths field is not reported in the registry record.

General: Observed outcomes and causal effects are different statistical questions. An outcome among treated participants describes what was observed in that group. A causal comparison asks what would have happened to comparable participants under an alternative condition. A single-group design does not directly observe that counterfactual, and no control group is reported. This design limitation remains even if an outcome count is available.

The study's stated purpose was to examine whether prenatal intervention could correct lung underdevelopment associated with severe diaphragmatic hernia. The registry record does not report results that answer that question. It therefore cannot establish benefit, lack of benefit, or a comparative safety conclusion. The absence of a result in the registry record is a reporting limitation, not an outcome finding.

14. Why This Trial Matters Statistically

This study is statistically important as an example of the distinction between an intended clinical question and the evidence actually available in a registry record. The trial is identified as phase 2 and single-group, with enrollment of 3. Its primary outcome is clearly named as newborn survival at birth, but the outcome result and analysis are not reported. A precise endpoint description helps readers understand what was intended to be measured; it cannot replace the missing estimate.

The design also makes the role of comparison explicit. A single-group study may provide descriptive information about participants receiving an intervention, but it does not offer a randomized estimate of what the outcome would have been under another approach. In a condition involving severe disease, this distinction matters for statistical interpretation: the observed course may be shaped by participant characteristics and other care as well as by the intervention. Those influences cannot be separated by the design as recorded.

The safety entries illustrate why counts need denominators and context. The record gives 0 affected among 2 at risk in each of two adverse-event fields, while enrollment is 3. The record does not explain the participant accounting or give safety follow-up details. Reporting the count alone would conceal these uncertainties; reading it with the denominator and missing context is more informative.

General: Small studies can be useful for feasibility, early description, or refining questions, depending on their aims and design. They usually provide limited precision for outcome estimates, and the absence of a comparison restricts causal inference. The registry record does not specify the study's detailed objectives beyond its brief purpose, so no further design rationale should be inferred. The statistical lesson is to distinguish recorded design details, posted outcomes, and conclusions the evidence can support.

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 main limitation for interpretation is that the registry record does not report the primary endpoint result or any analysis. Although newborn survival at birth is named as the primary outcome, its observed count and uncertainty are unavailable. Results for the listed secondary outcomes are also not reported in the registry record. The intended outcome framework is therefore visible, but the corresponding evidence is not.

The study is classified as single-group, with no separate control arm. This prevents a direct randomized comparison and limits what could be inferred about differences attributable to the intervention. Enrollment was 3, so even a complete set of outcome data would describe a very small group. No confidence interval or other measure of precision is reported.

Further limitations arise from missing design and reporting detail. Eligibility criteria, baseline characteristics, endpoint definitions beyond the registry labels, follow-up completeness, analysis populations, and missing-data procedures are not reported in the registry record. The record does not explain why the study was terminated. It also does not report the protocol's statistical analysis plan, multiplicity strategy, interim analyses, or sample-size justification.

The safety entries identify 2 participants at risk and 0 affected in both the serious and other adverse event counts, while total enrollment is 3. The record does not explain the denominator difference, provide follow-up duration, or state how events were defined and collected. The deaths field is not reported in the registry record. These omissions limit interpretation of the safety counts as well as the outcome data.

These are limitations of the information available in the registry record, not proof that the study lacked procedures or that unreported outcomes had a particular value. The record supports only a cautious description of the registered design and posted safety counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fetal Tracheal Balloon Study in Diaphragmatic Hernia — NCT00966823.
• Registry record last updated 2017-05-30; status last verified 2017-05.
• Results first posted 2017-05-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a phase 2 study of fetal tracheal balloon intervention for diaphragmatic hernia. It is classified as single-group, with no masking, and enrollment of 3. Rhode Island Hospital is listed as sponsor. The study status is terminated; the recorded start was 2008-09 and primary completion was 2015-01.

The primary endpoint is newborn survival at birth during the newborn period (1 day). Listed secondary outcomes include newborn survival at 30 days, maternal complications, fetal morbidity, and in utero lung growth (LHR) >1.4. Results and analyses for these outcomes are not reported in the registry record.

The adverse event record lists 2 participants at risk and 0 affected in both serious and other adverse event counts. No serious adverse event terms are listed; deaths are not reported in the registry record. The design has no control group, and the available record does not support a comparative estimate of intervention effect.