Tolerability of Hypertonic Saline in Infants With Cystic Fibrosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Tolerability of Hypertonic Saline in Infants With Cystic Fibrosis (NCT00753987), a na phase 1 study. The primary outcome is Decrease in FEV0.5 After Inhalation of Hypertonic Saline.

2. Clinical Question

This is a descriptive question about observations after an intervention in a single group, not a comparison of outcomes between treatment and control groups. The registry also lists oxygen saturation below 92% as a secondary outcome, but does not report its result. The available record therefore identifies what the investigators intended to examine, but does not provide enough outcome information to quantify the primary finding or determine how it relates to the study’s tolerability objective.

3. Trial Design

The registry identifies NCT00753987 as a completed Phase 1 study titled Tolerability of Hypertonic Saline in Infants With Cystic Fibrosis. The sponsor is The Hospital for Sick Children. The recorded start was 2006-03, and primary completion was 2006-07. Enrollment is listed as 13.

The design is recorded as single-group, with allocation listed as NA and masking as none. The intervention was hypertonic saline, and the arm description specifies administration of a single dose of 7% hypertonic saline. No separate control arm is described. Consequently, the study record does not support a like-for-like comparison between groups, and changes observed after administration cannot be contrasted with outcomes under a separately recorded control condition.

The primary outcome is a participant count concerning decrease in FEV0.5 after inhalation, with a timeframe of 100 minutes. The registry description says that 2 infants had to be excluded from this outcome because they woke before administration and post-administration lung-function measurements could not be performed. This is a specific limitation of the recorded endpoint population; the record does not provide a complete account of all analysis populations or other exclusions.

The registry lists oxygen saturation below 92% as a secondary outcome. It records 4 outcome measures and 0 analyses, but does not give the result for the primary endpoint or the secondary outcome. The sample-size assumptions describe planning illustrations based on an observed effect; they are not evidence of the study’s original design rationale. The protocol’s sample-size justification, any interim analyses, and a detailed statistical analysis plan are not reported in the registry 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

Analysis population for the primary outcome, as defined in the registry: 2 infants had to excluded, since they woke up before administration of the study medication and thus lung function measurements after administration could not be performed

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.

Population: infants with CF

6. Primary Endpoint

The registry lists the primary outcome as Decrease in FEV0.5 After Inhalation of Hypertonic Saline, measured over 100 minutes.

The primary endpoint is titled Decrease in FEV0.5 After Inhalation of Hypertonic Saline. It is a binary, participant-count outcome: each participant is classified according to whether the specified decrease occurred. FEV0.5 is the lung-function measure named in the registry, and the endpoint concerns its change after inhalation. The timeframe is 100 minutes.

The endpoint description says the count concerns participants with a decrease in FEV0.5 by 0% or more. It then states that the reported number is for participants with a change in FEV0.5 of more than 0%. These phrases differ at the boundary of 0%; the registry record does not clarify the distinction. That wording matters because a threshold defines which observations are counted as events. Without a clearly stated operational definition, readers should avoid assuming that the two formulations are interchangeable.

A participant count can describe how often an event occurred in the recorded group. It does not, by itself, describe the size of each participant’s lung-function change, the timing or duration of any change, or a comparison with an untreated group. The registry record does not report the primary endpoint count, so its frequency cannot be interpreted from the information recorded. The endpoint is relevant to the stated objective of examining lung function after inhalation, but the record does not establish how the endpoint was used to determine overall tolerability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is classified as binary, meaning it records whether a participant met a defined event criterion rather than retaining the full range of the lung-function measurement as the primary result. The listed unit is participants, and the parameter is a number. In general, a binary endpoint is often described by a count and a proportion. The registry record does not report the event count, so no proportion can be interpreted from the recorded endpoint. No new estimate can be recovered from the enrollment figure alone.

What does the event threshold mean?

A threshold converts a measured change into an event classification. For this endpoint, the title refers to a decrease in FEV0.5, and the description refers to a decrease by 0% or more. The description also says that the reported number concerns a change of more than 0%. Those definitions do not match at the zero boundary. The registry record does not clarify whether the boundary wording reflects a distinction in the intended definition or a wording inconsistency. Because event classification depends on the threshold, this uncertainty should be kept in mind when interpreting the endpoint.

Threshold-based outcomes are easy to count, but they discard information about the magnitude of change. Participants just above and far beyond a threshold may receive the same event classification, while a small difference around the boundary may change classification. General statistical interpretation therefore benefits from knowing both the threshold and, when available, the underlying measurement. The record gives the endpoint description but does not report participant-level measurements or a distribution of FEV0.5 changes.

What would uncertainty estimates add?

A count describes the observations recorded in a study group. An uncertainty interval, in general, conveys how much estimation uncertainty remains when using those observations to represent a broader population. Its width depends on the amount and pattern of information and on the method used. A p-value addresses a particular statistical hypothesis under stated assumptions; it is not a measure of clinical importance, nor does it directly state the probability that a hypothesis is true. No confidence interval or p-value for the primary outcome is reported in the registry record, so these concepts cannot be used to characterize the trial’s result.

For a binary outcome, the analysis should also make clear which participants were eligible for classification, how missing measurements were handled, and what denominator was used. The record states that 2 infants were excluded from the lung-function endpoint because post-administration measurements could not be performed. It does not report a complete analysis population, a missing-data method, or the endpoint denominator. Without those details and the outcome count, the event frequency and its precision cannot be evaluated.

Why does over-dispersion matter?

Over-dispersion is a general issue in count modelling: observed variation can exceed what a model assumes. If a count model assumes more uniform variation than the data actually have, standard errors may be too small and uncertainty may be understated. This can affect confidence intervals and tests. The primary endpoint in this registry is a participant count for a binary event, not a reported rate or a repeated-event count model. The record gives no dispersion estimate or count-model analysis. Over-dispersion therefore cannot be assessed as a feature of this endpoint from the information recorded.

How should the planning calculations be read?

The registry’s sample-size assumptions describe planning illustrations computed from an observed effect, rather than the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustrations consider an effect at a stated fraction of the observed effect. Such calculations answer a conditional planning question: how many participants per arm would be needed under those assumptions to detect a target effect at a specified power. They are not the number enrolled, do not describe observed outcomes, and are never observed power.

These planning assumptions do not match the recorded single-group design, which has no two-arm allocation. The record does not report the observed primary effect or numerical planning results, so their scale cannot be assessed. The original sample-size justification and the reasoning behind the study’s enrollment are not reported in the registry record. No inference should be drawn about the trial’s design intent from the planning illustration alone.

The record lists 0 analyses. That does not establish which methods may have been used outside the registry; it means no analysis is recorded in this entry. In particular, the registry does not report an adjusted model, an unadjusted estimate, a test of a prespecified hypothesis, or an analysis population for the primary endpoint. General statistical explanations can clarify what such methods would mean, but they cannot substitute for trial-specific results.

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("Decrease in FEV05")
n      <- c(11)
events <- c(0)
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  Decrease in FEV05  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, including the primary FEV0.5 endpoint and oxygen saturation below 92% as a secondary outcome. It records 0 analyses. The record does not describe a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for interpreting multiple endpoints. When several outcomes are examined, multiplicity can increase the chance of obtaining at least one apparently notable result by chance. General approaches include specifying a primary endpoint in advance or adjusting inference across tests, but the record does not say whether or how these approaches were used.

The primary outcome description states that 2 infants were excluded because they woke before administration and could not have post-administration lung-function measurements. This is the only specific missing-measurement information given for the primary endpoint. The registry does not report whether any other measurements were missing, how missing values were handled, or whether any imputation or sensitivity analysis was conducted. Those details are not reported in the registry record.

The record does not define a complete analysis population, such as whether eligibility for each outcome was based on enrollment, receipt of the intervention, or availability of measurements. It also does not provide the denominator used for the primary result. The stated exclusion makes those details especially relevant, but no additional handling can be inferred. Without an outcome count and analysis-population description, the effect of missing measurements on the estimate cannot be assessed.

The registry’s outcome list and the number of analyses recorded are not enough to establish which outcomes were included in any formal testing or whether analyses were planned before results were observed. The statistical analysis plan and interim-analysis details are not reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The safety record lists a single arm titled SIngle Arm Trial, with 13 participants at risk for serious adverse events and 0 affected. It also lists 13 at risk for other adverse events and 0 affected, with 0 deaths. No serious adverse-event terms are listed. These are the recorded counts for the study group; they are not a comparison with a control group.

A zero count means that no affected participants were recorded for the specified category in this registry entry. It does not show that the underlying risk is zero, and it does not establish that no event occurred outside the categories or recording process represented by these fields. With no comparator, the figures also cannot estimate a difference in safety outcomes between intervention and control.

The serious adverse-event counts are separate from the primary lung-function endpoint and the secondary oxygen-saturation outcome. The registry does not report the result for the oxygen-saturation outcome, so the safety counts should not be treated as a substitute for that result. The record does not give additional event definitions, follow-up details, or a fuller account of safety assessment procedures. Those details are not reported in the registry record.

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

The registry record establishes that the study examined a single dose of 7% hypertonic saline in infants with cystic fibrosis and identifies a primary endpoint concerning decrease in FEV0.5 over 100 minutes. It also identifies oxygen saturation below 92% as a secondary outcome. These entries describe the study question and endpoint definitions, not the results of those assessments.

The primary endpoint count is not reported in the registry record. Neither is the secondary oxygen-saturation result. Therefore, the record does not quantify how often either outcome occurred. It also does not report an interval or test that would describe statistical uncertainty. The safety entry records 0 serious adverse events, 0 other adverse events, and 0 deaths, but these descriptive counts do not establish the absence of risk or a causal safety conclusion.

Because the design is single-group and has no separate comparator, it cannot provide a randomized or controlled estimate of the difference between hypertonic saline and another condition. Any observed change after administration, if available elsewhere, would need to be interpreted in light of the absence of a control group and the endpoint exclusions. The registry does not provide the primary outcome result needed to describe such a change.

The endpoint definition also contains a boundary ambiguity: it refers both to a decrease by 0% or more and to a reported change of more than 0%. The record does not clarify that wording. Along with the missing endpoint count and incomplete information about the analysis population, this limits interpretation. The study record is useful for identifying the design, intended measures, and recorded safety counts, but it does not support a conclusion about the magnitude or precision of the primary outcome.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why design and result reporting must be read together. The registry describes a single-group study with no separate comparator. That design can document observations after an intervention, but it cannot distinguish those observations from what would have happened under a control condition. The limitation follows from the design, regardless of whether an outcome count is large or small.

Clear endpoint definitions are also essential. A binary threshold makes an outcome countable, but the registry’s primary description includes both a decrease by 0% or more and a reported change of more than 0%. The difference at the threshold boundary may affect which measurements count as events. When the operational definition is unclear, readers cannot be certain that the endpoint has been applied as intended.

Missing measurements matter as well. The record states that 2 infants could not contribute post-administration lung-function measurements because they woke before dosing. A sound interpretation would need the endpoint denominator, the resulting event count, and an account of how missingness was handled. Those details are not reported in the registry record. An enrollment figure alone cannot replace them.

Finally, planning calculations and observed study results answer different questions. A planning illustration based on an observed effect is not observed power, and its assumptions of equal allocation between two arms do not describe this single-group design. Keeping those concepts separate helps prevent hypothetical design calculations from being mistaken for evidence about the enrolled group. The registry’s missing primary result is the central limit: without it, neither the event frequency nor its precision can be evaluated.

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 most direct limitation is that the registry does not report the primary endpoint count. The endpoint title and description identify what was meant to be counted, but without the result there is no basis for estimating its frequency or describing its precision. The secondary oxygen-saturation result is also not reported in the registry record.

The design is single-group, allocation is listed as NA, and masking is listed as none. There is no separate comparator in the record. Accordingly, the study cannot estimate a between-group treatment contrast, and observations after administration cannot be attributed to the intervention through a controlled comparison.

The primary endpoint description notes that 2 infants were excluded because they woke before administration and post-administration lung-function measurements could not be performed. The record does not report the primary analysis denominator, other missing measurements, a missing-data method, or whether sensitivity analyses were performed. The wording of the endpoint also differs at the zero boundary, because it refers to a decrease by 0% or more and then to a change of more than 0%.

The record lists 4 outcome measures but 0 analyses. It does not report a statistical analysis plan, multiplicity approach, interim analyses, or the original sample-size justification. The planning assumptions are described as illustrations based on an observed effect, but no observed primary effect or numerical planning results are reported in the record. These omissions restrict both clinical interpretation and assessment of statistical methods. They do not establish that such information was absent from all study documents; they are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Tolerability of Hypertonic Saline in Infants With Cystic Fibrosis — NCT00753987.
• Registry record last updated 2025-02-13; status last verified 2025-01.
• Results first posted 2025-02-13.
• 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

NCT00753987 is a completed Phase 1, single-group study titled Tolerability of Hypertonic Saline in Infants With Cystic Fibrosis and sponsored by The Hospital for Sick Children. The registry lists enrollment of 13, a start of 2006-03, and primary completion in 2006-07. The intervention was a single dose of 7% hypertonic saline, with no separate comparator and no masking.

The primary endpoint concerns the number of participants with a decrease in FEV0.5 after inhalation, assessed over 100 minutes. The registry notes that 2 infants were excluded from this outcome because post-administration lung-function measurements could not be performed. The primary outcome count and the secondary oxygen-saturation result are not reported in the registry record. Safety entries list 0 participants affected by serious adverse events, 0 affected by other adverse events, and 0 deaths. The entry records 4 outcome measures and 0 analyses.