Physiological Flow of Liquids in Healthy Swallowing: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Physiological Flow of Liquids in Healthy Swallowing (NCT04114617), a registered phase not stated study. The primary outcome is Number of Participants With Unsafe Swallowing.

2. Clinical Question

The primary endpoint concerns swallowing safety, classified from the Penetration-Aspiration Scale. Scores of 1 and 2 are considered safe; scores greater than 2 are considered unsafe. The planned report is a frequency count of participants with unsafe scores by bolus consistency.

The broader scientific question concerns the interaction between consistency and forces applied during swallowing, including tongue pressures and swallowing muscle contraction. The registry record identifies amplitude of tongue-palate pressure as a secondary outcome. It does not report the results of these measurements, how the broader interactions were analyzed, or whether the primary endpoint was evaluated against a prespecified comparator.

Because the participants were healthy adults, the record describes measurements of physiological swallowing rather than a treatment comparison in people with swallowing impairment. The study’s stated motivation is that thickened liquids are commonly used for dysphagia, while the way this intervention works is not fully understood. The record does not establish that the results apply to people with dysphagia.

3. Trial Design

This completed study, NCT04114617, is titled “Physiological Flow of Liquids in Healthy Swallowing.” The sponsor is University Health Network, Toronto. The recorded start date is 2016-01-01, and the primary completion date is 2019-09-12. Enrollment was 80.

The described population is healthy adults. The arm description says participants would be asked to swallow a series of up to 54 liquid stimuli. These include liquid barium in different brands and concentrations, and a 20% w/v concentration of liquid barium thickened to different consistencies using either a starch-based or xanthan-gum-based food thickener. The description is cut off after mentioning lemon-flavored water, so further details about that stimulus are not reported in the registry record.

The study lists starch-thickened liquids, xanthan-gum thickened liquids, and barium concentration as interventions. These labels describe the stimuli or their formulation; they do not establish that participants were allocated to separate treatment groups. The registry record does not state an allocation procedure. It also cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison.

The primary outcome is a count of participants with unsafe swallowing at baseline, described as a single time point. The record also lists amplitude of tongue-palate pressure as a secondary outcome and reports 12 outcome measures overall. It lists no analyses. Details of sequence assignment, masking, a formal comparator, and the statistical analysis plan are not reported in the registry record.

The study is therefore best read as a physiological measurement study involving multiple liquid stimuli, not as evidence from a randomized treatment comparison. The protocol details needed to determine exactly how stimulus order, repeated measurements, or participant-level dependence were handled 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: A sample of 80 adults was enrolled. Due data quality issues, partial data were missing for thin liquid for 4 participants, and for 3 participants for the remaining consistencies.

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: Adults with no history of dysphagia or related conditions.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Unsafe Swallowing, measured over Baseline (single timepoint only).

The primary endpoint is the number of participants classified as having unsafe swallowing, reported by bolus consistency. Swallowing safety is assessed with the Penetration-Aspiration Scale, an 8-point categorical scale describing how deeply material enters the airway and whether it is ejected. Scores of 1 and 2 are designated safe; scores greater than 2 are designated unsafe. The planned binary classification is scores less than 3 versus scores greater than or equal to 3.

This endpoint turns an ordered scale into a yes-or-no classification for the purpose of counting participants. The resulting count describes how many people meet the registry’s unsafe threshold for a particular consistency. It does not retain the distinctions among the individual scores from 1 through 8, nor does it describe the severity or pattern of scores within the unsafe category.

In general, a binary endpoint can make a clinically defined threshold easier to interpret, but it discards information contained in the original scale. A count also needs a clearly stated denominator to be interpreted as a frequency in context. The registry record reports an enrolled sample of 80 and notes partial missing data for some consistencies, but does not provide analyzed denominators or the observed counts for the primary endpoint.

The endpoint is used to characterize swallowing safety across bolus consistencies in healthy adults. It is not, by itself, a measure of the full flow pattern or the forces involved in swallowing. The record’s broader objective includes bolus flow and swallowing forces, and it lists amplitude of tongue-palate pressure as a secondary outcome. Results for those measures are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record specifies a binary primary endpoint based on the Penetration-Aspiration Scale, but does not report a statistical analysis plan or any analyses. The concepts below are general explanations of how such data can be understood; they do not describe methods confirmed to have been used in this study.

What does a binary count represent?

A binary outcome assigns each measurement to one of two categories. In this study description, scores of 1 and 2 are safe, and scores greater than 2 are unsafe. A count of participants with unsafe swallowing would tally participants in the unsafe category for a given bolus consistency. To interpret a count fully, readers also need the number of participants with usable data for that consistency. The registry record does not report those analyzed denominators or the observed counts.

Counts and proportions answer related but distinct questions. A count gives the number meeting the endpoint; a proportion relates that number to an explicitly stated denominator. The registry record describes reporting frequency counts by bolus consistency, but does not provide results or analyzed denominators. No proportion should be inferred from the enrolled sample alone when the record also notes incomplete data.

Why might uncertainty matter?

In general, a confidence interval describes a range of values compatible with a statistical estimate under the method’s assumptions. For a binary outcome, an interval around a proportion or risk difference can communicate how precisely the data locate the underlying quantity. An interval is not a guarantee that the true value lies within its limits, and its interpretation depends on the analysis and sampling assumptions. No confidence intervals or inferential estimates are reported in the registry record.

A p-value, when used, addresses how compatible the data are with a specified null hypothesis under a statistical model. It does not measure the size or practical importance of an effect. A p-value would be especially difficult to interpret without a clearly described comparison, analysis population, and model. The registry record does not report p-values, hypotheses, or a statistical plan.

What is important about multiple stimuli?

The study description says participants would swallow a series of up to 54 liquid stimuli. In general, when the same participant contributes measurements under multiple conditions, those measurements may be correlated. Treating all measurements as independent can make uncertainty estimates too optimistic because it ignores that measurements from one person share participant-specific features. Methods for repeated or clustered observations can account for this dependence. The registry record does not report whether such methods were used or how stimulus order was handled.

Over-dispersion is a general concern for count or binary data when the observed variability is greater than a simple statistical model expects. Ignoring excess variability can understate uncertainty and affect tests and intervals. Whether over-dispersion is relevant depends on the outcome structure and analysis model. No model or diagnostic assessment is reported in the registry record, so it is not possible to say whether this issue arose in the study.

What would a comparison require?

A comparison across bolus consistencies needs a clearly specified contrast: which consistencies are being compared, what quantity is estimated, and which participants contribute to each estimate. A model could account for participant-level dependence where appropriate, but the correct model depends on the design and data. The registry record does not specify a primary contrast, an adjusted or unadjusted model, covariates, or a method for handling repeated measurements.

The record describes the study as not being a randomized comparison and cautions that arms are not a like-for-like control comparison. In general, random allocation can help make groups comparable for causal comparisons, while nonrandomized comparisons can reflect differences beyond the intervention or stimulus itself. That general distinction is not a claim about any unreported result in this study; the registry record does not report an effect estimate to interpret.

How should planning calculations be read?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and analysis. A planning illustration based on an observed effect is not an observed-power result and does not show how likely the study was to detect an effect after the data were collected. The registry record does not report the numerical planning counts or observed effect needed to interpret a calculation.

The listed assumptions for a planning illustration include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect described as a fraction of the observed effect. Those assumptions do not establish the trial’s own design or statistical plan. The registry record does not report that the study used equal allocation, had two like-for-like arms, or adopted those assumptions for its original design.

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("Thin Liquid Barium", "Slightly Thick Liquid Barium", "Mildly Thick Liquid Barium", "Moderately Thick Liquid Barium", "Extremely Thick Liquid Barium")
n      <- c(76, 77, 77, 77, 77)
events <- c(7, 1, 3, 0, 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  Thin Liquid Barium  76  7  9.2  3.8  18.1  4.5  17.8  4.6  17.8
ARM  Slightly Thick Liquid Barium  77  1  1.3  0.0  7.0  0.2  7.0  0.3  6.9
ARM  Mildly Thick Liquid Barium  77  3  3.9  0.8  11.0  1.3  10.8  1.4  10.8
ARM  Moderately Thick Liquid Barium  77  0  0.0  0.0  4.7  0.0  4.8  0.0  4.6
ARM  Extremely Thick Liquid Barium  77  0  0.0  0.0  4.7  0.0  4.8  0.0  4.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures, including the primary endpoint of unsafe swallowing and the secondary outcome of amplitude of tongue-palate pressure. It lists no analyses. The registry record does not describe which outcomes were analyzed, which were designated primary for statistical testing, or how comparisons across multiple outcomes or bolus consistencies were handled.

Multiplicity is a general concern when several outcomes, groups, time points, or contrasts are tested. With many tests, the chance of at least one apparently unusual result can increase. Statistical approaches can address multiplicity by adjusting significance thresholds or by using a prespecified hierarchy of hypotheses. The appropriate approach depends on the questions and analysis plan. No multiplicity procedure or testing hierarchy is reported in the registry record, so it is not possible to assess whether one was used.

The primary endpoint is described at baseline, at a single time point, and by bolus consistency. The record does not state how many consistency-specific comparisons were planned, whether one was primary, or how any repeated measurements within a participant were incorporated. These missing details limit interpretation of any result that might be reported elsewhere.

For missing data, the record reports partial data missing for thin liquid for 4 participants and for 3 participants for the remaining consistencies, attributed to data quality issues. It does not describe the pattern of missingness in further detail, the measurements affected, or the method used to address missing observations. No imputation strategy, sensitivity analysis, or complete-case rule is reported in the registry record.

The enrolled sample was 80 adults, but that number should not automatically be treated as the analysis denominator for each consistency or outcome. The record does not provide analyzed participant counts. It also does not define analysis populations, such as whether all enrolled participants or only those with complete measurements were included. Therefore, neither the effect of missing data nor the representativeness of analyzed observations can be evaluated from 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 adverse-event record lists 80 participants at risk in the Healthy Adults group. It reports 0 participants affected by serious adverse events and 0 deaths. It also reports 80 participants at risk for other adverse events and 0 affected. No serious adverse-event terms are listed.

These are registry counts, not a detailed clinical description of every event monitored. The record does not report event definitions, collection procedures, duration of follow-up, or attribution to a particular liquid stimulus. It also does not provide a narrative explaining how safety events were assessed. Therefore, the counts should be read as the recorded adverse-event figures, not as a complete account of every possible safety observation.

In general, a zero count means that no affected participants were recorded in the stated category; it does not establish that an event is impossible or that no unrecorded event occurred. Interpretation also depends on the size and nature of the population observed and how events were collected. The record identifies a healthy-adult group, so these figures should not be generalized to other populations based on this study description alone.

The safety figures are separate from the primary swallowing-safety endpoint. The latter classifies Penetration-Aspiration Scale scores by bolus consistency; it is not the same measure as adverse events. The registry record does not report the primary endpoint counts, so the zero adverse-event figures cannot stand in for those results.

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

The record describes a study intended to characterize liquid flow and swallowing in healthy adults. Its primary endpoint classifies Penetration-Aspiration Scale scores as safe or unsafe and proposes reporting counts by bolus consistency. This provides a defined measurement question, but the registry record does not report the observed counts or other primary outcome results.

Accordingly, the record does not establish how frequently unsafe scores occurred, whether those frequencies differed across consistencies, or how precisely any difference was estimated. No confidence intervals, statistical tests, or analysis results are reported. The absence of posted results is not evidence that the endpoint had no events or that conditions were equivalent.

The stated objective also includes the relation between consistency, swallowing forces, and bolus flow through the mouth and throat. The record lists amplitude of tongue-palate pressure as a secondary outcome, but does not report measured values or analyses of interactions. It therefore does not show which factors were associated with flow, or how large any association might have been.

The study is described in healthy adults. It does not directly answer whether a thickened liquid improves outcomes for people with dysphagia. The registry’s background explains why the field is interested in thickened liquids, but a physiological study in healthy swallowing is not, by itself, a treatment-effect comparison in people with swallowing impairment. The record also cautions that the study was not a randomized comparison and that its arms were not like-for-like controls.

The posted information can still clarify the intended endpoint, threshold, stimulus types, enrollment, and noted missing data. Those details help readers understand what the study sought to measure and what information would be needed to assess its findings. They do not substitute for outcome estimates, denominators, uncertainty intervals, or a documented analysis plan. The registry record does not report those elements.

14. Why This Trial Matters Statistically

This study raises an important statistical distinction between describing a physiological measurement and evaluating a treatment effect. The stated objective is to examine how liquid or food consistency and swallowing forces relate to bolus flow in healthy swallowing. Its primary endpoint is a threshold-based count of participants with unsafe swallowing by bolus consistency. These questions concern measurement and association; they are not automatically equivalent to a randomized comparison of treatments.

The design description involves a series of liquid stimuli, up to 54 for a participant. In general, repeated measurements from one person can be statistically dependent. Recognizing the unit of analysis matters: a participant-level count and a stimulus-level measurement do not have the same denominator or structure. The registry record does not report the analysis method, which makes it impossible to determine how dependence was handled.

The use of a binary threshold also highlights a trade-off. It makes a safety classification straightforward to communicate, but it compresses the original 8-point scale into two groups. The individual score distribution could contain information not retained in the binary count. The record describes the threshold but does not report either the binary results or the detailed score distribution.

Missing data are relevant because the record notes partial missingness for some consistencies. A complete interpretation would need denominators by condition and a clear account of the affected measurements. Without those details, readers cannot tell how much information contributed to each comparison or whether the missing observations could influence the pattern.

Finally, the registry record lists 12 outcome measures but no analyses. This makes transparent reporting of prespecified questions, comparisons, and multiplicity handling particularly important for interpretation. The record does not document those methods. Its value statistically is therefore in making clear the questions and measurement challenges, while also showing which information is needed before estimates 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 registry record does not report primary outcome counts, analyzed denominators, effect estimates, confidence intervals, or statistical tests. Without these results, the frequency of unsafe scores and any differences by bolus consistency cannot be assessed. The record lists 12 outcome measures but no analyses, and it does not identify a formal statistical analysis plan.

The record reports partial missing data attributed to data quality issues: thin-liquid data were partially missing for 4 participants, and data for the remaining consistencies were partially missing for 3 participants. It does not specify exactly which measurements were missing, whether these participants overlapped, how missingness was handled, or the denominator for each analysis. The impact of missing data therefore cannot be evaluated.

The endpoint converts an 8-point scale into a binary classification. This matches the stated safe and unsafe threshold, but loses distinctions among scores within either category. The registry record does not report the original score distribution alongside the planned binary outcome.

The study description includes multiple stimuli, but does not report stimulus order, the analysis of repeated observations, or how participant-level dependence was handled. It also does not state a primary contrast among consistencies. The registry record cautions that this was not a randomized comparison and that arms are not like-for-like control comparisons; allocation is not stated.

The population is described as healthy adults, limiting what the record can establish about people with dysphagia. The record does not report results for the secondary pressure outcome or the broader flow objective. Finally, no protocol rationale, sample-size justification, interim analysis plan, or detailed statistical plan is reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Physiological Flow of Liquids in Healthy Swallowing — NCT04114617.
• Registry record last updated 2022-12-21; status last verified 2022-11.
• Results first posted 2022-12-21.
• 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

NCT04114617 is a completed study titled “Physiological Flow of Liquids in Healthy Swallowing,” sponsored by University Health Network, Toronto. The recorded start date is 2016-01-01, primary completion date is 2019-09-12, and enrollment is 80 healthy adults.

Participants were described as swallowing a series of up to 54 liquid stimuli, including liquid barium in different brands and concentrations and barium thickened with starch-based or xanthan-gum-based food thickener. The primary endpoint is the number of participants with unsafe swallowing by bolus consistency, based on Penetration-Aspiration Scale scores greater than 2. Amplitude of tongue-palate pressure is listed as a secondary outcome.

The record notes partial missing data for some consistencies and reports 0 serious adverse events, 0 other adverse events, and 0 deaths. It lists 12 outcome measures but no analyses. Primary results, analyzed denominators, and a detailed statistical analysis plan are not reported in the registry record.