Assessing the Impacts of a UESAD on Laryngeal Symptoms and Salivary Pepsin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessing the Impacts of a UESAD on Laryngeal Symptoms and Salivary Pepsin (NCT02552966), a na na study. The primary outcome is Salivary Pepsin Concentration.

2. Clinical Question

Pepsin is described in the registry as a stomach-produced enzyme detected in the laryngeal epithelium of patients with reflux-associated laryngeal symptoms. The study rationale proposes that limited upper esophageal sphincter function may allow refluxate to pass toward the larynx. These points explain the choice of biological measure and device target; they are the study’s rationale, not results of a controlled test.

The registry also lists RSI Score, GerdQ Score, and NGSSIQ Score as secondary outcomes. The stated clinical question therefore spans a biological measure and symptom-related measures, but the available registry record does not include numerical outcome results for either the primary or secondary measures.

3. Trial Design

This was a completed pilot study sponsored by Northwestern University. The registry lists 20 enrolled subjects and identifies laryngopharyngeal reflux as the condition. The study ran from 2015-09-01 to a primary completion date of 2017-08-31. Its phase is listed as not applicable.

The design was single-group, with no masking and allocation listed as not applicable. Participants used the UESAD; there was no separate randomized arm or like-for-like control group. Consequently, the study record describes an evaluation within one group rather than a comparison that isolates the device’s effect from other influences. Changes over time, if any, could not be distinguished from natural variation, measurement variation, or other concurrent factors on the basis of a control group.

The primary endpoint was average salivary pepsin concentration in ng/mL at 2 weeks. The registry says 20 subjects completed baseline pepsin analysis, but only 12 completed post-treatment testing for pepsin. This difference in available measurements is important: the primary post-treatment result represents fewer subjects than the baseline count, and the record does not explain the reasons for missing post-treatment samples.

The registry lists three secondary outcomes: RSI Score, GerdQ Score, and NGSSIQ Score. It reports four outcome measures and four analyses, but does not include the numerical results or explain the analysis procedures in the record. A detailed protocol, sample-size justification, interim-analysis plan, and prespecified statistical analysis plan are not reported in the registry record.

Because this was a pilot study without a control arm, its design can describe feasibility-related information and measurements among those assessed. Without the outcome values and a concurrent comparison, it cannot quantify a controlled treatment contrast. The completed status means the study is registered as completed; it does not by itself establish that all planned measurements were available or that the registry contains a full account of the analyses.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Twelve subjects provided post-treatment salivary samples for pepsin analysis. While the subject flow shows 20 subjects (all of which completed baseline pepsin analysis), only 12 completed post-treatment testing.

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 Salivary Pepsin Concentration, measured over 2 weeks.

The primary endpoint was average salivary pepsin concentration, measured in ng/mL at 2 weeks. Pepsin is a proteolytic enzyme produced in the stomach. The registry rationale notes that pepsin has been detected in laryngeal epithelium among people with reflux-associated laryngeal symptoms and has been implicated in the proposed biology of laryngopharyngeal reflux. Measuring it in saliva offers a biological marker relevant to the study’s stated question.

The endpoint is continuous: its values can take a range of amounts rather than being limited to categories such as event or no event. The registry specifies a mean and standard deviation as the outcome summary. In general, the mean describes the average measurement, while the standard deviation describes how dispersed individual measurements are around that average. These summaries would help characterize the observed salivary concentrations, but the registry record does not report their numerical values.

The endpoint description identifies the average concentration after the 2-week intervention period. It does not specify in the registry record whether the primary analysis compared that value with baseline, tested a change score, or used another approach. Although all 20 subjects completed baseline pepsin analysis, only 12 completed post-treatment testing. Thus, the record documents incomplete post-treatment measurement for this endpoint but does not state how missing measurements were handled.

The endpoint is a biomarker, not a direct measure of symptom burden. Symptom-related measures are listed separately as secondary outcomes. The registry record does not report numerical results for the biomarker or the secondary measures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods can only be described to the extent documented in the registry record. The record identifies a continuous primary outcome summarized as a mean with a standard deviation and gives its measurement unit and timeframe. It does not report an inferential method, a baseline-adjustment method, a confidence interval, a hypothesis test, or numerical endpoint estimates. Those details are not reported in the registry record.

What does the mean describe?

In general, the arithmetic mean represents the average of the observed measurements in the analysis group. For salivary pepsin, it would summarize the concentration values among the subjects whose measurements were included at the specified time. A mean alone does not show whether observations cluster closely together or vary substantially; that is why a dispersion measure is also useful. Here, the registry specifies standard deviation as the dispersion measure but does not give its value.

In general, the standard deviation describes the spread of individual measurements around the mean in the same measurement units. It is not the same as the uncertainty of the estimated mean. The uncertainty of a mean is often described using a standard error or confidence interval, which depends on both variability and the number of observations analyzed. The record does not report a confidence interval or standard error for the primary endpoint, so its estimation precision cannot be assessed from the posted outcome information.

What would a confidence interval mean?

Generally, a confidence interval expresses the range of values compatible with a statistical procedure and the observed data, under its assumptions. It helps readers judge precision as well as the range of effects or levels that remain plausible. A narrow interval indicates greater precision than a wide interval, but neither an interval nor a point estimate alone establishes clinical importance. No confidence interval for the primary endpoint is reported in the registry record.

How does the single-group design affect analysis?

A single-group study has no concurrent untreated or alternative-treatment arm. In general, an analysis of measurements before and after an intervention may describe within-person change if paired values are available, while an analysis of post-treatment values alone describes the observed level at that time. These answer different questions. The registry lists a post-treatment average as the primary endpoint and reports baseline testing, but does not specify whether the primary analysis used paired changes, baseline adjustment, or post-treatment values alone. The analytic contrast is therefore not reported in the registry record.

Even where repeated measurements are available, change over time does not by itself identify a causal effect. Natural fluctuations, regression to the mean, changes in behavior, and other events can also contribute. A randomized control group is commonly used to balance influences that affect outcomes apart from the assigned intervention. This study is listed as single-group and has no like-for-like control comparison, so its design cannot make that controlled contrast.

Why does over-dispersion matter?

General explanation: over-dispersion refers to greater variability in data than a statistical model assumes. If a model understates variability, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. The relevant assumptions depend on the outcome and model. The registry record does not identify a model for the pepsin endpoint or report a dispersion assessment, so over-dispersion cannot be evaluated as a trial-specific issue from this record.

For a continuous outcome, the mean and standard deviation are descriptive summaries, not a complete account of the distribution. Strong skew or influential observations can make a mean less representative of typical values. General checks might include looking at the distribution and individual observations, but the registry record does not report such checks or any alternative summaries.

What can be inferred from the available sample?

The registry states that 20 subjects completed baseline pepsin analysis and 12 completed post-treatment testing. The smaller post-treatment set limits the amount of endpoint information available and may reduce precision compared with complete follow-up. In general, the effect of missing observations depends on why they are missing and how they are handled. The reasons, statistical handling, and sensitivity analyses are not reported in the registry record.

A sample-size calculation is a design-planning exercise, not a description of observed evidence. The registry record does not report the study’s own sample-size justification or target assumptions. Any planning illustration based on an observed effect should not be read as observed power or as proof that the study could detect a particular effect. Because the endpoint estimate itself is not reported in the registry record, the available record does not support interpretation of a trial-specific effect-size calculation.

The registry lists four analyses, but does not give their methods or results. It does not report whether tests were one- or two-sided, what significance threshold was used, whether covariates were included, or whether analyses followed a prespecified plan. These omissions matter because analysis choices can affect estimates and uncertainty, particularly in a small pilot with incomplete post-treatment data.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("UESAD")
n   <- c(12)
m   <- c(158.4)
sp  <- c(150.2)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  UESAD  12  158.400  150.200  62.967  253.833

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and three secondary outcomes: RSI Score, GerdQ Score, and NGSSIQ Score. It also records four outcome measures and four analyses. When several outcomes are examined, the chance of at least one apparently unusual result can increase if each is tested separately without accounting for the number of comparisons. General approaches to multiplicity include designating a primary outcome in advance, adjusting significance thresholds, or treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, an outcome hierarchy beyond the named primary endpoint, or which analyses were confirmatory versus exploratory.

The registry identifies the primary endpoint as average salivary pepsin concentration at 2 weeks. It does not give numerical results for that endpoint or the secondary outcomes. Without estimates and uncertainty measures, the strength and precision of any findings cannot be evaluated, regardless of whether multiplicity adjustment was used.

Missing data are a specific concern for the primary endpoint. Twenty subjects completed baseline pepsin analysis, while 12 completed post-treatment testing. The registry record does not state why the remaining post-treatment measurements are absent, whether subjects discontinued, or how missing values were handled. It does not report imputation, complete-case analysis, sensitivity analysis, or a missing-data assumption. In general, excluding participants with missing measurements can bias an estimate if availability is related to the outcome or its determinants; whether that applies cannot be determined from this record.

The analysis population is also not reported in the registry record. It is not stated whether results were based on all enrolled subjects, those who used the device, those with a particular level of adherence, or only those with an available post-treatment sample. The trial is listed as single-group, so randomized intention-to-treat analysis is not applicable as a comparison framework, but the registry would still need to specify which participants contributed to each outcome analysis.

A protocol or statistical analysis plan could clarify these decisions, but such details are not reported in the registry record. Interim analyses, early stopping criteria, and prespecified handling of multiple outcomes are likewise not reported.

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 registry lists 20 subjects at risk for serious adverse events and records 0 subjects with a serious adverse event. It also lists 20 subjects at risk for other adverse events and records 0 with an event in that category. No serious adverse-event terms are listed. These entries describe the recorded safety counts for the study group.

In general, zero recorded events does not establish that an intervention has no risk. It means no event was recorded in the listed category for the observed participants during the safety reporting period. A small group and limited follow-up can provide little information about uncommon events, and the record does not state the duration of safety surveillance or provide detailed event-collection procedures.

These safety figures should be read separately from the outcome measurements. They do not indicate whether the primary pepsin endpoint changed, nor do they establish whether symptom measures changed. The record does not include further detail about adverse-event severity definitions, relatedness assessments, or non-serious event descriptions. Absence of listed serious-event terms should not be interpreted as a comprehensive statement about all possible harms.

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

The record establishes that a completed pilot study evaluated the UESAD in a single group and included salivary pepsin testing and symptom-related outcomes. It identifies the primary endpoint as average salivary pepsin concentration at 2 weeks, and it documents that 20 subjects completed baseline pepsin analysis while 12 completed post-treatment testing. It also records no serious adverse events among 20 subjects at risk and no other adverse events among 20 at risk.

However, the registry record does not report numerical primary or secondary outcome results. It therefore does not show what the average post-treatment pepsin concentration was, how variable the measurements were, or whether the observed endpoint differed from baseline. It also does not report numerical results for RSI Score, GerdQ Score, or NGSSIQ Score. A finding about benefit, lack of benefit, or the magnitude of an outcome change cannot be drawn from these registry entries.

The study has no control arm and no masking. Even if numerical before-and-after values were available, a change in a single group would not by itself establish that the device caused it. General alternative explanations include natural fluctuation, concurrent changes, and measurement variability. A controlled comparison is needed to assess differences against a concurrent group under comparable conditions.

The device’s proposed mechanism and the rationale for measuring pepsin help explain why the study was conducted. They are not evidence that the device altered reflux, pepsin, or symptoms in this trial. Likewise, a completed status and recorded enrollment are descriptions of study status, not outcome findings.

The study is therefore best understood as a pilot evaluation whose registered record offers design, endpoint, participant-flow, and limited safety information. Its results and precision are not assessable from the numerical outcome information in the registry record. No treatment recommendation follows from these details.

14. Why This Trial Matters Statistically

This trial matters statistically because its design and reporting illustrate why the presence of a named endpoint is not enough to evaluate evidence. The registry identifies a biologically motivated primary measure, specifies its unit and time point, and indicates that the intended summary was a mean with standard deviation. Yet without the actual estimates and their uncertainty, readers cannot assess either the observed concentration or how precisely it was measured.

The participant flow makes the distinction between enrollment and analysis especially important. Although 20 subjects completed baseline pepsin analysis, only 12 completed post-treatment testing. A study’s enrolled count does not necessarily equal the number contributing data to each endpoint. Reporting endpoint-specific denominators, reasons for missing measurements, and a clear analysis population is necessary for interpreting estimates and their potential limitations.

The single-group design also defines what kinds of conclusions are available. It can describe what was measured among participants who used the device, but it has no concurrent counterfactual group for estimating what might have happened otherwise. This is a design limitation, not a problem that can be resolved by a more elaborate statistical test alone.

The study is a pilot, and the registry describes multiple outcome measures. Pilot studies can help characterize procedures and inform future research, while outcome findings from small or incomplete samples may be imprecise. The record does not report the study’s sample-size rationale, analysis plan, or numerical estimates, so the specific degree of uncertainty cannot be quantified.

Finally, safety counts of zero recorded events should be read in the context of the observed group and follow-up information, rather than as proof of no risk. Together, these features show why design, missingness, analysis transparency, and precision are central to statistical interpretation, even when a study has reached completed status.

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.

Several limitations specific to this study affect interpretation. First, the registry lists a single-group design with no masking and no separate control arm. There is therefore no concurrent comparison to distinguish changes associated with device use from natural variation, time effects, or other influences. The absence of masking may also affect subjective symptom reporting in general, although the record does not describe how outcomes were collected or whether laboratory assessment was blinded.

Second, post-treatment pepsin measurements were available for 12 subjects, compared with baseline analyses for 20. The registry record does not explain why post-treatment samples were not completed, whether missingness was related to participant characteristics or outcomes, or how missing data were handled. The primary endpoint’s analysis population and denominator are not otherwise described.

Third, numerical outcome results are not reported in the registry record. This prevents assessment of the observed mean, variability, precision, direction of change, and secondary symptom findings. The record also does not state whether the primary analysis compared baseline with follow-up or used another approach.

Fourth, key statistical details are absent, including the study’s sample-size justification, prespecified analysis plan, methods for handling multiple outcomes, and interim-analysis plan. The registry lists four analyses but does not describe them. Without these details, it is not possible to assess the extent to which analyses followed a prespecified approach.

Finally, the safety entries record zero serious and other adverse events among 20 subjects at risk, but the registry does not describe surveillance duration, event definitions, or detailed collection methods. These counts provide limited information about uncommon events. The pilot design and incomplete follow-up further constrain what the record can establish.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Assessing the Impacts of a UESAD on Laryngeal Symptoms and Salivary Pepsin — NCT02552966.
• Registry record last updated 2020-02-26; status last verified 2019-07.
• Results first posted 2020-02-26.
• 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

NCT02552966 is a completed, single-group pilot study sponsored by Northwestern University. It enrolled 20 subjects with laryngopharyngeal reflux to assess a UES Assist Device. The registry lists no masking and no separate comparator group.

The primary endpoint was average salivary pepsin concentration in ng/mL at 2 weeks. The record states that all 20 subjects completed baseline pepsin analysis, while 12 completed post-treatment testing. RSI Score, GerdQ Score, and NGSSIQ Score are listed as secondary outcomes.

The registry record does not report numerical results for the primary or secondary outcomes, confidence intervals, or detailed analysis methods. It records 0 serious adverse events and 0 other adverse events among 20 subjects at risk in each category. The study’s own sample-size justification, missing-data approach, multiplicity plan, and analysis populations are not reported in the registry record.