Do Laryngeal Tissue Changes in Patients Suspected of Having Laryngopharyngeal Reflux Predict Response to Treatment?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Do Laryngeal Tissue Changes in Patients Suspected of Having Laryngopharyngeal Reflux Predict Response to Treatment? (NCT00444145), a na phase 4 study. The primary outcome is Number of Patients With Dilation of Intracellular Spaces 3 Months After Therapy.

2. Clinical Question

3. Trial Design

The registry classifies this as a phase 4, single-group study with no allocation and no masking. It lists an enrollment of 38 and describes one group: patients with documented GERD or newly diagnosed laryngopharyngeal reflux. The group description identifies erosive esophagitis or endoscopic diagnosis as ways those conditions were established. The record does not describe a randomized treatment assignment or a separate control group.

The listed interventions are Prevacid and esophageal and laryngeal biopsies. The study’s stated purpose is to determine whether tissue changes predict clinical response to therapy. Its hypothesis focuses on ultrastructural changes in laryngeal biopsy tissue among patients with laryngeal signs and symptoms related to acid reflux. The registry does not report the dose or schedule of Prevacid, detailed biopsy procedures, or the criteria used to define clinical response.

The registry records the study as completed. The recorded start is 2007-03 and the primary completion is 2009-03. Those dates describe the study record and do not establish when any individual participant was treated or assessed. The primary outcome timeframe is 3 months after therapy.

Because the record describes a single group without a stated comparator, the design does not establish a treatment contrast. Its stated predictive aim would require an analysis relating biopsy findings to a defined clinical response, but no such analysis is reported in the registry record. The record also does not explain how participants were selected for analysis, whether there were protocol changes, or how the study enrollment figure relates to the reported safety group.

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:

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: Patients diagnosed with GERD as evidenced by erosive esophagitis and patients diagnosed with laryngopharyngeal reflux (LPR)

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Dilation of Intracellular Spaces 3 Months After Therapy, measured over 3 months.

The primary outcome is the number of patients with dilation of intracellular spaces 3 months after therapy. The registry describes dilation of intercellular spaces as an early morphological marker reported in gastro-oesophageal reflux. It says that electron microscopy is used to quantify the distance between epithelial cells. The outcome is therefore a count of participants meeting an endpoint based on a tissue measurement, rather than a direct measure of symptoms or a continuous summary of cell-to-cell distance.

As a general statistical matter, a binary endpoint represents whether each participant meets a defined criterion or does not. A count can summarize how many participants meet that criterion, while a proportion can describe that count relative to an analyzed group. The registry record gives the endpoint title and timeframe but does not report the count, the threshold used to classify dilation, or the population denominator for this outcome. It also does not report whether measurements were assessed by blinded readers or how measurement variability was handled.

The tissue measure is relevant to the study’s stated aim because the hypothesis concerns whether laryngeal biopsy changes predict response to therapy. However, an endpoint count at follow-up alone would not establish prediction. That would require a reported relationship between baseline biopsy findings and a defined clinical response. The registry record does not report that relationship or an outcome result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study and a binary primary outcome, expressed as a number of participants with dilation of intracellular spaces at 3 months after therapy. The record does not report an analysis method for that outcome. The concepts below are general explanations of how such data might be summarized and what additional information would be needed; they are not claims about methods used in this study.

What does a binary outcome represent?

A binary outcome classifies each assessed participant into one of two categories, such as meeting or not meeting a specified criterion. For a count to be interpretable, the criterion needs to be operationally defined. In this study, the registry describes dilation and the use of electron microscopy to quantify the distance between epithelial cells, but it does not state a threshold for classifying a participant as having dilation. It also does not report how borderline or technically unreadable measurements would be treated.

A count is meaningful only alongside its denominator: the number of participants assessed for that endpoint. A proportion can then describe the share of the analyzed group meeting the criterion. Neither the endpoint count nor its denominator is reported in the registry record. The enrollment figure cannot safely stand in for the endpoint denominator because the record does not say whether every enrolled participant had an evaluable biopsy and follow-up measurement.

How should uncertainty be expressed?

In general, a confidence interval communicates the uncertainty around an estimate under a specified statistical method. For a binary outcome, the interval would usually be tied to the estimated proportion and the number of participants assessed. A narrow interval indicates greater precision under the method’s assumptions; a wide interval indicates less precision. An interval does not by itself establish that an association is causal or clinically important. No confidence interval or underlying outcome estimate is reported in the registry record, so precision cannot be evaluated.

A p-value, when used, describes how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not describe the size or importance of an effect. The record does not report a p-value or test for the primary endpoint. It would therefore be inappropriate to infer statistical significance or lack of significance from the study’s stated purpose or from its completed status.

What analysis would address the predictive aim?

The stated hypothesis is about whether biopsy changes predict clinical response, rather than solely about the frequency of a tissue finding. A predictive analysis would need a defined response outcome and information connecting that outcome with the biopsy measurement. Depending on how the measures were recorded, general approaches could include comparing response across biopsy categories or modeling the response as a function of biopsy findings. Such analyses require clear definitions, an analysis population, and a plan for handling relevant participant characteristics and incomplete observations. The registry record does not report these details or any predictive analysis. These examples describe general statistical requirements, not methods confirmed for this trial.

Why does the single-group design matter?

A single-group study can describe outcomes among the participants observed, if results are reported. It does not, by itself, supply a concurrent treatment contrast. When there is no comparator, an observed outcome cannot distinguish a treatment effect from other possible explanations, including the natural course of the condition, changes in measurement, or participant selection. The registry reports no allocation and no masking, and it does not describe a separate control group. These design features should shape the interpretation of any result, even if an outcome estimate were available.

How should planning illustrations be read?

Any sample-size illustrations associated with this record are planning exercises, not observed power. The stated assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of an observed effect. Those assumptions describe hypothetical planning, not the registry’s single-group design. The registry record does not report the study’s own sample-size justification or establish that the planning assumptions were used to design the trial. A planning illustration cannot replace a reported outcome estimate, and it cannot show whether the trial actually had adequate precision for its predictive aim.

For a binary outcome, over-dispersion is a general concern when observations vary more than the assumed model allows. Ignoring such extra variability can make uncertainty estimates too small. Whether over-dispersion is relevant depends on the data structure and model. The registry record does not report a model, clustered observations, or an assessment of over-dispersion, so no conclusion about its presence or handling can be drawn.

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("Patients Receiving Prevacid")
n      <- c(19)
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  Patients Receiving Prevacid  19  0  0.0  0.0  17.6  0.0  16.8  0.1  16.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analysis records. It does not report a statistical analysis plan, a hierarchy of outcomes, or whether additional outcomes were collected but not entered in the record. With no reported analyses, it is not possible to determine whether multiple comparisons were made or whether any multiplicity adjustment was used. In general, testing many hypotheses can increase the chance of finding an apparently notable result by chance; a prespecified plan helps readers understand which analyses were primary and how others were treated.

The record does not report missing-data counts or methods. It does not say whether participants lacked a biopsy, had an unreadable specimen, missed the 3-month assessment, or were excluded for another reason. Nor does it state whether missing observations were omitted, imputed, or addressed through another method. These possibilities should not be assumed to have occurred; they are examples of information needed to judge completeness.

The analysis population for the primary endpoint is not reported in the registry record. The enrollment figure alone does not establish how many participants contributed to the endpoint. The safety group’s at-risk counts refer to safety reporting and cannot be substituted for the primary outcome denominator. Without a stated analysis population and missing-data account, readers cannot assess how participant availability may have affected the reported result. No primary outcome result is reported to evaluate in the first place.

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 registry lists the group as patients receiving Prevacid. For serious adverse events, it reports 0 affected among 19 at risk. The record also reports 0 affected among 19 at risk for other adverse events. These are the posted safety counts for that group; they should not be read as the primary endpoint results.

The serious adverse event list contains no terms. The deaths field is not reported in the registry record, so the record does not establish a death count. The safety figures are limited to the group and at-risk counts recorded; they do not explain how events were defined, how long participants were followed for safety, or whether all participants had complete safety follow-up.

In general, a count of 0 reported events does not prove that an event is impossible or that there is no risk. Its interpretation depends on the size and follow-up of the population observed and on how events were collected. Here, the registry does not provide enough detail to assess those factors or to compare safety with another group. The figures should be read as registry-reported counts, not as evidence from a controlled safety comparison.

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

The record describes a study designed to investigate whether laryngeal biopsy findings predict clinical response to therapy in patients with documented GERD or newly diagnosed laryngopharyngeal reflux. It identifies dilation of intracellular spaces 3 months after therapy as the primary outcome and describes electron microscopy as the means of quantifying distance between epithelial cells. These details clarify the intended biological measure, but they do not constitute an outcome finding.

No primary outcome count, denominator, estimate, or analysis is reported in the registry record. The record also does not report a defined clinical response measure or a statistical analysis relating biopsy findings to response. It is therefore not possible to determine from the posted results whether the proposed tissue marker was associated with response, how strong any association might have been, or how precise an estimate would be.

The study is classified as single-group, with no allocation and no masking, and no separate comparator is described. Even if an outcome count were available, this design would not by itself establish what would have happened under an alternative treatment or without treatment. It also would not establish that a tissue finding caused a clinical response. The study’s hypothesis and its endpoint should be distinguished from evidence that the hypothesis was supported.

The safety record reports 0 serious adverse events among 19 at risk and 0 other adverse events among 19 at risk in the Prevacid group. Those counts provide limited descriptive safety information in the registry; they do not constitute a comparison or establish that no risk exists. The record does not report the deaths field or the follow-up details needed to interpret event ascertainment.

Overall, the registry entry identifies a clinically motivated predictive question and a tissue-based endpoint, but does not post the results needed to answer that question. No conclusion about treatment benefit or lack of benefit follows from the absence of a reported outcome in the registry.

14. Why This Trial Matters Statistically

This study raises a statistical question that goes beyond whether a tissue feature can be measured: can that feature help predict a clinically defined response? Prediction requires a clear outcome definition and an analysis that connects the predictor with that outcome. A biological rationale or a study hypothesis is not, on its own, evidence that the predictor performs as intended. The registry record makes this distinction especially important because it describes the hypothesis but does not report a prediction analysis.

The outcome also illustrates why measurement definitions matter. The record describes electron microscopy and distance between epithelial cells, but does not state the threshold used to classify dilation or how that classification was evaluated. Without an operational definition and information about measurement reliability, readers cannot tell how consistently the endpoint could be assessed or how a tissue result would map to a participant-level outcome.

The design matters just as much as the endpoint. A single-group record without a comparator can describe observations if those results are reported, but cannot establish a controlled treatment contrast. The posted registry information does not report the primary result or an analysis of clinical response. This prevents assessment of both the predictive question and the precision of any estimate.

Finally, the entry illustrates the value of complete outcome reporting. A study can be marked completed while the registry record still lacks an outcome count, analysis population, uncertainty estimate, and account of missing observations. Those details are essential for readers to judge what the evidence does and does not support. Here, the registry identifies the intended question and its measurement framework, but leaves the statistical answer unreported.

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 of the registry record is that it does not report a result for the primary outcome. Without the observed count and denominator, the frequency of dilation at the stated follow-up cannot be assessed. No estimate, confidence interval, or test result is reported, so neither the magnitude nor the precision of an outcome finding can be evaluated.

The predictive aim is also not matched by a reported predictive analysis. The record does not define clinical response or report how response was related to biopsy findings. It does not provide a threshold for classifying dilation, details of measurement reliability, or an analysis population. These omissions prevent assessment of how well the proposed tissue measure would distinguish participants with different clinical outcomes.

The single-group design, no allocation, and absence of a described comparator limit treatment comparisons. The registry record does not report masking, a control group, or a controlled estimate of treatment effect. It also does not give the dose or schedule of Prevacid, detailed eligibility criteria, or enough information to assess treatment and biopsy procedures.

Other important analysis details are not reported in the registry record: handling of missing outcome data, the statistical analysis plan, multiplicity procedures, and the relationship between enrollment and the endpoint population. Safety follow-up details and the deaths field are also not reported. These limitations concern what can be established from the registry entry; they do not demonstrate that the study itself failed to collect or analyze such information elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Do Laryngeal Tissue Changes in Patients Suspected of Having Laryngopharyngeal Reflux Predict Response to Treatment? — NCT00444145.
• Registry record last updated 2017-03-29; status last verified 2017-02.
• Results first posted 2017-03-29.
• 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 identifies a completed phase 4, single-group study sponsored by Vanderbilt University Medical Center, with an enrollment of 38. The recorded start is 2007-03 and primary completion is 2009-03. The listed interventions are Prevacid and esophageal and laryngeal biopsies. The study’s stated aim is to determine whether tissue changes predict clinical response to therapy.

The primary outcome is the number of patients with dilation of intracellular spaces 3 months after therapy. The registry describes electron microscopy measurement of distance between epithelial cells, but does not report an outcome result or analysis. It lists 0 serious adverse events among 19 at risk and 0 other adverse events among 19 at risk in the Prevacid group. The registry record does not report a comparator, primary outcome analysis, or deaths figure.