Elucidation of Acid-Induced Pulmonary Inflammation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Elucidation of Acid-Induced Pulmonary Inflammation (NCT00361972), a randomized phase 2, phase 3 study. The primary outcome is Change in Lymphocyte Count.

2. Clinical Question

The clinical question is focused on a tissue measurement of airway inflammation, rather than on asthma symptoms alone. The registry’s study description also mentions heartburn and asthma symptoms as areas of interest, but the primary posted endpoint is lymphocyte count in bronchial biopsy tissue. A secondary outcome listed in the record is log change in tumor necrosis factor alpha measurement. The registry record does not report whether participants were selected for a particular pattern or severity of symptoms, nor does it provide details of the biopsy assessment beyond the named tissue and measure.

3. Trial Design

The registry identifies this as a randomized, double-masked, parallel-group study, with phases listed as Phase 2 and Phase 3. The sponsor is the University of Utah. Enrollment is recorded as 17. The listed conditions are gastroesophageal reflux and asthma, and the two interventions are lansoprazole and placebo. The lansoprazole arm received 30 mg orally twice daily; the placebo arm received placebo orally twice daily.

The recorded study start is 2006-08, and primary completion is listed as 2009-04. The study status is terminated. The registry record does not report why the study was terminated, whether the planned enrollment was reached, or whether the study stopped before or after the intended follow-up. It also does not report the planned recruitment target, the rationale for choosing the sample size, or details about the sequence generation and implementation of randomization.

The primary outcome was change in lymphocyte count, expressed in lymphocytes per square millimeter, between baseline and six weeks. The analysis description defines change as the post-intervention mean minus the pre-intervention mean and compares the groups’ overall mean changes. The posted arm summaries list 8 participants for lansoprazole and 9 for placebo. These are the sample sizes attached to the reported outcome summaries; the registry record does not explain whether any enrolled participants were excluded from this analysis or whether these counts represent every randomized participant.

The record lists one secondary outcome, log change in tumor necrosis factor alpha measurement. It also reports two outcome measures and two analyses in its summary counts, while the displayed analysis information includes a Wilcoxon (Mann-Whitney) comparison for the primary outcome. Further details of the analysis plan, including how outcomes were prioritized and whether additional analyses were conducted, 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.

Before assignment: washout after lansoprazole or placebo given

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Lymphocyte Count, measured over Baseline and 6 weeks.

The primary endpoint is change in lymphocyte count in bronchus intermedius biopsy tissue, measured in lymphocytes per square millimeter. The stated timeframe is baseline and six weeks. The registry defines each participant’s change using the post-intervention mean lymphocyte count minus the pre-intervention mean, then describes a comparison of the overall mean changes between the lansoprazole and placebo groups.

Lymphocyte count is a tissue-based measure of airway inflammation. In the context of the study’s stated aim, it provides a way to examine whether treatment assignment is associated with a change in an inflammatory feature observed in biopsy tissue. It is distinct from a symptom score: the primary endpoint does not itself measure heartburn symptoms, asthma symptoms, lung function, or a clinical event. The registry’s broader description mentions symptom improvement as an interest, but the primary posted outcome is the biopsy lymphocyte measure.

The arm summaries report a mean change of -57.0 for lansoprazole, with a standard deviation of 10.0, and -3.0 for placebo, with a standard deviation of 2.0. These are changes expressed in the stated measurement unit. A negative value indicates that the reported post-intervention mean was lower than the pre-intervention mean according to the registry’s subtraction convention. The available record does not give confidence limits for either arm summary, and the reported group comparison uses a rank-based test rather than a direct test of the difference between means.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary comparison uses the Wilcoxon (Mann-Whitney) method. In general, this rank-based test compares observations between two independent groups after ordering the values, rather than relying directly on the arithmetic means. It is often described as a test of whether values in one group tend to rank differently from values in the other. Its interpretation is not automatically a test of medians: that interpretation requires additional assumptions about the shapes and spreads of the group distributions. The registry record does not report distributional checks or explain how the test was selected.

The primary outcome is continuous: it records lymphocyte count change on a numerical scale. The registry also gives arm-level means and standard deviations. A mean describes the arithmetic average, while a standard deviation describes the spread of observations around that average. These summaries are useful for describing the reported arm results, but a mean and standard deviation do not determine the ranks of individual observations. Without participant-level values, they cannot reproduce the Wilcoxon result or supply the missing details of its calculation.

General: a confidence interval describes a range of values that are compatible with the data and a chosen statistical procedure, under its assumptions. It conveys uncertainty around an estimate, which a p value alone does not do. The registry record reports no confidence limits for the arm summaries or the between-group contrast. It also gives no estimated rank-based effect and no uncertainty interval for the reported Wilcoxon comparison. As a result, the direction and statistical test are available, but the precision of the between-group effect is not fully characterized.

The reported means are -57.0 for lansoprazole and -3.0 for placebo. These are arm-specific mean changes, not a reported between-group effect estimate. The record describes the target comparison as the groups’ overall mean changes but lists a rank-based test as the analysis. A rank test and a comparison of means answer related but not identical statistical questions. The registry record does not clarify whether the test was intended as a test of a distributional shift, whether the means were also compared using a separate procedure, or whether the wording reflects a general outcome description.

General: over-dispersion means that observed variability is greater than a model or method expects. It matters because a model that understates variability can produce uncertainty that is too small and inference that is too confident. No over-dispersion assessment is reported for this outcome, and no model-based analysis is described. This concept is relevant to statistical modeling generally, but it should not be attributed to this trial’s analysis based on the registry record.

The reported analysis includes p = 0.03. General: a p value is calculated by comparing the observed result, or a more extreme result, with what would be expected under a null hypothesis and the statistical method’s assumptions. It is not an estimate of effect size and does not indicate the probability that a treatment is effective. Here, the registry gives the p value but does not report the test statistic, degrees of freedom, or a confidence interval. The reported p value therefore cannot communicate the magnitude or precision of the group contrast on its own.

The sample sizes attached to the outcome summaries are 8 for lansoprazole and 9 for placebo. Small group sizes make estimates potentially sensitive to individual observations, and they limit how much can be learned about the shape of each outcome distribution from summary values alone. General: with limited observations, assumptions about distributional form and analysis choices can have a noticeable effect on estimates and inference. The registry record does not report diagnostics or sensitivity analyses that would show how robust the result is to alternative methods.

The registry record does not report a protocol-based sample-size justification, the targeted effect size, the planned statistical power, or any interim analysis plan. Planning calculations based on observed results, where available, are illustrations rather than descriptions of the study’s original design and are not observed power. No numerical planning result is stated in the registry information. The record also does not report whether analyses were adjusted for baseline values or other covariates, or whether the primary comparison used all randomized participants.

The posted information notes that values are missing or not estimable for a two-arm continuous-endpoint comparison. This means no recalculated comparison is available from the posted summary information. General: recalculation from summary statistics requires enough information to define the intended contrast and its uncertainty. Even when arm means and standard deviations are reported, that information may not support a recalculation of a rank-based analysis. In this case, the reported Wilcoxon analysis remains the inferential result in the registry record.

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("Lansoprazole", "Placebo")
n   <- c(8, 9)
m   <- c(-57, -3)
sp  <- c(10, 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  Lansoprazole  8  -57.000  10.000  -65.360  -48.640
CARM  Placebo  9  -3.000  2.000  -4.537  -1.463

11. Analyses Reported by the Sponsor

The registry reports a Wilcoxon (Mann-Whitney) comparison between lansoprazole and placebo, with p = 0.03. It does not report an estimated between-group contrast or confidence interval for that analysis. The arm-level mean changes and standard deviations are descriptive summaries; they are not a recalculation of the rank-based test.

A recalculated two-arm comparison is not available because the registry states that values are missing or not estimable for a continuous-endpoint comparison. The information needed to reproduce the reported rank-based analysis, including participant-level ranks, is not reported in the registry record. Accordingly, there is no recalculated estimate to compare with the registry’s analysis. The registry record does not identify a discrepancy between a sponsor analysis and a recalculation, so there is no competing recalculated result to displace the reported analysis.

The sponsor’s reported p value should be interpreted as a test result, not as a measure of effect size or precision. The posted means describe changes in each arm, while the reported rank test addresses the between-group outcome distributions. The registry record does not provide enough detail to reconcile those two forms of description further.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists one secondary outcome: log change in tumor necrosis factor alpha measurement. It also reports two outcome measures and two analyses in its summary counts. The available primary result is a comparison of change in lymphocyte count. The registry record does not provide a complete analysis plan that identifies every prespecified endpoint, analysis, or decision rule.

When several outcomes or statistical tests are examined, the chance of finding at least one apparently notable result can increase. General: multiplicity procedures are sometimes used to control that risk, for example by adjusting significance thresholds or interpreting results within a prespecified hierarchy. The registry record does not report whether any adjustment for multiple outcomes or analyses was planned or applied. It also does not report whether the listed secondary outcome had a posted result, despite identifying it as an outcome.

Missing-data handling is not described. The arm summaries give outcome sample sizes of 8 and 9, but the registry record does not state whether all randomized participants had usable biopsy measurements, whether any measurements were excluded, or why the outcome counts might differ from enrollment. The record does not report imputation, a missing-at-random assumption, sensitivity analyses, or a comparison of participants with and without observed outcomes.

The analysis population is also not described in detail. Although the study is listed as randomized, the record does not say whether the posted comparison follows an intention-to-treat principle, a per-protocol definition, or another population rule. It does not report protocol deviations, treatment adherence, or participant flow between randomization and analysis. Those omissions make it difficult to assess how closely the posted outcome summaries represent the full randomized groups.

The registry record does not report a prespecified statistical analysis plan, an interim analysis, or a stopping rule. Because the status is terminated, the absence of a reported reason for termination is relevant to interpretation: the record does not establish whether termination was related to recruitment, feasibility, safety, or results. These details should not be inferred from the status alone.

13. 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 5% reporting threshold.

The serious adverse event summaries report 0 affected participants among 8 at risk in the lansoprazole group and 0 among 9 at risk in the placebo group. The registry also reports 0 participants with other adverse events among 8 at risk in the lansoprazole group and 0 among 9 at risk in the placebo group. No serious adverse event terms are listed.

These figures describe what was recorded for the listed groups and event categories. They do not establish that no adverse events occurred outside the registry’s definitions, collection period, or reporting process. The registry record does not provide details of how adverse events were monitored, the duration of safety follow-up, event definitions, or completeness of reporting. Death counts are not reported as numerical values in the record, so they should not be interpreted as zero.

The small group sizes also limit how much the observed event counts can say about less common harms. General: a lack of recorded events in a small study does not rule out risks that may occur infrequently or after longer exposure. The safety figures should be read as limited event-count information, not as a comprehensive estimate of comparative safety.

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

The central posted statistical result is a Wilcoxon (Mann-Whitney) comparison of primary-endpoint change between the lansoprazole and placebo groups, with p = 0.03. The arm summaries report mean changes of -57.0 and -3.0, respectively. The outcome is a biopsy-based lymphocyte count measured at baseline and six weeks. Together, these data describe a difference in the reported outcome distributions and show the direction of the arm-level mean changes, but the record does not provide an effect estimate with a confidence interval for the between-group contrast.

The result does not, by itself, establish the size or clinical importance of the group difference. A p value is not an effect measure, and the arm means do not provide the rank-based comparison’s uncertainty. The record gives no clinical threshold for interpreting the lymphocyte count change. It also does not report whether the observed tissue measurement is associated with improvement in asthma or heartburn symptoms.

The trial’s stated research interest includes the relationship between gastroesophageal reflux and airway inflammation, and the broader study description mentions symptoms as well as biopsy findings. The primary posted endpoint, however, is lymphocyte count change. The listed secondary outcome is log change in tumor necrosis factor alpha measurement. A tissue biomarker result should not be treated as a direct finding about symptoms or longer-term clinical outcomes when those results are not reported in the registry record.

The study is described as randomized and double-masked, but enrollment was 17 and the outcome summaries include 8 and 9 participants. The registry status is terminated, and the reason is not reported in the registry record. These features leave important questions about study completion, missing outcomes, and analysis populations unresolved. The record also does not report a sample-size justification, a protocol-based statistical plan, or multiplicity handling.

Accordingly, the result is best understood as a small-study, short-term comparison of a specific biopsy measure, with a reported rank-based p value and limited information about precision. It is not a complete account of treatment effects on symptoms or clinical outcomes, and it does not support conclusions about outcomes or populations that the registry record does not report.

15. Why This Trial Matters Statistically

This trial illustrates why a p value should be read together with the outcome definition, arm summaries, and analysis method. The primary endpoint is described as a comparison of mean changes, yet the reported method is Wilcoxon (Mann-Whitney), a rank-based test. Those methods summarize different aspects of the data. Without the individual observations or a reported between-group effect estimate, readers cannot translate the p value into a mean difference or judge the precision of the comparison.

It also shows the importance of separating a biological measurement from a clinical outcome. Lymphocyte count in bronchial biopsy tissue is the primary posted endpoint. The study description raises broader questions about heartburn, asthma symptoms, and airway inflammation, but the available primary result addresses the tissue measure. Clear outcome definitions help prevent a statistical finding on one measure from being extended to unreported outcomes.

The record’s limited enrollment and terminated status make reporting details especially important. The registry gives arm-level sample sizes and a p value, but does not report the reason for termination, missing-data handling, analysis population, or sample-size rationale. Such information helps readers understand how results relate to the intended study and how much confidence to place in an analysis.

Finally, the record demonstrates the limits of recalculation from summary statistics. Arm means and standard deviations do not reconstruct a rank-based test, and the registry indicates that a recalculated comparison is not estimable from the available information. The sponsor’s reported analysis therefore remains the available inferential result. Statistical interpretation depends not only on numerical summaries but also on matching the reported method to the estimand and having enough information to assess uncertainty.

16. 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 study has small outcome groups, with 8 participants in the lansoprazole arm and 9 in the placebo arm. The registry reports no confidence interval for the between-group comparison, so precision cannot be assessed directly. The posted means and standard deviations describe each arm but do not quantify uncertainty around the rank-based result.

The relationship between the endpoint description and the reported test is not fully explained. The endpoint text describes comparing overall mean changes, while the reported method is Wilcoxon (Mann-Whitney). The registry record does not report the test statistic, distributional checks, or a separate estimate of the difference between means. It is therefore not possible to determine from the record whether the analysis directly addressed the stated mean-based contrast or whether another interpretation was intended.

The registry lists the study as terminated, but the reason is not reported in the registry record. Nor does the record explain whether the outcome sample sizes reflect all randomized participants, whether missing biopsy measurements occurred, or how missing observations were handled. The analysis population and treatment adherence are not described. These omissions limit assessment of participant flow and potential bias.

Other trial details that would inform interpretation are not reported in the registry record, including the sample-size justification, a complete statistical analysis plan, procedures for multiplicity, and any interim analyses. The registry also does not report detailed eligibility criteria, the duration of follow-up beyond the primary timeframe, or a clinical threshold for the biopsy measure. Safety monitoring details and numerical death counts are not reported. These limits mean the posted result should be read as a narrow summary of the registered primary comparison, rather than a complete evaluation of the study’s conduct or outcomes.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Elucidation of Acid-Induced Pulmonary Inflammation — NCT00361972.
• Registry record last updated 2016-08-05; status last verified 2016-06.
• Results first posted 2016-08-05.
• 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.

20. Record Summary

The registry describes a randomized, double-masked, parallel-group study sponsored by the University of Utah, with phases listed as Phase 2 and Phase 3. It enrolled 17 participants and is recorded as terminated. The study start is 2006-08 and primary completion is 2009-04.

The primary outcome was change in bronchus intermedius biopsy lymphocyte count from baseline to six weeks. The posted mean changes were -57.0 for lansoprazole and -3.0 for placebo, with a reported Wilcoxon (Mann-Whitney) p value of 0.03. The registry does not report a confidence interval for the between-group comparison, and a recalculated comparison is not available from the posted information.

The record lists log change in tumor necrosis factor alpha measurement as a secondary outcome. Serious adverse events and other adverse events were recorded as affecting 0 participants in either group; death counts are not reported as numerical values. The reason for termination and several key analysis details are not reported in the registry record.