Physiology of GERD and Treatment Response: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Physiology of GERD and Treatment Response (NCT04292470), a na na study. The primary outcome is Change in GERD Symptoms.

2. Clinical Question

3. Trial Design

This completed study, titled “Physiology of GERD and Treatment Response,” lists GERD as its condition and amitriptyline as its intervention. The registry records 7 enrolled participants, a single-group model, no masking, and allocation as NA. The study is not described as a randomized comparison. Its phase is listed as NA. The sponsor is the University of California, Davis.

The registry records a start date of 2020-11-05 and a primary completion date of 2021-11-04. Its status is COMPLETED. Those dates and status do not, by themselves, establish how many participants completed follow-up or contributed to each outcome. The primary-outcome population is specified as enrolled participants who attended both baseline and 8-week follow-up visits, but the number meeting that definition is not reported in the registry record.

The intervention description is amitriptyline 10 mg daily. The study summary says the study was designed to assess physiologic and behavioral mechanisms associated with enhanced medication effects in adults with functional GERD-related symptoms. It also lists a secondary outcome concerning the relationship between physiologic concordance in skin conductance between patient and physician and patients’ GERD symptom change.

There is an unresolved design-description issue. The primary outcome refers to an expanded versus standard group, and safety entries are labeled Standard Visit and Expanded Visit, while the formal model is single group and allocation is NA. The registry does not explain whether these visit labels represent study conditions, subgroups, or something else. They should not be read as proof of a randomized or like-for-like treatment comparison.

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: All enrolled participants who attended both baseline and 8 week follow-up visits.

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 GERD Symptoms, measured over Time 0 (baseline) to 8 weeks.

The primary endpoint is change in GERD symptom severity from baseline to 8 weeks. Severity is based on average daily scores over a 7-day period for daytime heartburn, nighttime heartburn, and acid reflux. Each symptom is scored from 0 to 4, with higher scores indicating worse symptoms; the sum has a possible range of 0-12. The change is defined as the average score at 8 weeks minus the average score at baseline.

This endpoint is used to represent how the recorded symptom burden changes over the study interval. Because the same participants may have different starting symptom levels, the registry’s outcome description says the statistical test used a general linear model of post-study symptoms adjusted for baseline GERD symptoms and randomization assignment. The rationale for including randomization assignment is not explained in a design recorded as single group with allocation NA.

A change score has a direct directional interpretation: a negative value means the follow-up average was lower than the baseline average, while a positive value means it was higher. That direction alone does not establish the size, precision, or significance of an observed result. The registry record does not report the primary endpoint’s estimate, standard deviation, confidence interval, or test result, so the amount and uncertainty of change cannot be described from the recorded results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a symptom score and its change over time, rather than a count of events or a time-to-event measure. The registry specifies a mean as the parameter of interest and standard deviation as the dispersion measure. Those choices describe how the outcome is intended to be summarized, but the numerical summaries and model results are not reported in the registry record.

What does a mean and standard deviation describe?

In general, a mean gives the average outcome among the participants included in an analysis. A standard deviation describes how dispersed individual measurements are around that average. The mean and standard deviation answer different questions: the first concerns the central value, while the second concerns variation among observations. Neither one alone gives the uncertainty of an estimated mean. A confidence interval is commonly used to express estimation uncertainty, but no interval for this endpoint is reported in the registry record.

The symptom score combines daytime heartburn, nighttime heartburn, and acid reflux, with each symptom rated from 0 to 4. Higher scores represent worse symptoms, and the possible sum ranges from 0-12. The change is calculated as the average score at 8 weeks minus the average score at baseline. In general, defining change this way preserves direction: negative change corresponds to a lower follow-up average than baseline. The actual mean change is not reported, so that definition cannot be used to characterize the participants’ observed course.

Why adjust for baseline?

In general, baseline adjustment models the follow-up outcome while accounting for the starting value. This can help distinguish follow-up differences associated with starting symptom levels from the outcome variation represented by the model. The registry says that the primary test used a general linear model of post-GERD symptoms adjusted for baseline GERD symptoms and randomization assignment. It does not report the model coefficients, standard errors, confidence intervals, p-values, or enough detail to establish the precise parameter being estimated. The mention of randomization assignment is also not reconciled with the single-group design and allocation listed as NA.

A general linear model is a broad framework for relating an outcome to one or more explanatory variables. Its interpretation depends on how the outcome, predictors, participant population, and assumptions are specified. The registry does not report details such as the fitted model equation, diagnostics, or handling of departures from model assumptions. There is no basis in the record to assert that a particular additional adjustment, transformation, or variance correction was used.

What can the design support?

In general, random assignment can support a causal comparison when groups are defined by assigned interventions and the analysis follows an appropriate plan. This record identifies no randomized comparison: its allocation is NA, its design model is single group, and the skip information explicitly says it is not a randomized comparison. Thus, the expanded and standard wording in the outcome description should be interpreted cautiously. The registry does not explain what those labels mean or establish that they represent comparable treatment groups.

A within-participant baseline-to-follow-up change can describe the course of scores among participants with both measurements. It does not, on its own, separate the intervention’s effect from other changes over time or other influences. That is a general limitation of interpreting change without a clearly described comparison condition. Here, the actual change result and number of participants analyzed are not reported in the registry record.

How should planning calculations be read?

In general, sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen type I error rate and power. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a fraction of the observed effect. These are planning assumptions, not a description of the trial’s design or observed evidence. The registry entries do not include the observed effect, the calculated participant counts, or the fractions used in any displayed planning illustration.

Such calculations are especially difficult to interpret as design guidance when the record describes a single-group study and no randomized control comparison. They do not establish that the trial had adequate power, and they are not observed power. Because the result estimate is not reported, the planning illustrations cannot be evaluated for sensitivity to the uncertainty in the observed effect. No sample-size justification for the trial’s own design is reported 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("Standard Visit", "Expanded Visit")
n   <- c(2, 4)
m   <- c(0.6, -1.7)
sp  <- c(1.6, 3.7)
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  Standard Visit  2  0.600  1.600  -13.775  14.975
CARM  Expanded Visit  4  -1.700  3.700  -7.588  4.188

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 2 analyses, including the primary symptom-change outcome and a secondary outcome relating skin-conductance concordance between patient and physician to patients’ GERD symptom change. Having multiple outcomes or analyses raises a general issue of multiplicity: when several statistical questions are tested, the chance of at least one apparently notable result can increase. Whether and how to address that issue depends on the prespecified analysis plan and the intended interpretation of each outcome.

Any multiplicity adjustment, hierarchy of tests, or distinction between confirmatory and exploratory analyses is not reported in the registry record. The numerical results for the primary and secondary outcomes are also not reported, so the impact of multiplicity on interpretation cannot be assessed. The description of a primary endpoint does not, by itself, establish what testing strategy was planned or applied.

The primary outcome population is defined as all enrolled participants who attended both baseline and 8-week follow-up visits. The record does not state how many participants met that definition or how missing measurements were handled. It does not report whether any imputation, complete-case method, or other missing-data procedure was used. The number enrolled cannot be assumed to equal the number analyzed.

The record also does not report an intention-to-treat population, a per-protocol population, or another analysis-population definition beyond the baseline-and-follow-up attendance criterion. It is therefore not possible to determine from the registry how participants with incomplete follow-up were treated in the primary analysis. These omissions matter because a mean change calculated among participants with both measurements may represent a selected subset if follow-up is incomplete.

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.

Most frequent non-serious adverse event terms

The registry reports safety figures separately for Standard Visit and Expanded Visit. In the Standard Visit group, 2 participants were at risk for serious adverse events and 0 were affected; 2 were at risk for other adverse events and 0 were affected. Deaths were 0. In the Expanded Visit group, 5 participants were at risk for serious adverse events and 0 were affected; 5 were at risk for other adverse events and 2 were affected. Deaths were 0. No serious adverse-event terms are listed.

These are small group counts, and the registry does not explain how the visit labels relate to the single-group study design or to the amitriptyline intervention. They should not be treated as a randomized safety comparison. The figures describe only the reported counts in those registry categories; they do not establish whether an event was caused by treatment or provide information about its clinical details.

The identities and descriptions of the 2 other adverse events are not reported in the registry record. The record also does not provide further detail on event timing, severity, duration, or how events were collected. Zero reported serious events and zero deaths in these entries should therefore be read as the counts recorded for the listed groups, not as proof that no safety events of any kind occurred.

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

The registry establishes that a completed study enrolled 7 participants and lists amitriptyline 10 mg daily as the intervention. It defines a primary symptom endpoint based on average daily GERD severity over 7-day periods at baseline and 8 weeks. These details describe the study question and the intended measurement, but the primary outcome results are not reported in the registry record. There is therefore no numerical estimate from which to describe the observed average symptom change or its precision.

The record does not report a confidence interval or p-value for the primary endpoint, nor does it give the number of participants who contributed both baseline and follow-up measurements. Statistical significance, variability, and the extent of missing follow-up cannot be evaluated from the reported details. A completed status does not substitute for these outcome details.

The findings also cannot be interpreted as a randomized comparison of expanded and standard conditions. The formal design is single group, allocation is NA, and the study is identified as not being a randomized comparison. Although the primary description uses expanded-versus-standard wording, the registry does not resolve how those labels relate to the design. The outcome description’s reference to adjustment for randomization assignment is similarly unexplained.

In general, a change over time describes what happened between measurement occasions among those with data; without an appropriate comparison, it does not isolate the cause of that change. This is relevant to any interpretation of the stated baseline-to-8-week endpoint. The registry’s design and missing outcome results do not support a causal estimate of amitriptyline’s effect.

The safety entries report no serious adverse events or deaths in either listed visit group, and 2 other adverse events in the Expanded Visit group. Those counts are descriptive, the event details are not reported, and the group definitions are unclear. They do not resolve efficacy or establish comparative safety.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a clearly reported result are both needed for statistical interpretation. The registry defines the symptom measure, its scoring direction, and the baseline-to-8-week change calculation. That makes the intended outcome understandable. But without the observed estimate and its uncertainty, readers cannot tell how much change was recorded or how precisely it was estimated.

It also illustrates the importance of consistency between a trial’s design description and its analysis description. The record identifies a single-group model and allocation NA, while the endpoint description refers to expanded and standard groups and mentions adjustment for randomization assignment. The registry does not explain these differences. Statistical language about group contrasts or adjustment cannot be interpreted reliably without knowing what the groups represent and how participants entered them.

The study’s small enrollment, 7 participants, makes careful reporting of the analysis population and individual outcome data especially consequential. The record’s primary population requires attendance at both baseline and 8-week follow-up, but the number analyzed is not reported. Without that information and a missing-data account, it is difficult to understand who the primary result would represent even if a mean were available.

Finally, this record distinguishes descriptive safety counts from evidence of a comparative treatment effect. Safety entries are organized under visit labels, but the design does not establish a randomized comparison and the event details are absent. These points are broadly useful in clinical biostatistics: interpret each estimate in light of its population, design, analysis, uncertainty, and reporting completeness rather than relying on a title or outcome definition alone.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for statistical interpretation is that the registry record does not report the primary symptom result. No numerical change estimate, group summary, standard deviation, confidence interval, or p-value is available in the stated details. Consequently, the size, direction, and precision of the primary outcome cannot be evaluated. The secondary outcome result is also not reported.

The design information is difficult to reconcile with the outcome wording. The study is listed as single group, with allocation NA, and is identified as not being a randomized comparison. Yet the primary outcome description refers to expanded versus standard groups and says the model adjusted for randomization assignment. The registry does not explain the group definitions, assignment process, or how the described model was implemented. This prevents a clear interpretation of any supposed between-group contrast.

The registered population for the primary outcome includes participants who attended both baseline and 8-week follow-up visits. The number who met this criterion, the extent of missing data, and the missing-data method are not reported. The record does not identify an intention-to-treat or per-protocol analysis population. The primary outcome’s result therefore cannot be linked to a clearly quantified analysis set.

Enrollment was 7, which limits the amount of information available for estimating variation and precision. The registry does not report a sample-size justification for the trial’s own design. Its separate planning assumptions concern a hypothetical two-arm calculation and do not resolve the design ambiguity or supply the missing outcome result. Safety group labels are also unexplained, and details of the other adverse events are not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Physiology of GERD and Treatment Response — NCT04292470.
• Registry record last updated 2023-03-28; status last verified 2023-03.
• Results first posted 2023-03-28.
• 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

NCT04292470 is a completed, single-group study titled “Physiology of GERD and Treatment Response,” sponsored by the University of California, Davis. The registry lists GERD, 7 enrolled participants, no masking, allocation NA, and amitriptyline 10 mg daily. The recorded study dates are 2020-11-05 and 2021-11-04 for start and primary completion.

The primary endpoint is change in average daily GERD symptom severity from baseline to 8 weeks, using daytime heartburn, nighttime heartburn, and acid reflux scores. The registry describes a general linear model adjusted for baseline symptoms and randomization assignment, but does not reconcile that description with the single-group design. It also uses expanded and standard group wording without explaining those labels.

Primary and secondary numerical results, the number analyzed, and missing-data methods are not reported in the registry record. Safety entries list no serious adverse events or deaths and 2 other adverse events in the Expanded Visit group; details of those events are not reported.