Small Volume Simethicone Before Gastroscopy: Any Benefit?: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Small Volume Simethicone Before Gastroscopy: Any Benefit? (NCT02555228), a randomized phase 2, phase 3 study. The primary outcome is Total Cumulative Mucosal Visibility Score.

2. Clinical Question

The clinical question is narrow: whether adding simethicone to a small volume of water was associated with a different total visibility score than water alone in this study. The registry also identifies volume of additional manual flushes and adverse events as secondary outcomes. These address related aspects of the procedure, but they do not replace the primary score or establish broader effects beyond the measures recorded.

The primary score is a procedural measure rather than a patient-reported outcome. Its value depends on how the endoscopist rated the visual field across the named areas. Endoscopist blinding is stated in the study description, while the registry classifies the masking as single. Other details about masking are not reported in the registry record.

3. Trial Design

The registry describes a randomized, parallel-group study, with single masking. Its official title calls it prospective and endoscopist-blinded. The study is listed as phase 2 and phase 3. It was sponsored by Changi General Hospital, registered as NCT02555228, and marked completed. The registry reports an enrollment of 54.

The comparison was between simethicone premedication and water placebo before diagnostic gastroscopy. The study summary specifies liquid simethicone (100mg) in 5 mls water versus 5mls water, given at least 30 minutes before the procedure. The arm description gives simethicone as a 1ml volume in 5mls of water, and describes placebo as 5 mls of water. The primary outcome was assessed during gastroscopy, with an expected duration of 10 minutes.

The registry lists a start date of 2015-08 and primary completion in 2015-11. It does not report the sequence-generation method, allocation concealment, the precise roles masked, or whether masking was maintained throughout outcome assessment. The registry also does not report the trial’s original sample-size justification or its planned statistical analysis methods.

The posted primary outcome summaries include 27 participants in each group. Those summaries should be distinguished from the registry’s overall enrollment field: the record does not explain the relationship between the enrollment figure and the analysis population, or report participant flow, exclusions, or missing primary outcomes. No sponsor-reported analysis entries are listed in the record. The posted numerical comparison can therefore be read as an unadjusted comparison of the group summaries, not as a fully documented account of the trial’s original analysis plan.

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

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 Total Cumulative Mucosal Visibility Score, measured over This will be calculated during the diagnostic gastroscopy, an expected duration of 10 minutes..

The primary endpoint is the total cumulative mucosal visibility score (TMVS), recorded during diagnostic gastroscopy. It combines Mc Nally ratings for the esophagus, duodenum, antrum and angularis, and body and fundus. Each area is rated on a scale where a score of 1 means no bubbles, a score of 2 means minimal or occasional bubbles that must be actively sought, a score of 3 means moderate bubbles that are obviously present, and a score of 4 means severe bubbles that obscure vision.

The score is intended to summarize the visibility of the mucosal field across the specified areas. Its direction is important: higher area ratings describe more bubbles and, at the severe end, obscured vision. A lower total is therefore consistent with less bubble-related obstruction under the score’s definition. The measure provides a structured way to compare the groups’ recorded visibility during the procedure, rather than relying only on an informal overall impression.

The registry says the total is calculated during diagnostic gastroscopy, with an expected procedure duration of 10 minutes. It does not report further details of the scoring protocol, such as assessor training, scoring reliability, or how incomplete area ratings would be handled. Those details matter when interpreting a composite score, because differences in rating practice can affect the recorded values even when the underlying visual field is similar.

7. Results Posted in the Registry

• Simethicone Premedication: mean 5.78 versus 8.89 on control; difference -3.11 (95% CI -4.08 to -2.14), standardized effect d = -1.71; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Volume of Additional Manual Flushes Required During Endoscopy in Mls

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Simethicone Premedication: mean 3.89 versus 84.81 on control; difference -80.92 (95% CI -122.70 to -39.14), standardized effect d = -1.03; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Simethicone Premedication than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes address procedural features related to visibility and the conduct of gastroscopy, alongside adverse events. The registry lists mucosal visibility score per area, additional manual flush volume, and adverse events as secondary outcomes. Numerical comparisons are posted for manual flushing, but the registry record does not contain numerical analysis results for the other listed secondary outcomes.

As a group, these measures may help describe whether the primary visibility finding sits alongside other procedural observations. They are not interchangeable: an area-specific score, the amount of flushing, and an adverse-event summary each capture a different aspect of the procedure. The registry record does not establish that secondary outcomes were intended as confirmatory tests of the primary result, and it does not report a prespecified hierarchy among them.

Unadjusted secondary results carry less weight when several outcomes may be examined. Each additional comparison creates more opportunities for an apparently notable result to arise by chance, and a collection of unadjusted p-values does not control that risk. The registry does not report a multiplicity strategy, such as a testing order or adjustment. The secondary results should therefore be treated as descriptive or exploratory rather than as independent proof of a primary conclusion.

The registry record also does not report analyses for each secondary outcome, the analysis populations, or missing-data handling. Without those details, the absence of a posted numerical result should not be interpreted as evidence that no difference occurred. It means the registry record does not provide a result for that measure. In reading the secondary evidence, the primary outcome remains the central comparison, while secondary measures offer limited supporting context rather than a basis for broader claims.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Mucosal Visibility Score Per Area as Determined by Mc Nally Score:
• Volume of Additional Manual Flushes Required During Endoscopy in Mls
• Adverse Events in Each Group Which May or May Not be Related to Simethicone Solution

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical methods are useful for separating the observed group difference from the uncertainty around it. They also clarify the assumptions involved when a simple comparison is reconstructed from group means and standard deviations. The registry record provides summary statistics and a comparison, but does not report the investigators’ complete original statistical plan.

What does the mean difference express?

The mean difference is the simethicone group mean minus the placebo group mean. A negative value means the recorded average score was lower in the simethicone group. On this score, lower ratings correspond to fewer bubbles and less visual obstruction, so the direction has a direct interpretation in terms of the endpoint’s scoring rules. The difference is expressed in score units, not as a percentage or a relative change.

A difference in means summarizes the distance between group averages. It does not show the full distribution of individual scores, whether the groups overlapped, or whether every person’s score moved in the same direction. Standard deviations describe spread around each mean, while the confidence interval for the difference describes uncertainty in the estimated contrast. These quantities answer different questions and should not be substituted for one another.

What does the confidence interval convey?

A confidence interval gives a range of values compatible with the observed data under the calculation’s assumptions. In repeated use of the same method, intervals constructed this way would cover the true parameter at the stated confidence level at the expected frequency. It is not a range containing a known proportion of individual participant scores, nor is it a guarantee that the true effect lies inside the particular interval.

For the primary comparison, the reported interval is wholly on the negative side of zero. This conveys both direction and statistical precision for the unadjusted mean difference. The interval does not measure uncertainty about unreported design features, scoring reliability, missing data, or generalizability. Those issues are not resolved by a narrow interval.

How should the p-value be read?

The reported p-value is for an unadjusted comparison. In general, a p-value measures how unusual data at least as incompatible with the null hypothesis would be if the null model and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not quantify the size or practical importance of a difference. A small p-value does not remove the need to examine the confidence interval, the outcome’s meaning, and the design’s limitations.

The registry record has no entries for reported analyses. The comparison is therefore best described as an unadjusted analysis of the posted summary statistics, rather than attributed to a documented sponsor analysis. The record does not state whether a different test, adjustment, or analysis population was used by the investigators.

Why does variation matter?

For a continuous outcome, the precision of a group comparison depends in part on the amount of variation within groups and on the amount of information available. Larger standard deviations mean observations are more dispersed around their group mean. With the same design and information, greater variation generally makes it harder to estimate a difference precisely. Here, the posted standard deviations describe the observed spread, but the registry does not provide participant-level data for checking distributional shape, influential observations, or unusual values.

General statistical methods for mean comparisons commonly rely on assumptions about how observations behave and how uncertainty is estimated. A normal approximation is explicitly listed for the planning illustration, but the registry does not report the assumptions or method used in the trial’s original primary analysis. It would be inappropriate to infer those details from the posted means and standard deviations alone.

What does unadjusted mean in this context?

An unadjusted comparison contrasts the outcome summaries between groups without accounting for other variables. Randomization is intended to support a fair group comparison, but chance imbalances can occur, especially in a small trial. Adjustment for prespecified baseline variables can sometimes improve precision or address a planned analysis strategy. The registry record does not report baseline characteristics or whether any adjusted analysis was performed, so the posted contrast should not be described as adjusted or as controlling for specific participant features.

Finally, statistical significance is not equivalent to clinical importance. The endpoint is a score of mucosal visibility during gastroscopy; the registry does not provide a threshold for a meaningful score difference or link the score to later patient outcomes. Interpretation should therefore remain tied to the measured procedural outcome and the uncertainty reported for that outcome.

11. Confidence Intervals and Precision

The primary mean difference was -3.11 units, with a 95% confidence interval from -4.079 to -2.141. This interval describes uncertainty in the unadjusted difference between the two group means under the calculation’s assumptions. Its endpoints are both negative, so the interval supports a lower average score in the simethicone group for this comparison. The score definition gives that direction a procedural interpretation: lower ratings represent fewer bubbles and less visual obstruction.

The interval is more informative than a p-value alone because it shows the range of estimated differences compatible with the observed data under the method. It does not imply that all plausible differences have equal probability, and it is not a prediction interval for individual scores. Nor does it cover uncertainties that are not represented in the calculation, such as the reliability of the endoscopist ratings, the handling of missing measurements, or possible deviations from the intended design.

The group standard deviations were 1.65 and 1.97, and the posted group summaries each include 27 participants. These standard deviations describe observed variability among scores. They should not be read as confidence intervals or as measures of uncertainty in the mean difference. The confidence interval instead reflects the uncertainty in comparing the group means using the posted summary information.

The registry does not report an original sponsor analysis or its statistical method, and the record contains no participant-level data with which to examine alternative assumptions. Thus the interval communicates precision for the posted unadjusted comparison, not certainty about all aspects of the study or the size of any broader effect. A confidence interval can be statistically clear while important questions about measurement, analysis populations, and generalizability remain unanswered.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. They are illustrations based on the observed effect and assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect: 100%, 75%, or 50%. These are planning scenarios, not a report of the trial’s original design assumptions, which are not reported in the registry record.

The 80% power column gives the planned participants per arm under the stated assumptions for a design with an 80% chance of detecting an effect of the specified size, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning count for a 90% chance. These are prospective design quantities: they describe how a future study might be planned, rather than the probability that the observed study result is correct.

Each row uses a different effect size relative to the observed difference. A smaller effect is harder to distinguish from random variation, so the planning illustration requires more participants per arm when the target effect is smaller. The curve is read in the same general way: planning needs rise as the target effect becomes less pronounced, subject to the calculation’s assumptions.

This is not observed power. The planning figures use the observed effect as their reference and do not establish that the original study was designed with those assumptions. The registry does not report the trial’s own sample-size justification, target effect, or planned power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -3.110; pooled standard deviation σ = 1.817.
2. n = 2 × (1.96 + 0.842)² × 1.817² / -3.110² = 5.4, rounded up to 6 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -3.11                      # observed difference in means
sigma <- 1.81705806181311                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2555228)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 6 (80% power), 8 (90% power)
 75% of observed effect: n per arm = 10 (80% power), 13 (90% power)
 50% of observed effect: n per arm = 22 (80% power), 29 (90% power)
power.t.test: 6.5 
Simulated power at n = 6 per arm: 0.763 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, time points, subgroups, or statistical contrasts. If each is tested separately without a plan to control the overall false-positive risk, the chance of at least one nominally positive result can increase. The registry lists four outcome measures and three secondary outcomes, but does not report a multiplicity adjustment, a hierarchy of outcomes, or a testing strategy. The posted p-value should therefore be understood as an unadjusted result, not as a multiplicity-controlled finding.

The record identifies a primary outcome, which helps distinguish the main endpoint from secondary measures. However, a named primary endpoint alone does not reveal whether the investigators planned additional analyses, how they would handle multiple comparisons, or whether those plans changed. The registry has no reported analysis entries, so the original statistical analysis plan and any deviations are not reported in the registry record.

Missing-data handling is also not reported. The record does not state whether all randomized participants contributed primary outcome data, whether any measurements were unavailable, or whether imputation or other methods were used. The posted primary summaries show 27 participants per group, but they do not by themselves establish the analysis population or explain any relationship to overall enrollment.

The registry does not report an intention-to-treat analysis, a per-protocol analysis, or criteria for including or excluding participants. It also does not provide participant flow or sensitivity analyses. These omissions matter because the interpretation of a randomized comparison depends not only on the allocation process but also on how participants and outcome data are handled after allocation. Without those details, the posted group summaries remain useful descriptive evidence, but their relationship to all randomized participants cannot be fully assessed.

These gaps do not prove that data were missing, that outcomes were selectively reported, or that a particular analysis population was used. They identify matters that the registry record does not resolve. Conclusions about multiplicity, missingness, or adherence to an original plan should not go beyond that record.

15. 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 adverse-event summaries list 27 participants at risk in each group for serious adverse events and for other adverse events, with 0 affected in each group for both categories. These are the figures recorded for the simethicone premedication and placebo groups. The outcome description says adverse events may or may not be related to the simethicone solution, so the figures should not be read as a causal attribution.

A zero in these summaries means no affected participants were recorded for that category in the posted group data. It does not establish that an event is impossible, nor does it rule out uncommon events that a study of this size could fail to observe. The registry record does not provide further event details or an explanation of ascertainment procedures. Death counts are not reported in the registry record.

These figures describe the recorded safety outcomes for this trial only. They do not provide a comprehensive estimate of risk beyond the study population, follow-up, and reporting available in the registry.

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

The posted results indicate that the average total mucosal visibility score was lower in the simethicone group than in the water-placebo group. The difference is in the direction of fewer bubbles and less visual obstruction according to the Mc Nally score’s definitions. The unadjusted confidence interval lies below zero, and the reported p-value is less than 0.001. These findings describe the recorded procedural score in this randomized study.

They do not establish that every gastroscopy had better visibility, that the observed difference would be the same in another setting, or that the score difference translated into improved patient outcomes. The registry does not report a threshold for a clinically meaningful change in the total score, nor does it report downstream outcomes that would show how a visibility difference affected diagnosis or care. No medical recommendation follows from this comparison.

The study also reports manual flushing as a secondary outcome, but not numerical results for every listed secondary measure. Secondary results are not a substitute for the primary endpoint, and the registry does not report a multiplicity plan or sponsor analyses. The safety summaries record zero affected participants in each group for serious and other adverse-event categories, but those observations do not rule out uncommon events.

Interpretation is constrained by missing information about the original sample-size justification, analysis plan, participant flow, missing outcomes, and analysis populations. The registry record also does not provide baseline characteristics or details of the scoring process beyond the score definition. Accordingly, the sound conclusion is limited to the posted group summaries and their unadjusted comparison. Wider claims about reproducibility, clinical importance, or general safety are not established by these data.

17. Why This Trial Matters Statistically

This trial illustrates why a randomized comparison should be read through both the endpoint definition and the statistical estimate. The direction of a score difference is not self-explanatory: here, the Mc Nally scale assigns higher ratings to more prominent bubbles and, at the severe end, visual obstruction. Once that direction is clear, the negative mean difference can be interpreted as a lower average recorded score in the simethicone group.

It also shows the value of separating an estimated difference from its uncertainty. The mean difference, confidence interval, and p-value convey related but distinct information. The estimate describes the average contrast; the interval expresses uncertainty under the comparison’s assumptions; and the p-value describes compatibility with a null model. None alone answers whether a difference is practically important or generalizable.

The registry record makes clear distinctions important for clinical-trial interpretation: a primary outcome is not the same as the secondary outcomes, an unadjusted calculation is not a documented original analysis, and planning illustrations are not evidence of observed power. The record’s missing information about multiplicity, missing data, and analysis populations also demonstrates why a numerical result cannot be interpreted independently of its analysis context.

Finally, this is a small, focused procedural study with a specific score and setting. Its posted results can inform understanding of that measurement in this trial, while leaving questions about broader applicability and clinical consequences unanswered. Statistical significance and a clearly directed score contrast do not remove those limits.

18. 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 the original sample-size justification, target effect, or planned power. Its planning illustration is based on the observed effect and cannot establish what the investigators intended when designing the study. The record also lacks a reported statistical analysis plan and sponsor-reported analysis entries, so it is not possible to determine whether the posted unadjusted comparison matches the investigators’ planned analysis.

Participant accounting is incomplete in the registry record. Although the primary group summaries include 27 participants per arm, the record does not describe participant flow, exclusions, missing outcome data, or the analysis population. It does not state whether the analysis followed intention-to-treat principles or another approach. These omissions prevent a full assessment of how the posted summaries relate to randomization and enrollment.

Measurement details are limited. The score categories and the anatomical areas are described, and the study is called endoscopist-blinded, but the registry does not report the scoring protocol in further detail, assessor reliability, or how ratings were combined when data were incomplete. The exact masking procedures beyond the endoscopist-blinded description are also not reported in the registry record.

There is no reported multiplicity strategy despite multiple outcomes, and numerical analysis results are not posted for every secondary endpoint. The registry also does not provide baseline characteristics, adjustment details, or sensitivity analyses. These gaps do not prove that the study had a particular flaw; they limit what can be verified from the record. Finally, the score is a procedural measure, and the registry does not report a threshold for meaningful change or patient outcomes linked to the score. Generalization beyond the recorded study setting should therefore be cautious.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Small Volume Simethicone Before Gastroscopy: Any Benefit? — NCT02555228.
• Registry record last updated 2016-03-15; status last verified 2016-02.
• Results first posted 2016-03-15.
• 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.

22. Record Summary

NCT02555228 is a completed, randomized, parallel-group study listed as phase 2 and phase 3 and sponsored by Changi General Hospital. The registry reports enrollment of 54, a start date of 2015-08, and primary completion in 2015-11. It compares liquid simethicone premedication with water placebo before diagnostic gastroscopy and describes the study as endoscopist-blinded.

The primary endpoint is total cumulative mucosal visibility score during gastroscopy. The posted summaries report 27 participants per arm, a lower mean score in the simethicone group, and an unadjusted mean difference of -3.11 units with a 95% confidence interval from -4.079 to -2.141 and p < 0.001. Manual flushing is the secondary outcome with a posted numerical comparison. Numerical results for the other listed secondary outcomes are not reported in the registry record.

The registry does not report the original sample-size justification, analysis plan, analysis populations, missing-data handling, or multiplicity approach. The posted findings should be interpreted as results for the recorded procedural measures, with those reporting limitations in mind.