Maintenance Intermittent Therapy for Symptomatic GERD Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Maintenance Intermittent Therapy for Symptomatic GERD Patients (NCT00165841), a randomized phase 2 study. The primary outcome is The Percentage of Heartburn-free Days (24-hour Periods) During the 6-month Maintenance Treatment Phase (ITT Population)..

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, parallel-group, phase 2 study with placebo as the comparator. The intervention was rabeprazole 20 mg, and the study concerned intermittent maintenance therapy after acute treatment for symptomatic gastroesophageal reflux disease. The registry record lists the study as completed. The recorded start was 2004-10, and the primary completion was 2005-12.

The registry reports enrollment of 200 subjects into the double-blind 6-month maintenance treatment phase. It separately states that 388 subjects were enrolled at the beginning of the acute phase. Those counts describe different points in the study, not the efficacy-analysis denominator. The primary outcome description identifies an ITT population of 187 subjects for efficacy analyses, while the safety population of 200 subjects was used for safety analysis and participant flow. The arm-level efficacy results report 96 subjects for rabeprazole and 91 for placebo.

The main endpoint was a continuous measure: the percentage of days without heartburn over the 6-month maintenance phase. The registry lists two secondary outcomes, the percentage of heartburn-free daytime periods and the percentage of heartburn-free nighttime periods during the same maintenance phase. It reports three outcome measures in all, but only one analysis is listed. The registry record does not report the original sample-size justification, detailed randomization procedures, or further protocol specifications.

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: After enrollment and before randomization (treatment assignment), there was a 2-week placebo run-in phase followed by a 4-week open-label Acute Phase during which subjects were treated with rabeprazole 20 mg once daily for the treatment of heartburn. Note the below participant flow is based on Safety Population (total 200 subjects).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population, total 187 subjects, was used for efficacy analyses. Safety population (total 200 subjects) was used for safety analysis and participant flow.

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 The Percentage of Heartburn-free Days (24-hour Periods) During the 6-month Maintenance Treatment Phase (ITT Population)., measured over 6 months double-blind maintenance phase.

The primary endpoint was the percentage of heartburn-free days, defined as 24-hour periods with no heartburn during either the daytime or nighttime period. It was assessed during the 6-month double-blind maintenance phase in the ITT population. The registry reports the outcome as a mean with standard deviation, making it a continuous measure rather than a count of participants who did or did not meet a threshold.

This endpoint combines daytime and nighttime symptom status into a day-level measure. It therefore represents the share of recorded days meeting the study’s heartburn-free definition, rather than the duration or intensity of symptoms on days when heartburn occurred. The registry also lists daytime and nighttime heartburn-free periods as secondary outcomes, which can describe those components separately.

Using the percentage of heartburn-free days allows a comparison of average symptom-free time across the treatment groups during the maintenance period. The endpoint is directly tied to the study’s stated question about maintenance therapy following acute treatment. It does not, on its own, describe every aspect of GERD, the course of symptoms outside the maintenance phase, or outcomes not included in the posted measures.

7. Results Posted in the Registry

• Rabeprazole 20 mg: mean 82.58 versus 62.17 on control; difference 20.41 (95% CI 13.62 to 27.20), standardized effect d = 0.88; z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean difference represent?

The endpoint is continuous, and the registry reports a mean for each treatment group. A mean is an average across the observations included in the analysis. The unadjusted recalculation contrasts those two group means and expresses the difference in percentage points. It is an absolute contrast on the endpoint’s scale, rather than a ratio or a percentage increase.

The reported group means are 82.58 for rabeprazole and 62.17 for placebo. The recalculated mean difference is 20.41. This contrast is unadjusted: it is calculated from the posted summary statistics rather than from a model adjusted for participant characteristics or other variables. The registry record does not report an adjusted estimate for this endpoint.

Why report standard deviations?

A mean describes the center of a group’s observed outcomes, while a standard deviation describes how spread out those observations are around the mean. The standard deviations are 14.39 for rabeprazole and 29.93 for placebo. They help readers see that the averages do not imply that all participants had the same percentage of heartburn-free days.

In general, variation matters because the precision of a group mean and the treatment contrast depends on both the amount of variation and the amount of information available. A group with more variation can have less precise estimates, all else being equal. The registry gives group sizes and standard deviations, allowing an unadjusted comparison to be calculated from the summaries.

What does the t-test assess?

The sponsor’s reported method is a two-sided t-test. In general, a two-sided test evaluates evidence for a difference in either direction, rather than limiting the test to a prespecified direction. A t-test compares group means while accounting for the observed variation and the amount of data in each group. Its p-value describes how incompatible the observed data are with a null hypothesis of no mean difference under the test’s assumptions. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of the contrast.

The registry reports p < 0.001 for the sponsor’s analysis, while the unadjusted recalculation reports p < 0.001. These are threshold-form p-values, not exact values. The recalculation and sponsor result are both statistically small by their reported thresholds, but the sponsor’s analysis is the trial’s reported analysis. A p-value alone does not communicate precision; the confidence interval provides information about the range of effect estimates compatible with the data.

What does the confidence interval add?

A confidence interval is an estimate accompanied by a range reflecting sampling uncertainty under the analysis assumptions. The recalculated interval for the mean difference is 13.62 to 27.2. In general, a narrower interval indicates greater precision than a wider interval for the same type of estimate. The interval does not describe the range of individual participant outcomes, and it does not guarantee that a future study’s estimate will fall within its limits.

The interval is for the difference in group means, not for either group mean separately. Its interpretation depends on the method used and the assumptions underlying the analysis. The registry reports the sponsor’s test but does not provide a sponsor confidence interval for the primary comparison. The recalculated interval is therefore a summary-statistic-based, unadjusted estimate rather than a replacement for an unreported sponsor interval.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. When a method assumes less variability than is present, uncertainty can be understated and intervals may be too narrow. The primary outcome is a percentage summarized by means and standard deviations, and the registry does not report a separate over-dispersion assessment or a model-based variance adjustment. The different reported standard deviations describe unequal spread between the groups, but unequal standard deviations alone do not establish that a particular model is over-dispersed.

What does the design contribute?

Random allocation and double masking are stated design features. In general, randomization is intended to make treatment groups comparable with respect to factors that could affect the outcome, while masking is intended to reduce the influence of treatment knowledge on care or assessment. These design features support interpretation of a between-group comparison, but their effectiveness depends on how they were implemented and maintained. The registry record does not report the randomization method, concealment details, or masking assessment.

The registry identifies a parallel-group design, meaning the comparison is between groups assigned to different study arms rather than a within-participant crossover comparison. The primary endpoint uses the ITT population, while the safety population is reported separately. The record does not give a detailed statistical analysis plan, missing-data method, or adjustment for multiple outcomes. Those omissions limit how fully the reported test and analysis populations can be evaluated.

10. Confidence Intervals and Precision

The unadjusted recalculated mean difference is 20.41 percentage points, with a 95% confidence interval from 13.62 to 27.2. The interval quantifies uncertainty around the estimated difference in group means under the recalculation’s assumptions. It is not an interval for individual participant responses and should not be interpreted as a guarantee about results in another study.

Because both confidence limits are above zero, the interval is consistent with a positive mean difference in this sample. Its width reflects uncertainty in the estimated contrast, which depends on the group sizes, the observed variability, and the calculation method. The standard deviations differ between groups: 14.39 for rabeprazole and 29.93 for placebo. That variability is relevant to precision even though the reported endpoint is an average percentage.

The confidence interval comes from an unadjusted recalculation based on the posted summary statistics. The registry reports a two-sided t-test with p < 0.001, but does not report a confidence interval for the sponsor’s primary analysis. The registry record does not provide further detail about whether the sponsor used an adjusted model or how missing observations were handled. Thus, the interval should be read as a descriptive estimate from the recalculation, alongside—not in place of—the trial’s reported analysis.

Precision and statistical significance answer related but different questions. The p-value addresses compatibility with a null hypothesis under a test, while the confidence interval conveys a range of plausible values under the interval method. Neither alone determines the clinical relevance of the result, and neither describes the full range of outcomes among participants.

11. 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 participants across arms or total events. The table considers planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For each assumed effect, the 80% power column gives the illustrative number of participants per arm needed to have an 80% chance of detecting that effect at the stated significance level under the planning assumptions. The 90% power column gives the corresponding illustration for a 90% chance.

The calculation assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It uses the stated fraction of the observed effect as the effect to detect. For example, planning for 75% of the observed effect gives 37 participants per arm for 80% power and 49 participants per arm for 90% power. Planning for 50% of the observed effect gives 82 participants per arm for 80% power and 110 participants per arm for 90% power. The full set of scenarios is displayed in the sample-size table and curve.

As the assumed effect becomes smaller, more participants are needed to distinguish it from random variation with the same power target. The planning figures are illustrations based on the observed result, not a reconstruction of the trial’s original design assumptions. The original sample-size justification and assumptions are not reported in the registry record. These values are not observed power: they describe hypothetical future planning under stated assumptions, not the probability that this completed trial detected an effect.

12. 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 = 20.410; pooled standard deviation σ = 23.284.
2. n = 2 × (1.96 + 0.842)² × 23.284² / 20.410² = 20.4, rounded up to 21 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 <- 20.41                      # observed difference in means
sigma <- 23.2837131918429                     # 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(165841)
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 = 21 (80% power), 28 (90% power)
 75% of observed effect: n per arm = 37 (80% power), 49 (90% power)
 50% of observed effect: n per arm = 82 (80% power), 110 (90% power)
power.t.test: 21.4 
Simulated power at n = 21 per arm: 0.790 (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.

13. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as a two-sided t-test with p < 0.001. The unadjusted recalculation from the posted group summaries gives a mean difference of 20.41 percentage points, a 95% confidence interval from 13.62 to 27.2, and p < 0.001. The registry’s discrepancy indicator is false, so there is no flagged disagreement between the posted recalculation and the sponsor’s result.

The recalculation is based on group-level means, standard deviations, and sample sizes. It is not necessarily identical in every analytical detail to the sponsor’s analysis. The sponsor’s result is the trial’s own reported analysis and takes precedence when describing the study’s stated analysis. The recalculation adds an unadjusted estimate and interval using the available summary statistics, but it cannot reveal unreported modeling choices or missing-data procedures.

Both p-values are reported as thresholds rather than exact values. They should not be treated as different estimates of the treatment effect: the effect estimate is expressed by the mean difference, while the p-values summarize evidence under their respective tests. The record does not provide a sponsor-reported effect estimate or confidence interval for the primary comparison.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes. The primary outcome is the percentage of heartburn-free days during the maintenance phase. The secondary outcomes are the percentages of heartburn-free daytime periods and heartburn-free nighttime periods. Although three outcome measures are listed, the registry reports one analysis. Results for the secondary outcomes are not included in the available outcome results, so their estimates and uncertainty are not reported in the registry record.

When several outcomes or comparisons are tested, the chance of at least one apparently significant result can increase if each is assessed without accounting for the others. In general, multiplicity procedures address this issue by controlling error across a defined family of tests. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or whether the primary outcome was the only formal confirmatory test. The primary comparison should therefore be distinguished from the unreported secondary results, rather than assuming that all outcomes were analyzed or adjusted in a particular way.

The primary efficacy population is described as the ITT population, total 187 subjects. The arm summaries report 96 for rabeprazole and 91 for placebo. Safety analyses and participant flow used a safety population of 200. The record also states that 200 subjects entered the double-blind maintenance phase and 388 entered at the beginning of the acute phase. These descriptions show that the populations and study stages differ, but do not explain the reasons for the different analysis counts.

The registry record does not report how missing primary-outcome observations were handled, whether imputation was used, or how adherence and withdrawals were incorporated. It also does not report interim analyses or a detailed statistical analysis plan. Without those details, the potential influence of missingness, multiplicity decisions, or deviations from planned analyses cannot be fully assessed from the registry entry.

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

The posted primary results describe a higher mean percentage of heartburn-free days in the rabeprazole 20 mg group than in the placebo group during the 6-month maintenance phase. The unadjusted mean difference is 20.41 percentage points, with a confidence interval from 13.62 to 27.2. The registry’s reported two-sided test gives p < 0.001. These findings describe the observed comparison in this randomized study and the precision of an unadjusted estimate.

The endpoint has a specific definition: a day counts as heartburn-free only when neither the daytime nor the nighttime period includes heartburn. The measure summarizes the percentage of such days, not symptom severity, the number of participants free from symptoms throughout the phase, or every aspect of GERD. The listed secondary outcomes separate daytime and nighttime periods, but their results are not reported in the registry record.

The result does not by itself establish how the same comparison would look in another population or under different care conditions. It also does not provide evidence about outcomes that were not measured or posted. Statistical evidence against a null hypothesis is not a measure of clinical importance, and the confidence interval does not describe individual treatment responses.

The registry describes a maintenance intervention following acute treatment. The finding therefore relates to that study context and phase; it should not be generalized to acute treatment or to treatment strategies not evaluated in this comparison. The record does not report enough detail about missing-data handling, protocol implementation, or analysis planning to resolve those aspects of interpretation.

16. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through both its effect estimate and its uncertainty. The difference in mean percentage of heartburn-free days gives the comparison on the endpoint’s original scale, while the confidence interval indicates the precision of the unadjusted estimate. A p-value alone would not show the estimated size or range of uncertainty.

The study also makes the distinction between analysis populations visible. The registry describes 200 subjects in the maintenance-phase safety population and 187 in the ITT efficacy population, while the arm-level efficacy summaries report 96 and 91. Keeping these denominators distinct is important when reading efficacy, safety, and participant-flow information. The record does not explain the differences in detail, so the counts should not be treated as interchangeable.

The primary outcome is a continuous percentage measure, while its definition combines daytime and nighttime symptom status. The separate secondary outcomes could help distinguish those components, but their results are not reported in the registry record. This highlights the importance of distinguishing posted results from outcomes merely listed in the record.

Finally, the sample-size illustrations show how planning depends on the assumed effect and desired power, but they do not reveal the trial’s original planning process. The registry does not report that process. Separating trial results from retrospective planning illustrations helps avoid confusing observed evidence with hypothetical future-study design.

17. 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 gives limited detail about how the study was conducted and analyzed. It identifies randomization, double masking, a parallel design, and a two-sided t-test, but does not describe the randomization procedure, allocation concealment, or how masking was maintained. The original sample-size justification is not reported in the registry record.

The efficacy population is reported as 187, whereas the maintenance-phase safety population is 200; arm-level efficacy counts are 96 and 91. The record also refers to 388 subjects at the beginning of the acute phase. These figures relate to different stages or populations, but the reasons for the differences and the handling of missing observations are not reported in the registry record. This limits assessment of possible effects of attrition or missingness on the primary estimate.

The sponsor reports a test result but no primary effect estimate or confidence interval in the analysis entry. The mean difference and confidence interval are unadjusted recalculations from the posted summaries, so they cannot incorporate analytical details that are not reported. The record does not report an adjusted analysis, an interim-analysis plan, or a detailed statistical analysis plan.

Two secondary outcomes are listed, but their results are not reported in the registry record. The record does not state whether multiplicity was addressed. Safety entries give counts of serious adverse events and other adverse events by group, but the at-risk denominators and death counts are not reported. The listed serious-event terms include Gallstone pancreatitis, Pneumonia, Chest pain, and Schizoaffective disorder/depression, each with 1.0%; the record does not provide additional context in those entries to establish a treatment-specific interpretation.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Maintenance Intermittent Therapy for Symptomatic GERD Patients — NCT00165841.
• Registry record last updated 2013-05-20; status last verified 2009-12.
• Results first posted 2009-12-03.
• 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.

21. Record Summary

This completed phase 2 study was randomized, double-blind, and parallel-group, comparing rabeprazole 20 mg with placebo as intermittent maintenance therapy after acute treatment for symptomatic GERD. The maintenance phase lasted 6 months.

The primary outcome was the mean percentage of heartburn-free days in the ITT efficacy population. Group means were 82.58 for rabeprazole and 62.17 for placebo. The unadjusted recalculated mean difference was 20.41 percentage points, with a 95% confidence interval from 13.62 to 27.2. The registry reports a two-sided t-test with p < 0.001.

The registry lists daytime and nighttime heartburn-free periods as secondary outcomes, but their results are not reported in the registry record. The original sample-size justification, missing-data procedures, and detailed statistical plan are also not reported in the registry record.