Sequential and Hybrid Therapies for H Pylori Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sequential and Hybrid Therapies for H Pylori Infection (NCT01085786), a randomized phase 4 study. The primary outcome is Number of Participants in Which H. Pylori Was Eradicated.

2. Clinical Question

The registry describes a comparison of two treatment schedules, not a comparison with no treatment or with an unrelated therapy. The main distinction in the schedules is that the hybrid regimen continues amoxicillin into the second 7-day phase, while the sequential regimen changes from the initial proton pump inhibitor and amoxicillin combination to a proton pump inhibitor with clarithromycin and metronidazole.

The record also describes antibiotic resistance as a secondary aim, asking about treatment effectiveness in relation to resistance. Adverse events and compliance rate are listed as secondary outcomes. Detailed results for antibiotic resistance and compliance are not reported in the registry record. The primary result therefore addresses the recorded eradication outcome, rather than all aspects of treatment effectiveness or tolerability.

3. Trial Design

This was a randomized, single-masked, parallel-group phase 4 trial. The registry lists an enrollment of 240 and identifies Kaohsiung Veterans General Hospital as the sponsor. The recorded start was 2008-08, primary completion was 2010-05, and trial status is completed. The primary outcome timeframe is Dec 2010.

Participants were assigned to one of two 14-day drug regimens. In the sequential group, the first 7 days consisted of a proton pump inhibitor and amoxicillin, followed by 7 days of a proton pump inhibitor, clarithromycin, and metronidazole. The hybrid group used esomeprazole 40 mg and amoxicillin 1 g twice daily for 7 days, followed by esomeprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 7 days. The registry does not report the sequential group’s drug doses.

There were 123 participants in the sequential group and 117 in the hybrid group in the posted primary outcome results. The registry identifies the outcome as the number of participants in whom H. pylori was eradicated, assessed by endoscopy with urease test or urea breath test. The listed secondary outcomes are adverse events and compliance rate; the study summary also identifies antibiotic resistance as a secondary endpoint or aim.

The registry does not report the masking details, the randomization method, or the trial’s original sample-size assumptions. It also does not describe the planned statistical analysis in detail. These design details should not be inferred from the phase, allocation, or outcome entries.

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: no significant events for the overall study

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 Number of Participants in Which H. Pylori Was Eradicated, measured over Dec 2010.

The primary endpoint is the number of participants in whom H. pylori was eradicated. The registry says eradication was evaluated by endoscopy with a urease test or by urea breath test, and gives Dec 2010 as the outcome timeframe. The posted results record 94 eradications among 123 participants in the sequential group and 99 among 117 in the hybrid group. The record also lists 95% confidence intervals for the group results.

Eradication is a binary outcome for each participant: the assessment indicates whether eradication was recorded or not. Reporting the count with the group size describes how many participants had the event and how many were included in the posted outcome group. The endpoint is used to compare the groups on the central question of whether the infection was eradicated under each regimen.

The registry’s outcome description does not explain how participants with an unavailable test or an indeterminate result were handled. It also does not report the analysis population or the precise rule used to combine the two assessment methods. Those details matter when interpreting an endpoint based on diagnostic testing, but they cannot be established from the registry record. The eradication result should therefore be read as the registry-posted outcome, without assuming additional assessment or missing-data procedures.

7. Results Posted in the Registry

• 14-day Hybrid Treatment: 84.6% (99/117) versus 76.4% (94/123) on control; risk difference 8.2 percentage points (95% CI -1.8 to 18.1), risk ratio 1.11 (0.98–1.25); unadjusted two-proportion z-test p = 0.110.

8. Statistical Interpretation

9. Statistical Methods Explained

What does a risk difference express?

A risk difference compares the proportion of participants with an event in one group with the proportion in another. It is an absolute measure: it describes the gap between the groups on the event scale. In this trial, the event is recorded eradication, and the comparison is hybrid treatment relative to sequential treatment. A positive estimate in that direction means the observed event frequency was higher in the hybrid group; it does not by itself show that the difference is precise or clinically important.

What does the confidence interval add?

A confidence interval gives a range of effect estimates compatible with the data under the method used to construct it. Its width describes precision: a wider interval reflects greater uncertainty about the effect’s size. For the reported risk difference, the interval includes values on both sides of no difference. This is why the point estimate should not be read as a settled estimate of the treatment contrast. The registry does not identify the calculation method for each interval, so no particular method should be assumed.

How should the p-value be understood?

The unadjusted p-value is 0.11. In general, a p-value measures how unusual data at least as discrepant as those observed would be under a stated null model, assuming the model and its assumptions apply. It is not a measure of effect size, a probability that the null hypothesis is true, or a measure of the chance that the result arose randomly. The registry does not report an adjusted p-value or a detailed statistical analysis plan. The p-value should therefore be interpreted as the posted unadjusted comparison, not as evidence about unreported analyses.

Why are there several effect scales?

The record reports a risk difference, relative risk, and odds ratio. The risk difference is absolute, while the relative risk compares event probabilities as a ratio and the odds ratio compares event odds as a ratio. These are different summaries of the same group data, so their numerical values are not interchangeable. A relative measure can make a contrast look different from an absolute measure, especially when the event occurs often. None of these measures alone resolves uncertainty; each needs to be read with its interval and with the outcome definition in mind.

What does randomization contribute?

Random allocation is intended to make treatment groups comparable, on average, with respect to factors that might affect outcomes. It supports a between-group comparison, but does not guarantee that every measured or unmeasured feature was balanced in the actual trial. The registry identifies the allocation as randomized, but does not describe sequence generation, concealment, stratification, or other implementation details. Those methods cannot be inferred from the allocation label.

What does single masking establish?

The registry labels the trial single-masked, but does not say which people were masked or how masking was maintained. Masking can reduce the influence of expectations on some trial procedures, but the label alone does not establish which outcome assessments, participants, clinicians, or analysts were unaware of allocation. The eradication endpoint uses diagnostic tests, but the record does not state whether assessors were masked.

What can be concluded about the analysis?

The primary outcome is a participant count, and the posted comparison includes group sizes and an unadjusted p-value. The record does not report the analysis population, treatment of missing test results, covariate adjustment, or a detailed model. It also does not identify interim analyses or specify a prespecified statistical plan. A description of the posted comparison should not be expanded into claims about analyses that the registry does not document.

10. Confidence Intervals and Precision

Precision concerns how narrowly the trial estimates the outcome or the difference between groups. The registry reports 94 eradications among 123 participants assigned to sequential treatment, with a 95% confidence interval from 90 to 98, and 99 among 117 assigned to hybrid treatment, with a 95% confidence interval from 95 to 100. These group intervals describe uncertainty around the posted group results; they are not themselves a direct interval for the difference between groups.

For the direct comparison, the registry reports a risk-difference estimate and a confidence interval that spans values on both sides of no difference. That interval indicates that the data do not pin down the direction and size of the contrast precisely. The observed point estimate favors the hybrid group numerically, but plausible values represented by the interval include a contrast in the other direction. The unadjusted p-value of 0.11 is consistent with the need to consider uncertainty rather than treating the point estimate as definitive.

Confidence intervals are not a guarantee that the true effect lies within the reported limits. In general, they describe the performance of an interval-producing method over repeated use under its assumptions. Their interpretation also depends on how the outcome and analysis were defined. The registry does not report enough detail to assess all such assumptions or how missing assessments were treated.

The group sizes and the comparison interval are relevant to precision, but they do not establish the importance of any possible difference. The record does not report a threshold for a clinically important difference. Statistical uncertainty and clinical importance are separate considerations, and the registry results alone do not settle the latter.

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 or total events. They illustrate the group size that would be needed under the stated planning assumptions to detect a chosen fraction of the observed effect. The entries are shown for planning at 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For each planning effect, the figures give the participants per arm for 80% power and for 90% power.

Power is the chance, under a specified planning model and effect assumption, of detecting an effect using a chosen statistical test. The 80% column represents a design with 80% power under those assumptions; the 90% column represents a design with 90% power. A higher target power generally requires a larger planned sample for the same effect assumption. Smaller effects are harder to distinguish from random variation, so the planning entries rise as the assumed effect becomes a smaller fraction of the observed effect.

The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is the stated fraction of the observed effect. The figures are planning illustrations computed from the observed effect, not the trial’s original design calculations; that original design justification is not reported in the registry record. These figures are not observed power. They are conditional planning quantities and should not be interpreted as a retrospective measure of how likely the trial was to find a result.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.764; treatment proportion p₁ = 0.846; average p̄ = 0.805.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5601 = 1.0978.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5571 = 0.4689.
4. n = (1.0978 + 0.4689)² / (0.0819)² = 365.7, rounded up to 366 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
p0 <- 0.764227642276423                          # control proportion
p1 <- 0.846153846153846                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1085786)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 366 (80% power), 490 (90% power)
 75% of observed effect: n per arm = 677 (80% power), 906 (90% power)
 50% of observed effect: n per arm = 1,580 (80% power), 2,114 (90% power)
power.prop.test: 365.7 
Simulated power at n = 366 per arm: 0.808 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies adverse events and compliance rate as secondary outcomes. The study summary also describes antibiotic resistance as a secondary endpoint or aim. The number of analyses recorded is 0, and detailed results for the secondary outcomes are not reported in the registry record. The registry does not explain how the outcomes relate to any prespecified analysis hierarchy.

When multiple outcomes or comparisons are examined, the chance of at least one apparently notable finding can increase. Statistical methods can address that issue through prespecified primary outcomes, testing hierarchies, or adjustment procedures. The registry record does not report whether any multiplicity strategy was planned or used. The reported p-value is explicitly unadjusted, so it should not be described as adjusted for multiple testing.

The record also does not report an analysis population, such as whether the primary comparison included all randomized participants or only participants with an evaluable test. It does not explain whether missing or indeterminate eradication assessments occurred, how they were handled, or whether participants were excluded from the posted outcome counts. This limits assessment of whether the reported group totals represent all randomized participants or an analyzed subset.

Information about the original statistical analysis plan, interim analyses, and handling of protocol deviations is not reported in the registry record. Without these details, it is not possible to determine whether the posted analysis follows a prespecified plan, whether other analyses were conducted, or how any such analyses were selected. These are reporting limitations, not evidence that a particular procedure was or was not used.

14. 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.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events in each group: 0 among 123 participants in the sequential group and 0 among 117 in the hybrid group. It also records 26 other adverse events in the sequential group and 17 in the hybrid group. The record does not give further detail about these other events in the posted safety information, and no serious adverse-event terms are listed.

These are counts, not adjusted comparisons. They should be read with the number at risk in each group and with the limits of the recorded information. A count of zero serious events in the registry does not establish that no serious event occurred outside the record or that the regimens have equivalent safety. The registry does not provide event definitions, severity breakdowns for other events, exposure-adjusted rates, or a detailed safety-analysis method. Death counts are not reported in the registry record.

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

The registry result shows that eradication was recorded for 94 participants in the sequential group and 99 in the hybrid group. The point estimate for the comparison is numerically in the direction of more eradications with hybrid treatment, but the reported interval includes values on both sides of no difference, and the unadjusted p-value is 0.11. Taken together, these results leave uncertainty about the size and direction of the group contrast.

The result does not establish that the regimens are equivalent. Equivalence requires a prespecified margin and an analysis designed to test whether the difference is sufficiently small; such a margin and analysis are not reported in the registry record. Nor does the result establish that either regimen is superior. A numerical difference in the observed groups is not, by itself, a conclusive treatment effect.

The registry record also does not support conclusions about the relationship between antibiotic resistance and effectiveness, because detailed resistance results are not reported. Adverse events and compliance are listed as secondary outcomes, but the available safety counts are limited and detailed compliance findings are not reported. The result therefore addresses the posted eradication outcome more directly than these other questions.

Interpretation is limited to the enrolled trial groups, the described treatment schedules, and the outcome as recorded. The registry does not provide all information needed to assess the analysis population, missing assessment handling, masking implementation, or prespecified statistical procedures. These gaps do not invalidate the posted counts, but they constrain how fully the comparison can be evaluated.

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 group counts place the observed eradication results in context, while the direct comparison interval shows that the estimated contrast is not sharply determined. A point estimate can suggest a direction, but it does not convey the range of values compatible with the data.

It also demonstrates the distinction between absolute and relative effect measures. A risk difference describes an absolute contrast; relative risk and odds ratio describe contrasts on ratio scales. Reporting more than one scale can help different readers understand the result, but the measures answer different descriptive questions and should not be interchanged.

Planning illustrations based on an observed effect are another useful statistical teaching point. Their required group sizes depend on the effect size selected for planning and the target power. They are not a record of the original trial’s design rationale, and they do not measure the trial’s observed power. In this record, the original sample-size assumptions are not reported.

Finally, registry reporting shapes what can be concluded. Randomization and a primary outcome are documented, but details of masking, missing data, analysis populations, multiplicity, and the analysis plan are not. Statistical interpretation is strongest when the reported estimates are considered alongside both the design information and the limits of the record.

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 does not report the method used to generate or conceal the random allocation, or identify who was masked. The label single-masked alone does not clarify whether participants, clinicians, outcome assessors, or analysts were masked. This makes it difficult to evaluate the implementation of two important design features from the record alone.

The original sample-size calculation and its assumptions are not reported. The available planning figures are retrospective illustrations based on the observed effect, not the trial’s design justification. The detailed statistical analysis plan, interim analyses, analysis population, and handling of missing or indeterminate test results are also not reported in the registry record.

The primary endpoint description identifies two possible assessment methods but does not specify how results from them were combined or how the timing of assessment was applied to individual participants. The record does not report detailed results for antibiotic resistance or compliance, despite their place in the study aims or listed secondary outcomes. Safety information is limited to event counts, with no further detail for the other adverse events and no death counts reported in the registry record.

These omissions limit independent assessment of the full trial methods and secondary findings. They do not change the counts and comparison posted for the primary outcome, but they leave important questions about conduct, analysis, and completeness unanswered.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Sequential and Hybrid Therapies for H Pylori Infection — NCT01085786.
• Registry record last updated 2015-09-21; status last verified 2015-09.
• Results first posted 2011-05-06.
• 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

NCT01085786 is a completed, randomized, single-masked, parallel-group phase 4 trial comparing 14-day sequential and hybrid therapies for Helicobacter pylori infection. The registry lists an enrollment of 240 and records the trial start as 2008-08, primary completion as 2010-05, and the primary outcome timeframe as Dec 2010.

The primary posted result records eradication in 94 of 123 participants assigned to sequential treatment and 99 of 117 assigned to hybrid treatment. The comparison’s risk-difference interval spans values on both sides of no difference, and its unadjusted p-value is 0.11. Secondary outcomes include adverse events and compliance; antibiotic resistance is also described as a secondary aim. Detailed results for resistance and compliance are not reported in the registry record.