Special Drug Use Surveillance of Vonoprazan for "Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Non-steroidal Anti-inflammatory Drugs: Long-term Use": Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Special Drug Use Surveillance of Vonoprazan for "Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Non-steroidal Anti-inflammatory Drugs: Long-term Use" (NCT03214198), a registered phase not stated study. The primary outcome is Percentage of Participants Who Had One or More Adverse Drug Reactions.

2. Clinical Question

This is a safety-surveillance question in a routine clinical setting, rather than a randomized estimate of a treatment effect against a control. The registry describes the intended purpose as investigating the safety and efficacy of long-term vonoprazan administration in patients receiving NSAIDs. However, the listed primary endpoint is the percentage of participants with one or more adverse drug reactions; the registry record does not report a primary efficacy result.

The record lists an enrollment of 1304 and defines the safety analysis set as all participants who completed the survey. The adverse-event summary gives 1268 participants at risk. Those figures describe different reported quantities, and the registry does not explain the difference. The condition listed is a history of gastric or duodenal ulcers. Further eligibility criteria, patient characteristics, or details of the NSAID regimens are not reported in the registry record. The clinical question is therefore best understood as a descriptive question about recorded events in the stated surveillance population, not as evidence from a controlled comparison.

3. Trial Design

The registry record describes a special drug use surveillance study of vonoprazan for prevention of recurrence of gastric or duodenal ulcers in patients receiving NSAIDs. It lists one intervention group, vonoprazan 10 mg, with once-daily oral use in routine medical care. The stated surveillance period was up to 12 months. The study status is completed, with a recorded start date of 2016-09-01 and primary completion date of 2020-04-30. Takeda is listed as the sponsor.

This is not a randomized comparison. The allocation method is not stated, and there is no control arm described. As a result, the study design does not provide a like-for-like group against which to compare event frequencies. Participants received the intervention as part of routine care, rather than through a described randomized assignment. The registry record does not report additional design details such as enrollment procedures, visit schedules, or how adherence was assessed.

The listed primary outcome is the percentage of participants who had one or more adverse drug reactions. The record also lists outcomes for gastric ulcers, duodenal ulcers, gastric hemorrhagic lesions, and duodenal hemorrhagic lesions. These outcomes describe different clinical events, but their definitions and corresponding results are not reported in the record. The record lists 1304 enrolled participants. For the safety analysis set, it states that participants had to complete the survey, and the adverse-event summary reports 1268 at risk. Reasons for the difference between those reported populations are not stated.

Details of the protocol’s sample-size justification, interim analyses, and complete statistical analysis plan are not reported in the registry record. The record lists no inferential analyses. The stated purpose includes safety and efficacy, but the information available does not establish a comparative efficacy analysis or explain how efficacy outcomes were to be analyzed.

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: Participants with a historical diagnosis of gastric or duodenal ulcers were enrolled. Participants received vonoprazan as part of a routine medical care.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.

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.

Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Had One or More Adverse Drug Reactions, measured over Up to 12 months.

The primary endpoint is the percentage of participants who had one or more adverse drug reactions during up to 12 months. The registry defines an adverse event as an untoward medical occurrence in a participant given a pharmaceutical product, whether or not the occurrence has a causal relationship with the treatment. An adverse drug reaction is an adverse event considered related to the administered drug. That distinction matters: the endpoint concerns events judged related to vonoprazan, not every medical occurrence recorded during follow-up.

A percentage endpoint is a participant-level summary of how often an event occurs within a defined analysis population. It can offer an accessible description of the observed burden of reactions in the surveillance group. It does not, by itself, establish that the drug caused the events, and without a comparator it cannot show whether the frequency differs from what would have occurred under another treatment or under no treatment.

The registry names the safety analysis set as all participants who completed the survey. However, it does not report the primary endpoint percentage or its numerator and denominator. The adverse-event summary includes counts for serious and other events, but it does not identify those counts as the primary adverse-drug-reaction result. The primary endpoint result is therefore not reported in the registry record. The reason for choosing this endpoint, including any prespecified threshold or decision rule, is also not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: interpreting a participant percentage. A percentage of participants with an event is a binary-outcome summary: each participant is classified according to whether the event occurred, and the result describes the share meeting that definition in the analysis population. The interpretation depends on having a clear event definition, a clearly specified denominator, and a consistent observation period. Here, the primary endpoint concerns participants with one or more adverse drug reactions over up to 12 months. The record defines the safety analysis set as participants who completed the survey, but does not report the primary endpoint percentage, its numerator, or a confidence interval.

General: endpoint definition and attribution. An adverse event is a medical occurrence after a participant receives a pharmaceutical product; it need not be caused by the product. An adverse drug reaction is an adverse event considered related to the drug. This moves the primary endpoint from a count of all events to a judgment about relationship. Such judgments depend on how events are reviewed and classified. The registry record does not describe the attribution procedure, criteria, or review process, so the reported adverse-event categories cannot be assumed to equal the primary adverse-drug-reaction outcome.

General: precision and uncertainty. A point estimate gives one summary value for an observed group, while a confidence interval describes the uncertainty around that estimate under a statistical model. Precision depends partly on the number of participants and the number of events, as well as the analysis method. An interval does not remove possible bias or establish causation. No confidence interval for the primary endpoint is reported in the registry record, so the precision of that endpoint estimate cannot be assessed from the stated results. No p-value or comparative effect estimate is reported either.

General: why over-dispersion can matter. Simple binary-outcome models generally rely on assumptions about how events vary across participants. If participants differ more than the model allows—for example, because their underlying risks or observation patterns vary—the observed data may be more dispersed than the model expects. This over-dispersion can make a model’s uncertainty estimates too small if it is not accounted for. This is a general consideration, not a reported feature of this study: the registry record does not describe a model for the primary endpoint or an assessment of over-dispersion.

General: why a comparator matters. A single-group event frequency describes what was recorded among participants who received the intervention. A comparative treatment effect requires a meaningful reference group and a design or analysis that supports the comparison. Random allocation can help make groups comparable on average, while adjustment in observational studies can address measured differences but cannot guarantee that all confounding is removed. This record describes no comparator and does not state an allocation method. It therefore does not support a controlled estimate of the effect of vonoprazan on adverse events or ulcer outcomes.

Planning illustrations are not trial results. The planning assumptions associated with the record describe an illustrative calculation using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe detecting a stated fraction of an observed effect. Those are assumptions for a planning illustration, not a description of the study’s actual design or proof of the study’s statistical power. The record does not report the trial’s own sample-size justification. Because the study is not a randomized comparison and has no stated comparator, a two-arm planning illustration should not be read as evidence that the surveillance study included two comparable groups. No planning output is reported in the record.

General: event counts and rates. Counts depend on the population being counted and on the definition of an event. A participant may experience more than one event, so event counts and counts of participants affected are not interchangeable. The adverse-event summary distinguishes participants at risk from those affected, but the record does not explain the detailed counting rules or whether the affected counts represent participants with at least one event in each category. The seven deaths are listed separately; the record does not establish a causal relationship with the intervention.

General: interpreting rare-event summaries. Low reported percentages for particular event terms can describe how frequently those terms appear in the recorded serious-event summary, but they do not on their own establish a stable estimate of risk or a causal association. Context includes the denominator, ascertainment, follow-up, and the clinical characteristics of participants. The registry lists percentages for selected serious-event terms, but does not provide further detail on how the terms were selected or how event coding was conducted.

Overall, the statistical information supports a limited descriptive reading of the reported safety categories. It does not provide the primary endpoint estimate or an inferential comparison. The registry record does not report the detailed analysis plan, missing-data methods, or other modeling choices needed to assess those aspects of the analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Vonoprazan 10 mg")
n      <- c(1268)
events <- c(9)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Vonoprazan 10 mg  1268  9  0.7  0.3  1.3  0.4  1.3  0.4  1.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary adverse-drug-reaction outcome and secondary outcomes for gastric ulcers, duodenal ulcers, gastric hemorrhagic lesions, and duodenal hemorrhagic lesions. When several outcomes are examined, the chance of finding at least one apparently notable result can increase, particularly if many statistical tests are conducted. General statistical approaches can address multiplicity through prespecified priorities or adjusted testing procedures. The registry record does not report a multiplicity strategy, and it lists no inferential analyses. The secondary outcome results and their analysis methods are not reported in the record.

The registry defines the safety analysis set as all participants who completed the survey. This definition makes completion part of eligibility for the safety analysis, but the record does not say how incomplete surveys or other missing outcome information were handled. It does not report the amount or pattern of missing data, whether follow-up was complete for all participants, or whether any imputation or sensitivity analyses were used. No missing-data method should be inferred from the stated analysis population.

The record reports an enrollment of 1304 and an adverse-event denominator of 1268, while defining the safety analysis set as survey completers. It does not explain why these population figures differ, identify exclusions, or give a flow of participants through the surveillance and analysis. This means the reader cannot assess whether the people included in the safety summary differed systematically from those not included. The primary endpoint numerator and denominator are also not reported.

The registry does not report whether outcomes were analyzed by subgroup, how multiple events per participant were treated, or whether any interim analyses were planned or conducted. Those details are not reported in the registry record. These omissions limit assessment of the risk of selective analysis and the completeness of the reported outcome information.

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 0.1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: benign prostatic hyperplasia (0.2%), pneumonia (0.1%), sepsis (0.1%), myelodysplastic syndrome (0.1%), pancreatic carcinoma (0.1%).

The safety summary lists 1268 participants at risk in the vonoprazan 10 mg group. It records 17 affected in the serious category, 21 affected in the other category, and 7 deaths. The record does not explain the event-counting rules or state that these figures represent adverse drug reactions. In particular, the primary endpoint requires an adverse event to be considered related to the administered drug; the category counts do not by themselves establish that relationship.

The listed serious-event terms and percentages are benign prostatic hyperplasia, 0.2%; pneumonia, 0.1%; sepsis, 0.1%; myelodysplastic syndrome, 0.1%; pancreatic carcinoma, 0.1%; and pancreatic carcinoma metastatic, 0.1%. These are descriptive entries in the registry’s serious-event summary. The record does not provide details about individual cases, timing, clinical context, or attribution. The presence of a term in the summary should not be read as evidence that vonoprazan caused it.

Deaths are reported separately, but the registry record does not state whether they were considered related to treatment. The summary also does not provide confidence intervals or a comparative group. Accordingly, these figures describe recorded safety events in the surveillance population; they do not establish a causal rate or a difference from another treatment.

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

The record describes routine-care surveillance of vonoprazan 10 mg in patients receiving NSAIDs who had a history of gastric or duodenal ulcers. Its primary safety question is the percentage of participants with one or more adverse drug reactions during up to 12 months. The registry’s event summary gives counts for serious and other categories, but it does not report the primary adverse-drug-reaction percentage. The available figures therefore do not directly answer the primary endpoint question as defined.

The reported counts can be read as descriptions of events recorded in the safety summary, using the stated group and denominator. They cannot establish that the events were caused by vonoprazan. The registry does not report whether the serious events or deaths were judged related to treatment. The distinction between adverse events and adverse drug reactions is central: an event may occur during treatment without being attributed to the drug.

The study has no stated comparator and is not a randomized comparison. Its event figures cannot show how the same population would have fared under another treatment or without vonoprazan. Differences in participants’ underlying health, NSAID use, and routine-care circumstances could influence what was observed. The registry does not report an adjusted analysis that would address such differences.

The title and summary frame the surveillance around long-term use and prevention of ulcer recurrence, but the primary endpoint listed is a safety outcome. Although ulcer-related secondary outcomes are listed, their results are not reported in the registry record. The record therefore does not establish an effect on ulcer recurrence or on the listed ulcer and hemorrhagic lesion outcomes.

More broadly, the study can contribute a description of recorded experience in its surveillance population, but the available reporting leaves important questions unanswered: the primary outcome result, the relationship of events to treatment, the handling of incomplete surveys, and the details of outcome analysis. Those limitations should be kept distinct from the fact that the study is recorded as completed.

14. Why This Trial Matters Statistically

Routine-care surveillance addresses a different statistical question from a randomized controlled comparison. It can describe events recorded during use in a clinical setting, where participants receive the intervention as part of care. That perspective is relevant to understanding how a safety endpoint is framed and what information is needed to interpret event counts. In this record, the stated primary outcome is the percentage of participants with one or more adverse drug reactions over up to 12 months.

The record also illustrates why endpoint definitions matter. All adverse events are not necessarily related to treatment, while an adverse drug reaction requires a judgment of relatedness. A summary of serious and other event categories cannot substitute for a reported result on the defined primary endpoint. Clear reporting of the endpoint numerator, denominator, analysis population, and uncertainty would help readers understand the result’s scope and precision.

It also highlights the role of design in interpretation. Without a comparator and a stated allocation method, the observed safety events are descriptive, not a controlled estimate of treatment effect. A completed surveillance study can still leave the principal statistical question unresolved if the relevant outcome result and analysis details are not reported.

The enrollment figure, safety-set definition, and adverse-event denominator are all important to the interpretation, but the record does not explain how they relate. Reporting participant flow and missing-data handling would clarify who contributed to the safety summary. Reporting event attribution procedures would clarify how the primary outcome was distinguished from broader adverse-event categories.

These are general lessons about statistical interpretation, not conclusions that a particular event was caused by treatment. The central value of careful reading is to separate what is described in the record from what remains unreported and from what a one-group surveillance design can establish.

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 main limitation is that the registry record does not report the primary endpoint result, despite defining the percentage of participants with one or more adverse drug reactions as the primary outcome. The adverse-event summary provides serious and other category counts, but does not identify them as the primary drug-related endpoint or report the attribution decisions needed to connect those categories to it.

The study has no comparator group described, and the allocation method is not stated. The event counts therefore cannot support a like-for-like comparison or a causal estimate. Routine-care administration reflects the stated setting, but the record does not provide details on participant characteristics, NSAID regimens, adherence, or co-interventions that would help describe the population and context of the observed events.

The registry reports enrollment of 1304, defines the safety analysis set as survey completers, and gives 1268 as the number at risk in the adverse-event summary. It does not explain the relationship between these figures, list exclusions, or describe missing-data handling. The primary endpoint numerator and denominator, confidence interval, and inferential analysis are not reported. Although several secondary outcomes are listed, their results and analysis methods are also not reported.

Further details that could affect interpretation—including the protocol’s sample-size justification, interim analyses, outcome ascertainment, event coding, and statistical analysis plan—are not reported in the registry record. The listed serious-event terms have no accompanying case-level context or reported treatment attribution. These limitations constrain both assessment of precision and interpretation of the safety findings. They do not establish that an unreported analysis was not conducted; they indicate that it is not documented in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Special Drug Use Surveillance of Vonoprazan for "Prevention of Recurrence of Gastric/Duodenal Ulcer in Patients Receiving Non-steroidal Anti-inflammatory Drugs: Long-term Use" — NCT03214198.
• Registry record last updated 2023-06-07; status last verified 2023-06.
• Results first posted 2021-05-19.
• 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

This completed special drug use surveillance study concerns vonoprazan for prevention of gastric or duodenal ulcer recurrence in patients receiving NSAIDs. The registry lists Takeda as sponsor, an enrollment of 1304, and vonoprazan 10 mg once daily as the intervention in routine medical care. The recorded study dates are 2016-09-01 and 2020-04-30 for start and primary completion.

The primary endpoint is the percentage of participants with one or more adverse drug reactions during up to 12 months. The safety analysis set is defined as participants who completed the survey. The adverse-event summary reports 1268 participants at risk, 17 affected in the serious category, 21 in the other category, and 7 deaths. The primary endpoint percentage is not reported in the registry record, and the event counts are not established as treatment-related.

No comparator is described, and the study is not a randomized comparison. The record lists ulcer and hemorrhagic lesion secondary outcomes but does not report their results. Details of the analysis plan, missing-data handling, and the relationship among the reported participant populations are not reported in the registry record.