This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for The Efficacy and Safety Study of Rikkunshito in Patients With Functional Dyspepsia (NCT02037776), a randomized phase 4 study. The primary outcome is Patient's Evaluation of Symptomatic Improvement by Overall Treatment Efficacy (OTE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02037776 |
| Phase | Phase 4 |
| Condition | Functional Dyspepsia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 128 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Osaka City University |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns Japanese subjects with functional dyspepsia. The registry record does not report detailed eligibility criteria, such as how the condition was confirmed or which other characteristics were required.
Intervention
The intervention was Rikkunshito. The registry record identifies it as a drug but does not report the dose, schedule, route, or treatment adherence information.
Comparator
The comparator was a Rikkunshito placebo. The trial is described as randomized, quadruple masked, and parallel-group. Details about how the placebo was matched or how masking was maintained are not reported in the registry record.
Primary question
The primary outcome was participants’ evaluation of symptomatic improvement using Overall Treatment Efficacy (OTE) at 8 weeks. The registry defines seven response categories, ranging from significantly improved to much worse. The category counts and a comparative efficacy estimate are not reported in the registry record.
In statistical terms, the trial asks whether the distribution of patient-rated overall symptom change differs between the Rikkunshito and placebo groups. The outcome reflects each participant’s overall assessment rather than a single symptom score. Because the categories have an order but the registry does not report their counts, the available record cannot establish how responses were distributed or how the groups compared.
The registry also names changes in reflux-related symptoms, upper gastrointestinal symptom severity, global overall symptoms, health survey scores, and anxiety and depression scores as secondary outcomes. Those measures broaden the questions the study could address, but their results and comparative estimates are not reported in the registry record. The question that can be evaluated from this record is therefore narrower than the full set of outcomes: it concerns the trial design and the way its patient-rated endpoint was defined, not a conclusion about the size or direction of an efficacy effect.
3. Trial Design
The DREAM Study is described as a phase 4, randomized, quadruple-masked, parallel-group, multicenter trial of Rikkunshito versus placebo in Japanese subjects with functional dyspepsia. The registry reports an enrollment of 128 and identifies Osaka City University as the sponsor. The study status is completed. The recorded start date is 2014-04-03, and the primary completion date is 2016-03-25.
Randomization is intended to make treatment groups comparable on average, while masking is intended to limit the influence of expectations or knowledge of assignment on participant reports and study assessments. These are general design purposes; the registry record does not report the randomization method, allocation concealment procedures, or the specific parties included in quadruple masking. It also does not give details about treatment delivery, adherence, or whether participants could change or stop assigned treatment.
A parallel-group design assigns participants to a treatment group for comparison with another group, rather than comparing each participant with themself across treatment periods. The registry identifies Rikkunshito and Rikkunshito placebo as the interventions and gives brief arm names, but the arm descriptions contain no additional regimen information. Equal allocation is mentioned as an assumption for planning illustrations, not as a reported feature of actual assignment.
The study’s primary endpoint was evaluated at 8 weeks. The registry describes the final evaluation as the latest evaluable time point for all patients, including discontinued patients. This indicates that the endpoint definition allowed an evaluable observation from a participant who had discontinued, but it does not explain how participants without an evaluable observation were handled. The protocol, sample-size justification, analysis populations, and detailed statistical analysis plan are not reported in the registry record.
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
| Stage | Rikkunshito Placebo | Rikkunshito |
|---|---|---|
| STARTED | 61 | 64 |
| COMPLETED | 56 | 60 |
| NOT COMPLETED | 5 | 4 |
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.
| Characteristic | Unit | Rikkunshito Placebo | Rikkunshito | Total |
|---|---|---|---|---|
| Participants analysed | 61 | 64 | 125 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 49 | 53 | 102 |
| Age, Categorical: >=65 years | Participants | 12 | 11 | 23 |
| Age, Continuous: Age | years | 50.4 (SD 13.7) | 50.4 (SD 14.9) | 50.4 (SD 14.3) |
| Sex: Female, Male: Female | Participants | 47 | 42 | 89 |
| Sex: Female, Male: Male | Participants | 14 | 22 | 36 |
| Region of Enrollment: Japan | Participants | 61 | 64 | 125 |
| Subtype of functional dyspepsia (FD): Postprandial distress syndrome (PDS) | Participants | 23 | 26 | 49 |
| Subtype of functional dyspepsia (FD): Epigastric pain syndrome (EPS) | Participants | 18 | 24 | 42 |
| Subtype of functional dyspepsia (FD): Both | Participants | 20 | 14 | 34 |
| Duration of FD: ≥6 months to <1 year | Participants | 19 | 24 | 43 |
| Duration of FD: ≥1 year | Participants | 42 | 40 | 82 |
6. Primary Endpoint
The registry lists the primary outcome as Patient's Evaluation of Symptomatic Improvement by Overall Treatment Efficacy (OTE), measured over 8 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is participants’ evaluation of symptomatic improvement by Overall Treatment Efficacy (OTE), assessed at 8 weeks. The registry describes seven ordered response categories: significantly improved, improved, slightly improved, no change, slightly worse, worse, and much worse. The endpoint is reported in participants, with the registry specifying that the final evaluation uses the latest evaluable time point and includes discontinued patients when evaluable data are available.
As a general measurement concept, a global rating asks participants to summarize their overall experience rather than report only one symptom or one instrument score. Such an endpoint can capture a broad personal judgment of change, but it also combines potentially different symptom experiences into one response. Its categories are ordered from improvement to worsening, yet the spacing between adjacent categories cannot be assumed to be equal. For example, the scale does not establish that a change from no change to slightly improved is quantitatively equivalent to a change from improved to significantly improved.
To compare groups using this endpoint, the distribution across categories matters. A summary that collapses categories into an improved/not-improved outcome would require a specified threshold and would discard distinctions retained by the seven-category scale. The registry record does not report category counts, a prespecified threshold, or a comparative analysis. Consequently, the endpoint is defined, but the reported record does not permit assessment of the observed response pattern or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed randomized comparison and defines a patient-rated primary endpoint, but it does not report the primary endpoint’s category counts. It also does not report a treatment-effect estimate, confidence interval, or hypothesis-test result for that endpoint. There is therefore no basis in the record for describing the direction, magnitude, or statistical precision of the primary comparison. The absence of those results is not evidence that the groups had the same outcomes.
The OTE endpoint has seven ordered categories. A useful interpretation would require knowing how many participants in each group selected each category, along with the analysis used to compare those distributions. Different patterns can yield different conclusions even if a summary proportion appears similar. The available registry record does not provide the category-level values or the statistical model, test, or effect measure used. No category-collapsed result is reported either.
The registry lists secondary outcomes involving modified FSSG, PAGI-SYM, GOS, SF-8, and HAD changes from baseline. It records six outcome measures and 17 analyses, but does not give the results or identify which analyses correspond to each measure. Without the estimates, uncertainty intervals, and analysis details, the secondary outcomes cannot add an interpretable estimate of treatment effect in this record. The number of analyses also makes it important to know whether the analysis plan addressed multiple comparisons; that plan is not reported.
Safety information is available as event counts. In the placebo group, 2 participants were recorded with serious adverse events among 63 at risk; in the Rikkunshito group, 0 were recorded among 65 at risk. Other adverse events were recorded for 5 participants among 63 at risk in the placebo group and 7 among 65 at risk in the Rikkunshito group. Deaths were recorded as 0 in both groups. These counts describe the registry entries, but the record does not provide enough detail to interpret differences as treatment effects. Definitions, event-level timing, exposure information, and comparative uncertainty are not reported.
Statistical interpretation depends on both an estimate and its uncertainty, as well as on the design and analysis that produced them. Here, design features are described, but efficacy estimates and their precision are not. The completed status and randomized, masked design do not substitute for outcome results. The appropriate reading is that the record defines the clinical question and provides limited safety counts, while leaving the primary efficacy result and its statistical interpretation unreported.
9. Statistical Methods Explained
Several statistical ideas are relevant to this trial, but the registry record does not identify the actual methods used for the primary or secondary analyses. The distinctions below explain how the design and outcome would ordinarily be considered without attributing an unreported analysis to the investigators.
What does randomization contribute?
Randomization assigns participants to treatment groups using a chance-based procedure. In general, this helps balance both measured and unmeasured characteristics across groups, though it does not guarantee identical groups in a particular trial. The registry identifies the study as randomized but does not report the sequence-generation method, allocation concealment, or checks of baseline comparability. The actual allocation procedure and baseline characteristics are therefore not available for assessment from this record.
Masking is another design feature. In general, keeping participants and study personnel unaware of assignment can reduce the influence of expectations on symptom reporting, care, and assessment. The trial is identified as quadruple masked, but the record does not specify which roles were masked or describe procedures for maintaining masking. The label alone does not establish how masking worked in practice.
How should the primary endpoint be analyzed?
OTE is an ordered categorical outcome: its responses have a meaningful direction from improvement through no change to worsening, but the gaps between categories are not known to be equal. General approaches can compare the full distribution of responses or model the ordered categories. A model for ordered categories may make assumptions about how treatment relates to the response scale; a distribution-based comparison may answer a different question. The appropriate choice depends on the analysis plan and data structure. The registry record does not report the selected method, its assumptions, or its results.
A binary analysis could be formed by defining some categories as improvement and the others as no improvement, but the choice of threshold changes the question and removes distinctions among the original responses. The registry’s primary endpoint description retains all seven categories, and the record does not report a threshold or a reduced two-category comparison. The primary outcome has several categories, so it is not represented by a single event comparison in the reported information.
What does a confidence interval communicate?
As a general concept, a confidence interval expresses the uncertainty around an estimated treatment contrast under a specified statistical method. Its width is influenced by the amount of information in the data and by variability. A point estimate without an uncertainty interval can make a result appear more definite than it is; an interval alone also needs to be interpreted in relation to the outcome scale and the clinical question. No confidence interval for the primary comparison is reported in the registry record, so its precision cannot be assessed.
For a categorical endpoint, precision depends on the distribution of participants among response categories, not only on the total enrollment. If some categories contain few participants, estimates involving those categories may be uncertain. The registry record does not give the category counts, so the extent of such sparsity cannot be evaluated. No assumption about a particular distribution or model can be verified.
How do the planning assumptions differ from trial results?
The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustrations are framed around detecting a stated fraction of the observed effect. These are planning assumptions, not evidence about the trial’s actual design justification. The sample-size justification and the trial’s own statistical plan are not reported in the registry record. Planning illustrations are not observed power and do not show whether a result is statistically significant or clinically important.
A normal approximation is a general way to estimate how a sampling distribution behaves when the approximation is suitable. Its adequacy depends on the outcome and the data available. For a multi-category response, the distribution across categories can matter, and an approximation intended for another outcome structure may not describe the primary endpoint. The registry record does not report a primary-outcome sample-size calculation or a method that links the planning assumptions to the seven-category endpoint.
Over-dispersion is a general concern when the observed variability exceeds what a statistical model assumes. If present, standard errors from a model that ignores it may be too small, which can make uncertainty appear lower than it is. Whether over-dispersion is relevant depends on the model and data. Since the registry record does not report the primary analysis model or results, it is not possible to assess this issue for the trial.
Why do analysis populations and missing observations matter?
An analysis population defines which randomized participants contribute to a particular analysis. Different choices can answer different questions, especially when participants discontinue or lack outcome data. The registry’s endpoint description refers to the latest evaluable time point, including discontinued patients, but the record does not state the full analysis population or how observations that were not evaluable were handled. Imputation, exclusion rules, and sensitivity analyses are not reported.
These omissions matter because results can depend on which observations are included and on the assumptions used for missing data. A complete description would also identify the statistical method, treatment contrast, uncertainty interval, and any planned adjustments for multiple outcomes or analyses. Those details are not reported in the registry record, so the posted information supports a description of the design and endpoint but not a reconstruction of the efficacy analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists secondary changes from baseline in modified FSSG, PAGI-SYM, GOS, SF-8, and HAD. It records six outcome measures and 17 analyses. Testing or estimating several outcomes can create multiple opportunities to find an apparently notable result by chance. As a general statistical principle, an analysis plan may address this by defining a primary comparison, specifying which secondary analyses are confirmatory, or using an adjustment procedure. The registry record does not report whether multiplicity was addressed, which outcomes were prioritized beyond the stated primary endpoint, or how the 17 analyses were organized.
Without results and a multiplicity plan, the secondary outcomes cannot be treated as independent confirmation of the primary question. The record does not provide estimates, uncertainty intervals, or analysis methods for those outcomes, so no comparison of their statistical evidence is possible.
The endpoint definition refers to the latest evaluable assessment and includes discontinued patients when they have evaluable data. It does not state what happened when a participant had no evaluable assessment, how missing baseline or follow-up measurements were handled, or whether any imputation or sensitivity analysis was used. The analysis populations are not reported in the registry record. In particular, it is not stated whether analyses followed an intention-to-treat, per-protocol, or another defined population.
These are material details rather than formalities. Excluding participants with missing outcomes, imputing values, or making different assumptions about unobserved outcomes can affect estimates. The available record does not show whether missingness differed by group or how it was addressed. Accordingly, the analysis of incomplete data and the control of multiplicity remain unreported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Rikkunshito Placebo | 2 | 63 | 3.2% |
| Rikkunshito | 0 | 65 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Rikkunshito Placebo | 0 of 63 |
| Rikkunshito | 0 of 65 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Rikkunshito Placebo | 5 of 63 |
| Rikkunshito | 7 of 65 |
Most frequent serious adverse event terms
| Event term | Organ system | Rikkunshito Placebo | Rikkunshito |
|---|---|---|---|
| Cervix carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 63 | 0 of 65 |
| Rash | Skin and subcutaneous tissue disorders | 1 of 63 | 0 of 65 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rikkunshito Placebo | Rikkunshito |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 1 of 63 | 1 of 65 |
| Constipation | Gastrointestinal disorders | 1 of 63 | 1 of 65 |
| Vomiting | Gastrointestinal disorders | 2 of 63 | 0 of 65 |
| Gingivitis | Infections and infestations | 0 of 63 | 1 of 65 |
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | 0 of 63 | 1 of 65 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 0 of 63 | 1 of 65 |
| Abdominal pain upper | Gastrointestinal disorders | 0 of 63 | 1 of 65 |
| Diarrhoea | Gastrointestinal disorders | 0 of 63 | 1 of 65 |
| Faeces soft | Gastrointestinal disorders | 0 of 63 | 1 of 65 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 63 | 0 of 65 |
Serious events with the highest arm-level rate: cervix carcinoma (1.6%), rash (1.6%).
The registry reports serious adverse events for 2 participants in the Rikkunshito placebo group, with 63 at risk, and for 0 participants in the Rikkunshito group, with 65 at risk. Other adverse events are reported for 5 participants in the placebo group and 7 in the Rikkunshito group; the corresponding numbers at risk are 63 and 65. Deaths are reported as 0 in each group. These are counts, not adjusted comparisons.
The registry lists Cervix carcinoma and Rash as the top serious adverse event terms, each at 1.6%. The record does not provide further context for these terms, including their timing, relationship to treatment, or participant-level detail. The listed percentages should be read as registry entries, not as a basis for deriving additional rates or comparative effects.
Safety counts are descriptive. They do not, by themselves, establish whether an event was caused by treatment or whether groups differ beyond what could occur by chance. The registry record does not report a statistical comparison, confidence intervals, adverse-event definitions, exposure duration, or detailed follow-up information. The counts should therefore be interpreted alongside those limitations and not as a complete safety assessment.
12. What the Result Does, and Does Not, Mean
The registry establishes that a randomized, quadruple-masked trial compared Rikkunshito with placebo in Japanese subjects with functional dyspepsia and used a patient-rated, seven-category OTE endpoint at 8 weeks. It also records limited adverse-event counts and names several secondary measures. These registry entries describe the study question and some of its reporting, but they do not provide the primary efficacy result.
The category counts for OTE, a comparative effect estimate, and an uncertainty interval are not reported in the registry record. Thus, the posted information does not show whether responses favored either group, how large any difference may have been, or how precisely it was estimated. Missing results must not be interpreted as proof of no effect, equivalence, or benefit.
The safety counts likewise do not determine causation or comparative risk. They are descriptive entries without the event-level information or statistical uncertainty needed for a treatment comparison. The serious adverse event terms and counts can be noted, but they do not support a complete assessment of safety.
As a general statistical principle, a trial’s design can strengthen the credibility of a comparison, but it cannot replace reporting the outcome data and analysis. Randomization and masking are relevant strengths in the design as recorded; the methods used to implement them and the analysis plan are not described in detail. No clinical recommendation follows from the information in the registry record. A reader can identify what the trial set out to measure and what limited safety information was recorded, while recognizing that efficacy and precision remain unreported.
13. Why This Trial Matters Statistically
This trial illustrates why the outcome’s scale matters to statistical interpretation. OTE is recorded in seven ordered categories, so the response pattern contains more information than a simple improved/not-improved label. A valid summary needs to preserve or deliberately simplify that structure, and any simplification should be defined in advance. The registry record describes the categories but does not report their counts or the analysis used to compare them.
The study also illustrates the difference between a well-defined design and an interpretable result. Randomization, masking, and a parallel-group structure describe how a comparison was intended to be conducted. Statistical conclusions still depend on estimates, uncertainty, analysis populations, missing-data handling, and the prespecified plan. Those elements are not fully reported in the registry record.
Multiplicity is another important issue because the record lists secondary outcomes and 17 analyses. Without a stated strategy for handling multiple analyses, it is not possible to know how secondary findings should be weighed. This is especially relevant when several measures address related but distinct aspects of symptoms or well-being.
Finally, the safety entries show why counts need context. Participants at risk and recorded event counts are useful descriptive information, but event definitions, timing, exposure, and uncertainty are needed for a more complete comparison. The trial is therefore statistically informative as an example of a clearly named patient-rated endpoint paired with incomplete reporting of efficacy analyses, rather than as a source of a quantifiable treatment-effect conclusion.
14. 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.
Important details needed to evaluate the trial are not reported in the registry record. These include the OTE category counts, the primary treatment-effect estimate, its confidence interval, and the statistical test or model used. Without those details, neither the direction nor the precision of the primary comparison can be assessed.
The record does not provide the full eligibility criteria, baseline characteristics, treatment dose or schedule, adherence information, or detailed arm descriptions. It also does not report the randomization procedure, allocation concealment, or the specific roles covered by quadruple masking. These gaps limit assessment of how the design was implemented and how representative the enrolled participants were.
The registry describes the final endpoint evaluation as the latest evaluable time point, including discontinued patients, but does not report participant flow, reasons for discontinuation, or handling of participants with no evaluable outcome. Analysis populations, missing-data methods, sensitivity analyses, and the statistical analysis plan are also not reported. These omissions prevent assessment of how incomplete data may have influenced the results.
The secondary outcome results and the relationship between the recorded 17 analyses and the listed outcomes are not reported. A multiplicity strategy and the trial’s sample-size justification are not reported either. For safety, event definitions, timing, treatment attribution, exposure information, and comparative uncertainty are unavailable. Together, these limitations mean that the registry record describes the study framework and some safety counts, but does not support a detailed assessment of efficacy, precision, or the completeness of safety reporting.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: The Efficacy and Safety Study of Rikkunshito in Patients With Functional Dyspepsia — NCT02037776.
- Registry record last updated 2017-07-27; status last verified 2017-07.
- Results first posted 2017-07-27.
- 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.
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18. Record Summary
NCT02037776 is the DREAM Study, a phase 4, randomized, quadruple-masked, parallel-group, multicenter trial sponsored by Osaka City University. It compared Rikkunshito with Rikkunshito placebo in Japanese subjects with functional dyspepsia. The registry reports an enrollment of 128, a start date of 2014-04-03, a primary completion date of 2016-03-25, and completed status.
The primary outcome was participants’ OTE evaluation of symptomatic improvement at 8 weeks, defined using seven response categories. Secondary measures included changes in modified FSSG, PAGI-SYM, GOS, SF-8, and HAD. Primary outcome category counts and comparative efficacy estimates are not reported in the registry record. Safety entries include serious and other adverse-event counts and 0 deaths in each group. Detailed statistical methods, missing-data handling, and multiplicity procedures are not reported.