# Berberine hydrochloride tablets × Reduced weekly diarrhea frequency in diarrhea-predominant irritable bowel syndrome Verdict 3071 · Evidence Check Stored-material review date: 2026-10-05 Original evidence review date: 2026-09-08 Review-criteria version: 1.1 Public page/material preparation date: 2026-10-27 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Adults with Rome III diarrhea-predominant irritable bowel syndrome. Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain unverified. Do not extend this to general diarrhea or all IBS. - Ingredient, formulation and route: Oral berberine hydrochloride 200 mg tablets. Plant source, manufacturer, excipients and supplier remain unverified. Do not substitute other extracts, derivatives, combinations or topical products. - Dose: The nominal plan was 200 mg 2 times daily (400 mg/day). Actual dosing, adherence, rescue treatment and handling of discontinuation remain unverified. This is not an instruction for personal use. - Comparator: The actual comparator was vitamin C tablets 400 mg/day. The historical placebo label does not automatically establish an inert placebo. Appearance, sensory matching and biological inertness remain unverified. - Measured outcome: The endpoint is diary-based weekly diarrhea frequency. Retained week 8 values are 1.39±0.80 versus 3.55±0.66, P=.032. Exact summary-statistic type, meaning of ±, time-specific analysis n, between-arm difference, CI, importance and analysis model remain unverified. The original C grade, 50 points and Warning are historical records. - Duration: Distinguish 8 weeks of treatment from the week 12 result after 4 weeks off treatment. Week 12 values are 3.58±0.73 versus 3.81±0.54, P=.805. Historical null/no-difference wording does not establish 0 effect, equivalence, sustained benefit, cure or relapse prevention. - Questions outside this scope: Retain the conflict among 196 recruited, 164 or 132 randomized, and 132 completing (70/62). Do not use completers as time-specific analysis denominators or subtract counts to create a dropout total.; Diarrhea and urgency were tracked together, but prospective co-primary hierarchy and multiplicity handling remain unverified. Do not extend the diarrhea result to the same effect on pain, quality of life or microbiome normalization.; Verification states concern narrow conditions within retained material. Counts of met conditions or the original verdict score do not provide new efficacy or safety certification.; Retain overlap between gastrointestinal reactions and baseline IBS symptoms, and the original cautions concerning pregnancy, lactation, infants and young children, and CYP-related concomitant drugs. Do not newly infer harm incidence or causality from improvement after stopping or rechallenge. ## Checklist items ### N01 · Which IBS-D diarrhea-frequency question is addressed? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original claim concerns reduced weekly diarrhea frequency in diarrhea-predominant irritable bowel syndrome. This sheet is limited to berberine hydrochloride versus vitamin C at 8 weeks in adults with Rome III IBS-D. - Why unverified: The original claim and claim conditions link intervention, population, comparator and endpoint, establishing the identity of this sheet. - Reason for missing information: The independent question has been identified. The result after stopping at 12 weeks and urgency are explained separately; this verification does not include IBS cure or relapse prevention. - Required materials and conditions: The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL. - Materials to obtain first: The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL. - Further research: Compare the original claim with the evidence comparison to check that persistence after stopping, urgency, pain and quality of life are not mixed into the principal effect. - Conditions for verification: Fix a single question about weekly diarrhea frequency at 8 weeks comparing oral berberine hydrochloride 400 mg/day with vitamin C 400 mg/day in adults with Rome III IBS-D. - Why this condition is needed: Needed to distinguish an ingredient-wide effect from a particular comparison and time point. - Application exceptions: The original subclaim list is empty. Do not invent subclaims or expand every combination of dimensions into a separate sheet. - Remaining uncertainty: The independent question has been identified. The result after stopping at 12 weeks and urgency are explained separately; this verification does not include IBS cure or relapse prevention. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N02 · Do the actual ingredient and tablet formulation match this question? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The claim conditions specify berberine hydrochloride tablets and 200 mg tablets. Retain the manuscript boundary that plant extracts, combinations, dihydroberberine, other derivatives and topical products are not interchangeable. - Why unverified: The labeled ingredient and dosage form were checked in the retained material, with other products excluded. - Reason for missing information: The labeled ingredient and dosage form were checked. Manufacturing source and complete excipients remain unverified in a separate item. - Required materials and conditions: The formulation name, composition, dosage form and reasons for including or excluding other products. - Materials to obtain first: The formulation name, composition, dosage form and reasons for including or excluding other products. - Further research: Compare product composition with Methods to distinguish whether results for berberine hydrochloride tablets can be transferred to other extracts, derivatives or combinations. - Conditions for verification: Distinguish the berberine hydrochloride tablets in the material from plant extracts, other derivatives, combinations and topical products. - Why this condition is needed: The same berberine name does not establish the same exposure. - Application exceptions: Unverified plant source or excipients do not establish that this was a different formulation. - Remaining uncertainty: The labeled ingredient and dosage form were checked. Manufacturing source and complete excipients remain unverified in a separate item. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N03 · To what extent are the experimental tablet’s labeled ingredient and dosage form, source, manufacturer and excipients established? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The source description specifies berberine hydrochloride tablets but states that the plant source is unverified. Direct information on the manufacturer and excipients was not found in the current retained summary. - Why unverified: The tablet ingredient is known, but source, manufacture and complete composition have not been established. - Reason for missing information: Plant source, manufacturer, excipients and experimental-product supplier remain missing. This is a limitation of the retained summary, not a finding of nonreporting across the entire original paper. - Required materials and conditions: The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records. - Materials to obtain first: The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records. - Further research: Compare the original product description and supply records to separate the labeled hydrochloride amount from complete product composition and origin. - Conditions for verification: Check separately the labeled berberine hydrochloride 200 mg tablet information and the extent of verification of the actual source, manufacturer and complete composition. The labeled ingredient alone does not establish source, manufacture or excipients. - Why this condition is needed: Product identity beyond the ingredient name is needed to explain whether the experimental exposure is the same. - Application exceptions: Do not convert an unverified source into a specific plant species or the presence of product impurities. - Remaining uncertainty: Plant source, manufacturer, excipients and experimental-product supplier remain missing. This is a limitation of the retained summary, not a finding of nonreporting across the entire original paper. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N04 · Are route, nominal dose and dosing frequency specified? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The claim conditions specify oral use, 200 mg 2 times daily and 400 mg/day. The manuscript also limits scope to IBS-D diarrhea frequency with 400 mg/day for 8 weeks. - Why unverified: Route and nominal administration information are directly present in the retained material. - Reason for missing information: Nominal route, dose and frequency were checked. Actual consumption and adherence are gaps in the next condition. - Required materials and conditions: Route, labeled tablet amount, dosing frequency and nominal daily dose. - Materials to obtain first: Route, labeled tablet amount, dosing frequency and nominal daily dose. - Further research: Compare administration instructions with formulation labeling to check for results from different doses or routes being mixed in. - Conditions for verification: Directly connect the nominal oral regimen of 200 mg 2 times daily, 400 mg/day. - Why this condition is needed: Needed to avoid substituting results from another product or dose for the nominal regimen. - Application exceptions: Do not interpret nominal 400 mg/day as actual adherent intake or blood exposure. - Remaining uncertainty: Nominal route, dose and frequency were checked. Actual consumption and adherence are gaps in the next condition. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N05 · Can actual intake, adherence and rescue treatment be established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The nominal 200 mg 2 times daily is known, but actual consumption, arm-specific adherence, rescue-treatment figures and handling methods were not established from the current material. - Why unverified: Data on actual intake and treatment changes beyond the administration plan are unavailable. - Reason for missing information: Actual intake, adherence, rescue treatment and analytical handling of drug discontinuation remain missing. - Required materials and conditions: Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records. - Materials to obtain first: Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records. - Further research: Compare nominal dose with actual dosing records and examine the effect of interest and analysis accounting for discontinuation and rescue treatment. - Conditions for verification: Check how arm-specific intake, adherence, drug discontinuation and rescue treatment affected the comparison at 8 weeks. - Why this condition is needed: Assigned administration instructions alone do not establish equal actual exposure. - Application exceptions: Unverified adherence does not establish nonadherence or an incorrect nominal dose. - Remaining uncertainty: Actual intake, adherence, rescue treatment and analytical handling of drug discontinuation remain missing. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N06 · Is the eligibility scope for adults with Rome III IBS-D established? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The claim conditions concern adults with Rome III diarrhea-predominant IBS. Detailed age range, severity, eligibility criteria and recruitment setting are not established in the retained summary. - Why unverified: Diagnosis and the adult population are known, but detailed selection and representativeness remain unresolved. - Reason for missing information: Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain missing, preventing extension to general diarrhea or all IBS. - Required materials and conditions: Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics. - Materials to obtain first: Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics. - Further research: Compare eligibility criteria and baseline tables to examine applicability to the current adult IBS-D question and differences from other diarrhea or IBS types. - Conditions for verification: Check age, severity, eligibility and recruitment setting of the diagnosed population without extending to general diarrhea or all IBS. - Why this condition is needed: The same diarrhea symptoms do not establish the same diagnosis or selection process. - Application exceptions: Unverified detailed selection does not establish no effect in other IBS types. - Remaining uncertainty: Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain missing, preventing extension to general diarrhea or all IBS. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N07 · What did the comparator arm actually receive? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The actual comparator was vitamin C tablets 400 mg/day. The manuscript’s key explanation emphasizes that the paper’s placebo was vitamin C. - Why unverified: The distinction between actual ingredient/nominal dose and placebo wording is directly specified. - Reason for missing information: The actual comparator ingredient and dose were checked. This does not establish appearance, sensory matching or biological inertness of the comparator tablet. - Required materials and conditions: The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording. - Materials to obtain first: The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording. - Further research: Review comparator formulation descriptions to distinguish the actual vitamin C comparison from assumptions of an inert control, and check administration differences between arms. - Conditions for verification: Distinguish that the actual comparator called placebo in the paper was vitamin C tablets 400 mg/day. - Why this condition is needed: Hiding the actual comparator ingredient changes the meaning of the comparative effect. - Application exceptions: Do not automatically judge the vitamin C comparator identical to an inert placebo or equivalent treatment to berberine. - Remaining uncertainty: The actual comparator ingredient and dose were checked. This does not establish appearance, sensory matching or biological inertness of the comparator tablet. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N08 · Are concomitant medication, diet and lifestyle changes in both arms established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The retained material specifies berberine versus vitamin C but does not present arm-specific information on concomitant medication, diet, lifestyle changes or rescue treatment. - Why unverified: Direct information for reviewing actual cointerventions and arm-specific changes is unavailable. - Reason for missing information: Arm-specific concomitant medication, diet, lifestyle changes and handling of changes/rescue treatment in the results remain missing. - Required materials and conditions: Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling. - Materials to obtain first: Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling. - Further research: Compare arm-specific cointervention and change timelines to examine whether factors beyond berberine versus vitamin C were mixed into the results. - Conditions for verification: Check how arm-specific concomitant treatment, diet, lifestyle interventions and rescue treatment during 8 weeks were handled in the actual comparison and analysis. - Why this condition is needed: Needed to avoid attributing differences in other treatments or behavior to berberine. - Application exceptions: Do not require all changes to be identical or fill unverified information with an absence of cointerventions. - Remaining uncertainty: Arm-specific concomitant medication, diet, lifestyle changes and handling of changes/rescue treatment in the results remain missing. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N09 · Can 8 weeks of treatment be distinguished from 4 weeks of off-treatment follow-up? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Treatment lasted 8 weeks, followed by 4 weeks off treatment. Week 8 is the end of treatment and week 12 is an assessment after stopping; do not combine them into a single result. - Why unverified: The nominal treatment/off-treatment follow-up and the two result time points are connected in the retained material. - Reason for missing information: Nominal time-point separation was checked. Actual visit schedules by arm, time-specific observation denominators and prospective schedules remain separate gaps. - Required materials and conditions: Administration, discontinuation and assessment schedules and results at each time point. - Materials to obtain first: Administration, discontinuation and assessment schedules and results at each time point. - Further research: Compare the time-point table to identify which results belong to on-treatment versus off-treatment observations. - Conditions for verification: Distinguish the end of 8 weeks of administration from assessment at week 12 after a further 4 weeks off treatment, without merging time points. - Why this condition is needed: Needed to avoid transferring the end-of-treatment result into a sustained effect. - Application exceptions: Differences in results at different time points do not constitute a numerical conflict at the same time point. - Remaining uncertainty: Nominal time-point separation was checked. Actual visit schedules by arm, time-specific observation denominators and prospective schedules remain separate gaps. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N10 · Are the diarrhea-diary event definition and collection procedures established? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The endpoint is diary-recorded weekly diarrhea episodes, described in the evidence table as a direct patient-experienced endpoint. Event definition, diary form, aggregation and handling of missing entries were not established in the current retained summary. - Why unverified: Diary use and weekly frequency are known, but actual measurement procedures remain unresolved. - Reason for missing information: Diarrhea event definition and diary collection, aggregation and missing-data handling remain unresolved. Urgency and pain values are not substitutes for this endpoint. - Required materials and conditions: Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries. - Materials to obtain first: Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries. - Further research: Compare diary forms and measurement instructions to examine how diarrhea episodes differ from bowel movements, urgency and pain. - Conditions for verification: Check the event definition for weekly diarrhea episodes, aggregation period, diary completion, missing-entry handling and scale direction. - Why this condition is needed: The definition and collection of patient-recorded diarrhea frequency must be distinguished from the actual effect. - Application exceptions: The description as a direct patient-experienced endpoint does not certify a validated diary or complete measurement. - Remaining uncertainty: Diarrhea event definition and diary collection, aggregation and missing-data handling remain unresolved. Urgency and pain values are not substitutes for this endpoint. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N11 · Is the prospective co-primary hierarchy for diarrhea and urgency established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The manuscript states that diarrhea and urgency were tracked together but the exact prospective co-primary hierarchy was unclear, retaining coprimary_split=true. - Why unverified: Material on the actual prospective co-primary hierarchy and multiplicity handling is not established. - Reason for missing information: Prospective endpoint status for diarrhea/urgency, testing order, multiplicity handling and the basis for result selection remain unresolved. - Required materials and conditions: Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP. - Materials to obtain first: Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP. - Further research: Compare plans and reports to examine whether selecting diarrhea alone matches the prospective hierarchy and whether separate urgency reporting is missing. - Conditions for verification: Check diarrhea/urgency status and handling of multiple testing and selective reporting in the prospective plan. - Why this condition is needed: Needed to avoid extending a favorable diarrhea result alone into success for all co-primary endpoints. - Application exceptions: Do not interpret the coprimary_split flag as definitive proof of a plan violation or selective reporting. - Remaining uncertainty: Prospective endpoint status for diarrhea/urgency, testing order, multiplicity handling and the basis for result selection remain unresolved. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N12 · Are the arm-specific weekly diarrhea values at 8 weeks connected? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Reported weekly diarrhea values at 8 weeks are berberine 1.39±0.80 versus vitamin C 3.55±0.66, P=.032. The reader answer, evidence table and citation connect these values to the same time point. - Why unverified: Arm values and P at 8 weeks are directly present in the evidence table and citation. No new effect difference was created. - Reason for missing information: The printed values at 8 weeks and their time-point attribution were checked. Exact statistical summary type such as a mean, meaning of ±, denominator, model and CI are outside this verification. - Required materials and conditions: Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point. - Materials to obtain first: Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point. - Further research: Compare arms, endpoint, time point and units in the table at 8 weeks and check agreement between summary and printed values. Do not newly calculate a difference or CI. - Conditions for verification: Connect the reported weekly diarrhea values, printed ± values and P for berberine and vitamin C at 8 weeks to that time point. - Why this condition is needed: Needed to avoid transferring retained figures to another endpoint or an off-treatment result. - Application exceptions: The meaning of ±, actual analysis denominator, between-arm difference and CI are separate conditions from checking these arm values. - Remaining uncertainty: The printed values at 8 weeks and their time-point attribution were checked. Exact statistical summary type such as a mean, meaning of ±, denominator, model and CI are outside this verification. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N13 · Was the off-treatment result at 12 weeks preserved separately? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Reported values at 12 weeks, or 4 weeks after stopping, are 3.58±0.73 versus 3.81±0.54, P=.805. The manuscript describes no difference/null. Retain this historical wording without creating a new conclusion of 0 effect or equivalence. - Why unverified: The original off-treatment values and unfavorable persistence result were retained and distinguished from values at 8 weeks. - Reason for missing information: Original off-treatment values and nonsignificance wording were checked. Exact effect difference, interval, equivalence, individual relapse and long-term persistence are not established. - Required materials and conditions: Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules. - Materials to obtain first: Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules. - Further research: Compare off-treatment result timing and arm-specific follow-up to examine persistence of the signal at 8 weeks within the reported scope, without newly estimating equivalence or relapse rates. - Conditions for verification: Retain arm values and P at 12 weeks after 4 weeks off treatment without converting nonsignificance into 0 effect or equivalence. - Why this condition is needed: Needed to avoid retaining only the favorable result at 8 weeks and presenting sustained benefit. - Application exceptions: Retain the manuscript’s null/no-difference wording as historical description. Do not newly judge P=.805 as exact 0 effect or equivalence. - Remaining uncertainty: Original off-treatment values and nonsignificance wording were checked. Exact effect difference, interval, equivalence, individual relapse and long-term persistence are not established. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N14 · Are arm values final values or changes, and are baseline data available? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Arm values at 8 and 12 weeks exist, but baseline values, exact statistical summary type and the original table’s definitions of final values versus changes are absent from retained material. - Why unverified: Time-specific figures alone cannot establish the original analysis’s value definition or change from baseline. - Reason for missing information: Baseline diarrhea frequency and definitions of final value/change and mean/other summary type remain unresolved. - Required materials and conditions: Baseline diarrhea, original table headings at each time point, statistical summary type and change definition. - Materials to obtain first: Baseline diarrhea, original table headings at each time point, statistical summary type and change definition. - Further research: Compare baseline and result tables to verify analysis definitions without substituting final values, changes and within-arm changes for one another. - Conditions for verification: Check statistical summary type, final value/change and baseline diarrhea data at each time point. - Why this condition is needed: The same number can address different questions as final frequency versus change from baseline. - Application exceptions: If baseline values are absent from the current summary, do not subtract time-point values to fill in a change. - Remaining uncertainty: Baseline diarrhea frequency and definitions of final value/change and mean/other summary type remain unresolved. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N15 · Are the analysis population, adjustment and effect of interest at 8 weeks established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original grade rationale describes limitations of completer data, but formal ITT/PP definitions, adjustment model and analysis denominator at 8 weeks are not established in the current retained summary. - Why unverified: Plan and analysis information specifying the actual analysis population and effect of interest is unavailable. - Reason for missing information: The analysis population at 8 weeks, ITT/PP definitions, adjustment model and connection to assignment or adherence effects remain unresolved. - Required materials and conditions: Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models. - Materials to obtain first: Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models. - Further research: Compare plans with result analyses to examine whether the effect concerns all assigned participants or completers, and how adjustment and missing-data handling connect. - Conditions for verification: Check assignment/adherence effects, ITT/PP, analysis population, adjustment and the actual between-arm analysis definition. - Why this condition is needed: Needed to avoid converting completers into the analysis population for the assignment effect. - Application exceptions: The manuscript’s assessment as completer data does not establish a formal PP analysis or arm-specific analysis n. - Remaining uncertainty: The analysis population at 8 weeks, ITT/PP definitions, adjustment model and connection to assignment or adherence effects remain unresolved. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N16 · Is it established whether ± values are SD or SE? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Values at 8 weeks, 1.39±0.80 versus 3.55±0.66, and at 12 weeks, 3.58±0.73 versus 3.81±0.54, are retained, but the type of ± is not specified. - Why unverified: The retained printed values lack a legend identifying SD, SE or another dispersion type. - Reason for missing information: Whether each ± value is SD/SE, the analysis denominator and original table legend remain unresolved; do not use them to calculate a new CI. - Required materials and conditions: Original table legend, SD/SE definitions, analysis n for each value and measurement units. - Materials to obtain first: Original table legend, SD/SE definitions, analysis n for each value and measurement units. - Further research: Compare table legends with Methods to distinguish SD, SE and other error expressions, checking only the meaning of reported statistics. - Conditions for verification: Use the original table legend to establish which dispersion/error statistic the printed ± values at 8 and 12 weeks represent. - Why this condition is needed: The ± string alone cannot support calculation of dispersion or precision. - Application exceptions: Do not convert ± into CI or infer SD/SE to create a new interval. - Remaining uncertainty: Whether each ± value is SD/SE, the analysis denominator and original table legend remain unresolved; do not use them to calculate a new CI. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N17 · Do recruitment and randomization counts agree? Verification status: Conflicting data Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The key explanation specifies inconsistent reports of 196 recruited, 164 or 132 randomized, and 132 completing. The evidence sample-size field also retains inconsistency in the reported randomization denominator. - Why unverified: Retain the manuscript’s conflict that the same randomization stage was reported as 164 or 132. - Reason for missing information: Original stage-specific text and correction/flow material needed to resolve 164 versus 132 randomized remain missing. No value was established or newly corrected here. - Required materials and conditions: CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections. - Materials to obtain first: CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections. - Further research: Compare recruitment flow and participant counts in the abstract, Methods and results by the same stages to establish whether 164 and 132 refer to different stages or an error. - Conditions for verification: Check recruitment flow and original report locations that could resolve inconsistent reports of 196 recruited, 164 or 132 randomized, and 132 completing. - Why this condition is needed: Needed to avoid hiding conflicting counts or using an arbitrary larger count as the analysis denominator. - Application exceptions: Do not automatically merge 196, 164 and 132 as counts for the same stage or select one as the correct answer. - Remaining uncertainty: Original stage-specific text and correction/flow material needed to resolve 164 versus 132 randomized remain missing. No value was established or newly corrected here. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N18 · Are 70/62 completers connected to time-specific analysis denominators? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The evidence sample-size field retains 70 versus 62 completers. This connects to the manuscript’s total of 132 completing, but the completion stage/time and analysis n for each result are unspecified. - Why unverified: Arm-specific completion counts are known, but they are not connected to actual analysis denominators at both time points. - Reason for missing information: The exact completion stage, measurement/analysis n at 8 and 12 weeks, and arm-specific allocation counts remain missing. - Required materials and conditions: Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks. - Materials to obtain first: Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks. - Further research: Connect each results table with the flow to distinguish completer counts, time-specific observation/analysis counts and shared participants. - Conditions for verification: Distinguish 70 versus 62 completers from analysis n at 8 and 12 weeks and check actual denominators for each result. - Why this condition is needed: Needed to avoid inheriting completers as actual analysis denominators at both time points. - Application exceptions: Do not automatically fill analysis n at 8 or 12 weeks with the completion counts 70/62. - Remaining uncertainty: The exact completion stage, measurement/analysis n at 8 and 12 weeks, and arm-specific allocation counts remain missing. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N19 · Who was lost, and how were missing diarrhea results handled? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The manuscript emphasizes recruitment, randomization and completion denominator limitations and completer data. Arm-specific dropout reasons, missing diaries, missing-data handling and sensitivity analyses are not currently established. - Why unverified: Inconsistent counts alone do not reveal actual observation losses or handling methods. - Reason for missing information: Arm-specific dropout, reasons for time-specific missingness, missing-data handling and sensitivity analyses remain unresolved. - Required materials and conditions: Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses. - Materials to obtain first: Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses. - Further research: Compare recruitment flow with missing diaries and examine robustness under missing-data handling and assumptions. Do not calculate a new missingness rate. - Conditions for verification: Check arm-specific dropout/missingness reasons and missing-data handling and sensitivity analyses for results at 8 and 12 weeks. - Why this condition is needed: Needed to establish which selection and losses preceded completer results. - Application exceptions: Do not treat the entire difference between recruitment and completion counts as on-treatment dropout. - Remaining uncertainty: Arm-specific dropout, reasons for time-specific missingness, missing-data handling and sensitivity analyses remain unresolved. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N20 · Are random sequence, allocation concealment and baseline balance established? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The evidence table describes a double-blind randomized vitamin C-controlled trial. Random sequence, concealment procedures, baseline balance and detailed design structure are not established in the current summary. - Why unverified: A randomized comparison is reported, but the actual allocation process remains unresolved. - Reason for missing information: Methods and baseline tables to establish sequence generation, allocation concealment, baseline balance and detailed design structure remain missing. - Required materials and conditions: Design, random sequence, allocation concealment in Methods and baseline tables. - Materials to obtain first: Design, random sequence, allocation concealment in Methods and baseline tables. - Further research: Compare allocation methods and baseline tables to examine allocation risk and balance beyond the randomized-trial label in the title. - Conditions for verification: Check actual randomization method, concealment, baseline balance and design structure. - Why this condition is needed: The randomized label alone does not establish that allocation concerns are resolved. - Application exceptions: Unverified sequence/concealment does not establish failed randomization; do not assign crossover/cluster NA without evidence. - Remaining uncertainty: Methods and baseline tables to establish sequence generation, allocation concealment, baseline balance and detailed design structure remain missing. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N21 · Is blinding for diary completion/assessment and comparator tablets established? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Double blinding is reported. Who was blinded, whether tablet appearance/sensory features matched, and diary assessment or unblinding remain unverified. - Why unverified: The blinding label is known, but actual procedures and effects on measurement remain unresolved. - Reason for missing information: Participant, assessor and analyst blinding, tablet matching, unblinding/awareness and diary assessment procedures remain unresolved. - Required materials and conditions: Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records. - Materials to obtain first: Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records. - Further research: Compare collection of the subjective diary endpoint with blinding procedures for both tablets to examine potential measurement differences. - Conditions for verification: Check participant, assessor and analyst blinding, matching of comparator tablets and any unblinding. - Why this condition is needed: The double-blind label alone does not establish that measurement differences in subjective diarrhea records disappeared. - Application exceptions: The fact that the comparator was vitamin C alone establishes neither blinding failure nor success. - Remaining uncertainty: Participant, assessor and analyst blinding, tablet matching, unblinding/awareness and diary assessment procedures remain unresolved. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N22 · To what extent are time-specific P values and their testing/adjustment definitions established? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: P=.032 at 8 weeks and P=.805 at 12 weeks are retained. Exact testing, model, one-/two-sided testing, adjustment and multiplicity definitions are not established in the summary. - Why unverified: Time-specific P values are known, but direct descriptions of the tests and models remain unresolved. - Reason for missing information: The target, model, one-/two-sided testing and adjustment for each P, and multiplicity handling for joint endpoints remain unresolved. - Required materials and conditions: Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling. - Materials to obtain first: Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling. - Further research: Compare Methods with result notes to examine whether P concerns a between-arm comparison and how it relates to repeated measurement, adjustment and multiple endpoints. - Conditions for verification: Check separately the reported P=.032 at 8 weeks and P=.805 at 12 weeks, their time points and the extent of verification of testing target, one-/two-sided testing, repeated measurement/adjustment and multiplicity handling. A P string does not establish the test definition. - Why this condition is needed: Needed to avoid using a P string as a substitute for precision or clinical importance. - Application exceptions: Do not newly calculate significance/nonsignificance or interpret it as an equivalence test. - Remaining uncertainty: The target, model, one-/two-sided testing and adjustment for each P, and multiplicity handling for joint endpoints remain unresolved. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N23 · Are the between-arm effect at 8 weeks and 95% CI directly reported? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The reader answer states that a 95% CI is absent. The current retained summary does not connect an exact between-arm effect estimate at 8 weeks, CI, dispersion type and analysis n. - Why unverified: Exact effect-interval material beyond reported arm values and P is unavailable. - Reason for missing information: A directly reported estimate and 95% CI for the effect of interest, with dispersion type, denominator and model for interpretation, remain missing. This is unverified within the current material scope. - Required materials and conditions: The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model. - Materials to obtain first: The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model. - Further research: Compare original result tables, estimate definitions, dispersion and analysis n to examine reported interval scope. Do not reconstruct a new CI from arm values. - Conditions for verification: Check the original estimate, 95% CI, dispersion and denominator for the effect of interest at 8 weeks. - Why this condition is needed: Significance and arm values alone do not reveal the effect interval. - Application exceptions: Do not subtract printed arm values to create a new effect difference or NNT. - Remaining uncertainty: A directly reported estimate and 95% CI for the effect of interest, with dispersion type, denominator and model for interpretation, remain missing. This is unverified within the current material scope. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N24 · Is a threshold for an important difference in diarrhea frequency justified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The manuscript explains that the immediate end-of-treatment signal may matter, but direct support for a prospective minimum important difference or responder threshold is absent. - Why unverified: Direct information for examining the relationship between patient importance thresholds and reported values is unavailable. - Reason for missing information: A patient-important frequency difference, responder threshold and prospective basis remain unresolved. An opinion that it may matter is not an established threshold. - Required materials and conditions: A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis. - Materials to obtain first: A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis. - Further research: Compare defined important differences and responder thresholds with original results to distinguish a statistical signal from patient-important improvement. - Conditions for verification: Check patient-important differences, responder thresholds and prospective support for this IBS-D endpoint. - Why this condition is needed: Needed to avoid establishing clinically sufficient benefit from P=.032 alone. - Application exceptions: Do not invent minimum participant counts, duration, effect size or proportion-of-conditions-met thresholds. - Remaining uncertainty: A patient-important frequency difference, responder threshold and prospective basis remain unresolved. An opinion that it may matter is not an established threshold. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N25 · Are trial registration, protocol and analysis plan established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The evidence registration field says not established. Original registration, protocol and SAP identity, content and versions are absent from the current retained summary, and external registration was not queried here. - Why unverified: Registration, protocol and SAP for actual plan-versus-report comparison are unavailable. - Reason for missing information: Registration identity, original registration, protocol, SAP and dates/versions remain missing. This does not establish absent registration or selective reporting. - Required materials and conditions: Trial registration identifier, original registration, protocol, SAP and versions/dates. - Materials to obtain first: Trial registration identifier, original registration, protocol, SAP and versions/dates. - Further research: Connect the paper’s identity with registration, protocol and SAP to compare prospective recruitment, joint endpoints, analyses and timing with reports. - Conditions for verification: Directly compare registration identity and the prospective protocol/SAP for this report. - Why this condition is needed: Needed to reveal which material is required to examine favorable-result selection. - Application exceptions: Do not convert an unestablished registration field into confirmed nonregistration or 0 registration identifiers. - Remaining uncertainty: Registration identity, original registration, protocol, SAP and dates/versions remain missing. This does not establish absent registration or selective reporting. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N26 · Is prospective-plan agreement for assessments and analyses at 8 and 12 weeks established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Treatment for 8 weeks, follow-up for 4 weeks off treatment and results at both time points are known. Documents for comparing those time points and analyses with the prospective plan are unavailable. - Why unverified: The reported schedule alone cannot establish agreement with the prospective plan. - Reason for missing information: Planned assessments/analyses at 8 and 12 weeks, report agreement and reasons for changes remain unresolved. - Required materials and conditions: Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes. - Materials to obtain first: Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes. - Further research: Compare planned visit, endpoint and analysis schedules with reported results and check for timing changes or additional analyses. - Conditions for verification: Check agreement between prospective plans and reports for end-of-treatment/off-treatment timing and the corresponding analyses. - Why this condition is needed: Knowing the nominal duration differs from agreement with a prospective plan. - Application exceptions: Unverified timing plans do not establish post hoc analysis. - Remaining uncertainty: Planned assessments/analyses at 8 and 12 weeks, report agreement and reasons for changes remain unresolved. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N27 · Were evidence and bibliographic descriptions of the same paper counted without duplication? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The current 1 evidence entry and 1 citation connect to the same Chen 2015 report, PMID 26400188, DOI 10.1002/ptr.5475. PMID and DOI entry points are not separate trials. - Why unverified: The single report’s attribution in the current retained summary was connected without creating additional independent trial counts. - Reason for missing information: The current evidence/bibliography connection to the same report was checked. Other reports, registration, unique participant relationships and total independent trial counts remain unverified. - Required materials and conditions: Report title, PMID, DOI, evidence/citation links, trial family and participant relationships. - Materials to obtain first: Report title, PMID, DOI, evidence/citation links, trial family and participant relationships. - Further research: Connect titles, identifiers and results to check whether evidence-table, citation and PMID/DOI entries concern one report, and separately compare family identity for later material. - Conditions for verification: Connect the same report in the corresponding evidence and citation entries without counting external identifier entry points as additional trials. - Why this condition is needed: Needed to avoid counting bibliography, abstract and paper links as multiple independent trials. - Application exceptions: Connecting one report does not establish a worldwide unique trial count of 1. - Remaining uncertainty: The current evidence/bibliography connection to the same report was checked. Other reports, registration, unique participant relationships and total independent trial counts remain unverified. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N28 · Is independent replication of the same question established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The current retained summary connects only one report for this question. Material to establish the same diarrhea comparison at 8 weeks in other independent unique trials is unavailable. - Why unverified: Report/family material needed to establish independent replication of the same question has not been acquired. - Reason for missing information: Independent replication and overall unique trial/participant relationships remain unresolved. No new literature search was performed, so this does not establish an absence of research. - Required materials and conditions: Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links. - Materials to obtain first: Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links. - Further research: Compare trial-specific eligibility and family links to examine independent result distributions, contrary results and condition differences. - Conditions for verification: Check the same formulation, population, comparator, diarrhea result at 8 weeks and family relationships in other unique trials. - Why this condition is needed: Needed to avoid extending one report’s result into independent confirmation. - Application exceptions: No new search and 1 linked report do not establish an absence of independent research. - Remaining uncertainty: Independent replication and overall unique trial/participant relationships remain unresolved. No new literature search was performed, so this does not establish an absence of research. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N29 · What was actually read, and what date scope is being described? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The complete retained summary was read here. The evidence reference date is 2026-09-08; historical wording describes checking original PDF tables/methods against the abstract. Current PubMed, DOI and original PDF access, acquisition and reading were not attempted. - Why unverified: Current local reading, historical descriptions and external unread status were recorded separately. - Reason for missing information: The reading scope of the retained summary was checked. Material-specific historical access dates, current external responses/full text, the latest complete literature and publication status were not checked. - Required materials and conditions: Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records. - Materials to obtain first: Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records. - Further research: Compare the access ledger with original material locations to distinguish summary versus external full-text reading and historical descriptions versus new actions, checking the scope of unverified wording. - Conditions for verification: Distinguish complete reading of the retained summary from historical PDF-review descriptions and current unattempted/unread external material, with dates. - Why this condition is needed: Needed to avoid overstating local-summary reading as new full-text reading or a current exhaustive search. - Application exceptions: Do not fill material-specific access dates from the global original-verdict review date or describe unattempted access as failed access. - Remaining uncertainty: The reading scope of the retained summary was checked. Material-specific historical access dates, current external responses/full text, the latest complete literature and publication status were not checked. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N30 · Are funding, product support and author interests established? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The evidence funding description retains the National Natural Science Foundation of China and China–Poland cooperation support. Product provision, author employment, patents and COI declarations are not directly established. Retain the original I2 only as a historical axis. - Why unverified: Reported funding exists, but direct content on product support and declared interests remains unresolved. - Reason for missing information: Product provision, employment/patents, COI and sponsor research roles remain unresolved. Funding information alone does not establish absence of bias or independent replication. - Required materials and conditions: Funding, product provision, author employment/patents, COI declarations, institutions and roles. - Materials to obtain first: Funding, product provision, author employment/patents, COI declarations, institutions and roles. - Further research: Compare funding, product provision and author/institutional roles separately to check against unsupported conclusions of independent funding or replication. - Conditions for verification: Check reported funding, product provision, employment, patents and declared interests separately from trial family. - Why this condition is needed: An academic-support name alone does not reveal product support or conflicts of interest. - Application exceptions: Do not use the existing I2 axis as new certification of complete independence. - Remaining uncertainty: Product provision, employment/patents, COI and sponsor research roles remain unresolved. Funding information alone does not establish absence of bias or independent replication. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N31 · Are arm-specific adverse-event/discontinuation counts and collection scope established? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The manuscript warns about gastrointestinal reactions including diarrhea, constipation and abdominal pain. Arm-specific AE event/person counts, safety denominators, collection, severity and discontinuation figures for the same trial are absent from the current retained summary. - Why unverified: Warning descriptions do not substitute for quantitative harm counts or collection scope in the actual trial. - Reason for missing information: AE events/persons, safety denominators, collection, severity, discontinuation and missingness for the same trial remain unresolved. Do not convert unverified harms into 0 events or harmlessness. - Required materials and conditions: AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness. - Materials to obtain first: AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness. - Further research: Connect safety tables, collection instructions and flow to distinguish event counts from person counts, exposure denominators, discontinuation reasons and missingness. - Conditions for verification: Check adverse-event events/persons, exposure denominators, collection, severity, discontinuation and missingness in the same trial. - Why this condition is needed: Needed to avoid converting the existence of efficacy reports into no harms or completed safety accounting. - Application exceptions: Do not delete efficacy results because harms are unreported or infer events/denominators. - Remaining uncertainty: AE events/persons, safety denominators, collection, severity, discontinuation and missingness for the same trial remain unresolved. Do not convert unverified harms into 0 events or harmlessness. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N32 · Can adverse reactions such as diarrhea be distinguished from IBS symptoms by timing and comparison? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The safety description warns that gastrointestinal reactions such as diarrhea, constipation and abdominal pain may confuse intervention effects with disease symptoms. Onset/worsening timing, arm-specific harm comparisons, stopping/recovery and other causes are not established. - Why unverified: The original warning alone cannot establish time/comparison attribution separating baseline IBS symptoms from intervention-related harms. - Reason for missing information: Baseline symptoms, new onset/worsening, arm-specific comparisons, stopping/recovery and concurrent exposures remain unresolved. Do not reinterpret the diarrhea result at 12 weeks as a harm dechallenge signal. - Required materials and conditions: Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures. - Materials to obtain first: Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures. - Further research: Compare symptom/administration timelines, arm-specific harms and alternative exposures to distinguish disease from intervention-related signals and examine limits on causal/risk interpretation. - Conditions for verification: Check baseline IBS symptoms, onset/worsening after dosing, stopping/recovery, arm-specific comparisons and alternative exposures. - Why this condition is needed: Needed to avoid merging IBS-D diarrhea and intervention-related gastrointestinal reactions into the same event. - Application exceptions: Reporting after exposure alone does not establish causality; do not infer that changes in diarrhea frequency after stopping represent AE recovery. - Remaining uncertainty: Baseline symptoms, new onset/worsening, arm-specific comparisons, stopping/recovery and concurrent exposures remain unresolved. Do not reinterpret the diarrhea result at 12 weeks as a harm dechallenge signal. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N33 · Is safety material available for pregnancy, lactation, infants and young children, concomitant drugs and long-term use? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The manuscript retains cautions to avoid use or check with clinicians concerning pregnancy, lactation, infants and young children, and CYP-related concomitant drugs. Direct material on vulnerable groups, interactions and long-term/rare harms is absent from current inputs. - Why unverified: Warnings are retained, but direct information to establish risks for those groups, concomitant use and long-term exposure is unavailable. - Reason for missing information: Direct information on vulnerable groups, drug interactions and long-term/rare harms remains unresolved. Do not create personal dosing instructions or a new safety grade. - Required materials and conditions: Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms. - Materials to obtain first: Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms. - Further research: Review safety material and drug-interaction evidence separately by exposure/population without extending a short-term adult efficacy trial into overall safety. - Conditions for verification: Check direct material on vulnerable groups, interactions and long-term/rare harms and the applicability limits of original warnings. - Why this condition is needed: Results in a limited adult population and duration cannot guarantee safety in vulnerable groups or long-term use. - Application exceptions: Do not require every rare-harm study as a condition for checking diarrhea efficacy at 8 weeks. - Remaining uncertainty: Direct information on vulnerable groups, drug interactions and long-term/rare harms remains unresolved. Do not create personal dosing instructions or a new safety grade. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N34 · Does this question require an optimal dose or effects in specific subgroups? Verification status: Not applicable Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The current question concerns 400 mg/day for 8 weeks in adults with Rome III IBS-D. There is no separate original question claiming an optimal dose or superiority in a specific subgroup. - Why unverified: Dose optimization and specific subgroup extensions are not requirements of the current question. - Reason for missing information: Dose/subgroup-extension requirements are not applicable to the current question. Extension would separately require direct comparison and prospective interaction material. - Required materials and conditions: For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results. - Materials to obtain first: For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results. - Further research: When proposing dose/subgroup extensions, design separate questions using direct comparisons and prospective interaction material without merging them into the current principal effect. - Conditions for verification: Distinguish the narrow question of 400 mg/day in adults with Rome III IBS-D from separate dose/subgroup-extension requirements. - Why this condition is needed: Needed to avoid converting a principal effect at one dose into an optimal dose or a specific subgroup effect. - Application exceptions: Do not add optimal-dose or all-subgroup research requirements to the current narrow question. - Remaining uncertainty: Dose/subgroup-extension requirements are not applicable to the current question. Extension would separately require direct comparison and prospective interaction material. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N35 · Does this cover cure, relapse, pain and quality of life beyond diarrhea frequency? Verification status: Not applicable Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The manuscript specifies that the same effect cannot be extended to IBS cure, relapse prevention, microbiome normalization, pain or quality of life. This sheet also addresses diarrhea frequency alone. - Why unverified: Separate clinical/mechanistic extensions are outside the current principal question. - Reason for missing information: Extension requirements are not applicable to the current diarrhea-frequency question. This does not establish sufficient direct evidence for other outcomes. - Required materials and conditions: For extensions: each separate endpoint’s definition, population, duration, comparison and direct results. - Materials to obtain first: For extensions: each separate endpoint’s definition, population, duration, comparison and direct results. - Further research: Design separate questions, measurements and follow-up for each endpoint to examine that a diarrhea-frequency signal does not replace conclusions about cure, relapse, mechanism or quality of life. - Conditions for verification: Distinguish weekly diarrhea frequency from cure, relapse prevention, microbiome normalization, pain and quality of life. - Why this condition is needed: Patient-experienced diarrhea frequency and other clinical/mechanistic outcomes are not the same effect. - Application exceptions: Do not require other clinical-event trials as conditions for checking weekly diarrhea frequency itself. - Remaining uncertainty: Extension requirements are not applicable to the current diarrhea-frequency question. This does not establish sufficient direct evidence for other outcomes. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N36 · Does this scope produce pooled results across studies or repeated harm signals? Verification status: Not applicable Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The current evidence/citation concerns one report, and both time points are results from that report. No pooled across-study estimate or repeated harm signal is produced; total unique trial count remains unrecorded. - Why unverified: Pooling across studies and repeated-harm claims are outside this sheet’s output scope. - Reason for missing information: Pooling/repeated-harm production is not applicable within the current scope. Other material and unique family relationships remain unverified without creating new independent counts. - Required materials and conditions: For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships. - Materials to obtain first: For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships. - Further research: If multiple materials are added, separately examine suitability for pooling and repeated signals after comparing unique families, condition differences, contrary results and recitation. - Conditions for verification: Do not create across-study pooling or repeated harms from one linked report; distinguish unverified family relationships from scope nonapplicability. - Why this condition is needed: Needed to avoid counting multiple time points/links in one report as across-study replication or repeated harms. - Application exceptions: Do not convert nonapplicability of current pooling into a finding of no independent research. Independent replication remains separately unverified. - Remaining uncertainty: Pooling/repeated-harm production is not applicable within the current scope. Other material and unique family relationships remain unverified without creating new independent counts. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N37 · Were the scope of the internal English correction and remaining generic wording distinguished? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The 2026-09-14 correction was an internal event changing 1 generic English evidence-table field while retaining grade, score, citation and verdict date. Several current generic English evidence/citation statements are not used as additional facts. - Why unverified: The current bilingual input and correction scope were read, retaining original types, empty values and absence. - Reason for missing information: The scope of the current internal correction and generic wording was checked. Old separate manuscripts, original PDF and current publication-correction status were not newly checked. - Required materials and conditions: The correction event, current original Korean/English correspondence, original field types, absent keys and empty values. - Materials to obtain first: The correction event, current original Korean/English correspondence, original field types, absent keys and empty values. - Further research: Compare the correction event with current bilingual fields to check that generic English verification wording is not read as new participant, funding or analysis facts. - Conditions for verification: Retain the scope of the 2026-09-14 internal English wording correction and current generic English wording, empty fields and absent keys. - Why this condition is needed: Needed to avoid inheriting a wording correction as new clinical verification or added content. - Application exceptions: A correction record describing one field change does not establish that all current generic wording has become specific. - Remaining uncertainty: The scope of the current internal correction and generic wording was checked. Old separate manuscripts, original PDF and current publication-correction status were not newly checked. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ### N38 · Were the existing grade, score and axes distinguished from this sheet review? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Retain the original C 50, Warning and B/P/R1/I2/EX/B2/CX, coprimary_split=true and all other original flags. Current work converts retained content and performs self-review; it is not a new clinical assessment, calculation or independent certification. - Why unverified: Original verdict fields and sheet states were separated without changing the original. - Reason for missing information: Preservation of the original verdict, score and axes was checked. Sheet states do not newly certify the original efficacy grade or clinical sufficiency. - Required materials and conditions: The original grade, score, safety, axes, grade decision and current review scope. - Materials to obtain first: The original grade, score, safety, axes, grade decision and current review scope. - Further research: Compare original fields with sheet states to check that historical verdicts, null wording and Codex cross-check descriptions are not upgraded into current reassessment or specialist certification. - Conditions for verification: Retain original C 50, Warning and axes/flags as preserved original information without converting them into a new sheet completion proportion, grade or clinical certification. - Why this condition is needed: The original verdict and verification states for producing an evidence-gap sheet are different information. - Application exceptions: Do not use original I2, EX, CX, coprimary_split or historical cross-check wording as evidence of new clinical validation. - Remaining uncertainty: Preservation of the original verdict, score and axes was checked. Sheet states do not newly certify the original efficacy grade or clinical sufficiency. - Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application. - Related sources: S01 ## Evidence and sources ### S01 A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome [PubMed](https://pubmed.ncbi.nlm.nih.gov/26400188/) Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Week 8: 1.39±0.80 versus 3.55±0.66, P=.032; week 12: 3.58±0.73 versus 3.81±0.54, P=.805. Retain conflicting reports of 196 recruited, 164 or 132 randomized, and 132 completing (70/62). Separate 8 weeks of treatment from the result after 4 weeks off treatment; the meaning of ±, analysis n, CI, model and prospective co-primary hierarchy remain unverified. Record level: Time-specific arm values reported in the retained summary. The external paper was not directly read and no new effect difference or CI was calculated in this work. Independent replication: The retained set contains 1 report linked to PMID 26400188 and DOI 10.1002/ptr.5475. The week 8/week 12 results and PubMed/DOI entry points are not counted as independent trials. Unique study and participant totals and independent replication counts remain unverified. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | PubMed bibliographic/abstract index entry | URL string retained; current response unverified | External access not attempted; not acquired | Not read | Current access, acquisition and reading of this material were not attempted. The historical PDF-review description is not inherited as this material’s access date or level. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted. | | DOI identifier entry | Constructed from a bibliographic identifier; current response unverified | External access not attempted; not acquired | Not read | Current access, acquisition and reading of this material were not attempted. The historical PDF-review description is not inherited as this material’s access date or level. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted. | | Paper PDF full text described in historical review | Historical review description retained; current file not acquired | External access not attempted; not acquired | Not read | The historical description of checking PDF tables and methods was retained, but no current PDF file or URL was acquired or read. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted. | | Retained bilingual bibliographic, evidence and manuscript summary | Retained copy acquired; summary read | Retained copy acquired; summary read | Stored existing review summary read | The material actually read here was the retained complete Korean/English summary. This does not establish reading of external full text. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Link studies and reports separately; do not omit studies solely because results are unreported. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Fix the result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. ## What the statuses mean - Met: The row’s narrow record, attribution, boundary or actual fact was checked. This does not certify efficacy, precision or safety. - Partly verified: Some required information is available, but actual exposure, definitions, denominators or other necessary material remain missing. - Unverified: The criterion cannot be established within the retained scope. This does not mean 0 effect, 0 studies or failed access. - Not applicable: The condition has no applicable subject within the current retained set and narrow question. This does not replace a material gap or unread status. - Review incomplete: A status for external original-material comparison not yet performed, distinguished from review of locally retained content. - Not applicable (alias): The condition has no applicable subject within the current retained set and narrow question. This does not replace a material gap or unread status. - Conflicting data: Participant reports for the same concept conflict, so no single value was selected. This is distinct from differences in results at different time points. - Not read: The material was not directly read in the current work. This is distinct from not reported, inaccessible or no research. ## Change history 2026-10-27 · Public page/materials 1.0. The public view and materials were prepared from the existing 38 items. No new clinical search, verification-state change or scoring was performed.