{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3071-main", "verdict_number": "3071", "title": "Berberine hydrochloride tablets × Reduced weekly diarrhea frequency in diarrhea-predominant irritable bowel syndrome", "view_version": "1.0", "view_created_date": "2026-10-27", "criteria_version": "1.1", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-08", "review_scope": { "materials_read": "Retained Korean/English summaries and case-specific condition/application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Prepared from retained summaries and condition-application records. External abstracts, full texts, registration, protocols and analysis plans remain unread. Historical review records do not establish current independent clinical validation.", "date_meaning": "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." }, "claim_context": { "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.", "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.", "endpoint": "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.", "intervention": "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.", "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.", "excluded_extensions": [ "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." ] }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Which IBS-D diarrhea-frequency question is addressed?", "needed": "The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL.", "role": "Required", "role_reason": "Needed to distinguish an ingredient-wide effect from a particular comparison and time point.", "application_exception": "The original subclaim list is empty. Do not invent subclaims or expand every combination of dimensions into a separate sheet.", "criterion": "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.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "The original claim and claim conditions link intervention, population, comparator and endpoint, establishing the identity of this sheet.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Do the actual ingredient and tablet formulation match this question?", "needed": "The formulation name, composition, dosage form and reasons for including or excluding other products.", "role": "Required", "role_reason": "The same berberine name does not establish the same exposure.", "application_exception": "Unverified plant source or excipients do not establish that this was a different formulation.", "criterion": "Distinguish the berberine hydrochloride tablets in the material from plant extracts, other derivatives, combinations and topical products.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare product composition with Methods to distinguish whether results for berberine hydrochloride tablets can be transferred to other extracts, derivatives or combinations.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "The labeled ingredient and dosage form were checked in the retained material, with other products excluded.", "missingness": "The labeled ingredient and dosage form were checked. Manufacturing source and complete excipients remain unverified in a separate item.", "uncertainty": "The labeled ingredient and dosage form were checked. Manufacturing source and complete excipients remain unverified in a separate item.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The formulation name, composition, dosage form and reasons for including or excluding other products." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "To what extent are the experimental tablet’s labeled ingredient and dosage form, source, manufacturer and excipients established?", "needed": "The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records.", "role": "Required", "role_reason": "Product identity beyond the ingredient name is needed to explain whether the experimental exposure is the same.", "application_exception": "Do not convert an unverified source into a specific plant species or the presence of product impurities.", "criterion": "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.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the original product description and supply records to separate the labeled hydrochloride amount from complete product composition and origin.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "The tablet ingredient is known, but source, manufacture and complete composition have not been established.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Are route, nominal dose and dosing frequency specified?", "needed": "Route, labeled tablet amount, dosing frequency and nominal daily dose.", "role": "Required", "role_reason": "Needed to avoid substituting results from another product or dose for the nominal regimen.", "application_exception": "Do not interpret nominal 400 mg/day as actual adherent intake or blood exposure.", "criterion": "Directly connect the nominal oral regimen of 200 mg 2 times daily, 400 mg/day.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare administration instructions with formulation labeling to check for results from different doses or routes being mixed in.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "Route and nominal administration information are directly present in the retained material.", "missingness": "Nominal route, dose and frequency were checked. Actual consumption and adherence are gaps in the next condition.", "uncertainty": "Nominal route, dose and frequency were checked. Actual consumption and adherence are gaps in the next condition.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Route, labeled tablet amount, dosing frequency and nominal daily dose." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "Can actual intake, adherence and rescue treatment be established?", "needed": "Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records.", "role": "Required", "role_reason": "Assigned administration instructions alone do not establish equal actual exposure.", "application_exception": "Unverified adherence does not establish nonadherence or an incorrect nominal dose.", "criterion": "Check how arm-specific intake, adherence, drug discontinuation and rescue treatment affected the comparison at 8 weeks.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare nominal dose with actual dosing records and examine the effect of interest and analysis accounting for discontinuation and rescue treatment.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Data on actual intake and treatment changes beyond the administration plan are unavailable.", "missingness": "Actual intake, adherence, rescue treatment and analytical handling of drug discontinuation remain missing.", "uncertainty": "Actual intake, adherence, rescue treatment and analytical handling of drug discontinuation remain missing.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "Is the eligibility scope for adults with Rome III IBS-D established?", "needed": "Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics.", "role": "Required", "role_reason": "The same diarrhea symptoms do not establish the same diagnosis or selection process.", "application_exception": "Unverified detailed selection does not establish no effect in other IBS types.", "criterion": "Check age, severity, eligibility and recruitment setting of the diagnosed population without extending to general diarrhea or all IBS.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Diagnosis and the adult population are known, but detailed selection and representativeness remain unresolved.", "missingness": "Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain missing, preventing extension to general diarrhea or all IBS.", "uncertainty": "Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain missing, preventing extension to general diarrhea or all IBS.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "What did the comparator arm actually receive?", "needed": "The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording.", "role": "Required", "role_reason": "Hiding the actual comparator ingredient changes the meaning of the comparative effect.", "application_exception": "Do not automatically judge the vitamin C comparator identical to an inert placebo or equivalent treatment to berberine.", "criterion": "Distinguish that the actual comparator called placebo in the paper was vitamin C tablets 400 mg/day.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Review comparator formulation descriptions to distinguish the actual vitamin C comparison from assumptions of an inert control, and check administration differences between arms.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "The actual comparator was vitamin C tablets 400 mg/day. The manuscript’s key explanation emphasizes that the paper’s placebo was vitamin C.", "condition_status": "Met", "status_reason": "The distinction between actual ingredient/nominal dose and placebo wording is directly specified.", "missingness": "The actual comparator ingredient and dose were checked. This does not establish appearance, sensory matching or biological inertness of the comparator tablet.", "uncertainty": "The actual comparator ingredient and dose were checked. This does not establish appearance, sensory matching or biological inertness of the comparator tablet.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Are concomitant medication, diet and lifestyle changes in both arms established?", "needed": "Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling.", "role": "Required", "role_reason": "Needed to avoid attributing differences in other treatments or behavior to berberine.", "application_exception": "Do not require all changes to be identical or fill unverified information with an absence of cointerventions.", "criterion": "Check how arm-specific concomitant treatment, diet, lifestyle interventions and rescue treatment during 8 weeks were handled in the actual comparison and analysis.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare arm-specific cointervention and change timelines to examine whether factors beyond berberine versus vitamin C were mixed into the results.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "The retained material specifies berberine versus vitamin C but does not present arm-specific information on concomitant medication, diet, lifestyle changes or rescue treatment.", "condition_status": "Unverified", "status_reason": "Direct information for reviewing actual cointerventions and arm-specific changes is unavailable.", "missingness": "Arm-specific concomitant medication, diet, lifestyle changes and handling of changes/rescue treatment in the results remain missing.", "uncertainty": "Arm-specific concomitant medication, diet, lifestyle changes and handling of changes/rescue treatment in the results remain missing.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Can 8 weeks of treatment be distinguished from 4 weeks of off-treatment follow-up?", "needed": "Administration, discontinuation and assessment schedules and results at each time point.", "role": "Required", "role_reason": "Needed to avoid transferring the end-of-treatment result into a sustained effect.", "application_exception": "Differences in results at different time points do not constitute a numerical conflict at the same time point.", "criterion": "Distinguish the end of 8 weeks of administration from assessment at week 12 after a further 4 weeks off treatment, without merging time points.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare the time-point table to identify which results belong to on-treatment versus off-treatment observations.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "The nominal treatment/off-treatment follow-up and the two result time points are connected in the retained material.", "missingness": "Nominal time-point separation was checked. Actual visit schedules by arm, time-specific observation denominators and prospective schedules remain separate gaps.", "uncertainty": "Nominal time-point separation was checked. Actual visit schedules by arm, time-specific observation denominators and prospective schedules remain separate gaps.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Administration, discontinuation and assessment schedules and results at each time point." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "Are the diarrhea-diary event definition and collection procedures established?", "needed": "Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries.", "role": "Required", "role_reason": "The definition and collection of patient-recorded diarrhea frequency must be distinguished from the actual effect.", "application_exception": "The description as a direct patient-experienced endpoint does not certify a validated diary or complete measurement.", "criterion": "Check the event definition for weekly diarrhea episodes, aggregation period, diary completion, missing-entry handling and scale direction.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare diary forms and measurement instructions to examine how diarrhea episodes differ from bowel movements, urgency and pain.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Diary use and weekly frequency are known, but actual measurement procedures remain unresolved.", "missingness": "Diarrhea event definition and diary collection, aggregation and missing-data handling remain unresolved. Urgency and pain values are not substitutes for this endpoint.", "uncertainty": "Diarrhea event definition and diary collection, aggregation and missing-data handling remain unresolved. Urgency and pain values are not substitutes for this endpoint.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "Is the prospective co-primary hierarchy for diarrhea and urgency established?", "needed": "Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP.", "role": "Required", "role_reason": "Needed to avoid extending a favorable diarrhea result alone into success for all co-primary endpoints.", "application_exception": "Do not interpret the coprimary_split flag as definitive proof of a plan violation or selective reporting.", "criterion": "Check diarrhea/urgency status and handling of multiple testing and selective reporting in the prospective plan.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare plans and reports to examine whether selecting diarrhea alone matches the prospective hierarchy and whether separate urgency reporting is missing.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "The manuscript states that diarrhea and urgency were tracked together but the exact prospective co-primary hierarchy was unclear, retaining coprimary_split=true.", "condition_status": "Unverified", "status_reason": "Material on the actual prospective co-primary hierarchy and multiplicity handling is not established.", "missingness": "Prospective endpoint status for diarrhea/urgency, testing order, multiplicity handling and the basis for result selection remain unresolved.", "uncertainty": "Prospective endpoint status for diarrhea/urgency, testing order, multiplicity handling and the basis for result selection remain unresolved.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "Are the arm-specific weekly diarrhea values at 8 weeks connected?", "needed": "Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point.", "role": "Required", "role_reason": "Needed to avoid transferring retained figures to another endpoint or an off-treatment result.", "application_exception": "The meaning of ±, actual analysis denominator, between-arm difference and CI are separate conditions from checking these arm values.", "criterion": "Connect the reported weekly diarrhea values, printed ± values and P for berberine and vitamin C at 8 weeks to that time point.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "Arm values and P at 8 weeks are directly present in the evidence table and citation. No new effect difference was created.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Was the off-treatment result at 12 weeks preserved separately?", "needed": "Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules.", "role": "Required", "role_reason": "Needed to avoid retaining only the favorable result at 8 weeks and presenting sustained benefit.", "application_exception": "Retain the manuscript’s null/no-difference wording as historical description. Do not newly judge P=.805 as exact 0 effect or equivalence.", "criterion": "Retain arm values and P at 12 weeks after 4 weeks off treatment without converting nonsignificance into 0 effect or equivalence.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "The original off-treatment values and unfavorable persistence result were retained and distinguished from values at 8 weeks.", "missingness": "Original off-treatment values and nonsignificance wording were checked. Exact effect difference, interval, equivalence, individual relapse and long-term persistence are not established.", "uncertainty": "Original off-treatment values and nonsignificance wording were checked. Exact effect difference, interval, equivalence, individual relapse and long-term persistence are not established.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "Are arm values final values or changes, and are baseline data available?", "needed": "Baseline diarrhea, original table headings at each time point, statistical summary type and change definition.", "role": "Required", "role_reason": "The same number can address different questions as final frequency versus change from baseline.", "application_exception": "If baseline values are absent from the current summary, do not subtract time-point values to fill in a change.", "criterion": "Check statistical summary type, final value/change and baseline diarrhea data at each time point.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare baseline and result tables to verify analysis definitions without substituting final values, changes and within-arm changes for one another.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Time-specific figures alone cannot establish the original analysis’s value definition or change from baseline.", "missingness": "Baseline diarrhea frequency and definitions of final value/change and mean/other summary type remain unresolved.", "uncertainty": "Baseline diarrhea frequency and definitions of final value/change and mean/other summary type remain unresolved.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Baseline diarrhea, original table headings at each time point, statistical summary type and change definition." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Are the analysis population, adjustment and effect of interest at 8 weeks established?", "needed": "Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models.", "role": "Required", "role_reason": "Needed to avoid converting completers into the analysis population for the assignment effect.", "application_exception": "The manuscript’s assessment as completer data does not establish a formal PP analysis or arm-specific analysis n.", "criterion": "Check assignment/adherence effects, ITT/PP, analysis population, adjustment and the actual between-arm analysis definition.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Plan and analysis information specifying the actual analysis population and effect of interest is unavailable.", "missingness": "The analysis population at 8 weeks, ITT/PP definitions, adjustment model and connection to assignment or adherence effects remain unresolved.", "uncertainty": "The analysis population at 8 weeks, ITT/PP definitions, adjustment model and connection to assignment or adherence effects remain unresolved.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "Is it established whether ± values are SD or SE?", "needed": "Original table legend, SD/SE definitions, analysis n for each value and measurement units.", "role": "Required", "role_reason": "The ± string alone cannot support calculation of dispersion or precision.", "application_exception": "Do not convert ± into CI or infer SD/SE to create a new interval.", "criterion": "Use the original table legend to establish which dispersion/error statistic the printed ± values at 8 and 12 weeks represent.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare table legends with Methods to distinguish SD, SE and other error expressions, checking only the meaning of reported statistics.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "The retained printed values lack a legend identifying SD, SE or another dispersion type.", "missingness": "Whether each ± value is SD/SE, the analysis denominator and original table legend remain unresolved; do not use them to calculate a new CI.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original table legend, SD/SE definitions, analysis n for each value and measurement units." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "Do recruitment and randomization counts agree?", "needed": "CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections.", "role": "Required", "role_reason": "Needed to avoid hiding conflicting counts or using an arbitrary larger count as the analysis denominator.", "application_exception": "Do not automatically merge 196, 164 and 132 as counts for the same stage or select one as the correct answer.", "criterion": "Check recruitment flow and original report locations that could resolve inconsistent reports of 196 recruited, 164 or 132 randomized, and 132 completing.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Conflicting data", "status_reason": "Retain the manuscript’s conflict that the same randomization stage was reported as 164 or 132.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Are 70/62 completers connected to time-specific analysis denominators?", "needed": "Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks.", "role": "Required", "role_reason": "Needed to avoid inheriting completers as actual analysis denominators at both time points.", "application_exception": "Do not automatically fill analysis n at 8 or 12 weeks with the completion counts 70/62.", "criterion": "Distinguish 70 versus 62 completers from analysis n at 8 and 12 weeks and check actual denominators for each result.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Connect each results table with the flow to distinguish completer counts, time-specific observation/analysis counts and shared participants.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Arm-specific completion counts are known, but they are not connected to actual analysis denominators at both time points.", "missingness": "The exact completion stage, measurement/analysis n at 8 and 12 weeks, and arm-specific allocation counts remain missing.", "uncertainty": "The exact completion stage, measurement/analysis n at 8 and 12 weeks, and arm-specific allocation counts remain missing.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Who was lost, and how were missing diarrhea results handled?", "needed": "Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses.", "role": "Required", "role_reason": "Needed to establish which selection and losses preceded completer results.", "application_exception": "Do not treat the entire difference between recruitment and completion counts as on-treatment dropout.", "criterion": "Check arm-specific dropout/missingness reasons and missing-data handling and sensitivity analyses for results at 8 and 12 weeks.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare recruitment flow with missing diaries and examine robustness under missing-data handling and assumptions. Do not calculate a new missingness rate.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Inconsistent counts alone do not reveal actual observation losses or handling methods.", "missingness": "Arm-specific dropout, reasons for time-specific missingness, missing-data handling and sensitivity analyses remain unresolved.", "uncertainty": "Arm-specific dropout, reasons for time-specific missingness, missing-data handling and sensitivity analyses remain unresolved.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Are random sequence, allocation concealment and baseline balance established?", "needed": "Design, random sequence, allocation concealment in Methods and baseline tables.", "role": "Required", "role_reason": "The randomized label alone does not establish that allocation concerns are resolved.", "application_exception": "Unverified sequence/concealment does not establish failed randomization; do not assign crossover/cluster NA without evidence.", "criterion": "Check actual randomization method, concealment, baseline balance and design structure.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare allocation methods and baseline tables to examine allocation risk and balance beyond the randomized-trial label in the title.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "A randomized comparison is reported, but the actual allocation process remains unresolved.", "missingness": "Methods and baseline tables to establish sequence generation, allocation concealment, baseline balance and detailed design structure remain missing.", "uncertainty": "Methods and baseline tables to establish sequence generation, allocation concealment, baseline balance and detailed design structure remain missing.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Design, random sequence, allocation concealment in Methods and baseline tables." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Is blinding for diary completion/assessment and comparator tablets established?", "needed": "Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records.", "role": "Required", "role_reason": "The double-blind label alone does not establish that measurement differences in subjective diarrhea records disappeared.", "application_exception": "The fact that the comparator was vitamin C alone establishes neither blinding failure nor success.", "criterion": "Check participant, assessor and analyst blinding, matching of comparator tablets and any unblinding.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare collection of the subjective diary endpoint with blinding procedures for both tablets to examine potential measurement differences.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "Double blinding is reported. Who was blinded, whether tablet appearance/sensory features matched, and diary assessment or unblinding remain unverified.", "condition_status": "Partly verified", "status_reason": "The blinding label is known, but actual procedures and effects on measurement remain unresolved.", "missingness": "Participant, assessor and analyst blinding, tablet matching, unblinding/awareness and diary assessment procedures remain unresolved.", "uncertainty": "Participant, assessor and analyst blinding, tablet matching, unblinding/awareness and diary assessment procedures remain unresolved.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "To what extent are time-specific P values and their testing/adjustment definitions established?", "needed": "Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling.", "role": "Required", "role_reason": "Needed to avoid using a P string as a substitute for precision or clinical importance.", "application_exception": "Do not newly calculate significance/nonsignificance or interpret it as an equivalence test.", "criterion": "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.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Time-specific P values are known, but direct descriptions of the tests and models remain unresolved.", "missingness": "The target, model, one-/two-sided testing and adjustment for each P, and multiplicity handling for joint endpoints remain unresolved.", "uncertainty": "The target, model, one-/two-sided testing and adjustment for each P, and multiplicity handling for joint endpoints remain unresolved.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Are the between-arm effect at 8 weeks and 95% CI directly reported?", "needed": "The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model.", "role": "Required", "role_reason": "Significance and arm values alone do not reveal the effect interval.", "application_exception": "Do not subtract printed arm values to create a new effect difference or NNT.", "criterion": "Check the original estimate, 95% CI, dispersion and denominator for the effect of interest at 8 weeks.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Exact effect-interval material beyond reported arm values and P is unavailable.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "Is a threshold for an important difference in diarrhea frequency justified?", "needed": "A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis.", "role": "Required", "role_reason": "Needed to avoid establishing clinically sufficient benefit from P=.032 alone.", "application_exception": "Do not invent minimum participant counts, duration, effect size or proportion-of-conditions-met thresholds.", "criterion": "Check patient-important differences, responder thresholds and prospective support for this IBS-D endpoint.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare defined important differences and responder thresholds with original results to distinguish a statistical signal from patient-important improvement.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Direct information for examining the relationship between patient importance thresholds and reported values is unavailable.", "missingness": "A patient-important frequency difference, responder threshold and prospective basis remain unresolved. An opinion that it may matter is not an established threshold.", "uncertainty": "A patient-important frequency difference, responder threshold and prospective basis remain unresolved. An opinion that it may matter is not an established threshold.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Are trial registration, protocol and analysis plan established?", "needed": "Trial registration identifier, original registration, protocol, SAP and versions/dates.", "role": "Required", "role_reason": "Needed to reveal which material is required to examine favorable-result selection.", "application_exception": "Do not convert an unestablished registration field into confirmed nonregistration or 0 registration identifiers.", "criterion": "Directly compare registration identity and the prospective protocol/SAP for this report.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Connect the paper’s identity with registration, protocol and SAP to compare prospective recruitment, joint endpoints, analyses and timing with reports.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Registration, protocol and SAP for actual plan-versus-report comparison are unavailable.", "missingness": "Registration identity, original registration, protocol, SAP and dates/versions remain missing. This does not establish absent registration or selective reporting.", "uncertainty": "Registration identity, original registration, protocol, SAP and dates/versions remain missing. This does not establish absent registration or selective reporting.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial registration identifier, original registration, protocol, SAP and versions/dates." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "Is prospective-plan agreement for assessments and analyses at 8 and 12 weeks established?", "needed": "Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes.", "role": "Required", "role_reason": "Knowing the nominal duration differs from agreement with a prospective plan.", "application_exception": "Unverified timing plans do not establish post hoc analysis.", "criterion": "Check agreement between prospective plans and reports for end-of-treatment/off-treatment timing and the corresponding analyses.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare planned visit, endpoint and analysis schedules with reported results and check for timing changes or additional analyses.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "The reported schedule alone cannot establish agreement with the prospective plan.", "missingness": "Planned assessments/analyses at 8 and 12 weeks, report agreement and reasons for changes remain unresolved.", "uncertainty": "Planned assessments/analyses at 8 and 12 weeks, report agreement and reasons for changes remain unresolved.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Were evidence and bibliographic descriptions of the same paper counted without duplication?", "needed": "Report title, PMID, DOI, evidence/citation links, trial family and participant relationships.", "role": "Required", "role_reason": "Needed to avoid counting bibliography, abstract and paper links as multiple independent trials.", "application_exception": "Connecting one report does not establish a worldwide unique trial count of 1.", "criterion": "Connect the same report in the corresponding evidence and citation entries without counting external identifier entry points as additional trials.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "The single report’s attribution in the current retained summary was connected without creating additional independent trial counts.", "missingness": "The current evidence/bibliography connection to the same report was checked. Other reports, registration, unique participant relationships and total independent trial counts remain unverified.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Report title, PMID, DOI, evidence/citation links, trial family and participant relationships." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Is independent replication of the same question established?", "needed": "Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links.", "role": "Required (independent-replication claim)", "role_reason": "Needed to avoid extending one report’s result into independent confirmation.", "application_exception": "No new search and 1 linked report do not establish an absence of independent research.", "criterion": "Check the same formulation, population, comparator, diarrhea result at 8 weeks and family relationships in other unique trials.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare trial-specific eligibility and family links to examine independent result distributions, contrary results and condition differences.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Report/family material needed to establish independent replication of the same question has not been acquired.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "What was actually read, and what date scope is being described?", "needed": "Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records.", "role": "Required", "role_reason": "Needed to avoid overstating local-summary reading as new full-text reading or a current exhaustive search.", "application_exception": "Do not fill material-specific access dates from the global original-verdict review date or describe unattempted access as failed access.", "criterion": "Distinguish complete reading of the retained summary from historical PDF-review descriptions and current unattempted/unread external material, with dates.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "Current local reading, historical descriptions and external unread status were recorded separately.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Are funding, product support and author interests established?", "needed": "Funding, product provision, author employment/patents, COI declarations, institutions and roles.", "role": "Supplementary; required for independence claims", "role_reason": "An academic-support name alone does not reveal product support or conflicts of interest.", "application_exception": "Do not use the existing I2 axis as new certification of complete independence.", "criterion": "Check reported funding, product provision, employment, patents and declared interests separately from trial family.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Compare funding, product provision and author/institutional roles separately to check against unsupported conclusions of independent funding or replication.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Partly verified", "status_reason": "Reported funding exists, but direct content on product support and declared interests remains unresolved.", "missingness": "Product provision, employment/patents, COI and sponsor research roles remain unresolved. Funding information alone does not establish absence of bias or independent replication.", "uncertainty": "Product provision, employment/patents, COI and sponsor research roles remain unresolved. Funding information alone does not establish absence of bias or independent replication.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Funding, product provision, author employment/patents, COI declarations, institutions and roles." }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Are arm-specific adverse-event/discontinuation counts and collection scope established?", "needed": "AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness.", "role": "Supplementary; required for safety questions", "role_reason": "Needed to avoid converting the existence of efficacy reports into no harms or completed safety accounting.", "application_exception": "Do not delete efficacy results because harms are unreported or infer events/denominators.", "criterion": "Check adverse-event events/persons, exposure denominators, collection, severity, discontinuation and missingness in the same trial.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Connect safety tables, collection instructions and flow to distinguish event counts from person counts, exposure denominators, discontinuation reasons and missingness.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Warning descriptions do not substitute for quantitative harm counts or collection scope in the actual trial.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness." }, { "item_id": "N32", "question_type": "Evidence condition", "question": "Can adverse reactions such as diarrhea be distinguished from IBS symptoms by timing and comparison?", "needed": "Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures.", "role": "Supplementary; required for harm attribution", "role_reason": "Needed to avoid merging IBS-D diarrhea and intervention-related gastrointestinal reactions into the same event.", "application_exception": "Reporting after exposure alone does not establish causality; do not infer that changes in diarrhea frequency after stopping represent AE recovery.", "criterion": "Check baseline IBS symptoms, onset/worsening after dosing, stopping/recovery, arm-specific comparisons and alternative exposures.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "The original warning alone cannot establish time/comparison attribution separating baseline IBS symptoms from intervention-related harms.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures." }, { "item_id": "N33", "question_type": "Evidence condition", "question": "Is safety material available for pregnancy, lactation, infants and young children, concomitant drugs and long-term use?", "needed": "Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms.", "role": "Supplementary; required for the relevant safety claim", "role_reason": "Results in a limited adult population and duration cannot guarantee safety in vulnerable groups or long-term use.", "application_exception": "Do not require every rare-harm study as a condition for checking diarrhea efficacy at 8 weeks.", "criterion": "Check direct material on vulnerable groups, interactions and long-term/rare harms and the applicability limits of original warnings.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "Review safety material and drug-interaction evidence separately by exposure/population without extending a short-term adult efficacy trial into overall safety.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Unverified", "status_reason": "Warnings are retained, but direct information to establish risks for those groups, concomitant use and long-term exposure is unavailable.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms." }, { "item_id": "N34", "question_type": "Evidence condition", "question": "Does this question require an optimal dose or effects in specific subgroups?", "needed": "For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results.", "role": "Supplementary; required for dose or subgroup extensions", "role_reason": "Needed to avoid converting a principal effect at one dose into an optimal dose or a specific subgroup effect.", "application_exception": "Do not add optimal-dose or all-subgroup research requirements to the current narrow question.", "criterion": "Distinguish the narrow question of 400 mg/day in adults with Rome III IBS-D from separate dose/subgroup-extension requirements.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "When proposing dose/subgroup extensions, design separate questions using direct comparisons and prospective interaction material without merging them into the current principal effect.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Not applicable", "status_reason": "Dose optimization and specific subgroup extensions are not requirements of the current question.", "missingness": "Dose/subgroup-extension requirements are not applicable to the current question. Extension would separately require direct comparison and prospective interaction material.", "uncertainty": "Dose/subgroup-extension requirements are not applicable to the current question. Extension would separately require direct comparison and prospective interaction material.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results." }, { "item_id": "N35", "question_type": "Evidence condition", "question": "Does this cover cure, relapse, pain and quality of life beyond diarrhea frequency?", "needed": "For extensions: each separate endpoint’s definition, population, duration, comparison and direct results.", "role": "Supplementary; required for the relevant extension claim", "role_reason": "Patient-experienced diarrhea frequency and other clinical/mechanistic outcomes are not the same effect.", "application_exception": "Do not require other clinical-event trials as conditions for checking weekly diarrhea frequency itself.", "criterion": "Distinguish weekly diarrhea frequency from cure, relapse prevention, microbiome normalization, pain and quality of life.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Not applicable", "status_reason": "Separate clinical/mechanistic extensions are outside the current principal question.", "missingness": "Extension requirements are not applicable to the current diarrhea-frequency question. This does not establish sufficient direct evidence for other outcomes.", "uncertainty": "Extension requirements are not applicable to the current diarrhea-frequency question. This does not establish sufficient direct evidence for other outcomes.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "For extensions: each separate endpoint’s definition, population, duration, comparison and direct results." }, { "item_id": "N36", "question_type": "Evidence condition", "question": "Does this scope produce pooled results across studies or repeated harm signals?", "needed": "For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships.", "role": "Supplementary; required for pooled or repeated-harm claims", "role_reason": "Needed to avoid counting multiple time points/links in one report as across-study replication or repeated harms.", "application_exception": "Do not convert nonapplicability of current pooling into a finding of no independent research. Independent replication remains separately unverified.", "criterion": "Do not create across-study pooling or repeated harms from one linked report; distinguish unverified family relationships from scope nonapplicability.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_research": "If multiple materials are added, separately examine suitability for pooling and repeated signals after comparing unique families, condition differences, contrary results and recitation.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Not applicable", "status_reason": "Pooling across studies and repeated-harm claims are outside this sheet’s output scope.", "missingness": "Pooling/repeated-harm production is not applicable within the current scope. Other material and unique family relationships remain unverified without creating new independent counts.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships." }, { "item_id": "N37", "question_type": "Evidence condition", "question": "Were the scope of the internal English correction and remaining generic wording distinguished?", "needed": "The correction event, current original Korean/English correspondence, original field types, absent keys and empty values.", "role": "Required (preservation accuracy)", "role_reason": "Needed to avoid inheriting a wording correction as new clinical verification or added content.", "application_exception": "A correction record describing one field change does not establish that all current generic wording has become specific.", "criterion": "Retain the scope of the 2026-09-14 internal English wording correction and current generic English wording, empty fields and absent keys.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "The current bilingual input and correction scope were read, retaining original types, empty values and absence.", "missingness": "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.", "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.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The correction event, current original Korean/English correspondence, original field types, absent keys and empty values." }, { "item_id": "N38", "question_type": "Evidence condition", "question": "Were the existing grade, score and axes distinguished from this sheet review?", "needed": "The original grade, score, safety, axes, grade decision and current review scope.", "role": "Required (preservation accuracy)", "role_reason": "The original verdict and verification states for producing an evidence-gap sheet are different information.", "application_exception": "Do not use original I2, EX, CX, coprimary_split or historical cross-check wording as evidence of new clinical validation.", "criterion": "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.", "basis": "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.", "condition_origin": "These conditions compare berberine hydrochloride with vitamin C in adults with IBS-D and were developed with knowledge of the retained content. They were frozen before application, with historical clarification of questions and criteria also retained. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.", "proposed_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.", "current_reports": [ "S01" ], "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "observation": "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.", "condition_status": "Met", "status_reason": "Original verdict fields and sheet states were separated without changing the original.", "missingness": "Preservation of the original verdict, score and axes was checked. Sheet states do not newly certify the original efficacy grade or clinical sufficiency.", "uncertainty": "Preservation of the original verdict, score and axes was checked. Sheet states do not newly certify the original efficacy grade or clinical sufficiency.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The original grade, score, safety, axes, grade decision and current review scope." } ], "reports": [ { "report_id": "S01", "title": "A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome", "url": "https://pubmed.ncbi.nlm.nih.gov/26400188/", "report_type": "Retained summary of a double-blind randomized trial comparing berberine hydrochloride with an actual vitamin C comparator.", "existence": "Retained bilingual research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material have not been separately established.", "acquired_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.", "study_family": "A provisional study family linked to the same Chen 2015 report. Original registration, other reports and participant relationships have not been cross-checked.", "independent_replication": false, "observed_result": "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.", "result_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.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "PubMed bibliographic/abstract index entry", "public_status": "URL string retained; current response unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "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." }, { "material_type": "DOI identifier entry", "public_status": "Constructed from a bibliographic identifier; current response unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "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." }, { "material_type": "Paper PDF full text described in historical review", "public_status": "Historical review description retained; current file not acquired", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "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." }, { "material_type": "Retained bilingual bibliographic, evidence and manuscript summary", "public_status": "Retained copy acquired; summary read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "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." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/26400188/" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Link studies and reports separately; do not omit studies solely because results are unreported.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." } ], "status_dictionary": { "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." }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "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." }, "history": [ { "date": "2026-10-27", "kind": "Separation of public-facing pages and materials", "view_version": "1.0", "change": "The public view and materials were prepared from the existing 38 items. No new clinical search, verification-state change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-27" }