Berberine hydrochloride tablets × Reduced weekly diarrhea frequency in diarrhea-predominant irritable bowel syndrome

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Met	Full text not readStored summary read	N01 · Evidence conditionWhich IBS-D diarrhea-frequency question is addressed?Required	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. S01	The original claim and claim conditions link intervention, population, comparator and endpoint, establishing the identity of this sheet.	The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL.	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.
2	Met	Full text not readStored summary read	N02 · Evidence conditionDo the actual ingredient and tablet formulation match this question?Required	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. S01	The labeled ingredient and dosage form were checked in the retained material, with other products excluded.	The formulation name, composition, dosage form and reasons for including or excluding other products.	Compare product composition with Methods to distinguish whether results for berberine hydrochloride tablets can be transferred to other extracts, derivatives or combinations.
3	Partly verified	Full text not readStored summary read	N03 · Evidence conditionTo what extent are the experimental tablet’s labeled ingredient and dosage form, source, manufacturer and excipients established?Required	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. S01	The tablet ingredient is known, but source, manufacture and complete composition have not been established.	The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records.	Compare the original product description and supply records to separate the labeled hydrochloride amount from complete product composition and origin.
4	Met	Full text not readStored summary read	N04 · Evidence conditionAre route, nominal dose and dosing frequency specified?Required	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. S01	Route and nominal administration information are directly present in the retained material.	Route, labeled tablet amount, dosing frequency and nominal daily dose.	Compare administration instructions with formulation labeling to check for results from different doses or routes being mixed in.
5	Unverified	Full text not readStored summary read	N05 · Evidence conditionCan actual intake, adherence and rescue treatment be established?Required	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. S01	Data on actual intake and treatment changes beyond the administration plan are unavailable.	Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records.	Compare nominal dose with actual dosing records and examine the effect of interest and analysis accounting for discontinuation and rescue treatment.
6	Partly verified	Full text not readStored summary read	N06 · Evidence conditionIs the eligibility scope for adults with Rome III IBS-D established?Required	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. S01	Diagnosis and the adult population are known, but detailed selection and representativeness remain unresolved.	Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics.	Compare eligibility criteria and baseline tables to examine applicability to the current adult IBS-D question and differences from other diarrhea or IBS types.
7	Met	Full text not readStored summary read	N07 · Evidence conditionWhat did the comparator arm actually receive?Required	The actual comparator was vitamin C tablets 400 mg/day. The manuscript’s key explanation emphasizes that the paper’s placebo was vitamin C. S01	The distinction between actual ingredient/nominal dose and placebo wording is directly specified.	The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording.	Review comparator formulation descriptions to distinguish the actual vitamin C comparison from assumptions of an inert control, and check administration differences between arms.
8	Unverified	Full text not readStored summary read	N08 · Evidence conditionAre concomitant medication, diet and lifestyle changes in both arms established?Required	The retained material specifies berberine versus vitamin C but does not present arm-specific information on concomitant medication, diet, lifestyle changes or rescue treatment. S01	Direct information for reviewing actual cointerventions and arm-specific changes is unavailable.	Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling.	Compare arm-specific cointervention and change timelines to examine whether factors beyond berberine versus vitamin C were mixed into the results.
9	Met	Full text not readStored summary read	N09 · Evidence conditionCan 8 weeks of treatment be distinguished from 4 weeks of off-treatment follow-up?Required	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. S01	The nominal treatment/off-treatment follow-up and the two result time points are connected in the retained material.	Administration, discontinuation and assessment schedules and results at each time point.	Compare the time-point table to identify which results belong to on-treatment versus off-treatment observations.
10	Partly verified	Full text not readStored summary read	N10 · Evidence conditionAre the diarrhea-diary event definition and collection procedures established?Required	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. S01	Diary use and weekly frequency are known, but actual measurement procedures remain unresolved.	Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries.	Compare diary forms and measurement instructions to examine how diarrhea episodes differ from bowel movements, urgency and pain.
11	Unverified	Full text not readStored summary read	N11 · Evidence conditionIs the prospective co-primary hierarchy for diarrhea and urgency established?Required	The manuscript states that diarrhea and urgency were tracked together but the exact prospective co-primary hierarchy was unclear, retaining coprimary_split=true. S01	Material on the actual prospective co-primary hierarchy and multiplicity handling is not established.	Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP.	Compare plans and reports to examine whether selecting diarrhea alone matches the prospective hierarchy and whether separate urgency reporting is missing.
12	Met	Full text not readStored summary read	N12 · Evidence conditionAre the arm-specific weekly diarrhea values at 8 weeks connected?Required	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. S01	Arm values and P at 8 weeks are directly present in the evidence table and citation. No new effect difference was created.	Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point.	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.
13	Met	Full text not readStored summary read	N13 · Evidence conditionWas the off-treatment result at 12 weeks preserved separately?Required	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. S01	The original off-treatment values and unfavorable persistence result were retained and distinguished from values at 8 weeks.	Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules.	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.
14	Unverified	Full text not readStored summary read	N14 · Evidence conditionAre arm values final values or changes, and are baseline data available?Required	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. S01	Time-specific figures alone cannot establish the original analysis’s value definition or change from baseline.	Baseline diarrhea, original table headings at each time point, statistical summary type and change definition.	Compare baseline and result tables to verify analysis definitions without substituting final values, changes and within-arm changes for one another.
15	Unverified	Full text not readStored summary read	N15 · Evidence conditionAre the analysis population, adjustment and effect of interest at 8 weeks established?Required	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. S01	Plan and analysis information specifying the actual analysis population and effect of interest is unavailable.	Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models.	Compare plans with result analyses to examine whether the effect concerns all assigned participants or completers, and how adjustment and missing-data handling connect.
16	Unverified	Full text not readStored summary read	N16 · Evidence conditionIs it established whether ± values are SD or SE?Required	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. S01	The retained printed values lack a legend identifying SD, SE or another dispersion type.	Original table legend, SD/SE definitions, analysis n for each value and measurement units.	Compare table legends with Methods to distinguish SD, SE and other error expressions, checking only the meaning of reported statistics.
17	Conflicting data	Full text not readStored summary read	N17 · Evidence conditionDo recruitment and randomization counts agree?Required	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. S01	Retain the manuscript’s conflict that the same randomization stage was reported as 164 or 132.	CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections.	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.
18	Partly verified	Full text not readStored summary read	N18 · Evidence conditionAre 70/62 completers connected to time-specific analysis denominators?Required	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. S01	Arm-specific completion counts are known, but they are not connected to actual analysis denominators at both time points.	Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks.	Connect each results table with the flow to distinguish completer counts, time-specific observation/analysis counts and shared participants.
19	Unverified	Full text not readStored summary read	N19 · Evidence conditionWho was lost, and how were missing diarrhea results handled?Required	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. S01	Inconsistent counts alone do not reveal actual observation losses or handling methods.	Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses.	Compare recruitment flow with missing diaries and examine robustness under missing-data handling and assumptions. Do not calculate a new missingness rate.
20	Partly verified	Full text not readStored summary read	N20 · Evidence conditionAre random sequence, allocation concealment and baseline balance established?Required	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. S01	A randomized comparison is reported, but the actual allocation process remains unresolved.	Design, random sequence, allocation concealment in Methods and baseline tables.	Compare allocation methods and baseline tables to examine allocation risk and balance beyond the randomized-trial label in the title.
21	Partly verified	Full text not readStored summary read	N21 · Evidence conditionIs blinding for diary completion/assessment and comparator tablets established?Required	Double blinding is reported. Who was blinded, whether tablet appearance/sensory features matched, and diary assessment or unblinding remain unverified. S01	The blinding label is known, but actual procedures and effects on measurement remain unresolved.	Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records.	Compare collection of the subjective diary endpoint with blinding procedures for both tablets to examine potential measurement differences.
22	Partly verified	Full text not readStored summary read	N22 · Evidence conditionTo what extent are time-specific P values and their testing/adjustment definitions established?Required	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. S01	Time-specific P values are known, but direct descriptions of the tests and models remain unresolved.	Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling.	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.
23	Unverified	Full text not readStored summary read	N23 · Evidence conditionAre the between-arm effect at 8 weeks and 95% CI directly reported?Required	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. S01	Exact effect-interval material beyond reported arm values and P is unavailable.	The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model.	Compare original result tables, estimate definitions, dispersion and analysis n to examine reported interval scope. Do not reconstruct a new CI from arm values.
24	Unverified	Full text not readStored summary read	N24 · Evidence conditionIs a threshold for an important difference in diarrhea frequency justified?Required	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. S01	Direct information for examining the relationship between patient importance thresholds and reported values is unavailable.	A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis.	Compare defined important differences and responder thresholds with original results to distinguish a statistical signal from patient-important improvement.
25	Unverified	Full text not readStored summary read	N25 · Evidence conditionAre trial registration, protocol and analysis plan established?Required	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. S01	Registration, protocol and SAP for actual plan-versus-report comparison are unavailable.	Trial registration identifier, original registration, protocol, SAP and versions/dates.	Connect the paper’s identity with registration, protocol and SAP to compare prospective recruitment, joint endpoints, analyses and timing with reports.
26	Unverified	Full text not readStored summary read	N26 · Evidence conditionIs prospective-plan agreement for assessments and analyses at 8 and 12 weeks established?Required	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. S01	The reported schedule alone cannot establish agreement with the prospective plan.	Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes.	Compare planned visit, endpoint and analysis schedules with reported results and check for timing changes or additional analyses.
27	Met	Full text not readStored summary read	N27 · Evidence conditionWere evidence and bibliographic descriptions of the same paper counted without duplication?Required	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. S01	The single report’s attribution in the current retained summary was connected without creating additional independent trial counts.	Report title, PMID, DOI, evidence/citation links, trial family and participant relationships.	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.
28	Unverified	Full text not readStored summary read	N28 · Evidence conditionIs independent replication of the same question established?Required (independent-replication claim)	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. S01	Report/family material needed to establish independent replication of the same question has not been acquired.	Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links.	Compare trial-specific eligibility and family links to examine independent result distributions, contrary results and condition differences.
29	Met	Full text not readStored summary read	N29 · Evidence conditionWhat was actually read, and what date scope is being described?Required	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. S01	Current local reading, historical descriptions and external unread status were recorded separately.	Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records.	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.
30	Partly verified	Full text not readStored summary read	N30 · Evidence conditionAre funding, product support and author interests established?Supplementary; required for independence claims	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. S01	Reported funding exists, but direct content on product support and declared interests remains unresolved.	Funding, product provision, author employment/patents, COI declarations, institutions and roles.	Compare funding, product provision and author/institutional roles separately to check against unsupported conclusions of independent funding or replication.
31	Unverified	Full text not readStored summary read	N31 · Evidence conditionAre arm-specific adverse-event/discontinuation counts and collection scope established?Supplementary; required for safety questions	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. S01	Warning descriptions do not substitute for quantitative harm counts or collection scope in the actual trial.	AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness.	Connect safety tables, collection instructions and flow to distinguish event counts from person counts, exposure denominators, discontinuation reasons and missingness.
32	Unverified	Full text not readStored summary read	N32 · Evidence conditionCan adverse reactions such as diarrhea be distinguished from IBS symptoms by timing and comparison?Supplementary; required for harm attribution	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. S01	The original warning alone cannot establish time/comparison attribution separating baseline IBS symptoms from intervention-related harms.	Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures.	Compare symptom/administration timelines, arm-specific harms and alternative exposures to distinguish disease from intervention-related signals and examine limits on causal/risk interpretation.
33	Unverified	Full text not readStored summary read	N33 · Evidence conditionIs safety material available for pregnancy, lactation, infants and young children, concomitant drugs and long-term use?Supplementary; required for the relevant safety claim	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. S01	Warnings are retained, but direct information to establish risks for those groups, concomitant use and long-term exposure is unavailable.	Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms.	Review safety material and drug-interaction evidence separately by exposure/population without extending a short-term adult efficacy trial into overall safety.
34	Not applicable	Full text not readStored summary read	N34 · Evidence conditionDoes this question require an optimal dose or effects in specific subgroups?Supplementary; required for dose or subgroup extensions	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. S01	Dose optimization and specific subgroup extensions are not requirements of the current question.	For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results.	When proposing dose/subgroup extensions, design separate questions using direct comparisons and prospective interaction material without merging them into the current principal effect.
35	Not applicable	Full text not readStored summary read	N35 · Evidence conditionDoes this cover cure, relapse, pain and quality of life beyond diarrhea frequency?Supplementary; required for the relevant extension claim	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. S01	Separate clinical/mechanistic extensions are outside the current principal question.	For extensions: each separate endpoint’s definition, population, duration, comparison and direct results.	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.
36	Not applicable	Full text not readStored summary read	N36 · Evidence conditionDoes this scope produce pooled results across studies or repeated harm signals?Supplementary; required for pooled or repeated-harm claims	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. S01	Pooling across studies and repeated-harm claims are outside this sheet’s output scope.	For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships.	If multiple materials are added, separately examine suitability for pooling and repeated signals after comparing unique families, condition differences, contrary results and recitation.
37	Met	Full text not readStored summary read	N37 · Evidence conditionWere the scope of the internal English correction and remaining generic wording distinguished?Required (preservation accuracy)	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. S01	The current bilingual input and correction scope were read, retaining original types, empty values and absence.	The correction event, current original Korean/English correspondence, original field types, absent keys and empty values.	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.
38	Met	Full text not readStored summary read	N38 · Evidence conditionWere the existing grade, score and axes distinguished from this sheet review?Required (preservation accuracy)	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. S01	Original verdict fields and sheet states were separated without changing the original.	The original grade, score, safety, axes, grade decision and current review scope.	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.

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38 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence review date: 2026-09-08
Scope actually checked: Retained Korean/English summaries and case-specific condition/application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: 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.
Population: Adults with Rome III diarrhea-predominant irritable bowel syndrome. Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain unverified. Do not extend this to general diarrhea or all IBS.
Ingredient, formulation and route: Oral berberine hydrochloride 200 mg tablets. Plant source, manufacturer, excipients and supplier remain unverified. Do not substitute other extracts, derivatives, combinations or topical products.
Dose: The nominal plan was 200 mg 2 times daily (400 mg/day). Actual dosing, adherence, rescue treatment and handling of discontinuation remain unverified. This is not an instruction for personal use.
Comparator: The actual comparator was vitamin C tablets 400 mg/day. The historical placebo label does not automatically establish an inert placebo. Appearance, sensory matching and biological inertness remain unverified.
Measured outcome: The endpoint is diary-based weekly diarrhea frequency. Retained week 8 values are 1.39±0.80 versus 3.55±0.66, P=.032. Exact summary-statistic type, meaning of ±, time-specific analysis n, between-arm difference, CI, importance and analysis model remain unverified. The original C grade, 50 points and Warning are historical records.
Duration: Distinguish 8 weeks of treatment from the week 12 result after 4 weeks off treatment. Week 12 values are 3.58±0.73 versus 3.81±0.54, P=.805. Historical null/no-difference wording does not establish 0 effect, equivalence, sustained benefit, cure or relapse prevention.
Questions outside this scope: Retain the conflict among 196 recruited, 164 or 132 randomized, and 132 completing (70/62). Do not use completers as time-specific analysis denominators or subtract counts to create a dropout total.; Diarrhea and urgency were tracked together, but prospective co-primary hierarchy and multiplicity handling remain unverified. Do not extend the diarrhea result to the same effect on pain, quality of life or microbiome normalization.; Verification states concern narrow conditions within retained material. Counts of met conditions or the original verdict score do not provide new efficacy or safety certification.; Retain overlap between gastrointestinal reactions and baseline IBS symptoms, and the original cautions concerning pregnancy, lactation, infants and young children, and CYP-related concomitant drugs. Do not newly infer harm incidence or causality from improvement after stopping or rechallenge.

Evidence and sources

The links below lead to the sources. A link alone does not mean the original source was read or its latest publication status verified.

S01 · A Randomized Clinical Trial of Berberine Hydrochloride in Patients with Diarrhea-Predominant Irritable Bowel Syndrome

PubMed

Material type: Retained summary of a double-blind randomized trial comparing berberine hydrochloride with an actual vitamin C comparator.
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Findings recorded in the stored summary: Week 8: 1.39±0.80 versus 3.55±0.66, P=.032; week 12: 3.58±0.73 versus 3.81±0.54, P=.805. Retain conflicting reports of 196 recruited, 164 or 132 randomized, and 132 completing (70/62). Separate 8 weeks of treatment from the result after 4 weeks off treatment; the meaning of ±, analysis n, CI, model and prospective co-primary hierarchy remain unverified.
Record level: Time-specific arm values reported in the retained summary. The external paper was not directly read and no new effect difference or CI was calculated in this work.
Study overlap and independent replication: The retained set contains 1 report linked to PMID 26400188 and DOI 10.1002/ptr.5475. The week 8/week 12 results and PubMed/DOI entry points are not counted as independent trials. Unique study and participant totals and independent replication counts remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic/abstract index entry	URL string retained; current response unverified	External access not attempted; not acquired	Not read	Current access, acquisition and reading of this material were not attempted. The historical PDF-review description is not inherited as this material’s access date or level. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted.
DOI identifier entry	Constructed from a bibliographic identifier; current response unverified	External access not attempted; not acquired	Not read	Current access, acquisition and reading of this material were not attempted. The historical PDF-review description is not inherited as this material’s access date or level. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted.
Paper PDF full text described in historical review	Historical review description retained; current file not acquired	External access not attempted; not acquired	Not read	The historical description of checking PDF tables and methods was retained, but no current PDF file or URL was acquired or read. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted.
Retained bilingual bibliographic, evidence and manuscript summary	Retained copy acquired; summary read	Retained copy acquired; summary read	Stored existing review summary read	The material actually read here was the retained complete Korean/English summary. This does not establish reading of external full text. These are material entry points and time points of the same report, not independent trials. Historical access level and access date for each material are not recorded. The original review date is 2026-09-08, the historical correction date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access level and access date for individual external materials are not recorded; current access was not attempted.

Report counts versus independent study counts

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.

Review criteria

Version 1.1 · Criteria record date 2026-10-05. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Which IBS-D diarrhea-frequency question is addressed?

Required materials and conditions: The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL.
Conditions for verification: Fix a single question about weekly diarrhea frequency at 8 weeks comparing oral berberine hydrochloride 400 mg/day with vitamin C 400 mg/day in adults with Rome III IBS-D.
Requirement and applicability: Required
Application exceptions: The original subclaim list is empty. Do not invent subclaims or expand every combination of dimensions into a separate sheet.
Why this condition is needed: Needed to distinguish an ingredient-wide effect from a particular comparison and time point.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N02 · Do the actual ingredient and tablet formulation match this question?

Required materials and conditions: The formulation name, composition, dosage form and reasons for including or excluding other products.
Conditions for verification: Distinguish the berberine hydrochloride tablets in the material from plant extracts, other derivatives, combinations and topical products.
Requirement and applicability: Required
Application exceptions: Unverified plant source or excipients do not establish that this was a different formulation.
Why this condition is needed: The same berberine name does not establish the same exposure.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N03 · To what extent are the experimental tablet’s labeled ingredient and dosage form, source, manufacturer and excipients established?

Required materials and conditions: The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records.
Conditions for verification: Check separately the labeled berberine hydrochloride 200 mg tablet information and the extent of verification of the actual source, manufacturer and complete composition. The labeled ingredient alone does not establish source, manufacture or excipients.
Requirement and applicability: Required
Application exceptions: Do not convert an unverified source into a specific plant species or the presence of product impurities.
Why this condition is needed: Product identity beyond the ingredient name is needed to explain whether the experimental exposure is the same.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N04 · Are route, nominal dose and dosing frequency specified?

Required materials and conditions: Route, labeled tablet amount, dosing frequency and nominal daily dose.
Conditions for verification: Directly connect the nominal oral regimen of 200 mg 2 times daily, 400 mg/day.
Requirement and applicability: Required
Application exceptions: Do not interpret nominal 400 mg/day as actual adherent intake or blood exposure.
Why this condition is needed: Needed to avoid substituting results from another product or dose for the nominal regimen.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N05 · Can actual intake, adherence and rescue treatment be established?

Required materials and conditions: Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records.
Conditions for verification: Check how arm-specific intake, adherence, drug discontinuation and rescue treatment affected the comparison at 8 weeks.
Requirement and applicability: Required
Application exceptions: Unverified adherence does not establish nonadherence or an incorrect nominal dose.
Why this condition is needed: Assigned administration instructions alone do not establish equal actual exposure.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N06 · Is the eligibility scope for adults with Rome III IBS-D established?

Required materials and conditions: Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics.
Conditions for verification: Check age, severity, eligibility and recruitment setting of the diagnosed population without extending to general diarrhea or all IBS.
Requirement and applicability: Required
Application exceptions: Unverified detailed selection does not establish no effect in other IBS types.
Why this condition is needed: The same diarrhea symptoms do not establish the same diagnosis or selection process.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N07 · What did the comparator arm actually receive?

Required materials and conditions: The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording.
Conditions for verification: Distinguish that the actual comparator called placebo in the paper was vitamin C tablets 400 mg/day.
Requirement and applicability: Required
Application exceptions: Do not automatically judge the vitamin C comparator identical to an inert placebo or equivalent treatment to berberine.
Why this condition is needed: Hiding the actual comparator ingredient changes the meaning of the comparative effect.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N08 · Are concomitant medication, diet and lifestyle changes in both arms established?

Required materials and conditions: Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling.
Conditions for verification: Check how arm-specific concomitant treatment, diet, lifestyle interventions and rescue treatment during 8 weeks were handled in the actual comparison and analysis.
Requirement and applicability: Required
Application exceptions: Do not require all changes to be identical or fill unverified information with an absence of cointerventions.
Why this condition is needed: Needed to avoid attributing differences in other treatments or behavior to berberine.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N09 · Can 8 weeks of treatment be distinguished from 4 weeks of off-treatment follow-up?

Required materials and conditions: Administration, discontinuation and assessment schedules and results at each time point.
Conditions for verification: Distinguish the end of 8 weeks of administration from assessment at week 12 after a further 4 weeks off treatment, without merging time points.
Requirement and applicability: Required
Application exceptions: Differences in results at different time points do not constitute a numerical conflict at the same time point.
Why this condition is needed: Needed to avoid transferring the end-of-treatment result into a sustained effect.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N10 · Are the diarrhea-diary event definition and collection procedures established?

Required materials and conditions: Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries.
Conditions for verification: Check the event definition for weekly diarrhea episodes, aggregation period, diary completion, missing-entry handling and scale direction.
Requirement and applicability: Required
Application exceptions: The description as a direct patient-experienced endpoint does not certify a validated diary or complete measurement.
Why this condition is needed: The definition and collection of patient-recorded diarrhea frequency must be distinguished from the actual effect.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N11 · Is the prospective co-primary hierarchy for diarrhea and urgency established?

Required materials and conditions: Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP.
Conditions for verification: Check diarrhea/urgency status and handling of multiple testing and selective reporting in the prospective plan.
Requirement and applicability: Required
Application exceptions: Do not interpret the coprimary_split flag as definitive proof of a plan violation or selective reporting.
Why this condition is needed: Needed to avoid extending a favorable diarrhea result alone into success for all co-primary endpoints.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N12 · Are the arm-specific weekly diarrhea values at 8 weeks connected?

Required materials and conditions: Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point.
Conditions for verification: Connect the reported weekly diarrhea values, printed ± values and P for berberine and vitamin C at 8 weeks to that time point.
Requirement and applicability: Required
Application exceptions: The meaning of ±, actual analysis denominator, between-arm difference and CI are separate conditions from checking these arm values.
Why this condition is needed: Needed to avoid transferring retained figures to another endpoint or an off-treatment result.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N13 · Was the off-treatment result at 12 weeks preserved separately?

Required materials and conditions: Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules.
Conditions for verification: Retain arm values and P at 12 weeks after 4 weeks off treatment without converting nonsignificance into 0 effect or equivalence.
Requirement and applicability: Required
Application exceptions: Retain the manuscript’s null/no-difference wording as historical description. Do not newly judge P=.805 as exact 0 effect or equivalence.
Why this condition is needed: Needed to avoid retaining only the favorable result at 8 weeks and presenting sustained benefit.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N14 · Are arm values final values or changes, and are baseline data available?

Required materials and conditions: Baseline diarrhea, original table headings at each time point, statistical summary type and change definition.
Conditions for verification: Check statistical summary type, final value/change and baseline diarrhea data at each time point.
Requirement and applicability: Required
Application exceptions: If baseline values are absent from the current summary, do not subtract time-point values to fill in a change.
Why this condition is needed: The same number can address different questions as final frequency versus change from baseline.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N15 · Are the analysis population, adjustment and effect of interest at 8 weeks established?

Required materials and conditions: Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models.
Conditions for verification: Check assignment/adherence effects, ITT/PP, analysis population, adjustment and the actual between-arm analysis definition.
Requirement and applicability: Required
Application exceptions: The manuscript’s assessment as completer data does not establish a formal PP analysis or arm-specific analysis n.
Why this condition is needed: Needed to avoid converting completers into the analysis population for the assignment effect.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N16 · Is it established whether ± values are SD or SE?

Required materials and conditions: Original table legend, SD/SE definitions, analysis n for each value and measurement units.
Conditions for verification: Use the original table legend to establish which dispersion/error statistic the printed ± values at 8 and 12 weeks represent.
Requirement and applicability: Required
Application exceptions: Do not convert ± into CI or infer SD/SE to create a new interval.
Why this condition is needed: The ± string alone cannot support calculation of dispersion or precision.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N17 · Do recruitment and randomization counts agree?

Required materials and conditions: CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections.
Conditions for verification: Check recruitment flow and original report locations that could resolve inconsistent reports of 196 recruited, 164 or 132 randomized, and 132 completing.
Requirement and applicability: Required
Application exceptions: Do not automatically merge 196, 164 and 132 as counts for the same stage or select one as the correct answer.
Why this condition is needed: Needed to avoid hiding conflicting counts or using an arbitrary larger count as the analysis denominator.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N18 · Are 70/62 completers connected to time-specific analysis denominators?

Required materials and conditions: Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks.
Conditions for verification: Distinguish 70 versus 62 completers from analysis n at 8 and 12 weeks and check actual denominators for each result.
Requirement and applicability: Required
Application exceptions: Do not automatically fill analysis n at 8 or 12 weeks with the completion counts 70/62.
Why this condition is needed: Needed to avoid inheriting completers as actual analysis denominators at both time points.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N19 · Who was lost, and how were missing diarrhea results handled?

Required materials and conditions: Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses.
Conditions for verification: Check arm-specific dropout/missingness reasons and missing-data handling and sensitivity analyses for results at 8 and 12 weeks.
Requirement and applicability: Required
Application exceptions: Do not treat the entire difference between recruitment and completion counts as on-treatment dropout.
Why this condition is needed: Needed to establish which selection and losses preceded completer results.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N20 · Are random sequence, allocation concealment and baseline balance established?

Required materials and conditions: Design, random sequence, allocation concealment in Methods and baseline tables.
Conditions for verification: Check actual randomization method, concealment, baseline balance and design structure.
Requirement and applicability: Required
Application exceptions: Unverified sequence/concealment does not establish failed randomization; do not assign crossover/cluster NA without evidence.
Why this condition is needed: The randomized label alone does not establish that allocation concerns are resolved.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N21 · Is blinding for diary completion/assessment and comparator tablets established?

Required materials and conditions: Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records.
Conditions for verification: Check participant, assessor and analyst blinding, matching of comparator tablets and any unblinding.
Requirement and applicability: Required
Application exceptions: The fact that the comparator was vitamin C alone establishes neither blinding failure nor success.
Why this condition is needed: The double-blind label alone does not establish that measurement differences in subjective diarrhea records disappeared.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N22 · To what extent are time-specific P values and their testing/adjustment definitions established?

Required materials and conditions: Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling.
Conditions for verification: Check separately the reported P=.032 at 8 weeks and P=.805 at 12 weeks, their time points and the extent of verification of testing target, one-/two-sided testing, repeated measurement/adjustment and multiplicity handling. A P string does not establish the test definition.
Requirement and applicability: Required
Application exceptions: Do not newly calculate significance/nonsignificance or interpret it as an equivalence test.
Why this condition is needed: Needed to avoid using a P string as a substitute for precision or clinical importance.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N23 · Are the between-arm effect at 8 weeks and 95% CI directly reported?

Required materials and conditions: The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model.
Conditions for verification: Check the original estimate, 95% CI, dispersion and denominator for the effect of interest at 8 weeks.
Requirement and applicability: Required
Application exceptions: Do not subtract printed arm values to create a new effect difference or NNT.
Why this condition is needed: Significance and arm values alone do not reveal the effect interval.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N24 · Is a threshold for an important difference in diarrhea frequency justified?

Required materials and conditions: A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis.
Conditions for verification: Check patient-important differences, responder thresholds and prospective support for this IBS-D endpoint.
Requirement and applicability: Required
Application exceptions: Do not invent minimum participant counts, duration, effect size or proportion-of-conditions-met thresholds.
Why this condition is needed: Needed to avoid establishing clinically sufficient benefit from P=.032 alone.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N25 · Are trial registration, protocol and analysis plan established?

Required materials and conditions: Trial registration identifier, original registration, protocol, SAP and versions/dates.
Conditions for verification: Directly compare registration identity and the prospective protocol/SAP for this report.
Requirement and applicability: Required
Application exceptions: Do not convert an unestablished registration field into confirmed nonregistration or 0 registration identifiers.
Why this condition is needed: Needed to reveal which material is required to examine favorable-result selection.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N26 · Is prospective-plan agreement for assessments and analyses at 8 and 12 weeks established?

Required materials and conditions: Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes.
Conditions for verification: Check agreement between prospective plans and reports for end-of-treatment/off-treatment timing and the corresponding analyses.
Requirement and applicability: Required
Application exceptions: Unverified timing plans do not establish post hoc analysis.
Why this condition is needed: Knowing the nominal duration differs from agreement with a prospective plan.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N27 · Were evidence and bibliographic descriptions of the same paper counted without duplication?

Required materials and conditions: Report title, PMID, DOI, evidence/citation links, trial family and participant relationships.
Conditions for verification: Connect the same report in the corresponding evidence and citation entries without counting external identifier entry points as additional trials.
Requirement and applicability: Required
Application exceptions: Connecting one report does not establish a worldwide unique trial count of 1.
Why this condition is needed: Needed to avoid counting bibliography, abstract and paper links as multiple independent trials.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N28 · Is independent replication of the same question established?

Required materials and conditions: Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links.
Conditions for verification: Check the same formulation, population, comparator, diarrhea result at 8 weeks and family relationships in other unique trials.
Requirement and applicability: Required (independent-replication claim)
Application exceptions: No new search and 1 linked report do not establish an absence of independent research.
Why this condition is needed: Needed to avoid extending one report’s result into independent confirmation.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N29 · What was actually read, and what date scope is being described?

Required materials and conditions: Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records.
Conditions for verification: Distinguish complete reading of the retained summary from historical PDF-review descriptions and current unattempted/unread external material, with dates.
Requirement and applicability: Required
Application exceptions: Do not fill material-specific access dates from the global original-verdict review date or describe unattempted access as failed access.
Why this condition is needed: Needed to avoid overstating local-summary reading as new full-text reading or a current exhaustive search.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N30 · Are funding, product support and author interests established?

Required materials and conditions: Funding, product provision, author employment/patents, COI declarations, institutions and roles.
Conditions for verification: Check reported funding, product provision, employment, patents and declared interests separately from trial family.
Requirement and applicability: Supplementary; required for independence claims
Application exceptions: Do not use the existing I2 axis as new certification of complete independence.
Why this condition is needed: An academic-support name alone does not reveal product support or conflicts of interest.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N31 · Are arm-specific adverse-event/discontinuation counts and collection scope established?

Required materials and conditions: AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness.
Conditions for verification: Check adverse-event events/persons, exposure denominators, collection, severity, discontinuation and missingness in the same trial.
Requirement and applicability: Supplementary; required for safety questions
Application exceptions: Do not delete efficacy results because harms are unreported or infer events/denominators.
Why this condition is needed: Needed to avoid converting the existence of efficacy reports into no harms or completed safety accounting.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N32 · Can adverse reactions such as diarrhea be distinguished from IBS symptoms by timing and comparison?

Required materials and conditions: Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures.
Conditions for verification: Check baseline IBS symptoms, onset/worsening after dosing, stopping/recovery, arm-specific comparisons and alternative exposures.
Requirement and applicability: Supplementary; required for harm attribution
Application exceptions: Reporting after exposure alone does not establish causality; do not infer that changes in diarrhea frequency after stopping represent AE recovery.
Why this condition is needed: Needed to avoid merging IBS-D diarrhea and intervention-related gastrointestinal reactions into the same event.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N33 · Is safety material available for pregnancy, lactation, infants and young children, concomitant drugs and long-term use?

Required materials and conditions: Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms.
Conditions for verification: Check direct material on vulnerable groups, interactions and long-term/rare harms and the applicability limits of original warnings.
Requirement and applicability: Supplementary; required for the relevant safety claim
Application exceptions: Do not require every rare-harm study as a condition for checking diarrhea efficacy at 8 weeks.
Why this condition is needed: Results in a limited adult population and duration cannot guarantee safety in vulnerable groups or long-term use.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N34 · Does this question require an optimal dose or effects in specific subgroups?

Required materials and conditions: For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results.
Conditions for verification: Distinguish the narrow question of 400 mg/day in adults with Rome III IBS-D from separate dose/subgroup-extension requirements.
Requirement and applicability: Supplementary; required for dose or subgroup extensions
Application exceptions: Do not add optimal-dose or all-subgroup research requirements to the current narrow question.
Why this condition is needed: Needed to avoid converting a principal effect at one dose into an optimal dose or a specific subgroup effect.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N35 · Does this cover cure, relapse, pain and quality of life beyond diarrhea frequency?

Required materials and conditions: For extensions: each separate endpoint’s definition, population, duration, comparison and direct results.
Conditions for verification: Distinguish weekly diarrhea frequency from cure, relapse prevention, microbiome normalization, pain and quality of life.
Requirement and applicability: Supplementary; required for the relevant extension claim
Application exceptions: Do not require other clinical-event trials as conditions for checking weekly diarrhea frequency itself.
Why this condition is needed: Patient-experienced diarrhea frequency and other clinical/mechanistic outcomes are not the same effect.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N36 · Does this scope produce pooled results across studies or repeated harm signals?

Required materials and conditions: For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships.
Conditions for verification: Do not create across-study pooling or repeated harms from one linked report; distinguish unverified family relationships from scope nonapplicability.
Requirement and applicability: Supplementary; required for pooled or repeated-harm claims
Application exceptions: Do not convert nonapplicability of current pooling into a finding of no independent research. Independent replication remains separately unverified.
Why this condition is needed: Needed to avoid counting multiple time points/links in one report as across-study replication or repeated harms.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N37 · Were the scope of the internal English correction and remaining generic wording distinguished?

Required materials and conditions: The correction event, current original Korean/English correspondence, original field types, absent keys and empty values.
Conditions for verification: Retain the scope of the 2026-09-14 internal English wording correction and current generic English wording, empty fields and absent keys.
Requirement and applicability: Required (preservation accuracy)
Application exceptions: A correction record describing one field change does not establish that all current generic wording has become specific.
Why this condition is needed: Needed to avoid inheriting a wording correction as new clinical verification or added content.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

N38 · Were the existing grade, score and axes distinguished from this sheet review?

Required materials and conditions: The original grade, score, safety, axes, grade decision and current review scope.
Conditions for verification: Retain original C 50, Warning and axes/flags as preserved original information without converting them into a new sheet completion proportion, grade or clinical certification.
Requirement and applicability: Required (preservation accuracy)
Application exceptions: Do not use original I2, EX, CX, coprimary_split or historical cross-check wording as evidence of new clinical validation.
Why this condition is needed: The original verdict and verification states for producing an evidence-gap sheet are different information.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Referenced methods and the sections actually reviewed

M03 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13

Referenced principle: Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M04 · Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03

Official methodology · §4.5, §4.6.1–4.6.3, MECIR C42

Referenced principle: Link studies and reports separately; do not omit studies solely because results are unreported.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M08 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §8.1–8.2.3, Table 8.2.a

Referenced principle: Fix the result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M15 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

M19 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.
Extent of review: Retained method-application records were reused. External originals were not reread and method content was not reassessed.

What the statuses mean

Met: The row’s narrow record, attribution, boundary or actual fact was checked. This does not certify efficacy, precision or safety.
Partly verified: Some required information is available, but actual exposure, definitions, denominators or other necessary material remain missing.
Unverified: The criterion cannot be established within the retained scope. This does not mean 0 effect, 0 studies or failed access.
Not applicable: The condition has no applicable subject within the current retained set and narrow question. This does not replace a material gap or unread status.
Review incomplete: A status for external original-material comparison not yet performed, distinguished from review of locally retained content.
Not applicable (alias): The condition has no applicable subject within the current retained set and narrow question. This does not replace a material gap or unread status.
Conflicting data: Participant reports for the same concept conflict, so no single value was selected. This is distinct from differences in results at different time points.
Not read: The material was not directly read in the current work. This is distinct from not reported, inaccessible or no research.

Change history

2026-10-27 · Public page/material version 1.0

The public view and materials were prepared from the existing 38 items. No new clinical search, verification-state change or scoring was performed.

The stored-material review date (2026-10-05) and original evidence review date (2026-09-08) were retained unchanged.

Researcher downloads

These materials provide the same evidence, scope and verification status as this page.

View all item details

N01 · Which IBS-D diarrhea-frequency question is addressed?

Current findings: The original claim concerns reduced weekly diarrhea frequency in diarrhea-predominant irritable bowel syndrome. This sheet is limited to berberine hydrochloride versus vitamin C at 8 weeks in adults with Rome III IBS-D.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The original claim and claim conditions link intervention, population, comparator and endpoint, establishing the identity of this sheet.
Reason for missing information: The independent question has been identified. The result after stopping at 12 weeks and urgency are explained separately; this verification does not include IBS cure or relapse prevention.
Required materials and conditions: The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL.
Materials to obtain first: The original claim, population, formulation, route, nominal dose, actual comparator, endpoint at 8 weeks and canonical URL.
Further research: Compare the original claim with the evidence comparison to check that persistence after stopping, urgency, pain and quality of life are not mixed into the principal effect.
Remaining uncertainty: The independent question has been identified. The result after stopping at 12 weeks and urgency are explained separately; this verification does not include IBS cure or relapse prevention.
Conditions for verification: Fix a single question about weekly diarrhea frequency at 8 weeks comparing oral berberine hydrochloride 400 mg/day with vitamin C 400 mg/day in adults with Rome III IBS-D.
Why this condition is needed: Needed to distinguish an ingredient-wide effect from a particular comparison and time point.
Application exceptions: The original subclaim list is empty. Do not invent subclaims or expand every combination of dimensions into a separate sheet.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N02 · Do the actual ingredient and tablet formulation match this question?

Current findings: The claim conditions specify berberine hydrochloride tablets and 200 mg tablets. Retain the manuscript boundary that plant extracts, combinations, dihydroberberine, other derivatives and topical products are not interchangeable.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The labeled ingredient and dosage form were checked in the retained material, with other products excluded.
Reason for missing information: The labeled ingredient and dosage form were checked. Manufacturing source and complete excipients remain unverified in a separate item.
Required materials and conditions: The formulation name, composition, dosage form and reasons for including or excluding other products.
Materials to obtain first: The formulation name, composition, dosage form and reasons for including or excluding other products.
Further research: Compare product composition with Methods to distinguish whether results for berberine hydrochloride tablets can be transferred to other extracts, derivatives or combinations.
Remaining uncertainty: The labeled ingredient and dosage form were checked. Manufacturing source and complete excipients remain unverified in a separate item.
Conditions for verification: Distinguish the berberine hydrochloride tablets in the material from plant extracts, other derivatives, combinations and topical products.
Why this condition is needed: The same berberine name does not establish the same exposure.
Application exceptions: Unverified plant source or excipients do not establish that this was a different formulation.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N03 · To what extent are the experimental tablet’s labeled ingredient and dosage form, source, manufacturer and excipients established?

Current findings: The source description specifies berberine hydrochloride tablets but states that the plant source is unverified. Direct information on the manufacturer and excipients was not found in the current retained summary.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The tablet ingredient is known, but source, manufacture and complete composition have not been established.
Reason for missing information: Plant source, manufacturer, excipients and experimental-product supplier remain missing. This is a limitation of the retained summary, not a finding of nonreporting across the entire original paper.
Required materials and conditions: The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records.
Materials to obtain first: The experimental tablet’s manufacturer, manufacturing source, complete composition and product-supply records.
Further research: Compare the original product description and supply records to separate the labeled hydrochloride amount from complete product composition and origin.
Remaining uncertainty: Plant source, manufacturer, excipients and experimental-product supplier remain missing. This is a limitation of the retained summary, not a finding of nonreporting across the entire original paper.
Conditions for verification: Check separately the labeled berberine hydrochloride 200 mg tablet information and the extent of verification of the actual source, manufacturer and complete composition. The labeled ingredient alone does not establish source, manufacture or excipients.
Why this condition is needed: Product identity beyond the ingredient name is needed to explain whether the experimental exposure is the same.
Application exceptions: Do not convert an unverified source into a specific plant species or the presence of product impurities.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N04 · Are route, nominal dose and dosing frequency specified?

Current findings: The claim conditions specify oral use, 200 mg 2 times daily and 400 mg/day. The manuscript also limits scope to IBS-D diarrhea frequency with 400 mg/day for 8 weeks.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Route and nominal administration information are directly present in the retained material.
Reason for missing information: Nominal route, dose and frequency were checked. Actual consumption and adherence are gaps in the next condition.
Required materials and conditions: Route, labeled tablet amount, dosing frequency and nominal daily dose.
Materials to obtain first: Route, labeled tablet amount, dosing frequency and nominal daily dose.
Further research: Compare administration instructions with formulation labeling to check for results from different doses or routes being mixed in.
Remaining uncertainty: Nominal route, dose and frequency were checked. Actual consumption and adherence are gaps in the next condition.
Conditions for verification: Directly connect the nominal oral regimen of 200 mg 2 times daily, 400 mg/day.
Why this condition is needed: Needed to avoid substituting results from another product or dose for the nominal regimen.
Application exceptions: Do not interpret nominal 400 mg/day as actual adherent intake or blood exposure.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N05 · Can actual intake, adherence and rescue treatment be established?

Current findings: The nominal 200 mg 2 times daily is known, but actual consumption, arm-specific adherence, rescue-treatment figures and handling methods were not established from the current material.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Data on actual intake and treatment changes beyond the administration plan are unavailable.
Reason for missing information: Actual intake, adherence, rescue treatment and analytical handling of drug discontinuation remain missing.
Required materials and conditions: Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records.
Materials to obtain first: Arm-specific tablet returns, adherence, actual administration, discontinuation and rescue-treatment records.
Further research: Compare nominal dose with actual dosing records and examine the effect of interest and analysis accounting for discontinuation and rescue treatment.
Remaining uncertainty: Actual intake, adherence, rescue treatment and analytical handling of drug discontinuation remain missing.
Conditions for verification: Check how arm-specific intake, adherence, drug discontinuation and rescue treatment affected the comparison at 8 weeks.
Why this condition is needed: Assigned administration instructions alone do not establish equal actual exposure.
Application exceptions: Unverified adherence does not establish nonadherence or an incorrect nominal dose.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N06 · Is the eligibility scope for adults with Rome III IBS-D established?

Current findings: The claim conditions concern adults with Rome III diarrhea-predominant IBS. Detailed age range, severity, eligibility criteria and recruitment setting are not established in the retained summary.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Diagnosis and the adult population are known, but detailed selection and representativeness remain unresolved.
Reason for missing information: Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain missing, preventing extension to general diarrhea or all IBS.
Required materials and conditions: Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics.
Materials to obtain first: Application of Rome III diagnostic criteria, age, severity, eligibility, recruitment setting and baseline characteristics.
Further research: Compare eligibility criteria and baseline tables to examine applicability to the current adult IBS-D question and differences from other diarrhea or IBS types.
Remaining uncertainty: Detailed age, severity, eligibility, recruitment setting and baseline characteristics remain missing, preventing extension to general diarrhea or all IBS.
Conditions for verification: Check age, severity, eligibility and recruitment setting of the diagnosed population without extending to general diarrhea or all IBS.
Why this condition is needed: The same diarrhea symptoms do not establish the same diagnosis or selection process.
Application exceptions: Unverified detailed selection does not establish no effect in other IBS types.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N07 · What did the comparator arm actually receive?

Current findings: The actual comparator was vitamin C tablets 400 mg/day. The manuscript’s key explanation emphasizes that the paper’s placebo was vitamin C.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The distinction between actual ingredient/nominal dose and placebo wording is directly specified.
Reason for missing information: The actual comparator ingredient and dose were checked. This does not establish appearance, sensory matching or biological inertness of the comparator tablet.
Required materials and conditions: The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording.
Materials to obtain first: The comparator tablet’s ingredient, dose, administration instructions and the trial’s placebo wording.
Further research: Review comparator formulation descriptions to distinguish the actual vitamin C comparison from assumptions of an inert control, and check administration differences between arms.
Remaining uncertainty: The actual comparator ingredient and dose were checked. This does not establish appearance, sensory matching or biological inertness of the comparator tablet.
Conditions for verification: Distinguish that the actual comparator called placebo in the paper was vitamin C tablets 400 mg/day.
Why this condition is needed: Hiding the actual comparator ingredient changes the meaning of the comparative effect.
Application exceptions: Do not automatically judge the vitamin C comparator identical to an inert placebo or equivalent treatment to berberine.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N08 · Are concomitant medication, diet and lifestyle changes in both arms established?

Current findings: The retained material specifies berberine versus vitamin C but does not present arm-specific information on concomitant medication, diet, lifestyle changes or rescue treatment.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Direct information for reviewing actual cointerventions and arm-specific changes is unavailable.
Reason for missing information: Arm-specific concomitant medication, diet, lifestyle changes and handling of changes/rescue treatment in the results remain missing.
Required materials and conditions: Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling.
Materials to obtain first: Records of concomitant medication, diet, lifestyle interventions, arm-specific changes, rescue treatment and analytical handling.
Further research: Compare arm-specific cointervention and change timelines to examine whether factors beyond berberine versus vitamin C were mixed into the results.
Remaining uncertainty: Arm-specific concomitant medication, diet, lifestyle changes and handling of changes/rescue treatment in the results remain missing.
Conditions for verification: Check how arm-specific concomitant treatment, diet, lifestyle interventions and rescue treatment during 8 weeks were handled in the actual comparison and analysis.
Why this condition is needed: Needed to avoid attributing differences in other treatments or behavior to berberine.
Application exceptions: Do not require all changes to be identical or fill unverified information with an absence of cointerventions.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N09 · Can 8 weeks of treatment be distinguished from 4 weeks of off-treatment follow-up?

Current findings: Treatment lasted 8 weeks, followed by 4 weeks off treatment. Week 8 is the end of treatment and week 12 is an assessment after stopping; do not combine them into a single result.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The nominal treatment/off-treatment follow-up and the two result time points are connected in the retained material.
Reason for missing information: Nominal time-point separation was checked. Actual visit schedules by arm, time-specific observation denominators and prospective schedules remain separate gaps.
Required materials and conditions: Administration, discontinuation and assessment schedules and results at each time point.
Materials to obtain first: Administration, discontinuation and assessment schedules and results at each time point.
Further research: Compare the time-point table to identify which results belong to on-treatment versus off-treatment observations.
Remaining uncertainty: Nominal time-point separation was checked. Actual visit schedules by arm, time-specific observation denominators and prospective schedules remain separate gaps.
Conditions for verification: Distinguish the end of 8 weeks of administration from assessment at week 12 after a further 4 weeks off treatment, without merging time points.
Why this condition is needed: Needed to avoid transferring the end-of-treatment result into a sustained effect.
Application exceptions: Differences in results at different time points do not constitute a numerical conflict at the same time point.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N10 · Are the diarrhea-diary event definition and collection procedures established?

Current findings: The endpoint is diary-recorded weekly diarrhea episodes, described in the evidence table as a direct patient-experienced endpoint. Event definition, diary form, aggregation and handling of missing entries were not established in the current retained summary.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Diary use and weekly frequency are known, but actual measurement procedures remain unresolved.
Reason for missing information: Diarrhea event definition and diary collection, aggregation and missing-data handling remain unresolved. Urgency and pain values are not substitutes for this endpoint.
Required materials and conditions: Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries.
Materials to obtain first: Diarrhea event definition, diary form, aggregation unit, assessment procedures and handling of missing diaries.
Further research: Compare diary forms and measurement instructions to examine how diarrhea episodes differ from bowel movements, urgency and pain.
Remaining uncertainty: Diarrhea event definition and diary collection, aggregation and missing-data handling remain unresolved. Urgency and pain values are not substitutes for this endpoint.
Conditions for verification: Check the event definition for weekly diarrhea episodes, aggregation period, diary completion, missing-entry handling and scale direction.
Why this condition is needed: The definition and collection of patient-recorded diarrhea frequency must be distinguished from the actual effect.
Application exceptions: The description as a direct patient-experienced endpoint does not certify a validated diary or complete measurement.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N11 · Is the prospective co-primary hierarchy for diarrhea and urgency established?

Current findings: The manuscript states that diarrhea and urgency were tracked together but the exact prospective co-primary hierarchy was unclear, retaining coprimary_split=true.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Material on the actual prospective co-primary hierarchy and multiplicity handling is not established.
Reason for missing information: Prospective endpoint status for diarrhea/urgency, testing order, multiplicity handling and the basis for result selection remain unresolved.
Required materials and conditions: Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP.
Materials to obtain first: Co-primary endpoints, testing hierarchy and multiplicity handling in registration, protocol and SAP.
Further research: Compare plans and reports to examine whether selecting diarrhea alone matches the prospective hierarchy and whether separate urgency reporting is missing.
Remaining uncertainty: Prospective endpoint status for diarrhea/urgency, testing order, multiplicity handling and the basis for result selection remain unresolved.
Conditions for verification: Check diarrhea/urgency status and handling of multiple testing and selective reporting in the prospective plan.
Why this condition is needed: Needed to avoid extending a favorable diarrhea result alone into success for all co-primary endpoints.
Application exceptions: Do not interpret the coprimary_split flag as definitive proof of a plan violation or selective reporting.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N12 · Are the arm-specific weekly diarrhea values at 8 weeks connected?

Current findings: Reported weekly diarrhea values at 8 weeks are berberine 1.39±0.80 versus vitamin C 3.55±0.66, P=.032. The reader answer, evidence table and citation connect these values to the same time point.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Arm values and P at 8 weeks are directly present in the evidence table and citation. No new effect difference was created.
Reason for missing information: The printed values at 8 weeks and their time-point attribution were checked. Exact statistical summary type such as a mean, meaning of ±, denominator, model and CI are outside this verification.
Required materials and conditions: Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point.
Materials to obtain first: Arm-specific reported values at 8 weeks, printed ± values, P and the original table’s endpoint and time point.
Further research: Compare arms, endpoint, time point and units in the table at 8 weeks and check agreement between summary and printed values. Do not newly calculate a difference or CI.
Remaining uncertainty: The printed values at 8 weeks and their time-point attribution were checked. Exact statistical summary type such as a mean, meaning of ±, denominator, model and CI are outside this verification.
Conditions for verification: Connect the reported weekly diarrhea values, printed ± values and P for berberine and vitamin C at 8 weeks to that time point.
Why this condition is needed: Needed to avoid transferring retained figures to another endpoint or an off-treatment result.
Application exceptions: The meaning of ±, actual analysis denominator, between-arm difference and CI are separate conditions from checking these arm values.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N13 · Was the off-treatment result at 12 weeks preserved separately?

Current findings: Reported values at 12 weeks, or 4 weeks after stopping, are 3.58±0.73 versus 3.81±0.54, P=.805. The manuscript describes no difference/null. Retain this historical wording without creating a new conclusion of 0 effect or equivalence.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The original off-treatment values and unfavorable persistence result were retained and distinguished from values at 8 weeks.
Reason for missing information: Original off-treatment values and nonsignificance wording were checked. Exact effect difference, interval, equivalence, individual relapse and long-term persistence are not established.
Required materials and conditions: Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules.
Materials to obtain first: Arm results at 12 weeks, printed ± values, P, and discontinuation/follow-up schedules.
Further research: Compare off-treatment result timing and arm-specific follow-up to examine persistence of the signal at 8 weeks within the reported scope, without newly estimating equivalence or relapse rates.
Remaining uncertainty: Original off-treatment values and nonsignificance wording were checked. Exact effect difference, interval, equivalence, individual relapse and long-term persistence are not established.
Conditions for verification: Retain arm values and P at 12 weeks after 4 weeks off treatment without converting nonsignificance into 0 effect or equivalence.
Why this condition is needed: Needed to avoid retaining only the favorable result at 8 weeks and presenting sustained benefit.
Application exceptions: Retain the manuscript’s null/no-difference wording as historical description. Do not newly judge P=.805 as exact 0 effect or equivalence.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N14 · Are arm values final values or changes, and are baseline data available?

Current findings: Arm values at 8 and 12 weeks exist, but baseline values, exact statistical summary type and the original table’s definitions of final values versus changes are absent from retained material.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Time-specific figures alone cannot establish the original analysis’s value definition or change from baseline.
Reason for missing information: Baseline diarrhea frequency and definitions of final value/change and mean/other summary type remain unresolved.
Required materials and conditions: Baseline diarrhea, original table headings at each time point, statistical summary type and change definition.
Materials to obtain first: Baseline diarrhea, original table headings at each time point, statistical summary type and change definition.
Further research: Compare baseline and result tables to verify analysis definitions without substituting final values, changes and within-arm changes for one another.
Remaining uncertainty: Baseline diarrhea frequency and definitions of final value/change and mean/other summary type remain unresolved.
Conditions for verification: Check statistical summary type, final value/change and baseline diarrhea data at each time point.
Why this condition is needed: The same number can address different questions as final frequency versus change from baseline.
Application exceptions: If baseline values are absent from the current summary, do not subtract time-point values to fill in a change.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N15 · Are the analysis population, adjustment and effect of interest at 8 weeks established?

Current findings: The original grade rationale describes limitations of completer data, but formal ITT/PP definitions, adjustment model and analysis denominator at 8 weeks are not established in the current retained summary.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Plan and analysis information specifying the actual analysis population and effect of interest is unavailable.
Reason for missing information: The analysis population at 8 weeks, ITT/PP definitions, adjustment model and connection to assignment or adherence effects remain unresolved.
Required materials and conditions: Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models.
Materials to obtain first: Analysis plan, ITT/PP definitions, time-specific analysis populations, covariates and models.
Further research: Compare plans with result analyses to examine whether the effect concerns all assigned participants or completers, and how adjustment and missing-data handling connect.
Remaining uncertainty: The analysis population at 8 weeks, ITT/PP definitions, adjustment model and connection to assignment or adherence effects remain unresolved.
Conditions for verification: Check assignment/adherence effects, ITT/PP, analysis population, adjustment and the actual between-arm analysis definition.
Why this condition is needed: Needed to avoid converting completers into the analysis population for the assignment effect.
Application exceptions: The manuscript’s assessment as completer data does not establish a formal PP analysis or arm-specific analysis n.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N16 · Is it established whether ± values are SD or SE?

Current findings: Values at 8 weeks, 1.39±0.80 versus 3.55±0.66, and at 12 weeks, 3.58±0.73 versus 3.81±0.54, are retained, but the type of ± is not specified.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The retained printed values lack a legend identifying SD, SE or another dispersion type.
Reason for missing information: Whether each ± value is SD/SE, the analysis denominator and original table legend remain unresolved; do not use them to calculate a new CI.
Required materials and conditions: Original table legend, SD/SE definitions, analysis n for each value and measurement units.
Materials to obtain first: Original table legend, SD/SE definitions, analysis n for each value and measurement units.
Further research: Compare table legends with Methods to distinguish SD, SE and other error expressions, checking only the meaning of reported statistics.
Remaining uncertainty: Whether each ± value is SD/SE, the analysis denominator and original table legend remain unresolved; do not use them to calculate a new CI.
Conditions for verification: Use the original table legend to establish which dispersion/error statistic the printed ± values at 8 and 12 weeks represent.
Why this condition is needed: The ± string alone cannot support calculation of dispersion or precision.
Application exceptions: Do not convert ± into CI or infer SD/SE to create a new interval.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N17 · Do recruitment and randomization counts agree?

Current findings: The key explanation specifies inconsistent reports of 196 recruited, 164 or 132 randomized, and 132 completing. The evidence sample-size field also retains inconsistency in the reported randomization denominator.
Verification status: Conflicting data
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Retain the manuscript’s conflict that the same randomization stage was reported as 164 or 132.
Reason for missing information: Original stage-specific text and correction/flow material needed to resolve 164 versus 132 randomized remain missing. No value was established or newly corrected here.
Required materials and conditions: CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections.
Materials to obtain first: CONSORT flow, original recruitment/randomization statements, abstract/body denominators and any corrections.
Further research: Compare recruitment flow and participant counts in the abstract, Methods and results by the same stages to establish whether 164 and 132 refer to different stages or an error.
Remaining uncertainty: Original stage-specific text and correction/flow material needed to resolve 164 versus 132 randomized remain missing. No value was established or newly corrected here.
Conditions for verification: Check recruitment flow and original report locations that could resolve inconsistent reports of 196 recruited, 164 or 132 randomized, and 132 completing.
Why this condition is needed: Needed to avoid hiding conflicting counts or using an arbitrary larger count as the analysis denominator.
Application exceptions: Do not automatically merge 196, 164 and 132 as counts for the same stage or select one as the correct answer.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N18 · Are 70/62 completers connected to time-specific analysis denominators?

Current findings: The evidence sample-size field retains 70 versus 62 completers. This connects to the manuscript’s total of 132 completing, but the completion stage/time and analysis n for each result are unspecified.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Arm-specific completion counts are known, but they are not connected to actual analysis denominators at both time points.
Reason for missing information: The exact completion stage, measurement/analysis n at 8 and 12 weeks, and arm-specific allocation counts remain missing.
Required materials and conditions: Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks.
Materials to obtain first: Arm-specific allocation, completion, measurement/analysis counts at 8 weeks and measurement/analysis counts at 12 weeks.
Further research: Connect each results table with the flow to distinguish completer counts, time-specific observation/analysis counts and shared participants.
Remaining uncertainty: The exact completion stage, measurement/analysis n at 8 and 12 weeks, and arm-specific allocation counts remain missing.
Conditions for verification: Distinguish 70 versus 62 completers from analysis n at 8 and 12 weeks and check actual denominators for each result.
Why this condition is needed: Needed to avoid inheriting completers as actual analysis denominators at both time points.
Application exceptions: Do not automatically fill analysis n at 8 or 12 weeks with the completion counts 70/62.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N19 · Who was lost, and how were missing diarrhea results handled?

Current findings: The manuscript emphasizes recruitment, randomization and completion denominator limitations and completer data. Arm-specific dropout reasons, missing diaries, missing-data handling and sensitivity analyses are not currently established.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Inconsistent counts alone do not reveal actual observation losses or handling methods.
Reason for missing information: Arm-specific dropout, reasons for time-specific missingness, missing-data handling and sensitivity analyses remain unresolved.
Required materials and conditions: Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses.
Materials to obtain first: Arm-specific reasons for dropout/missingness, missing diaries, time-specific analytical handling and sensitivity analyses.
Further research: Compare recruitment flow with missing diaries and examine robustness under missing-data handling and assumptions. Do not calculate a new missingness rate.
Remaining uncertainty: Arm-specific dropout, reasons for time-specific missingness, missing-data handling and sensitivity analyses remain unresolved.
Conditions for verification: Check arm-specific dropout/missingness reasons and missing-data handling and sensitivity analyses for results at 8 and 12 weeks.
Why this condition is needed: Needed to establish which selection and losses preceded completer results.
Application exceptions: Do not treat the entire difference between recruitment and completion counts as on-treatment dropout.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N20 · Are random sequence, allocation concealment and baseline balance established?

Current findings: The evidence table describes a double-blind randomized vitamin C-controlled trial. Random sequence, concealment procedures, baseline balance and detailed design structure are not established in the current summary.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: A randomized comparison is reported, but the actual allocation process remains unresolved.
Reason for missing information: Methods and baseline tables to establish sequence generation, allocation concealment, baseline balance and detailed design structure remain missing.
Required materials and conditions: Design, random sequence, allocation concealment in Methods and baseline tables.
Materials to obtain first: Design, random sequence, allocation concealment in Methods and baseline tables.
Further research: Compare allocation methods and baseline tables to examine allocation risk and balance beyond the randomized-trial label in the title.
Remaining uncertainty: Methods and baseline tables to establish sequence generation, allocation concealment, baseline balance and detailed design structure remain missing.
Conditions for verification: Check actual randomization method, concealment, baseline balance and design structure.
Why this condition is needed: The randomized label alone does not establish that allocation concerns are resolved.
Application exceptions: Unverified sequence/concealment does not establish failed randomization; do not assign crossover/cluster NA without evidence.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

Related sources S01

N21 · Is blinding for diary completion/assessment and comparator tablets established?

Current findings: Double blinding is reported. Who was blinded, whether tablet appearance/sensory features matched, and diary assessment or unblinding remain unverified.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The blinding label is known, but actual procedures and effects on measurement remain unresolved.
Reason for missing information: Participant, assessor and analyst blinding, tablet matching, unblinding/awareness and diary assessment procedures remain unresolved.
Required materials and conditions: Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records.
Materials to obtain first: Who was blinded, tablet appearance/sensory matching, assessment procedures and unblinding or awareness records.
Further research: Compare collection of the subjective diary endpoint with blinding procedures for both tablets to examine potential measurement differences.
Remaining uncertainty: Participant, assessor and analyst blinding, tablet matching, unblinding/awareness and diary assessment procedures remain unresolved.
Conditions for verification: Check participant, assessor and analyst blinding, matching of comparator tablets and any unblinding.
Why this condition is needed: The double-blind label alone does not establish that measurement differences in subjective diarrhea records disappeared.
Application exceptions: The fact that the comparator was vitamin C alone establishes neither blinding failure nor success.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N22 · To what extent are time-specific P values and their testing/adjustment definitions established?

Current findings: P=.032 at 8 weeks and P=.805 at 12 weeks are retained. Exact testing, model, one-/two-sided testing, adjustment and multiplicity definitions are not established in the summary.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Time-specific P values are known, but direct descriptions of the tests and models remain unresolved.
Reason for missing information: The target, model, one-/two-sided testing and adjustment for each P, and multiplicity handling for joint endpoints remain unresolved.
Required materials and conditions: Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling.
Materials to obtain first: Statistical Methods, testing target, model, covariates, one-/two-sided testing and multiplicity handling.
Further research: Compare Methods with result notes to examine whether P concerns a between-arm comparison and how it relates to repeated measurement, adjustment and multiple endpoints.
Remaining uncertainty: The target, model, one-/two-sided testing and adjustment for each P, and multiplicity handling for joint endpoints remain unresolved.
Conditions for verification: Check separately the reported P=.032 at 8 weeks and P=.805 at 12 weeks, their time points and the extent of verification of testing target, one-/two-sided testing, repeated measurement/adjustment and multiplicity handling. A P string does not establish the test definition.
Why this condition is needed: Needed to avoid using a P string as a substitute for precision or clinical importance.
Application exceptions: Do not newly calculate significance/nonsignificance or interpret it as an equivalence test.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N23 · Are the between-arm effect at 8 weeks and 95% CI directly reported?

Current findings: The reader answer states that a 95% CI is absent. The current retained summary does not connect an exact between-arm effect estimate at 8 weeks, CI, dispersion type and analysis n.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Exact effect-interval material beyond reported arm values and P is unavailable.
Reason for missing information: A directly reported estimate and 95% CI for the effect of interest, with dispersion type, denominator and model for interpretation, remain missing. This is unverified within the current material scope.
Required materials and conditions: The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model.
Materials to obtain first: The between-arm effect estimate at 8 weeks, 95% CI, dispersion type, analysis n and model.
Further research: Compare original result tables, estimate definitions, dispersion and analysis n to examine reported interval scope. Do not reconstruct a new CI from arm values.
Remaining uncertainty: A directly reported estimate and 95% CI for the effect of interest, with dispersion type, denominator and model for interpretation, remain missing. This is unverified within the current material scope.
Conditions for verification: Check the original estimate, 95% CI, dispersion and denominator for the effect of interest at 8 weeks.
Why this condition is needed: Significance and arm values alone do not reveal the effect interval.
Application exceptions: Do not subtract printed arm values to create a new effect difference or NNT.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N24 · Is a threshold for an important difference in diarrhea frequency justified?

Current findings: The manuscript explains that the immediate end-of-treatment signal may matter, but direct support for a prospective minimum important difference or responder threshold is absent.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Direct information for examining the relationship between patient importance thresholds and reported values is unavailable.
Reason for missing information: A patient-important frequency difference, responder threshold and prospective basis remain unresolved. An opinion that it may matter is not an established threshold.
Required materials and conditions: A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis.
Materials to obtain first: A prospective minimum important difference in weekly diarrhea frequency, responder definition and patient-centered basis.
Further research: Compare defined important differences and responder thresholds with original results to distinguish a statistical signal from patient-important improvement.
Remaining uncertainty: A patient-important frequency difference, responder threshold and prospective basis remain unresolved. An opinion that it may matter is not an established threshold.
Conditions for verification: Check patient-important differences, responder thresholds and prospective support for this IBS-D endpoint.
Why this condition is needed: Needed to avoid establishing clinically sufficient benefit from P=.032 alone.
Application exceptions: Do not invent minimum participant counts, duration, effect size or proportion-of-conditions-met thresholds.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N25 · Are trial registration, protocol and analysis plan established?

Current findings: The evidence registration field says not established. Original registration, protocol and SAP identity, content and versions are absent from the current retained summary, and external registration was not queried here.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Registration, protocol and SAP for actual plan-versus-report comparison are unavailable.
Reason for missing information: Registration identity, original registration, protocol, SAP and dates/versions remain missing. This does not establish absent registration or selective reporting.
Required materials and conditions: Trial registration identifier, original registration, protocol, SAP and versions/dates.
Materials to obtain first: Trial registration identifier, original registration, protocol, SAP and versions/dates.
Further research: Connect the paper’s identity with registration, protocol and SAP to compare prospective recruitment, joint endpoints, analyses and timing with reports.
Remaining uncertainty: Registration identity, original registration, protocol, SAP and dates/versions remain missing. This does not establish absent registration or selective reporting.
Conditions for verification: Directly compare registration identity and the prospective protocol/SAP for this report.
Why this condition is needed: Needed to reveal which material is required to examine favorable-result selection.
Application exceptions: Do not convert an unestablished registration field into confirmed nonregistration or 0 registration identifiers.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N26 · Is prospective-plan agreement for assessments and analyses at 8 and 12 weeks established?

Current findings: Treatment for 8 weeks, follow-up for 4 weeks off treatment and results at both time points are known. Documents for comparing those time points and analyses with the prospective plan are unavailable.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The reported schedule alone cannot establish agreement with the prospective plan.
Reason for missing information: Planned assessments/analyses at 8 and 12 weeks, report agreement and reasons for changes remain unresolved.
Required materials and conditions: Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes.
Materials to obtain first: Prospective visit schedules, endpoints at 8/12 weeks, analysis plans and reasons for changes.
Further research: Compare planned visit, endpoint and analysis schedules with reported results and check for timing changes or additional analyses.
Remaining uncertainty: Planned assessments/analyses at 8 and 12 weeks, report agreement and reasons for changes remain unresolved.
Conditions for verification: Check agreement between prospective plans and reports for end-of-treatment/off-treatment timing and the corresponding analyses.
Why this condition is needed: Knowing the nominal duration differs from agreement with a prospective plan.
Application exceptions: Unverified timing plans do not establish post hoc analysis.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N27 · Were evidence and bibliographic descriptions of the same paper counted without duplication?

Current findings: The current 1 evidence entry and 1 citation connect to the same Chen 2015 report, PMID 26400188, DOI 10.1002/ptr.5475. PMID and DOI entry points are not separate trials.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The single report’s attribution in the current retained summary was connected without creating additional independent trial counts.
Reason for missing information: The current evidence/bibliography connection to the same report was checked. Other reports, registration, unique participant relationships and total independent trial counts remain unverified.
Required materials and conditions: Report title, PMID, DOI, evidence/citation links, trial family and participant relationships.
Materials to obtain first: Report title, PMID, DOI, evidence/citation links, trial family and participant relationships.
Further research: Connect titles, identifiers and results to check whether evidence-table, citation and PMID/DOI entries concern one report, and separately compare family identity for later material.
Remaining uncertainty: The current evidence/bibliography connection to the same report was checked. Other reports, registration, unique participant relationships and total independent trial counts remain unverified.
Conditions for verification: Connect the same report in the corresponding evidence and citation entries without counting external identifier entry points as additional trials.
Why this condition is needed: Needed to avoid counting bibliography, abstract and paper links as multiple independent trials.
Application exceptions: Connecting one report does not establish a worldwide unique trial count of 1.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N28 · Is independent replication of the same question established?

Current findings: The current retained summary connects only one report for this question. Material to establish the same diarrhea comparison at 8 weeks in other independent unique trials is unavailable.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Report/family material needed to establish independent replication of the same question has not been acquired.
Reason for missing information: Independent replication and overall unique trial/participant relationships remain unresolved. No new literature search was performed, so this does not establish an absence of research.
Required materials and conditions: Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links.
Materials to obtain first: Full reports and registration of independent trials, population/regimen/comparator/timing, results tables and family links.
Further research: Compare trial-specific eligibility and family links to examine independent result distributions, contrary results and condition differences.
Remaining uncertainty: Independent replication and overall unique trial/participant relationships remain unresolved. No new literature search was performed, so this does not establish an absence of research.
Conditions for verification: Check the same formulation, population, comparator, diarrhea result at 8 weeks and family relationships in other unique trials.
Why this condition is needed: Needed to avoid extending one report’s result into independent confirmation.
Application exceptions: No new search and 1 linked report do not establish an absence of independent research.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N29 · What was actually read, and what date scope is being described?

Current findings: The complete retained summary was read here. The evidence reference date is 2026-09-08; historical wording describes checking original PDF tables/methods against the abstract. Current PubMed, DOI and original PDF access, acquisition and reading were not attempted.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Current local reading, historical descriptions and external unread status were recorded separately.
Reason for missing information: The reading scope of the retained summary was checked. Material-specific historical access dates, current external responses/full text, the latest complete literature and publication status were not checked.
Required materials and conditions: Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records.
Materials to obtain first: Original input, byte hash, evidence reference date, actual review date and material-specific historical/current access records.
Further research: Compare the access ledger with original material locations to distinguish summary versus external full-text reading and historical descriptions versus new actions, checking the scope of unverified wording.
Remaining uncertainty: The reading scope of the retained summary was checked. Material-specific historical access dates, current external responses/full text, the latest complete literature and publication status were not checked.
Conditions for verification: Distinguish complete reading of the retained summary from historical PDF-review descriptions and current unattempted/unread external material, with dates.
Why this condition is needed: Needed to avoid overstating local-summary reading as new full-text reading or a current exhaustive search.
Application exceptions: Do not fill material-specific access dates from the global original-verdict review date or describe unattempted access as failed access.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N30 · Are funding, product support and author interests established?

Current findings: The evidence funding description retains the National Natural Science Foundation of China and China–Poland cooperation support. Product provision, author employment, patents and COI declarations are not directly established. Retain the original I2 only as a historical axis.
Verification status: Partly verified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Reported funding exists, but direct content on product support and declared interests remains unresolved.
Reason for missing information: Product provision, employment/patents, COI and sponsor research roles remain unresolved. Funding information alone does not establish absence of bias or independent replication.
Required materials and conditions: Funding, product provision, author employment/patents, COI declarations, institutions and roles.
Materials to obtain first: Funding, product provision, author employment/patents, COI declarations, institutions and roles.
Further research: Compare funding, product provision and author/institutional roles separately to check against unsupported conclusions of independent funding or replication.
Remaining uncertainty: Product provision, employment/patents, COI and sponsor research roles remain unresolved. Funding information alone does not establish absence of bias or independent replication.
Conditions for verification: Check reported funding, product provision, employment, patents and declared interests separately from trial family.
Why this condition is needed: An academic-support name alone does not reveal product support or conflicts of interest.
Application exceptions: Do not use the existing I2 axis as new certification of complete independence.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N31 · Are arm-specific adverse-event/discontinuation counts and collection scope established?

Current findings: The manuscript warns about gastrointestinal reactions including diarrhea, constipation and abdominal pain. Arm-specific AE event/person counts, safety denominators, collection, severity and discontinuation figures for the same trial are absent from the current retained summary.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Warning descriptions do not substitute for quantitative harm counts or collection scope in the actual trial.
Reason for missing information: AE events/persons, safety denominators, collection, severity, discontinuation and missingness for the same trial remain unresolved. Do not convert unverified harms into 0 events or harmlessness.
Required materials and conditions: AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness.
Materials to obtain first: AE definitions, arm-specific event/person counts, safety denominators, duration, collection, severity and discontinuation/missingness.
Further research: Connect safety tables, collection instructions and flow to distinguish event counts from person counts, exposure denominators, discontinuation reasons and missingness.
Remaining uncertainty: AE events/persons, safety denominators, collection, severity, discontinuation and missingness for the same trial remain unresolved. Do not convert unverified harms into 0 events or harmlessness.
Conditions for verification: Check adverse-event events/persons, exposure denominators, collection, severity, discontinuation and missingness in the same trial.
Why this condition is needed: Needed to avoid converting the existence of efficacy reports into no harms or completed safety accounting.
Application exceptions: Do not delete efficacy results because harms are unreported or infer events/denominators.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N32 · Can adverse reactions such as diarrhea be distinguished from IBS symptoms by timing and comparison?

Current findings: The safety description warns that gastrointestinal reactions such as diarrhea, constipation and abdominal pain may confuse intervention effects with disease symptoms. Onset/worsening timing, arm-specific harm comparisons, stopping/recovery and other causes are not established.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The original warning alone cannot establish time/comparison attribution separating baseline IBS symptoms from intervention-related harms.
Reason for missing information: Baseline symptoms, new onset/worsening, arm-specific comparisons, stopping/recovery and concurrent exposures remain unresolved. Do not reinterpret the diarrhea result at 12 weeks as a harm dechallenge signal.
Required materials and conditions: Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures.
Materials to obtain first: Baseline symptoms, onset/worsening timing, stopping/recovery, arm-specific harm comparisons and concurrent exposures.
Further research: Compare symptom/administration timelines, arm-specific harms and alternative exposures to distinguish disease from intervention-related signals and examine limits on causal/risk interpretation.
Remaining uncertainty: Baseline symptoms, new onset/worsening, arm-specific comparisons, stopping/recovery and concurrent exposures remain unresolved. Do not reinterpret the diarrhea result at 12 weeks as a harm dechallenge signal.
Conditions for verification: Check baseline IBS symptoms, onset/worsening after dosing, stopping/recovery, arm-specific comparisons and alternative exposures.
Why this condition is needed: Needed to avoid merging IBS-D diarrhea and intervention-related gastrointestinal reactions into the same event.
Application exceptions: Reporting after exposure alone does not establish causality; do not infer that changes in diarrhea frequency after stopping represent AE recovery.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N33 · Is safety material available for pregnancy, lactation, infants and young children, concomitant drugs and long-term use?

Current findings: The manuscript retains cautions to avoid use or check with clinicians concerning pregnancy, lactation, infants and young children, and CYP-related concomitant drugs. Direct material on vulnerable groups, interactions and long-term/rare harms is absent from current inputs.
Verification status: Unverified
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Warnings are retained, but direct information to establish risks for those groups, concomitant use and long-term exposure is unavailable.
Reason for missing information: Direct information on vulnerable groups, drug interactions and long-term/rare harms remains unresolved. Do not create personal dosing instructions or a new safety grade.
Required materials and conditions: Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms.
Materials to obtain first: Exposure, population, duration and result material for vulnerable groups, CYP-related concomitant use and long-term/rare harms.
Further research: Review safety material and drug-interaction evidence separately by exposure/population without extending a short-term adult efficacy trial into overall safety.
Remaining uncertainty: Direct information on vulnerable groups, drug interactions and long-term/rare harms remains unresolved. Do not create personal dosing instructions or a new safety grade.
Conditions for verification: Check direct material on vulnerable groups, interactions and long-term/rare harms and the applicability limits of original warnings.
Why this condition is needed: Results in a limited adult population and duration cannot guarantee safety in vulnerable groups or long-term use.
Application exceptions: Do not require every rare-harm study as a condition for checking diarrhea efficacy at 8 weeks.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N34 · Does this question require an optimal dose or effects in specific subgroups?

Current findings: The current question concerns 400 mg/day for 8 weeks in adults with Rome III IBS-D. There is no separate original question claiming an optimal dose or superiority in a specific subgroup.
Verification status: Not applicable
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Dose optimization and specific subgroup extensions are not requirements of the current question.
Reason for missing information: Dose/subgroup-extension requirements are not applicable to the current question. Extension would separately require direct comparison and prospective interaction material.
Required materials and conditions: For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results.
Materials to obtain first: For extensions: direct dose comparisons, prospective subgroups, interaction tests and population-specific results.
Further research: When proposing dose/subgroup extensions, design separate questions using direct comparisons and prospective interaction material without merging them into the current principal effect.
Remaining uncertainty: Dose/subgroup-extension requirements are not applicable to the current question. Extension would separately require direct comparison and prospective interaction material.
Conditions for verification: Distinguish the narrow question of 400 mg/day in adults with Rome III IBS-D from separate dose/subgroup-extension requirements.
Why this condition is needed: Needed to avoid converting a principal effect at one dose into an optimal dose or a specific subgroup effect.
Application exceptions: Do not add optimal-dose or all-subgroup research requirements to the current narrow question.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N35 · Does this cover cure, relapse, pain and quality of life beyond diarrhea frequency?

Current findings: The manuscript specifies that the same effect cannot be extended to IBS cure, relapse prevention, microbiome normalization, pain or quality of life. This sheet also addresses diarrhea frequency alone.
Verification status: Not applicable
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Separate clinical/mechanistic extensions are outside the current principal question.
Reason for missing information: Extension requirements are not applicable to the current diarrhea-frequency question. This does not establish sufficient direct evidence for other outcomes.
Required materials and conditions: For extensions: each separate endpoint’s definition, population, duration, comparison and direct results.
Materials to obtain first: For extensions: each separate endpoint’s definition, population, duration, comparison and direct results.
Further research: Design separate questions, measurements and follow-up for each endpoint to examine that a diarrhea-frequency signal does not replace conclusions about cure, relapse, mechanism or quality of life.
Remaining uncertainty: Extension requirements are not applicable to the current diarrhea-frequency question. This does not establish sufficient direct evidence for other outcomes.
Conditions for verification: Distinguish weekly diarrhea frequency from cure, relapse prevention, microbiome normalization, pain and quality of life.
Why this condition is needed: Patient-experienced diarrhea frequency and other clinical/mechanistic outcomes are not the same effect.
Application exceptions: Do not require other clinical-event trials as conditions for checking weekly diarrhea frequency itself.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N36 · Does this scope produce pooled results across studies or repeated harm signals?

Current findings: The current evidence/citation concerns one report, and both time points are results from that report. No pooled across-study estimate or repeated harm signal is produced; total unique trial count remains unrecorded.
Verification status: Not applicable
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Pooling across studies and repeated-harm claims are outside this sheet’s output scope.
Reason for missing information: Pooling/repeated-harm production is not applicable within the current scope. Other material and unique family relationships remain unverified without creating new independent counts.
Required materials and conditions: For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships.
Materials to obtain first: For extensions: unique families, outcome-specific tables, contrary records, original repeated-harm material and recitation relationships.
Further research: If multiple materials are added, separately examine suitability for pooling and repeated signals after comparing unique families, condition differences, contrary results and recitation.
Remaining uncertainty: Pooling/repeated-harm production is not applicable within the current scope. Other material and unique family relationships remain unverified without creating new independent counts.
Conditions for verification: Do not create across-study pooling or repeated harms from one linked report; distinguish unverified family relationships from scope nonapplicability.
Why this condition is needed: Needed to avoid counting multiple time points/links in one report as across-study replication or repeated harms.
Application exceptions: Do not convert nonapplicability of current pooling into a finding of no independent research. Independent replication remains separately unverified.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N37 · Were the scope of the internal English correction and remaining generic wording distinguished?

Current findings: The 2026-09-14 correction was an internal event changing 1 generic English evidence-table field while retaining grade, score, citation and verdict date. Several current generic English evidence/citation statements are not used as additional facts.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: The current bilingual input and correction scope were read, retaining original types, empty values and absence.
Reason for missing information: The scope of the current internal correction and generic wording was checked. Old separate manuscripts, original PDF and current publication-correction status were not newly checked.
Required materials and conditions: The correction event, current original Korean/English correspondence, original field types, absent keys and empty values.
Materials to obtain first: The correction event, current original Korean/English correspondence, original field types, absent keys and empty values.
Further research: Compare the correction event with current bilingual fields to check that generic English verification wording is not read as new participant, funding or analysis facts.
Remaining uncertainty: The scope of the current internal correction and generic wording was checked. Old separate manuscripts, original PDF and current publication-correction status were not newly checked.
Conditions for verification: Retain the scope of the 2026-09-14 internal English wording correction and current generic English wording, empty fields and absent keys.
Why this condition is needed: Needed to avoid inheriting a wording correction as new clinical verification or added content.
Application exceptions: A correction record describing one field change does not establish that all current generic wording has become specific.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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N38 · Were the existing grade, score and axes distinguished from this sheet review?

Current findings: Retain the original C 50, Warning and B/P/R1/I2/EX/B2/CX, coprimary_split=true and all other original flags. Current work converts retained content and performs self-review; it is not a new clinical assessment, calculation or independent certification.
Verification status: Met
Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted.
Why unverified: Original verdict fields and sheet states were separated without changing the original.
Reason for missing information: Preservation of the original verdict, score and axes was checked. Sheet states do not newly certify the original efficacy grade or clinical sufficiency.
Required materials and conditions: The original grade, score, safety, axes, grade decision and current review scope.
Materials to obtain first: The original grade, score, safety, axes, grade decision and current review scope.
Further research: Compare original fields with sheet states to check that historical verdicts, null wording and Codex cross-check descriptions are not upgraded into current reassessment or specialist certification.
Remaining uncertainty: Preservation of the original verdict, score and axes was checked. Sheet states do not newly certify the original efficacy grade or clinical sufficiency.
Conditions for verification: Retain original C 50, Warning and axes/flags as preserved original information without converting them into a new sheet completion proportion, grade or clinical certification.
Why this condition is needed: The original verdict and verification states for producing an evidence-gap sheet are different information.
Application exceptions: Do not use original I2, EX, CX, coprimary_split or historical cross-check wording as evidence of new clinical validation.
Referenced methods: Existing method principles distinguish population, formulation, actual comparator, weekly diarrhea frequency, time points, participant reports, dispersion, analysis, study families, funding and harms. Detailed conditions are Chamgap’s own application.

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