{ "schema_version": "chamgap-public-criteria-1.0", "title": "Berberine hydrochloride plus lifestyle intervention × Reduction of ¹H-MRS liver fat in adults with NAFLD", "language": "en", "translation_date": "2026-10-27", "criteria_version": "1.0", "criteria_date": "2026-10-05", "condition_origin": "Chamgap's own application conditions", "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Link studies and reports separately; do not omit studies solely because results are unreported.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." } ], "status_dictionary": { "Partly verified": "Some retained information is available while required unverified material remains.", "Unverified": "The criterion cannot be established within the retained scope; this does not mean 0 studies, 0 effect or no harm.", "Review incomplete": "Original-material comparison/search was not performed within the permitted scope.", "Not reported": "A scope-limited status meaning the item was not stated in the particular material/section that was read.", "Inaccessible": "Used only for material for which access was actually attempted and failed. It was not assigned to clinical material in this conversion.", "Insufficient evidence matching the conditions": "Used only after relevant studies within a defined scope have been reviewed and evidence is insufficient to answer the criterion. It was not applied indiscriminately in this conversion.", "Not applicable": "A specific exception based on applicability conditions, not a substitute for unread material.", "Conflicting data": "Used when incompatible information for the same question, time and analysis has been compared. Different review estimates alone do not establish this status.", "Met": "The specified retained information and reading/attribution/counting boundary were checked; this is not certification of efficacy, full-text reading or reassessment." }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Which liver-fat question is being checked?", "needed": "The current original claim, formulation, population, comparator, measurement and timing", "role": "Required", "role_reason": "The claim boundary must be fixed to avoid mixing results from other MASLD trials.", "application_exception": "Cirrhosis prevention or histologic recovery is not imposed as a requirement for the 16-week liver-fat question.", "criterion": "Link the original claim unchanged and identify 1.5 g/day plus lifestyle, 16 weeks, relative ¹H-MRS change and the lifestyle comparator.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "If the question changes, review different interventions, comparators and endpoints as separate comparisons." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Do the actual product and salt form match?", "needed": "Hydrochloride tablets, product specifications, purity, batch, manufacturing and botanical source", "role": "Required", "role_reason": "An ingredient name alone does not make different extracts, derivatives or combination products the same intervention.", "application_exception": "The berberine description in S2 does not automatically fill in the exact product or salt form in S1.", "criterion": "Link tablet specifications, manufacturing and composition/batch records for each trial to establish whether they match the selected intervention.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Distinguish product variants and do not treat an unverified product as interchangeable." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "What are the nominal dose and actual intake?", "needed": "Nominal 500 mg TID, actual intake, adherence, discontinuation and exposure", "role": "Required", "role_reason": "Differences between prescribed dose and actual exposure affect interpretation of the effect of interest and harms.", "application_exception": "The 1 g/day in S2 is not used as actual intake or a dose-reduction record for S1.", "criterion": "Link the nominal schedule to actual arm-specific intake/adherence, changes and discontinuation to assess actual exposure.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Retain actual dosing/change information relevant to the effect of interest and do not combine it with other doses." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Which adults with NAFLD were selected?", "needed": "Diagnosis, eligibility/exclusions, age, baseline liver fat, diabetes composition and concomitant medicines", "role": "Required", "role_reason": "The labels NAFLD and diabetes-free obese MASLD alone do not establish identical populations.", "application_exception": "The diabetes-free obese eligibility in S2 is not retrospectively assigned to S1.", "criterion": "Check S1 diagnosis, eligibility and baseline state/diabetes composition to explain matches and differences from the selected population.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Limit interpretation to populations with direct material; application to other populations is a separate question." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "What was the actual comparator strategy?", "needed": "Lifestyle alone, medicines/management in each of the 3 arms, and the S2 placebo", "role": "Required", "role_reason": "Different comparator contents change the question answered by a between-arm difference.", "application_exception": "The open-label lifestyle comparator is not converted into a blinded placebo comparator.", "criterion": "Check whether actual S1 arm contents, the selected lifestyle comparator and rescue/common management correspond to original material.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Specify the complete comparator and interpret trials with different common management separately." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "How was background lifestyle intervention applied in each arm?", "needed": "Diet, activity, visits, education, support, actual implementation and differences", "role": "Required", "role_reason": "In an add-on comparison, differences in lifestyle implementation cannot be merged into the selected drug contribution.", "application_exception": "Identical behavioral change is not imposed, but actual arm differences and their handling must be checked.", "criterion": "Check lifestyle contents, implementation/changes and analysis implications in both arms to interpret the added-drug difference.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Observe common management and actual implementation and analyze them in relation to the add-on effect of interest." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Do the 16-week treatment and observation periods match?", "needed": "Start, actual treatment, 16-week assessment, discontinuation and follow-up schedule", "role": "Required", "role_reason": "Nominal treatment duration cannot be converted into actual exposure or every participant’s observation time.", "application_exception": "The 6 months in S2 are not counted as extension follow-up for S1.", "criterion": "Check S1 treatment, assessment, discontinuation and missingness timing and link it to the 16-week result.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Retain differences between the specified outcome time and actual observation; persistence requires separate follow-up." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Which test measured liver fat?", "needed": "¹H-MRS equipment, acquisition, region, quality control and test timing", "role": "Required", "role_reason": "A matching test name alone does not establish measurement conditions or bias.", "application_exception": "S1 ¹H-MRS is not replaced by MRI-PDFF, and the detailed MRI technique in S2 is not inferred.", "criterion": "Check test protocol, assessment region, quality control and identical arm-specific measurement to interpret the selected result.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Match measurement methods and conditions; do not substitute different technologies as an identical measure." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Can relative reduction be distinguished from percentage points?", "needed": "Baseline/final liver fat, relative-change definition, dispersion and between-arm estimate units", "role": "Required", "role_reason": "Numbers under different units and times must not be read as the same effect.", "application_exception": "52.7%/36.4% are not converted into percentage points, and no new difference against S2 is calculated.", "criterion": "Check each result’s measure, reference value, direction, unit and actual between-arm estimate/interval to explain whether they match.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Retain original units and do not convert, add or generate new effects without original data." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "What was the planned hierarchy of the selected liver-fat endpoint?", "needed": "Primary/secondary status and change times in the initial registration, protocol and SAP", "role": "Required", "role_reason": "A principal-outcome label and prespecified primary designation are different information.", "application_exception": "Failure to read the registry currently does not establish nonregistration or selective reporting.", "criterion": "Check liver-fat hierarchy, change timing and reasons in relevant registration/plan versions and compare them with actual reporting.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Retain the original endpoint-hierarchy description; distinguish changes from added evidence after actual version comparison." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "Were planned analyses/times compared with actual reporting?", "needed": "Planned analysis populations, missing-data handling, adjustment, timing and reasons for changes", "role": "Required", "role_reason": "Having seen a result does not establish agreement with the planned analysis.", "application_exception": "A historical registration-comparison statement in the public text is not promoted to current SAP reading.", "criterion": "Compare planned and actual analysis, timing and population for the selected result using original versions, retaining differences and reasons for changes.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Link material that permits planned-versus-reported comparison; lack of comparison does not establish selective reporting." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "What was the randomized design?", "needed": "3-arm parallel randomization, allocation ratio, sequence generation and recruitment/allocation timing", "role": "Required", "role_reason": "A randomized label alone does not verify the actual allocation process.", "application_exception": "Unverified design is not replaced by nonapplicability of crossover/cluster designs.", "criterion": "Check the actual design, random sequence/allocation ratio and implementation for the selected comparison to explain confounding limitations.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Check actual allocation and implementation; a label alone does not establish absence of bias." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Was allocation concealed?", "needed": "Allocation-concealment method, predictability and enrollment/allocation responsibilities", "role": "Required", "role_reason": "Open-label treatment and allocation concealment are different procedures that require separate checks.", "application_exception": "An open-label design alone does not establish allocation-concealment failure.", "criterion": "Check who could see the sequence before allocation and the evidence of actual concealment implementation.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Check actual allocation procedures relevant to selection bias; do not describe an unverified item as established failure." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "How were assessor blinding and arm-specific measurements handled?", "needed": "Blinded reading, identical tests, measurement/exclusion decisions and missingness", "role": "Required", "role_reason": "Objective tests can still be affected by acquisition, reading and exclusion decisions.", "application_exception": "Participant open-label information does not automatically determine assessor-blinding status.", "criterion": "Check assessor access to information and arm-specific differences in testing, reading and quality control to explain measurement limitations.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Assess limitations according to observed measurement conditions; inability to blind does not automatically establish efficacy failure." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Were baseline states balanced in the selected comparison?", "needed": "Arm-specific liver fat, diabetes/weight, medicines, sex and baseline risk", "role": "Required", "role_reason": "The results of selection and allocation are needed to interpret actual between-arm differences.", "application_exception": "S2 population composition is not evidence of baseline balance in S1.", "criterion": "Check arm-specific baseline tables, selection processes and relevant adjustments to explain important differences.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Check analysis information relevant to the direct population and arm-specific baseline differences." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "What were the randomized, completed and analyzed counts in each arm?", "needed": "Arm-specific randomized n, 16-week measured n, completed n and n for each analysis", "role": "Required", "role_reason": "Using 184 or completion counts as the selected effect’s analysis denominator would introduce error.", "application_exception": "Completion counts of 53/47/55 are not assigned to arms, summed or used to calculate new attrition rates.", "criterion": "Link randomized, measured, completed and analyzed counts for the selected arms and the overall 3 arms to actual flow/result tables.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Directly check denominator type and arm attribution; do not infer unreported denominators." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "How were missingness, attrition and outcome measurement handled?", "needed": "Reasons/timing for missingness and attrition, arm differences, missing-data handling and sensitivity analyses", "role": "Required", "role_reason": "Analysis attrition can affect interpretation of both actual effects and harms.", "application_exception": "Completion tables alone do not establish attrition causes, adverse-event discontinuations or random missingness.", "criterion": "Check arm-specific missingness/attrition, liver-fat measurement, handling models and sensitivity analyses to explain limitations.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Check missing-data handling and interpretation for the effect of interest; do not calculate new effects from attrition counts." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Which analysis population and model produced the reported effect?", "needed": "ITT/PP/completers, between-arm change, adjustment, model and effect of interest", "role": "Required", "role_reason": "It is necessary to know whether arm-specific relative reductions estimate assignment effects or completer effects.", "application_exception": "Without analysis information, do not label the result as ITT, PP or adjusted effect.", "criterion": "Check the actual analysis population, model, adjustment and effect of interest for the selected between-arm result and explain alignment with the question.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Distinguish assignment/adherence effects of interest from actual estimates; do not invent an analysis label." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Were the 16-week between-arm estimate and interval adequately reported?", "needed": "Exact between-arm effect, CI level, dispersion, denominator and estimation model", "role": "Required", "role_reason": "Statistical significance alone cannot establish effect magnitude or precision.", "application_exception": "The 97.5% CI in S2 is not inherited as the S1 interval or changed into a 95% CI.", "criterion": "Link the effect estimate, interval and dispersion/denominator for the selected 16-week comparison to interpret the range of effects it permits.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Retain reported numbers only; do not calculate new differences, CIs or meta-analyses." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "What defines clinical importance for liver-fat change?", "needed": "A justified important liver-fat difference, measure, population, duration and interval", "role": "Required", "role_reason": "Statistical P values and clinically meaningful changes must be distinguished.", "application_exception": "Do not invent universal minimum sample-size, duration or effect-magnitude thresholds.", "criterion": "Check a justified importance threshold for relative ¹H-MRS change in the relevant population and its relationship to the selected effect/interval.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Explain an evidence-based importance threshold first; do not create new efficacy scores or grades." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Which study family is each report linked to?", "needed": "Reports, PMID/DOI/PMCID, registration identity, population/arms and overlapping participants", "role": "Required", "role_reason": "Multiple paper, bibliography and registration gateways do not imply multiple trials.", "application_exception": "Identifier strings alone do not establish trial families or total independent-trial counts.", "criterion": "Link each report’s identity and same/different/uncertain family relationship using original material, retaining the undetermined total unique-trial count.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Link reports separately from study families; do not count identifiers as independent trials." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Were the conditions of the opposing 2026 result retained?", "needed": "S2 population, 1 g/day, placebo, 6 months, MRI and original effect/interval", "role": "Required", "role_reason": "Keeping only the favorable 16-week result would lose related opposing results and applicability differences.", "application_exception": "S2 under different conditions is not converted into direct failure of the exact 16-week comparison or replication at the same dose.", "criterion": "Retain the recorded S2 direction, original numbers and condition differences together; do not combine them as the same estimate as S1.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Do not hide opposing results under different conditions; review individually whether they answer the same question." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Were unique trials and participants protected from double counting?", "needed": "Relationships among reports, trials, participants and endpoints/times/analyses", "role": "Required", "role_reason": "Simply adding Korean/English text, PubMed/PMC/registration gateways or reports under different conditions inflates evidence counts.", "application_exception": "Do not add 184 and 337 or sum completion counts of 53/47/55.", "criterion": "Retain established report relationships and uncertainties; do not generate overall unique-trial/participant totals without evidence.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Group related reports into families before counting; do not create totals without independence information." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "How were funding, product provision and interests checked?", "needed": "Funding, product supply/manufacturer roles, author employment/patents, COI and design control", "role": "Supplementary; required for independence claims", "role_reason": "Checking public funding differs from checking product/design control and author interests.", "application_exception": "Academic/public support or the original I2 is not inherited as complete verification of independence.", "criterion": "Link funding, product provision, author/patent/COI information and design-control scope for each report to actual disclosures.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Review funding, product provision and author interests separately; unverified information is not independent funding." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Which materials were acquired and read in this review?", "needed": "Current material type, original bytes, actual reading scope and external access/reading attempts", "role": "Required", "role_reason": "Reading a local summary must be distinguished from reading an external paper/registration in full.", "application_exception": "The existence of PMC/DOI/registration links is not converted into full-text acquisition or successful access.", "criterion": "Ensure acquisition, actual reading, times/locations/SHA for each material match actual actions, retaining unattempted external access.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "When new material is actually read, link its type, time, scope and original location/SHA separately." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "Were the evidence date and this review date distinguished?", "needed": "Original verdict-review date, historical search records, current reading date and item-specific access dates", "role": "Required", "role_reason": "A historical text’s review date cannot be retrospectively assigned as current external access.", "application_exception": "The original 2026-09-08 is not used as a new search date or an individual PubMed/PMC access date.", "criterion": "Link the meaning of the original date, current reading date, unperformed search/access and the scope of absence statements.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Record dates and actual verification scope of additional material separately, updating only the linked rows." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "How were citation registration identifiers and the structured registration field handled?", "needed": "Bibliographic identifiers, original registration-check values, original-registry links and corrections", "role": "Required", "role_reason": "Unverified structured fields and bibliographic clues cannot overwrite each other.", "application_exception": "S1/S2 identifiers are not interchanged or presented as actual current registration comparison.", "criterion": "Retain both unverified original registration-check fields and citation identifiers; verify exact trial links against original material.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Retain conflicting/unverified identifiers; do not upgrade linkage without original-material comparison." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Were generic English descriptions and the existing correction retained?", "needed": "Original Korean/English values, 2026-09-14 correction scope and original verdict/score", "role": "Required", "role_reason": "Generic English descriptions cannot substitute for actual denominator/CI verification.", "application_exception": "The existence of a correction note is not promoted to additional clinical verification in this conversion.", "criterion": "Link original Korean/English text, correction and score/axes unchanged; do not use generic descriptions to fill specific unknowns.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Keep new evidence additions separate from wording/condition changes and preserve complete before/after texts." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Were persistence and discontinuation effects beyond 16 weeks checked?", "needed": "Extension/post-discontinuation follow-up under the same conditions, with effects/denominators at additional times", "role": "Supplementary; required when extending to persistence", "role_reason": "Short-term liver-fat results alone cannot establish post-discontinuation persistence or long-term benefit.", "application_exception": "The 6 months in S2 are not used as extension follow-up of the same S1 participants.", "criterion": "Link direct extension/discontinuation follow-up under the same 16-week conditions, with time-specific estimates and denominators, to the persistence question.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "When claiming persistence, review a separate question using direct follow-up; do not impose an arbitrary minimum duration." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Were the doses directly compared?", "needed": "Randomized dose comparisons in the same population/comparator/test, with adherence and estimates", "role": "Supplementary; required for optimal-dose claims", "role_reason": "Differences between 1.5 g and 1 g in separate trials do not show a direct dose response.", "application_exception": "A dose-comparison trial is not imposed unconditionally for the narrow 16-week question.", "criterion": "Link direct dose-comparison design, actual exposure and between-arm estimates to optimal-dose/dose-response questions.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "When extending the dose question, use a direct design that separates differences in other conditions." }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Can effects by diabetes status and disease stage be distinguished?", "needed": "Prespecified subgroups, composition, interactions, estimates/intervals and denominators", "role": "Supplementary; required for subgroup application", "role_reason": "Overall effects in different populations cannot be converted into effect modification by diabetes status.", "application_exception": "Diabetes-free eligibility in S2 alone does not establish an interaction relative to a diabetic group.", "criterion": "Check prespecified relevant subgroups, composition, interactions and subgroup estimates/denominators to assess effect modification.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Subgroup application requires direct plans/estimates; different significance across separate trials is not an interaction." }, { "item_id": "N32", "question_type": "Evidence condition", "question": "Does the liver-fat result answer cirrhosis or histologic-recovery questions?", "needed": "Direct data for the selected liver-fat measure versus histology, clinical events and quality of life", "role": "Supplementary; required when extending to clinical events", "role_reason": "A reduction in a surrogate cannot automatically be extended to cirrhosis prevention or benefit in all MASLD.", "application_exception": "Not every clinical-event trial is imposed as required for a liver-fat numerical question.", "criterion": "Review extensions to clinical events, histology or quality of life using their direct results, denominators and estimates.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "When extending to clinical-event questions, review a separate table of direct endpoints." }, { "item_id": "N33", "question_type": "Evidence condition", "question": "How were recorded gastrointestinal adverse effects defined and collected?", "needed": "Symptom/diagnosis definitions, collection methods, severity, harm-related discontinuation and each arm", "role": "Supplementary; required for the harm in question", "role_reason": "Warnings or general symptom descriptions differ from complete harm counts.", "application_exception": "Keep liver-fat efficacy status separate from harm-record status.", "criterion": "Check event definitions, ascertainment/collection, severity and arm-specific reporting for the selected exposure to explain the harm-information level.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Check actual harm counts and event definitions separately from efficacy." }, { "item_id": "N34", "question_type": "Evidence condition", "question": "How do harm onset/recovery and dosing timing relate?", "needed": "Exposure start, discontinuation, onset, recovery, re-exposure and follow-up duration", "role": "Supplementary; required for harm timing", "role_reason": "A nominal 16-week treatment period alone cannot establish event latency or recovery.", "application_exception": "Without recovery-after-discontinuation or re-exposure information, do not create a causal timeline.", "criterion": "Link actual exposure, harm onset/recovery timelines and observation limits to direct material.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Obtain timing material appropriate to the harm question; temporal order alone does not establish cause." }, { "item_id": "N35", "question_type": "Evidence condition", "question": "Against which exposures and concurrent treatments were harms compared?", "needed": "Arm-specific exposure, lifestyle, diabetes/concomitant medicines, baseline disease and event comparisons", "role": "Supplementary; required for comparative harm/causation", "role_reason": "Without concurrent-treatment, baseline-risk and actual event comparisons, a particular drug contribution cannot be established.", "application_exception": "The existence of an efficacy comparator is not converted into completed harm-event comparison.", "criterion": "Link arm-specific events, exposure/concomitant medicines, baseline risks, alternative explanations and adjustments to explain comparative-harm limitations.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Review harm comparisons and alternative causes individually; theoretical warnings are not observed incidence." }, { "item_id": "N36", "question_type": "Evidence condition", "question": "Are event counts and exposure denominators available for harm frequency?", "needed": "People/events affected, arm-specific safety denominators, exposure time, discontinuation and CI", "role": "Supplementary; required for incidence", "role_reason": "Randomized totals or warnings alone cannot be used to calculate harm frequency.", "application_exception": "Do not use 184, 337 or completion counts of 53/47/55 as safety denominators or create 0 events.", "criterion": "Directly link each event’s counts, arm-specific exposed/safety denominators, observation time and reported estimates.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Link reported harm frequencies only to their denominators/times; do not calculate new incidence." }, { "item_id": "N37", "question_type": "Evidence condition", "question": "Were missing harm reports and overlapping related reports checked?", "needed": "Collection/detection, spontaneous/systematic reporting, attrition, related reports and opposing records", "role": "Supplementary; required for repeated signals", "role_reason": "Unreported harms differ from absent events, and repeat citations differ from independent events.", "application_exception": "Regulatory warnings or repeated citations of the same case are not counted as independent events.", "criterion": "Link actual event collection/selection, missingness, the full disclosure scope and related-report families/overlap to original material.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Retain opposing/unreported records and actual event families; do not infer new replication counts." }, { "item_id": "N38", "question_type": "Evidence condition", "question": "What is known about long-term/rare harms and vulnerable groups?", "needed": "Long-term/rare events, liver disease/diabetes medicines, pregnancy/lactation/infants and interactions", "role": "Supplementary; required for that safety extension", "role_reason": "Short-term results in a restricted population cannot be extended to every person’s safety.", "application_exception": "Not all rare-harm studies are imposed as efficacy requirements for the selected 16-week liver-fat question.", "criterion": "Explain direct harm material and applicability limits for the duration, vulnerable population or concurrent exposure to which claims are extended.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Review safety extensions using separate questions, designs and material; unverified information is not personal safety." }, { "item_id": "N39", "question_type": "Evidence condition", "question": "How far does the current warning support harm statements?", "needed": "Event reports, comparisons, denominators, timing, alternatives and the evidence level behind the warning", "role": "Supplementary; required for harm causation", "role_reason": "General warnings differ from actual causation, incidence and personal-safety assessments.", "application_exception": "Do not remove the original warning or convert it into a new safety grade or personal dosing instruction.", "criterion": "Link the warning’s actual evidence level and distinguish verified scope and limits for signals, comparative harms, causation and frequency.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Describe only the observable harm-information level; do not generate safety certification or a new verdict." }, { "item_id": "N40", "question_type": "Evidence condition", "question": "Which rows should be updated when new material arrives?", "needed": "Identity, material type, date, actual reading, original location/SHA and condition/observation versions", "role": "Required", "role_reason": "New file collection must be tracked separately from condition revisions and actual review/display changes.", "application_exception": "New API responses or historical verification dates alone do not automatically satisfy a condition.", "criterion": "Identify facts, locations, versions and linked rows for each added material; preserve the complete previous material and condition-revision event.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained reports. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are in-house conditions for adding berberine hydrochloride versus lifestyle intervention alone on 16-week ¹H-MRS liver fat, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Preserve the complete previous version, separate material additions from condition revisions, then recheck linked-row evidence, statuses and reading links." } ] }