{
  "schema_version": "chamgap-public-criteria-1.0",
  "title": "Oral berberine added to conventional heart-failure therapy × Reduction of all-cause mortality in chronic congestive heart failure",
  "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": {
    "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 reported": "A scope-limited status indicating that an item was not stated in a specific material or section actually read.",
    "Conflicting data": "Used when incompatible material for the same question, time and analysis has actually been compared. Different review numbers alone do not establish this status.",
    "Not applicable": "Used only with a reason that an item is outside the actual scope of the selected question. It does not replace unverified or unread status.",
    "Inaccessible": "Used only for material for which access was actually attempted and failed. Not assigned to clinical material in this work.",
    "Review incomplete": "Original-material comparisons or searches were not performed within the authorized scope."
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Evidence condition",
      "question": "Are the independent claim and inclusion/exclusion boundaries linked to the original article?",
      "needed": "Canonical locations for the original claim, population, add-on treatment, comparator, mortality endpoint, timing and exclusions",
      "role": "Required",
      "role_reason": "Needed to keep mean 24-month all-cause mortality separate from 8-week functional assessment and other heart-failure outcomes.",
      "application_exception": "Korean and English concern the same claim. Do not invent and count separate claims from an empty subclaim list.",
      "criterion": "Link the original claim to the question of all-cause mortality with oral berberine added to then-conventional common therapy versus placebo in the selected heart-failure population.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "If article boundaries change, preserve the whole previous article and compare intervention, comparator, endpoint and timing again."
    },
    {
      "item_id": "N02",
      "question_type": "Evidence condition",
      "question": "Are actual diagnosis, severity, eligibility and baseline characteristics verified?",
      "needed": "Eligibility tables, heart-failure severity, baseline function, etiologic composition and arm-specific baseline tables",
      "role": "Required",
      "role_reason": "Needed to distinguish all heart-failure patients from the selected population with ventricular arrhythmia and dilated cardiomyopathy.",
      "application_exception": "Retain the mixed ischemic/idiopathic population. Do not infer its proportions or subgroup effects.",
      "criterion": "Verify actual inclusion/exclusion criteria, severity and arm-specific baseline characteristics in addition to the recorded diagnosis and ventricular arrhythmia.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare original recruitment criteria and baseline tables; examine representativeness of the selected population and balance between arms."
    },
    {
      "item_id": "N03",
      "question_type": "Evidence condition",
      "question": "Are mortality effects separately verified for ischemic/idiopathic etiologies and ventricular-arrhythmia subgroups?",
      "needed": "Denominators by etiology/arrhythmia type, prespecified subgroup plans, effects and interaction material",
      "role": "Supplementary; required for subgroup extensions",
      "role_reason": "Needed to prevent extending the main effect in a mixed population to specific etiologic or arrhythmia subgroups.",
      "application_exception": "Do not require every subgroup effect when examining the narrowly defined overall-population claim.",
      "criterion": "Verify prespecified definitions by etiology/arrhythmia type, actual denominators, interactions or separate comparative estimates.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Examine prespecified subgroups and interaction analyses separately from the overall population result."
    },
    {
      "item_id": "N04",
      "question_type": "Evidence condition",
      "question": "Are the actual berberine salt, formulation, product and manufacturing specifications verified?",
      "needed": "Original product name, salt/formulation/content specifications and manufacturing, batch and quality documents",
      "role": "Required",
      "role_reason": "Needed to prevent automatically substituting berberine hydrochloride, plant extracts or other derivatives for the actual trial product.",
      "application_exception": "Do not fill unverified salt, plant-source or product information from a title or generic ingredient name.",
      "criterion": "Verify the actual administered product's salt form, formulation, purity, manufacturing batch and quality material.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Cross-compare original methods and product documents; examine identity with other salts, extracts and combinations separately."
    },
    {
      "item_id": "N05",
      "question_type": "Evidence condition",
      "question": "Are actual dose, frequency, titration and adherence for 1.2–2.0 g/day verified?",
      "needed": "Dosing schedules, dose-selection/titration records, exposure definitions, adherence and discontinuation records",
      "role": "Required",
      "role_reason": "Needed to avoid turning a nominal dose range into actual individual exposure or an optimal dose.",
      "application_exception": "Do not choose an arbitrary representative dose or convert salt mass into active-ingredient mass.",
      "criterion": "Verify oral route, reported daily dose, actual frequency, dose selection/titration and arm-specific adherence.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare actual prescribing/use records with the original protocol; examine handling of adherence for the effect of interest."
    },
    {
      "item_id": "N06",
      "question_type": "Evidence condition",
      "question": "Are actual exposure, changes and discontinuation during mean 24-month follow-up after the 8-week assessment verified?",
      "needed": "Treatment, discontinuation, concomitant changes, individual follow-up/exposure and event-time records after 8 weeks",
      "role": "Required",
      "role_reason": "Needed to avoid treating the 8-week treatment assessment and long-term mortality follow-up as the same dosing duration.",
      "application_exception": "Mean follow-up is not identical exposure duration for every participant.",
      "criterion": "Distinguish the 8-week treatment assessment from mean 24-month follow-up; verify subsequent actual continuation, changes, discontinuation and exposure at event times.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Link time-varying exposure and treatment changes to mortality follow-up and compare them with the analysis effect of interest."
    },
    {
      "item_id": "N07",
      "question_type": "Evidence condition",
      "question": "Are actual arm-specific placebo and then-conventional common treatment, including changes, verified?",
      "needed": "Placebo specifications and documents for arm-specific background-treatment doses, changes, rescue treatment and handling",
      "role": "Required",
      "role_reason": "Needed to avoid replacing the additional-berberine comparison with a difference in all then-conventional therapy or an effect under modern treatment.",
      "application_exception": "Do not require every change to be identical in both arms; verify the actual effect of interest and handling methods.",
      "criterion": "Verify placebo plus then-standard treatment and actual arm-specific prescribing, changes and rescue use of ACE inhibitors, digoxin, diuretics and nitrates.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare original prescribing/common-treatment documents by arm; examine attribution of add-on effects and concurrent changes."
    },
    {
      "item_id": "N08",
      "question_type": "Evidence condition",
      "question": "Are random-sequence generation, allocation concealment and baseline balance verified?",
      "needed": "Original allocation methods, concealment procedures, implementation responsibilities and arm-specific baseline tables",
      "role": "Required",
      "role_reason": "Needed to avoid claiming that an RCT label resolves allocation procedures and selection differences.",
      "application_exception": "Retain the randomized-trial description without inventing detailed procedures.",
      "criterion": "Verify actual sequence generation, concealment, allocation implementation and baseline balance.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Read actual allocation procedures and baseline tables; examine limitations relevant to the selected all-cause mortality result."
    },
    {
      "item_id": "N09",
      "question_type": "Evidence condition",
      "question": "Is blinding of participants, clinicians, death adjudicators and analysts verified?",
      "needed": "Blinding methods, role-specific maintenance/unblinding and death-adjudicator/analyst material",
      "role": "Required",
      "role_reason": "Needed to distinguish placebo use from verified blinding of everyone involved.",
      "application_exception": "Even with relatively objective all-cause mortality, actual adjudication, follow-up and analysis conditions require separate verification. Unverified blinding is not automatic failure.",
      "criterion": "Verify actual blinding, maintenance, unblinding and conditions affecting outcome collection for each role.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare role-specific blinding procedures with original methods and outcome collection/adjudication."
    },
    {
      "item_id": "N10",
      "question_type": "Evidence condition",
      "question": "Are the all-cause mortality definition, ascertainment sources, adjudication and collection times verified?",
      "needed": "Death definitions, ascertainment sources, adjudicators, follow-up collection methods and event dates",
      "role": "Required",
      "role_reason": "Needed to avoid interpreting death counts as automatically complete and identically ascertained events.",
      "application_exception": "The original endpoint is all-cause mortality. Do not replace it with cardiovascular, sudden or arrhythmic death.",
      "criterion": "Verify the all-cause mortality label, actual death-ascertainment sources, adjudication criteria, arm-specific collection routes and dates.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare definitions and collection routes in death-adjudication/follow-up material between arms."
    },
    {
      "item_id": "N11",
      "question_type": "Evidence condition",
      "question": "Are the prespecified hierarchy and assessment timing for all-cause mortality verified?",
      "needed": "Dated registration/protocol endpoint hierarchies, assessment times and change histories",
      "role": "Required",
      "role_reason": "Needed to avoid automatically designating the current claim as the trial's prespecified primary endpoint.",
      "application_exception": "Neither the original principal-endpoint contract nor the current table's main endpoint proves trial prespecification.",
      "criterion": "Verify the primary/secondary hierarchy of mortality endpoints and planned follow-up times in documents preceding trial initiation.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare prospective documents with actual reporting chronologically to examine endpoint selection and changes."
    },
    {
      "item_id": "N12",
      "question_type": "Evidence condition",
      "question": "Is the relationship of 156 participants and 79/77 to allocated, exposed, completed and analyzed denominators verified?",
      "needed": "Participant-flow diagrams, arm-specific allocation/exposure/completion/analysis counts and exclusion reasons",
      "role": "Required",
      "role_reason": "Needed to distinguish sample-size and death-count denominators from ITT populations or complete-follow-up denominators.",
      "application_exception": "Do not invent actual completed/analyzed counts from generic English wording about distinct denominators.",
      "criterion": "Verify actual recruitment, allocation, exposure, completion and mortality-analysis flow and denominators in addition to reported 156 participants and 79/77.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Link original flow diagrams to mortality-analysis tables and compare each denominator's definition separately."
    },
    {
      "item_id": "N13",
      "question_type": "Evidence condition",
      "question": "Are original death counts and the paper P value attributed to exact reporting locations?",
      "needed": "Original result wording, exact death-count/P-value locations and editions",
      "role": "Required",
      "role_reason": "Needed to distinguish original-value preservation from new effect estimation and retain the favorable event direction.",
      "application_exception": "Met for this recording condition does not establish a risk ratio, HR, CI or analysis validity.",
      "criterion": "Link 7/79 versus 13/77 and paper P<.02 to original evidence, citations and bilingual articles without adding newly calculated values.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "When new material arrives, compare original result tables and time-to-event analysis while preserving them separately from the current original record."
    },
    {
      "item_id": "N14",
      "question_type": "Evidence condition",
      "question": "Are individual follow-up duration, censoring, study termination and complete death ascertainment verified?",
      "needed": "Individual or arm-specific follow-up distributions, censoring/loss-of-contact/termination records and survival-curve risk sets",
      "role": "Required",
      "role_reason": "Needed to avoid turning mean 24 months into complete, identical follow-up for every participant.",
      "application_exception": "Unverified completeness does not establish actual missed deaths or a particular magnitude of bias.",
      "criterion": "Verify arm-specific follow-up distributions, reasons for censoring, termination, vital-status ascertainment and risk sets.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Examine survival-follow-up flow and risk sets to compare event ascertainment and censoring assumptions."
    },
    {
      "item_id": "N15",
      "question_type": "Evidence condition",
      "question": "Are arm-specific dropout, exclusion and missingness counts and their handling in mortality analysis verified?",
      "needed": "Dropout/exclusion/missingness tables, arm-specific reasons and documents for handling missing mortality status",
      "role": "Required",
      "role_reason": "Needed to avoid treating original denominators as complete analysis of all allocated participants.",
      "application_exception": "Do not fill unrecorded dropout counts with 0 or derive them backwards from event counts.",
      "criterion": "Verify arm-specific missingness, dropout, analysis-exclusion reasons, missing vital-status handling and sensitivity material.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Examine consistency among original flow diagrams, analysis populations, missing-data handling and mortality reporting."
    },
    {
      "item_id": "N16",
      "question_type": "Evidence condition",
      "question": "Are formal between-arm mortality effects, the effect of interest, model and 95% CI verified?",
      "needed": "Formal between-arm estimates, 95% CI, estimation measure, model, effect of interest and analysis-population definitions",
      "role": "Required",
      "role_reason": "Needed to distinguish the direction of aggregate death counts from time-to-event effect magnitude and precision.",
      "application_exception": "Valid unadjusted between-arm estimates are possible. Do not require an adjusted model or HR as the only format for every analysis.",
      "criterion": "Verify actual between-arm estimates, measure, model, analysis population and interval appropriate to the selected effect of interest.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare the original survival/mortality analysis effect of interest, model and interval, attributing them separately from aggregate events."
    },
    {
      "item_id": "N17",
      "question_type": "Evidence condition",
      "question": "Are the test, contrast, time handling and multiplicity underlying paper P<.02 verified?",
      "needed": "Original statistical methods/result tables, tests, contrasts, time handling and multiplicity plans",
      "role": "Required",
      "role_reason": "Needed to avoid recalculating or reattributing the original P value as a simple event-count test.",
      "application_exception": "Currently absent analysis details do not establish that the paper P value is wrong.",
      "criterion": "Verify the test, contrast of interest, time-to-event handling, multiplicity and analysis population corresponding to the reported P value.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare the original P value with the analysis description; do not equate it automatically with a different test on aggregate event counts."
    },
    {
      "item_id": "N18",
      "question_type": "Evidence condition",
      "question": "Is material available to judge mortality-effect magnitude, precision and clinical importance?",
      "needed": "Effects, intervals, baseline risk, follow-up and rationale for interpreting importance",
      "role": "Required",
      "role_reason": "Needed to avoid declaring adequate precision from a hard endpoint, significance or a single sample-size figure alone.",
      "application_exception": "Do not adopt arbitrary minimum participants, trial counts, duration or effect size. The 200-participant wording in the original grade rationale is historical explanation.",
      "criterion": "Verify valid between-arm effects and intervals, actual follow-up, baseline risk and justified interpretation of importance.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare effect/interval interpretation appropriate to the endpoint and population with the original analysis without deriving a new grade."
    },
    {
      "item_id": "N19",
      "question_type": "Evidence condition",
      "question": "Are assignment/adherence effects, ITT/PP populations and handling of treatment changes verified?",
      "needed": "ITT/PP or other analysis-population definitions, long-term adherence/change handling and actual implementation documents",
      "role": "Required",
      "role_reason": "Needed to distinguish the effect of add-on assignment from effects among actual long-term users.",
      "application_exception": "Do not invent ITT or PP labels when analysis names are absent.",
      "criterion": "Verify analysis populations, effect of interest, deviation/change/death-handling rules and their actual application.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare assignment, actual use and change records with analysis plans and state the effect of interest."
    },
    {
      "item_id": "N20",
      "question_type": "Evidence condition",
      "question": "Are the actual trial-registration/protocol identity, editions, dates and originals verified?",
      "needed": "Registration/protocol identifiers, dates, editions, originals or actual access records",
      "role": "Required",
      "role_reason": "Needed to distinguish an unidentified NCT from confirmed nonregistration or results of a current registry search.",
      "application_exception": "Do not borrow registration numbers from other berberine trials. Failure to acquire full text does not prove nonexistence.",
      "criterion": "Verify the trial's registration/protocol identifiers, initial/change dates, editions and originals.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare trial identity for the report before establishing registration/protocol histories and actual provision scope."
    },
    {
      "item_id": "N21",
      "question_type": "Evidence condition",
      "question": "Is consistency between prospective analysis plans and actual endpoints, timing and reporting verified?",
      "needed": "Prospective SAP, analysis lists, change histories and complete actual result tables",
      "role": "Required",
      "role_reason": "Needed to avoid turning absent plans into confirmed selective reporting or retrospectively calling current mortality reports prospective analyses.",
      "application_exception": "Unverified protocol/SAP does not establish presence or absence of selective reporting.",
      "criterion": "Compare dated SAP/plans with actual mortality/functional outcomes, times, analyses and reasons for changes.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare prospective/post hoc documents' endpoint, timing and analysis lists; record the verified scope of selection and changes."
    },
    {
      "item_id": "N22",
      "question_type": "Evidence condition",
      "question": "Are report/trial-family identity and direct independent mortality replication verified?",
      "needed": "Related reports/registration identities of the same trial and population, product and mortality-result material from direct replication trials",
      "role": "Required; independence verification needed for replication claims",
      "role_reason": "Needed to distinguish a single citation and the original R1 from externally verified replication counts.",
      "application_exception": "Neither a new search not performed nor unverified replication in the original article establishes 0 replication trials worldwide.",
      "criterion": "Verify the Zeng 2003 evidence/citation link, related reports of the same trial and identity/independence of other direct mortality trials.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Link reports to trial families and mortality times/analyses; compare whether recruited populations are independent."
    },
    {
      "item_id": "N23",
      "question_type": "Evidence condition",
      "question": "Is the same adjunctive treatment's mortality effect directly verified under modern standard treatment?",
      "needed": "Direct comparative trials under modern treatment, arm-specific background treatment, products and mortality estimates",
      "role": "Supplementary; required for application to modern treatment",
      "role_reason": "Needed to avoid directly transferring results under 2003 common treatment to current treatment backgrounds.",
      "application_exception": "No new lookup of modern drugs or guidelines occurs in this work. The original claim remains tied to the then-conventional trial.",
      "criterion": "Verify direct comparisons and treatment differences under modern background therapy for the same population, product, exposure and mortality endpoint.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "When new direct material is available, compare background treatment, populations, times and effects of interest with the original trial."
    },
    {
      "item_id": "N24",
      "question_type": "Evidence condition",
      "question": "Are other salts, extracts, combinations and derivatives distinguished from the actual trial product?",
      "needed": "Original product-boundary wording and restrictions on transfer to other products",
      "role": "Required (product-extension boundary)",
      "role_reason": "Needed to avoid applying mortality results to different products solely because they share an ingredient name.",
      "application_exception": "Met for product-boundary distinction does not verify the original product's salt/specifications. Actual product verification is asked separately in N04.",
      "criterion": "Do not automatically equate berberine hydrochloride, plant extracts, compound prescriptions, dihydroberberine, other derivatives or topical products with the original exposure.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "When product material is added, examine salt, route, composition, exposure equivalence and direct comparisons separately."
    },
    {
      "item_id": "N25",
      "question_type": "Evidence condition",
      "question": "Is all-cause mortality distinguished from LVEF, arrhythmia, walking and cause-specific mortality?",
      "needed": "Original wording and locations distinguishing all-cause mortality from other endpoints",
      "role": "Required (endpoint-extension boundary)",
      "role_reason": "Needed to avoid replacing the original all-cause mortality question with other symptoms, function or cause-specific deaths.",
      "application_exception": "Do not generate new independent tables for other results or combine their values with the mortality effect in this table.",
      "criterion": "Select only mean 24-month all-cause mortality; keep extended endpoints such as LVEF, arrhythmia, walking and cardiovascular death separate.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "If endpoint scope changes, examine definitions, denominators, timing and estimates under new independent boundaries."
    },
    {
      "item_id": "N26",
      "question_type": "Evidence condition",
      "question": "Are direct dose comparisons, optimal dosing and persistence after stopping verified?",
      "needed": "Prospective dose comparisons, dose-specific denominators/mortality estimates and post-discontinuation follow-up",
      "role": "Supplementary; required for the relevant extension claim",
      "role_reason": "Needed to distinguish a dose range and long-term follow-up from optimal dosing or effects persisting after stopping.",
      "application_exception": "Do not universally require optimal-dose or discontinuation studies for the narrow then-conventional add-on question.",
      "criterion": "Verify direct dose comparisons, actual arm-specific exposure, mortality follow-up after stopping and separate estimates.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Examine designs/analyses directly comparing doses and discontinuation separately from the original single add-on report."
    },
    {
      "item_id": "N27",
      "question_type": "Evidence condition",
      "question": "Are funding, product provision, author employment, full COI and sponsor roles verified?",
      "needed": "Original funding, product provision, employment, COI declarations and sponsor-role documents",
      "role": "Supplementary; required for interpretation of independence",
      "role_reason": "Needed to distinguish the original I1 or generic English wording from evidence verifying independent funding or conflicts.",
      "application_exception": "Do not infer industry involvement without material or automatically exclude results.",
      "criterion": "Verify original funding, product provision, author relationships, COI declarations and sponsor design/analysis/publication roles.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare individual author declarations, funding and product support separately from trial-family independence."
    },
    {
      "item_id": "N28",
      "question_type": "Evidence condition",
      "question": "Are identity, public availability and editions of external abstracts, papers and registration/plans actually verified?",
      "needed": "External bibliography, abstracts, paper editions, registration/plan identities and actual access/acquisition records",
      "role": "Required",
      "role_reason": "Needed to distinguish bibliographic entry points from acquisition or successful reading of full texts and registration originals.",
      "application_exception": "Do not label current access not attempted as failed access. Do not invent registration/plan URLs without established identity.",
      "criterion": "Verify recorded PMID, DOI and PubMed entry points alongside actual editions, availability and acquisition of external originals.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "During authorized subsequent acquisition, record identity, availability, access and acquisition separately for each physical material type."
    },
    {
      "item_id": "N29",
      "question_type": "Evidence condition",
      "question": "Are generic English wording and the 2026-09-14 correction history retained as original values?",
      "needed": "Current bilingual evidence tables, citations, correction originals, dates and scope",
      "role": "Required (original-text and correction attribution)",
      "role_reason": "Needed to avoid promoting English placeholders to current specific clinical-material verification.",
      "application_exception": "The correction records replacement of 1 English field. Retain remaining generic wording historically without arbitrary translation/replacement.",
      "criterion": "Link correction dates/scope and current generic English wording to original bytes and typed literals without using them as new verified facts.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "If subsequent editing is needed, preserve the whole previous article and distinguish clinical-value changes from translation/display events."
    },
    {
      "item_id": "N30",
      "question_type": "Evidence condition",
      "question": "Are actual adverse-event definitions, collection, severity and discontinuation verified for the same population/exposure?",
      "needed": "Original adverse-event definitions, collection, timing, severity, discontinuation and causality assessment material",
      "role": "Supplementary; required for harm/safety interpretation",
      "role_reason": "Needed to distinguish original warnings or safety in a title from actual safety results.",
      "application_exception": "Efficacy and harms have separate states. Do not remove mortality reporting because harm material remains unverified.",
      "criterion": "Verify actual adverse-event definitions, collection methods/times, severity, discontinuation and causality assessment material.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare harm collection/adjudication material for the same exposure separately from efficacy reporting."
    },
    {
      "item_id": "N31",
      "question_type": "Evidence condition",
      "question": "Are harm counts, exposed denominators, observation periods and missingness verified?",
      "needed": "Harm-specific event counts, exposed denominators, periods, missingness and collection systems",
      "role": "Supplementary; required for frequency/safety interpretation",
      "role_reason": "Needed to avoid transferring 156 participants and death counts to nonfatal-adverse-event denominators or incidence.",
      "application_exception": "Do not fill absent event counts with 0 or derive harm incidence from warnings.",
      "criterion": "Verify exposed persons, persons/events, follow-up periods, missingness and collection systems for each harm.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Link harm collection tables to exposure/follow-up flow; distinguish spontaneous records from systematic counts."
    },
    {
      "item_id": "N32",
      "question_type": "Evidence condition",
      "question": "Is direct harm material verified for bradycardia, hypotension, interactions and electrolyte, renal and liver status?",
      "needed": "Original exposure, event, comparison and follow-up material by concomitant drugs and baseline function",
      "role": "Supplementary; required for the relevant harm scope",
      "role_reason": "Needed to distinguish original cautions from verified risks or interaction magnitudes.",
      "application_exception": "Retain original warnings without newly confirming particular drug interactions or vulnerable-population risks.",
      "criterion": "Verify concomitant drugs, baseline status, events, follow-up and comparative material under the same actual exposure.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Examine prospectively defined concomitant-drug/baseline-function harm collection or comparisons, distinguishing other causes."
    },
    {
      "item_id": "N33",
      "question_type": "Evidence condition",
      "question": "Are original advertising/safety boundaries distinguished from new survival treatment, drug replacement or personal dosing instructions?",
      "needed": "Original advertising restrictions, safety warnings and locations",
      "role": "Required (interpretation-extension boundary)",
      "role_reason": "Needed to prevent advertising favorable death counts as established survival treatment or halved risk.",
      "application_exception": "This table does not direct individual treatment, dosing or discontinuation. Do not reduce original warnings.",
      "criterion": "Do not extend results to established survival treatment, antiarrhythmic replacement or halved mortality risk; link original warnings to historical text.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "If clinical application scope changes, examine direct material, safety and comparator treatment separately before updating presentation."
    },
    {
      "item_id": "N34",
      "question_type": "Evidence condition",
      "question": "Are actual historical search, preservation, verification scope and evidence-date specifications verified?",
      "needed": "Dates, databases, strategies, scope and retained documents for historical search/review records",
      "role": "Required",
      "role_reason": "Needed to distinguish the original review date from a current comprehensive literature search or report-specific access dates.",
      "application_exception": "Do not infer absent evidence cut-offs, search databases or search strategies.",
      "criterion": "Verify actual search dates, databases, strategies and preservation-scope documents in addition to the global original review date and search description.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare actual historical search records by date, identifier and material type separately from current actions."
    },
    {
      "item_id": "N35",
      "question_type": "Evidence condition",
      "question": "Are actual documents, dates and scope of bibliographic-edition and retraction/concern/correction checks verified?",
      "needed": "Bibliographic editions and actual publication-status-check documents, dates, original locations and scope",
      "role": "Required",
      "role_reason": "Needed to avoid reusing historical check descriptions as new verification of current publication status.",
      "application_exception": "Bibliography, internal English corrections and publisher correction/retraction documents are different materials. No current external lookup occurs.",
      "criterion": "Verify PMID, DOI, bibliographic editions and actual publication-status-check documents, original locations, dates and scope.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "When authorized new material arrives, compare publication status and edition links by PMID/DOI separately from internal correction history."
    },
    {
      "item_id": "N36",
      "question_type": "Evidence condition",
      "question": "Are original C50, axes, empty values and absent fields retained without inheritance into new condition states?",
      "needed": "Complete original bytes, SHA, grade, axes, corrections, empty values and absent fields",
      "role": "Required (original verdict preserved)",
      "role_reason": "Needed to avoid presenting the current conversion as reevaluation of the original grade or a new condition score.",
      "application_exception": "Original axes such as H, R1 and I1 are historical values; they do not replace actual independence or precision verification.",
      "criterion": "Preserve the complete original material and C50, safety, axes, empty subclaim/review-note lists and absent structures as typed original values without calculating new scores.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "If correction is needed, preserve the whole previous article and grading event; handle it under separate authorization/versioning from the current conversion."
    },
    {
      "item_id": "N37",
      "question_type": "Evidence condition",
      "question": "Are current local-summary reading, external access not attempted, historical descriptions and unverified access dates separated?",
      "needed": "Material-specific actual reading, acquisition and access events; distinction among historical descriptions, original review dates and individual access dates",
      "role": "Required (actual reading record)",
      "role_reason": "Needed to avoid turning summary-reader links into external full-text-reading badges.",
      "application_exception": "Do not copy original review/correction dates into access dates. Do not inherit one included document's access level into another physical material.",
      "criterion": "Record only current local-summary reading as true; retain external access not attempted/not acquired/not read and absent actual access dates/levels as unrecorded values.",
      "basis": "Existing method principles distinguish population, product, add-on treatment, comparator, all-cause mortality, timing, analysis, follow-up, study families, funding and harms. Detailed conditions are Chamgap’s own application.",
      "condition_origin": "These conditions for adjunctive berberine and heart-failure all-cause mortality were developed with knowledge of the retained content. Conditions were frozen before a separate application event. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "During authorized subsequent reading, append only that material type's actions, dates and locations as separate events."
    }
  ]
}