{ "schema_version": "chamgap-public-criteria-1.0", "title": "Oral single-ingredient berberine × Reduction of LDL-C in adults with dyslipidemia", "language": "en", "translation_date": "2026-10-27", "criteria_version": "1.1", "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": "Verification of a scoped identity, record or boundary; not a new efficacy conclusion", "Partly verified": "Some actual retained information is available alongside remaining material needs", "Unverified": "Required material is unverified within the retained scope; this does not mean no studies, an effect of 0 or safety", "Conflicting data": "Mismatch between specific current fields and historical correction descriptions; separate from clinical-result conflict", "Not applicable": "Separate extension conditions are not imposed as additional requirements for the narrow selected question" }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Does the table address oral single-ingredient berberine versus placebo for treatment-end LDL-C?", "needed": "The current claim, claim conditions in both languages and original locations for the inclusion/exclusion boundary.", "role": "Required", "role_reason": "This boundary condition distinguishes the whole ingredient page from the narrow comparison question.", "application_exception": "TG, HDL, apoB, cardiovascular events, statin replacement, other derivatives and combinations do not substitute for this LDL-C question.", "criterion": "Link the original claim to the population, single ingredient, oral route, placebo and treatment-end LDL-C scope; exclude other lipid and event 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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Future comparative trials should prespecify the ingredient, formulation, population, placebo and treatment-end LDL-C measure." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Can actual dyslipidemia diagnoses and eligibility criteria by sex and risk group be verified?", "needed": "Trial-specific eligibility criteria and baseline tables, sex composition and dyslipidemia definitions.", "role": "Required", "role_reason": "Similar population labels do not establish representativeness or directness.", "application_exception": "Do not transfer results from another sex, high-risk populations or people with normal lipids to the same target effect.", "criterion": "Link each trial's diagnosis, baseline LDL-C, age, sex, cardiovascular risk and inclusion/exclusion criteria to the relevant result 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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Use consistent diagnostic criteria in placebo-controlled trials and report baseline LDL-C, eligibility by sex/risk group and recruitment flow." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "Can each trial's berberine ingredient, salt form, content, formulation and absence of other active ingredients be verified?", "needed": "Product names, ingredient lists, salt/purity, standardization and trial-specific formulations.", "role": "Required", "role_reason": "Distinguish single-ingredient effects from contributions of other products or combined interventions.", "application_exception": "Do not interchange berberine hydrochloride, dihydroberberine, mixed formulations, botanical extracts and topical products.", "criterion": "Verify product-specific ingredient, purity, content and formulation; distinguish mixed nutraceuticals, Berberis extracts and derivatives.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Design placebo-controlled trials of the same single-active-ingredient product, recording batch-specific content, purity, impurities and administered formulation." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Can nominal doses, dosing frequency and actual intake in each trial be linked to LDL-C results?", "needed": "Trial-specific dosing schedules, nominal/actual content and adherence records.", "role": "Required", "role_reason": "Distinguish nominal ranges from actual exposure, and the main effect from dose-extension claims.", "application_exception": "Do not declare this range an optimal dose, safe dose or identical dose across all trials.", "criterion": "Link trial-specific mg/day, divided doses, formulation and adherence-related actual exposure to the corresponding result time.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Record actual dose and adherence for the same product. Add a separate randomized dose contrast only when asking about dose effects." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "Can arm-specific lipid medicines, diet, lifestyle, rescue treatment and adherence be verified?", "needed": "Trial-specific concomitant lipid medicines, diet/activity plans, rescue treatment, adherence and arm-specific changes.", "role": "Required", "role_reason": "Avoid attributing effects of other treatment changes solely to berberine.", "application_exception": "Do not require absence of every concomitant medicine; verify actual changes and handling appropriate to the common background and effect of interest.", "criterion": "Verify common treatments, changes and deviations in both arms; explain how other intervention differences may enter the LDL-C comparison.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Define and maintain common treatment; collect arm-specific changes, adherence and rescue treatment to distinguish assignment effects from treatment deviations." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "Can treatment-end values, changes, adjustment methods and LDL-C units be verified for each result?", "needed": "Trial-specific result tables, baseline/end values, change definitions, adjustment models and unit descriptions.", "role": "Required", "role_reason": "Avoid presenting numbers with different measures or analysis definitions as the same effect.", "application_exception": "Do not convert TG, HDL, apoB or standardized SD results into an absolute LDL-C difference in original units.", "criterion": "Assign estimates to the treatment-end absolute between-arm-difference question; distinguish mmol/L from SD scales and final values from 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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Report baseline, end and change values in mmol/L with a prespecified between-arm model; report SD-scale results separately." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Can the exact end time and observation window for each LDL-C result be verified?", "needed": "Trial-specific dosing/blood-sampling times, analysis windows and meta-analysis end-time selection rules.", "role": "Required", "role_reason": "Avoid hiding duration differences or turning short-term end values into persistence effects.", "application_exception": "Do not arbitrarily convert 3 months into 12 weeks or extend short-term data to long-term persistence.", "criterion": "Link included-trial times and the 12-week/3-month records to their own results without converting them into an identical duration.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Prespecify blood-sampling windows and target times, report all available times and investigate persistence with separate follow-up." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Are each RCT's design labels and actual sequence generation, concealment and baseline balance verified?", "needed": "Original-trial protocols, allocation methods, concealment procedures and baseline tables.", "role": "Required", "role_reason": "Distinguish design titles from the actual allocation conditions for causal comparison.", "application_exception": "Do not say an RCT title establishes absence of bias or completion of a formal RoB assessment.", "criterion": "Verify actual sequence generation, concealment and baseline tables separately from retained placebo-RCT/double-blind labels. Design titles alone do not establish adequate allocation.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Conduct placebo-controlled trials reporting sequence generation, concealment and balance in baseline LDL-C and associated factors." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Can LDL-C assay methods, specimen conditions and assessor blinding be verified?", "needed": "Specimen collection, fasting time, LDL-C assay/calculation methods, quality control and analyst blinding.", "role": "Required", "role_reason": "Distinguish differences in assay/collection conditions from actual LDL-C differences.", "application_exception": "An objective lipid test alone does not resolve arm-specific measurement differences or specimen conditions.", "criterion": "Verify sampling/fasting conditions, direct or calculated LDL-C assays, laboratory/assessment procedures and differences between arms.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Apply consistent assays and prespecified blood-sampling/fasting windows; report laboratory quality control and assessor blinding." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "What are S01's reported LDL-C-specific and whole-review denominators?", "needed": "S01's original records of endpoint-specific included-trial and participant counts.", "role": "Required", "role_reason": "This limited record condition prevents confusion between endpoint-specific totals and whole-review size.", "application_exception": "Do not substitute whole-review or other lipid-endpoint totals for LDL-C analysis denominators or add direct-trial reports to them.", "criterion": "Keep the original 14 LDL-C RCTs/1,447 participants separate from 18 RCTs/1,788 overall; do not use the overall total as LDL-C analysis n.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Future reviews should link endpoint-specific trials and analysis denominators to original trial families in a public table." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "Can S01's included trials and overlap/independent families involving S02–S04 be verified?", "needed": "S01's included-trial tables, exclusions, original-trial identities and S02–S04 registration/report links.", "role": "Required", "role_reason": "Distinguish report counts from independent replication and retain unknown family relationships honestly.", "application_exception": "Do not add the review and individual papers as separate independent trials. Retain the identified S02/S03 overlap separately.", "criterion": "Compare included-trial lists and report/registration relationships; do not estimate unverified unique study or participant totals.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Publish identifiers linking reports, registrations, trials and endpoint-specific analyses; connect duplicates within one family." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "What LDL-C MD and 95% CI did S01 report?", "needed": "S01's original pooled LDL-C result record and units.", "role": "Required", "role_reason": "Separate verification of reported numbers from assessment of clinical sufficiency.", "application_exception": "Do not transfer this interval to other formulations, risk groups or event prevention, or calculate a new value.", "criterion": "Link S01's MD −0.46 mmol/L, 95% CI −0.62~−0.30 as a pooled estimate; do not interpret it as a guaranteed product-specific effect.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Publish original-trial estimates, variances and models with the pooled result and specify its applicability." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Can S01's weights, model, heterogeneity and sensitivity analyses be verified?", "needed": "Meta-analysis methods, trial-specific effects/variances, heterogeneity measures, sensitivity analyses and analysis code.", "role": "Required", "role_reason": "Examine pooled averages together with between-trial conditions and analysis uncertainty.", "application_exception": "Do not calculate missing I² or prediction intervals or arbitrarily designate a fixed/random-effects model.", "criterion": "Verify fixed/random-effects models, variance handling, endpoint-specific heterogeneity, sensitivity analyses and result selection.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Prespecify heterogeneity hypotheses and publish trial-specific results and sensitivity analyses to assess directness by product and population." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "Can bias and geographic/product representativeness data for S01's included trials be verified?", "needed": "Included-trial baseline/method tables, geographic composition, product information and result-specific bias-assessment evidence.", "role": "Required", "role_reason": "Distinguish review-summary limitations from actual assessment evidence.", "application_exception": "Do not promote the original B2 axis or sample size into a current formal RoB/GRADE judgment or bias magnitude.", "criterion": "Link trial-specific methods, geography, populations, formulation differences and assessment evidence to actual 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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Provide trial-specific evidence for design, missingness, measurement and selective reporting with geography/product/population tables to examine result limitations." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Can S02's 84 people be distinguished from actual allocation, completion and LDL-C analysis denominators?", "needed": "S02 recruitment flow, arm-specific allocation/completion, week 12 LDL-C analysis n and missing-data handling.", "role": "Required", "role_reason": "Distinguish nominal participant counts from actual result-analysis denominators.", "application_exception": "Do not add the 84 men reused in S03 as newly recruited participants.", "criterion": "Verify what the reported 84 represents and arm-specific allocation, completion, sampling and analysis n without substituting one count for another.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Report arm-specific flow from allocation through week 12 sampling/analysis, including exclusions and reasons for missingness." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "What is the scope of S02's week 12 LDL-C result and nonsignificant interpretation?", "needed": "S02's LDL-C estimate, interval, P value and original direction description.", "role": "Required", "role_reason": "Prevent significance-based result selection and overinterpretation of no significant difference.", "application_exception": "Do not delete this nonsignificant result in favor of a positive result in another sex/unit or establish efficacy retrospectively.", "criterion": "Retain MD −0.21 mmol/L, 95% CI −0.50~0.08, P=.15; do not turn nonsignificance into an effect of 0, equivalence or confirmed harm.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Future trials should report target between-arm differences and intervals; if equivalence is claimed, prespecify that hypothesis and its margins separately." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "Can actual analysis denominators for S03's 100 women and stored samples from 84 men be verified?", "needed": "S03 female participant flow, arm-specific analysis n and remeasurement/analysis records for existing male specimens.", "role": "Required", "role_reason": "Distinguish reused people/specimens from new recruitment and nominal n from analysis n.", "application_exception": "Do not turn 100+84 into a new unique-participant total or count stored male samples as a new independent trial.", "criterion": "Verify female recruitment/allocation/completion and LDL analysis n separately from measurement/analysis n for existing male specimens.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Publish female participant flow and the scope of male specimen reuse separately, linking analysis denominators to results and times." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Can the SD scale and standardization/adjustment methods for S03 women's LDL be verified?", "needed": "S03 original-unit LDL means, variances, analysis n and SD-scale construction/adjustment methods.", "role": "Required", "role_reason": "Keep differences in scale and analysis definition visible.", "application_exception": "Do not convert SD to mmol/L or SE, or arbitrarily specify a particular raw-mean-difference/SMD calculation.", "criterion": "Retain women's LDL −1.06 SD, 95% CI −1.44~−0.69 on an SD scale; verify original units, variance and standardization/adjustment methods.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Report original-unit means, variances, between-arm estimates and the SD standardization reference together; analyze different units separately." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Can S03's primary apoB/secondary LDL-C hierarchy be compared with prospective plans and analyses?", "needed": "S03 registration, protocols and analysis plans covering endpoint hierarchy, multiplicity and changes.", "role": "Required", "role_reason": "Distinguish the interpretation hierarchy of favorable subordinate results from actual plan verification.", "application_exception": "Do not convert primary apoB results into primary LDL-C confirmation or automatically discard secondary results as invalid.", "criterion": "Compare the retained female primary apoB/secondary LDL hierarchy with registration/protocol endpoint, time and multiplicity plans.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Future trials should prespecify whether LDL-C is primary, the target time, multiplicity handling and analysis-change rules." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Does the retained text connect S02 and S03 male data to the same trial family?", "needed": "S02/S03 original citations, designs and textual links to the same male data.", "role": "Required", "role_reason": "This identity condition directly distinguishes repeat reports from unique studies.", "application_exception": "Retain new female recruitment while distinguishing shared male data and investigator overlap from independent replication.", "criterion": "Retain the stored-sample, 84-men and NCT03770325 links; do not count the two reports as independent LDL replications.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Publish a family table linking each report to trial/registration, recruitment, specimens, endpoints and times." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Can S04's 144 enrolled people be distinguished from allocation, completion and LDL-C analysis denominators?", "needed": "S04 enrollment/allocation/completion flow, arm-specific 3-month sampling/analysis n and exclusion reasons.", "role": "Required", "role_reason": "Separate enrollment from actual analysis denominators.", "application_exception": "Do not convert enrollment into ITT/PP, completer or placebo/treatment-arm n.", "criterion": "Distinguish enrollment of 144 from arm-specific randomization, completion and 3-month LDL-C analysis n.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Report arm-specific flow from enrollment through allocation, follow-up and LDL analysis, including missing-data handling." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Can S04's actual between-arm LDL-C effect, unit and CI be verified?", "needed": "S04 arm-specific LDL-C result tables, estimation model, effect value and 95% CI.", "role": "Required", "role_reason": "Distinguish directional descriptions from quantitative effects and precision.", "application_exception": "Do not establish clinical importance from abstract direction alone or copy effects/intervals from other reports.", "criterion": "Verify exact between-arm estimates, units, analysis and intervals separately from the abstract's reduction direction.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Report the prespecified 3-month LDL-C between-arm estimate, variance, denominator and CI in original units." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Are result directions by sex/analysis and prospective subgroup/interaction evidence explaining them verified?", "needed": "Prospective sex hypotheses, interaction models, original-unit effects/intervals and population/formulation differences across trials.", "role": "Required", "role_reason": "Distinguish directional heterogeneity, subgroup effects and reporting conflict.", "application_exception": "Do not establish effects only in women or an effect of 0 in men, or select only favorable directions.", "criterion": "Retain S02 nonsignificance, S03 female positivity, S01 averages and S04 direction; verify prospective subgroup/interaction plans, estimates and CIs using the same scale and analysis.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Prespecify consistent measures and sex subgroup/interaction models; report estimates and intervals for every group." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "Can citation registration numbers and unconfirmed registration fields be compared with actual registration records?", "needed": "Review/trial registration originals, trial identity links for each report and change histories.", "role": "Required", "role_reason": "Distinguish bibliographic identifiers from actual registration/plan comparison.", "application_exception": "Constructing an NCT link does not establish reading registration documents or verifying plan consistency.", "criterion": "Retain PROSPERO CRD42021293218 and NCT03770325/NCT06782646 clues alongside unconfirmed evidence-table registration fields; verify actual documents and trial links.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare official registration identity, interventions, populations, endpoints, times and change histories with reports; record correction reasons separately." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Are retained prospective/endpoint-hierarchy summaries and actual LDL-C analysis, timing and reporting consistent with plans?", "needed": "S01–S04 protocols/registrations, statistical analysis plans, complete lipid results, changes and multiplicity records.", "role": "Required", "role_reason": "Expose the material needed to examine selection of favorable analyses.", "application_exception": "Do not turn unavailable plans into confirmed nonregistration or selective reporting.", "criterion": "Verify retained descriptions of a preregistered review, prospective lipid group and secondary LDL; compare registration/protocol/analysis plans with actual LDL-C results, times and between-arm models, including reasons for changes and multiplicity handling.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Prespecify LDL-C results, times, analysis populations and multiplicity; publish every planned result and reasons for changes." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "Can ITT/PP, adjustment and the effect of interest for each LDL-C estimate be verified?", "needed": "Result-specific analysis n, ITT/PP definitions, adjustment covariates and statistical analysis plans/models.", "role": "Required", "role_reason": "Avoid falsely presenting different analyses as the same effect of interest.", "application_exception": "Do not arbitrarily label unspecified analysis populations ITT or convert within-arm changes into between-arm differences.", "criterion": "Verify assignment/adherence effects, actual analysis populations, adjustment covariates and result definitions.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Specify whether assignment effects are primary; distinguish and report actual analysis populations, models and adherence-related supplementary analyses." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Can LDL-C missingness, attrition reasons, arm-specific handling and sensitivity analyses be verified?", "needed": "Arm-specific follow-up losses, missing blood samples, discontinuation reasons, missing-data handling and sensitivity results.", "role": "Required", "role_reason": "Distinguish denominator losses from selection in effect estimation.", "application_exception": "Do not calculate missing attrition counts, CIs or missing-data effects, or turn unverified information into no missingness.", "criterion": "Link allocation/completion/analysis flow to LDL-C missingness, discontinuation reasons, handling and sensitivity analyses.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Collect arm-specific reasons for loss to follow-up and missing blood samples; report prespecified handling and sensitivity analyses." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Can funding, product support, author interests and investigator overlap be verified against actual declarations?", "needed": "S01 trial/review COI, S02–S04 funding/product support, author declarations and institutional relationships.", "role": "Supplementary; required for independence claims", "role_reason": "Distinguish independence claims from actual declarations, funding and research families.", "application_exception": "A report of no COI does not prove no bias or independent replication; funding alone does not justify deleting results.", "criterion": "Distinguish the verification scope of report-specific funding, product provision, employment/COI declarations and institutional/research-family links.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Disclose funding, supplied products, author employment/declarations and recruitment/research-family relationships separately." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Is there a prospective criterion for judging the clinical importance of this LDL-C difference?", "needed": "Evidence and prospective criteria for important LDL-C differences in dyslipidemia populations, with original-unit results/CIs.", "role": "Required", "role_reason": "Distinguish reported intervals from judgments of clinical importance.", "application_exception": "Do not invent universal minimum sample sizes, trial counts, durations or effect thresholds, or import event-prevention thresholds into this measure.", "criterion": "Compare justified important-difference criteria for the population, units and time with reported CIs; do not invent missing thresholds.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Justify an important difference appropriate to the population and result; prespecify trial-design and interpretation criteria." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Are optimal dose or post-discontinuation persistence imposed as additional requirements for this narrow treatment-end LDL-C question?", "needed": "The selected-question scope and separate direct evidence if dose/persistence extensions are sought.", "role": "Supplementary; required for dose/persistence extension claims", "role_reason": "This supplementary condition distinguishes the narrow main-effect question from applicability of extension conditions.", "application_exception": "Do not infer an optimal dose or long-term safety from 900~1,500 mg/day and 4~24 weeks.", "criterion": "Do not add separate optimal-dose or long-term-persistence claims to the selected treatment-end LDL-C question; assess extension material separately.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Only if an extension is sought, design a separate direct dose comparison or post-discontinuation follow-up question/trial." }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Are LDL-C comparisons separated from myocardial infarction, death and statin-replacement questions?", "needed": "The original endpoint and exclusions covering cardiovascular events and medicine replacement.", "role": "Supplementary; required for clinical-event extension claims", "role_reason": "Distinguish surrogate endpoints from clinical-event extensions.", "application_exception": "Do not impose event trials as an additional requirement for the numerical-change question or promote numerical effects into event effects.", "criterion": "Keep LDL-C as the selected numerical endpoint; do not claim event prevention or medicine replacement as the same 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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Event-prevention or medicine-replacement questions require separate research prespecifying the relevant events, comparator and duration." }, { "item_id": "N32", "question_type": "Evidence condition", "question": "Are gastrointestinal warnings and actual event definitions, placebo-relative frequencies, denominators and discontinuations verified?", "needed": "Trial-specific gastrointestinal-event definitions, arm-specific events/exposure/follow-up tables and collection/discontinuation records.", "role": "Supplementary; required for comparative harm claims", "role_reason": "This supplementary condition is needed because efficacy summaries and short-term RCTs do not establish overall safety.", "application_exception": "Do not promote reported warnings into new causal/frequency judgments or delete LDL-C results because safety material is unverified.", "criterion": "Retain the original warning that gastrointestinal adverse effects may be more frequent than with placebo; separately verify affected people/event counts, arm-specific exposure denominators, duration, collection and discontinuation reasons.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Under the same population/exposure conditions, report prespecified event definitions, systematic collection, arm-specific denominators/duration and discontinuation reasons." }, { "item_id": "N33", "question_type": "Evidence condition", "question": "Are original pregnancy/lactation/infant and CYP-comedication cautions and actual exposure/harm evidence verified?", "needed": "Population-specific exposure, concomitant medicines, events/timing, baseline risk and direct-material identity.", "role": "Supplementary; required for vulnerable-group/comedication safety claims", "role_reason": "This supplementary condition separates the selected efficacy population from vulnerable-group/comedication harms.", "application_exception": "Do not extrapolate vulnerable-group safety from adult lipid trials or turn warnings into personal dosing instructions or established risk rates.", "criterion": "Retain original caution groups and wording; separately verify direct exposure, events, timing and alternative-cause evidence for those populations/comedications.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Collect direct observational and drug-interaction evidence using designs suited to a separate harm question." }, { "item_id": "N34", "question_type": "Evidence condition", "question": "Does the correction about replacing English placeholders match specific values in the current English evidence table?", "needed": "Original bytes before/after the 2026-09-14 English correction and specific correspondence of the four current fields.", "role": "Required", "role_reason": "Distinguish historical correction descriptions from current field values.", "application_exception": "Do not delete the correction record or promote generic current wording into full-text verification or specific denominator/analysis evidence.", "criterion": "Compare the correction description with actual English sample-size, funding, endpoint and result fields; distinguish before/after versions that have not been compared.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare original English bytes before/after correction and record Korean correspondence and reasons for changes. This row does not request additional clinical trials." }, { "item_id": "N35", "question_type": "Evidence condition", "question": "Are original C50, all axes and native values kept separate from approval of new conditions or regrading?", "needed": "Exact original locations for grade, score, axes, original true/false values, arrays, corrections and dates.", "role": "Required", "role_reason": "Traceability distinguishes original judgment from the material-conversion status.", "application_exception": "Do not convert false into 0 or unrecorded, or expand a false no-human-study indicator into complete verification of every human study.", "criterion": "Retain original grade, score, axes, true/false values, empty arrays, corrections and dates exactly; separate table statuses from new efficacy grades.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "When original judgments or evidence are corrected, retain separate events, original bytes and versions; revisit the question boundary first." }, { "item_id": "N36", "question_type": "Evidence condition", "question": "Are locally read summaries separated from external bibliographic, full-text and registration states?", "needed": "Current input hashes, actual reading scope, material-specific access/acquisition/reading records and original-location links.", "role": "Required", "role_reason": "Avoid confusing links or acquired summaries with full-text reading.", "application_exception": "Do not turn unattempted access into failed access or label local summaries as clinical full texts or original-binary reading.", "criterion": "Connect exact local-summary inputs, locations, identity checks and actual summary reading; separately record unattempted/unread external 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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "If future acquisition is authorized, link identity, material type, date, actual location/value and hash to update the relevant rows only." }, { "item_id": "N37", "question_type": "Evidence condition", "question": "Can past access levels and dates for each external material be verified from original records?", "needed": "Original acquisition/reading records, access dates, document versions and access levels for each material.", "role": "Required", "role_reason": "Distinguish attribution of original review dates, individual access dates and current reading times.", "application_exception": "Distinguish current external nonreading from unknown historical reading; do not retrospectively establish that full texts were not read then.", "criterion": "Verify actual original fields for each report's access level/date; distinguish original review, correction and current-review dates.", "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 oral single-ingredient berberine versus placebo on treatment-end LDL-C, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "If historical verification material exists, link each document's actual access date, version and location to original records. Do not create missing records retrospectively." } ] }