{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3068-main", "verdict_number": "3068", "title": "Oral single-ingredient berberine × Reduction of LDL-C in adults with dyslipidemia", "view_version": "1.0", "view_created_date": "2026-10-27", "criteria_version": "1.1", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-08", "review_scope": { "materials_read": "Retained Korean/English summaries and case-specific condition/application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Prepared from retained summaries and condition-application records. External abstracts, full texts, registration, protocols and analysis plans remain unread. Historical review records do not establish current independent clinical validation.", "date_meaning": "The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, "claim_context": { "population": "Adults with dyslipidemia, mainly at low cardiovascular risk. Sex, diagnosis, baseline LDL-C, eligibility and actual analysis counts require report-specific verification.", "intervention": "Oral single-ingredient berberine tablets/capsules. Botanical sources differ or are partly unknown. Mixed nutraceuticals, Berberis extracts, other derivatives and topical products are not interchangeable.", "dose": "The nominal range is mainly 900~1,500 mg/day. Trial-specific products, salt forms, purity, dosing schedules, actual intake and adherence remain unverified. This is not presented as an optimal or safe dose.", "comparator": "Versus placebo. Actual comparison of common treatment, including arm-specific lipid medicines, diet, activity, rescue treatment and adherence, remains unverified.", "endpoint": "The absolute between-arm difference in treatment-end LDL-C. Distinguish mmol/L MD, SD-scale estimates and direction-only reports. TG, HDL, apoB and cardiovascular events are different questions.", "duration": "The overall nominal range is 4~24 weeks. Retain S02/S03 week 12 and S04 at 3 months separately, without arbitrary conversion or extension to long-term persistence.", "excluded_extensions": [ "Original C, 50 points, Warning and B/S/R0/I2/EX/B2/CX are retained. Table statuses are not new efficacy scores or clinical certification.", "Distinguish S01 LDL-C 14 RCTs/1,447 participants from the whole review of 18 RCTs/1,788 participants. Pooled MD −0.46 mmol/L, 95% CI −0.62~−0.30 is not a guaranteed effect for a specific product or person.", "S02 data from 84 men were reused as stored samples in S03. Distinguish S03 recruitment of 100 women; do not count the reports as two independent LDL confirmations or newly add participant totals.", "Retain the SD scale for S03 women’s LDL and the primary apoB/secondary LDL hierarchy. Do not convert against male mmol/L results or calculate a new sex interaction.", "Statin replacement, cardiovascular-event prevention, optimal dose, long-term persistence and personal safety are not established. Retain original gastrointestinal and pregnancy/lactation/infant/CYP-comedication cautions; actual harm frequencies, denominators and causality remain unverified.", "Retain the mismatch between the English evidence-table correction’s specific-replacement description and current generic wording. This is separate from clinical-result conflict; the new reader translation does not establish the historical correction event." ] }, "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The selected question compares oral single-ingredient berberine with placebo for treatment-end LDL-C in adults with dyslipidemia. Products, durations and populations differ across reports and are not combined into a guaranteed effect.", "condition_status": "Met", "status_reason": "The original question and table boundary are verified. This status verifies question identity and does not establish a new efficacy judgment.", "missingness": "The original question and table boundary are verified. This status verifies question identity and does not establish a new efficacy judgment.", "uncertainty": "This boundary condition distinguishes the whole ingredient page from the narrow comparison question.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The current claim, claim conditions in both languages and original locations for the inclusion/exclusion boundary." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The original claim conditions mainly concern adults with dyslipidemia at low cardiovascular risk. S02 lists 84 Chinese men, S03 lists 100 women and 84 existing male participants, and S04 lists 144 low-risk people enrolled; detailed eligibility criteria are absent.", "condition_status": "Partly verified", "status_reason": "Population labels and nominal composition are available, but actual diagnostic criteria, baseline distributions and recruitment settings remain unverified.", "missingness": "Population labels and nominal composition are available, but actual diagnostic criteria, baseline distributions and recruitment settings remain unverified.", "uncertainty": "Similar population labels do not establish representativeness or directness.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific eligibility criteria and baseline tables, sex composition and dyslipidemia definitions." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The scope includes single-ingredient tablets/capsules and reportedly excludes combinations and Berberis extracts. Botanical sources differ or are partly unknown; salt form, purity and actual content for each trial are not provided.", "condition_status": "Partly verified", "status_reason": "The single-ingredient inclusion scope is known, but product equivalence, quality and actual ingredient content cannot be verified.", "missingness": "The single-ingredient inclusion scope is known, but product equivalence, quality and actual ingredient content cannot be verified.", "uncertainty": "Distinguish single-ingredient effects from contributions of other products or combined interventions.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Product names, ingredient lists, salt/purity, standardization and trial-specific formulations." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The original claim conditions state mainly 900~1,500 mg/day. Individual dosing schedules and actual intake in S01's included trials and S02–S04 are unverified in this retained summary.", "condition_status": "Partly verified", "status_reason": "A dose range for the overall article is available, but the product and exact exposure behind each result remain unverified.", "missingness": "A dose range for the overall article is available, but the product and exact exposure behind each result remain unverified.", "uncertainty": "Distinguish nominal ranges from actual exposure, and the main effect from dose-extension claims.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific dosing schedules, nominal/actual content and adherence records." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The retained text describes a single ingredient versus placebo but provides no arm-specific lipid medicines, diet/activity, rescue treatment or actual adherence information. Statin-replacement claims are excluded.", "condition_status": "Unverified", "status_reason": "A single-product label and placebo design do not verify identical background treatment or absence of confounding.", "missingness": "A single-product label and placebo design do not verify identical background treatment or absence of confounding.", "uncertainty": "Avoid attributing effects of other treatment changes solely to berberine.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific concomitant lipid medicines, diet/activity plans, rescue treatment, adherence and arm-specific changes." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The claim conditions specify an absolute between-arm difference in treatment-end LDL-C. S01/S02 use mmol/L MD, S03 women use an SD scale, and S04 supplies only a reduction direction; final-value/change and adjustment details are absent.", "condition_status": "Partly verified", "status_reason": "The endpoint and some units are specified, but identical analysis definitions are unverified, so the results cannot be combined into one number.", "missingness": "The endpoint and some units are specified, but identical analysis definitions are unverified, so the results cannot be combined into one number.", "uncertainty": "Avoid presenting numbers with different measures or analysis definitions as the same effect.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific result tables, baseline/end values, change definitions, adjustment models and unit descriptions." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The overall range is 4~24 weeks. S02/S03 record week 12 LDL-C and S04 records 3-month LDL-C. S01's trial-specific end times and result-selection rules are not provided.", "condition_status": "Partly verified", "status_reason": "Some nominal report times are verified, but actual blood-sampling windows and selection of pooled times remain unresolved.", "missingness": "Some nominal report times are verified, but actual blood-sampling windows and selection of pooled times remain unresolved.", "uncertainty": "Avoid hiding duration differences or turning short-term end values into persistence effects.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific dosing/blood-sampling times, analysis windows and meta-analysis end-time selection rules." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S01 pools placebo-controlled RCTs; S02/S04 are labeled double-blind randomized placebo trials; S03 is labeled a randomized placebo trial plus stored-sample analysis. Actual sequence generation, concealment and baseline-balance data are absent.", "condition_status": "Partly verified", "status_reason": "Design names are available, but the allocation process and arm-specific baseline balance for the selected LDL-C result remain unverified.", "missingness": "Design names are available, but the allocation process and arm-specific baseline balance for the selected LDL-C result remain unverified.", "uncertainty": "Distinguish design titles from the actual allocation conditions for causal comparison.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original-trial protocols, allocation methods, concealment procedures and baseline tables." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The retained article contains LDL-C results and double-blind labels but no specific assay methods, fasting conditions, laboratory quality-control or assessor-blinding data.", "condition_status": "Unverified", "status_reason": "Actual measurement conditions cannot be read from this summary. This does not establish nonreporting in the full original papers.", "missingness": "Actual measurement conditions cannot be read from this summary. This does not establish nonreporting in the full original papers.", "uncertainty": "Distinguish differences in assay/collection conditions from actual LDL-C differences.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Specimen collection, fasting time, LDL-C assay/calculation methods, quality control and analyst 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.", "current_reports": [ "S01" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S01 specifies 14 LDL-C RCTs/1,447 participants and 18 RCTs/1,788 participants overall. These are the retained review's endpoint-specific totals, not current certification of unique trials or participants.", "condition_status": "Met", "status_reason": "Attribution of the two totals is directly specified. Completeness of trial-specific analysis denominators is examined separately in the next condition.", "missingness": "Attribution of the two totals is directly specified. Completeness of trial-specific analysis denominators is examined separately in the next condition.", "uncertainty": "This limited record condition prevents confusion between endpoint-specific totals and whole-review size.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S01's original records of endpoint-specific included-trial and participant counts." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The review supplies a total of 14 LDL-C trials but no actual included-trial table. Overlap between S02–S04 and the review cannot be established from this summary alone.", "condition_status": "Partly verified", "status_reason": "Review identity and totals are verified, but trial-specific overlap and total unique participants remain unverified.", "missingness": "Review identity and totals are verified, but trial-specific overlap and total unique participants remain unverified.", "uncertainty": "Distinguish report counts from independent replication and retain unknown family relationships honestly.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S01's included-trial tables, exclusions, original-trial identities and S02–S04 registration/report links." }, { "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.", "current_reports": [ "S01" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S01's retained result is MD −0.46 mmol/L, 95% CI −0.62~−0.30. It does not establish the expected effect of a specific product or for an individual.", "condition_status": "Met", "status_reason": "Attribution of the specified pooled value, unit and interval is verified. Clinical importance and pooling-model validity are separate questions.", "missingness": "Attribution of the specified pooled value, unit and interval is verified. Clinical importance and pooling-model validity are separate questions.", "uncertainty": "Separate verification of reported numbers from assessment of clinical sufficiency.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S01's original pooled LDL-C result record and units." }, { "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.", "current_reports": [ "S01" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The retained text notes geographic concentration, bias and formulation differences and describes pooling direct placebo RCTs. Actual weights, model, heterogeneity statistics and sensitivity results are not supplied.", "condition_status": "Unverified", "status_reason": "The existence of a pooled MD alone does not establish that the analysis model, robustness or trial differences have been explained.", "missingness": "The existence of a pooled MD alone does not establish that the analysis model, robustness or trial differences have been explained.", "uncertainty": "Examine pooled averages together with between-trial conditions and analysis uncertainty.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Meta-analysis methods, trial-specific effects/variances, heterogeneity measures, sensitivity analyses and analysis code." }, { "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.", "current_reports": [ "S01" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The article describes geographic concentration and substantial trial bias/formulation differences. Trial-specific assessments and geographic/product composition tables are absent; the original B2 axis is historical judgment metadata.", "condition_status": "Partly verified", "status_reason": "Limitations are described, but actual trial-specific bias evidence and applicability data have not been compared.", "missingness": "Limitations are described, but actual trial-specific bias evidence and applicability data have not been compared.", "uncertainty": "Distinguish review-summary limitations from actual assessment evidence.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Included-trial baseline/method tables, geographic composition, product information and result-specific bias-assessment evidence." }, { "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.", "current_reports": [ "S02", "S03" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S02 records 84 Chinese men. Their flow stage, arm-specific completion counts and LDL-C analysis denominators are absent from this summary.", "condition_status": "Partly verified", "status_reason": "The nominal sample size is verified, but inclusion of all 84 in week 12 LDL-C analysis cannot be verified.", "missingness": "The nominal sample size is verified, but inclusion of all 84 in week 12 LDL-C analysis cannot be verified.", "uncertainty": "Distinguish nominal participant counts from actual result-analysis denominators.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S02 recruitment flow, arm-specific allocation/completion, week 12 LDL-C analysis n and missing-data handling." }, { "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.", "current_reports": [ "S02" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S02's retained result is MD −0.21 mmol/L, 95% CI −0.50~0.08, P=.15. The original wording calls LDL ineffective; here it is limited to the reported nonsignificant result without declaring an effect of 0 or equivalence.", "condition_status": "Met", "status_reason": "The unfavorable direct result and interval remain linked. This status creates no new efficacy or equivalence-test result.", "missingness": "The unfavorable direct result and interval remain linked. This status creates no new efficacy or equivalence-test result.", "uncertainty": "Prevent significance-based result selection and overinterpretation of no significant difference.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S02's LDL-C estimate, interval, P value and original direction description." }, { "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.", "current_reports": [ "S03", "S02" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S03 specifies 100 women and 84 men and includes analysis of stored samples from the existing male trial. Actual female/male LDL-C analysis denominators and completion counts are absent.", "condition_status": "Partly verified", "status_reason": "Nominal counts by sex and the reuse design are verified, but result-specific analysis denominators cannot be newly established.", "missingness": "Nominal counts by sex and the reuse design are verified, but result-specific analysis denominators cannot be newly established.", "uncertainty": "Distinguish reused people/specimens from new recruitment and nominal n from analysis n.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S03 female participant flow, arm-specific analysis n and remeasurement/analysis records for existing male specimens." }, { "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.", "current_reports": [ "S03" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S03 records women's LDL as −1.06 SD, 95% CI −1.44~−0.69. The SD definition, analysis model and between-arm difference in mmol/L are unverified in this summary.", "condition_status": "Partly verified", "status_reason": "The numbers and SD label are specified, but conversion/variance evidence for comparison with mmol/L effect sizes is absent.", "missingness": "The numbers and SD label are specified, but conversion/variance evidence for comparison with mmol/L effect sizes is absent.", "uncertainty": "Keep differences in scale and analysis definition visible.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S03 original-unit LDL means, variances, analysis n and SD-scale construction/adjustment methods." }, { "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.", "current_reports": [ "S03" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S03 describes apoB as the female trial's primary endpoint and LDL as secondary. Planning documents were not read in this work; prospective LDL hierarchy, adjustment and analysis changes were not directly verified.", "condition_status": "Partly verified", "status_reason": "The retained summary states a hierarchy, but no evidence establishes comparison with actual prospective plans and reporting.", "missingness": "The retained summary states a hierarchy, but no evidence establishes comparison with actual prospective plans and reporting.", "uncertainty": "Distinguish the interpretation hierarchy of favorable subordinate results from actual plan verification.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S03 registration, protocols and analysis plans covering endpoint hierarchy, multiplicity and changes." }, { "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.", "current_reports": [ "S02", "S03" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S03 includes stored-sample analysis from the existing male trial, and S02/S03 citations share NCT03770325. The retained text explicitly states these were not counted as two independent LDL confirmations.", "condition_status": "Met", "status_reason": "Reuse within the same male family is verified in the current summary. This does not certify total unique trials or participants.", "missingness": "Reuse within the same male family is verified in the current summary. This does not certify total unique trials or participants.", "uncertainty": "This identity condition directly distinguishes repeat reports from unique studies.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S02/S03 original citations, designs and textual links to the same male data." }, { "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.", "current_reports": [ "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S04 reports 144 enrolled people. Arm-specific allocation/completion and actual 3-month LDL-C analysis denominators are not supplied.", "condition_status": "Partly verified", "status_reason": "Only enrollment is known; inclusion of all 144 in comparative analysis cannot be verified.", "missingness": "Only enrollment is known; inclusion of all 144 in comparative analysis cannot be verified.", "uncertainty": "Separate enrollment from actual analysis denominators.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S04 enrollment/allocation/completion flow, arm-specific 3-month sampling/analysis n and exclusion reasons." }, { "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.", "current_reports": [ "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S04's retained summary says the abstract reports a reduction versus placebo, while explicitly marking the exact between-arm effect and CI unverified.", "condition_status": "Partly verified", "status_reason": "A positive-direction summary exists, but effect magnitude, precision and analysis definitions cannot be filled in.", "missingness": "A positive-direction summary exists, but effect magnitude, precision and analysis definitions cannot be filled in.", "uncertainty": "Distinguish directional descriptions from quantitative effects and precision.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S04 arm-specific LDL-C result tables, estimation model, effect value and 95% CI." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The retained text notes nonsignificant male and positive female findings with directional/population heterogeneity. Female SD and male mmol/L are different scales; formal sex-interaction estimates and CIs are not supplied.", "condition_status": "Partly verified", "status_reason": "Results differ in direction, but material separating formal effect modification from condition differences is absent. Numerical differences alone are not designated conflict for an identical result.", "missingness": "Results differ in direction, but material separating formal effect modification from condition differences is absent. Numerical differences alone are not designated conflict for an identical result.", "uncertainty": "Distinguish directional heterogeneity, subgroup effects and reporting conflict.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Prospective sex hypotheses, interaction models, original-unit effects/intervals and population/formulation differences across trials." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "Citations list PROSPERO and two NCT numbers, but all four evidence-table registration fields say unconfirmed. Current access to and comparison of original registration records totals 0.", "condition_status": "Partly verified", "status_reason": "Bibliographic clues exist, but unconfirmed registration fields cannot be overwritten as actual registration verification. S04 registration identity also remains unverified.", "missingness": "Bibliographic clues exist, but unconfirmed registration fields cannot be overwritten as actual registration verification. S04 registration identity also remains unverified.", "uncertainty": "Distinguish bibliographic identifiers from actual registration/plan comparison.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Review/trial registration originals, trial identity links for each report and change histories." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S01 is described as a preregistered review, S02 as a direct prospective lipid group, and S03 LDL as secondary. There is no current record of externally reading each plan and complete result table.", "condition_status": "Partly verified", "status_reason": "Prospective descriptions exist, but original material for checking actual analysis/time consistency and selective reporting remains unverified.", "missingness": "Prospective descriptions exist, but original material for checking actual analysis/time consistency and selective reporting remains unverified.", "uncertainty": "Expose the material needed to examine selection of favorable analyses.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S01–S04 protocols/registrations, statistical analysis plans, complete lipid results, changes and multiplicity records." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The current summary provides MD/SD results but no specific analysis-population, effect-of-interest or adjustment-model data. Generic English verification wording does not fill these gaps.", "condition_status": "Unverified", "status_reason": "RCT titles and generic English wording do not establish ITT, PP or a particular analysis model.", "missingness": "RCT titles and generic English wording do not establish ITT, PP or a particular analysis model.", "uncertainty": "Avoid falsely presenting different analyses as the same effect of interest.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Result-specific analysis n, ITT/PP definitions, adjustment covariates and statistical analysis plans/models." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The retained summary lacks result-specific attrition/missingness counts, reasons and handling tables. There is no evidence that enrollment of 144, 84 men or 100 women equals completion or analysis n.", "condition_status": "Unverified", "status_reason": "Nominal counts alone do not establish missing-data effects or inclusion of all participants.", "missingness": "Nominal counts alone do not establish missing-data effects or inclusion of all participants.", "uncertainty": "Distinguish denominator losses from selection in effect estimation.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-specific follow-up losses, missing blood samples, discontinuation reasons, missing-data handling and sensitivity results." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "S01 notes mixed original-trial funding and separately unverified review COI; S02 lists Hong Kong's Health and Medical Research Fund; S03 lists the same funding and reports no related COI; S04 funding/product-support details remain unverified. Investigator overlap is also noted.", "condition_status": "Partly verified", "status_reason": "Funding/declaration summaries exist, but product provision, employment, institutional relationships and actual declaration documents have not been compared.", "missingness": "Funding/declaration summaries exist, but product provision, employment, institutional relationships and actual declaration documents have not been compared.", "uncertainty": "Distinguish independence claims from actual declarations, funding and research families.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "S01 trial/review COI, S02–S04 funding/product support, author declarations and institutional relationships." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "A pooled MD and some intervals are available, but no important-difference criterion for this question is supplied. The original text also identifies LDL-C as a surrogate endpoint.", "condition_status": "Unverified", "status_reason": "Significance, 14 trials, participant counts and original C50 alone do not establish clinical sufficiency.", "missingness": "Significance, 14 trials, participant counts and original C50 alone do not establish clinical sufficiency.", "uncertainty": "Distinguish reported intervals from judgments of clinical importance.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Evidence and prospective criteria for important LDL-C differences in dyslipidemia populations, with original-unit results/CIs." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "This table compares treatment-end LDL-C within the stated formulation, population and duration. It does not select a question establishing optimal dose, persistence after stopping or long-term effects.", "condition_status": "Not applicable", "status_reason": "Optimal dose and persistence are not imposed as additional requirements for the current selected question. This does not establish absence of such effects or safety.", "missingness": "Optimal dose and persistence are not imposed as additional requirements for the current selected question. This does not establish absence of such effects or safety.", "uncertainty": "This supplementary condition distinguishes the narrow main-effect question from applicability of extension conditions.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The selected-question scope and separate direct evidence if dose/persistence extensions are sought." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The retained text explicitly describes LDL-C as a surrogate rather than myocardial infarction/death and excludes statin-replacement and cardiovascular-event-prevention wording.", "condition_status": "Met", "status_reason": "The boundary between the endpoint and separate clinical questions is directly verified. Event-prevention or medicine-replacement efficacy is not established.", "missingness": "The boundary between the endpoint and separate clinical questions is directly verified. Event-prevention or medicine-replacement efficacy is not established.", "uncertainty": "Distinguish surrogate endpoints from clinical-event extensions.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The original endpoint and exclusions covering cardiovascular events and medicine replacement." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The safety warning says gastrointestinal adverse effects may be more frequent than with placebo. Event definitions, actual between-arm frequencies, people/event counts, denominators, follow-up and discontinuation reasons are absent from this summary.", "condition_status": "Partly verified", "status_reason": "The original warning is retained, but material attributing quantitative harms, incidence and discontinuations is absent.", "missingness": "The original warning is retained, but material attributing quantitative harms, incidence and discontinuations is absent.", "uncertainty": "This supplementary condition is needed because efficacy summaries and short-term RCTs do not establish overall safety.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific gastrointestinal-event definitions, arm-specific events/exposure/follow-up tables and collection/discontinuation records." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The original text calls for clinician review in pregnancy, lactation, infants and use with CYP-related medicines. It supplies no actual exposure, events, timing, denominators or interaction results for those groups.", "condition_status": "Partly verified", "status_reason": "Caution groups are verified, but material addressing personal safety, special-population harm magnitude and causality remains unverified.", "missingness": "Caution groups are verified, but material addressing personal safety, special-population harm magnitude and causality remains unverified.", "uncertainty": "This supplementary condition separates the selected efficacy population from vulnerable-group/comedication harms.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Population-specific exposure, concomitant medicines, events/timing, baseline risk and direct-material identity." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The correction says 4 generic verification fields were replaced with specific English, but the current evidence-table sample-size, funding, endpoint and result English fields remain generic. Specific numbers/denominators were read from their Korean locations.", "condition_status": "Conflicting data", "status_reason": "Current generic English fields directly disagree with the historical description of specific replacements. Before/after correction versions were not acquired, so the event history is not newly established; this is separate from clinical-result conflict.", "missingness": "Current generic English fields directly disagree with the historical description of specific replacements. Before/after correction versions were not acquired, so the event history is not newly established; this is separate from clinical-result conflict.", "uncertainty": "Distinguish historical correction descriptions from current field values.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original bytes before/after the 2026-09-14 English correction and specific correspondence of the four current fields." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "Original values are C50, Warning and B/S/R0/I2/EX/B2/CX. The co-primary-split, large hard-endpoint RCT, no-human-study and failed-primary/positive-secondary indicators are false, and the original subclaim list is empty. Original values remain in the input.", "condition_status": "Met", "status_reason": "Preservation of original judgment metadata and separation from new condition statuses are verified. The original score is not inherited as new efficacy certification or a condition score.", "missingness": "Preservation of original judgment metadata and separation from new condition statuses are verified. The original score is not inherited as new efficacy certification or a condition score.", "uncertainty": "Traceability distinguishes original judgment from the material-conversion status.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Exact original locations for grade, score, axes, original true/false values, arrays, corrections and dates." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The whole retained summary and exact Korean/English, evidence, citation and correction locations were read. PubMed, PMC, DOI, registrations and original papers were not accessed or read in this work; links do not establish full-text reading.", "condition_status": "Met", "status_reason": "Actual local-summary reading and external material states are recorded separately. This does not verify current accuracy of all external content.", "missingness": "Actual local-summary reading and external material states are recorded separately. This does not verify current accuracy of all external content.", "uncertainty": "Avoid confusing links or acquired summaries with full-text reading.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Current input hashes, actual reading scope, material-specific access/acquisition/reading records and original-location links." }, { "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.", "current_reports": [ "S01", "S02", "S03", "S04" ], "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread, with access not attempted.", "observation": "The original verdict-review date is 2026-09-08 and the correction date is 2026-09-14. Individual citations lack access-level/access-date keys; only a whole-record comparison narrative exists. Report-specific historical access dates/levels remain unrecorded.", "condition_status": "Unverified", "status_reason": "The original review date and comparison narrative cannot be copied into individual-paper access dates or full-text reading levels.", "missingness": "The original review date and comparison narrative cannot be copied into individual-paper access dates or full-text reading levels.", "uncertainty": "Distinguish attribution of original review dates, individual access dates and current reading times.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original acquisition/reading records, access dates, document versions and access levels for each material." } ], "reports": [ { "report_id": "S01", "title": "Blais 2023 placebo-controlled RCT meta-analysis", "url": "https://pubmed.ncbi.nlm.nih.gov/36941490/", "report_type": "Retained summary of a preregistered placebo-controlled RCT review", "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "Retained Korean/English summaries, evidence and citations were read. External bibliography, abstracts, full texts, registration and protocols remain unattempted, unacquired and unread.", "study_family": "Overlap between the review’s included trials and S02–S04 remains unverified. Distinguish endpoint-specific totals from whole-review size.", "observed_result": "LDL-C 14 RCTs/1,447 participants: MD −0.46 mmol/L, 95% CI −0.62~−0.30. The whole review has 18 RCTs/1,788 participants. This is not a guaranteed product effect or current certification of unique trials.", "result_level": "A retained pooled reported value. Included-trial tables, pooling models, bias and sensitivity analyses were not externally compared in this work.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "Retained judgment evidence/bibliographic summary", "public_status": "Retained summary acquired/read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "Retained evidence, bibliography and text summaries were read. Distinguish these from clinical full texts and original binaries. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External PubMed bibliography/abstract gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A retained citation URL gateway. Current external document existence, content, access and reading were not newly verified. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External DOI bibliographic gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A bibliographic gateway formed from the original DOI; it does not establish a direct publisher full-text address or acquisition. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "Article full text; direct address unverified", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Original article full text remains unacquired/unread. A bibliographic gateway is not converted into a direct publisher full-text address. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "Original prospective review-registration material", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The registration number is a retained bibliographic clue. Preserve the unconfirmed evidence-table registration field; actual registration access, reading and plan comparison were not performed. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/36941490/" } ], "independent_replication": "Do not add the review and individual reports into an independent-trial count." }, { "report_id": "S02", "title": "Chan 2021 male 12-week trial", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8401658/", "report_type": "Retained summary of a male randomized double-blind placebo-controlled trial", "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "Retained Korean/English summaries, evidence and citations were read. External bibliography, abstracts, full texts, registration and protocols remain unattempted, unacquired and unread.", "study_family": "A trial of 84 men whose stored samples were reused in S03. Actual completion and LDL-C analysis denominators remain unverified.", "observed_result": "Week 12 LDL-C MD −0.21 mmol/L, 95% CI −0.50~0.08, P=.15. Nonsignificance does not establish an effect of 0 or equivalence.", "result_level": "A retained direct reported value. Actual allocation, completion and analysis denominators, measurement methods and models remain unverified.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "Retained judgment evidence/bibliographic summary", "public_status": "Retained summary acquired/read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "Retained evidence, bibliography and text summaries were read. Distinguish these from clinical full texts and original binaries. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External PMC article HTML full-text gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A retained PMC HTML full-text gateway. Distinguish its URL from current full-text acquisition/reading; external access was not attempted in this work. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External DOI bibliographic gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A bibliographic gateway formed from the original DOI; it does not establish a direct publisher full-text address or acquisition. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "Trial protocol/analysis plan; direct address unverified", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Registration-identifier clues are separate from actual protocol/analysis-plan acquisition and reading. Direct addresses remain unverified. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External original trial-registration material", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Retain citation registration-number clues alongside unconfirmed evidence-table fields. A link does not establish registration-version or plan verification. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." } ], "links": [ { "label": "Official source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8401658/" } ], "independent_replication": "Do not count the same male data in S03 as additional independent replication." }, { "report_id": "S03", "title": "Zhao 2026 sex/stored-sample report", "url": "https://pubmed.ncbi.nlm.nih.gov/42470424/", "report_type": "Retained summary of a female randomized trial and existing male stored-sample analysis", "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "Retained Korean/English summaries, evidence and citations were read. External bibliography, abstracts, full texts, registration and protocols remain unattempted, unacquired and unread.", "study_family": "Distinguish recruitment of 100 women from stored samples of 84 existing male participants. Two reports in the same research series are not two independent LDL confirmations.", "observed_result": "Women’s week 12 LDL −1.06 SD, 95% CI −1.44~−0.69. The original summary describes a larger effect than in men, but formal interaction, SD definitions, original units and denominators remain unverified. Distinguish primary apoB from secondary LDL.", "result_level": "A retained SD-scale reported value, not converted into mmol/L. Prospective plans, multiplicity and actual analyses were not externally compared in this work.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "Retained judgment evidence/bibliographic summary", "public_status": "Retained summary acquired/read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "Retained evidence, bibliography and text summaries were read. Distinguish these from clinical full texts and original binaries. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External PubMed bibliography/abstract gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A retained citation URL gateway. Current external document existence, content, access and reading were not newly verified. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External DOI bibliographic gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A bibliographic gateway formed from the original DOI; it does not establish a direct publisher full-text address or acquisition. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "Article full text; direct address unverified", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Original article full text remains unacquired/unread. A bibliographic gateway is not converted into a direct publisher full-text address. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External original trial-registration material", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Retain citation registration-number clues alongside unconfirmed evidence-table fields. A link does not establish registration-version or plan verification. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/42470424/" } ], "independent_replication": "Distinguish shared male stored samples and investigator overlap from new female recruitment." }, { "report_id": "S04", "title": "Derosa 2013 low-risk lipid trial", "url": "https://pubmed.ncbi.nlm.nih.gov/23441841/", "report_type": "Retained summary of a low-risk lipid randomized double-blind placebo-controlled trial", "existence": "Stored research and bibliographic summaries exist. Existence, public availability, acquisition and reading of external abstracts, full texts, registration, protocols, analysis plans and original product, funding and harm material remain separately unverified.", "acquired_read": "Retained Korean/English summaries, evidence and citations were read. External bibliography, abstracts, full texts, registration and protocols remain unattempted, unacquired and unread.", "study_family": "Retained as a separate low-risk trial citation. Review inclusion, overlap and actual analysis denominators remain unverified.", "observed_result": "144 enrolled, 3-month LDL-C. Only a summary saying the abstract reported a reduction versus placebo is available; the exact between-arm effect and CI remain unverified.", "result_level": "A retained direction-only summary. Do not turn enrollment into allocation, completion or analysis denominators, or fill effects/intervals from other reports.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "Retained judgment evidence/bibliographic summary", "public_status": "Retained summary acquired/read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "Retained evidence, bibliography and text summaries were read. Distinguish these from clinical full texts and original binaries. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External PubMed bibliography/abstract gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A retained citation URL gateway. Current external document existence, content, access and reading were not newly verified. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External DOI bibliographic gateway", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "A bibliographic gateway formed from the original DOI; it does not establish a direct publisher full-text address or acquisition. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "Article full text; direct address unverified", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Original article full text remains unacquired/unread. A bibliographic gateway is not converted into a direct publisher full-text address. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." }, { "material_type": "External original trial-registration material", "public_status": "Public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Retain citation registration-number clues alongside unconfirmed evidence-table fields. A link does not establish registration-version or plan verification. Historical individual access levels/dates are unrecorded. Original review narratives do not establish current external full-text reading. The displayed material date is the case-record review date. Original verdict review, correction and case review dates are not historical access dates for individual external materials or search cut-offs. Historical external access dates and reading scope are unrecorded; external access was not attempted in this conversion." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/23441841/" } ], "independent_replication": "Do not establish independent-replication counts while review overlap remains unverified." } ], "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" }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "Without S01’s actual included-trial table, overlap with S02–S04 remains unverified. S02/S03 share the same male stored-sample family, while new female recruitment is retained separately. S04 is a separate low-risk trial citation. Total unique trials and participants remain unverified." }, "history": [ { "date": "2026-10-27", "kind": "Separation of public-facing pages and materials", "view_version": "1.0", "change": "The public view and materials were prepared from the existing 37 items. No new clinical search, verification-state change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-27" }