{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3067-main", "verdict_number": "3067", "title": "Oral single-ingredient berberine hydrochloride × Reduction of HbA1c in adults with type 2 diabetes", "view_version": "1.0", "view_created_date": "2026-10-27", "criteria_version": "1.2", "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 type 2 diabetes. Detailed diagnosis, age, baseline HbA1c, eligibility/exclusion and losses during pretreatment remain unverified in the current summary.", "comparator": "Under identical gentamicin pretreatment: the 98-person berberine-only active-ingredient arm versus the 103-person berberine/probiotic double-placebo arm. These are allocation counts, not analysis counts.", "endpoint": "The between-arm difference in absolute HbA1c change at week 13. Retained LS mean changes are −0.99 %p versus −0.59 %p, difference −0.40 %p (95% CI −0.67 to −0.13; adjusted P=.0006). Actual model, selected-arm analysis n and adjustment definitions remain unverified.", "intervention": "Oral industrially synthesized single-ingredient berberine hydrochloride tablets. Botanical extracts, other derivatives and combinations are not interchangeable; actual batch, purity, added ingredients and standardization remain unverified.", "dose": "The nominal dose is 600 mg 2 times daily (1.2 g/day). Actual intake, adherence, dose reduction, discontinuation and rescue treatment remain unverified.", "duration": "All arms received 7 days of gentamicin pretreatment, followed by 12 weeks of trial agent and assessment at week 13. This is not expanded to effects without antibiotics, pretreatment effects or persistence after stopping.", "excluded_extensions": [ "Original C, 54 points, Warning and B/S/R1/I1/E+/B0/CX are retained. Table statuses do not establish a new score, effect or clinical certification.", "409 randomized, 391 with primary data and 18 (4.4%) missing refer to all 4 arms. They are not transferred to actual analysis, completion or missing-data denominators for selected-arm allocation of 98/103 or newly added together.", "The 2008 pilot’s 36 randomized, 15/16 analyzed and 9.5±0.5%→7.5±0.4%/within-arm P<.01 are active-comparator context. Exact between-arm differences, CI and type of ± remain unverified; this is not independent placebo-comparison replication or metformin equivalence.", "No new claim is made of diabetes cure, complication prevention, metformin replacement, identical effects across all berberine products, optimal dose, long-term persistence or subgroup confirmation.", "Original warnings concerning gastrointestinal adverse effects, hypoglycemia with glucose-lowering drugs, checking CYP2D6, 2C9 and 3A4 substrate medicines, and avoiding use in pregnancy/lactation/infants are retained. Actual event/person counts, harm denominators, follow-up and interaction magnitudes remain unverified; personal safety is not certified." ] }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Is the week 13 HbA1c question fixed for the single-active-ingredient and double-placebo arms?", "needed": "The formulation, population, timing, endpoint and comparison conditions, and their change history.", "role": "Required", "role_reason": "Prevent mixing results with different interventions, comparators or times.", "application_exception": "The original subclaim list is empty; English wording is not counted as another independent claim.", "criterion": "Link common pretreatment, the single active ingredient, double placebo and the between-arm difference in absolute HbA1c change at week 13; exclude other conditions.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "If the boundary changes, retain the existing conditions and separately assess whether the new comparison asks the same question.", "current_reports": [ "S01", "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": "This concerns the between-arm difference in absolute HbA1c change at week 13 with industrially synthesized single-ingredient berberine hydrochloride. Combination arms, metformin comparisons and effects without pretreatment are excluded from this question.", "condition_status": "Met", "status_reason": "The current claim conditions and text specify the selected comparison, fixing this limited scope.", "missingness": "The question's boundary is verified. This is neither new verification of the full original paper nor confirmation of identical effects for other berberine products.", "uncertainty": "The question's boundary is verified. This is neither new verification of the full original paper nor confirmation of identical effects for other berberine products.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The formulation, population, timing, endpoint and comparison conditions, and their change history." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Are the stated ingredient, source and formulation and actual product specifications verified?", "needed": "Trial-product descriptions, ingredient lists, batch and purity/added-ingredient specifications.", "role": "Required", "role_reason": "Actual product identity is needed to avoid transferring results to other extracts, derivatives or combinations.", "application_exception": "Dihydroberberine, botanical extracts and topical products are not identical to the single-ingredient tablet.", "criterion": "Retain the stated identity as synthetic single-ingredient berberine hydrochloride tablets; verify actual trial-product manufacturing, batch, purity, added ingredients and standardization against that identity. Recording the distinction between stated identity and unverified specifications does not replace actual product-identity verification.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare product-analysis and manufacturing records to verify agreement between stated amounts and the actual molecule/formulation.", "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 claim conditions specify industrially synthesized berberine hydrochloride as a single-ingredient tablet, not a botanical extract. Actual batch, purity, added ingredients and standardization remain unverified in the retained summary.", "condition_status": "Partly verified", "status_reason": "The stated molecule and formulation are known, but product specifications for identity matching remain unresolved.", "missingness": "Manufacturing, batch, purity, added-ingredient and supplied-product comparison information for the tablet is unavailable.", "uncertainty": "Manufacturing, batch, purity, added-ingredient and supplied-product comparison information for the tablet is unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-product descriptions, ingredient lists, batch and purity/added-ingredient specifications." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "Are the nominal dose and actual intake/adherence verified?", "needed": "Arm-level intake records, adherence criteria and dose-reduction/discontinuation/rescue-treatment information.", "role": "Required", "role_reason": "A nominal dose does not automatically establish actual exposure.", "application_exception": "Unverified adherence does not mean that every participant took none of the treatment.", "criterion": "Retain the stated 600 mg 2 times daily (1.2 g/day) while verifying actual intake, adherence and 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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Distinguish assignment effects from actual adherence effects when comparing intake records and planned analyses.", "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 nominal dose is 600 mg 2 times daily (1.2 g/day). Arm-level intake verification, adherence rates, dose reductions, discontinuation and rescue treatment are absent from the current summary.", "condition_status": "Partly verified", "status_reason": "The nominal intake is stated, but actual exposure and adherence effects remain unverified.", "missingness": "Adherence and medication-change information needed to establish the stated dose as actual intake is unavailable.", "uncertainty": "Adherence and medication-change information needed to establish the stated dose as actual intake is unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-level intake records, adherence criteria and dose-reduction/discontinuation/rescue-treatment information." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "Are common gentamicin pretreatment and the selected intervention's contribution distinguished?", "needed": "Pretreatment plans, actual intake and separate material comparing conditions without pretreatment.", "role": "Required", "role_reason": "Distinguish the common antibiotic condition from applicability to ordinary supplements.", "application_exception": "Do not interpret the 7-day pretreatment as tolerability run-in selection, washout or an effect without pretreatment.", "criterion": "Retain 7 days of gentamicin pretreatment in every arm; do not transfer results to berberine effects without that condition.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "If a question without pretreatment is needed, examine a separate comparison with pretreatment presence/absence designed in advance.", "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": "All arms first received gentamicin for 7 days, including the berberine-only active-ingredient and double-placebo arms. This comparison does not estimate effects without antibiotics or the pretreatment's own effect.", "condition_status": "Met", "status_reason": "The text and claim conditions specify common pretreatment, fixing it as a condition of the current contrast.", "missingness": "The common pretreatment's identity and duration are verified. Effects without pretreatment, pretreatment adherence and selection effects remain separately unverified.", "uncertainty": "The common pretreatment's identity and duration are verified. Effects without pretreatment, pretreatment adherence and selection effects remain separately unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Pretreatment plans, actual intake and separate material comparing conditions without pretreatment." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "Is the sequence of pretreatment, trial-agent duration and week 13 assessment verified?", "needed": "Visit schedules, assessment windows, administration/discontinuation dates and actual arm-level exposure durations.", "role": "Required", "role_reason": "Exposure duration and outcome-assessment time are separate information.", "application_exception": "Do not change 12 weeks of trial agent into assessment at week 12 or calculate a new calendar duration.", "criterion": "Separate 7 days of pretreatment, 12 weeks of trial agent and assessment at week 13, linking them as the conditions of a single assessment.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare planned visits with actual measurement dates to examine timing deviations and handling of missing data.", "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 conditions describe 7 days of gentamicin pretreatment followed by 12 weeks of trial agent and HbA1c assessment at week 13.", "condition_status": "Met", "status_reason": "The timing conditions and the week 13 endpoint in the evidence agree.", "missingness": "Nominal duration and assessment time are verified. Visit windows, actual arm-level exposure durations and sustained long-term effects were not verified.", "uncertainty": "Nominal duration and assessment time are verified. Visit windows, actual arm-level exposure durations and sustained long-term effects were not verified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Visit schedules, assessment windows, administration/discontinuation dates and actual arm-level exposure durations." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "Are the type 2 diabetes population, baseline status and selection process verified?", "needed": "Protocol eligibility/exclusion criteria, baseline tables and pretreatment/allocation flow diagrams.", "role": "Required", "role_reason": "A population label alone does not establish applicability to every adult with diabetes.", "application_exception": "Pretreatment's presence does not establish that tolerability selection occurred.", "criterion": "Verify the adult type 2 diabetes population, diagnosis, age, baseline HbA1c, co-medication, eligibility/exclusion and allocation after pretreatment.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare baseline tables and flow diagrams to assess whether the actual analysis population matches the selected 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 population is adults with type 2 diabetes. The current summary lacks detailed diagnostic and age information, baseline HbA1c distributions, eligibility/exclusion and arm-level losses during pretreatment.", "condition_status": "Partly verified", "status_reason": "Disease and adulthood are known, but information needed to assess detailed population matching and representativeness remains unresolved.", "missingness": "Detailed selection, baseline characteristics and losses during pretreatment remain unverified.", "uncertainty": "Detailed selection, baseline characteristics and losses during pretreatment remain unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Protocol eligibility/exclusion criteria, baseline tables and pretreatment/allocation flow diagrams." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Are the berberine-only active ingredient and double-placebo compositions verified?", "needed": "The 4-arm administration table, placebo ingredients/appearance and arm-level co-use/adherence information.", "role": "Required", "role_reason": "Do not transfer contributions from combination arms to a single active ingredient's effect.", "application_exception": "The single-active-ingredient arm does not mean exposure without common gentamicin.", "criterion": "Link the berberine-only active-ingredient arm and berberine/probiotic double-placebo arm as a contrast under identical pretreatment.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Link the administration table to analysis contrasts to check for mixing results from other active arms.", "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 selected contrast is the 98-person berberine-only active-ingredient arm versus the 103-person double-placebo arm. The probiotic-combination arm is excluded; the comparator received the same gentamicin pretreatment.", "condition_status": "Met", "status_reason": "The retained arm identities and double-placebo composition make the selected contrast clear.", "missingness": "The comparison composition is verified within the retained summary. Placebo appearance/ingredients and actual arm-level co-use/adherence require separate verification.", "uncertainty": "The comparison composition is verified within the retained summary. Placebo appearance/ingredients and actual arm-level co-use/adherence require separate verification.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The 4-arm administration table, placebo ingredients/appearance and arm-level co-use/adherence information." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Are the 4-arm randomization/blinding, concealment and baseline balance verified?", "needed": "Randomization-generation/concealment procedures, baseline tables and placebo/assessor-blinding procedures.", "role": "Required", "role_reason": "Distinguish a design label from actual conduct.", "application_exception": "A blinding label certifies neither absence of bias nor successful blinding of every assessment.", "criterion": "Retain the prospectively registered 4-arm randomized double-blind design label; verify actual allocation generation/concealment, maintained assessment blinding and baseline balance from methods and baseline data. Recording the design label separately from unverified procedures does not replace procedure verification.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare methods, protocols and baseline tables by outcome to examine possible allocation and measurement differences.", "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": "PREMOTE is retained as a prospectively registered 4-arm randomized double-blind placebo trial. Actual sequence generation, concealment, maintenance of assessment blinding and baseline balance remain unverified in the current summary.", "condition_status": "Partly verified", "status_reason": "The design name is known, but procedural information for assessing bias remains unresolved.", "missingness": "RCT and double-blind labels alone cannot verify actual allocation and measurement procedures.", "uncertainty": "RCT and double-blind labels alone cannot verify actual allocation and measurement procedures.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Randomization-generation/concealment procedures, baseline tables and placebo/assessor-blinding procedures." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Are HbA1c change units and actual testing methods verified?", "needed": "HbA1c measurement methods, standardization and baseline/week 13 measurement timing and repetition rules.", "role": "Required", "role_reason": "Distinguish absolute change from relative change and final values.", "application_exception": "Do not substitute clinical complications, cure or mortality outcomes for HbA1c.", "criterion": "Verify the %p unit and direction of absolute HbA1c change at week 13, methods, laboratories and time-specific standards.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare measurement plans and results for use of identical methods and handling of missing measurements.", "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 selected endpoint is the between-arm difference in absolute HbA1c change at week 13. A decrease in %p is neither a relative % decrease in HbA1c nor final HbA1c itself. Testing methods and laboratory standardization remain unverified.", "condition_status": "Partly verified", "status_reason": "The absolute-change unit and direction are stated, but actual measurement conditions remain unresolved.", "missingness": "Testing methods, laboratories and consistency between baseline/final measurements are unavailable.", "uncertainty": "Testing methods, laboratories and consistency between baseline/final measurements are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "HbA1c measurement methods, standardization and baseline/week 13 measurement timing and repetition rules." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "Do retained LS mean changes, the between-arm difference, CI and P describe the same contrast?", "needed": "Original result tables, analysis plans and definitions of adjusted P and CI.", "role": "Required", "role_reason": "Retain original values and interpretation conditions accurately even for favorable results.", "application_exception": "Do not present the original difference as new arithmetic or a new clinical verdict, or convert it into a raw mean.", "criterion": "Link the original −0.99 versus −0.59 %p, difference −0.40 %p, 95% CI −0.67 to −0.13 and adjusted P=.0006 unchanged.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare the original table's contrast, units and model against planned analyses to verify attribution of displayed values.", "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": "PREMOTE's LS mean changes are −0.99 %p versus −0.59 %p, with a between-arm difference of −0.40 %p (95% CI −0.67 to −0.13; adjusted P=.0006). These are retained original reported values; no new difference or interval was calculated.", "condition_status": "Met", "status_reason": "The evidence results and reader answer state the numbers, direction and interval for the same contrast.", "missingness": "Attribution of displayed values to the original text is verified. The original paper's model, analysis n and calculation definitions for intervals/adjustments were not newly verified.", "uncertainty": "Attribution of displayed values to the original text is verified. The original paper's model, analysis n and calculation definitions for intervals/adjustments were not newly verified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original result tables, analysis plans and definitions of adjusted P and CI." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "Are the LS mean label, actual model, analysis population and adjustments verified?", "needed": "Statistical analysis plans, model equations, analysis-population definitions, arm-level analysis n and missing-data handling.", "role": "Required", "role_reason": "Do not interpret an LS mean as a raw mean or an effect in everyone randomized.", "application_exception": "Do not delete original effect values because analysis methods are unavailable or fill the gap with ITT.", "criterion": "Verify the least-squares mean label together with the actual model, ITT/PP, missing-data handling, adjustment variables and analysis n for the selected contrast.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare planned models with result-table populations and adjustment variables to distinguish the estimated effects.", "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 LS mean change label is known, but the retained summary does not verify model equations, covariates, ITT/PP, missing-data handling or actual analysis n in the two arms.", "condition_status": "Partly verified", "status_reason": "The estimate type is known, but the population and adjustments underlying it remain unresolved.", "missingness": "The actual LS mean model, analysis population, covariates and selected-arm analysis n remain unverified.", "uncertainty": "The actual LS mean model, analysis population, covariates and selected-arm analysis n remain unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Statistical analysis plans, model equations, analysis-population definitions, arm-level analysis n and missing-data handling." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "Are the adjusted P/95% CI labels and testing/multiplicity definitions verified?", "needed": "Original statistical methods, analysis plans and contrast-specific adjustment tables.", "role": "Required", "role_reason": "Do not confuse adjusted values in a multi-arm trial with raw P.", "application_exception": "Do not calculate new P/CI or automatically treat printing differences between values as a conflict.", "criterion": "Verify the testing target, adjustment method, significance level and scope of multiple contrasts in the 4-arm trial for displayed adjusted P=.0006 and 95% CI.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare testing/adjustment definitions with result tables; do not replace original rounded values with new calculations.", "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": "P=.0006 is labelled adjusted P, and the original 95% CI is retained. The test/multiplicity adjustment method and whether the CI uses the same adjustment scope remain unverified in the current summary.", "condition_status": "Partly verified", "status_reason": "P and interval strings are known, but detailed testing and adjustment definitions remain unresolved.", "missingness": "Multiplicity methods, test type, significance level and adjustment scopes for CI and P are unavailable.", "uncertainty": "Multiplicity methods, test type, significance level and adjustment scopes for CI and P are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original statistical methods, analysis plans and contrast-specific adjustment tables." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Are the overall 409 participants distinguished from allocation counts for the two selected arms?", "needed": "The 4-arm flow diagram and arm-level allocation/analysis/completion/missing-data tables.", "role": "Required", "role_reason": "Do not mix overall trial denominators with those of the selected contrast.", "application_exception": "Do not calculate 98+103 as a new sample size or use all 409 as analysis n for the selected contrast.", "criterion": "Record 409 people across all 4 arms and selected-arm allocation of 98/103 unchanged; do not repurpose them as analysis/completion 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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Link identical arm identities across allocation, completion, measurement and analysis stages to check for cross-use of denominators.", "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": "409 is the overall allocation count across 4 arms; allocation for the selected contrast is 98 versus 103 people. These numbers are not arm-level HbA1c analysis n or completion counts.", "condition_status": "Met", "status_reason": "The original evidence and crux specify overall and selected-arm allocation roles, allowing their distinction.", "missingness": "Allocation-count attribution is verified. Actual analysis, completion and missing-data n for the selected contrast remain unverified.", "uncertainty": "Allocation-count attribution is verified. Actual analysis, completion and missing-data n for the selected contrast remain unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The 4-arm flow diagram and arm-level allocation/analysis/completion/missing-data tables." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "Are the overall primary-data count and selected-arm analysis n/missing-data handling verified?", "needed": "HbA1c analysis n by the 4 arms, attrition reasons, imputation/model handling and sensitivity analyses.", "role": "Required", "role_reason": "Do not transfer an assessment of low overall missingness to actual selected-arm denominators.", "application_exception": "Do not recalculate 391/409 or distribute the same proportion to selected arms.", "criterion": "Retain 391/409 and 18 people (4.4%) as information for all 4 arms while verifying actual analysis n, attrition reasons and handling by selected arm.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Link arm-level flow to model handling of missing data to distinguish complete-case and assignment effects.", "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 overall primary-data count is 391/409, with 18 people (4.4%) missing. Analysis, completion and missing-data denominators and reasons/handling for the selected 98/103 arms are not separately verified.", "condition_status": "Partly verified", "status_reason": "Overall loss is known, but material verifying actual selected-contrast denominators and missing-data effects remains unresolved.", "missingness": "Overall missingness alone cannot establish the selected arms' analysis n, attrition distribution or handling.", "uncertainty": "Overall missingness alone cannot establish the selected arms' analysis n, attrition distribution or handling.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "HbA1c analysis n by the 4 arms, attrition reasons, imputation/model handling and sensitivity analyses." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Are arm-level variance and important-difference criteria verified separately from the original CI?", "needed": "Arm-level variance/SE, model covariance and evidence for prespecified important-difference criteria.", "role": "Required", "role_reason": "Statistical significance and clinical importance are separate conditions.", "application_exception": "Do not inherit historical CX or C54 as a new precision/importance judgment.", "criterion": "Retain the between-arm CI while verifying arm-level SD/SE, estimation variance and justified HbA1c important-difference criteria.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare the range allowed by the CI against verified important-difference criteria without creating a new sufficiency score.", "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 between-arm 95% CI −0.67 to −0.13 %p is retained. Arm-level SD/SE, covariance and minimum-important-difference criteria/support remain unverified in the current summary.", "condition_status": "Partly verified", "status_reason": "The interval exists, but direct material on variance and clinical-importance criteria remains unresolved.", "missingness": "Arm-level variance/covariance and justified important-difference criteria for this population/time are unavailable.", "uncertainty": "Arm-level variance/covariance and justified important-difference criteria for this population/time are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-level variance/SE, model covariance and evidence for prespecified important-difference criteria." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "Are the NCT clue and detailed registration comparison for the prespecified primary endpoint verified?", "needed": "Initial/amended NCT02861261 registrations, protocols, analysis plans and paper tables.", "role": "Required", "role_reason": "Distinguish identifiers and historical comparisons from current direct reading.", "application_exception": "Do not turn an unconfirmed registration field into nonregistration or a citation identifier into successful current registration verification.", "criterion": "Retain the historical prespecified-primary/prior-registration account, citation NCT02861261 and unconfirmed original registration field together; verify the scope of actual registration/plan-version comparisons.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare initial plans with published endpoints, timing and analyses, recording reasons for changes.", "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 text describes HbA1c as a prespecified primary endpoint and registration before recruitment; the citation includes NCT02861261. The original registration field says 'Unconfirmed'. Registration, protocol and plan originals remain unread in this work.", "condition_status": "Partly verified", "status_reason": "The registration identifier and historical account exist; the unconfirmed structured field and current original-registration comparison gap remain retained.", "missingness": "Detailed comparison of registration versions, recruitment start, primary endpoints and analysis plans is currently unavailable.", "uncertainty": "Detailed comparison of registration versions, recruitment start, primary endpoints and analysis plans is currently unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Initial/amended NCT02861261 registrations, protocols, analysis plans and paper tables." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "Is the 2008 pilot's within-arm reduction kept separate from replication of the placebo comparison?", "needed": "Original pilot tables, metformin administration, each arm's baseline/final values and between-arm analyses.", "role": "Required", "role_reason": "Favorable adjacent results do not establish independent confirmation when their analysis direction and comparator differ.", "application_exception": "Do not use within-arm P<.01 as between-arm P or an effect equivalent to metformin.", "criterion": "Separate metformin active-comparator/within-arm results from the current between-arm placebo comparison; retain every original number and unverified item.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare actual active-comparator between-arm results while retaining separate conditions from the placebo question.", "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": "The 2008 pilot randomized 36 people, with 15 berberine and 16 metformin participants analyzed. The retained account reports berberine 9.5±0.5%→7.5±0.4%, within-arm P<.01, and no reported exact between-arm difference/CI. It is not counted as independent confirmation of PREMOTE's placebo comparison.", "condition_status": "Met", "status_reason": "Comparator and analysis-direction differences are stated; within-arm reduction is not transferred as replication under identical conditions.", "missingness": "The active-comparator/within-arm boundary is verified. The pilot's exact between-arm difference, CI and type of ± remain unverified.", "uncertainty": "The active-comparator/within-arm boundary is verified. The pilot's exact between-arm difference, CI and type of ± remain unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original pilot tables, metformin administration, each arm's baseline/final values and between-arm analyses." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Are the pilot's allocation/analysis counts and type of ± verified?", "needed": "The 2008 flow diagram, table footnotes, ± definitions, analysis populations and between-arm result tables.", "role": "Required", "role_reason": "Do not repurpose allocation counts from an adjacent study as analysis n for the current trial.", "application_exception": "Do not convert ± into CI or state that all 36 were analyzed.", "criterion": "Distinguish 36 randomized from 15/16 analyzed; verify SD/SE definitions for ±, endpoint-specific analysis n, missing data and between-arm intervals.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Link allocation and analysis populations and verify table-footnote variance definitions and between-arm contrasts.", "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": "The pilot randomized 36 people; 15 berberine and 16 metformin participants were analyzed. The type of ± in 9.5±0.5%→7.5±0.4%, endpoint-specific n, exact between-arm difference and CI remain unverified in the current summary.", "condition_status": "Partly verified", "status_reason": "Some denominator roles are known, but variance definitions and endpoint-specific analysis/precision remain unresolved.", "missingness": "The type of ±, attrition reasons, missing-data handling, endpoint-specific n and between-arm precision information are unavailable.", "uncertainty": "The type of ±, attrition reasons, missing-data handling, endpoint-specific n and between-arm precision information are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The 2008 flow diagram, table footnotes, ± definitions, analysis populations and between-arm result tables." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Are reports, registration and different arms distinguished from unique trials?", "needed": "Trial-specific registration/paper linkage, recruitment/sites/periods and related-report lists.", "role": "Required", "role_reason": "Do not automatically add papers, registrations, arms or participants.", "application_exception": "A separate 2008 report does not establish independent replication of this placebo comparison.", "criterion": "Link the PREMOTE paper/registration/4 arms and the separate 2008 pilot as trial families, leaving unique direct-replication counts unverified.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare identifiers and recruitment conditions to organize report-trial families and exclude duplicate arms/recitations.", "current_reports": [ "S01", "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": "PREMOTE's citation PMID, PMCID, DOI, NCT and 4 arms are gateways/arms of the same trial report. The 2008 pilot is a different report with an active comparator. No new total direct-replication or unique-participant count is calculated.", "condition_status": "Met", "status_reason": "Retained identities and comparison differences are linked; multiple gateways/arms of the same trial are not counted as independent replications.", "missingness": "The relationship between the two current reports is verified within a limited scope. Unique direct replications and exhaustive overlap checks across the current literature were not newly established.", "uncertainty": "The relationship between the two current reports is verified within a limited scope. Unique direct replications and exhaustive overlap checks across the current literature were not newly established.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial-specific registration/paper linkage, recruitment/sites/periods and related-report lists." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Are funding, product support and the supplier's actual role verified?", "needed": "Paper funding/COI, author affiliations, product-support agreements and role statements.", "role": "Supplementary; required for independence claims", "role_reason": "Public funding and product support can coexist.", "application_exception": "A report of no supplier role certifies neither current independent verification nor absence of bias.", "criterion": "Retain public funding and Northeast Pharmaceutical BBR/placebo provision/no-role reports; verify authors, institutions, COI and support agreements.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare funding, product provision and author identities separately; do not automatically discard results solely because of product support.", "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": "PREMOTE reports public funding and BBR/placebo supply by Northeast Pharmaceutical, with no design/data role reported. Specific support agreements, author employment/patents and complete COI remain unverified in the current summary.", "condition_status": "Partly verified", "status_reason": "Public funding, product provision and declared roles are known; detailed independence information remains unresolved.", "missingness": "Details of product-support agreements, author employment/patents, declared COI and institutional roles are unavailable.", "uncertainty": "Details of product-support agreements, author employment/patents, declared COI and institutional roles are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Paper funding/COI, author affiliations, product-support agreements and role statements." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Are the 2008 pilot's support and product/author interests verified?", "needed": "Original pilot funding/COI, product-provision and author-affiliation material.", "role": "Supplementary", "role_reason": "Do not inherit adjacent material's funding as main-trial independence.", "application_exception": "Government support does not establish absence of interests.", "criterion": "Retain the original NIH/NCCIH, NIDDK and non-US government support account; verify actual pilot product provision, author employment, patents and declared COI. Distinguishing government support from unverified details does not replace verification of product/author independence.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare funding declarations separately from actual product/author relationships.", "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": "The 2008 pilot is retained as supported by NIH/NCCIH, NIDDK and non-US government research funding. Product provision, author employment, patents and declared COI details remain unverified.", "condition_status": "Partly verified", "status_reason": "Funding institutions are known, but product/author independence for this adjacent report is unverified.", "missingness": "Pilot product provision, author affiliations/patents and declared COI information are unavailable.", "uncertainty": "Pilot product provision, author affiliations/patents and declared COI information are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original pilot funding/COI, product-provision and author-affiliation material." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Is independent replication with matching pretreatment, product, placebo and timing verified?", "needed": "Trial identities, registration, products, endpoint/analysis results and overlap tables under identical conditions.", "role": "Required", "role_reason": "Do not expand a single direct trial's results into broad replication.", "application_exception": "With 0 new searches, do not establish the worldwide direct-study count as 1 or 0.", "criterion": "Verify results and differences among unique independent trials matching this comparison; do not count a different active-comparator trial as replication.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Predefine unique trials under identical conditions and compare replication results and condition differences individually.", "current_reports": [ "S01", "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": "Current evidence comprises direct PREMOTE and the adjacent metformin pilot. Other independent direct results for identical gentamicin pretreatment, single-ingredient tablets, double placebo and week 13 HbA1c are unverified in retained material.", "condition_status": "Unverified", "status_reason": "The pilot uses different conditions; material verifying direct independent replication within the current scope is unavailable.", "missingness": "Other unique trials and their result distribution under identical conditions remain unverified. This does not establish absence of all research.", "uncertainty": "Other unique trials and their result distribution under identical conditions remain unverified. This does not establish absence of all research.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Trial identities, registration, products, endpoint/analysis results and overlap tables under identical conditions." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Are optimal dose, persistence after stopping and subgroup confirmation required for this question?", "needed": "Direct dose comparisons, discontinuation/long-term follow-up and prespecified interaction data if a separate extension is asked.", "role": "Supplementary; required only for extension claims", "role_reason": "Existence of a narrow result differs from broad extensions.", "application_exception": "Not applicable means neither current unread original papers nor an extension effect of 0.", "criterion": "Distinguish the selected 1.2 g/day/week 13 average HbA1c comparison from separate dose, persistence and subgroup claims.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "When a separate extension question arises, review prespecified dose/follow-up/interaction comparisons under independent conditions.", "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": "This question concerns 1.2 g/day, common pretreatment and week 13 HbA1c. It makes no new claim of optimal dose, persistence after stopping or genotype/special-subgroup effects.", "condition_status": "Not applicable", "status_reason": "These extensions are outside the selected question; extension confirmation is not imposed as mandatory.", "missingness": "Limits of the narrow comparison remain; separate optimal-dose, long-term persistence and subgroup results are not added as new mandatory gaps.", "uncertainty": "Limits of the narrow comparison remain; separate optimal-dose, long-term persistence and subgroup results are not added as new mandatory gaps.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Direct dose comparisons, discontinuation/long-term follow-up and prespecified interaction data if a separate extension is asked." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "Does an HbA1c difference also answer complication-prevention and cure questions?", "needed": "Clinical-event definitions, follow-up, comparators, denominators and effect material for a separate event question.", "role": "Supplementary; required only for event claims", "role_reason": "Do not promote a favorable surrogate result into clinical-event prevention.", "application_exception": "Do not delete retained HbA1c results because event results are unavailable.", "criterion": "Distinguish the HbA1c surrogate endpoint from separate complication, mortality and cure outcomes.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "If an event question arises, review studies with adequate follow-up and event analyses separately from HbA1c trials.", "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": "This concerns week 13 HbA1c only; it is not converted into evidence supporting diabetes cure, complication prevention or metformin replacement.", "condition_status": "Not applicable", "status_reason": "Clinical events and cure are not outcomes of the selected numerical-change question; event trials are not imposed as mandatory for this question.", "missingness": "Only the HbA1c interpretation boundary is verified. Direct event-prevention/cure information was not verified by this table.", "uncertainty": "Only the HbA1c interpretation boundary is verified. Direct event-prevention/cure information was not verified by this table.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Clinical-event definitions, follow-up, comparators, denominators and effect material for a separate event question." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Are gastrointestinal-harm collection, event/person counts, denominators and discontinuation verified?", "needed": "Arm-level AE definitions, person/event counts, severe events/discontinuation, collection/follow-up and exposure denominators.", "role": "Supplementary; required for numerical harm claims", "role_reason": "Efficacy significance establishes neither guaranteed safety nor harm causality.", "application_exception": "Do not turn the original warning into 0 events or use overall 409/391 as harm-analysis denominators.", "criterion": "Retain the original gastrointestinal warning; verify actual event definitions/collection, arm-level person/event counts, severity, discontinuation, exposure duration and harm denominators. Recording the distinction between warnings and tallies does not replace verification; efficacy denominators are not inherited as harm denominators.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Distinguish efficacy and safety populations when comparing event collection, timing and discontinuation.", "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 text describes gastrointestinal adverse effects as common. Selected-arm event/person counts, severity, discontinuation, collection, harm denominators and temporal ordering remain unverified in the current summary.", "condition_status": "Partly verified", "status_reason": "The observed harm category and warning are known, but tallies needed to assess frequency, severity and causality remain unresolved.", "missingness": "Arm-level harm collection, tallies, discontinuation and actual exposure denominators are unavailable; risk values are not calculated.", "uncertainty": "Arm-level harm collection, tallies, discontinuation and actual exposure denominators are unavailable; risk values are not calculated.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Arm-level AE definitions, person/event counts, severe events/discontinuation, collection/follow-up and exposure denominators." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "Are original co-medication/vulnerable-group warnings and actual safety-information scope verified?", "needed": "Exposure, events, follow-up, interactions and original warning sources by co-use/vulnerable group.", "role": "Supplementary; required for the stated safety claim", "role_reason": "Do not automatically transfer general efficacy-population results to vulnerable-group safety.", "application_exception": "No clinical dosing instructions, new risk values, causality-tool execution or personal-safety certification are provided.", "criterion": "Retain original hypoglycemia co-use, CYP-drug and pregnancy/lactation/infant warnings; verify actual group-specific exposure, events, follow-up, interactions, alternative causes/adjustment and warning sources needed to assess the safety claim. Distinguishing original warnings from unverified direct data verifies neither safety, causality nor personal safety.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare population/drug/exposure-specific safety data separately against support for original warnings.", "current_reports": [ "S01", "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": "Warnings concern hypoglycemia risk with glucose-lowering drugs, checking CYP2D6, 2C9 and 3A4 substrate medicines, and avoiding use in pregnancy, lactation and infants. Direct denominators, follow-up and interaction magnitudes for these populations remain unverified.", "condition_status": "Partly verified", "status_reason": "The original warning's populations and co-use scope are known, but direct safety-evidence details remain unresolved.", "missingness": "Exposure, events, follow-up and alternative-cause/adjustment information by vulnerable group/co-use are unavailable.", "uncertainty": "Exposure, events, follow-up and alternative-cause/adjustment information by vulnerable group/co-use are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Exposure, events, follow-up, interactions and original warning sources by co-use/vulnerable group." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Are the retained summary read in this work and unread external materials distinguished?", "needed": "Actual responses, versions, access/reading records and original locations when external material is reviewed.", "role": "Required", "role_reason": "A link or historical account does not establish current full-text reading.", "application_exception": "There were 0 external requests in this work; unattempted access is not labelled failed access.", "criterion": "Display actual reading of the retained local summary separately from current unattempted, unacquired and unread PubMed/DOI/paper/registration 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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "In authorized later review, record actual reading level and location by material and compare against the current summary.", "current_reports": [ "S01", "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": "The current input's Korean/English text, 2 evidence entries, 2 citations, structure and history were read. External PubMed, DOI, original full papers and NCT registration were neither accessed nor read in this work.", "condition_status": "Met", "status_reason": "Actual reading and unattempted external access are distinguished, and summary-reading links point to exact local locations.", "missingness": "The current summary-reading scope is verified. External abstracts, full texts, registration and URL responses/document types remain unverified.", "uncertainty": "The current summary-reading scope is verified. External abstracts, full texts, registration and URL responses/document types remain unverified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Actual responses, versions, access/reading records and original locations when external material is reviewed." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Are retained reference, correction and access dates distinguished?", "needed": "Original material-specific access/version records and complete preserved correction events.", "role": "Required", "role_reason": "Review dates and external access dates are different facts.", "application_exception": "Do not inherit a report-level paper/registration comparison account as historical full-text access through every DOI gateway.", "criterion": "Retain original verdict-review date 2026-09-08 and correction 2026-09-14 historically; distinguish current actual review from null individual access 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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Separate historical access and current-reading events when comparing dates, versions and material identities.", "current_reports": [ "S01", "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": "The retained reference date is 2026-09-08; the generic English-wording correction is 2026-09-14. Actual material-specific access dates/levels are absent and remain null; current review time is recorded separately.", "condition_status": "Met", "status_reason": "Event attribution and absent date fields are retained without inferring report-specific access dates from a global date.", "missingness": "Historical access dates/levels by material remain unverified. Only the distinction between current local-reading and original reference dates is verified.", "uncertainty": "Historical access dates/levels by material remain unverified. Only the distinction between current local-reading and original reference dates is verified.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Original material-specific access/version records and complete preserved correction events." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Is the scope of checking current literature, corrections and unpublished results available?", "needed": "Contemporaneous queries, search dates, eligibility/exclusion and unpublished/correction/retraction logs.", "role": "Required", "role_reason": "Reading the complete retained summary differs from searching the complete current literature.", "application_exception": "Do not turn absence of new searching into 0 studies, no retractions or complete literature verification.", "criterion": "Verify contemporaneous queries, eligibility/exclusion, unpublished/correction records and current complete-literature coverage for the same comparison from actual material. State the absence of a new search 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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "In a separately authorized evidence update, reproduce the original search scope and compare missing/changed material by identity.", "current_reports": [ "S01", "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": "The retained research account describes comparison of PREMOTE, NCT02861261 and the 2008 pilot, with stated exclusions. No current complete-literature, unpublished/correction/retraction check or new clinical search was performed.", "condition_status": "Unverified", "status_reason": "Converting the current summary alone cannot establish completeness of current evidence.", "missingness": "Search logs and exhaustive unpublished/correction/retraction material beyond the historical comparison scope are unavailable.", "uncertainty": "Search logs and exhaustive unpublished/correction/retraction material beyond the historical comparison scope are unavailable.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Contemporaneous queries, search dates, eligibility/exclusion and unpublished/correction/retraction logs." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Is the scope of specific English text and generic placeholder wording retained?", "needed": "Complete before/after versions of the English correction and corresponding actual Korean fields.", "role": "Required", "role_reason": "A formal verification sentence does not establish actual clinical verification.", "application_exception": "Do not promote English placeholders or the original independent-cross-check wording into current full-text certification.", "criterion": "Distinguish actual Korean/English text from generic sample-size/result wording; do not create new numbers or acquisition facts from generic wording.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "In a separate correction, preserve the original location and reason for changes when comparing the scope of accurate translation.", "current_reports": [ "S01", "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": "The English text specifically describes the original comparison. Generic verification wording remains in evidence sample-size, result and funding fields; it is not used as evidence of additional denominators, CI or verified funding.", "condition_status": "Met", "status_reason": "The actual retained English text and generic wording remain unchanged, with the generic wording's factual scope limited.", "missingness": "Generic wording provides no additional analysis n, variance or COI information. No new correction to the original English text was performed in this work.", "uncertainty": "Generic wording provides no additional analysis n, variance or COI information. No new correction to the original English text was performed in this work.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "Complete before/after versions of the English correction and corresponding actual Korean fields." }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Are original C 54, axes and Warning distinguished from new table statuses?", "needed": "The complete original summary, verdict/correction events, input identity and in-house application history.", "role": "Required", "role_reason": "Table conversion creates neither a new original verdict nor an efficacy grade.", "application_exception": "Do not reuse the original historical Codex independent cross-check as current other-author QA or clinical certification.", "criterion": "Retain original grade/score/axes/safety, null/empty values and numerical values unchanged; distinguish new clinical verdicts from condition statuses.", "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 application conditions for the HbA1c comparison of berberine hydrochloride under common pretreatment, developed with knowledge of retained content. They do not establish blinding, clinical preregistration, official-method certification or independent clinical validation.", "proposed_research": "Compare complete original/case identity and change events, separating content reassessment from technical preservation.", "current_reports": [ "S01", "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": "Original C, 54 points, B/S/R1/I1/E+/B0/CX, Warning, all original values and the empty subclaim list are retained. No new score, grade, effect, CI or NNT is created.", "condition_status": "Met", "status_reason": "The complete original summary is retained with its original types; condition statuses are separated from the historical verdict.", "missingness": "The original verdict's preservation scope is verified. Table preparation or technical checks are not new clinical certification or a grade update.", "uncertainty": "The original verdict's preservation scope is verified. Table preparation or technical checks are not new clinical certification or a grade update.", "review_date": "2026-10-05", "reading_status": "Full text not read · Stored summary read", "additional_material": "The complete original summary, verdict/correction events, input identity and in-house application history." } ], "reports": [ { "report_id": "S01", "title": "Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)", "url": "https://pubmed.ncbi.nlm.nih.gov/33024120/", "report_type": "Retained summary of a prospectively registered 4-arm 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 PubMed, DOI, full text and registration remain unattempted, unacquired and unread.", "study_family": "The PREMOTE paper, NCT02861261 and 4 arms belong to one trial. The selected contrast is berberine-only active ingredient versus double placebo under common gentamicin pretreatment.", "independent_replication": "The paper, registration and other arms are not counted as separate replications. Other direct independent replications under identical conditions remain unverified.", "observed_result": "LS mean changes −0.99 %p versus −0.59 %p; difference −0.40 %p, 95% CI −0.67 to −0.13, adjusted P=.0006. Distinguish overall 409 randomized/391 with primary data from selected-arm allocation of 98/103. Selected-arm analysis n, actual model and adjustment definitions remain unverified.", "result_level": "These are retained original reported values. External full text/registration were not reread and no new calculation was performed.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "External PubMed bibliographic/abstract gateway", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "This is the retained PubMed link. Its current response, abstract provision/content and public access were not checked. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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/publisher gateway", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "This is the retained DOI link. Its current response, publisher provision, original-text version and public access were not checked. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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 paper full text; direct location/version unverified", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The original paper’s direct physical location, version, provision, public availability, acquisition and actual reading remain unverified. No direct URL is invented. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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 clinical-trial registration NCT02861261", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "This is the retained citation’s NCT02861261 link. The original evidence-table registration field remains unconfirmed; current responses, registration versions and endpoint/analysis plans were not newly verified. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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": "Retained verdict summary", "public_status": "Retained verdict summary read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "Relevant retained summary, evidence and citation content was read. This is not the original clinical paper’s bytes or full text. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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/33024120/" } ] }, { "report_id": "S02", "title": "Efficacy of berberine in patients with type 2 diabetes mellitus", "url": "https://pubmed.ncbi.nlm.nih.gov/18442638/", "report_type": "Retained summary of a randomized metformin active-comparator pilot", "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 PubMed, DOI and full text remain unattempted, unacquired and unread.", "study_family": "The 2008 pilot is an active-comparator report distinct from PREMOTE. It is not counted as replication of the current double-placebo comparison.", "independent_replication": "Within-arm reduction and a different active comparator are not counted as independent confirmation or equivalence for the current placebo comparison.", "observed_result": "36 randomized; 15 berberine and 16 metformin participants analyzed. Berberine 9.5±0.5%→7.5±0.4%, within-arm P<.01; exact between-arm difference, CI and type of ± remain unverified.", "result_level": "This is active-comparator/within-arm context. It is not converted into a direct result for the current placebo comparison.", "source_evidence_date": "2026-09-08", "materials": [ { "material_type": "External PubMed bibliographic/abstract gateway", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "This is the retained PubMed link. Its current response, abstract provision/content and public access were not checked. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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/publisher gateway", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "This is the retained DOI link. Its current response, publisher provision, original-text version and public access were not checked. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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 paper full text; direct location/version unverified", "public_status": "External access not attempted; not acquired; unread", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "The original paper’s direct physical location, version, provision, public availability, acquisition and actual reading remain unverified. No direct URL is invented. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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": "Retained verdict summary", "public_status": "Retained verdict summary read", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Stored existing review summary read", "as_of": "2026-10-05", "qualification": "Relevant retained summary, evidence and citation content was read. This is not the original clinical paper’s bytes or full text. A report linked to retained summaries and citations. External gateways, full texts, registration, protocols and analysis plans remain unread, with access not attempted in this conversion. 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/18442638/" } ] } ], "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, and distinguish variations in interventions.", "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": "Distinguish studies from reports and link them; do not omit a study 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": "Define the outcome and effect of interest, then examine randomization, deviations, missing data, 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 rates.", "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed." } ], "status_dictionary": { "Met": "Limited verification of the retained identity, observation or scope required by this row. This is separate from clinical sufficiency or full-text certification.", "Partly verified": "Some facts needed by the question are known, while the stated analysis, population, formulation or denominator remains unverified.", "Unverified": "Direct information for this question is unverified in the retained scope. This does not mean an effect of 0, no studies, no harm or an unreviewed table.", "Not applicable": "A specific extension obligation lies outside the narrow question. This does not substitute for unread or unverified material.", "Not applicable (alias)": "A grey-display alias of Not applicable.", "Not read": "The external material was not directly read in the current work. This is separate from reading the retained local summary.", "Conflicting data": "Actual disagreement between reports under the same conditions. Differences between other questions alone do not establish conflict." }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "PREMOTE’s paper, registration and 4 arms are reports/gateways for the same trial. The 2008 pilot is a different active-comparator report. Unique direct replications under identical pretreatment, single-ingredient, double-placebo and week 13 HbA1c conditions, and total unique 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 31 items. No new clinical search, verification-state change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-27" }