{ "schema_version": "chamgap-public-criteria-1.0", "title": "Oral single-ingredient berberine hydrochloride × Reduction of HbA1c in adults with type 2 diabetes", "language": "en", "translation_date": "2026-10-27", "criteria_version": "1.2", "criteria_date": "2026-10-05", "condition_origin": "Chamgap's own application conditions", "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility conditions and reasons for changes, 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." }, "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." } ] }