{ "schema_version": "chamgap-public-criteria-1.0", "title": "Aged garlic extract 2,400 mg/day × Reduced progression of low-attenuation coronary plaque in metabolic syndrome", "language": "en", "translation_date": "2026-10-25", "criteria_version": "1.0", "criteria_date": "2026-10-06", "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": "The retained identity, observation or scope required by this item was checked within stated limits. This does not establish clinical sufficiency or full-text certification.", "Partly verified": "Some required facts are known, but the stated conditions involving analyses, populations, formulation or denominators remain unverified.", "Unverified": "Direct information is unverified in the retained record. This does not establish an effect of 0, no studies, absence of harm or an unreviewed table.", "Not applicable": "An extension obligation outside the narrow question does not apply. This state does not substitute for unread or unverified material.", "Not applicable (alias)": "This is the gray-display alias of Not applicable.", "Not read": "External material was not directly read in this conversion. This is distinguished from reading the retained verdict summary.", "Conflicting data": "This covers an actual discrepancy between reports of the same question, denominator and timing. Differences between separate questions are not automatically treated as conflicting data." }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Which AGE product, population, time frame and imaging endpoint does this question concern?", "needed": "The original protocol and result tables linking this population, formulation, route, dose, comparator and time point.", "role": "Required", "role_reason": "Different question identities can mix different effects under the same garlic or plaque label.", "application_exception": "Do not combine total plaque, noncalcified plaque, dense calcium, plaque disappearance, myocardial infarction/death or other garlic formulations with this question.", "criterion": "Limit the question to change in CCTA %LAP after about 12 months of AGE capsules at 2,400 mg/day versus matching placebo plus usual care in adults with metabolic syndrome continuing their usual risk-factor treatment.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: The original protocol and result tables linking this population, formulation, route, dose, comparator and time point. This records needed materials; no new research was executed." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "Are multiple analyses or repeated citations of a report being counted as separate trials?", "needed": "Study-family material linking registration, recruitment identity, the population/time points of each report, related reports and an included-trial table.", "role": "Required", "role_reason": "A paper citation and an evidence table, or group values and a regression coefficient, do not each constitute independent replication.", "application_exception": "Without a study-family linkage and an independent citation for the diabetes report, do not estimate the unique study count or participant total.", "criterion": "Link the first evidence summary and first citation within the same retained report context, and distinguish group percentage changes from adjusted β as different analyses of the same endpoint. Leave the background diabetes trial unidentified.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Study-family material linking registration, recruitment identity, the population/time points of each report, related reports and an included-trial table. This records needed materials; no new research was executed." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "Is the summary actually read distinguished from unread external material?", "needed": "For each material, the actual access date, attempts/success, acquired file, source location, reading scope and safe link.", "role": "Required", "role_reason": "An identifier or the word verified in the original English text is not evidence of full-text reading during this work.", "application_exception": "Do not describe an unattempted access as a failed access, or replace an absent historical access date with the current reading date.", "criterion": "Link the reading of all fields, Korean and English text, evidence and citations in the retained summary to source locations and identity checks, and distinguish existence, access, acquisition and reading for PubMed, DOI, full text and registration separately.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: For each material, the actual access date, attempts/success, acquired file, source location, reading scope and safe link. This records needed materials; no new research was executed." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "How were the analyzed adults with metabolic syndrome selected?", "needed": "Eligibility/exclusion criteria, the metabolic-syndrome definition, baseline tables, age, comorbidities, recruitment setting and a flow diagram.", "role": "Required", "role_reason": "The analyzed sample of 55 alone cannot establish representativeness for all people with metabolic syndrome or all patients with diabetes.", "application_exception": "Do not reinterpret the 55 adults in the population description as the entire enrollment denominator or as participants in the separate diabetes trial.", "criterion": "Retain the population definition of metabolic syndrome with continued usual treatment, and distinguish diagnostic criteria, age, eligibility/exclusions, baseline balance and analysis losses.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Eligibility/exclusion criteria, the metabolic-syndrome definition, baseline tables, age, comorbidities, recruitment setting and a flow diagram. This records needed materials; no new research was executed." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "Are the AGE capsule product and SAC specifications identified?", "needed": "Product name, manufacturing/aging process, standardization specifications such as SAC, and trial-batch analyses.", "role": "Required", "role_reason": "The same AGE dose in mg does not establish identical SAC content or processed formulation.", "application_exception": "Do not interchange raw garlic, powder, oil, stabilized allicin, black garlic, fermented garlic or isolated SAC with AGE, or convert AGE mg into SAC mg.", "criterion": "Separately compare the AGE capsule formulation of aged Allium sativum clove extract with SAC standardization, aging process, content and product identity.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Product name, manufacturing/aging process, standardization specifications such as SAC, and trial-batch analyses. This records needed materials; no new research was executed." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "What are the actual oral exposure and placebo comparison?", "needed": "Dosing records, capsule schedule, placebo composition/appearance, adherence and actual exposure by group.", "role": "Required", "role_reason": "A planned dose or placebo label does not establish actual exposure or the full implementation of blinding.", "application_exception": "Do not invent capsule counts, SAC amounts or adherence rates without source material, or turn this into a trial of replacing usual treatment.", "criterion": "Link nominal oral add-on AGE at 2,400 mg/day with matching placebo plus usual care, and separately compare actual intake, capsule count, placebo content and adherence.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Dosing records, capsule schedule, placebo composition/appearance, adherence and actual exposure by group. This records needed materials; no new research was executed." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Which imaging component and denominator does %LAP measure?", "needed": "The LAP measurement definition, attenuation cutoff, segmentation criteria, percentage calculation specification and result-table notes.", "role": "Required", "role_reason": "The low-attenuation plaque component, total plaque, calcium and volume scales are different endpoints.", "application_exception": "Do not convert the original percentage into a new percentage-point or relative change, or interpret it as plaque disappearance.", "criterion": "Attribute the result to change in CCTA percent low-attenuation plaque volume, and compare the attenuation cutoff, segmentation, percentage numerator/denominator and scale direction.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: The LAP measurement definition, attenuation cutoff, segmentation criteria, percentage calculation specification and result-table notes. This records needed materials; no new research was executed." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "How are treatment duration and the CCTA scan interval distinguished?", "needed": "Treatment duration by group, scan dates/windows and baseline-to-follow-up image matching.", "role": "Required", "role_reason": "Differences between treatment duration and outcome collection time can affect interpretation of progression.", "application_exception": "Do not assume the dispersion type of 354±41, or convert it into exactly 12 months or long-term persistence.", "criterion": "Retain the original notation of about 12 months of treatment and a CCTA interval of 354±41 days, and verify group scan windows, individual time points and the scope of baseline/follow-up image pairs.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Treatment duration by group, scan dates/windows and baseline-to-follow-up image matching. This records needed materials; no new research was executed." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "Which values describe unadjusted group percentage changes?", "needed": "Group result tables, change definitions, dispersion notes, testing specifications and the analysis population.", "role": "Required", "role_reason": "Simple subtraction of group changes does not substitute for the effect the trial estimated.", "application_exception": "Do not calculate a new between-group difference or RR/OR, or turn the ± values into confidence intervals.", "criterion": "Retain −1.5±2.3% versus +0.2±2.0%, P=.0049, at the group-change level, distinct from adjusted β and new between-group calculations.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Group result tables, change definitions, dispersion notes, testing specifications and the analysis population. This records needed materials; no new research was executed." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "Which analysis does the adjusted β estimate come from?", "needed": "The regression model, adjustment variables and selection rationale, SAP, coefficient unit and result table.", "role": "Required", "role_reason": "A regression coefficient and group changes are different analysis levels of the same imaging endpoint.", "application_exception": "Do not turn β into a separate trial, OR/RR or new clinical effect, or invent its unit.", "criterion": "Retain β −1.61, 95% CI −2.79~−0.43, P=.008, and compare adjustment variables, model, target effect and analysis set.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: The regression model, adjustment variables and selection rationale, SAP, coefficient unit and result table. This records needed materials; no new research was executed." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "What are the enrollment, analysis and group denominators?", "needed": "A group flow diagram from recruitment through allocation, treatment, scanning, completion and analysis, and the outcome denominators.", "role": "Required", "role_reason": "Enrollment of 65 does not prove randomized allocation of 65 or the ITT denominator for each outcome.", "application_exception": "Do not newly subtract dropout counts/rates, or relabel 27 and 28 as the originally allocated group sizes.", "criterion": "Keep 65 enrolled, 55 analyzed and AGE 27/placebo 28 as separate levels, and compare total/group randomized allocation, completion and imaging-analysis denominators.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: A group flow diagram from recruitment through allocation, treatment, scanning, completion and analysis, and the outcome denominators. This records needed materials; no new research was executed." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "How do missing data, completer analysis and ITT differ?", "needed": "Missingness/dropout by group, exclusion rules, ITT/completer specifications, missing-data handling and sensitivity analyses.", "role": "Required", "role_reason": "Whether results only from scannable participants equal the effect in all allocated participants requires separate verification.", "application_exception": "Do not treat generic English participant-count wording as proof of ITT, or turn unverified missingness into confirmed selection bias.", "criterion": "Compare losses from enrollment to analysis, reasons, handling, sensitivity and the target effect, and state that full ITT remains unverified.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Missingness/dropout by group, exclusion rules, ITT/completer specifications, missing-data handling and sensitivity analyses. This records needed materials; no new research was executed." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "Are the meanings of dispersion and reported intervals verified?", "needed": "SD/SE/CI notes, interval estimation method, denominators, distributions and the original result table.", "role": "Required", "role_reason": "Sample size or P alone cannot establish precision or the meaning of an interval.", "application_exception": "Do not calculate a new CI from ± or substitute the adjusted CI for an unadjusted between-group interval.", "criterion": "Keep group ± and the β 95% CI as different statistical expressions, and compare dispersion type, denominator and interval estimation method.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: SD/SE/CI notes, interval estimation method, denominators, distributions and the original result table. This records needed materials; no new research was executed." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "Is a threshold for the importance of the imaging signal justified?", "needed": "Material justifying LAP measurement error and an importance/interpretation threshold, together with the relevant intervals.", "role": "Required", "role_reason": "A statistically significant imaging value and a clinically important patient effect are different judgments.", "application_exception": "Do not automatically inherit C46/EX as this row's status or as a new efficacy score.", "criterion": "Distinguish statistical reporting of CCTA %LAP/β from a justified threshold for important or clinical change in this population.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Material justifying LAP measurement error and an importance/interpretation threshold, together with the relevant intervals. This records needed materials; no new research was executed." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "Are results showing no difference outside LAP also retained?", "needed": "Component-specific result tables, time points, denominators, scales, analyses and selection rationales.", "role": "Required", "role_reason": "Keeping only a signal in a component can encourage extending the answer to total plaque.", "application_exception": "These are other imaging measures; do not newly designate them as confirmed prespecified secondary (2nd) endpoints. Do not convert nonsignificance into exactly 0 or equivalence.", "criterion": "Attribute the LAP signal and original null descriptions of TPV, noncalcified plaque and dense calcium separately; do not label different endpoints as conflicting results from the same analysis.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Component-specific result tables, time points, denominators, scales, analyses and selection rationales. This records needed materials; no new research was executed." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "Which dates and verification scope define these evidence gaps?", "needed": "The historical search scope, access history, evidence cutoff, checks for unpublished material/corrections/retractions, and a new update event.", "role": "Required", "role_reason": "The historical review date and conversion date are not dates of a current comprehensive literature check.", "application_exception": "Do not label this unverified status as 0 studies, no recent retractions, or nonreporting throughout the paper.", "criterion": "Distinguish the verdict date 2026-09-08, correction 09-14 and retained-summary review date, and state that no new literature or registration search was performed.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: The historical search scope, access history, evidence cutoff, checks for unpublished material/corrections/retractions, and a new update event. This records needed materials; no new research was executed." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "What is known about product-company support and research independence?", "needed": "Funding, product provision, author employment/patents/interests, design/analysis roles and research-lineage declarations.", "role": "Required (independence interpretation boundary)", "role_reason": "Funding, recruitment family and product identity are separate elements of independence.", "application_exception": "Do not automatically exclude a report solely because of company funding, or treat generic English funding wording as verification of detailed conflicts of interest.", "criterion": "Distinguish Wakunaga/industry support from product provision, authors/institutions and analytical involvement; do not promote unverified information into independent replication.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Funding, product provision, author employment/patents/interests, design/analysis roles and research-lineage declarations. This records needed materials; no new research was executed." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "Does the randomized/blinded label match the actual allocation process?", "needed": "Allocation methods, concealment, baseline tables, implementation of blinding and the methods section.", "role": "Required", "role_reason": "The RCT/double-blind label is not certification that allocation problems or confounding were resolved.", "application_exception": "Do not replace unverified design information with crossover/cluster NA, or treat double-blind as confirmation of blinded CCTA assessors.", "criterion": "Retain the prospective double-blind randomized placebo-controlled label, and compare sequence generation/concealment, baseline balance, implementation and analysis unit.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Allocation methods, concealment, baseline tables, implementation of blinding and the methods section. This records needed materials; no new research was executed." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "Could usual risk-factor treatment and adherence differences be mixed into the result?", "needed": "Group background drugs/treatment, lifestyle factors, changes, adherence, rescue treatment and handling of these factors.", "role": "Required", "role_reason": "Attributing changes in other treatment to AGE would change the add-on treatment question.", "application_exception": "Do not require every change to be identical, or reinterpret this as a trial replacing usual treatment.", "criterion": "Retain continued usual treatment and placebo plus usual care, and compare the contributions of group drugs, diet, changes, adherence and rescue treatment.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Group background drugs/treatment, lifestyle factors, changes, adherence, rescue treatment and handling of these factors. This records needed materials; no new research was executed." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "Are CCTA reading, reproducibility and assessor blinding verified?", "needed": "Imaging conditions, image quality, reading/segmentation procedures, blinding, reproducibility and error handling.", "role": "Required", "role_reason": "Differences in measurement conditions must be distinguished from actual differences in plaque.", "application_exception": "Do not certify assessor blinding from the double-blind label or assume an objective image is free of bias.", "criterion": "Separately compare scanning/segmentation, readers, reproducibility, group measurement conditions and assessor blinding.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Imaging conditions, image quality, reading/segmentation procedures, blinding, reproducibility and error handling. This records needed materials; no new research was executed." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Were the prespecified LAP endpoint hierarchy and SAP compared?", "needed": "Dated registration text, protocol, SAP, endpoint/analysis change history and actual result tables.", "role": "Required", "role_reason": "The original plan is needed to assess possible selection of favorable components or analyses.", "application_exception": "The NCT string does not establish successful reading of registration/SAP. Do not turn unverified information into confirmed nonregistration, selective reporting or a positive secondary endpoint after a failed primary endpoint.", "criterion": "Retain both the named endpoint in the intervention/population description and the evidence summary's unverified prespecified LAP-only primary (1st) hierarchy, and compare registration/protocol/SAP with actual results.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Dated registration text, protocol, SAP, endpoint/analysis change history and actual result tables. This records needed materials; no new research was executed." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Is another report an independent replication of the same product and population question?", "needed": "Recruitment, product specifications, population, endpoint/time point, funding/lineage and a trial-family table.", "role": "Required", "role_reason": "Signals in another population and reports sharing a product company cannot be combined as independent confirmation.", "application_exception": "Do not create S02 from the diabetes background or transfer effects of AGE+B vitamins+folic acid+L-arginine to AGE alone. Do not turn an unverified family into NA.", "criterion": "Distinguish metabolic-syndrome AGE-LAP from the diabetes background and excluded combinations, and compare whether product, population, institution/funding and recruitment family are the same, different or unknown.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Recruitment, product specifications, population, endpoint/time point, funding/lineage and a trial-family table. This records needed materials; no new research was executed." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Does this question also require an optimal dose?", "needed": "For a dose-optimization claim: direct comparisons of doses with matching specifications, exposure/adherence and a separate estimate.", "role": "Supplementary; required to extend to optimal dosing", "role_reason": "A dose is not certification of an optimal dose, but dose research is not required for the narrow question.", "application_exception": "NA applies only to the obligation for a dose-optimization extension. Unverified direct dose evidence and specification gaps remain.", "criterion": "Separate the selected imaging question at 2,400 mg/day from additional dose-optimization/dose-response claims.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: For a dose-optimization claim: direct comparisons of doses with matching specifications, exposure/adherence and a separate estimate. This records needed materials; no new research was executed." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "Is persistence of the imaging effect after treatment stops being claimed?", "needed": "For a persistence claim: post-treatment scan times, exposure, treatment changes, group follow-up denominators and results.", "role": "Supplementary; required for persistence after stopping", "role_reason": "Observation during treatment and persistence after stopping treatment have different time specifications.", "application_exception": "NA applies only to the post-treatment extension obligation; it does not exclude the current duration or scan conditions.", "criterion": "Distinguish observation over about 12 months from separate questions of post-treatment persistence or long-term progression.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: For a persistence claim: post-treatment scan times, exposure, treatment changes, group follow-up denominators and results. This records needed materials; no new research was executed." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "Is a larger effect in a particular subgroup being claimed?", "needed": "For a subgroup claim: prespecified hypotheses, denominators, direct interaction estimates and plans.", "role": "Supplementary; required for subgroup extensions", "role_reason": "A favorable subgroup value or a trial in another population is not the magnitude of the overall result.", "application_exception": "NA applies only to the subgroup-extension obligation; population representativeness and the diabetes family remain unverified.", "criterion": "Separate the selected metabolic-syndrome result from prespecified subgroups/interactions and the separate diabetes population.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: For a subgroup claim: prespecified hypotheses, denominators, direct interaction estimates and plans. This records needed materials; no new research was executed." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "Is the LAP signal being extended to plaque disappearance or prevention of clinical events?", "needed": "For an event extension: event definitions, denominators/follow-up, direct between-group results and plans.", "role": "Required (clinical interpretation boundary)", "role_reason": "A signal in an imaging surrogate component does not prove clinical prevention or plaque disappearance.", "application_exception": "Retain the imaging observation without requiring an event trial as a condition for the existence of that result.", "criterion": "Distinguish the imaging component from separate questions of total plaque disappearance, myocardial infarction and death; retain the boundary around unmeasured events.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: For an event extension: event definitions, denominators/follow-up, direct between-group results and plans. This records needed materials; no new research was executed." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Are harm-event definitions and collection verified?", "needed": "Adverse-event definitions, collection methods, group reports, discontinuation/severity and source data.", "role": "Supplementary; required for harm and safety questions", "role_reason": "An efficacy summary or caution does not establish complete accounting of actual harms.", "application_exception": "Do not turn caution into actual bleeding counts or causality, or delete the imaging result because harm remains unverified.", "criterion": "Distinguish actual bleeding/adverse events, definitions, collection, severity and discontinuation for the same AGE/population from general caution.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Adverse-event definitions, collection methods, group reports, discontinuation/severity and source data. This records needed materials; no new research was executed." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Is the temporal sequence of exposure and harm events known?", "needed": "Times of exposure initiation, events, discontinuation, recovery and re-exposure, with follow-up records.", "role": "Supplementary; required for harm timing questions", "role_reason": "An imaging interval does not substitute for the timing of bleeding or interactions.", "application_exception": "Do not infer events, improvement or re-exposure without source text, or fill harm timelines solely from treatment duration.", "criterion": "Distinguish AGE initiation/discontinuation, events/recovery, re-exposure and harm-observation duration from the imaging interval.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Times of exposure initiation, events, discontinuation, recovery and re-exposure, with follow-up records. This records needed materials; no new research was executed." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "Are event and exposure denominators available to interpret harm comparisons?", "needed": "Group harm-exposure/event denominators, people/event counts, duration, placebo comparisons and result tables.", "role": "Supplementary; required for incidence or comparative-risk claims", "role_reason": "Imaging-analysis denominators are not denominators for harm frequency or increased risk.", "application_exception": "Do not substitute 55, 27 or 28 as safety denominators, or newly calculate incidence, background rates or RR.", "criterion": "Link exposed participants, people/event counts, duration and placebo events, distinct from imaging-analysis counts of 55/27/28.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Group harm-exposure/event denominators, people/event counts, duration, placebo comparisons and result tables. This records needed materials; no new research was executed." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "Were concomitant drugs and alternative explanations verified?", "needed": "Concomitant drugs/doses, surgery, baseline risks, simultaneous exposure, alternatives and relevant harm material.", "role": "Supplementary; required for causal or comparative harm", "role_reason": "A warning list does not verify actual concomitant use in the trial or the cause of an event.", "application_exception": "Do not interpret unverified alternatives as absence of other causes, or extend the original caution into new individual dosing instructions.", "criterion": "Distinguish usual treatment from anticoagulant/antiplatelet and surgery warnings, and compare actual simultaneous exposure, baseline risks and alternatives.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Concomitant drugs/doses, surgery, baseline risks, simultaneous exposure, alternatives and relevant harm material. This records needed materials; no new research was executed." }, { "item_id": "N31", "question_type": "Evidence condition", "question": "Is the scope missed by harm collection and follow-up known?", "needed": "Group safety follow-up, reasons for missingness, detection differences and the disclosure scope for all events.", "role": "Supplementary; required for the scope of harm surveillance", "role_reason": "There is no guarantee that imaging loss and harm-surveillance loss are identical.", "application_exception": "Do not turn unverified collection into event absence or a confirmed magnitude of bias.", "criterion": "Distinguish harm detection, follow-up loss, collection and disclosure from imaging-analysis losses.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Group safety follow-up, reasons for missingness, detection differences and the disclosure scope for all events. This records needed materials; no new research was executed." }, { "item_id": "N32", "question_type": "Evidence condition", "question": "Are repeated harm warnings being counted as independent events?", "needed": "Unique harm report/case identifiers, exposure/event matching, repeated citations and family material.", "role": "Supplementary; required for repeated harm signals", "role_reason": "Repetition of caution across Korean, English and synthesized summaries does not increase independent event counts.", "application_exception": "Do not query new regulatory/case material during this work or turn diabetes efficacy background into repeated harm evidence.", "criterion": "Distinguish general caution and recitation of the same material from new harm events/studies, and link product, population and event families.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Unique harm report/case identifiers, exposure/event matching, repeated citations and family material. This records needed materials; no new research was executed." }, { "item_id": "N33", "question_type": "Evidence condition", "question": "What about long-term or rare harms and vulnerable groups beyond the imaging observation?", "needed": "Suitable designs and denominators/follow-up for long-term/rare events and interactions under the same exposure and by population.", "role": "Supplementary; required for long-term or vulnerable-group harms", "role_reason": "An imaging study in a limited population does not guarantee overall safety.", "application_exception": "Do not require every long-term harm study for the narrow imaging question, or convert unverified information into harmlessness.", "criterion": "Separate the imaging question over about 12 months from harms involving long-term bleeding, interactions and surgical/anticoagulant conditions.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Suitable designs and denominators/follow-up for long-term/rare events and interactions under the same exposure and by population. This records needed materials; no new research was executed." }, { "item_id": "N34", "question_type": "Evidence condition", "question": "How far can harms and safety be described from this material?", "needed": "Harm source data connecting events, exposure/denominators, timing, comparison and alternatives, with the interpretation scope.", "role": "Required (safety interpretation boundary)", "role_reason": "Historical caution and the current verification level of harm source data are separate matters.", "application_exception": "Do not create individual dosing instructions, a new safety grade, a guarantee of harmlessness or a confirmed causal link to bleeding.", "criterion": "Distinguish caution from actual signals, comparative risk and causality, and limit the current scope separately from imaging efficacy and the historical safety label.", "basis": "Existing method principles distinguish population, formulation, dose, timing, endpoint, comparison, denominators, overlap, funding and harms in the retained report. Detailed conditions are Chamgap’s own application.", "condition_origin": "These are Chamgap in-house application conditions developed with knowledge of the retained AGE and low-attenuation coronary-plaque record. They do not establish blinding, trial preregistration, official-tool certification or new independent clinical validation.", "proposed_research": "Material needed: Harm source data connecting events, exposure/denominators, timing, comparison and alternatives, with the interpretation scope. This records needed materials; no new research was executed." } ] }