{
  "schema_version": "chamgap-public-criteria-1.0",
  "title": "Lorcaserin × Cardiovascular event superiority (MACE+) — Evidence checklist",
  "language": "en",
  "translation_date": "2026-10-11",
  "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": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work."
    },
    {
      "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": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work."
    },
    {
      "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": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work."
    },
    {
      "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": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work."
    },
    {
      "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": "Methodological principles stated in existing pilot materials and condition templates were referenced. The methodological text was not reviewed again in this work."
    }
  ],
  "status_dictionary": {
    "Met": "The original content has been reviewed as meeting the conditions. This status is not used in this preparation.",
    "Partly verified": "Some information in the stored summary was linked during preparation; clinical verification or review is not complete.",
    "Unverified": "Required direct values, definitions or materials have not been established within the current storage and reading scope. This does not mean zero effect, no papers or failed access.",
    "Review incomplete": "Review of existing content or actual review incomplete.",
    "Not reported": "Used only when original materials were actually read and the outcome was judged unreported. Not used for external materials unread in this work.",
    "Inaccessible": "Used only when an actual access attempt has a recorded failure. Not used for access that was not attempted in this work.",
    "Insufficient evidence for the conditions": "Indicates insufficient direct materials for the relevant scope or conditions; it is not a new grade.",
    "Not applicable": "Used when the reason it does not apply to the original question is stated.",
    "Conflicting data": "Retains the scope of conflicting statements in original materials; it is not an arbitrary reassessment."
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Evidence condition",
      "question": "Is the selected question cardiovascular event superiority?",
      "needed": "Links between the selected subclaim, parent and MACE+ results",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Is the selected question cardiovascular event superiority?",
      "application_exception": "Do not create new questions, hypothetical main questions or splits.",
      "criterion": "Preserve exact existing wording and question/verdict records separately.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are our own design / M03 §3.2.4; our own extension boundary",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If the question actually changes, record the original question and excluded scope separately."
    },
    {
      "item_id": "N02",
      "question_type": "Evidence condition",
      "question": "Are subclaim grade D and its note separated from parent grade C and 50 points?",
      "needed": "Original locations of actual and absent subclaim fields and the parent verdict",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Are subclaim grade D and its note separated from parent grade C and 50 points?",
      "application_exception": "Do not fill subclaim-specific values with parent C50/E+/S/I0.",
      "criterion": "Retain the distinct verdict scope of selected subclaim values and the parent.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are our own design / M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If subclaim fields are actually added, separate the original version and change in a new event."
    },
    {
      "item_id": "N03",
      "question_type": "Evidence condition",
      "question": "Are parent axes, cross-checking and the grade decision current verification?",
      "needed": "Parent Korean and English text, axes, synthesis and verdict/correction history",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Are parent axes, cross-checking and the grade decision current verification?",
      "application_exception": "Do not repurpose parent endpoint S or the false large hard-endpoint RCT flag as new classification or review of the selected cardiovascular endpoint.",
      "criterion": "Preserve original verdict history while leaving current review of the existing content incomplete.",
      "basis": "M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design / M08 §8.1–8.2.3; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "Record subsequent evidence updates as separate events within the user’s requested scope."
    },
    {
      "item_id": "N04",
      "question_type": "Evidence condition",
      "question": "At what material level did actual reading occur?",
      "needed": "Acquisition and reading scope for the stored summary and each external material",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: At what material level did actual reading occur?",
      "application_exception": "Do not convert a URL’s presence to full-text acquisition, link verification or access failure.",
      "criterion": "Mark local material as summary read and external material as unread.",
      "basis": "M04 §4.5–4.6 material-collection and selection principles; separation of access and reading and hyperlink rules are our own design / M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If material or reading history is supplied, record the actual reading level of the corresponding slot."
    },
    {
      "item_id": "N05",
      "question_type": "Evidence condition",
      "question": "How are trials, regulatory reanalysis, reports and weight trials connected?",
      "needed": "Relationships among citations, registrations, reports, trials and populations",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: How are trials, regulatory reanalysis, reports and weight trials connected?",
      "application_exception": "Do not add people, cancer events or regulatory documents from the same CAMELLIA trial as new trials or participants.",
      "criterion": "Distinguish report-entry counts from unestablished unique-trial and population counts.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort and outcome linking is our own application / M04 §4.6.1–4.6.2, M15 §15.3.1; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original lists are supplied, record links between the same family and separate reports."
    },
    {
      "item_id": "N06",
      "question_type": "Evidence condition",
      "question": "Who were the actual CAMELLIA participants?",
      "needed": "Participant age, diseases/risks, eligibility/exclusion and baseline characteristics",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Who were the actual CAMELLIA participants?",
      "application_exception": "Do not certify event effects for all adults or all patients with obesity from a citation title alone.",
      "criterion": "Retain the original participant wording and gaps in detailed selection conditions.",
      "basis": "M03 §3.2.1; detailed population conditions are our own design / M03 §3.2.1–3.2.4; dose, persistence and effect-modification details are our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original participant tables are supplied, distinguish the selected population and generalization scope."
    },
    {
      "item_id": "N07",
      "question_type": "Evidence condition",
      "question": "What were the actual lorcaserin formulation, amount and duration of use?",
      "needed": "Trial formulation, actual intervention amount, frequency, administration/discontinuation and exposure records",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What were the actual lorcaserin formulation, amount and duration of use?",
      "application_exception": "Do not create medication instructions or doses absent from the source.",
      "criterion": "Separate the original intervention name from gaps in actual exposure details.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and assessment adaptations are our own design / M03 §3.2.3, M08 §8.2.2–8.2.3; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original intervention records are supplied, distinguish nominal and actual exposure and duration."
    },
    {
      "item_id": "N08",
      "question_type": "Evidence condition",
      "question": "What were the placebo and accompanying lifestyle care or medications?",
      "needed": "Placebo characteristics, shared care, accompanying medications and baseline changes",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What were the placebo and accompanying lifestyle care or medications?",
      "application_exception": "Do not convert placebo control to a no-care or no-treatment comparison.",
      "criterion": "Separate the original comparator type from unverified specific comparison conditions.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and assessment adaptations are our own design / M03 §3.2.3, M08 §8.2.2–8.2.3; our own application / M19 §19.2.2–19.2.4 design considerations; detailed confounding records are our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original comparator and accompanying-intervention material is supplied, record actual between-group differences and shared exposure."
    },
    {
      "item_id": "N09",
      "question_type": "Evidence condition",
      "question": "What were the original randomization size and follow-up duration?",
      "needed": "Arm-specific allocation, observation, completion and analysis flow and individual follow-up windows",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What were the original randomization size and follow-up duration?",
      "application_exception": "Do not make median 3.3-year follow-up the same follow-up time for every participant.",
      "criterion": "Record allocation denominators and median follow-up separately from actual endpoint-specific denominators.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap design / M08 §8.1–8.2.3; Chamgap adaptation / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original flow/follow-up tables are supplied, record the roles of each denominator and duration."
    },
    {
      "item_id": "N10",
      "question_type": "Evidence condition",
      "question": "What were the components and event definitions of the MACE+ efficacy endpoint?",
      "needed": "MACE+ components, event adjudication, repeated/first events and endpoint definitions",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What were the components and event definitions of the MACE+ efficacy endpoint?",
      "application_exception": "Do not fill in guessed conventional MACE definitions or components from other material.",
      "criterion": "Preserve the original MACE+ name and leave specific components unverified.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations by question are our own design / M08 Table 8.2.a, M03 §3.2.4; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original plans/result tables are supplied, separate the composite endpoint and each component event."
    },
    {
      "item_id": "N11",
      "question_type": "Evidence condition",
      "question": "What were the original MACE+ event counts, percentages and denominators?",
      "needed": "People with events/event counts, at-risk population and endpoint analysis denominators",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What were the original MACE+ event counts, percentages and denominators?",
      "application_exception": "Do not recalculate original percentages or add the two arms or events together.",
      "criterion": "Retain original people/percentages and allocation denominators unchanged.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap design / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original event/flow tables are supplied, record whether each value concerns people, repeated events or an analysis denominator."
    },
    {
      "item_id": "N12",
      "question_type": "Evidence condition",
      "question": "What were the MACE+ HR, interval and P value?",
      "needed": "Estimation model, interval confidence level, adjustments and effect of interest",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What were the MACE+ HR, interval and P value?",
      "application_exception": "Do not automatically copy the explicit MACE 95% level to the MACE+ interval or calculate new HRs/CIs.",
      "criterion": "Preserve original MACE+ HR, interval and P value at each originally stated level.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design / M15 §15.3.1–15.3.3; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original analysis methods/result tables are supplied, record the definitions of the original HR and interval."
    },
    {
      "item_id": "N13",
      "question_type": "Evidence condition",
      "question": "Does null superiority mean zero effect or equivalence?",
      "needed": "Prespecified superiority hypothesis, analysis plan and original uncertainty",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Does null superiority mean zero effect or equivalence?",
      "application_exception": "Do not convert nonsignificance to zero event difference, equivalence or a personal safety guarantee.",
      "criterion": "Preserve the original null-result description together with the uncertainty interval.",
      "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is Chamgap design / M15 §15.3.1–15.3.3; Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original plans are supplied, distinguish the superiority hypothesis from actual estimates and uncertainty."
    },
    {
      "item_id": "N14",
      "question_type": "Evidence condition",
      "question": "Are the MACE cardiovascular safety results preserved separately?",
      "needed": "MACE definitions, denominators, model and original safety estimates",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Are the MACE cardiovascular safety results preserved separately?",
      "application_exception": "Do not repurpose MACE numbers/CIs as MACE+ efficacy results.",
      "criterion": "Keep original MACE safety values separate from MACE+ efficacy values.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations by question are our own design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are our own design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original safety methods/result tables are supplied, link MACE and MACE+ separately."
    },
    {
      "item_id": "N15",
      "question_type": "Evidence condition",
      "question": "To which endpoint does the HR 1.40 noninferiority margin apply?",
      "needed": "Planned basis for the noninferiority margin, applicable endpoint and analysis population",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: To which endpoint does the HR 1.40 noninferiority margin apply?",
      "application_exception": "Do not use HR 1.40 as a threshold for MACE+ superiority, cancer safety or overall harmlessness.",
      "criterion": "Link the original margin, applicable MACE endpoint and unread external plans.",
      "basis": "M15 §15.3.1–15.3.3; Chamgap adaptation / M08 Table 8.2.a, M04 §4.6.3; Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original plans are supplied, distinguish the margin’s definition at the time and the reported results."
    },
    {
      "item_id": "N16",
      "question_type": "Evidence condition",
      "question": "Are the safety/efficacy endpoint hierarchy and testing order known?",
      "needed": "Endpoint hierarchy, testing order, multiplicity and change records",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Are the safety/efficacy endpoint hierarchy and testing order known?",
      "application_exception": "Do not promote the two primary-endpoint labels to direct certification of all testing procedures.",
      "criterion": "Distinguish original endpoint roles and unverified hierarchy details.",
      "basis": "M08 Table 8.2.a, M04 §4.6.3; Chamgap adaptation / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If the original SAP/registration is supplied, record the prespecified relationship between safety noninferiority and efficacy superiority."
    },
    {
      "item_id": "N17",
      "question_type": "Evidence condition",
      "question": "Are composite and individual cardiovascular events distinguished?",
      "needed": "Definitions, aggregation, HRs/CIs and prespecified hierarchy of individual component events",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Are composite and individual cardiovascular events distinguished?",
      "application_exception": "Do not copy a composite HR as every individual-event HR or mortality benefit.",
      "criterion": "Retain the boundary between composite endpoints and unverified individual clinical outcomes.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design / M03 §3.2.4; our own extension boundary",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If individual-event tables are supplied, separate direct results for the overall composite and each component."
    },
    {
      "item_id": "N18",
      "question_type": "Evidence condition",
      "question": "What was the actual cardiovascular analysis observation window?",
      "needed": "Endpoint-specific start/end times, follow-up after discontinuation and censoring",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What was the actual cardiovascular analysis observation window?",
      "application_exception": "Do not replace all event windows with the one-year weight time point or median 3.3 years.",
      "criterion": "Separate original duration descriptions from endpoint-specific timing gaps.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations by question are our own design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original follow-up/analysis records are supplied, distinguish median follow-up and actual event windows."
    },
    {
      "item_id": "N19",
      "question_type": "Evidence condition",
      "question": "What were the HR effect of interest, censoring and competing-risk treatment?",
      "needed": "Effect of interest, statistical model, censoring/competing events and sensitivity analyses",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What were the HR effect of interest, censoring and competing-risk treatment?",
      "application_exception": "Do not interpret an HR as a simple risk ratio or individual prevention probability, or convert it to new values.",
      "criterion": "Separate original HRs from unverified analysis assumptions.",
      "basis": "M08 §8.2.2, M15 §15.3.1; our own application / M15 §15.3.1–15.3.3; our own application / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original methods/SAPs are supplied, record the actual estimands and assumptions for each cardiovascular HR."
    },
    {
      "item_id": "N20",
      "question_type": "Evidence condition",
      "question": "What is the scope of blinding and cardiovascular event adjudication?",
      "needed": "Role-specific blinding, event diagnosis/adjudication and unblinding/detection differences",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What is the scope of blinding and cardiovascular event adjudication?",
      "application_exception": "Do not extend a double-blind label to certification of every outcome-adjudication or analysis process.",
      "criterion": "Separate the original design label from gaps in adjudication details.",
      "basis": "M08 Table 8.2.a, M03 §3.2.4; our own application / M08 §8.1–8.2.3; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original adjudication/methods material is supplied, record actual roles and event-collection scope."
    },
    {
      "item_id": "N21",
      "question_type": "Evidence condition",
      "question": "What are the details of randomization, concealment and baseline balance?",
      "needed": "Allocation process, concealment, stratification and baseline-characteristic tables",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What are the details of randomization, concealment and baseline balance?",
      "application_exception": "Do not declare all bias conditions satisfied from a randomized label alone.",
      "criterion": "Keep original allocation labels separate from gaps in direct methods.",
      "basis": "M08 §8.1–8.2.3; our own application / M03 §3.2.1; detailed population conditions are our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original allocation/baseline material is supplied, distinguish the design description from actual processes."
    },
    {
      "item_id": "N22",
      "question_type": "Evidence condition",
      "question": "How were CAMELLIA attrition, missing data and treatment crossover handled?",
      "needed": "Arm-specific flow, discontinuation/crossover, missing-data reasons, ITT/PP and sensitivity analyses",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: How were CAMELLIA attrition, missing data and treatment crossover handled?",
      "application_exception": "Do not transfer BLOOM retention as CAMELLIA follow-up/analysis percentages.",
      "criterion": "Do not mix denominators and missing-data material across trials.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are our own design / M08 §8.2.2, M15 §15.3.1; our own application / M19 §19.1.2–19.2.4, M04 §4.6.3; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original flow/analysis material is supplied, distinguish allocation, use, measurement and analysis denominators."
    },
    {
      "item_id": "N23",
      "question_type": "Evidence condition",
      "question": "Are people, composite events and repeated measurements different units?",
      "needed": "Aggregation rules for people/events/first/repeated events, time points and overlapping outcomes",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Are people, composite events and repeated measurements different units?",
      "application_exception": "Do not add counts from different endpoints/time points as independent populations or total events.",
      "criterion": "Retain original units and do not create unestablished totals.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap design / M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linking is Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original aggregation tables are supplied, record each unit and reporting relationship."
    },
    {
      "item_id": "N24",
      "question_type": "Evidence condition",
      "question": "Were the NCT and prespecified plans actually compared?",
      "needed": "Preregistration timing, endpoints/hierarchy, plan changes and analysis documents",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Were the NCT and prespecified plans actually compared?",
      "application_exception": "Do not count the same NCT as two independent-trial registrations or convert it to certification of prespecification.",
      "criterion": "Distinguish original registration strings and the scope of unread external material.",
      "basis": "M04 §4.5–4.6 provide collection and selection principles; separating access from reading and the hyperlink convention are our own design / M08 Table 8.2.a, M04 §4.6.3; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original registration/plan material is supplied, link actual timing and prespecified definitions."
    },
    {
      "item_id": "N25",
      "question_type": "Evidence condition",
      "question": "Are subgroup- and duration-specific cardiovascular effects known?",
      "needed": "Prespecified subgroup hypotheses, interactions and arm-specific denominators/HRs/intervals",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Are subgroup- and duration-specific cardiovascular effects known?",
      "application_exception": "Do not copy the overall HR as an effect for specific populations, durations or optimal exposure.",
      "criterion": "Retain gaps in direct evidence outside the overall results.",
      "basis": "M03 §3.2.1; detailed population conditions are our own design / M03 §3.2.1–3.2.4; dose, persistence and effect-modification details are our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If subgroup analyses are supplied, separate overall comparisons and subgroup interactions."
    },
    {
      "item_id": "N26",
      "question_type": "Evidence condition",
      "question": "Are superiority’s clinical importance and interpretation of all outcomes the same?",
      "needed": "Prespecified efficacy-importance criteria, absolute outcomes and individual components/quality of life",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Are superiority’s clinical importance and interpretation of all outcomes the same?",
      "application_exception": "Do not use the MACE noninferiority HR 1.40 as an efficacy-importance threshold.",
      "criterion": "Retain the original superiority result’s scope without thresholds from other endpoints.",
      "basis": "M15 §15.3.1–15.3.3; our own application / M03 §3.2.4; our own boundary on extensions",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original importance/outcome material is supplied, record statistical estimates and criteria for clinical scope separately."
    },
    {
      "item_id": "N27",
      "question_type": "Evidence condition",
      "question": "Is the CAMELLIA one-year weight response an event effect?",
      "needed": "Boundaries between weight-response definitions, denominators/time points and direct event results",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Is the CAMELLIA one-year weight response an event effect?",
      "application_exception": "Do not transfer positive weight response as MACE+ superiority or a selected subclaim score.",
      "criterion": "Preserve sibling context without adding it as new questions or trials.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap design / M03 §3.2.4; Chamgap extension boundary / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is Chamgap design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original results are added, record weight and direct cardiovascular outcomes separately."
    },
    {
      "item_id": "N28",
      "question_type": "Evidence condition",
      "question": "Are BLOOM weight response and retention separate context?",
      "needed": "BLOOM actual analysis denominators, missing data/retention and registration information",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Are BLOOM weight response and retention separate context?",
      "application_exception": "Do not repurpose BLOOM weight/retention values as CAMELLIA events or attrition.",
      "criterion": "Retain the boundary between a separate weight trial and selected cardiovascular results.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linking is Chamgap adaptation / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap design / M03 §3.2.4; Chamgap extension boundary",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original BLOOM material is supplied, link weight results and denominators/retention only to that trial."
    },
    {
      "item_id": "N29",
      "question_type": "Evidence condition",
      "question": "What were the maintenance trial’s 24-week and 52-week results?",
      "needed": "Time-specific/co-primary outcome denominators, definitions, intervals, meaning of ± and registration/analysis plans",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: What were the maintenance trial’s 24-week and 52-week results?",
      "application_exception": "Do not transfer a 24-week signal as 52-week weight maintenance or CAMELLIA cardiovascular events.",
      "criterion": "Preserve original maintenance results and time-specific gaps separately.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are Chamgap design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is Chamgap design / M08 Table 8.2.a, M04 §4.6.3; Chamgap adaptation / M03 §3.2.4; Chamgap extension boundary",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original maintenance material is supplied, record time points, co-primary endpoints, denominators and uncertainty."
    },
    {
      "item_id": "N30",
      "question_type": "Evidence condition",
      "question": "What is the extension scope from weight/maintenance to long-term clinical events?",
      "needed": "Actual duration-specific clinical outcomes, weight maintenance and follow-up after discontinuation",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: What is the extension scope from weight/maintenance to long-term clinical events?",
      "application_exception": "Do not automatically extend weight loss to improved long-term events, mortality or quality of life.",
      "criterion": "Preserve the different outcomes of weight signals and direct cardiovascular events.",
      "basis": "M03 §3.2.1–3.2.4; dose, duration and effect-modification details are Chamgap design / M03 §3.2.4; Chamgap extension boundary",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If direct long-term results are supplied, separate trials/time points and surrogates/clinical events."
    },
    {
      "item_id": "N31",
      "question_type": "Evidence condition",
      "question": "What is the original history of the developer program and independent replication?",
      "needed": "Original lists of report/developer/author/funding relationships and independent material",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: What is the original history of the developer program and independent replication?",
      "application_exception": "Do not calculate independent-replication counts from separate trial/citation counts or regulatory reviews.",
      "criterion": "Preserve original nonindependent-program history without new independence certification.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linking is Chamgap adaptation / Chamgap’s own independence/attribution conditions. The official methodological sections in this pilot do not warrant all these detailed items / M04 §4.6.1–4.6.2, M15 §15.3.1; Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If relevant material is supplied, distinguish clinical-trial families from funding/author independence."
    },
    {
      "item_id": "N32",
      "question_type": "Harm and regulatory scope",
      "question": "In which material context do the original FDA cancer-reanalysis results belong?",
      "needed": "Original FDA communications/review material, cancer definitions, collection/adjudication and event-specific results",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: In which material context do the original FDA cancer-reanalysis results belong?",
      "application_exception": "Do not turn regulatory reanalysis into a separate efficacy trial, new participants or directly read paper results.",
      "criterion": "Preserve the original FDA summary as regulatory/safety context.",
      "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is Chamgap design / M19 §19.1.2–19.2.4; Chamgap adaptation / M19 §19.1.2–19.2.4; detailed discrimination is Chamgap design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original regulatory material is supplied, record the decision at the time, clinical aggregation and direct content separately."
    },
    {
      "item_id": "N33",
      "question_type": "Harm and regulatory scope",
      "question": "Are people diagnosed with cancer and primary-cancer counts distinguished?",
      "needed": "People/primary cancers/overlap/duration and at-risk population denominators",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Are people diagnosed with cancer and primary-cancer counts distinguished?",
      "application_exception": "Do not add people with cancer and cancer counts or back-calculate duplicate people.",
      "criterion": "Keep original people, counts and percentages separated and unchanged.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap design / M19 §19.1.2–19.2.4; Chamgap adaptation / M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linking is Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original cancer-aggregation tables are supplied, link units and observation periods for people and multiple primary cancers."
    },
    {
      "item_id": "N34",
      "question_type": "Harm and regulatory scope",
      "question": "Is one additional cancer per 470 patient-years the original estimate?",
      "needed": "Patient-year estimation method, observation windows and time-specific cancer/exposure denominators",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Is one additional cancer per 470 patient-years the original estimate?",
      "application_exception": "Do not convert the original 470 patient-years value to individual risk, a new NNH or back-calculated events.",
      "criterion": "Retain time/units and estimation limitations in the original regulatory summary.",
      "basis": "M19 §19.2 design-specific harm questions; temporal-relationship details are Chamgap design / M19 §19.1.2–19.2.4; Chamgap adaptation / M19 §19.1.2–19.2.4; Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original time/analysis material is supplied, record the estimate’s observation scope and denominator."
    },
    {
      "item_id": "N35",
      "question_type": "Harm and regulatory scope",
      "question": "Are regulatory cancer decisions and statistical confirmation distinguished?",
      "needed": "Original overall-cancer estimates/intervals, basis for regulatory decisions and prespecified thresholds",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Are regulatory cancer decisions and statistical confirmation distinguished?",
      "application_exception": "Do not calculate or invent new cancer HRs/CIs/P values, statistical significance or causal certification.",
      "criterion": "Distinguish original regulatory judgments from gaps in direct statistical material.",
      "basis": "Chamgap’s own interpretation boundary, informed by M19 principles, without running an official causality tool / M19 §19.1.2–19.2.4; Chamgap adaptation / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is Chamgap design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original statistical/regulatory material is supplied, record original decisions, estimates and uncertainty separately."
    },
    {
      "item_id": "N36",
      "question_type": "Harm and regulatory scope",
      "question": "What are the original date and scope of the market-withdrawal record?",
      "needed": "Original FDA communication, withdrawal date/region and separate update scope for current product status",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: What are the original date and scope of the market-withdrawal record?",
      "application_exception": "Do not promote original historical status to a completed current authorization/marketing lookup.",
      "criterion": "Retain original dates and US withdrawal alongside the scope not currently looked up.",
      "basis": "M04 §4.5, §4.6.3; limitations of the current material conversion follow the review scope and Chamgap design / Chamgap’s own interpretation boundary, informed by M19 principles, without running an official causality tool",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If actual status material is supplied, record withdrawal at the time and verification of current status as separate events."
    },
    {
      "item_id": "N37",
      "question_type": "Harm and regulatory scope",
      "question": "Does cardiovascular noninferiority substitute for cancer or overall safety?",
      "needed": "Endpoint-specific safety results, harm collection and scope of decisions",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Does cardiovascular noninferiority substitute for cancer or overall safety?",
      "application_exception": "Do not convert meeting MACE noninferiority to absence of all harms or permission to take the drug.",
      "criterion": "Separate endpoint-specific safety scope and other long-term harms.",
      "basis": "M19 §19.2.2–19.2.4, M03 §3.2.3; Chamgap adaptation / Chamgap’s own interpretation boundary, informed by M19 principles, without running an official causality tool / M19 §19.1.2–19.2.4; Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If harm material is supplied, record cardiovascular safety, cancer signals and other harms as separate endpoints."
    },
    {
      "item_id": "N38",
      "question_type": "Harm and regulatory scope",
      "question": "Are harm collection, discontinuation and missing follow-up verified?",
      "needed": "All-harm collection, event definitions, discontinuation, attrition/missing data and follow-up",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Are harm collection, discontinuation and missing follow-up verified?",
      "application_exception": "Do not label a safety summary’s presence as complete collection of all harms or zero events.",
      "criterion": "Distinguish currently unread material from confirmation that original results were unreported.",
      "basis": "M19 §19.1.2–19.2.4; detailed discrimination is Chamgap design / M19 §19.1.2–19.2.4, M04 §4.6.3; Chamgap adaptation / M08 §8.2.2, M15 §15.3.1; Chamgap adaptation",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original safety flow/tables are supplied, distinguish event collection, unreported results and unread material."
    },
    {
      "item_id": "N39",
      "question_type": "Harm and regulatory scope",
      "question": "What are alternative harm causes and long-term/rare harms or vulnerable populations?",
      "needed": "Baseline/concurrent risks, exposure/follow-up, population-specific harms and alternative explanations",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: What are alternative harm causes and long-term/rare harms or vulnerable populations?",
      "application_exception": "Do not establish a regulatory signal as causality or risk magnitude for all participants, exposures or the class.",
      "criterion": "Distinguish original signals from unverified alternatives or extension scope.",
      "basis": "M19 §19.2.2–19.2.4 design considerations; detailed confounding records are Chamgap design / M19 §19.1.2–19.2.4; Chamgap adaptation / M03 §3.2.1–3.2.4; dose, duration and effect-modification details are Chamgap design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original long-term/population-specific material is supplied, distinguish original observations from gaps for other populations and rare harms."
    },
    {
      "item_id": "N40",
      "question_type": "Harm and regulatory scope",
      "question": "Are harm records from regulatory reanalysis, a paper and a communication independent replication?",
      "needed": "Aggregation relationships among original material/re-citations, reviews, communications and papers",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Are harm records from regulatory reanalysis, a paper and a communication independent replication?",
      "application_exception": "Do not count three documents, the same registration and the same cancer records as three independent populations.",
      "criterion": "Preserve relationships between document slots and the original population.",
      "basis": "M04 §4.6.1–4.6.2; harm-material adaptations are Chamgap designs / M04 §4.6.1–4.6.2 on distinguishing studies from reports; cohort and outcome connections are Chamgap adaptations",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If relevant original documents are supplied, record identity and event relationships between reanalysis and independent material."
    },
    {
      "item_id": "N41",
      "question_type": "Evidence condition",
      "question": "At what level are each report’s funding, author and operational roles recorded?",
      "needed": "Original report-specific funding, product provision, analysis/reporting, author affiliations and COI disclosures",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: At what level are each report’s funding, author and operational roles recorded?",
      "application_exception": "Do not convert “reported in the original text” to full-text reading in this production or establishment of a specific sponsor.",
      "criterion": "Retain original report-specific roles/funding descriptions and gaps separately.",
      "basis": "CHAMGAP's own independence and attribution conditions. Official methodological sections used in this pilot do not guarantee every detail of this item / M04 §4.6.1–4.6.2, M15 §15.3.1; our own application",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If original disclosures are supplied, record funding and operational/author roles for each report."
    },
    {
      "item_id": "N42",
      "question_type": "Evidence condition",
      "question": "How much of the FDA review paper was actually read?",
      "needed": "Paper full text, citation/review context and original conflict-of-interest disclosures",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: How much of the FDA review paper was actually read?",
      "application_exception": "Do not claim FDA communication values were directly read in the paper because its title mentions the same trial.",
      "criterion": "Retain original citation/no-abstract labels and unread status.",
      "basis": "M04 §4.5–4.6 material-collection/selection principles; separation of access/reading and the hyperlink contract are Chamgap design / M04 §4.5, §4.6.3; limitations of the current material conversion follow the review scope and Chamgap design / Chamgap’s own independence/attribution conditions. The official methodological sections in this pilot do not warrant all these detailed items",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If the user supplies the original full text, record material actually read separately from the FDA communication/summary."
    },
    {
      "item_id": "N43",
      "question_type": "Evidence condition",
      "question": "Is extension to other weight-loss drugs or the class avoided?",
      "needed": "Direct product/mechanism/harm-specific material and comparison scope",
      "role": "Supplementary",
      "role_reason": "A condition for separately recording original information and gaps for: Is extension to other weight-loss drugs or the class avoided?",
      "application_exception": "Do not apply lorcaserin results to other products or the whole class, or create new treatment-selection instructions.",
      "criterion": "Retain original extension limitations and do not mix results from other products.",
      "basis": "M03 §3.2.1; detailed population conditions are Chamgap design / M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are Chamgap design / M03 §3.2.4; Chamgap extension boundary / Chamgap’s own interpretation boundary, informed by M19 principles, without running an official causality tool",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If material for a separate question is supplied, write each product’s original context separately."
    },
    {
      "item_id": "N44",
      "question_type": "Evidence condition",
      "question": "Are the reference date, corrections, Korean/English text and empty-value history preserved?",
      "needed": "Original dates, corrections, current update scope and original empty values",
      "role": "Required",
      "role_reason": "A condition for separately recording original information and gaps for: Are the reference date, corrections, Korean/English text and empty-value history preserved?",
      "application_exception": "Do not borrow the existing reference date as a current review date or convert an empty corrections array to certification that no corrections exist anywhere.",
      "criterion": "Link original languages, dates and empty values with the actual current reading scope.",
      "basis": "M04 §4.5, §4.6.3; current material-conversion limits reflect review scope and our own design / M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are our own design",
      "condition_origin": "Production based on original materials; existing content review remains incomplete",
      "proposed_research": "If actual update material is supplied, distinguish the original version and a new correction event."
    }
  ]
}