{
  "schema_version": "chamgap-public-criteria-1.0",
  "title": "Camu-camu fruit extract · 12-week MRI liver fat — Evidence Check",
  "language": "en",
  "translation_date": "2026-10-13",
  "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": "Efficacy, boundaries and materials",
      "question": "What is the selected subclaim and its original record?",
      "needed": "Original Korean/English wording and the question/record relationship for reduced 12-week MRI liver fat",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of original Korean/English wording and the question/record relationship for reduced 12-week MRI liver fat.",
      "application_exception": "Do not turn parent/subclaim overlap into new independent trials or additional structural units.",
      "criterion": "Link original Korean/English wording and the question/record relationship for reduced 12-week MRI liver fat to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are our own design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "If the question boundary changes, retain the original wording separately from the change event."
    },
    {
      "item_id": "N02",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How are the subclaim C and parent C54, axes and history distinguished?",
      "needed": "Subclaim grade/note, absence of score/status/axes and preservation of parent values",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of subclaim grade/note, absence of score/status/axes and preservation of parent values.",
      "application_exception": "C54, B2 and historical cross-checks are preserved history, not new score calculation, RoB execution or completed content review.",
      "criterion": "Link subclaim grade/note, absence of score/status/axes and preservation of parent values to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When a separate evidence-update event occurs, distinguish preservation of original values from the new decision."
    },
    {
      "item_id": "N03",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Which selected adult population was actually studied?",
      "needed": "Eligibility and baseline liver fat in overweight adults with elevated fasting triglycerides",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of eligibility and baseline liver fat in overweight adults with elevated fasting triglycerides.",
      "application_exception": "Fatty-liver/MASLD tag names alone do not establish every participant’s diagnosis or severity.",
      "criterion": "Link eligibility and baseline liver fat in overweight adults with elevated fasting triglycerides to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.1; detailed population conditions are Chamgap's own design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish applicability to other populations using direct eligibility and baseline-characteristic materials."
    },
    {
      "item_id": "N04",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What was the tested extract?",
      "needed": "Actual formulation, quantification and manufacture of Myrciaria dubia fruit extract",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of actual formulation, quantification and manufacture of Myrciaria dubia fruit extract.",
      "application_exception": "Do not convert 1.5 g of extract into 1.5 g of vitamin C, fruit raw-material quantity or equivalents of other products.",
      "criterion": "Link actual formulation, quantification and manufacture of Myrciaria dubia fruit extract to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.2–3.2.3; reverse labeling and test adaptations are Chamgap's own design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish other camu-camu products when actual composition/formulation and direct materials are available."
    },
    {
      "item_id": "N05",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What were the research exposure and actual implementation?",
      "needed": "Research exposure of 1.5 g/day for each 12-week period and actual adherence",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of research exposure of 1.5 g/day for each 12-week period and actual adherence.",
      "application_exception": "No intake, capsule-count, dose-conversion, product-selection or treatment-implementation guidance is written.",
      "criterion": "Link research exposure of 1.5 g/day for each 12-week period and actual adherence to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §§3.2.2–3.2.3; reverse-direction labels and assessment adaptation are Chamgap-designed; M03 §§3.2.1–3.2.4; dose, durability and effect-modification details are Chamgap-designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Link follow-up materials while distinguishing nominal exposure from actual exposure."
    },
    {
      "item_id": "N06",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What was in the placebo and which comparison was made?",
      "needed": "Placebo composition/appearance, masking and treatment comparison",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of placebo composition/appearance, masking and treatment comparison.",
      "application_exception": "Prepare only the preserved-summary scope without adding definitions, values or denominators absent from original materials.",
      "criterion": "Link placebo composition/appearance, masking and treatment comparison to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.2–3.2.3; Reverse-direction labels and assessment adaptation are Chamgap design; M03 §3.2.3 and M08 §8.2.2–8.2.3; Chamgap application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Do not automatically combine materials using a different control into the same contrast."
    },
    {
      "item_id": "N07",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How are intervention periods and washout distinguished?",
      "needed": "Each 12-week period, crossover after washout and actual schedule",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of each 12-week period, crossover after washout and actual schedule.",
      "application_exception": "Do not add the two 12-week periods into a new total duration or claim that everyone completed identical total exposure.",
      "criterion": "Link each 12-week period, crossover after washout and actual schedule to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP; Design-specific harm questions in M19 §19.2; Detailed temporal relationships are internally designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When timing materials become available, link baseline/end measurements separately for each period."
    },
    {
      "item_id": "N08",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What were crossover allocation and comparison units?",
      "needed": "Randomized intervention sequence and repeated comparison in the same participants",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of randomized intervention sequence and repeated comparison in the same participants.",
      "application_exception": "Do not count camu-camu and placebo periods as independent parallel groups or two trials.",
      "criterion": "Link randomized intervention sequence and repeated comparison in the same participants to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 §8.1–8.2.3; CHAMGAP adaptation; Distinction between studies and reports in M04 §4.6.1–4.6.2; Cohort/outcome connections are CHAMGAP adaptations",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Retain distinctions between sequence, period and the same participants in new reports."
    },
    {
      "item_id": "N09",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Are the actual roles and maintenance of double blinding known?",
      "needed": "Masking/unmasking of participants, assessors and analysts",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of masking/unmasking of participants, assessors and analysts.",
      "application_exception": "Prepare only the preserved-summary scope without adding definitions, values or denominators absent from original materials.",
      "criterion": "Link masking/unmasking of participants, assessors and analysts to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish the double-blind label from actual roles and procedures in additional materials."
    },
    {
      "item_id": "N10",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What accompanying diet, weight and medication changes occurred?",
      "needed": "Period-specific co-exposure, weight changes and medication/behavior conditions",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of period-specific co-exposure, weight changes and medication/behavior conditions.",
      "application_exception": "Do not newly establish a weight-independent effect or causal effect of an individual ingredient.",
      "criterion": "Link period-specific co-exposure, weight changes and medication/behavior conditions to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; own application; M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are our own design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Retain actual measurement/adjustment of accompanying changes together with extract exposure in follow-up research."
    },
    {
      "item_id": "N11",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How was MRI liver fat actually measured?",
      "needed": "MRI hepatic fat fraction, change from baseline and equipment/methods",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of mRI hepatic fat fraction, change from baseline and equipment/methods.",
      "application_exception": "Prepare only the preserved-summary scope without adding definitions, values or denominators absent from original materials.",
      "criterion": "Link mRI hepatic fat fraction, change from baseline and equipment/methods to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "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, M03 §3.2.4; our own application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When methods are supplied, link actual technique, units and reading scope to the result."
    },
    {
      "item_id": "N12",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Are five regions of interest distinguished from participant counts?",
      "needed": "Mean MRI regions of interest per participant and analysis unit",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of mean MRI regions of interest per participant and analysis unit.",
      "application_exception": "Do not count five regions as five times the participants, independent observations or new trials.",
      "criterion": "Link mean MRI regions of interest per participant and analysis unit to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 Table 8.2.a, M03 §3.2.4; Chamgap application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap's own design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish regions, averages and participant-level analysis units in new measurement reports."
    },
    {
      "item_id": "N13",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Are relative change from baseline and final HFF distinguished?",
      "needed": "Period-specific baseline, change, relative/absolute measures and final values",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of period-specific baseline, change, relative/absolute measures and final values.",
      "application_exception": "Do not turn relative-change proportions into final hepatic fat fraction or percentage-point absolute decreases.",
      "criterion": "Link period-specific baseline, change, relative/absolute measures and final values to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are our own design; M08 §8.2.2, M15 §15.3.1; our own application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Link baseline, final values, absolute change and relative change separately when result tables are added."
    },
    {
      "item_id": "N14",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What were the original relative changes by period?",
      "needed": "Attribution of -7.43% to camu-camu and +8.42% to placebo",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of attribution of -7.43% to camu-camu and +8.42% to placebo.",
      "application_exception": "Do not turn placebo increases or extract decreases into guaranteed individual effects or changes in everyone.",
      "criterion": "Link attribution of -7.43% to camu-camu and +8.42% to placebo to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.4 and M15 §§15.3.1–15.3.3; question-specific outcome adaptation is Chamgap-designed; M04 §4.6.3 and M15 §§15.3.1–15.3.3; status separation is Chamgap-designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When original results are supplemented, link each period/measure and preserve current original values."
    },
    {
      "item_id": "N15",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Which contrast does the original -15.85% relative difference represent?",
      "needed": "Between-treatment contrast in relative change from baseline and P value",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of between-treatment contrast in relative change from baseline and P value.",
      "application_exception": "Do not recalculate from -7.43 and +8.42 or newly define -15.85 as an absolute percentage-point or adjusted effect.",
      "criterion": "Link between-treatment contrast in relative change from baseline and P value to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 §8.2.2, M15 §15.3.1; CHAMGAP adaptation; M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When analysis materials arrive, link the relative-change contrast and original adjustment to that analysis."
    },
    {
      "item_id": "N16",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How is the approximately 1.6-percentage-point median absolute HFF decrease retained?",
      "needed": "Absolute-change median, population/contrast and separate relative-measure labeling",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of absolute-change median, population/contrast and separate relative-measure labeling.",
      "application_exception": "Do not assert that approximately 1.6 percentage points is a new adjusted between-treatment mean difference or conversion of -15.85%.",
      "criterion": "Link absolute-change median, population/contrast and separate relative-measure labeling to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations by question are our own design; M15 §15.3.1–15.3.3; our own application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When materials are added, link the original median to its actual population, measure and interval."
    },
    {
      "item_id": "N17",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What is the scope of the account that the effect CI was unreported?",
      "needed": "Original unreported-CI record and actual external reading scope",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of original unreported-CI record and actual external reading scope.",
      "application_exception": "Do not newly calculate CI, variance or effect size from P values or sample size.",
      "criterion": "Link original unreported-CI record and actual external reading scope to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M15 §15.3.1–15.3.3; Chamgap adaptation; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Link supplied intervals with their actual original location, measure and analysis while preserving the original record."
    },
    {
      "item_id": "N18",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What was the clinically important HFF threshold?",
      "needed": "Prespecified importance criterion, measure and uncertainty",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of prespecified importance criterion, measure and uncertainty.",
      "application_exception": "Do not newly establish clinically sufficient reduction from a positive P value or 1.6 percentage points.",
      "criterion": "Link prespecified importance criterion, measure and uncertainty to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M15 §§15.3.1–15.3.3; Chamgap adaptation",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When direct criteria are supplied, distinguish prespecified/post hoc status, measure and applicable population."
    },
    {
      "item_id": "N19",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Which denominators are 35 allocated and 30 completing both periods?",
      "needed": "Allocation, sequence, period completion and completer analysis",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of allocation, sequence, period completion and completer analysis.",
      "application_exception": "Do not copy the 30 completers as the actual MRI analysis denominator for every result.",
      "criterion": "Link allocation, sequence, period completion and completer analysis to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are Chamgap design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When flow is supplemented, record allocation, each-period completion and both-period completion separately."
    },
    {
      "item_id": "N20",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How do the MRI analysis counts of 20 and 25 differ?",
      "needed": "Actual endpoint denominators of 20 in the camu-camu period and 25 in the placebo period",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of actual endpoint denominators of 20 in the camu-camu period and 25 in the placebo period.",
      "application_exception": "Do not calculate 20+25 as total participants or interpret them as two independent groups.",
      "criterion": "Link actual endpoint denominators of 20 in the camu-camu period and 25 in the placebo period to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; Design-specific adaptation is Chamgap design; M08 §8.2.2 and M15 §15.3.1; Chamgap application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Link completer counts separately from actual endpoint-analysis denominators in new analysis materials."
    },
    {
      "item_id": "N21",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How were completion, MRI selection and missingness handled?",
      "needed": "Completer analysis, missing MRI, missingness reasons/handling and sensitivity",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of completer analysis, missing MRI, missingness reasons/handling and sensitivity.",
      "application_exception": "Do not calculate or invent unmeasured counts, withdrawal/analysis-exclusion rates or new ITT results.",
      "criterion": "Link completer analysis, missing MRI, missingness reasons/handling and sensitivity to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 §8.2.2 and M15 §15.3.1: in-house application; M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4: design-specific adaptation is in-house.",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Retain reasons/assumptions for differences between all allocated participants and actual outcome analysis in follow-up research."
    },
    {
      "item_id": "N22",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How were sequence, period and carryover effects handled?",
      "needed": "Crossover model, washout, sequence/period/carryover effects and correlation",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of crossover model, washout, sequence/period/carryover effects and correlation.",
      "application_exception": "Washout alone does not establish no carryover, independent periods or a complete paired analysis.",
      "criterion": "Link crossover model, washout, sequence/period/carryover effects and correlation to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 §8.2.2, M15 §15.3.1; internal application; M08 §8.1–8.2.3; internal application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Link both periods in the same participants and report carryover/period assumptions separately in crossover analysis materials."
    },
    {
      "item_id": "N23",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What was the hierarchy of the prespecified MRI endpoint and other outcomes?",
      "needed": "Hepatic-steatosis planning, primary MRI and other markers",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of hepatic-steatosis planning, primary MRI and other markers.",
      "application_exception": "Do not use liver injury markers in the paper title to create the same numerical effect as MRI or additional clinical efficacy.",
      "criterion": "Link hepatic-steatosis planning, primary MRI and other markers to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 Table 8.2.a, M04 §4.6.3; own application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific result adaptation is our own design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When plans are supplied, distinguish actual prespecified/post hoc and primary/supporting results."
    },
    {
      "item_id": "N24",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What is the status of NCT04130321 and the current original registration?",
      "needed": "Original registration identity, planning/change history and actual reading",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of original registration identity, planning/change history and actual reading.",
      "application_exception": "A number’s presence does not establish registration reading, prespecification certification or a completed link check.",
      "criterion": "Link original registration identity, planning/change history and actual reading to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.6.1–4.6.2 distinguish studies from reports; cohort/outcome linkage is internally applied",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish the original number, historical records and current reading scope when registration materials are supplied."
    },
    {
      "item_id": "N25",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What are the report identity and actual preserved-summary locations?",
      "needed": "Marette 2024, Cell Reports Medicine, PMID and original evidence/citation records",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of marette 2024, Cell Reports Medicine, PMID and original evidence/citation records.",
      "application_exception": "Do not infer or generate DOI/PMCID from the PMID or article number.",
      "criterion": "Link marette 2024, Cell Reports Medicine, PMID and original evidence/citation records to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M04 §§4.6.1–4.6.2 distinction between studies and reports; cohort/outcome links are Chamgap adaptations",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When bibliography is supplemented, retain original literal wording together with the change event."
    },
    {
      "item_id": "N26",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Are the same trial, periods and regions kept separate from new independent replication?",
      "needed": "Same crossover population, two periods, regions of interest and report family",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of same crossover population, two periods, regions of interest and report family.",
      "application_exception": "Do not sum 35, 30, 20, 25, five regions or parent/subclaim sheets into new participant or independent-trial totals.",
      "criterion": "Link same crossover population, two periods, regions of interest and report family to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "Study/report distinction in M04 §4.6.1–4.6.2; Cohort/outcome linkage is Chamgap application; M04 §4.6.1–4.6.2 and M15 §15.3.1; Chamgap application",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish recruitment, registration and participant relationships when new independent materials are supplied."
    },
    {
      "item_id": "N27",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Are MRI reduction and actual liver-disease outcomes distinguished?",
      "needed": "Imaging surrogate versus cirrhosis, hospitalization, death and other clinical events",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of imaging surrogate versus cirrhosis, hospitalization, death and other clinical events.",
      "application_exception": "Do not extend positive 12-week MRI results to liver-disease treatment, complication/death prevention or long-term efficacy.",
      "criterion": "Link imaging surrogate versus cirrhosis, hospitalization, death and other clinical events to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §3.2.4; internally defined extension boundary; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Link new clinical outcomes with definitions, timing and denominators separate from MRI."
    },
    {
      "item_id": "N28",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What are the product, duration and ingredient boundaries?",
      "needed": "Tested extract, 1.5 g/day, 12 weeks and other polyphenols",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of tested extract, 1.5 g/day, 12 weeks and other polyphenols.",
      "application_exception": "Preserve the historical mention of verdict 2962 for a different plant extract without opening its materials/page or treating it as the same trial.",
      "criterion": "Link tested extract, 1.5 g/day, 12 weeks and other polyphenols to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M03 §§3.2.1–3.2.4; dose, durability and effect-modification details are Chamgap-designed; M03 §§3.2.2–3.2.3; reverse-direction labels and assessment adaptation are Chamgap-designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish replication of the same question from applicability to different ingredients/products in independent follow-up research."
    },
    {
      "item_id": "N29",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What is the scope of opposing, conflicting and individual-difference materials?",
      "needed": "Positive result, uncertainty and differences between ingredients/subgroups",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of positive result, uncertainty and differences between ingredients/subgroups.",
      "application_exception": "No search does not mean no other studies; results for other ingredients do not become direct refutation of this trial.",
      "criterion": "Link positive result, uncertainty and differences between ingredients/subgroups to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed; M03 §3.2.1–3.2.4; dose, duration and effect-modification details are internally designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish actual conflict for the same question from differences between ingredients/measures in new materials."
    },
    {
      "item_id": "N30",
      "question_type": "Efficacy, boundaries and materials",
      "question": "Which original records describe support and industry relationships?",
      "needed": "Nonprofit/public support, manufacturer-reporting status and research-chair disclosures",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of nonprofit/public support, manufacturer-reporting status and research-chair disclosures.",
      "application_exception": "Do not convert public/nonprofit funding or unreported-support records into new certification of no conflicts or no manufacturer support.",
      "criterion": "Link nonprofit/public support, manufacturer-reporting status and research-chair disclosures to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "Chamgap's own conditions for independence and attribution. The official methodological sections used in this example do not validate every detail of these items.",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish direct support, external relationships and analysis/publication roles in newly disclosed materials."
    },
    {
      "item_id": "N31",
      "question_type": "Efficacy, boundaries and materials",
      "question": "How are original dates, corrections, empty values, Korean/English wording and history preserved?",
      "needed": "2026-08-26, empty correction/deliberation records and original verdict/axes",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of 2026-08-26, empty correction/deliberation records and original verdict/axes.",
      "application_exception": "Do not fill unrecorded original precision/empty values with new numbers or axes, or transfer historical cross-checks into current review.",
      "criterion": "Link 2026-08-26, empty correction/deliberation records and original verdict/axes to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M04 §§4.5 and 4.6.3; limits of the current material conversion follow the review scope and Chamgap design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When materials change, record the complete earlier text, event, version and separate application distinctly."
    },
    {
      "item_id": "N32",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What was actually read and what are the material-slot states?",
      "needed": "Distinction between preserved summary and external abstract, full text, registration and plans",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of distinction between preserved summary and external abstract, full text, registration and plans.",
      "application_exception": "URLs, citations or preserved copies do not establish external reading, successful access or a completed link check.",
      "criterion": "Link distinction between preserved summary and external abstract, full text, registration and plans to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M04 §4.5–4.6 material collection/selection principles; acquisition/reading separation and hyperlink specifications are internally designed; M04 §4.5, §4.6.3; limits of this material conversion follow the review scope and internal design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When materials are supplied, separately record acquisition, publication, access, actual reading scope and dates."
    },
    {
      "item_id": "N33",
      "question_type": "Efficacy, boundaries and materials",
      "question": "What should be linked when new evidence or corrections arrive?",
      "needed": "Separation of conditions, original materials, observations, reading and change events",
      "role": "Required",
      "role_reason": "Preparation condition retaining the actual scope of separation of conditions, original materials, observations, reading and change events.",
      "application_exception": "Original candidate review-pending/production-eligibility markers are history; they do not revive an active review wait or approval process.",
      "criterion": "Link separation of conditions, original materials, observations, reading and change events to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M04 §§4.5 and 4.6.3; limits of the current material conversion follow the review scope and Chamgap design",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Only for new materials and actual changes, distinguish complete earlier files, events, condition version/freeze, separate application and current handoff."
    },
    {
      "item_id": "H01",
      "question_type": "Harms",
      "question": "How were gastrointestinal discomfort and adverse events defined and collected?",
      "needed": "Mild gastrointestinal discomfort, relatedness and adverse-event collection/grading",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of mild gastrointestinal discomfort, relatedness and adverse-event collection/grading.",
      "application_exception": "Prepare only the preserved-summary scope without adding definitions, values or denominators absent from original materials.",
      "criterion": "Link mild gastrointestinal discomfort, relatedness and adverse-event collection/grading to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M19 §§19.1.2–19.2.4; detailed distinctions are Chamgap-designed; M19 §§19.1.2–19.2.4; Chamgap adaptation",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Retain consistent collection/grading for gastrointestinal events and other harms in follow-up research."
    },
    {
      "item_id": "H02",
      "question_type": "Harms",
      "question": "What were actual event timing and exposure?",
      "needed": "Intervention period, washout/switching and onset/discontinuation timing",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of intervention period, washout/switching and onset/discontinuation timing.",
      "application_exception": "Without original timing, do not convert the record into a confirmed camu-camu-period event rate or long-term harm.",
      "criterion": "Link intervention period, washout/switching and onset/discontinuation timing to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M19 §19.2 design-specific harm questions; timing details are Chamgap-designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish event periods, actual exposure at risk and postdiscontinuation course in harms reports."
    },
    {
      "item_id": "H03",
      "question_type": "Harms",
      "question": "Are harms compared by camu-camu/placebo period?",
      "needed": "Period-specific events, relatedness, severity and control comparison",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of period-specific events, relatedness, severity and control comparison.",
      "application_exception": "Historical absence of arm-specific counts does not establish zero events or safety equivalence.",
      "criterion": "Link period-specific events, relatedness, severity and control comparison to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M19 §§19.2.2–19.2.4 and M03 §3.2.3; Chamgap adaptation",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When actual harms materials are added, link period-specific exposure in the same participants to original definitions."
    },
    {
      "item_id": "H04",
      "question_type": "Harms",
      "question": "How do withdrawal and harms denominators differ?",
      "needed": "Original five withdrawals, one gastrointestinal-discomfort withdrawal and actual safety population",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of original five withdrawals, one gastrointestinal-discomfort withdrawal and actual safety population.",
      "application_exception": "Do not use new calculations such as 35-30 or 1/5 to create withdrawal reasons or adverse-effect rates.",
      "criterion": "Link original five withdrawals, one gastrointestinal-discomfort withdrawal and actual safety population to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M19 §§19.1.2–19.2.4; Chamgap adaptation; M08 Table 8.2.a, M15 §15.3 and M19 §§19.1.2–19.2.4; design-specific adaptation is Chamgap-designed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish allocation, exposure, period-specific collection and analysis denominators in harms materials."
    },
    {
      "item_id": "H05",
      "question_type": "Harms",
      "question": "What level of signal does possible capsule relatedness represent?",
      "needed": "Discomfort timing, alternative factors and possible-relatedness judgment",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of discomfort timing, alternative factors and possible-relatedness judgment.",
      "application_exception": "One case does not establish confirmed camu-camu toxicity, a general incidence rate or absence of harm.",
      "criterion": "Link discomfort timing, alternative factors and possible-relatedness judgment to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed; Chamgap’s own interpretation boundaries. M19 principles are referenced; no official causality tool was executed",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish a possible-relatedness signal from direct causal judgment in additional harms materials."
    },
    {
      "item_id": "H06",
      "question_type": "Harms",
      "question": "Are unread, unreported, uncollected and actual zero outcomes distinguished?",
      "needed": "Unread external scope and gaps in harms results",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of unread external scope and gaps in harms results.",
      "application_exception": "Unread external materials do not mean zero adverse effects, no paper or failed access.",
      "criterion": "Link unread external scope and gaps in harms results to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M19 §§19.1.2–19.2.4 and M04 §4.6.3; Chamgap adaptation",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Link actual zero, missing, unreported and uncollected states separately only for supplied materials."
    },
    {
      "item_id": "H07",
      "question_type": "Harms",
      "question": "Are crossover harms and reports protected from duplicate summing?",
      "needed": "Harms linkage in the same participants across two periods and one report",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of harms linkage in the same participants across two periods and one report.",
      "application_exception": "Do not sum the two periods or allocation/completion/measurement counts as harms participants or independent trials.",
      "criterion": "Link harms linkage in the same participants across two periods and one report to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M04 §§4.6.1–4.6.2; harm-material adaptation is Chamgap-designed; M04 §§4.6.1–4.6.2 distinction between studies and reports; cohort/outcome links are Chamgap adaptations",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Distinguish rereporting of the same event from new events when harms materials are supplemented."
    },
    {
      "item_id": "H08",
      "question_type": "Harms",
      "question": "What gaps remain in long-term safety and other risk populations?",
      "needed": "12-week research exposure and safety for longer periods, other formulations/populations/diseases",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of 12-week research exposure and safety for longer periods, other formulations/populations/diseases.",
      "application_exception": "Do not extend positive 12-week imaging results into long-term safety guarantees or safety of other polyphenols.",
      "criterion": "Link 12-week research exposure and safety for longer periods, other formulations/populations/diseases to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "M19 §§19.1.2–19.2.4; Chamgap adaptation",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "Retain actual exposure, population, duration and collection methods in long-term safety research."
    },
    {
      "item_id": "H09",
      "question_type": "Harms",
      "question": "Are limitations of imaging benefits and harms signals retained together?",
      "needed": "Separation of positive MRI, uncertainty, gastrointestinal discomfort and systematic-harms gaps",
      "role": "Supporting harm information",
      "role_reason": "Preparation condition retaining the actual scope of separation of positive MRI, uncertainty, gastrointestinal discomfort and systematic-harms gaps.",
      "application_exception": "Do not turn positive imaging results into liver-treatment recommendations, usage/product-selection or treatment-replacement guidance, or a definitive harms verdict.",
      "criterion": "Link separation of positive MRI, uncertainty, gastrointestinal discomfort and systematic-harms gaps to the corresponding research exposure, period, measure and denominator, distinguishing unverified matters.",
      "basis": "Chamgap interpretive boundary informed by M19 principles; no formal causality tool was run",
      "condition_origin": "Chamgap-designed production based on originals; existing content review remains assigned separately",
      "proposed_research": "When new materials are supplied, link imaging, clinical and harms results and their change events separately."
    }
  ]
}